overactive bladder ( oab ) is defined as urgency with or without urgency incontinence , usually with frequency ( > 8 micturitions/24  h ) and nocturia . conservative management of oab usually includes pelvic floor physical therapy and/or use of pharmacotherapy such as antimuscarinic medications . however , a significant number of patients are refractory to pharmacotherapy , and long - term compliance is poor , so much so that only 30% of individuals with oab syndrome still take their medication 1  year after initiation . traditionally , patients who failed conservative measures were left with highly invasive treatment options , such as myomectomy , augmentation cystoplasty , and various urinary diversions . in 1997 , the us food and drug administration approved neuromodulation for urgency incontinence , and subsequently for urgency - frequency syndrome and nonobstructive chronic urinary retention . although its mode of action is still not completely understood , recent research indicates that this therapy involves not just electrostimulation of sacral nerves but also neuromodulation due to somatosensory bladder afferents projecting into the pontine micturition center in the brainstem . the objective of this article is to review the current literature and discuss the latest advances , significant trends , and current debates in the treatment of oab with neuromodulation . of particular interest are the articles focusing on peripheral nerve stimulation ( pns ) , cost - effectiveness , and nontraditional patient populations . during the past year , several articles examined the efficacy and cost - effectiveness of neuromodulation , as well as the adverse effects and safety profile of this procedure . in one such article , siddiqui et al . [ 5 ] systematically reviewed the literature regarding the efficacy of sacral nerve stimulation ( sns ) using the interstim ( medtronic , minneapolis , mn ) for women with refractory oab . the highest - quality data were found in three independent studies of efficacy . in these studies , incontinent episodes per day and pad usage significantly decreased after sns therapy . after sns , there was a significant decrease in mean incontinent episodes per day ( 23 ) and mean daily pad use ( 13 ) . about 45% of patients reported  cure ,  or lack of daily incontinence episodes , up to 3  years after implant . amundsen et al .   reported a 65- to 67-point decrease in incontinence impact questionnaire ( iiq ) scores 2  years after sns implant . in a separate article , siddiqui et al . [ 7 ] compared the cost - effectiveness of sns versus that of intravesical botulinum a toxin ( bont - a ) for treatment of refractory urge incontinence . using the markov decision model to compare cost ( 2008 us dollars ) and effectiveness ( quality - adjusted life - years [ qalys ] ) , they calculated the incremental cost - effectiveness ratio ( icer ) , which compares the difference in cost with the difference in effectiveness ( ie , qalys ) . in the best - case scenario , sns was more expensive ( $ 15,743 vs $ 4,392 ) and more effective ( 1.73 vs 1.63 qalys ) than bont - a during a 2-year period . during a 2-year period , the icer was $ 116,427 per qaly , indicating that although sns was more effective , bont - a was the more cost - effective option . one could argue that the cost - effectiveness comparison could change dramatically if it were recalculated beyond the 2-year period . however , the authors were limited to a 2-year period because long - term data regarding bont - a injections are limited . in addition to demonstrating that this procedure is effective , the literature also suggests that neuromodulation is relatively safe . adverse events mainly encompassed pain , infection , and change in clinical effect , often due to lead migration . the surgical revision rates when using tined leads ranged from 3% to 16% , as most complications were managed conservatively . six percent of patients were explanted due to lack of efficacy , and 5% to 11% were explanted due to infection . another safety issue regarding sacral neuromodulation is the potential for cross - talk between the interstim device and cardiac pacemakers . roth   recently presented a series of three patients with cardiac pacemakers who subsequently underwent staged sns implantation , and two patients who had successful internal pulse generator ( ipg ) implantation who later required cardiac pacemaker implantation . patients had continuous cardiac monitoring by anesthesia , and there were no observed changes in rhythm perioperatively . this case series includes the two patients who did not have their ipgs turned off at the time of cardiac pacemaker implantation . at the time of 2-week follow - up , interrogation of the ipgs revealed that the settings had remained the same on both devices . they were implanted on the contralateral side of the cardiac pacemakers in the three patients who had previously undergone cardiac pacemaker placement . of note , none of the pacemakers had cardioversion or defibrillator capabilities . based on this study , sns can be safely used in patients with cardiac pacemakers . during the past year , the bulk of the literature regarding advancements in neuromodulation for oab has focused on alternatives to sns . the literature suggests that pns via the posterior tibial nerve or the pudendal nerve may be viable options . posterior tibial nerve stimulation ( ptns ) was first introduced by mcguire and colleagues in 1983 , and more recent studies have confirmed a 60% to 80% positive response rate after 10 to 12  weekly treatments . ptns is performed by inserting a 34-gauge needle about 3 to 4  cm cephalad to the medial malleous , between the posterior margin of the tibia and soleus muscle . once connected , an adjustable voltage pulse intensity of 0 to 10  ma , a fixed pulse width of 200 , and a frequency of 20  hz were delivered during weekly 30-min sessions . correct position is confirmed by flexion of the great toe or fanning of the toes and a tingling sensation . adverse events associated with ptns are minimal , mostly minor hematomas at the site of needle insertion . peters et al . [ 10 ] published a randomized , multicenter study that compared the efficacy of ptns with that of extended - release tolterodine , also known as the orbit ( overactive bladder innovative therapy ) trial . a total of 100 adults with urinary frequency were randomly assigned to 12  weeks of treatment with ptns or 4  mg / d of extended - release tolterodine . after 12  weeks of therapy , the ptns arm reported a 79.5% cure or improvement rate , compared with 54.8% of those on tolterodine ( p  =  0.01 ) on the global response assessments . the two groups had similar improvements on objective measures , including reductions in urinary frequency , urge urinary incontinence episodes , urge severity , and nighttime voids , and increased voided volume . the authors concluded that ptns was safe and efficacious , with statistically significant subjective and objective improvements comparable to that of pharmacotherapy . peters et al . [ 11 ] also compared the efficacy of ptns to that of sham in a multicenter , double - blind , randomized trial known as sumit ( study of urgent pc versus sham effectiveness in treatment of overactive bladder symptoms ) . after 12  weeks , 54.5% of the ptns patients reported moderate or markedly improved response from baseline , compared with 20.9% of sham patients ( p  <  0.001 ) . ptns also increased voided volume when compared with baseline from 83 to 169.5  ml ( p  =  0.01 ) . patients were not able to correctly identify if they were part of the sham or ptns group , as both groups had leads placed . the results from this study suggest that the therapeutic effect of ptns is a result of stimulation of the posterior tibial nerve and not a placebo effect . following the encouraging results from the sumit and orbit studies demonstrating true therapeutic effects comparable to those of tolterodine , other authors focused on various treatment courses and durability . the traditional ptns treatment course runs for 12  weeks , with weekly 30-min sessions . forty - three women underwent this shortened treatment course and were evaluated with bladder symptom diaries and the incontinence impact questionnaire ( iiq-7 ) , which is a health - related quality - of - life questionnaire . a positive response to therapy was defined as 1 ) oab symptoms no longer being bothersome , 2 ) reduction by half in frequency episodes , and 3 ) reduction by 25% in iiq-7 outcomes . the positive response rate was 69.7% , with an almost 50% decrease in the median daytime and nocturnal frequency ( 11.8 vs 6.9 and 3.5 vs 1.8 ; p  <  0.05 ) . patients reported fewer urge incontinence episodes per 24  h , from a median of 3.5 to 2.4 ( p  <  0.05 ) . the median iiq-7 scores decreased by 25% ( 30.4 vs 24.3 ; p  <  0.05 ) , and the median number of pads used in 24 hours decreased by 34% ( 3.8 vs 2.5 ; p  <  0.05 ) . however , the participants reported return of symptoms 3  weeks after the treatment , and no predictors of duration of symptomatic relief could be identified . these early data suggest that the ptns treatment course can be halved , but more conclusive studies are needed to determine the optimal duration of initial treatment and maintenance program . thirty - three of the 35 responders from the initial 12-week treatment course elected for maintenance therapy . a total of 32 completed 6  months of maintenance , and 25 completed 12  months . the participants received a mean of 12.1    4.9 treatments over an average of 263  days , with a mean of 21  days ( median , 17 ) between treatments . however , the participants had longer time intervals during the second 6  months than during the first 6  months of the evaluation ( 14 vs 24  days ) . subjective global assessments showed a sustained improvement of symptoms from 12  weeks at the 6-month and 12-month evaluations ( 94% and 96% , respectively ) . there were also objective improvements from baseline , with decreases of 2.8 voids per day ( p  <  0.001 ) , 1.6 urge incontinence episodes per day ( p  <  0.001 ) , 0.8 nocturnal voids ( p  <  0.05 ) , and an increase of 39  ml in voided volume ( p  <  0.01 ) . the authors concluded that ptns can be a viable long - term therapeutic option for oab patients . a global evaluation of ptns as a treatment option for oab was performed by ridout and yoong   with a review of the published literature . these studies used various criteria for  positive response ,  such as objective reduction in symptoms and the request for maintenance therapy following completion of the 12-week course . using these varying definitions of success most authors agree that ptns requires indefinite maintenance therapy , but the specifics of the maintenance program have not yet been defined . van der pal et al .   showed that 64% of patients reported greater than 50% worsening in frequency and incontinence episodes after a 6-week pause in treatment . overall , ptns seems to offer symptomatic relief for oab patients who are refractory to conservative therapy , but standard guidelines for initial therapy and maintenance regimens are lacking . in addition to the sacral and the posterior tibial nerves , physicians can target the pudendal nerves for neuromodulation . the sacral nerve sensory afferent fibers originate in the pudendal nerve , which innervates the pelvic floor muscles , external urethral and anal sphincters , and pelvic organs . performed a retrospective review of patients undergoing tined lead placement at the pudendal nerve via the ischial - rectal approach for chronic pudendal neuromodulation . there were 84 patients with various primary urologic diagnoses , including interstitial cystitis / painful bladder syndrome , urgency / frequency or urge incontinence , nonobstructive urinary retention , and pelvic / bladder pain without interstitial cystitis . almost all individuals with a history of failed sacral neuromodulation responded to the pudendal lead stimulation ( 93.2% [ 41 of 44 ] ) . overall , positive pudendal response ( 50% improvement on the pudendal lead ) was achieved in 60 of 84 participants ( 71.4% ) . these are encouraging results that warrant further investigation and suggest that pudendal nerve  targeted neuromodulation may be a viable alternative to sns . during the past year , the bulk of the literature regarding advancements in neuromodulation for oab has focused on alternatives to sns . the literature suggests that pns via the posterior tibial nerve or the pudendal nerve may be viable options . posterior tibial nerve stimulation ( ptns ) was first introduced by mcguire and colleagues in 1983 , and more recent studies have confirmed a 60% to 80% positive response rate after 10 to 12  weekly treatments . ptns is performed by inserting a 34-gauge needle about 3 to 4  cm cephalad to the medial malleous , between the posterior margin of the tibia and soleus muscle . once connected , an adjustable voltage pulse intensity of 0 to 10  ma , a fixed pulse width of 200 , and a frequency of 20  hz were delivered during weekly 30-min sessions . correct position is confirmed by flexion of the great toe or fanning of the toes and a tingling sensation . adverse events associated with ptns are minimal , mostly minor hematomas at the site of needle insertion . peters et al . [ 10 ] published a randomized , multicenter study that compared the efficacy of ptns with that of extended - release tolterodine , also known as the orbit ( overactive bladder innovative therapy ) trial . a total of 100 adults with urinary frequency were randomly assigned to 12  weeks of treatment with ptns or 4  mg / d of extended - release tolterodine . after 12  weeks of therapy , the ptns arm reported a 79.5% cure or improvement rate , compared with 54.8% of those on tolterodine ( p  =  0.01 ) on the global response assessments . the two groups had similar improvements on objective measures , including reductions in urinary frequency , urge urinary incontinence episodes , urge severity , and nighttime voids , and increased voided volume . the authors concluded that ptns was safe and efficacious , with statistically significant subjective and objective improvements comparable to that of pharmacotherapy . peters et al . [ 11 ] also compared the efficacy of ptns to that of sham in a multicenter , double - blind , randomized trial known as sumit ( study of urgent pc versus sham effectiveness in treatment of overactive bladder symptoms ) . after 12  weeks , 54.5% of the ptns patients reported moderate or markedly improved response from baseline , compared with 20.9% of sham patients ( p  <  0.001 ) . ptns also increased voided volume when compared with baseline from 83 to 169.5  ml ( p  =  0.01 ) . patients were not able to correctly identify if they were part of the sham or ptns group , as both groups had leads placed . the results from this study suggest that the therapeutic effect of ptns is a result of stimulation of the posterior tibial nerve and not a placebo effect . following the encouraging results from the sumit and orbit studies demonstrating true therapeutic effects comparable to those of tolterodine , other authors focused on various treatment courses and durability . the traditional ptns treatment course runs for 12  weeks , with weekly 30-min sessions . forty - three women underwent this shortened treatment course and were evaluated with bladder symptom diaries and the incontinence impact questionnaire ( iiq-7 ) , which is a health - related quality - of - life questionnaire . a positive response to therapy was defined as 1 ) oab symptoms no longer being bothersome , 2 ) reduction by half in frequency episodes , and 3 ) reduction by 25% in iiq-7 outcomes . the positive response rate was 69.7% , with an almost 50% decrease in the median daytime and nocturnal frequency ( 11.8 vs 6.9 and 3.5 vs 1.8 ; p  <  0.05 ) . patients reported fewer urge incontinence episodes per 24  h , from a median of 3.5 to 2.4 ( p  <  0.05 ) . the median iiq-7 scores decreased by 25% ( 30.4 vs 24.3 ; p  <  0.05 ) , and the median number of pads used in 24 hours decreased by 34% ( 3.8 vs 2.5 ; p  <  0.05 ) . however , the participants reported return of symptoms 3  weeks after the treatment , and no predictors of duration of symptomatic relief could be identified . these early data suggest that the ptns treatment course can be halved , but more conclusive studies are needed to determine the optimal duration of initial treatment and maintenance program . thirty - three of the 35 responders from the initial 12-week treatment course elected for maintenance therapy . a total of 32 completed 6  months of maintenance , and 25 completed 12  months . the participants received a mean of 12.1    4.9 treatments over an average of 263  days , with a mean of 21  days ( median , 17 ) between treatments . however , the participants had longer time intervals during the second 6  months than during the first 6  months of the evaluation ( 14 vs 24  days ) . subjective global assessments showed a sustained improvement of symptoms from 12  weeks at the 6-month and 12-month evaluations ( 94% and 96% , respectively ) . there were also objective improvements from baseline , with decreases of 2.8 voids per day ( p  <  0.001 ) , 1.6 urge incontinence episodes per day ( p  <  0.001 ) , 0.8 nocturnal voids ( p  <  0.05 ) , and an increase of 39  ml in voided volume ( p  <  0.01 ) . the authors concluded that ptns can be a viable long - term therapeutic option for oab patients . a global evaluation of ptns as a treatment option for oab was performed by ridout and yoong   with a review of the published literature . these studies used various criteria for  positive response ,  such as objective reduction in symptoms and the request for maintenance therapy following completion of the 12-week course . using these varying definitions of success most authors agree that ptns requires indefinite maintenance therapy , but the specifics of the maintenance program have not yet been defined . van der pal et al .   showed that 64% of patients reported greater than 50% worsening in frequency and incontinence episodes after a 6-week pause in treatment . overall , ptns seems to offer symptomatic relief for oab patients who are refractory to conservative therapy , but standard guidelines for initial therapy and maintenance regimens are lacking . in addition to the sacral and the posterior tibial nerves , physicians can target the pudendal nerves for neuromodulation . the sacral nerve sensory afferent fibers originate in the pudendal nerve , which innervates the pelvic floor muscles , external urethral and anal sphincters , and pelvic organs performed a retrospective review of patients undergoing tined lead placement at the pudendal nerve via the ischial - rectal approach for chronic pudendal neuromodulation . there were 84 patients with various primary urologic diagnoses , including interstitial cystitis / painful bladder syndrome , urgency / frequency or urge incontinence , nonobstructive urinary retention , and pelvic / bladder pain without interstitial cystitis . almost all individuals with a history of failed sacral neuromodulation responded to the pudendal lead stimulation ( 93.2% [ 41 of 44 ] ) . overall , positive pudendal response ( 50% improvement on the pudendal lead ) was achieved in 60 of 84 participants ( 71.4% ) . these are encouraging results that warrant further investigation and suggest that pudendal nerve  targeted neuromodulation may be a viable alternative to sns . since its introduction , medtronic has made some advancement in the design of the sns device . the introduction of the tined lead 5  years ago changed sacral neuromodulation from a single - stage open surgery requiring general anesthesia to a two - stage , minimally invasive , percutaneous procedure with local anesthesia . because there is less lead migration , the permanent tined lead allows for a longer trial period , during which the physician and patient can reprogram the device until they achieve optimal settings . as a result of this extended test period , the technical failure rate has decreased , and the response rate has almost doubled to approximately 80% . the most recent technological development in the interstim apparatus has been the interstim ii device . this change purportedly increases patient comfort and makes the implant procedure easier and quicker for the surgeon . a postmarket , web - based survey among 11 european experts in urology , gynecology , and gastroenterology evaluated their initial experience with the new interstim ii therapy in 55 patients . the less bulky interstim ii implantable neurostimulator allowed for a tinier incision and shallower pocket ( 3.5  cm less ) , which made implantation more tolerable , especially for thinner patients . moreover , the new device does not require an extension cable , which reduced operative time . the new small icon patient programmer also offers the patient more flexibility , with four preset programs to optimize the response rate . during the past year , several authors reported their experience with sacral neuromodulation in nontraditional patient populations , including patients with neurogenic detrusor overactivity , failed augmentation cystoplasty , and children . a recent article from italy looked at ptns as a treatment option for children with lower urinary tract dysfunction . forty - four children with a variety of urologic diagnoses ( including idiopathic oab , dysfunctional voiding , underactive bladder , underactive valve bladder , and neurogenic bladder ) were enrolled in a prospective clinical trial of ptns efficacy . a total of 25 were female and 18 were male ( average age , 10.7    4.8  years ) . follow - up assessment was performed every 6  months for 2  years after treatment . symptomatic improvement was greater in non - neurogenic than in neurogenic cases ( 78% vs 14% ; p  <  0.002 ) . at 1-year follow - up , the cure rate was greater in dysfunctional voiding than in oab cases ( 71% vs 41% ) , and it remained the same at 2  years . chronic neuromodulation was required to maintain results in 29% of patients with dysfunctional voiding and 50% of patients with oab . thus , ptns appears to be a viable option for treating pediatric lower urinary tract dysfunction , especially in non - neurogenic cases . as in the pediatric population , however , apart from spinal cord injury patients , neuromodulation is not commonly offered to this group of patients . van rey and heesakkers [ 18 ] wrote a review article on the applications of neurostimulation for urinary storage and voiding dysfunction in neurological patients . this article reviewed the use and results of pudendal nerve stimulation , sns , and lower limb stimulation in patients with neurogenic detrusor overactivity . some evidence has demonstrated sns efficacy in treating neurogenic bladder disorders in multiple sclerosis patients , but this population has a chance of negative test stimulation that is four times higher [ 18 ] . pudendal nerve stimulation via dorsal penile / clitoral nerve stimulation has been shown to benefit spinal cord injury patients by increasing cystometric capacity and inhibiting neurogenic bladder overactivity . the current use of pudendal nerve stimulation is limited by a lack of reliable stimulation technique , as pudendal nerve stimulation via tined leads and surface electrodes is still in the preliminary stages . as a third alternative to sacral and pudendal nerve stimulation , ptns also has been reported to be effective for a patient population of individuals with multiple sclerosis , myelitis , incomplete spinal cord injury , stroke , and parkinson s disease [ 20 , 21 ] . these studies suggest there is significant benefit to neuromodulation among this special patient population that warrants further study . part of the advantage of sns is that it provides treatment for refractory oab patients without requiring extensive surgery ( eg , augmentation cystoplasty ) . however , some patients have already undergone augmentation cystoplasty and continue to suffer with oab symptoms . .   reported on their case series of two such patients who were treated with sacral neuromodulation . one patient continued to void every 30 to 60  min despite medical therapy , intravesical treatment with bont - a , and augmentation cystoplasty . this patient ultimately underwent staged sacral approach implantation and was able to wait 3  h between voids during the trial period . she had durable improvement at 14  months of follow - up after the second - stage implantation . the second patient had undergone a supratrigonal ileocystoplasty but still voided every 1.5  h with volumes ranging from 50 to 220  ml . after her staged sacral neuromodulator implantation , she was able to wait 3 to 4  h , and her voided volume ranged from 300 to 500  ml . both patients had videourodynamics as part of their preoperative assessment , which demonstrated good compliance and capacity . this case series indicates that sns may be an important adjunctive therapy for patients with truly refractory oab despite bladder augmentation . during the past year , the literature regarding neuromodulation for treating oab has focused heavily on validating ptns and pudendal nerve stimulation as reasonable alternatives to sns . other significant articles re - examined sns in terms of safety , efficacy , and cost - effectiveness . the general conclusion is that neuromodulation is an efficacious and safe treatment option for patients with medically refractory oab . the inclusion criteria for sns treatment have expanded to embrace the neurogenic and pediatric populations , as well as those who have undergone augmentation cystoplasty . future efforts should focus on defining optimal treatment and maintenance schedules for less invasive ptns and reporting the preliminary experience with the new interstim ii device . the current developments in technology and clinical applicability will continue to broaden the field of neuromodulation for urologic patients .
from the time that it was granted us food and drug administration approval , neuromodulation has secured a firm position in the treatment algorithm for overactive bladder . with neuromodulation 
 , physicians were able to bridge the gap between the two ends of the treatment spectrum ( medical therapy and open surgery ) . 
 sacral nerve stimulation has been the most widely used form of neuromodulation . 
 recent modifications to its design , namely the development of the tined lead and the launching of the refined interstim ii ( medtronic , minneapolis , mn ) , have made sacral nerve simulation even less invasive and more effective . while interstim is maintaining a level of success with these advancements , peripheral means of neuromodulation are being explored . 
 the current literature takes a closer look at posterior tibial and pudendal nerve stimulation as alternatives to sacral nerve stimulation . 
 the field of neuromodulation is also expanding in terms of the target patient population , as it is being used to treat children , patients with neurological disease , and others . as the role of neuromodulation increases 
 , we must continue to assess its efficacy , safety , and cost - effectiveness in comparison to other therapeutic options .