Lower urinary tract electrical sensory assessment: A systematic review and meta-analysis

OBJECTIVE To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs). The applied methods will be discussed in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics. METHODS The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched upon October 13, 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk-of-bias (RoB) as well as confounding. RESULTS After screening 9925 articles, 80 studies (5 randomized controlled trials (RCTs) and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects. 61 studies investigated exclusively CPTs and 19 studies reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and -SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in healthy subjects and patients. LUTESA demonstrated significant differences in LUT sensitivity between healthy subjects and neurological patients as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses revealed that several stimulation parameters (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies. CONCLUSIONS Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complement already established diagnostics such as urodynamics, allowing for a more comprehensive patient workup. The high RoB and confounding rate was rather related to inconsistency and inaccuracy in reporting than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool

Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials

Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of much-needed RCTs, we aimed to develop a suitable sham-control protocol for a clinical setting to maintain blinding but avoid meaningful stimulation of the tibial nerve. Three potential electrode positions (lateral malleolus/5th metatarsal/plantar calcaneus) and two electrode sizes (diameter: 2.5 cm/3.2 cm) were tested to determine which combination provided the optimal sham configuration for a TTNS approach, based on a visible motor response. Sixteen healthy volunteers underwent sensory and motor assessments for each sham configuration. Eight out of them came back for an extra TTNS visit. Sensory thresholds were present for all sham configurations, with linear regression models revealing a significant effect regarding electrode position (highest at plantar calcaneus) but not size. In addition, motor thresholds varied with the position-lowest for the 5th metatarsal. Only using this position and 3.2 cm electrodes attained a 100% response rate. Compared to TTNS, sensory and motor thresholds were generally higher for the sham configurations; meanwhile, perceived pain was only higher at the lateral malleolus. In conclusion, using the 5th metatarsal position and 3.2 cm electrodes proved to be the most suitable sham configuration. Implemented as a four-electrode setup with standardized procedures, this appears to be a suitable RCT protocol for maintaining blinding and controlling for nonspecific TTNS effects in a clinical setting

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction

OBJECTIVE To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end

Value of SUVmax for the prediction of bone invasion in oral squamous cell carcinoma

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUVmax) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUVmax in an almost linear manner. A pretherapeutic SUVmax of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUVmax between 9.5-14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning

Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23

The authors would like to make a correction to their published paper [1][...]

Transcutaneous Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Pilot Study for an International Multicenter Randomized Controlled Trial

BACKGROUND Tibial nerve stimulation (TNS) is an effective and safe treatment for idiopathic lower urinary tract dysfunction (LUTD), but its value in neurological patients is unclear. OBJECTIVE To test the feasibility, acceptability, and safety of a randomized, sham-controlled, double-blind transcutaneous TNS (TTNS) setup for treating neurogenic LUTD. DESIGN, SETTING, AND PARTICIPANTS A pilot study including nine patients with refractory neurogenic LUTD investigated prospectively at a university neuro-urology department. INTERVENTION Randomized, sham-controlled, double-blind verum and sham TTNS was performed for 30min twice a week, for 6 wks. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Outcomes were feasibility, acceptability, and safety of the TTNS protocol. Secondarily, potential efficacy was investigated. Descriptive statistics were used. RESULTS AND LIMITATIONS All procedures were feasible and well tolerated by all nine patients. Using verum TTNS, a motor response could be triggered in all patients and a sensory response in all but one. At the beginning and end of treatment, seven and six (78% and 67%) patients believed to receive verum TTNS, and five and six (56% and 67%) correctly guessed their group allocation, respectively. No treatment-related adverse events occurred. A comparison of baseline versus 6 wks of verum and sham TTNS led to relevant symptom and functional changes in only a limited number of piloted patients. CONCLUSIONS Verum and sham TTNS combined with the blinding procedures proved feasible and safe. Both interventions and procedures, as well as the randomization process, were well accepted by the patients. While the subsensory threshold TTNS approach in combination with the sham condition is advantageous for patients' blinding, the clinical findings raised some doubt regarding sufficient TNS. Hence, relevant methodological adjustments concerning the adequate stimulation current and corresponding sham condition are needed before starting randomized controlled trials to clarify the value and role of TTNS in neuro-urology. PATIENT SUMMARY Transcutaneous tibial nerve stimulation is a promising treatment option for neurogenic lower urinary tract dysfunction, but methodological adjustments in treatment application are required before further prospective studies can be initiated

Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials

Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of much-needed RCTs, we aimed to develop a suitable sham-control protocol for a clinical setting to maintain blinding but avoid meaningful stimulation of the tibial nerve. Three potential electrode positions (lateral malleolus/5th metatarsal/plantar calcaneus) and two electrode sizes (diameter: 2.5 cm/3.2 cm) were tested to determine which combination provided the optimal sham configuration for a TTNS approach, based on a visible motor response. Sixteen healthy volunteers underwent sensory and motor assessments for each sham configuration. Eight out of them came back for an extra TTNS visit. Sensory thresholds were present for all sham configurations, with linear regression models revealing a significant effect regarding electrode position (highest at plantar calcaneus) but not size. In addition, motor thresholds varied with the position—lowest for the 5th metatarsal. Only using this position and 3.2 cm electrodes attained a 100% response rate. Compared to TTNS, sensory and motor thresholds were generally higher for the sham configurations; meanwhile, perceived pain was only higher at the lateral malleolus. In conclusion, using the 5th metatarsal position and 3.2 cm electrodes proved to be the most suitable sham configuration. Implemented as a four-electrode setup with standardized procedures, this appears to be a suitable RCT protocol for maintaining blinding and controlling for nonspecific TTNS effects in a clinical setting.ISSN:2227-905