Introduction
Overactive bladder (OAB) is characterized by urinary urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia, if there is no proven infection or other obvious pathology. The American Urologic Association (AUA) defines the refractory patient as the patient who has failed a sufficient trial of behavioral therapy and at least one medication (antimuscarinic or β-3 agonist) for 4 to 8 weeks. This may be because of lack of efficacy and/or intolerable side effects ( ). Currently accepted options for third-line therapy for refractory OAB include: (1) percutaneous tibial nerve stimulation (PTNS), (2) intradetrusor onabotulinumtoxinA (BTX-A), and (3) sacral neuromodulation (SNM). Emerging therapies may include selective bladder denervation, newer, smaller, magnetic resonance imaging (MRI)-compatible and rechargeable SNM devices, and chronic peripheral neuromodulation. This chapter will focus on the three common options for refractory OAB, with a brief discussion of emerging therapies.
Botulinum toxin
Background
The US Food and Drug Administration (FDA) approved BTX-A for cosmetic use in 1991. It has since been FDA approved for many indications including blepharospasm, cervical neck dystonia, hyperhidrosis, chronic migraine, and upper limb spasticity. In August 2011, BTX-A was approved for the treatment of neurogenic bladder; in January 2013, it was approved for treatment of OAB. BTX-A is a potent neurotoxin derived from the anaerobic bacterium’ Clostridium botulinum. Initially, the proposed method of action was based on data extrapolated from skeletal muscle, where BTX-A acts primarily as a muscle paralytic, inhibiting the presynaptic release of acetylcholine from motor neurons at the neuromuscular junction. As a result, a flaccid paralysis ensues. By cleaving protein receptors within the nerve terminals, BTX-A prevents the normal vesicular transport and release of acetylcholine from the motor nerve terminals into the neuromuscular junction. Since these initial theories were formulated, BTX-A has been found to also affect the afferent side of the nervous system by inducing changes like decreasing the sensory response of C-fibers ( ). It is likely that BTX-A has a complex inhibitory effect on vesicular release of excitatory neurotransmitters and on the axonal expression of other important mediators. Based on histologic evidence, recovery of chemodenervation occurs after 3 to 6 months. This is thought to be the result of turnover of the presynaptic molecules and nerve sprouting from the nerve terminal, forming a new functional synapse.
There are seven immunologically distinct subtypes of botulinum toxin, but only types A and B are available for use in clinical practice. BTX-A, which is approved for OAB treatment, is available as Botox (Allergan Inc., Irvine, CA) in the United States and as Dysport (Medicis Aesthetics) in the United Kingdom. Type B is less potent and is commercially available as MyoBloc in the United States and as NeuroBloc in Europe (Solstice Neurosciences, Louisville, KY). BTX-A is administered by cystoscopic injection of multiple aliquots into the detrusor muscle. The FDA-approved dosage for the treatment of neurogenic bladder is 200 U; the FDA-approved dose for OAB is 100 U.
Efficacy
An extensive Cochrane review’ and AUA systematic review summarize the literature surrounding the use of BTX-A for OAB ( ; ). The results summarized in these reviews and newer, relevant randomized controlled trials (RCTs) are presented here and in Table 32.1 . Four early randomized trials with placebo control groups evaluated intradetrusor injections of 50 to 300 U ( ; ; ; ). Overall, significant reductions in incontinence episodes and in urgency were reported in the active treatment groups. Voiding frequency results are less clear, with studies reporting a large range of reductions (e.g., from a nonsignificant 1.3 episodes per day to up to 14.2 episodes per day). This is likely because of the inclusion of patients with different baseline voiding frequency levels in these studies.
| Author | N | Baseline UUIE/Day | Outcome Definition | Outcome | Urinary Retention or Postvoid Residual |
| 200 U | |||||
| 43 | 5.17 | Failure = PGI-I score ≥4; | 60% response BTX group; median duration response: 373 days (BTX) vs. 62 (placebo) | 12/28 (43%) BTX vs. 0 Placebo (PVR >200 mL) | |
| 34 | 4.98 (BTX); 3.91 (placebo) | UUIE on diary, QOL | Sig changes in freq and UUIE/day | 6/18 (33%) BTX with PVR >150 mL | |
| 22 | 8 (BTX) 7.9 (placebo) | UUIE/day, QOL | QOL sig change; decreased UUIE/day in BTX (3.4/day) at 6 weeks | 26.6% PVR >200 mL at 6 weeks, 1 symptomatic requiring ISC | |
| 264 | 5.4 (BTX); 5.2 (SNM) | UUIE/day (average over 6 months) | Change 3.9 UUIE/day (BTX) vs. 3.3 (SNM) | 8% ISC at 1 month, 2% at 6 months | |
| 240 | 6.2 both groups | Voiding frequency/24hours at 6 months | Voiding frequency (8.3/24 hours [BTX] vs. 9.67/24 hours [placebo]) | 16% ISC (BTX), 4% ISC (placebo) | |
| 39 | 4.2 (100 U), 3.8 (200 U) | Improvement in urodynamic parameters at 3 months | Improved urodynamic both groups, no difference between groups | 10% (100 U), 20% (200 U) | |
| 100–150 U | |||||
| 44 | 9.8 (BTX) 9.3 (placebo) | >50% reduction of UUIE at 3 months | 100 U: 8/12 (67%), 150 U 9/12 (75%) | 2 pts, 1 in each group, ISC (PVR >350 mL) | |
| 45 | 6.8 (suburo), 11.3 (detrusor), 11.1 (bladder base) | Satisfaction based on symptom improvement | Satisfied (order of detrusor, suburo, bladder base): 3 months: 93%, 80%, 67%; 9 months: 20%, 20%, 6.7% | Acute retention: 2 detrusor, 2 suburo, 0 bladder base; PVR >150 mL: 33%, 47%, and 13% | |
| 313 | Not reported | Change from baseline in UUIE/week at 12 weeks | -17.4 (placebo), –20.7 (50 U), –18.4 (100 U), –23 (150 U), –19.6 (200 U), –19.4 (300 U) | PVR >200 mL at any visit; 2.3% (placebo), 8.9%–25.5% (BTX) | |
| 75 | Not reported | Self-reported UI (0 = none to 3 = severe), VD (0 = none to 3 = severe); Excellent (UI = 0 and VD increase <2), Improved (UI improved and VD increase <2) | Excellent or improved: 100 U 73.3%; 150 U 77.7%; 200 U 81.8% | PVR >150 mL: 100 U 30%, 150 U 72%, 200 U 52% | |
| 241 | 5.2 (medication), 4.8 (BTX) | Mean UUIE/day at 6 months | 3.4 (medication) and 3.3 (BTX) | 5% in the BTX group ISC | |
| 548 | 5.2 | Change from baseline UUIE/day | –2.95 (BTX) vs. –1.03 (placebo) | 6.9% of BTX performed ISC | |
| 99 | 5.9 (placebo), 3.9 (50 U), 5.9 (100 U), 3.9 (150 U) | >50% improvement in baseline urgency and UUI at 3 months | 65% (100 U), 56% (150 U) | 8 pts performed ISC | |
| 21 | 5.0 (placebo), 6.1 (BTX) | Maximum bladder capacity at cystoscopy | Mean max bladder capacity 161 mL higher in BTX vs. placebo | No ISC | |
The 2015 AUA literature review retrieved four additional RCTs with placebo control groups ( ; ; ; ) and two with nonplacebo comparator groups ( ; ). In general, most trials reported statistically significant improvements in measured voiding outcomes (UUI, urinary frequency, urgency, nocturia, pad use) and in quality-of-life (QOL) outcomes compared with placebo groups. Not included in these literature reviews was the Anticholinergic versus Botox Comparison (ABC) study, a multicenter RCT that compared the effectiveness of 6 months of daily anticholinergic therapy to a single intradetrusor injection of 100 U of BTX-A in patients with OAB symptoms ( ). This study included women who were either drug-naïve or who had tried two or fewer prior anticholinergic medications. The results demonstrated that anticholinergic medication had similar rates of improvement in daily UUI episodes compared with BTX-A injections (3.4 anticholinergic vs. 3.3 BTX-A; P = .81). However, patients who underwent BTX-A injections had significantly higher cure rates compared with patients who received anticholinergic medication (13% anticholinergic vs. 27% BTX-A; P < .01).
Finally, in the 2016 Refractory Overactive Bladder: Sacral Neuromodulation Versus Botulinum Toxin Assessment (ROSETTA) study, 364 women were randomized to cystoscopic intradetrusor injection of 200 U of BTX-A or to SNM ( ). The women in the BTX-A group had a greater reduction in 6-month mean number of episodes of UUI per day than did those in the SNM group (–3.9 vs. –3.3 episodes per day; P = .01).
Dosing considerations
Although the current FDA-approved dose of BTX-A for idiopathic OAB is 100 U, there is significant variation in reported dose and comparator arms in the literature. RCTs with different doses are reported in Table 32.1 . The studies reporting on active BTX-A (doses from 50–200 U) generally demonstrate improved efficacy of BTX-A compared with placebo, but there is not a clear relationship between dose and efficacy across these trials. One of the largest trials, performed by , randomized patients with idiopathic OAB (≥3 UUI episodes/3 days and ≥8 micturitions per day) to BTX-A at a dose of 100 U ( n = 277) or placebo ( n = 271). They found that, at 12 weeks, BTX-A significantly decreased UUI episodes/day compared with the control group (–2.95 BTX-A vs. –1.03 placebo; P < .001). As previously discussed, noted similar improvement in patients treated with BTX-A 100 U or anticholinergic medications, but an improved cure rate with BTX-A. compared responses across a wide range of BTX-A doses (50–300 U) and reported that doses of 100 U or greater were sufficient to reduce UUI episodes and improve QOL measures, but without clear dose-response effects above 150 U. This study was limited by lack of statistical comparison between groups.
randomized a total of 240 women with refractory OAB to receive either 200 U of BTX-A or placebo injection. The primary outcome was voiding frequency at 6 months. The median voiding frequency was lower after treatment with BTX-A compared with placebo (8.3 vs. 9.67, P < .01). Episodes of UUI also decreased (1.67 vs. 6.0, P < .01). Cure rates were higher in the BTX-A group compared with the placebo group (31% vs. 11%; P = .002). Given the available literature, our expert opinion is that patients should be counseled regarding the option for 100 U versus 200 U for refractory OAB.
Duration of effect and repeat injections
Most studies suffer from lack of long-term follow-up, but longer-term efficacy has been demonstrated in some studies. investigated clinical responders in the ROSETTA trial to determine efficacy up to 2 years. Clinical responders were defined as those experiencing at least a 50% reduction in UUI episodes 1 month after administration of BTX-A. Over the course of 2 years, up to two additional BTX-A injections were allowed after the initial 6-month study. No difference in decreased mean UUI episodes per day was found between the BTX-A and SNM groups over 24 months (–3.88 vs. –3.50, P = .15). The BTX-A group maintained high satisfaction and treatment endorsement throughout the 24-month period. Importantly, of the 115 participants who requested a second BTX-A injection, the median interval between first and second injection was 350 days (interquartile range 242–465 days).
Other prospective and retrospective studies have helped illustrate the duration of efficacy of BTX-A, especially after the first injection.’ reported on 68 women (baseline 5.7 UUI episodes/day) who underwent an intradetrusor injection of 100 U BTX-A and were followed for 12 months. Patients were allowed repeat injection at 12 months if they experienced symptom relapse. On average, patients had sustained improvement in UUI episodes/day up to 9 months (5.7 at baseline vs. 1.9 at 9 months). Twenty-five of the 54 patients with 12-month data requested a second injection, with similar improvements. reported on 125 patients who had two or more 200 U BTX-A injections (667 injections total). The median interval between injections was 14.4 months. There was sustained efficacy after repeat injections, with statistically similar times to repeat injections after the first four injections. Finally, reported similar significant reductions in frequency, urgency, and UUI after BTX-A injections in 100 patients, 63 of whom had two or more injections (mostly of 200 U). Again, the average time between injections ranged between 300 and 450 days.
Rates of BTX-A discontinuation are difficult to estimate because of differences in reporting and poor patient follow-up in many studies. Reasons for BTX-A discontinuation are more consistently reported and include failure of therapy (either subjective or objective) and low tolerability (e.g., having to perform intermittent self-catheterization [ISC], urinary retention, and recurrent urinary tract infections [UTIs]). Given the wide range of times until return of symptoms reported in the literature, it is likely prudent to avoid scheduled repeat injections and to proceed only with return of bothersome symptoms.
Location and depth of botulinum toxin injection
The location and depth of intradetrusor BTX-A injections vary across studies. Two systematic reviews evaluated adverse events and short-term efficacy associated with trigonal and extratrigonal BTX-A ( ; ). Importantly, both included studies that involved patients with neurogenic bladder. The earlier review by evaluated six studies (258 patients) that were carried out between 2006 and 2011. This meta-analysis did not show significant differences between trigonal and extratrigonal BTX-A for acute urinary retention (4.2% vs. 3.7%, P = .93), UTI, or short-term cure rates. In 2018, Jo et al. evaluated eight studies published from 2007 to 2016, only one of which was included in the previous systematic review. They found overall improved outcomes in the trigone inclusion arms based on higher complete dryness rates (odds ratio [OR] = 2.19, 95% confidence interval [CI] 1.32–3.63, P = .002) and fewer incontinence episodes (–0.85 per day, 95% CI –1.55 to –0.16, P = .02). No differences in safety or adverse events, including bladder discomfort, were seen between groups. A limitation of this meta-analysis was an overall small number of patients per study. In terms of depth of injection, the more recent systematic review evaluated an intradetrusor versus suburothelial approach and did not find a difference in reduction in UUI between groups (–1.32 episodes per day, 95% CI –5.69 to –3.06, P = .56; ).
Technique for botulinum toxin injection
The technique of mixing the BTX-A and how to inject it is described on the package insert and is standard ( http://www.allergan.com/assets/pdf/botox_pi.pdf ). The procedure is described here and demonstrated in 
.
BTX-A is a vacuum-dried protein available in 50-, 100-, and 200-U vials that must be refrigerated. Before injection, the vials of toxin must be reconstituted with preservative-free saline, and the mixture can be stored at 2° to 8° C for up to 24 hours. This outpatient procedure is easily performed in a clinical setting or, in rare circumstances, in an operating room. One trial reported similar pain scores of approximately 4/10 on a visual analog scale for subjects who had either local or general anesthetic ( ). Experts agree that intravesical premedication can be given in the office, with approximately 30 to 40 mL of 2% lidocaine instilled via catheter into the bladder for about 20 minutes before injection. There is little evidence regarding other management options or the impact of this strategy, and future research would help standardize recommendations.
Cystoscopy may be performed using a 30-degree, 12-degree, or even 0-degree lens with a rigid cystoscope plus working element with channel for injection needle or disposable injection needle. A flexible cystoscope with injection needle may also be used. The bladder is filled with approximately 100 mL of 0.9% normal saline to achieve some tautness to the bladder wall. Injections are spread over different rows to equally cover the bladder dome and posterior base, sparing the ureteral orifices ( Fig. 32.1 ). Some studies included a tiny amount of indigo carmine or methylene blue in the injection solution to facilitate visualization of the injection pattern. Again, depth of injection may not significantly impact efficacy, but visualization of injection may improve the ability to avoid extravasation of the injection through the bladder wall ( ). The concentration of toxin and volume of fluid that is injected are not consistent across studies. Although one study showed that a single BTX-A injection can spread the neurotoxin activity to the opposite side of the bladder ( ), the standard technique uses between 10 and 20 injections. prospectively compared the therapeutic effects and safety of different numbers of BTX-A injections for patients with OAB and found that injection of 1 mL of BTX-A (10 U) at 10 sites was adequate for an optimal therapeutic effect. The BTX-A package insert recommends administering 100 U as 0.5-mL (5 U) injections across 20 sites into the detrusor, for a total volume of 10 cc, but, given the literature, a total of 10 to 20 sites is likely similarly efficacious.
Complications and their management
Urinary retention and self-catheterization recommendations.
One of the most common complications after BTX-A injection is urinary retention. Rates of urinary retention range from 0% to 43% ( ). The definition of elevated postvoid residual (PVR) varies across studies, from 100 mL to 400 mL, with most studies defining an elevated PVR as 100 to 150 mL. Meta-analysis of data from RCTs comparing BTX-A to placebo showed a significant difference between BTX-A and placebo in terms of PVR-related catheterization (relative risk [RR]: 5.25; 95% CI 2.47–11.16; P < .01; ). The onset of urinary retention typically coincides with the clinical efficacy, beginning within the first week after injection. The duration of retention is variable, with some patients only requiring clean ISC for a few days, whereas for others the condition persists for the duration of the effects of the drug. Importantly, examined QOL outcomes in women who had to perform ISC post–BTX-A treatment compared with those who did not and found no differences between groups.
We tend to recommend teaching patients ISC before injection, because if patients report minimal voiding or dribbling they are then able to perform ISC at home. Patients can be seen in the office for an assessment of PVR urine volume by catheterization or bladder ultrasonography either at a standard interval (1–2 weeks) or with symptoms of urinary retention. Multiple previous randomized trials chose to require self-catheterization at residual volumes greater than 300 mL (without symptoms) or greater than 150 to 200 mL in the presence of bothersome retention symptoms ( ; ). In light of recent AUA guidelines regarding management of patients with nonneurogenic urinary retention ( ), we continue to recommend ISC only for PVRs greater than 300 mL in the asymptomatic patient or greater than 200 mL in the presence of bothersome retention symptoms. For those patients sent home who require ISC, a clear follow-up plan should be outlined, including how often to use the catheter and at what volumes catheterization should be continued or discontinued.
Urinary tract infection and antibiotic prophylaxis.
The other most common complication after BTX-A injection is UTI. Rates of UTI range from 3.6% to 54.5%, with four RCTs reporting rates of greater than 40%. In the aforementioned meta-analysis, there was a higher risk of UTI in the BTX-A group compared with the placebo group (RR: 2.36; 95% CI 1.58–3.53; P < .0001; ).
In terms of post–BTX-A UTI prevention, we adhere to AUA guideline recommendations for the use of prophylactic antibiotics for cystoscopy with manipulation for all patients ( ). These guidelines suggest administering antibiotics at the time of BTX-A, but specific recommendations are lacking. Antibiotic regimens can range from a single dose to use for 3 days before and 3 days after injection. A recent retrospective review of different prophylactic protocols found that starting antibiotics 1 day before BTX-A injection decreased the odds of postinjection UTI compared with postprocedure antibiotic prophylaxis only (OR’ = 0.23; 95% CI 0.07–0.73; P = .01; ). Based on these results, the authors recommended beginning antibiotic prophylaxis before the procedure and continuing it for 4 total days to decrease the risk of UTI. Similarly, the largest RCT to date used ciprofloxacin 500 mg on the day of procedure and for 3 days postprocedure ( ). The aforementioned AUA guidelines recommend fluoroquinolones, trimethoprim/sulfamethoxazole, or even a second-generation cephalosporin. Considering patient antibiotic allergies or intolerances, any of the options are reasonable to give on at least day of procedure and may be continued for 1 to 3 days, per provider preference.
Additionally, the FDA-provided safety instructions for BTX-A state that it should not be administered to a patient suffering from a UTI, owing to concerns over adverse events ( ). Although this recommendation seems prudent, given the discrepancy in UTI diagnostic criteria across studies and the high rates of asymptomatic bacteriuria in the elderly, we feel that current or recent bacteriuria is not an absolute contraindication to injection. In a cohort of patients undergoing BTX-A injection for either idiopathic or neurogenic detrusor overactivity, 38.8% of patients had asymptomatic bacteriuria ( ). Whereas postprocedure symptomatic UTI was more frequent in the asymptomatic bacteriuria group, there was no difference in serious adverse events like urosepsis, and there was similar efficacy between groups. Furthermore, performing BTX-A injection within 30 days of a recent UTI does not increase the odds of postprocedure UTI ( ). Our practice is to inquire about clinical symptoms and perform a urine dip on the day of injection. If patients are mildly symptomatic with a negative dipstick, we generally proceed with injection and send a urine culture to guide additional therapy in case they develop an increasingly symptomatic UTI. If patients have UTI symptoms and a positive dipstick, we tend to delay injection until a later date.
Conclusion
In conclusion, symptoms of OAB have been shown to significantly improve after BTX-A injections. Patients who are candidates for cystoscopic BTX-A injections should be counseled about the need for reinjections and possible postprocedure adverse events, including the risk of urinary retention requiring clean ISC and UTIs. Health care providers who perform BTX-A injections must have appropriate training and experience in treating women with pelvic floor disorders, operative cystoscopy privileges, and the ability to diagnose and manage any adverse outcomes after BTX-A injections into the bladder.
Sacral neuromodulation
Background and possible method of action
SNM for treatment of refractory OAB has undergone modifications since the initial FDA approval of InterStim (Medtronic Inc., Minneapolis, MN) for urinary urgency/frequency in 1999. The initial one-step process was altered in 2003 to create a two-step algorithm for permanent implantation. Afferent neural activity from the pelvic and pudendal nerves is thought to be primarily responsible for the effects of neuromodulation at the sacral level of the spinal cord (S2–S4) ( ; ). Normal voiding relies on intact neural pathways in the central nervous system. Pelvic parasympathetic nerves that arise at the sacral level of the spinal cord (S2–S4) are responsible for exciting the bladder and relaxing the urethra. The somatic nervous system acts on the external urethral sphincter via the pudendal nerve. The lumbar, pelvic, and pudendal nerves each contain both afferent and efferent axons that participate in feedback loops to manage voiding responses, which, if uninhibited, can result in urgency, frequency, and incontinence. Studies have evaluated multiple sites for neuromodulation, such as the sacral, tibial, pudendal, and genital nerves. However, the most commonly described site of neuromodulation for treatment of OAB is the third sacral nerve root (S3).
Efficacy
A variety of single-group observational studies were initially included in the evidence for SNM. The InSite Trial was a randomized, multicenter study evaluating the success rate of SNM compared with standard medical therapy in 147 patients with OAB ( ). Standard medical therapy was defined as antimuscarinic therapy, and inclusion criteria included failure of at least one medication. The primary objective was to compare the therapeutic success rate at 6 months, defined as 50% or greater improvement from baseline symptoms. For patients who were incontinent at baseline, 71% of those treated with SNM responded, compared with 47% of patients treated with standard medical therapy. Rates of complete continence were higher in those treated with SNM (39% vs. 21%), and this group showed statistically significant improvement over the standard medical therapy group in all measures of QOL. Follow-up studies continued to evaluate safety and efficacy of SNM over 5 years ( ). During the study period, 340 patients received test stimulation, and of those 272 (80%) had the SNM implanted. The overall therapeutic success rate at 5 years was 82% with sustained improvements in quality-of-life measurements. The 5-year cumulative rate of adverse events that required surgical intervention after the full SNM was implanted was 22%. The most common adverse event was an undesirable change in stimulation. Of note, the InSite trial does differ from many BTX-A trials in that patients had less severe symptoms at baseline. Again, in the ROSETTA trial, patients were randomized to receive either BTX-A 200 U or SNM. These patients had significant UUI, with an average of 5.2 UUI episodes per day in the SNM group. At 6 months, there were significant improvements in frequency of UUI episodes with a reduction to 3.3/day ( ). Two-year outcomes confirmed that improvements in UUI episodes/day (–3.5) and QOL were sustained ( ).
Progression from the advanced evaluation to pulse generator implantation ranges from approximately 70% to 80% ( ; ; ). One of the largest evaluations of SNM ( n = 2765) found that 69% of patients undergoing an advanced evaluation via staged approach progressed to pulse generator implantation ( ). This study found that a diagnosis of UUI was associated with the highest success with advanced evaluation (72%).
Surgical technique
The procedure is performed in one of two ways: an initial advanced evaluation (stage I, test stimulation) or basic evaluation (percutaneous nerve evaluation [PNE]). In some circumstances the procedure may involve a combined insertion of the lead and neurostimulator. The advanced evaluation (commonly referred to as test stimulation or stage I) is a clinical trial of a permanent tined lead with four electrodes using external stimulation. If the patient has appropriate symptom improvement with the test stimulation, a subcutaneous implantable pulse generator (IPG) is implanted. The basic evaluation (PNE) is placement of a temporary wire containing one electrode using external stimulation. Monitored anesthesia supplemented with local anesthesia is used for advanced evaluation, and local anesthesia alone is used for basic evaluation.
Advanced evaluation (test stimulation or stage I).
The current commercially available electrode lead incorporates four equally spaced electrode contact points on a flexible lead that is inserted percutaneously under image guidance and anchored in place by several plastic tines. After the patient receives sedation and local anesthesia, the S3 foramina are identified. The location of the S3 foramina is identified via fluoroscopy and should correspond to approximately 9 cm cephalad to the drop-off of the sacrum and 1 to 2 cm lateral to the midline on either side. Important anatomic landmarks are shown in Fig. 32.2 . The foramen needle is then inserted into the S3 foramen, ideally at a 45-degree angle. The position of the needle is confirmed using fluoroscopy. The nerve is test-stimulated for the appropriate motor and sensory responses, as listed in Table 32.2 ( ).
