Ambulatory, Office-based, and Geriatric Urology Electrical Stimulation of the Posterior Tibialis Nerve Improves Symptoms of Poststroke Neurogenic Overactive Bladder in Men: A Randomized Controlled Trial Santos Monteiro, Luciane Bizari Coin de Carvalho, Marcia Maiumi Fukujima, Ebe Mayra Ivanoff Lora, and Gilmar Fernandes do Prado OBJECTIVE
MATERIALS AND METHODS
RESULTS
CONCLUSION
To evaluate the effectiveness of electrical stimulation of the posterior tibialis nerve in men with neurogenic overactive bladder secondary to ischemic stroke at 45 days and 12 months after treatment. We studied 24 patients older than 18 years, with ischemic stroke that occurred between 6 months and 3 years previously and with no prior urinary symptoms. These patients were randomly allocated to receive electrical stimulation of the posterior tibialis nerve twice weekly for 6 weeks (treatment group, n ¼ 12) or general advice and stretching sessions 1 to 3 times monthly for 6 weeks (control group, n ¼ 12). Each session lasted 30 minutes in both groups. The primary outcomes were reduction in urinary frequency, reduction in urinary urgency, and overall improvement in voiding diary variables. Patients in the electrical stimulation group, in relation to baseline and to control group, experienced improvement in urinary symptoms, reducing urinary urgency and frequency, and reported subjective improvement after treatment. This effect persisted after 12 months of follow-up. The patients with lesion in right hemisphere, advanced age, and with higher body mass index presented more chance to develop urinary symptoms. Electrical stimulation of the posterior tibialis nerve is a safe and effective option for the treatment of poststroke neurogenic overactive bladder in men, reducing urinary frequency and urgency. UROLOGY 84: 509e514, 2014. 2014 Elsevier Inc.
T
he prevalence of urinary incontinence in US adults ranges from 3% to 43%.1,2 Poststroke overactive bladder prevalence is even higher (up to 47%) and is associated with high morbidity.3,4 In 2000, the financial burden of poststroke overactive bladder was approximately US $12.02 billion, a figure comparable with the expenditures associated with osteoporosis and breast cancer.5
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Medicine, Universidade Federal de São Paulo—UNIFESP, São Paulo, São Paulo, Brazil; the Department of Neurology, Universidade Federal de São Paulo—UNIFESP, São Paulo, São Paulo, Brazil; and the School of Economics, Getulio Vargas Foundation, São Paulo, São Paulo, Brazil Reprint requests: Luciane Bizari Coin de Carvalho, Ph.D., R. Claudio Rossi, 394. CEP 01547-000, São Paulo, São Paulo, Brazil. E-mail: [email protected] Submitted: March 12, 2014, accepted (with revisions): May 21, 2014
ª 2014 Elsevier Inc. All Rights Reserved
Some therapeutic options are already well established for this condition, such as physical therapy, behavioral interventions, surgery, and pharmacotherapy.6,7 One physical therapy option, electrical stimulation of the posterior tibialis nerve, may improve the symptoms of poststroke neurogenic overactive bladder. Electrical stimuli applied through the posterior tibialis nerve modify the integrated efferent and afferent responses in the lumbosacral spinal cord.8 This study sought to evaluate the effectiveness of electrical stimulation of the posterior tibialis nerve in men with neurogenic overactive bladder due to ischemic stroke 45 days and 12 months after treatment, as compared with control group. The main hypothesis was that electrical stimulation leads to long-term symptom improvement. http://dx.doi.org/10.1016/j.urology.2014.05.031 0090-4295/14
509
MATERIALS AND METHOD Population and Setting We recruited participants for the clinical trial from February 2007 through June 2008 from the Stroke Outpatient Clinic of the Department of Medicine of Hospital São Paulo, Escola Paulista de Medicina at the Universidade Federal de São Paulo. The participants were adult men who had stroke. The diagnostics were assessed with clinical and neuroimaging evaluations according to established criteria.9 We included patients aged 18 years, with stroke occurring between 6 months and 3 years before recruitment. We excluded men who had an implanted cardiac pacemaker, urinary tract infection, bladder cancer, pre-existing urinary incontinence before stroke, or surgery in the urogenital region. The Research Ethics Committee of UNIFESP-EPM (number 436.488) approved this study. All patients signed the consent form for participation. The sample size was calculated with the Pocock formula, with 47% of neurogenic overactive bladder prevalence and decrease of 30% after treatment. Of 602 patients, 116 had stroke 6 months to 3 years before initial evaluation. Of these 116 men, we recruited 30 patients with neurogenic overactive bladder; 6 did not complete a bladder voiding diary and 24 patients completed the treatment (Fig. 1). Each patient had muscle strength evaluated with the Oxford Grading Scale10 at the beginning of the study, and there was no patient with limitations on muscle strength.
Randomization We randomized 24 participants into 2 groups of 12. To ensure random allocation, all participants were numbered sequentially from 1 to 24 and divided into 2 groups of 12 patients assigned to the treatment group (electrical stimulation of the posterior tibialis nerve) and 12 to the control group. Of the 24 patients randomized, 1 in the placebo group died after the treatment period. Therefore, 23 patients were available for follow-up analysis.
Procedure Treatment Group. Participants in the treatment group underwent electrical stimulation with the Duplex-961 system (Quark, Piracicaba, São Paulo, Brazil). With the patient seated, surface electrodes were placed on the skin with conductive gel and secured with adhesive tape. A negative electrode was placed on the medial malleolus, and the positive electrode was placed 10 cm above the negative electrode, also on the medial side. The rhythmic flexion of the second toe during the stimulation determined the correct position of the negative electrode. The intensity level was set below the threshold that causes motor contraction because the patient should be comfortable and no pain should occur during the procedure. Electrical stimulation of the posterior tibialis nerve was performed for 30 minutes twice weekly over 12 sessions (45 days), with a frequency of 10 Hz and a pulse width of 200 ms in continuous mode. Control Group. This group received 12 stretching sessions of the lower limbs. We conducted 3 muscle-stretching training sessions to instruct patients how to perform each of these 3 series of 30-second stretching exercises at home.11 Patients did not receive other types of physical therapy or any specific behavioral guidelines for overactive bladder during the 12 months of follow-up. 510
Evaluation. All patients completed a 3-day voiding diary before treatment, after 12 sessions (45 days), and after 12 months. The voiding diary included the following components: urgency, urge incontinence, nocturia, nocturnal enuresis, and increased daytime frequency. In addition to the voiding diary, we obtained information on demographic data, personal (diabetes mellitus, smoking, and alcohol consumption) and family history, and medication usage from each patient. The Barthel index, which evaluates functional capacity, was also administered.12 For subjective assessment of symptoms after treatment and at 12-month follow-up, patients were asked whether their symptoms had improved.
Definition of Outcomes Independent Variables. Age, body mass index (BMI), Barthel index (bladder item), smoking, alcoholism, diabetes mellitus, hypertension, laterality of hemispheric involvement, and diuretic use. Dependent Variables. The outcomes of interest were defined and characterized in accordance with the International Continence Society parameters13: (1) urinary urgency: a sudden compelling desire to pass urine. Improvement of urinary urgency: complete resolution of this symptom; (2) urge incontinence: involuntary loss of urine accompanied by or immediately proceeded by urgency, ranging from small losses to a catastrophic leak with complete bladder emptying. Improvement of urge incontinence: complete resolution of this symptom; (3) nocturnal enuresis: any involuntary loss of urine during sleep. Improvement of enuresis: absence of involuntary loss of urine during sleep; (4) nocturia: waking 2 times a night to void. Improvement of nocturia: waking at night 1 or 0 times to void; (5) increased daytime frequency: 9 voidings daily as recorded in voiding diary. Improvement of urinary frequency: voiding eight or fewer times daily; (6) subjective improvement in symptoms: on follow-up, a report by the patient that symptoms had improved, regardless of the parameter considered relevant by the patient. Matching Analysis. Mean age and BMI, number of smokers, number of drinkers, number of patients with diabetes mellitus, number of patients with hypertension, laterality of hemispheric involvement (right or left), diuretic use, and Barthel score were compared to check whether participants were adequately matched.
Statistical Analysis Numerical variables (age and BMI) were normally distributed, as determined by the Kolmogorov-Smirnov test, analyzed with the Student t test and presented as mean standard deviation. Absolute risk, relative risk, and number needed to treat (NNT) were calculated for the electrical stimulation and placebo groups at 45-day and 12-month follow-up. Dichotomous variables (presence of urinary urgency, urge incontinence, nocturnal enuresis, nocturia, increased daytime frequency, and subjective improvement in symptoms) and other discrete variables (number of smokers, number of drinkers, number of patients with diabetes mellitus, number of patients with hypertension, number of patients with right hemisphere involvement, number of patients with left hemisphere involvement, number of patients on diuretics, and Barthel score indicative of dependence/independence) were analyzed by UROLOGY 84 (3), 2014
602 patients recruited (Stroke outpatient service)
To be included, patients had to be 18 years of age or older with their stroke occurring between 6 months and 3 years prior
116 men
30 had neurogenic overactive bladder 6 did not complete a bladder voiding diary The 24 participants had neurogenic overactive bladder Randomization
12 treatment group (electrical stimulation of the posterior tibialis nerve)
12 control group
One death
Figure 1. Flowchart of patient allocation. (Color version available online.)
means of the chi square test and the Fisher exact test. We used logistic regression to assess the interaction between variables and symptom improvement. We considered 95% of confidence interval (CI) and P
MATERIALS AND METHODS
RESULTS
CONCLUSION
To evaluate the effectiveness of electrical stimulation of the posterior tibialis nerve in men with neurogenic overactive bladder secondary to ischemic stroke at 45 days and 12 months after treatment. We studied 24 patients older than 18 years, with ischemic stroke that occurred between 6 months and 3 years previously and with no prior urinary symptoms. These patients were randomly allocated to receive electrical stimulation of the posterior tibialis nerve twice weekly for 6 weeks (treatment group, n ¼ 12) or general advice and stretching sessions 1 to 3 times monthly for 6 weeks (control group, n ¼ 12). Each session lasted 30 minutes in both groups. The primary outcomes were reduction in urinary frequency, reduction in urinary urgency, and overall improvement in voiding diary variables. Patients in the electrical stimulation group, in relation to baseline and to control group, experienced improvement in urinary symptoms, reducing urinary urgency and frequency, and reported subjective improvement after treatment. This effect persisted after 12 months of follow-up. The patients with lesion in right hemisphere, advanced age, and with higher body mass index presented more chance to develop urinary symptoms. Electrical stimulation of the posterior tibialis nerve is a safe and effective option for the treatment of poststroke neurogenic overactive bladder in men, reducing urinary frequency and urgency. UROLOGY 84: 509e514, 2014. 2014 Elsevier Inc.
T
he prevalence of urinary incontinence in US adults ranges from 3% to 43%.1,2 Poststroke overactive bladder prevalence is even higher (up to 47%) and is associated with high morbidity.3,4 In 2000, the financial burden of poststroke overactive bladder was approximately US $12.02 billion, a figure comparable with the expenditures associated with osteoporosis and breast cancer.5
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Medicine, Universidade Federal de São Paulo—UNIFESP, São Paulo, São Paulo, Brazil; the Department of Neurology, Universidade Federal de São Paulo—UNIFESP, São Paulo, São Paulo, Brazil; and the School of Economics, Getulio Vargas Foundation, São Paulo, São Paulo, Brazil Reprint requests: Luciane Bizari Coin de Carvalho, Ph.D., R. Claudio Rossi, 394. CEP 01547-000, São Paulo, São Paulo, Brazil. E-mail: [email protected] Submitted: March 12, 2014, accepted (with revisions): May 21, 2014
ª 2014 Elsevier Inc. All Rights Reserved
Some therapeutic options are already well established for this condition, such as physical therapy, behavioral interventions, surgery, and pharmacotherapy.6,7 One physical therapy option, electrical stimulation of the posterior tibialis nerve, may improve the symptoms of poststroke neurogenic overactive bladder. Electrical stimuli applied through the posterior tibialis nerve modify the integrated efferent and afferent responses in the lumbosacral spinal cord.8 This study sought to evaluate the effectiveness of electrical stimulation of the posterior tibialis nerve in men with neurogenic overactive bladder due to ischemic stroke 45 days and 12 months after treatment, as compared with control group. The main hypothesis was that electrical stimulation leads to long-term symptom improvement. http://dx.doi.org/10.1016/j.urology.2014.05.031 0090-4295/14
509
MATERIALS AND METHOD Population and Setting We recruited participants for the clinical trial from February 2007 through June 2008 from the Stroke Outpatient Clinic of the Department of Medicine of Hospital São Paulo, Escola Paulista de Medicina at the Universidade Federal de São Paulo. The participants were adult men who had stroke. The diagnostics were assessed with clinical and neuroimaging evaluations according to established criteria.9 We included patients aged 18 years, with stroke occurring between 6 months and 3 years before recruitment. We excluded men who had an implanted cardiac pacemaker, urinary tract infection, bladder cancer, pre-existing urinary incontinence before stroke, or surgery in the urogenital region. The Research Ethics Committee of UNIFESP-EPM (number 436.488) approved this study. All patients signed the consent form for participation. The sample size was calculated with the Pocock formula, with 47% of neurogenic overactive bladder prevalence and decrease of 30% after treatment. Of 602 patients, 116 had stroke 6 months to 3 years before initial evaluation. Of these 116 men, we recruited 30 patients with neurogenic overactive bladder; 6 did not complete a bladder voiding diary and 24 patients completed the treatment (Fig. 1). Each patient had muscle strength evaluated with the Oxford Grading Scale10 at the beginning of the study, and there was no patient with limitations on muscle strength.
Randomization We randomized 24 participants into 2 groups of 12. To ensure random allocation, all participants were numbered sequentially from 1 to 24 and divided into 2 groups of 12 patients assigned to the treatment group (electrical stimulation of the posterior tibialis nerve) and 12 to the control group. Of the 24 patients randomized, 1 in the placebo group died after the treatment period. Therefore, 23 patients were available for follow-up analysis.
Procedure Treatment Group. Participants in the treatment group underwent electrical stimulation with the Duplex-961 system (Quark, Piracicaba, São Paulo, Brazil). With the patient seated, surface electrodes were placed on the skin with conductive gel and secured with adhesive tape. A negative electrode was placed on the medial malleolus, and the positive electrode was placed 10 cm above the negative electrode, also on the medial side. The rhythmic flexion of the second toe during the stimulation determined the correct position of the negative electrode. The intensity level was set below the threshold that causes motor contraction because the patient should be comfortable and no pain should occur during the procedure. Electrical stimulation of the posterior tibialis nerve was performed for 30 minutes twice weekly over 12 sessions (45 days), with a frequency of 10 Hz and a pulse width of 200 ms in continuous mode. Control Group. This group received 12 stretching sessions of the lower limbs. We conducted 3 muscle-stretching training sessions to instruct patients how to perform each of these 3 series of 30-second stretching exercises at home.11 Patients did not receive other types of physical therapy or any specific behavioral guidelines for overactive bladder during the 12 months of follow-up. 510
Evaluation. All patients completed a 3-day voiding diary before treatment, after 12 sessions (45 days), and after 12 months. The voiding diary included the following components: urgency, urge incontinence, nocturia, nocturnal enuresis, and increased daytime frequency. In addition to the voiding diary, we obtained information on demographic data, personal (diabetes mellitus, smoking, and alcohol consumption) and family history, and medication usage from each patient. The Barthel index, which evaluates functional capacity, was also administered.12 For subjective assessment of symptoms after treatment and at 12-month follow-up, patients were asked whether their symptoms had improved.
Definition of Outcomes Independent Variables. Age, body mass index (BMI), Barthel index (bladder item), smoking, alcoholism, diabetes mellitus, hypertension, laterality of hemispheric involvement, and diuretic use. Dependent Variables. The outcomes of interest were defined and characterized in accordance with the International Continence Society parameters13: (1) urinary urgency: a sudden compelling desire to pass urine. Improvement of urinary urgency: complete resolution of this symptom; (2) urge incontinence: involuntary loss of urine accompanied by or immediately proceeded by urgency, ranging from small losses to a catastrophic leak with complete bladder emptying. Improvement of urge incontinence: complete resolution of this symptom; (3) nocturnal enuresis: any involuntary loss of urine during sleep. Improvement of enuresis: absence of involuntary loss of urine during sleep; (4) nocturia: waking 2 times a night to void. Improvement of nocturia: waking at night 1 or 0 times to void; (5) increased daytime frequency: 9 voidings daily as recorded in voiding diary. Improvement of urinary frequency: voiding eight or fewer times daily; (6) subjective improvement in symptoms: on follow-up, a report by the patient that symptoms had improved, regardless of the parameter considered relevant by the patient. Matching Analysis. Mean age and BMI, number of smokers, number of drinkers, number of patients with diabetes mellitus, number of patients with hypertension, laterality of hemispheric involvement (right or left), diuretic use, and Barthel score were compared to check whether participants were adequately matched.
Statistical Analysis Numerical variables (age and BMI) were normally distributed, as determined by the Kolmogorov-Smirnov test, analyzed with the Student t test and presented as mean standard deviation. Absolute risk, relative risk, and number needed to treat (NNT) were calculated for the electrical stimulation and placebo groups at 45-day and 12-month follow-up. Dichotomous variables (presence of urinary urgency, urge incontinence, nocturnal enuresis, nocturia, increased daytime frequency, and subjective improvement in symptoms) and other discrete variables (number of smokers, number of drinkers, number of patients with diabetes mellitus, number of patients with hypertension, number of patients with right hemisphere involvement, number of patients with left hemisphere involvement, number of patients on diuretics, and Barthel score indicative of dependence/independence) were analyzed by UROLOGY 84 (3), 2014
602 patients recruited (Stroke outpatient service)
To be included, patients had to be 18 years of age or older with their stroke occurring between 6 months and 3 years prior
116 men
30 had neurogenic overactive bladder 6 did not complete a bladder voiding diary The 24 participants had neurogenic overactive bladder Randomization
12 treatment group (electrical stimulation of the posterior tibialis nerve)
12 control group
One death
Figure 1. Flowchart of patient allocation. (Color version available online.)
means of the chi square test and the Fisher exact test. We used logistic regression to assess the interaction between variables and symptom improvement. We considered 95% of confidence interval (CI) and P
