Gaspar Msangi1 and Kenneth M. Peters1
(1)
Department of Urology, Oakland University, William Beaumont School of Medicine, 3535 West 13 Mile Road, 438, Royal Oak, MI 48073, USA
Kenneth M. Peters
Email: kmpeters@beaumont.edu
Abstract
Overactive bladder (OAB) is a syndrome characterized by urinary urgency with or without urge incontinence. Patients suffer significantly, affecting multiple areas of their lives and reducing their quality of life. OAB has significant economic impact, with first-line therapies (behavioral modification and anticholinergics) showing poor compliance due to significant side effects, treatment failures, and high costs. Surgical interventions for OAB result in significant perioperative and long-term morbidity. Percutaneous tibial nerve stimulation (PTNS) offers a minimally invasive, nonsurgical and reversible means to treat OAB with minimal side effects. Stimulation of the nerve inhibits bladder activity by depolarizing somatic sacral and lumbar afferents with central nervous system effects. Through prospective double-blind and sham-controlled studies, there is ample data to show efficacy of PTNS on OAB. Patients tolerate the procedure very well, with very minor discomfort and no significant side effects reported thus far.
PTNS is a safe, effective, and well-tolerated therapy for OAB. This chapter will focus on the history of PTNS, the concept of neuromodulation, review of the literature supporting the effect of PTNS, patient selection, and technique for administering PTNS.
The International Continence Society (ICS) defines OAB syndrome as urinary urgency with or without urge incontinence usually with increased daytime frequency and nocturia in the absence of a pathologic or metabolic condition [1]. Using this definition, recent surveys estimate the prevalence of OAB to be 18.6 %, being higher in women (26.1 %) than in men (10.7 %). This corresponds to 42.2 million adults in the USA having OAB. The societal cost of OAB among community dwelling adults is estimated to be at least 24.9 billion per year [2].
OAB has a negative impact on quality of life, with patients reporting the lowest levels of quality of life and work productivity and the highest levels of anxiety and depression [3]. Many patients have impaired mobility, disturbed sleep, impaired domestic function, social isolation, and decreased sexual enjoyment [4].
Treatment of OAB
Behavioral therapy should be the first-line treatment for OAB. Patients are instructed to limit fluid intake, eliminate foods like caffeine, alcohol, and medications like diuretics that could exacerbate symptoms. Other measures include timed voiding and pelvic floor physical therapy. Antimuscarinics are the mainstay of pharmacologic therapy. These drugs are effective in blocking muscarinic receptors but their action is not bladder-specific. Within 12 months, the majority of patients discontinue their antimuscarinic drug due to their cost, insufficient symptom relief, and significant side effects [5]. If behavioral and pharmacologic methods fail to resolve the OAB symptoms, neuromodulation is the next logical step.
Neuromodulation
Concept of Neuromodulation
Neuromodulation is the electrical or chemical modulation of a nerve to influence the physiologic behavior of an organ. Tanagho et al. in 1989 pioneered the initial investigations into electrical stimulation for neuromodulation [6]. Neuromodulation has become an important tool in the treatment of bladder dysfunction. Neuromodulation has been avidly embraced for the treatment of OAB primarily when noninvasive therapies such as behavioral modification, pelvic floor rehabilitation, and pharmacological therapy have failed. In the past once these noninvasive therapies were exhausted surgical procedures such as augmentation enterocystoplasty, detrusor myomectomy, bladder denervation, and urinary diversion were often employed to treat OAB and resulted in significant perioperative and long-term morbidity [7]. Neuromodulation offers a minimally invasive, nonsurgical and reversible means to treat voiding dysfunction. Sacral neuromodulation has been FDA approved for over 13 years to treat urinary urgency, frequency, urge incontinence, and non-obstructive urinary retention.
Neuromodulation of the Posterior Tibial Nerve
The posterior tibial nerve is a peripheral mixed sensory–motor nerve that originates from spinal roots L4 through S3, which also contribute directly to sensory and motor control of the urinary bladder and pelvic floor. Stimulation of the posterior tibial nerve was pioneered by Stoller and colleagues with the introduction of the stoller afferent nerve stimulator (SANS) which delivers electrical stimulation to the posterior tibial nerve via a 34-gauge needle just cephalad to the medial malleolus [8]. Multiple studies have demonstrated that posterior tibial nerve stimulation shows some efficacy in treating symptoms of OAB and altering urodynamic findings in patients with OAB [9, 10]. Stimulation of the nerve inhibits bladder activity by depolarizing somatic sacral and lumbar afferent fibers. Afferent stimulation provides central inhibition of the preganglionic bladder motor neurons through a direct route in the sacral cord [11].
Tibial nerve stimulation was first described in 1983. McGuire and colleagues showed efficacy in the treatment of a variety of voiding dysfunctions related to detrusor overactivity (DO) by electrical stimulation of the tibial nerve. His group reported on 16 patients with involuntary bladder contractions of varying etiology who were treated with common peroneal or posterior tibial nerve patch electrode stimulation. Twelve patients initially were dry, three were improved, and one was “possibly improved.” Okada and coworkers reported a positive experience with transcutaneous stimulation of the thigh muscle in 19 patients with detrusor overactivity; the maximal cystometric capacity was increased by 57 % in 11 of 19 patients [12, 13]. Vereecker and associates [14], however, were unable to suppress hyperactivity by this method in patients with suprasacral spinal cord injury or disease [14].
More recently, Vandoninck et al. in 2004 reported on their outcomes in 39 patients with chronic voiding dysfunction who were treated with tibial nerve stimulation. All patients had detrusor overactivity with elevated post-void residual urine or complete urinary retention; each patient performed self-catheterization. Each patient underwent 12 weekly tibial nerve stimulations at the medial malleolus for 30 min. The primary outcome was measured as total voided volume along with total catheterized volume. In 41 % of the patients, 24-h catheterized volume was reduced by 50 %. An additional 26 % noted 25–50 % reduction in their residuals. After the study, 59 % chose to continue treatment. Urodynamic testing was also performed. While patients’ cystometric capacity remained the same, detrusor pressure at maximum flow increased from 25 to 33 cm H2O, a statistically significant difference. In addition, both the bladder contractility index (BCI = P det × Qmax + 5 × Q max) as well as the bladder voiding efficiency (BVE = 100 × (voided volume/total bladder capacity)) showed statistically significant increases. Detrusor overactivity did exist in five patients at baseline. After stimulation, DO continued in three patients, disappeared in two and appeared de novo in seven patients. No significant side effects were reported [15].
Van Balken et al. reported on their treatment of patients with bladder overactivity as well as idiopathic urinary retention. In 37 patients with overactive bladder, 22 reported subjective improvement and requested continuation of therapy. However, all 37 showed significant improvement in day and night voiding frequency. In 30 urge incontinent patients, all 30 showed reduction in their incontinent episodes, pad use, and severity of leakage. Finally, for 12 patients with idiopathic urinary retention, a decrease in number and volume of catheterization was reported, but this did not reach statistical significance. They concluded that percutaneous tibial nerve stimulation is a promising, cost-effective, and easily applicable treatment for lower urinary tract dysfunction [10].
Ruiz and colleagues from Spain reported on 51 patients treated over 3 years for similar symptom complexes. Twenty-six patients described the frequency–urgency syndrome, 22 described urge incontinence and 3 carried a diagnosis of interstitial cystitis. Patients underwent 10, 30-min sessions wherein the tibial nerve was stimulated using a similar technique as in prior articles. Mean follow up was 21 months. Across the entire patient population, they reported statistically significant improvement in all seven categories measured: daytime frequency, daytime voided volume, daytime leakage episodes, nighttime frequency, nighttime leakage episodes, nighttime voided volume, and hypogastric/suprapubic pain [16].
Posterior tibial nerve stimulation was also evaluated in the acute setting by Amarenco et al. in 2003 [11]. They studied 44 patients with irritative lower urinary tract symptoms, including uninhibited detrusor contractions as seen on filling cystometrogram. The etiology was demonstrable in 37 patients, including multiple sclerosis, spinal cord injury, brain injury, and Parkinson’s disease; the remaining seven patients had idiopathic detrusor overactivity. Cystometry was performed at a rate of 50 cc/min using an 8 french catheter. Patients were filled until they experienced uninhibited bladder contractions, leakage was observed or if they achieved a volume of 400 cc. CMG was performed again after posterior tibial nerve stimulation was initiated. A positive test consisted of an increase in the bladder volume at which a contraction occurred of 100 cc or greater, or if that involuntary contraction occurred at a bladder volume that was 50 % greater than baseline. Twenty-two of 44 (50 %) cases tested positive. Further urodynamic data was collected. Mean bladder volume that the first involuntary contraction occurred was 162 cc at baseline, and increased to 232 cc after stimulation. Maximum cystometric capacity was 221 cc at baseline and increased to 277 cc after stimulation.
Finally, posterior tibial nerve stimulation has been applied to the interstitial cystitis population, a subset of patients with voiding dysfunction. Zhao and Nordling applied posterior tibial nerve stimulation to 14 patients diagnosed with IC. Patients were treated during a total of 10, 30-min sessions. One patient withdrew from the study, leaving 13 patients who completed the course of therapy. The results did not meet clinical significance in pain, voided volume, and quality of life scores [17].
The lure of the tibial nerve is that it is easily accessible without requiring an operating room or an anesthetic. As with all novel techniques, the data was initially anecdotal and non-randomized. Studies with modest numbers have shown efficacy. One of the most significant studies was the OrBIT trial comparing PTNS versus tolterodine. This was a multicenter study where a total of 100 adult patients with OAB symptoms were randomized 1:1 to either PTNS or tolterodine therapy. PTNS arm patients received 30 min weekly treatments for 12 consecutive weeks while the pharmacotherapy patient arm received 4 mg Tolterodine-ER daily (decreased to 2 mg if intolerability was experienced) for 12 weeks. Two-day voiding diaries were collected at baseline and at study end. The primary end point was to compare whether PTNS was better than tolterodine at reducing the frequency of urinary voids per day after 12 weeks of therapy. Secondary endpoints included change in urge incontinence episodes per 24 h, number of voids causing waking, volume voided per day as well as number of urgency episodes per day. Subject and investigator ratings of improvement in OAB symptoms were assessed. Adverse reactions were also monitored.
Results
79.5 % of PTNS patients compared to 54.8 % of tolterodine patients considered themselves improved or cured. This was paralleled to investigator assessment showing improvement or cure in 79.5 % of PTNS patients versus 60.5 % of tolterodine patients. Each group showed significant improvement in all OAB symptoms from baseline to 12 weeks but when compared between groups, there was no significant difference. The improvements were seen in more PTNS patients than in tolterodine patients even though there was no statistical significance [18].
Effects of PTNS are long term. In the phase II OrBIT trial which looked at long-term effects of PTNS, study subjects continued to receive periodic PTNS treatments. At 6 and 12 months, there was still significant improvement in urinary frequency, urge incontinence, nocturia, and voided volume. Both patients and investigators classified OAB symptoms as improved. Treatment intervals were tapered during this long-term follow-up period with a mean of 21 days between treatments. PTNS treatment frequency can be individualized according to patients’ response which would allow for better compliance [19].
Sham-Controlled Data
The placebo effect on patients with OAB cannot be ignored, with placebo-controlled drug trials showing a placebo effect as high as 64 % for some incontinence symptoms [20]. Effects of PTNS have been shown to be not due to placebo effect. First a sham was designed and validated [21] and then subsequently used in a multicenter, double-blind, randomized trial that provided level one evidence to the safety and efficacy of PTNS. The SumiT trial had 220 adults with OAB randomized 1:1–12 weeks of treatment with weekly PTNS or sham. In this study 54.5 % of the PTNS subjects showed moderately or markedly improvement in bladder symptoms compared to 20.9 % of the sham which was statistically different. Urinary frequency, nighttime voids, moderate to severe urgency, and urge incontinence episodes all improved significantly compared to sham [22]. A smaller prospective double-blind placebo-controlled trial had 35 female patients 17 receiving PTNS while 18 had a sham. Seventy-one percentage of the PTNS showed greater than 50 % reduction in urge incontinence episodes while 0 in the placebo group responded [23].
PTNS offers a significant new modality for management of this debilitating condition; it provides an option for patients who are refractory to drugs, is less invasive and costly than SNS, and is clinically and cost-effective when considering the alternatives within the current algorithm of practice.
Patient Selection
Patients with bothersome symptoms of OAB who have not responded or could not tolerate behavioral or pharmacologic therapy should be considered for PTNS. Baseline voiding diaries evaluating urinary urgency, frequency, voided volume, and urge incontinent episodes should be completed. Urodynamic evaluation would be at the discretion of the clinician.
Technique
Patients are placed in the sitting position with their leg elevated (Fig. 14.1). The medial aspect of the foot is inspected. The needle insertion site is palpated about 5 cm cephalad to the medial malleolus between the posterior margin of the tibia and the soleus muscle (Fig. 14.2). A 34-gauge needle electrode is inserted at a 60° angle cephalad, about 3–4 cm deep to the tibial nerve (Fig. 14.3). A self-adhesive grounding pad is placed on the lower foot and the grounding pad and hook electrode are connected to the stimulator (Urgent® PC, Uroplasty, Minneapolis MN). The hook electrode is attached to the needle (Fig. 14.4). Current is slowly increased from 0 to 10 mA while assessing sensory and motor responses. If the needle is correctly placed, patient will experience flexion of the toes and sensory stimulation of the bottom of the foot. If this does not happen, the needle is advanced or withdrawn until it is confirmed to be in the correct position. The electrical current is set at an intensity that is well tolerated. A 30-min stimulation session is given at 20 Hz with a 200 μs fixed pulse width. After treatment, the needle and grounding pad are removed and disposed.
Fig. 14.1
Patient positioning
Fig. 14.2
Palpation of needle insertion site
Fig. 14.3
Needle positioning
Fig. 14.4
Connection of the stimulator
Treatment Interval
Patients return weekly for 12 weeks to obtain a 30-min treatment session. If at the end of 12 treatments there has been a documented significant improvement in symptoms, the patient returns once per month for a maintenance treatment. The treatment interval can be tailored to the patient’s clinical response.
Contraindication and Complications of Tibial Nerve Stimulation
Tibial nerve stimulation is very safe. A few patients may complain of pain at the needle puncture site, mild bruising or bleeding, but no serious adverse events have been reported. Safety of PTNS has not been studied in pregnant women and should therefore not be used in this population. The stimulation point (acupuncture point SP6) is associated with ripening of the cervix and induction of labor [24]. As with any neuromodulation device, there is a relative contraindication in patients with a cardiac pacemaker.
Conclusions
OAB is a syndrome characterized by urinary urgency with or without urge incontinence. OAB has significant economic impact, with first-line therapies showing poor compliance due to significant side effects, treatment failures, and high costs. Surgical interventions for OAB result in significant perioperative and long-term morbidity. PTNS offers a minimally invasive, non-ablative, and reversible means to treat OAB with minimal side effects. Stimulation of the nerve inhibits bladder activity by depolarizing somatic sacral and lumbar afferents with central nervous system effects. Through prospective double-blind and sham-controlled studies, there is ample data to show efficacy of PTNS on OAB. No significant side effects have been reported.
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