Neurogenic Detrusor Overactivity In Patients Research Articles

Therapeutic effects of detrusor botulinum toxin A injection on neurogenic detrusor overactivity in patients with different levels of spinal cord injury and types of detrusor sphincter dyssynergia

The study was designed as a single-arm clinical trial. To investigate the therapeutic effects of detrusor botulinum toxin A (BoNT-A) treatment in patients with different levels of spinal cord injury (SCI) and types of detrusor sphincter dyssynergia (DSD). Patients with chronic suprasacral SCI and neurogenic detrusor overactivity (NDO) were treated with 200-U BoNT-A detrusor injection in a tertiary university hospital in Taiwan. Outcome assessment of urodynamic parameters and therapeutic satisfaction were performed at 3 and 6 months among patients with different demographics, SCI levels and types of DSD. The treatment outcomes were assessed by changes in Urogenital Distress Inventory 6-item short form (UDI-6), quality of life (QoL) index and detrusor pressure at maximum flow rate (Pdet.Qmax). A total of 38 patients with a mean age of 40.1±12.4 years and median duration of SCI of 10.3 years were enrolled. Satisfactory response was reported in 23 (60%) patients. Significant improvements in the UDI-6 and QoL were reported and significant increases of cystometric bladder capacity and post-void residual were noted in overall patients after treatment. Patients with different clinical demographics and urodynamic parameters had similar treatment outcomes and UDI-6 scores. In 11 patients receiving repeat injections of 300 U of BoNT-A after failure of a previous 200 U injection, the treatment outcomes were not significantly different, except that the PdetQmax at 6 months were higher in the group that received 200 U of BoNT-A. Patients with different SCI levels or DSD types had similar treatment outcomes after detrusor 200 U BoNT-A injections for NDO.

Semiconditional Electrical Stimulation of Pudendal Nerve Afferents Stimulation to Manage Neurogenic Detrusor Overactivity in Patients with Spinal Cord Injury

ObjectiveTo evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study.MethodPatients with neurogenic detrusor overactivity were subdivided into complete injury and incomplete injury groups by ASIA classification and subdivided into tetraplegia and paraplegia groups by neurologic level of injury. Bladder function, such as bladder volumes infused to the bladder until the first occurrence of neurogenic detrusor overactivity (Vini) and the last contraction suppressed by electrical stimulation (Vmax) was measured by water cystometry (CMG) and compared with the results of each subgroup.ResultsAmong the 40 subjects, 35 patients showed neurogenic detrusor overactivity in the CMG study. Among these 35 patients, detrusor overactivity was suppressed effectively by pudendal nerve afferent electrical stimulation in 32 patients. The infusion volume until the occurrence of the first reflex contraction (Vini) was 99.4±80.3 ml. The volume of saline infused to the bladder until the last contraction suppressed by semiconditional pudendal nerve stimulation (Vmax) was 274.3±93.2 ml, which was significantly greater than Vini. In patients with good response to the pudendal nerve afferent stimulation, the bladder volume significantly increased by stimulation in all the patients.ConclusionIn this study, semiconditional electrical stimulation on the dorsal penile afferent nerve could effectively inhibit neurogenic detrusor overactivity and increase bladder volume in patients with spinal cord injury.

Effects of potassium channel modulators on myogenic spontaneous phasic contractile activity in human detrusor from neurogenic patients

To characterize the spontaneous contractile activity (SCA) developed by detrusor from patients with neurogenic detrusor overactivity (NDO) because the alteration of detrusor properties plays a critical role in the pathogenesis of detrusor overactivity, as well as to evaluate the role of K(ATP) and K(Ca) channels on this SCA because these channels regulate detrusor SCA in many species, including humans without overactive bladder (OAB). Human bladder samples were obtained from 44 patients undergoing cystectomy for bladder cancer with no known OAB symptoms and from 38 patients suffering from urodynamically diagnosed NDO. Detrusor strips with or without urothelium/suburothelium were mounted isometrically in organ baths filled with Krebs-HEPES (37 °C; 95% O(2) /5% CO(2) ). Strips were incubated with 10 µm pinacidil (K(ATP) opener) followed by 10 µm glibenclamide (K(ATP) blocker). In another set of experiments, strips were incubated with 30 µm NS-1619 (BK(Ca) opener) followed by 100 nm iberiotoxin (BK(Ca) blocker) or with 100 nm apamin (SK(Ca) blocker). SCA occurred more frequently with larger amplitude and area under the curve in detrusor strips from NDO patients compared to control patients. The presence of urothelium/suburothelium did not significantly modify SCA in either patient population. Pinacidil markedly inhibited SCA of detrusor strips from control and NDO patients. This effect was reversed by glibenclamide. By contrast, NS-1619 followed by iberiotoxin did not elicit any significant changes in SCA from NDO patients, contrary to control patients. K(ATP) and SK(Ca) channels regulate SCA of NDO patients' detrusor strips. By contrast, BK(Ca) channels are not involved in the regulation of detrusor SCA in NDO patients, whereas they regulate SCA in control patients. These results should be considered in the development of K(+) channels openers for the treatment of NDO. Moreover, SCA observed in vitro should be regarded as an in vitro modelling of human NDO.

Risk of urinary tract infection after detrusor botulinum toxin A injections for refractory neurogenic detrusor overactivity in patients with no antibiotic treatment

To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization. Injections were performed using a rigid cystoscope, under local anaesthetic. Patients received BoNT-A as either Botox® (Allergan Inc., Irvine, CA, USA) 300 U in 30 sites or Dysport® (Ipsen Ltd, Ipsen, Paris, France) 750 U in 20 sites. Urine culture was done 6 days and 6 weeks after the injections. If urinary tract infection (UTI) was suspected, a physician performed a complete physical examination. The primary outcome criterion was the occurrence of UTI during the first week after injections. In all, 42 patients (22 women, 20 men) with a mean (sd) age 45.3 (16.4) years were included. A symptomatic UTI occurred during the first week after the injections in three patients (7.1%). The urinary colonization rate was 31% and 26% at 6 days and 6 weeks after injection, respectively. The most common bacterium was Escherichia coli (62.5%). There were no differences between 20 and 30 injection sites or between the sexes. The rate of UTI after intradetrusor injections of BoNT-A was 7.1%. The most frequent bacterium involved was Escherichia coli. These results indicate that antibiotic prophylaxis for intradetrusor BoNT-A injections seems necessary.

S3 neuromodulation using Chinese electro-acupuncture on BL-33 to treat neurogenic detrusor overactivity in patients with spinal cord injury

Objective To observe the effects of electrical acupuncture for the treatment of neurogenic detrusor overactivity （DO） caused by spinal cord injury （SCI）.Methods Twenty SCI patients with DO were included in this study. There were 18 males and 2 females;age ranged from 17 to 58 years. Patients were given electro-acupuncture treatment at the bilateral S3 foramen at the lateral position during the vidio-urodynamic investigation when the detrusor of the patients began to contract.The different intensities of electrical stimulation were used when the DO appeared during cystometry and the most effective intensity to inhibit DO was determined. Then, the bladder was emptied and the stimulation with selected intensity was used at the beginning of cystometry. The changes of parameters in the urodynamics, the urinary incontinence times per day and the pad used per day were recorded. The acute effects were observed. Ten days were set as one course and after 3 courses and 9 courses the patients underwent urodynamic test again. The long-term effects were observed.Results After treatment, the urinary incontinence times per day and the pad used per day decreased obviously （P〈0. 05）. The bladder capacity increased significantly and the maximum intravesical pressure decreased significantly. There were 3 patients having the long terms treatment. Conclusions The Chinese electro-acupuncture at S3 foramen in the SCI patients with DO is demonstrated effective. After the treatment bladder capacity could increase and the times of the urinary incontinence per week decrease. Key words: Detrusor overactivity; Electro acupuncture; Spinal cord injury; S3 foramen neuromodulation

Comparison of the impact on health‐related quality of life of repeated detrusor injections of botulinum toxin in patients with idiopathic or neurogenic detrusor overactivity

Therapy (case series). 4. What's known on the subject? and What does the study add? We know that repeated injections of botulinum toxin A are effective in treating refractory detrusor overactivity particularly in NDO. This study shows that in both NDO and IDO repeated injections of the toxin improve quality of life as assessed by three validated questionnaires. The effect is most marked after the first injection in NDO patients but thereafter similar in both groups. To compare the effect of repeated detrusor injections of botulinum toxin (BoNT-A) on health-related quality of life (HRQL) in patients with idiopathic (IDO) or neurogenic detrusor overactivity (NDO). Between 2003 and 2009, 151 patients (109 with NDO and 42 with IDO) were treated by BoNT-A (Botox®, Allergan Inc., Irvine, CA, USA). Changes in HRQL were assessed using the validated short forms of Urogenital Distress Inventory (UDI-6), the Incontinence Impact Questionnaire (IIQ-7) and EuroQOL-5D (EQ-5D) before and 4 weeks after BoNT-A. The maximum number of repeated injections was five (mean±sd, 2.8±1.05). Mean±sd follow-up was 27.49±17.01 months. The UDI-6 and IIQ-7 questionnaires showed a consistent improvement after repeated injections in both groups with detrusor overactivity. The EQ-5D was not statistically different before and after each injection in either the NDO or IDO population. After repeated injections, no statistical differences in the change on the UDI-6 and IIQ-7 scores were found between NDO and IDO, except after the first treatment, when the decrease in UDI-6 was higher in NDO than in IDO. The EQ-5D anxiety and depression subscore improved in both groups after each injection and with the number of injections. In IDO, after the second injection, no patient reported extreme anxiety or depression and, after the fourth injection, none had anxiety or depression. The inter-injection interval was shorter after the first injection in those with NDO than in IDO but was similar thereafter. Intradetrusor injections of BoNT-A improved the HRQL of both NDO and IDO patients. Although improvement in HRQL was greater and the duration of efficacy shorter in NDO patients after the first injection, there was no significant difference after subsequent injections. Mean inter-injection interval in IDO and in NDO patients was similar from the second injection onwards and improvements in HRQL score were the same.

Treatment of Neurogenic Detrusor Overactivity with Botulinum Toxin A: The First Seven Years

Introduction: This retrospective study describes the results of botulinum toxin A detrusor injections following a fixed protocol in 216 patients with untreatable neurogenic detrusor overactivity and incontinence. A comparison is made between the two preparations currently available, and the efficacy of multiple treatments is studied. Patients and Methods: Botox® 300 MU (mouse units) or Dysport® 750 MU were injected into the detrusor wall in 365 sessions in 216 patients. The average age of the 144 men and 72 women was 32.3 years. Patients were investigated before treatment and at 6 weeks and 6 months after treatment. Maximal detrusor pressure, detrusor compliance, reflex volume and cystometric capacity were recorded. Use of anticholinergics and patient satisfaction were ascertained from questionnaires. Appropriate statistics were applied. Results: All urodynamic parameters improved. The use of anticholinergics decreased substantially. No differences were noted between the two preparations. The incontinence situation improved markedly. The effect of the treatment was noted after about 2 weeks and lasted for about 9 months. Conclusions: Botulinum toxin A treatment in neurogenic detrusor overactivity patients is effective, long-lasting and repeatable. The treatment is minimally invasive and might be considered as an alternative to high-dosage anticholinergic medication.

Has botulinum toxin therapy come of age: what do we know, what do we need to know, and should we use it?

To review the most recent data concerning the clinical use of botulinum toxin type A (BoNT/A) in different human lower urinary tract dysfunctions, with particular emphasis on neurogenic detrusor overactivity. The most recent findings indicate that the repeated application of BoNT/A is effective in patients with neurogenic detrusor overactivity, maintaining sustained control of incontinence, protection of upper urinary tract and reduction of urinary infectious complications. In addition, BoNT/A injections have proved to be well tolerated and the risk of bladder fibrosis nonexistent. Other BoNT/A indications under investigation are idiopathic detrusor overactivity, benign prostatic enlargement and bladder pain syndrome/interstitial cystitis. Although still waiting for approval, BoNT/A detrusor injections can be safely offered to well informed patients with refractory neurogenic detrusor overactivity, as an alternative to more invasive therapies, such as bladder augmentation. Ongoing studies are expected to come up with the necessary information for definitive approval of BoNT/A in neurogenic detrusor overactivity patients. Regarding other possible applications such as idiopathic detrusor overactivity, benign prostatic enlargement and bladder pain syndrome/interstitial cystitis, its use should still be restricted to research centres in well designed clinical trials.

Suburothelial Myofibroblasts in the Human Overactive Bladder and the Effect of Botulinum Neurotoxin Type A Treatment

BackgroundAn increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO). ObjectiveTo determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA). Design, setting, and participantsPatients with NDO (n=10) or IDO (n=11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064. InterventionsBladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit. MeasurementsDifferences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes). Results and limitationsCx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment. ConclusionsIncreased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.

Acute urodynamic effects of percutaneous posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with Parkinson's disease

Lower urinary tract dysfunction is often occurs in patients with Parkinson's disease (PD), that is primarily induced by neurogenic detrusor overactivity (NDO) and negatively effect the quality of the patient's life. The aim of this study is to evaluate the acute effects of posterior tibial nerve stimulation (PTNS) on the urodynamic findings in the PD patients with NDO. Thirty-two patients with PD (19 [59.3%] men and 13 [40.6%] women) with NDO were included in the study. Mean age of the patients was 64.2 +/- 8.7 years (range 44-78). Urodynamic studies before and during PTNS were performed. Electrical stimulation was applied unilaterally from the medial malleolus and posterior to the edge of the tibia by using charge-compensated 200 microsec pulses with a pulse rate of 20 Hz. Mean first involuntary detrusor (1st IDCV) contractions and means maximum cystometric capacity (MCC) before and during PTNS was compared. Mean 1st IDCV on standard cystometry was 145.2 +/- 41.1 (55-265) ml, while it was 244.7 +/- 51.7 (145-390) ml during PTNS. MCC on standard cystometry was 204.8 +/- 40.5 (115-320) ml, while it was 301.2 +/- 51.5 (230-395) ml during stimulation. Mean 1st IDC and mean MCC were significantly improved during PTNS. These results have demonstrated the objective acute effect of PTNS on urodynamic parameters. PTNS is acutely effective to suppress detrusor overactivity in PD patients.

Urinary Nerve Growth Factor Levels are Elevated in Patients with Detrusor Overactivity and Decreased in Responders to Detrusor Botulinum Toxin-A Injection

Increased nerve growth factor (NGF) levels have been reported in the bladder tissue and urine of patients with overactive bladder and detrusor overactivity (DO). Determination of urinary NGF level could serve as a valuable biomarker for the diagnosis and monitoring of disease progression of DO. To investigate NGF levels in patients with DO and after treatment including detrusor botulinum toxin A (BoNT-A) injections. A cross-sectional study was performed in a referred center. Participants included 143 patients with idiopathic DO (IDO) and 100 with neurogenic DO (NDO) who were untreated, well-treated, and failed-treated with antimuscarinics. Thirty-eight subjects without lower urinary tract symptoms served as controls. Detrusor injection of BoNT-A (100 U for IDO, 200 U for NDO) was given to 24 patients with IDO and 19 with NDO who had failed antimuscarinic treatment. Urine samples were obtained from controls and patients. Urinary NGF levels were measured by ELISA and normalized by urine creatinine level (NGF/Cr). The urinary NGF/Cr levels in controls and patients with DO at baseline and 3 mo after BoNT-A injection were compared. The mean urinary NGF/Cr levels were significantly higher in 66 patients with untreated IDO (mean+/-standard deviation, 1.44+/-2.66, p=0.000) and 59 with untreated NDO (0.62+/-1.22, p=0.000) compared to controls (0.005+/-0.019). Patients with well-treated IDO or NDO had reduced NGF/Cr levels, whereas those with failed-treated IDO or NDO did not. Patients who responded to BoNT-A treatment had significantly reduced urinary NGF/Cr levels in both the IDO (0.07+/-0.12, p=0.025) and NDO (0.096+/-0.17, p=0.033) groups compared to baseline levels. However, the NGF levels remained significantly higher at 3 mo in 7 IDO (1.01+/-1.25) and 5 NDO (1.64+/-2.39) patients who failed BoNT-A treatment. The major limitation of this study is the wide deviation of the urinary NGF levels and lack of age controls. Urinary NGF level is a sensitive biomarker for the diagnosis of IDO and NDO and can be used as a tool to evaluate the therapeutic effect of detrusor BoNT-A injection.

Acute Effect of Posterior Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Patients with Multiple Sclerosis: Urodynamic Study

The aim of this study was to determine the acute urodynamic effects of posterior tibial nerve stimulation (PTNS) in patients with neurogenic detrusor overactivity (NDO) caused by multiple sclerosis (MS). A total of 29 patients of whom there were 12 (41.3%) men and 17 (58.6%) women with NDO, mean age 46.5 +/- 8.5 years (range 29 to 55 years) enrolled in the study. Mean duration of MS was 8.80 +/- 3.6 years; duration of urinary disorder was 4.3 +/- 1.8 years. The expanded disability status scale (EDSS) of the study was detected 4.8 +/- 1.9. Urodynamic studies before and during PTNS were performed. Electrical stimulation was applied unilaterally from the medial malleolus and posterior to the edge of the tibia by using charge-compensated 200 microsecond pulses with a pulse rate of 20 Hz. Mean first involuntary detrusor contractions and mean maximum cystometric capacity before and during PTNS were compared. Mean first involuntary detrusor contraction on standard cystometry was 138.34 +/- 6.36 mL (60 to 225 mL), whereas it was 230.48 +/- 8.89 mL (145 to 375 mL) during PTNS. Mean maximum cystometric capacity on standard cystometry was 193.93 +/- 9.90 mL (110 to 304 mL), whereas it was 286.48 +/- 9.09 mL (221 to 376 mL) during stimulation. The improvements in the first involuntary detrusor contraction and maximum cystometric capacity were statistically significant during stimulation (P <0.001). The difference of mean first involuntary detrusor contraction volume and mean maximum cystometric capacity at baseline and after PTNS was statistically significant (P <0.001). These results have demonstrated the objective effect of acute PTNS on urodynamic parameters. PTNS is effective to suppress detrusor overactivity in MS patients.

EFFECTS OF POTASSIUM CHANNEL MODULATORS ON MYOGENIC SPONTANEOUS PHASIC CONTRACTILE ACTIVITY IN HUMAN DETRUSOR FROM NEUROGENIC PATIENTS

OBJECTIVE To characterize the spontaneous contractile activity (SCA) developed by detrusor from patients with neurogenic detrusor overactivity (NDO) because the alteration of detrusor properties plays a critical role in the pathogenesis of detrusor overactivity, as well as to evaluate the role of KATP and KCa channels on this SCA because these channels regulate detrusor SCA in many species, including humans without overactive bladder (OAB). PATIENTS AND METHODS Human bladder samples were obtained from 44 patients undergoing cystectomy for bladder cancer with no known OAB symptoms and from 38 patients suffering from urodynamically diagnosed NDO. Detrusor strips with or without urothelium/suburothelium were mounted isometrically in organ baths filled with Krebs-HEPES (37 °C; 95% O2/5% CO2). Strips were incubated with 10 µm pinacidil (KATP opener) followed by 10 µm glibenclamide (KATP blocker). In another set of experiments, strips were incubated with 30 µm NS-1619 (BKCa opener) followed by 100 nm iberiotoxin (BKCa blocker) or with 100 nm apamin (SKCa blocker). RESULTS SCA occurred more frequently with larger amplitude and area under the curve in detrusor strips from NDO patients compared to control patients. The presence of urothelium/suburothelium did not significantly modify SCA in either patient population. Pinacidil markedly inhibited SCA of detrusor strips from control and NDO patients. This effect was reversed by glibenclamide. By contrast, NS-1619 followed by iberiotoxin did not elicit any significant changes in SCA from NDO patients, contrary to control patients. CONCLUSIONS KATP and SKCa channels regulate SCA of NDO patients’ detrusor strips. By contrast, BKCa channels are not involved in the regulation of detrusor SCA in NDO patients, whereas they regulate SCA in control patients. These results should be considered in the development of K+ channels openers for the treatment of NDO. Moreover, SCA observed in vitro should be regarded as an in vitro modelling of human NDO.

Acute Urodynamic Effects of Posterior Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Patients with MS

ObjectivesThe aim of this study was to investigate whether acute electrical stimulation of the posterior tibial nerve could suppress detrusor contractions in multiple sclerosis (MS) patients with neurogenic detrusor overactivity. MethodsTwo successive slow-fill cystometries (16ml/min) were carried out in eight MS patients with neurogenic detrusor overactivity. The first filling served as control without stimulation. In the second filling, electrical stimulation using needle electrodes was applied automatically to the posterior tibial nerve when the detrusor pressure exceeded 10cm H2O. An additional filling in which the needle electrodes were replaced by surface electrodes was carried out in three patients. ResultsThe control filling showed detrusor overactivity in eight patients, but electrical stimulation of the posterior tibial nerve failed to suppress detrusor contractions in all tested patients. ConclusionsAlthough neuromodulative effects may be obtained with therapeutic electrical stimulation of the posterior tibial nerve, no acute effects were demonstrated. For this reason, electrical stimulation of pudendal afferents remains the only option if acute suppression of a detrusor contraction is required.

Botulinum toxin‐type A in the treatment of drug‐resistant neurogenic detrusor overactivity secondary to traumatic spinal cord injury

To assess, in a prospective study, whether botulinum toxin-type A (BTX-A) injected into the detrusor muscle, can be used as a day-case treatment for drug-resistant neurogenic detrusor overactivity (NDO) in patients with spinal cord injury (SCI). BTX-A (Dysport, Ipsen, Luxembourg; 1000 units) was injected cystoscopically into the detrusor muscle of 37 patients with drug-resistant NDO and SCI, as a day-case procedure. The maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), NDO, continence, and anticholinergic requirement were used as outcome variables. The International Consultation on Incontinence questionnaire (ICIQ) was used to assess the patient's quality of life before and after the BTX-A injection. The mean follow-up was 7 months. The MCC increased from a mean of 259 to 522 mL, and the MDP decreased from a mean of 54 to 24 cmH2O. Incontinence and NDO were abolished in 82% and 76% patients, respectively. In all, 86% of the patients were able to stop or reduce anticholinergics, with a similar proportion of patients scoring favourably on the ICIQ. The mean duration of improvement was 9 months. Injection with BTX-A is an effective day-case treatment that bridges the gap between oral and invasive surgical treatment of drug-resistant NDO in patients with SCI.

Managing Patients with Neurogenic Detrusor Overactivity—A Global Approach

Patients with neurogenic detrusor overactivity (NDO) usually have other disorders or disabilities, in addition to bladder dysfunction, that require treatment. A number of different medical specialists are, therefore, involved in the management of an individual patient and may well be working towards different treatment goals. This, together with the possible impact on NDO of treatments for other disabilities and vice versa, means that a global approach to management of a given patient is needed to ensure that patients receive the best possible treatment for all their conditions. This is particularly true for treatments that are used for multiple indications in the same patient, such as botulinum toxin, which has been used for many years as an effective treatment for dystonia and spasticity, and has more recently shown promise in the treatment of NDO and idiopathic detrusor overactivity. The appropriate choice of total dose and staging of dosing is required to maximise safety and efficacy in both indications. Development of multidisciplinary treatment algorithms for the various types of NDO patients could help to promote a global approach to the management of these individuals and to optimise their care.

Event driven electrical stimulation of the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in multiple sclerosis

The aim of this study was to evaluate the effect of automatic event driven electrical stimulation on the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in patients suffering from Multiple Sclerosis. A total of 10 patients participated in the study. Detrusor pressure was recorded during physiological filling of the bladder and electrical stimulation was applied with surface electrodes whenever the detrusor pressure exceeded 10 cm H(2)O. In seven of the eight patients, where neurogenic detrusor overactivity was observed an average of 12 detrusor contractions could be inhibited by stimulation. In one patient, however, stimulation failed to inhibit the detrusor contractions. The average increase in bladder volume from first suppressed detrusor contraction until leakage was 94% (range: 22-366%). On average, the time from first suppressed contraction until leakage was 15 min and 50 sec (range: 4 min 58 sec-32 min 5 sec) with an average physiological filling rate of 8 ml/min. Urgency was effectively suppressed at the onset of stimulation. The results indicate that involuntary detrusor contractions in patients with multiple sclerosis can effectively be inhibited with event driven stimulation, hereby improving bladder capacity and reducing the number of incontinence episodes. However, the used method for detecting detrusor contractions is not suitable in a chronic setting and alternative techniques needs to be investigated if stimulation should be applied automatically.

Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: A double blind controlled randomized study

Many studies report the use of alcoholic capsaicin instillation to treat neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple sclerosis (MS) patients. However, poor tolerability due to the irritative effect of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy and tolerability of a new formulation of capsaicin in a glucidic solution in a multicenter clinical trial. Thirty-three patients (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were prospectively enrolled in a double-blind placebo controlled study and randomized to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively received an intravesical instillation of 100 ml capsaicin diluted in glucidic solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30 and 90. On D0, groups were homogeneous. On D30, significant improvement of overactive bladder syndrome and an increase in MCC were shown in CG, whereas there were no improvement in SG. No significant improvement was shown on D90 in both groups. There were no significant differences between groups regarding prevalence, duration, or intensity of side effects, except for short duration pubic pain during instillation more often reported in CG (58.8%) than in SG (12.5%) (P < 0.01). This placebo controlled study using glucidic capsaicin confirms its short-term efficacy in NDO patients. Global tolerance of glucidic capsaicin appeared satisfactory. Long-term efficacy and tolerance of repeated glucidic capsaicin instillations need to be evaluated.

Botulinum Toxin Type A Injections for Treating Neurogenic Detrusor Overactivity Combined With Low-Compliance Bladder in Patients With Spinal Cord Lesions

Klaphajone J, Kitisomprayoonkul W, Sriplakit S. Botulinum toxin type A injections for treating neurogenic detrusor overactivity combined with low-compliance bladder in patients with spinal cord lesions. Objective To evaluate botulinum toxin type A (BTX-A) for treating neurogenic detrusor overactivity in patients with spinal cord lesions, including those with abnormally low bladder compliance. Design Nonrandomized, before-after trial (9-mo follow-up). Setting Hospitalized care. Participants Ten patients with high detrusor contraction pressure and/or poor response to oxyphencyclimine with incontinence selected as a consecutive sample. Intervention BTX-A (Botox; 300U) was injected into the detrusor muscle. Main Outcome Measures Urinary continence, functional bladder capacity, bladder compliance, detrusor contraction pressure, and volume at first reflex voiding. Measurements were taken before and 6, 16, and 36 weeks posttreatment. Results Six weeks after treatment, complete continence was restored in 7 patients without oxyphencyclimine. Mean functional bladder capacity ( P=.008), compliance ( P=.012), and reflex volume ( P=.045) significantly increased, whereas maximal detrusor contraction pressure significantly decreased ( P<.001). Urodynamic variables remained significantly improved at 16 weeks, but values were returning toward baseline levels by 36 weeks. The procedure was generally uneventful, without any serious side effects. Conclusions BTX-A injections are an effective, well-tolerated treatment for neurogenic detrusor overactivity in patients with spinal cord lesions, even in patients with abnormally low bladder compliance. Patients may require repeat injections after 16 weeks to remain continent.

INTRAOPERATIVE RECORDING OF ELECTRONEUROGRAPHIC SIGNALS FROM CUFF ELECTRODES ON EXTRADURAL SACRAL ROOTS IN SPINAL CORD INJURED PATIENTS

A safe and reliable method for monitoring intravesical pressure on a long-term basis is needed for conditional electrical stimulation to be feasible as a treatment option for neurogenic detrusor overactivity in patients with a spinal cord injury. Therefore, we investigated the possibility of recording afferent nerve activity related to mechanical activity of the bladder and other pelvic organs from the extradural sacral nerve root in human. Nerve cuff electrodes were temporary placed on the extradural S3 sacral root in 6 spinal cord injured patients who underwent implantation of an extradural FineTech-Brindley Bladder System (Finetech Medical Lt., Welwyn Garden City, United Kingdom). The dorsal penile/clitoral nerve was electrically stimulated to evoke compound action potentials. Electroneurographic signals were recorded together with bladder and rectal pressure during mechanical stimulation of the dermatome rapid bladder filling and rectal distention, and during bladder contraction evoked by electrical stimulation of the contralateral sacral root. Compound action potentials and electroneurographic responses during stimulation of the dermatome and rectum were present in all 6 patients and during bladder filling in 5 of 6. However, recorded responses from the bladder and rectum were small and mainly phasic in nature. Nerve responses following bladder contractions were present in 4 of 5 stimulated patients. Afferent nerve activity from the dermatome, bladder and rectum can be recorded using cuff electrodes placed on the extradural S3 sacral root in humans but improvements in recording quality and sophisticated signal processing methods are needed for chronic application.