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      Detecting Bladder Biomarkers for Closed-Loop Neuromodulation: A Technological Review

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          Abstract

          Neuromodulation was introduced for patients with poor outcomes from the existing traditional treatment approaches. It is well-established as an alternative, novel treatment option for voiding dysfunction. The current system of neuromodulation uses an open-loop system that only delivers continuous stimulation without considering the patient’s state changes. Though the conventional open-loop system has shown positive clinical results, it can cause problems such as decreased efficacy over time due to neural habituation, higher risk of tissue damage, and lower battery life. Therefore, there is a need for a closed-loop system to overcome the disadvantages of existing systems. The closed-loop neuromodulation includes a system to monitor and stimulate micturition reflex pathways from the lower urinary tract, as well as the central nervous system. In this paper, we reviewed the current technological status to measure biomarker for closed-loop neuromodulation systems for voiding dysfunction.

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          Most cited references54

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          Adaptive Deep Brain Stimulation for Movement Disorders: The Long Road to Clinical Therapy

          Continuous high-frequency DBS is an established treatment for essential tremor and Parkinson’s disease. Current developments focus on trying to widen the therapeutic window of DBS. Adaptive DBS (aDBS), where stimulation is dynamically controlled by feedback from biomarkers of pathological brain circuit activity, is one such development. Relevant biomarkers may be central, such as local field potential activity, or peripheral, such as inertial tremor data. Moreover, stimulation may be directed by the amplitude or the phase (timing) of the biomarker signal. In this review, we evaluate existing aDBS studies as proof-of-principle, discuss their limitations, most of which stem from their acute nature, and propose what is needed to take aDBS into a chronic setting.
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            Effectiveness of percutaneous posterior tibial nerve stimulation for overactive bladder: a systematic review and meta-analysis.

            To evaluate the effectiveness of posterior percutaneous tibial nerve stimulation (PTNS) in treating overactive bladder (OAB) symptoms by systematic review of the literature.
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              Percutaneous afferent neuromodulation for the refractory overactive bladder: results of a multicenter study.

              More than 20 million Americans have an overactive bladder, the predominant symptoms being frequency, urgency, urge incontinence and pelvic pain. While the etiology is not completely understood, most investigators believe the causes to be many and the pelvic floor to be intimately related. Whatever the etiology, traditional therapies, including dietary manipulation, bladder drill, medications and physical therapy, are often poorly tolerated and/or ineffective. We report a prospective, multicenter clinical trial that was undertaken to determine the safety and efficacy of percutaneous peripheral afferent nerve stimulation for treatment of refractive overactive bladder and/or pelvic floor dysfunction. A total of 53 patients with overactive bladders, in whom all traditional therapy failed, were enrolled in 1 of 5 sites within the United States. Patients received weekly percutaneous electrical stimulations via a 34 gauge needle placed near the tibial nerve 3 finger breadths above the ankle. Urodynamic studies, detailed voiding diaries, quality of life surveys, and incontinence impact questionnaires were completed before, during and after the study. Of the patients with a mean age of 57.4 years 89% (47 of 53) completed the 12-week study. A total of 71% of patients were classified as treatment successes by the investigators and were started on long-term treatment. On average patients noticed a 25% reduction in mean daytime and 21% reduction in mean nighttime voiding frequencies (p <0.05). Urge incontinence was reduced by an average of 35% (p <0.05). Statistically significant improvements were noted in selective pain and quality of life indexes. No significant adverse events related to treatment were noted in any patients. Percutaneous peripheral afferent nerve stimulation offers a safe, minimally invasive and effective treatment for managing refractive overactive bladder and/or pelvic floor dysfunction.

                Author and article information

                Journal
                Int Neurourol J
                Int Neurourol J
                INJ
                International Neurourology Journal
                Korean Continence Society
                2093-4777
                2093-6931
                December 2018
                31 December 2018
                : 22
                : 4
                : 228-236
                Affiliations
                [1 ]Smart Healthcare & Device Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
                [2 ]Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea
                [3 ]Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
                Author notes
                Corresponding author: Kyu-Sung Lee http://orcid.org/0000-0003-0891-2488 Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea E-mail: ksleedr@ 123456skku.edu / Tel: +82-2-3410-3554 / Fax: +82-2-3410-3027
                Co-corresponding author: Baek Hwan Cho http://orcid.org/0000-0002-4106-9042 Smart Healthcare & Device Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea E-mail: baekhwan.cho@ 123456samsung.com / Tel: +82-2-3410-0885 / Fax: +82-2-3410-2968
                Author information
                http://orcid.org/0000-0002-4106-9042
                http://orcid.org/0000-0003-0891-2488
                Article
                inj-1836246-123
                10.5213/inj.1836246.123
                6312967
                30599493
                b4bc8fcc-fef1-49fa-ba83-02e257448422
                Copyright © 2018 Korean Continence Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 November 2018
                : 11 December 2018
                Categories
                Review Article

                Neurology
                implantable neurostimulators,voiding dysfunction,urinary bladder diseases,biomarkers
                Neurology
                implantable neurostimulators, voiding dysfunction, urinary bladder diseases, biomarkers

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