Capsaicin and neurogenic detrusor hyperreflexia: A double-blind placebo-controlled study in 20 patients with spinal cord lesions

The aim of this study was to investigate the efficacy and tolerance of capsaicin, a neurotoxin for C-fiber afferents, applied intravesically in the treatment of detrusor hyperreflexia. Eleven male and nine female patients who had spinal cord lesions caused by multiple sclerosis (12) or trauma (eight) resulting in detrusor hyperreflexia with urge incontinence and pollakiuria were randomized to receive one intravesical instillation of either 30 mg capsaicin in 100 ml 30% ethanol or 100 ml 30% ethanol alone. The patients were evaluated clinically (voiding diary) and urodynamically (maximum cystometric capacity, maximum detrusor pressure, first and normal desire to void) before and 30 days after the instillation. On day 30, the 10 patients who received capsaicin had significant decreases in 24-h voiding frequency from 9.3 ± 6.1 to 6.7 ± 3.8 (P = 0.016) and leakages from 3.9 ± 1.6 to 0.6 ± 0.8 (P = 0.0008); their maximum cystometric capacity increased from 169 ± 68 to 299 ± 96 ml (P = 0.01) and maximum detrusor pressure decreased from 77 ± 24 to 53 ± 27 cm H₂O. There were no significant changes in the control group. In seven subjects in each group, instillation triggered immediate side effects (suprapubic pain, sensory urgency, flushes, hematuria, autonomic hyperreflexia) that resolved within 2 weeks. Intravesical capsaicin significantly improves clinical and urodynamic parameters of detrusor hyperreflexia in spinal cord–injured patients. Side effects are frequent, tolerable, and identical to those induced by 30% ethanol alone. Neurourol. Urodynam. 17:513–524, 1998. © 1998 Wiley-Liss, Inc.     

Detrusor hyperreflexia in neurogenic bladder disorders caused by localized partial lesions of the spinal cord and cauda equina

In 70 patients studied by cystometry, detrusor hyperreflexia seen with localized partial lesions of the spinal cord and cauda equina could be differentiated into two types. In one type, in which the hyperreflexia was of a reflex nature and bladder compliance was unchanged, the detrusor contractility was described as compliant hyperreflexic. In the other type, in which the contractions were of a rhythmic nature and accompanied by reduced compliance, the contractility of the detrusor was described as noncompliant hyperreflexic. The compliant hyperreflexic contractions correlated well with signs of upper motor neuron disturbance, the noncompliant hyperreflexic contractions with lower motor neuron disturbance.     

Micturitional Reflexes in Chronic Spinalized Cats: The Underactive Detrusor and Detrusor-Sphincter Dyssynergia

We studied micturitional reflexes in 46 unanesthetized adult male cats spinalized at C5-C6 17 to 125 days previously and in eight intact central nervous system chloralosed cats that were used as controls. Urethral pressure profiles, cystosphincterograms with the urethrovesical junction opened and closed, and mechanograms of detrusor and circular and longitudinal urethral muscles were performed. The effect of vesical, urethral, pelvic, or pudendal anesthesia and vesical and urethral mechanical stimulation were studied. Our results suggest that spinalization produces two major types of neurourologic disorders: (1) weakness of detrusor contractor reflexes (vesicovesical and urethrovesical contraction reflexes) and (2) exaggeration of urethral contractor reflexes (urethrourethral contraction reflex, guarding reflex). Secondarily the weakness of detrusor contractions diminishes the efficiency of the urethral reflex relaxation needed for voiding (vesicourethral relaxation reflex). Because of these abnormalities, two main syndromes appear: (1) underactive detrusor function and (2) detrusor sphincter dyssynergia. Isolated peripheral manipulations of the bladder or urethra do not improve micturition: (1) increase in detrusor contraction strength induces detrusor sphincter dyssynergia, and (2) relaxation of the external sphincter facilitates voiding, but urinary retention persists. It is proposed that spinalization produces a central micturitional dysreflexia responsible for the peripheral dysfunction, and treatment must be oriented toward the central dysreflexia rather than the peripheral dysfunction.     

Detrusor Areflexia in a Patient with Myasthenia Gravis

Myasthenia gravis (MG) is a common neuromuscular disorder, however, voiding dysfunction in conjunction with MG is rare. A review of the literature yielded only 7 prior reports of such a combination. Most of the reported cases involved incontinence in males which developed after a transurethral resection of the prostate. Only 3 cases described de novo voiding dysfunction. We report a fourth patient. In all 4 cases of de novo dysfunction, the voiding problem either heralded a new diagnosis of MG or an exacerbation of the disease process. It is hypothesized that autonomic dysfunction in patients with MG might indicate a unique subset with a worse prognosis.     

Anticholinergic Drugs for Adult Neurogenic Detrusor Overactivity: A Systematic Review and Meta-analysis

Context

There is a lack of evidence about the efficacy and safety of anticholinergic drugs and about the optimal anticholinergic drug, if any, for the treatment of adult neurogenic detrusor overactivity (NDO).

Objective

Review the current evidence on the efficacy, safety, and tolerability of anticholinergic drugs in the treatment of adult NDO.

Evidence acquisition

A literature search was conducted from 1966 to May 2011. Meta-analysis of all published randomised controlled trials (RCTs) comparing anticholinergic drugs with placebo and comparing different types, doses, and routes of administration of anticholinergic drugs, in adults with NDO, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The primary outcome was patient-reported cure/improvement of overactive bladder symptoms. Secondary outcomes were quality of life (QoL) changes, bladder diary events, urodynamic outcomes, adverse events, and costs to health services.

Evidence synthesis

A total of 960 patients from 16 RCTs with mean follow-up of 3.8 wk were included. Anticholinergic drugs were associated with statistically significantly better patient-reported cure/improvement (risk ratio: 2.80; 95% confidence interval [CI], 1.64 to 4.77), higher maximum cystometric capacity (weighted mean difference [WMD]: 49.49; 95% CI, 15.38 to 84.20), higher volume at first contraction (WMD: 49.92; 95% CI, 20.06 to 79.78), and lower maximum detrusor pressure (WMD: −38.30; 95% CI, −53.17 to −23.43) when compared with placebo. The dry-mouth rates were statistically significantly higher with anticholinergics, with no difference in withdrawals because of adverse events. There was no statistically significant difference in any of the outcomes between oxybutynin and other anticholinergics or among different doses and preparations of anticholinergic drugs. No study reported QoL changes or costs to health services.

Conclusions

Compared with placebo, anticholinergic treatment in patients with NDO is associated with better patient-reported cure/improvement and significant reduction of maximum detrusor pressure; however, there is a higher incidence of adverse events. None of the anticholinergic drugs or different dosages assessed in this review was superior to another.     

Perioperative autonomic hyperreflexia in high spinal cord lesions: a case report

We report the case of a 20-year-old man with serious perioperative attacks of autonomic hyperreflexia starting during urological surgery 14 months after a complete C6-C7 spinal cord injury. The intraoperative attacks were controlled by deepening the level of anaesthesia, while the postoperative attacks were treated with emepronium bromide. A brief discussion of the pathophysiology and treatment is given.     

Electrical sphincter stimulation in the treatment of detrusor hyperreflexia of paraplegics

Strong anal stimulation at the onset of the vesical pressure increase during an uninhibited bladder contraction prevented further bladder pressure increase and urine loss in 11 out of 15 paraplegics; 5 Hz, 10-Hz and 20—Hz stimuli were equally effective. This effect is probably a spinal reflex. In the acute experiments, stimulation of the peroneal or anterior tibial nerve was without effect on bladder pressure.     

Efficacy and safety of oxybutynin in children with detrusor hyperreflexia secondary to neurogenic bladder dysfunction

PURPOSE: We evaluated the efficacy and safety of oxybutynin in children with detrusor hyperreflexia due to neurological conditions. MATERIALS AND METHODS: Study 1--A prospective, open label trial of 3 formulations of oxybutynin (tablets, syrup and extended release tablets) was conducted for 24 weeks in children 6 to 15 years old with detrusor hyperreflexia who used oxybutynin and clean intermittent catheterization. The effect of treatment on average urine volume per catheterization and on secondary urodynamic outcomes was evaluated. Study 2--The efficacy and safety of oxybutynin syrup were evaluated urodynamically in an open label study of children 1 to 5 years old with detrusor hyperreflexia who used oxybutynin and clean intermittent catheterization. RESULTS: Study 1--Mean urine volume per catheterization (+/- SEM) increased by 25.5 +/- 5.9 ml (p <0.001). Maximal cystometric capacity increased by 75.4 +/- 9.8 ml (p <0.001). Mean detrusor and intravesical pressures were significantly decreased by -9.2 +/- 2.3 (p < or =0.001) and -7.5 +/- 2.5 cm H2O (p <0.004), respectively, at week 24. Of 61 children with uninhibited detrusor contractions 15 cm H2O or greater at baseline 34 did not have them at week 24 (p <0.001). Improvements in bladder function were consistent across all oxybutynin formulations. Study 2--Mean maximal cystometric capacity increased significantly by 71.5 +/- 21.99 ml (p = 0.005). At study end only 12.5% of patients had uninhibited detrusor contractions 15 cm H2O or greater compared with 68.8% at baseline (p = 0.004). Oxybutynin was well tolerated in both studies. There were no serious treatment related adverse events. CONCLUSIONS: All 3 formulations of oxybutynin are safe and effective in children with neurogenic bladder dysfunction.     

Intravesical Capsaicin in Neurologic Impaired Patients With Detrusor Hyperreflexia

ABSTRACT

Capsaicin is known to be neurotoxic for C-fiber afferents. We investigated the intravesical application of capsaicin in the treatment of detrusor hyperreflexia (DH) in seven patients (ages 23–52) with neurologic impairment. The patients were evaluated with both ice-water cystometry and formal video-urodynamic studies. Four biweekly courses of intravesical capsaicin treatment were administered using increasing concentrations (100 μM, 500 μM, 1 mM and 2 mM). Treatment effect was monitored using a bladder diary and urodynamic evaluation one month after capsaicin treatment. Prior to treatment, six of the seven patients demonstrated a positive ice-water test and DH. Two patients were not able to complete the study due to discomfort attributed to capsaicin. Five of the seven patients completed the four courses of increasingly concentrated capsaicin. Three patients noted symptomatic improvement while two did not. The mean urodynamic bladder capacity significantly increased from 124±39 ml pre-capsaicin to 231 ±62 ml one month post-cap-saicin in the three patients with symptomatic improvement (p<0.05). Urodynamic testing revealed that one of the six patients with a positive ice-water test lost that response after intravesical capsaicin. Intravesical capsaicin is a novel and promising treatment for detrusor hyperreflexia in neurologically impaired patients. (J Spinal Cord Med 19:190–193)     

脊髓损伤患者的反射性排尿与自主神经过反射

Ｔ６以上脊髓损伤所致的截瘫或四肢瘫患者在损伤平面以下受到强烈刺激后，可引起自主神经过反射。为了明确膀胱叩击与自主神经过反射的关系，对１０例颈髓损伤四肢瘫和１０例Ｔ６以下脊髓损伤截瘫患者，测量安静时及膀胱充盈后连续叩击膀胱时的血压和心率，将所测得参数行统计学处理和比较。结果表明：四肢瘫病人在膀胱充盈后连续叩击膀胱可以引起反射性排尿，但也引起明显的自主神经过反射。通过反复试验，发现在髂前上棘与耻骨结节连线中点偏下处连续叩击腹壁可引起反射性排尿，但并不诱发自主神经过反射。     

Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study

PURPOSE: Chemical defunctionalization of C-fiber bladder afferents with intravesical vanilloids such as capsaicin (CAP) or resiniferatoxin (RTX) improves detrusor hyperreflexia in humans and animals. The little existing data comparing the efficacy and tolerance of these 2 vanilloid agents seem to favor RTX in 10% alcohol over CAP, which is usually diluted in 30% alcohol. We compared the efficacy and tolerability of the 2 vanilloid agonists in what to our knowledge is the first randomized, controlled study comparing nonalcohol CAP vs RTX in 10% alcohol in neurogenic patients with detrusor hyperreflexia. MATERIALS AND METHODS: This single center, randomized, double-blind, parallel groups study included 39 spinal cord injured adults with detrusor hyperreflexia. On day 0 patients were randomized to receive 1, 100 ml intravesical instillation of 100 nMol/l RTX diluted in 10% ethanol or 1 mmol/l CAP diluted in glucidic solvent. Efficacy (voiding chart and cystomanometry) and tolerability were evaluated during a 3-month followup. RESULTS: On day 30 clinical and urodynamical improvement was found in 78% and 83% of patients with CAP vs 80% and 60% with RTX, respectively, without a significant difference between the 2 treated groups. The benefit remained in two-thirds of the 2 groups on day 90. There were no significant differences in regard to the incidence, nature or duration of side effects in CAP vs RTX treated patients. CONCLUSIONS: Our results strongly argue for the importance of accounting for the role of vanilloid solute when interpreting the efficacy and tolerance of vesical vanilloid instillation in detrusor hyperreflexia cases. They suggest that a glucidic solute is a valuable solvent for vanilloid instillation.     

A device for treatment of destrusor hyperreflexia by bio-feedback

Summary Treatment of detrusor hyperreflexia is still a difficult field. Recently bio-feedback has been described as a successful treatment of voiding dysfunction. In this paper we describe a device, which makes it possible for the patients to registrate any pressure changes in the bladder.     

Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats

PURPOSE: We evaluated the effects of beta-adrenoceptor agonists on detrusor hyperreflexia in cerebral infarcted rats. MATERIALS AND METHODS: To produce cerebral infarction in Sprague-Dawley rats the left middle cerebral artery was occluded by introducing a monofilament nylon thread into the artery. In sham operated rats the same artery was exposed but not occluded. After these operations cystometric and cardiovascular experiments were performed with no anesthesia or restraint. RESULTS: After the operation bladder capacity was significantly decreased and voiding pressure was significantly increased in cerebral infarcted but not in sham operated animals. The difference in cerebral infarcted and sham operated rats was significant for each parameter (p <0.01). Post-void residual urine volume was not affected in either group. In the cerebral infarction group intravenous administration of CL316243 ([R,R]-5-2-[[2-(3-chlorophenyl-2-hydroxyethyl]-amino]propyl] -1,3-benzodioxole-2,2-dicarboxylate) (Kissei Central Laboratories, Hotaka, Japan) a selective beta3-adrenoceptor agonist, significantly increased bladder capacity at 10 and 100 microgram./kg. without affecting voiding pressure or post-void residual urine volume. Procaterol, a selective beta2-adrenoceptor agonist, significantly increased bladder capacity and post-void residual urine volume at 10 microgram/kg. intravenously without affecting voiding pressure. In separate experiments procaterol (1 to 100 microgram./kg. intravenously) decreased mean blood pressure and increased heart rate in a dose dependent manner. In contrast, the effects of CL316243 (0.1 to 100 microgram./kg. intravenously) on mean blood pressure and heart rate were minimal. CONCLUSIONS: These results indicate that in cerebral infarcted rats detrusor hyperreflexia can be suppressed by the selective beta3-adrenoceptor agonist CL316243 without increasing post-void residual volume and without significant cardiovascular side effects. If the current results hold true in humans, selective beta3-adrenoceptor agonists may prove useful for treating detrusor hyperreflexia associated with cerebral infarction.     

Dose-ranging study of tolterodine in patients with detrusor hyperreflexia

Tolterodine is a potent antimuscarinic agent specifically developed for the treatment of urinary urge incontinence and other symptoms related to the overactive bladder. In order to assess the optimum dosage for use in future clinical studies, a double-blind, randomized, placebo-controlled, parallel-group, multicenter study was performed in 90 patients with detrusor hyperreflexia and symptoms of urinary urgency, frequency, and/or urge incontinence. Urodynamic variables, micturition diary variables, and subjective urinary symptoms were measured before and after 2 weeks' treatment with either placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily (bd). Serum drug concentrations, electrocardiogram recordings, blood pressure, and incidence of adverse events were also assessed. Linear regression analysis showed a significant dose-response relationship for several clinically relevant urodynamic variables, while there was a trend towards an improvement in micturition diary variables and subjective assessment of symptoms with increasing dosages of tolterodine. There were no safety or tolerability concerns regarding any of the dosages of tolterodine investigated, although 2 patients treated with a dosage of 4 mg bd experienced urinary retention that necessitated dosage reduction. The results of this study suggest that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with detrusor hyperreflexia. The optimum dosage of tolterodine for use in future studies is 1–2 mg bd. Neurourol. Urodynam. 17:499–512, 1998. © 1998 Wiley-Liss, Inc.     

Intrinsic neuromuscular defects in the neurogenic bladder. III. Transjunctional,short- and long-term ultrastructural changes in muscle cells of the decentralized feline bladder base following unilateral sacral ventral rhizotomy

We have shown previously that vesicourethral decentralization by unilateral sacral ventral rhizotomy in the cat results in sequential degenerative and regenerative ultrastructural changes in intrinsic nerves of the bladder base. The present study in the same model provides evidence that these neural changes are associated with both degenerative and regenerative ultrastructural changes in smooth muscle cells of the feline base, representing the first example of transjunctional postdecentralization change in an effector tissue to be documented in a mammalian autonomically innervated smooth muscle system. The nature of the observed changes in the sarcoplasm, sarcoplasmic organelles, sarcolemma, and cell-to-cell relationships will be discusssed, and their physiologic significance as well as implications in the phenomenon of neurogenic muscular supersensitivity will be presented.     

Bladder function in patients with myotonic dystrophy

Ten patients with a clinically and neurophysiologically established diagnosis of myotonic dystrophy underwent urodynamic evaluation of the lower urinary tract. Eighty percent of the patients had urinary complaints by history, but we were not able to identify a homogeneous bladder dysfunction pattern by voiding and incontinence chart, flowmetry, cystometry, or sphincter electromyography. © 1992 Wiley-Liss, Inc.