Overactive bladder symptoms of urgency, frequency, and urge incontinence have a high impact on many individuals, especially with increasing age. In the last two decades, the use of sacral neuromodulation has become quite common for the treatment of refractory overactive bladder. Studies have shown its efficacy in reducing voids, increasing bladder capacity, and decreasing leakage events, with effects persisting for multiple years post-implantation. Albeit a relatively high incidence of adverse events, SN is a cost-effective choice for long term compared to botulinum toxin A. This article explores how SN is an effective treatment for refractory OAB, the mechanisms underlying this, its outcomes, complications, and cost-effectiveness.
Introduction:
OAB was first defined in 1996 as a symptom complex of urinary urgency, frequency, nocturia, and incontinence. The International Continence Society separates OAB from detrusor overactivity, describing this disorder as related to involuntary detrusor contractions. OAB wet, associated with the symptom of involuntary loss of urine with urgency, causes a significant diminution in the quality of life.
In large numbers, the population is affected by OAB, and increasing age is associated with an increased prevalence. Although carried out in both men and women, it is in older-age groups that there is a substantial increase in prevalence studies. The social, psychological, and economic burdens are huge, and the estimated economic burden is approximated at US$76.2 billion in 2015 in the US alone.
Treatment modality classically begins with conservative therapies like biofeedback and behavioral therapy. Anticholinergics and beta-3 agonists are first-line medical therapies, with surgical modalities used in more severe cases. Sacral neuromodulation has been used since its approval by the FDA in 1997 for refractory OAB with long-term benefits mainly in those who had not previously responded to other modalities.
What is Sacral Neuromodulation?
Neuromodulation therapy slightly manipulates the functioning of the nerves by introducing small electrical impulses in the nerves. In sacral neuromodulation, the stimulation is delivered to the sacral nerves that arise from the region of the tailbone. The nerves connecting the spinal cord to the bladder are those that arise from the sacral region, and their signals malfunction in OAB. The abnormal signals in the case of OAB are interrupted by SN, which relieves the symptoms.
Mechanism of Sacral Neuromodulation
The most studied form of SN utilizes the InterStim device from Medtronic. InterStim acts by stimulating the sacral nerves to alter abnormal reflexes in the sacral and pelvic nerves which supply the bladder and pelvic floor. It also helps to control the abnormal communications between the brain and the bladder.
The abnormal reflexes controlled by InterStim include the following:
Overactive bladder with frequency, urgency, and urge urinary incontinence.
Some cases of urinary retention or inability to empty the bladder, unrelated to block of the urinary tract.
Pathophysiology/Mechanism
Urinary tract dysfunction is part of central nervous system abnormalities. Abnormalities or procedures that affect the nerves S2-S3 disrupt the lower urinary tract, leading to its compensatory responses, which have been proposed to result in bladder overactivity, the hallmark of OAB. Theories postulate that the symptoms of OAB are a result of intermittent spasms of the pelvic floor musculature and/or the bladder. Four main etiologies have been identified to contribute to OAB: phasic smooth muscle detrusor contractions, activation of sensory afferent nerves, enhanced excitatory transmission in the CNS, and reduced CNS inhibition.
SN will try to preserve the native bladder and provide relief without invasive surgeries. It was introduced by Tanagho and Schmidt in 1988 and consists of placing an electrode in the S3-S4 sacral foramen for chronic electrical stimulation. It was initially a one-stage process but was modified into a two-step algorithm in 2003, after which it hugely increased the success rate and minimized the complications.
Even though SN's mechanism is not well understood, it is believed to take part in the inhibition of the afferent activity of the bladder sensory processing in the spinal cord. The stimulation of alpha myelinated afferent fibers and unmyelinated C fibers of S3 and S4 nerve roots brings about changes in the micturition reflex and functions based on the concept of electrical stimulation, which inhibits or incites neural reflexes that might even suppress the over-activity of the bladder.
Treatment process with Sacral Neuromodulation.
InterStim® works like a cardiac pacemaker but for the bladder. InterStim® is surgically inserted in two stages.
Stage 1: The Trial Stage
During this stage, a "pacing wire" is inserted under X-ray guidance, adjacent to one of your sacral nerves. This is done as a day case. If this trial period reduces urinary symptoms due to bladder overactivity by at least 50%, then the full pacemaker can be implanted in the patient. There exists a test stage where patients can have the InterStim® implanted for a few days to try it out before opting for permanent treatment. Approximately 7 out of 10 patients progress from test stimulation to having the permanent pacemaker, known as InterStim®, implanted.
Stage 2: Permanent InterStim® Pacemaker Insertion
The permanent InterStim® pacemaker is a device smaller than a matchbox, which lies in the fat of the buttock and is not visible. It is attached via the pacing wire that was inserted during the trial stage.
Details of the Trial Stage (Stage 1 InterStim® Implant)
The trial stage is performed as a day-case under anaesthesia. A fine wire is inserted through the skin over the sacrum, then positioned beside a sacral nerve with the use of fluoroscopic guidance. The wire is secured to the skin and covered with surgical dressings to prevent disturbance. This wire feeds an external controller that is generally carried like a pager under clothing during the trial phase of 10 to 14 days. The final pacemaker device is not implanted during this phase. The patient receives an external controller and keeps a bladder log to assess improvement in the OAB symptoms.
Permanent Pacemaker Information (Stage 2 InterStim ® Implant)
The permanent implantation of the pacemaker is determined by the patient and the physician before starting stage two. In case the InterStim ® has reduced the symptoms significantly, then the permanent pacemaker is implanted with anesthesia. A small incision is made in the buttock skin, and the pacing wire is attached to the permanent InterStim pacemaker implanted deep in the fat of the buttock. It is controlled by a patient hand-held programmer with no external visible wires. An extensive amount of education is given to the patients on the use of the patient programmer, which is no more complicated than a mobile phone. Settings generally do not need to be changed on a routine basis.
Who is a Candidate for Treatment with Sacral Neuromodulation?
InterStim ® therapy is indicated for patients who are at least 18 years old and who have failed medical and conservative treatments that have been in place for a minimum of 12 months. Indications include:
Overactive bladder resulting from detrusor overactivity
Urinary retention without urinary tract obstruction.
In Australia, this therapy is also indicated for a subset of patients with refractory fecal incontinence that has failed to respond to prior treatment.
Who is Not a Candidate for Sacral Neuromodulation Treatment?
InterStim® treatment is contraindicated for:
Any patient with an unsuccessful Stage 1 trial or test stimulation.
Patients unable to operate the hand-held patient programmer.
Patient with urinary obstruction.
Pregnancy (InterStim device should be turned off during pregnancy).
People with severe or progressive neurological diseases such as Multiple Sclerosis.
Patients who may need to have future MRI scans of the spine. The InterStim device is not currently compatible with MRI although brain and limb MRI's may be performed after consulting with the radiologist
InterStim therapy is NOT designed to address:
Stress incontinence incontinence where urine leaks when you cough, sneeze or exercise.
Mechanical obstruction in the urinary tract such as an enlarged prostate or urethral strictures.
Results
Urge Incontinence
Studies have documented the short- and long-term efficacy of SN in the treatment of urge incontinence. Latini et al. noted 90% of patients had ≥50% symptomatic improvement with significant reductions in incontinence episodes and pad usage. Van Kerrebroeck et al. noted persistence of improvement at 5-year follow-up, with reductions in incontinence episodes and pad usage. Siegel et al. reported similar findings, noting long-term significant reductions in leakage events and pad usage.
Urgency/Frequency
SN has also been shown to benefit importantly in urgency and frequency symptoms. Chartier-Kastler et al. noted that voids per day decreased from 16.1 to 8.2 with increased bladder capacity and improvement in voided volumes. Hassouna et al. showed improvement in water cystometry and quality of life, which was directly attributable to the neuromodulators. Siegel et al. and van Kerrebroeck et al. reported that the reductions in daily voids were sustained at 2 and 5 years, respectively, with increased voided volumes.
Predictors of Response
The predicting factors of SN response include age, presence of chronic conditions, and neurologic status. Younger patients seem to have higher cure rates than those < 55 years. However, several studies reveal that there is no significant difference in outcomes between patients with or without neurologic disorders.
Complications
SN has a considerable rate of complication, and 30-40% of patients report problems after 5 years. The most common AEs reported are pain at the stimulator site, new pain, lead migration, infection, and transient electric shock. Surgical intervention for complications in 42.1% of the patients was reported by Van Kerrebroeck et al. after 5 years. Several studies indicate that predictive factors can include those like trauma history, changes in BMI, and pain clinic enrollment.
Cost-effectiveness
SN is an expensive surgical procedure, but it can be cost-effective if taken for a longer period. A study has shown a 73% decrease in office visit costs per year and considerable decrease in drug costs during the postimplant period.
