Mean Reflex Volume Research Articles

Effect of intravesical botulinum neurotoxin-A injection on detrusor hyperreflexia in spinal cord injured patients.

To evaluate the effects of Botulinum Toxin A injection into the detrusor muscle on various voiding parameters in spinal cord injured patients with neurogenic detrusor hyperreflexia Materials and methods: 24 patients with spinal cord injuries who had detrusor overactivity and urinary incontinence and were refractory to oral medications, were injected 300 IU of BTX-A into the detrusor muscle. The pre-and post-treatment evaluations included determination of bladder urinary continence status, frequency/volume chart of CIC, Incontinence Quality of Life questionnaire (I-QOL) and patient satisfaction. The urodynamic parameters measured included maximum cystometric capacity (MCC), reflex detrusor volume (RDV) and maximum detrusor pressure during bladder contraction (MDP) were analyzed at the outset and during the follow-up (2, 6, and 24 weeks) examinations. The evaluation of urodynamic parameters during follow-up examinations (2, 6 and 24 weeks) revealed significant increase in mean reflex volume (p<0.05) and cystometric capacity (p<0.05), on the other detrusor pressure decreased significantly (p<0.05). In majority of patients there was considerable reduction in incontinence episodes and no complications or side effects were reported. Most of the patents were satisfied with the treatment. The use of Botulinum toxin type A for treatment of neurogenic detrusor overactivity in spinal cord injured patients is safe and efficacious. In our 24-week study period, there was significant improvement in most urodynamic parameters with consistence and subjective satisfaction indicated by the treated patients.

Injections of Botulinum Toxin A into the detrusor to treat neurogenic detrusor overactivity secondary to spinal cord injury

To present a comprehensive experience of botulinum toxin A (BTX-A) injected into the detrusor muscle in patients with spinal cord injuries (SCI) causing neurogenic detrusor overactivity. Three hundred units of BTX-A were injected cystoscopically into the detrusor muscle of 108 patients with neurogenic detrusor overactivity secondary to SCI at 30 different locations. Evaluations were performed before the injections and 6 weeks after, and they included determination of bladder urinary continence status, frequency/volume chart of CIC, concomitant anticholinergic medication use, Incontinence Quality of Life questionnaire (I-QOL) and patient satisfaction. Key urodynamic parameters (reflex volume, maximum detrusor pressure during voiding, detrusor compliance and maximum cystometric capacity) were analyzed at the outset and during the follow-up (6, 12 and 36 weeks) examinations. By the time of the urodynamic follow-up examinations (6, 12 and 36 weeks), the mean cystometric capacity (P < 0.05) and the mean reflex volume (P < 0.05) increased significantly, while the mean voiding pressure (P < 0.05) decreased significantly. No complications or side effects were reported. Most patients considerably reduced or even stopped taking anticholinergic drugs and were satisfied with the treatment. This retrospective study indicates that BTX-A injections into the detrusor muscle to treat neurogenic detrusor overactivity secondary to SCI are safe and valuable. Significant improvement of bladder function corresponded with continence and subjective satisfaction indicated by the treated patients.

Intravesical Electromotive Botulinum Toxin Type A Administration—Part II: Clinical Application

To assess the effect of electromotive botulinum toxin type A administration on urodynamic variables, urinary/fecal incontinence, and vesicoureteral reflux (VUR) due to refractory neurogenic detrusor overactivity in children with myelomeningocele. A total of 15 children (mean age 7.8 years) were included. Using a specially designed catheter, 10 IU/kg of electromotive botulinum toxin type A was inserted into the distended bladder. While connected to the indwelling catheter and 2 dispersive pads, a pulsed current generator delivered 10 mA for 15 minutes. The urodynamic parameters, including reflex volume, maximal bladder capacity, maximal detrusor pressure, and end-fill pressure, and the urinary/fecal incontinence status and VUR grade were evaluated before and at 1, 4, and 9 months after treatment. The mean reflex volume and maximal bladder capacity had increased considerably (99 ± 35 mL versus 216 ± 35 mL and 121 ± 39 mL versus 262 ± 41 mL, respectively; P < .001). In contrast, the mean maximal detrusor pressure and end-fill pressure had significantly decreased (75 ± 16 cm H(2)O versus 39 ± 10 cm H(2)O and 22 ± 7 cm H(2)O versus 13 ± 2 cm H(2)O) after treatment. The difference was statistically significant (P < .001). Urinary incontinence improved in 12 patients (80%). The VUR grade substantially decreased in 7 of the 12 children (mean VUR grade 2.25 ± 1.3 versus 1.37 ± 0.7; P = .001), and none of the children required surgical intervention. Fecal incontinence was alleviated in 10 (83.3%) of the 12 children. Skin erythema and burning sensation were observed in 6 children. The results of our study have shown that electromotive botulinum toxin type A administration is a feasible and safe method with no need for anesthesia. This novel delivery system resulted in considerable improvement in the urodynamic parameters, urinary/fecal incontinence, and VUR in patients with refractory neurogenic detrusor overactivity.

Evaluación urodinámica de la eficacia de la toxina botulínica en el detrusor hiperactivo neurogénico refractairo

Proper treatment of neurogenic hyperactive detrusor muscle is responsible for several features essential for life such as renal function, and quality of life relevant issues such as urinary incontinence. Anticholinergic drugs allow treatment in most cases, but their failure in cases of refractory neurogenic hyperactive detrusor is a challenge. To evaluate the efficacy of detrusor injection of type A botulin toxin in patients with refractory neurogenic hyperactive detrusor, on the following urodynamic parameters: maximum cystomanometric capacity, detrusor compliance, reflex volume, maximum detrusor pressure and post void residual. Prospective study in 16 patients with the diagnosis of neurogenic hyperactive detrusor refractory to anticholinergic therapy. Urodynamic studies were performed 30 and 60 days before the procedure and after at least two weeks from stopping anticholinergic therapy. 300 units of type A botulin toxin (BTX-A) were endoscopically injected in 30 punction sites, 10 units per ml each punction. Urodynamic control was performed 30 to 45 days after injection. Six of the 16 patients in the study where females and 11 males; mean age was 39.5 years (22 to 63 years). Urodynamic results: mean maximum capacity on cystomanometry before BTXA was 204.73 ml and after BTX-A 381.87 ml. Maximum detrusor capacity before was 91.46 H2O cm whereas post-treatment was 41.2 H2O cm. Mean final filling pressure was 68 H2O cm before treatment and 34 H2O cm after. Mean reflex volume was 111.33 ml before and 310.8 ml after. Finally, mean post void residual before BTX-A was 129.6 ml whereas post-BTX-A was 345.9 ml. The injection of 300 U of type A botulin toxin in the detrusor muscle has demonstrated to be effective and safe for the treatment of refractory neurogenic hyperactive detrusor. There were statistically significant differences in the urodynamic parameters before and after the injection. There were no significant adverse events.

Experience With 100 Cases Treated With Botulinum-A Toxin Injections in the Detrusor Muscle for Idiopathic Overactive Bladder Syndrome Refractory to Anticholinergics

In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.

Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: a prospective analysis

To evaluate prospectively the efficacy and tolerability of propiverine for treating neurogenic detrusor overactivity (NDO) in children. Twenty children (mean age 8.9 years; median 5.6) with NDO due to an upper motor neurone lesion were enrolled (17 had myelomeningocele). In the urodynamic examination, reflex volume (RV), maximum detrusor pressure (MDP), maximum cystometric bladder capacity (MCBC) and bladder compliance (BC) before and after a twice-daily propiverine hydrochloride regimen were determined. The urodynamic follow-up was after 3-6 months. Incontinence was assessed by an incontinence score. The mean (sem) RV increased from 103.8 (21.3) to 174.5 (33.7) mL (P < 0.005), MDP decreased from 52.5 (7.9) to 40.1 (6.2) cmH(2)O (P < 0.05), MCBC increased from 166 (28.8) to 231.9 (34.8) mL (P < 0.005), and BC improved from 11.2 (2.8) to 30.6 (9.7) mL/cmH(2)O (P < 0.01), with propiverine treatment. The incontinence score (scale 0-3) improved from 2.4 (0.2) to 1.6 (0.3) (P < 0.05). Propiverine was well tolerated, although some children were given higher doses than recommended. Propiverine hydrochloride is effective and well tolerated in the treatment of children with NDO. Because of its dual mode of action, it is well tolerated even in children who need higher doses. Propiverine hydrochloride is a preferable alternative to oxybutynin, the anticholinergic most frequently used in children with NDO to date.

Effect of the intravesical resiniferatoxin instillation evaluated by the ice provocative urodynamic study

Prospective urodynamic investigation before and after intravesical resiniferatoxin instillation treatment. To evaluate the effectiveness of intravesical resiniferatoxin instillation for the treatment of neurogenic detrusor overactivity (NDO), using conventional and ice provocative urodynamic studies to monitor the activity of the unmyelinated C-fiber. Spinal Cord Injury Unit, Yonsei Rehabilitation Hospital, Seoul, Korea. A measure of 100 ml of resiniferatoxin solution, at a concentration of 100 nM diluted in 10% ethanol, was intravesically instilled into the bladder of 15 spinal cord injury patients with NDO. Conventional and ice provocative urodynamic studies were performed to evaluate the change in the involuntary detrusor activity, reflex volume, maximal bladder capacity, compliance, maximal detrusor pressure and reflex volume ratio 7 days before and 30 days after the instillation. Before the intravesical resiniferatoxin instillation, all patients exhibited NDO in both the conventional and ice provocative urodynamic studies, with a mean reflex volume ratio of 0.45+/-0.22. There was no significant change in the maximal bladder capacity, compliance and maximal detrusor pressure at the follow-up urodynamic study, but the reflex volume ratio was significantly increased (P<0.05) after the intravesical resiniferatoxin instillation. Among the 15 patients, three (20%) showed complete and nine (60%) partial suppression of the unmyelinated C-fiber activities. Intravesical resiniferatoxin instillation was partially controlled by the unmyelinated C-fiber activities, which were estimated by an ice provocative urodynamic study. Therefore, further studies on the optimal dosage and accurate indications for resiniferatoxin instillation are required.

European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity.

To present a comprehensive experience with botulinum-A toxin (BTA) injected into the detrusor muscle in patients with spinal cord injuries/diseases causing neurogenic incontinence. Ten European medical centers provided the results of 231 patients with neurogenic detrusor overactivity who were treated with BTA. 300 units of Botox (Allergan Inc.) were injected cystoscopically into the detrusor muscle at 30 different locations, while sparing the trigonum. Urinary continence status, concomitant anticholinergic medication use and patient satisfaction were recorded. Key urodynamic parameters (reflex volume, maximum detrusor pressure during voiding, detrusor compliance and maximum cystometric bladder capacity) at baseline and at the first and second urodynamic follow-up examinations were analyzed. By the time of the initial (mean 12 weeks after injection) as well as at the second urodynamic follow-up examinations (mean 36 weeks after injection), the mean cystometric bladder capacity (p < 0.0001) and the mean reflex volume (p < 0.01) increased significantly, while the mean voiding pressure (p < 0.0001) decreased significantly. The mean bladder compliance had increased significantly (p < 0.0001) by the first follow-up examination and non-significantly by the time of the second follow-up. No injection related complications or toxin related side effects were reported. The patients considerably reduced or even stopped taking anticholinergic drugs without recurrence of reflex incontinence and were satisfied with the treatment. This retrospective European multicenter study presents the most extensive experience to date with BTA injections into the detrusor muscle to treat neurogenic incontinence due to detrusor overactivity and confirms that this new treatment is safe and valuable. Significant improvement of bladder function corresponds with continence and the subjective satisfaction indicated by the treated patients.

Botulinum-a toxin detrusor injection as a novel approach in the treatment of bladder spasticity in children with neurogenic bladder.

Children with neurogenic hyper-reflexive bladder in whom classical therapy with anticholinergic drugs and intermittent catheterization fails are threatened by high intravesical pressure, vesicoureteral reflux, and impairment of kidney function. Surgery, such as bladder augmentation, is often necessary in such cases. To obviate surgery in these high-risk children, we investigated the use of detrusor injection of botulinum-A toxin (Botox). Our subjects were 20 children with hyper-reflexive detrusor muscle and high bladder pressure, over 40 cmH(2)O despite anticholinergic therapy. After baseline urodynamic measurements, we injected botulinum-A toxin into the detrusor muscle at 30-50 sites at 12 U/kg of body weight up to a maximum of 300 U. Follow-up cystometric measurements were taken two to four weeks and three and six months after injection. From basic measurements to follow-up cystometry, mean reflex volume changed from 97.1 ml before injection to 178.6 ml after four weeks (p<0.01) and to 162.8 ml after three months (p<0.01). After six months mean reflex volume returned to 119.3 ml (n.s.). Maximal bladder capacity changed from 163.1 ml to 219.9 ml (p<0.01), to 200.6 ml (p<0.01) and to 222.4 ml (p<0.01), respectively, and maximal detrusor pressure changed from 59.6 cmH(2)O to 34.9 cmH(2)O (p<0.01), to 46.7 cmH(2)O (n.s.) and to 61.8 cmH(2)O (n.s.), respectively. Botulinum-A toxin (Botox) is effective when injected into the hyper-reflexive detrusor muscle. It is a valuable treatment option in the management of neurogenic bladder. The effect lasts about six months, and then reinjection is necessary.

Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results

Objectives.The established treatment of children with neurogenic bladder consists of the use of anticholinergic drugs, such as oxybutynin and tolterodine, and clean intermittent catheterization four or five times a day. If anticholinergic drugs and clean intermittent catheterization fail, surgery is often necessary. With the intent of avoiding surgery, we investigated the effect of botulinum-A toxin for treating detrusor hyperreflexia in this group of patients.Methods.The subjects were 17 children (average age 10.8 years) who had detrusor hyperreflexia and were using clean intermittent catheterization four or five times a day. Urodynamic studies were followed by injection of 85 to 300 U of botulinum-A toxin into 30 to 40 sites in the detrusor muscle. Urodynamic follow-up was done 2 to 4 weeks after injection.Results.The mean reflex volume increased by 112.1%, from 95.00 ± 34.54 mL (range 47 to 147) to 201.45 ± 68.57 mL (range 77 to 310) (P <0.005). The maximal bladder capacity increased by 56.5%, from 137.53 ± 59.96 mL (range 59 to 242) to 215.25 ± 96.36 mL (range 60 to 380) (P <0.005). The maximal detrusor pressure decreased by 32.6%, from 58.94 ± 32.32 cm H2O (range 19 to 149) to 39.75 ± 26.12 cm H2O (range 7 to 100) (P <0.005). Detrusor compliance increased by 121.6%, from 20.39 ± 26.5 mL/cm H2O (range 4.5 to 40) to 45.18 ± 45.4 mL/cm H2O (range 5.3 to 100) (P <0.01).Conclusions.Botulinum-A toxin injection into the hyperreflexive detrusor muscle seems to be very effective and might be a therapeutic alternative to anticholinergic drugs.

Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results.

We evaluated the efficacy of botulinum-A toxin injections into the detrusor muscle in patients with spinal cord injury, detrusor hyperreflexia and urge incontinence resistant to anticholinergic drugs. The purpose of treatment was to suppress incontinence episodes and increase functional bladder capacity. Included in our prospective nonrandomized study done at 2 clinics were 31 patients with traumatic spinal cord injury who emptied the bladder by intermittent self-catheterization. These patients had severe detrusor hyperreflexia and incontinence despite a high dose of anticholinergic medication. Pretreatment evaluation included a clinical examination and complete urodynamic investigation. Under cystoscopic control a total of 200 to 300 units of botulinum-A toxin were injected into the detrusor muscle at 20 to 30 sites (10 units per ml. per site), sparing the trigone. Clinical and urodynamic followup was planned for 6, 16 and 36 weeks after treatment. Patients were asked to decrease their intake of anticholinergic drugs during week 1 after treatment. Of the 21 patients 19 underwent a complete examination 6 weeks after the botulinum-A toxin injections, and 11 at 16 and 36 weeks. At the 6-week followup complete continence was restored in 17 of 19 cases in which anticholinergic medication was markedly decreased or withdrawn. Less satisfactory results in 2 cases were associated with an insufficient dose of 200 units botulinum-A toxin. After the injections overall mean reflex volume and mean maximum cystometric bladder capacity plus or minus standard deviation significantly increased from 215.8 +/- 90.4 ml. to 415.7 +/- 211.1 (p <0.016) and 296.3 +/- 145.2 to 480.5 +/- 134.1 (p <0.016), respectively. There was also a significant decrease after treatment in mean maximum detrusor voiding pressure from 65.6 +/- 29.2 cm. water to 35 +/- 32. 1 (p <0.016). Mean post-void residual urine volume catheterized at the end of the urodynamic examination increased significantly from a mean of 261.8 +/- 241.3 ml. to 490.5 +/- 204.8 (p <0.016). Moreover, autonomic dysreflexia associated with bladder emptying that manifested as a hypertensive crisis during voiding disappeared after treatment in the 3 patients with tetraplegia. Satisfaction was high in all successfully treated patients and no side effects were observed. Ongoing improvement in urodynamic parameters and incontinence was already present in all patients reevaluated at 16 and 36 weeks. Botulinum-A toxin injections into the detrusor seem to be a safe and valuable therapeutic option in spinal cord injured patients with incontinence resistant to anticholinergic medication who perform clean intermittent self-catheterization. Successfully treated patients become continent again and may withdraw from or markedly decrease anticholinergic drug intake. A dose of 300 units botulinum-A toxin seems to be needed to counteract an overactive detrusor. The duration of bladder paresis induced by the toxin is at least 9 months, when repeat injections are required.