Tibial Nerve Stimulation: Recent Progress and Challenges.

27. Sural and tibial nerve SEPs are mediated by the same spinal pathway

AimsTo determine time course of the bladder inhibitory response to unilateral or bilateral stimulation of the tibial nerve (TN) and spinal nerve (SN) as well as the interaction of stimulation at these two sites.MethodsIn anesthetized female rats, a wire electrode was placed under either one or both of the TN or L6 SN. A cannula was placed into the bladder via the urethra. Saline infusion induced bladder rhythmic contraction (BRC).ResultsCompared to SN neuromodulation, TN neuromodulation is less efficacious. The first 5-min stimulation at three times motor threshold on the SN and TN decreased the BRC frequency to 9% and 69% of controls, respectively. In contrast to SN stimulation, bilateral TN neuromodulation is not more effective than unilateral and sustained TN stimulation results in an apparent desensitization of the bladder response. If a 15-min TN stimulation was applied, BRCs were shutdown only during the first 5 min of stimulation. If a 5-min stimulation, using sufficient current to abolish BRC, is repeated, at least 20 min between stimulations was required in order for the responses to the first and second stimulations to be equivalent. Finally, stimulation of the TN combined with SN never produced a significantly greater effect than TN or SN stimulation alone.ConclusionsBased on the current experiments, it would appear that SN neuromodulation of bladder activity is preferable to TN stimulation and there is no evidence to suggest that stimulation at both sites would offer a therapeutic advantage over spinal stimulation alone. Neurourol. Urodynam. 34:92–97, 2015. © 2013 The Authors. Neurourology & Urodynamics published by Wiley Periodicals, Inc.

Spinal nerve (SN) stimulation inhibits the bladder rhythmic contraction (BRC) in anesthetized rats. This preparation was used to study the effects of electrical stimulation of the tibial nerve (TN) and the dorsal nerve of the clitoris (DNC) on BRC. Stimulation of the TN and DNC for 10 min produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. As observed with the SN, 10-Hz stimulation of either TN or DNC produced the greatest degree of inhibition, with lower or higher frequencies being either less efficacious or inactive. In contrast to the prolonged inhibition produced by SN stimulation, both TN and DNC stimulation produced "short" lasting inhibition of bladder contractions and the maximal inhibition occurred during stimulation. TN stimulation was effective over only a narrow range of current intensities [3-4 × motor threshold current for inducing a toe twitch (T(mot))] and only at a frequency of 10 Hz. Stimulation of TN at 10 Hz, 3 × T(mot) inhibited BRC to 23% of control. Ten-hertz DNC stimulation at 2 × T(EAS), the threshold current for evoking a reflex anal sphincter contraction, decreased the frequency of contractions to 4% of control. Although compared with the respective threshold current the BRC response was more sensitive to DNC compared with TN stimulation, the absolute current required to reduce BRC using DNC stimulation appeared to be higher. Comparing the effects of TN and DNC stimulation to our previous results with SN stimulation, SN stimulation produces the largest duration and efficacy of bladder inhibition.

Chronic pelvic pain (CPP) and bladder pain syndrome (BPS) can have a negative impact on quality of life. Neuromodulation has been suggested as a possible treatment for refractory pain. To assess the effectiveness of tibial and sacral nerve stimulation in the treatment of BPS and CPP. We searched until July 2012: the Cochrane Library, EMBASE (1980-2012), Medline (1950-2012), Web of knowledge (1900-2012), LILACS (1982-2012) and SIGLE (1990-2012) with no language restrictions. We manually searched through bibliographies and conference proceedings of the International Continence Society. Randomized and prospective quasi-randomized controlled studies vs. sham nerve stimulation treatment or usual care of patients with CPP and BPS who underwent sacral or tibial nerve stimulation were included. Any studies involving transcutaneous stimulation were excluded. The outcome was a cure or improvement in symptoms. Three studies with 169 patients treated with tibial nerve stimulation were included; two for CPP and one for BPS. There were improvements in pain, urinary and quality of life scores. There were no reported data for sacral nerve stimulation. There is scanty literature reporting variable success of posterior tibial nerve stimulation in improving pain, urinary symptoms and quality of life in CPP and BPS. In view of the dearth of quality literature, a large multi-centered clinical trial investigating the effectiveness of electrical nerve stimulation to treat BPS and CPP along with the cost-analysis of this treatment is recommended.

Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Sham Efficacy in the Treatment of Overactive Bladder Syndrome: Results From the SUmiT Trial

Somatosensory evoked cortical potentials (SSEP's) were recorded in 27 healthy subjects using tibial and peroneal nerve stimulation with cephalic and non-cephalic references. Four major peaks were present in all recordings. Analysis of these components showed that SSEP's collected after tibial nerve stimulation with non-cephalic reference (linked earlobes) produced the most consistent clearly defined component peaks. Average latency, amplitude, and interpeak latency differences are presented for these SSEP's. Significant correlations were obtained between the height of the individual and the P1, N2, P2, and N3 latencies, and the N3-P1 interpeak latency. These results suggest that reproducible SSEP's can be obtained from tibial nerve stimulation in normal subjects using minimal numbers of stimulus presentations (28 to 64). The SSEP's from 34 patients with varying degrees of spinal cord trauma were compared with the SSEP's from normal subjects. These comparisons involved the P1, N2, P2, and N3 latencies and the interpeak latency values, as well as the amplitude values. Patients with normal sensory and motor neurological examinations could be distinguished from patients showing decreased sensory and motor findings or clinically complete lesions on the basis of peak latency and interpeak latency values. The latter two groups could not be distinguished from one another. In general, all patient groups had SSEP's of lower amplitude than did normal individuals, but the groups could not be distinguished from one another. These results indicate that SSEP's can be a useful clinical tool for differentiation of complete from incomplete spinal cord lesions, but do not invariably predict recovery of function.

Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function—in particular, non-voiding bladder contractions and intravesical pressure—immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.

MP1-14 POST-STIMULATION INHIBITION OF BLADDER ACTIVITY INDUCED BY TIBIAL NERVE STIMULATION IN RATS

Pre-movement modulation of tibial nerve SEPs caused by a self-initiated dorsiflexion

Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Extended-Release Tolterodine: Results From the Overactive Bladder Innovative Therapy Trial

Frequency Dependent Tibial Neuromodulation of Bladder Underactivity and Overactivity in Cats

Giant early components of somatosensory evoked potentials to tibial nerve stimulation in cortical myoclonus

Réflexes du muscle soléaire évoqués par la stimulation du nerf tibial postérieur versus réflexe tendineux chez l'homme

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve.

In humans, peripheral sensory stimulation inhibits subsequent motor evoked potentials (MEPs) induced by transcranial magnetic stimulation; this process is referred to as short- or long-latency afferent inhibition (SAI or LAI, respectively), depending on the inter-stimulus interval (ISI) length. Although upper limb SAI and LAI have been well studied, lower limb SAI and LAI remain under-investigated. Here, we examined the time course of the soleus (SOL) muscle MEP following electrical tibial nerve (TN) stimulation at the popliteal fossa at ISIs of 20–220 ms. When the conditioning stimulus intensity was three-fold the perceptual threshold, MEP amplitudes were inhibited at an ISI of 220 ms, but not at shorter ISIs. TN stimulation just below the Hoffman (H)-reflex threshold intensity inhibited MEP amplitudes at ISIs of 30, 35, 100, 180 and 200 ms. However, the relationship between MEP inhibition and the P30 latency of somatosensory evoked potentials (SEPs) did not show corresponding ISIs at the SEP P30 latency that maximizes MEP inhibition. To clarify whether the site of afferent-induced MEP inhibition occurs at the cortical or spinal level, we examined the time course of SOL H-reflex following TN stimulation. H-reflex amplitudes were not significantly inhibited at ISIs where MEP inhibition occurred but at an ISI of 120 ms. Our findings indicate that stronger peripheral sensory stimulation is required for lower limb than for upper limb SAI and LAI and that lower limb SAI and LAI are of cortical origin. Moreover, the direct pathway from the periphery to the primary motor cortex may contribute to lower limb SAI.