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      A Proof-of-Concept Study of Transcutaneous Magnetic Spinal Cord Stimulation for Neurogenic Bladder

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          Abstract

          Patients with chronic spinal cord injury (SCI) cannot urinate at will and must empty the bladder by self-catheterization. We tested the hypothesis that non-invasive, transcutaneous magnetic spinal cord stimulation (TMSCS) would improve bladder function in individuals with SCI. Five individuals with American Spinal Injury Association Impairment Scale A/B, chronic SCI and detrusor sphincter dyssynergia enrolled in this prospective, interventional study. After a two-week assessment to determine effective stimulation characteristics, each patient received sixteen weekly TMSCS treatments and then received “sham” weekly stimulation for six weeks while bladder function was monitored. Bladder function improved in all five subjects, but only during and after repeated weekly sessions of 1 Hz TMSCS. All subjects achieved volitional urination. The volume of urine produced voluntarily increased from 0 cc/day to 1120 cc/day (p = 0.03); self-catheterization frequency decreased from 6.6/day to 2.4/day (p = 0.04); the capacity of the bladder increased from 244 ml to 404 ml (p = 0.02); and the average quality of life ranking increased significantly (p = 0.007). Volitional bladder function was re-enabled in five individuals with SCI following intermittent, non-invasive TMSCS. We conclude that neuromodulation of spinal micturition circuitry by TMSCS may be used to ameliorate bladder function.

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          Most cited references29

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          The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder.

          Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4-6 weeks (20-30 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. In 2011, leading TMS clinical providers and researchers created the Clinical TMS Society (cTMSs) (www.clinicaltmssociety.org, Greenwich, CT, USA), incorporated in 2013.
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            Noninvasive Reactivation of Motor Descending Control after Paralysis

            The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2-6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord.
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              Molecular and cellular development of spinal cord locomotor circuitry

              The spinal cord of vertebrate animals is comprised of intrinsic circuits that are capable of sensing the environment and generating complex motor behaviors. There are two major perspectives for understanding the biology of this complicated structure. The first approaches the spinal cord from the point of view of function and is based on classic and ongoing research in electrophysiology, adult behavior, and spinal cord injury. The second view considers the spinal cord from a developmental perspective and is founded mostly on gene expression and gain-of-function and loss-of-function genetic experiments. Together these studies have uncovered functional classes of neurons and their lineage relationships. In this review, we summarize our knowledge of developmental classes, with an eye toward understanding the functional roles of each group.
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                Author and article information

                Contributors
                dclu@mednet.ucla.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                22 August 2018
                22 August 2018
                2018
                : 8
                : 12549
                Affiliations
                [1 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Department of Neurosurgery, David Geffen School of Medicine, , University of California, Los Angeles, ; Los Angeles, California 90095 USA
                [2 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Department of Orthopedic Surgery, David Geffen School of Medicine, , University of California, Los Angeles, ; Los Angeles, California 90095 USA
                [3 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Neuromotor Recovery and Rehabilitation Center, David Geffen School of Medicine, , University of California, Los Angeles, ; Los Angeles, California 90095 USA
                [4 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Brain Research Institute, , University of California, Los Angeles, ; Los Angeles, California 90095 USA
                [5 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Department of Urology, David Geffen School of Medicine, , University of California, ; Los Angeles, CA 90095 USA
                [6 ]Department of Surgery, Division of Urology, Greater Los Angeles VA Healthcare System, Los Angeles, CA 90073 USA
                [7 ]ISNI 0000 0001 2179 2404, GRID grid.254880.3, Department of Molecular and Systems Biology, , Geisel School of Medicine at Dartmouth, ; Lebanon, NH 03756 USA
                Article
                30232
                10.1038/s41598-018-30232-z
                6105631
                30135433
                0a5c8110-081a-4edf-9a12-3760076391ca
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 April 2018
                : 25 July 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000005, U.S. Department of Defense (DOD);
                Award ID: SC103209
                Award Recipient :
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