Magnetic stimulation of the spinal cord to restore control of bladder and/or bowel

{
  "publication_number": "US11097122B2",
  "country": "US",
  "kind": "B2",
  "title": "Magnetic stimulation of the spinal cord to restore control of bladder and/or bowel",
  "abstract": "In various embodiments methods and devices are provided for facilitating locomotor function and/or voiding of bladder and/or bowel in a subject with a neuromotor disorder. In certain embodiments the methods involve providing magnetic stimulation of the spinal cord at a location, frequency and intensity sufficient to facilitate locomotor function and/or voiding of bladder and/or bowel.",
  "claims": [
    "1. A method of facilitating voiding or control of bladder and/or bowel in a subject with a neuromotor disorder, said method comprising: providing a plurality of treatments comprising magnetic stimulation of the thoracic and/or lumbosacral spinal cord at a location, a frequency and an intensity sufficient to alter the activity of spinal circuitry, rather than peripheral nerve or muscle stimulation, wherein the altered activity of spinal circuitry provides volitional voiding or control of bladder and/or bowel, wherein said plurality of treatments are provided at a treatment frequency of at least one treatment or more per week; reducing the treatment frequency of said treatments after said subject retains volitional voiding or control between treatments in the plurality of treatments even when magnetic stimulation is not present; and wherein said frequency ranges from 0.5 Hz up to 100 Hz, said magnetic stimulation is applied over one or more regions selected from the group consisting of T11-T12, L1-L2, and L2-L3; and treatment gains in the volitional voiding or control of bladder and/or bowel from the magnetic stimulation are hardwired and present even without magnetic stimulation.",
    "2. The method of claim 1, wherein said magnetic stimulation comprises stimulation at a frequency ranging from 0.5 Hz up to 20 Hz to induce micturition.",
    "3. The method of claim 1, wherein said magnetic stimulation comprises stimulation at a frequency from 20 Hz up to 100 Hz to suppress micturition.",
    "4. The method of claim 1, wherein said magnetic stimulation comprises magnetic pulses ranging in duration from 5 μs up to 500 μs.",
    "5. The method of claim 1, wherein a single treatment of said magnetic stimulation comprises 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10 or more periods of continuous magnetic stimulation and where there are two or more periods of continuous magnetic stimulation, the periods are separated by delay times in which there is no magnetic stimulation.",
    "6. The method of claim 5, wherein each of said period(s) of continuous stimulation independently ranges in duration from 10 seconds up to 10 minutes.",
    "7. The method of claim 5, wherein a single treatment comprises two or more periods of continuous magnetic stimulation separated by a delay period(s) where said delay periods independently range in duration from 5 seconds up to 5 minutes.",
    "8. The method of claim 7, wherein said treatment frequency is daily or weekly over a period of time of at least 4 weeks.",
    "9. The method of claim 8, wherein said treatment frequency is weekly.",
    "10. The method of claim 9, where said treatment comprises at least three stimulation periods with a break of 30 seconds between each stimulation period.",
    "11. The method of claim 9, where said subject obtains voluntary control of bladder and/or bowel after 16 weeks of weekly treatment.",
    "12. The method of claim 7, wherein said treatment frequency is daily, or every 2 days, or every 3 days, or every 4 days, or every 5 days, or every 6 days, or weekly until the subject obtains volitional control of micturition.",
    "13. The method of claim 12, wherein said treatment frequency is daily, or every 2 days, or every 3 days, or every 4 days, or every 5 days, or every 6 days, or weekly until the subject obtains their maximal volitional control of micturition.",
    "14. The method of claim 13, wherein the treatment frequency is reduced after the subject obtains maximal volitional control of micturition.",
    "15. The method of claim 14, wherein the treatment frequency is reduced to a level sufficient to maintain volitional control of micturition.",
    "16. The method of claim 15, wherein the treatment frequency is reduced to every three days, or to a weekly treatment, or to every 10 days, or to every 2 weeks.",
    "17. The method of claim 1, wherein said magnetic stimulation is applied over one or more regions selected from the group consisting of T1-T1, T1-T2, T1-T3, T1-T4, T1-T5, T1-T6, T1-T7, T1-T8, T1-T9, T1-T10, T1-T11, T1-T12, T2-T2, T2-T3, T2-T4, T2-T5, T2-T6, T2-T7, T2-T8, T2-T9, T2-T10, T2-T11, T2-T12, T3-T3, T3-T4, T3-T5, T3-T6, T3-T7, T3-T8, T3-T9, T3-T10, T3-T11, T3-T12, T4-T4, T4-T5, T4-T6, T4-T7, T4-T8, T4-T9, T4-T10, T4-T11, T4-T12, T5-T5, T5-T6, T5-T7, T5-T8, T5-T9, T5-T10, T5-T11, T5-T12, T6-T6, T6-T7, T6-T8, T6-T9, T6-T10, T6-T11, T6-T12, T7-T7, T7-T8, T7-T9, T7-T10, T7-T11, T7-T12, T8-T8, T8-T9, T8-T10, T8-T11, T8-T12, T9-T9, T9-T10, T9-T11, T9-T12, T10-T10, T10-T11, T10-T12, T11-T11, T11-T12, T12-T12, L1-L1, L1-L2, L1-L3, L1-L4, L1-L5, L1-S1, L1-S2, L1-S3, L1-S4, L1-S5, L2-L2, L2-L3, L2-L4, L2-L5, L2-S1, L2-S2, L2-S3, L2-S4, L2-S5, L3-L3, L3-L4, L3-L5, L3-S1, L3-S2, L3-S3, L3-S4, L3-S5, L4-L4, L4-L5, L4-S1, L4-S2, L4-S3, L4-S4, L4-S5, L5-L5, L5-S1, L5-S2, L5-S3, L5-S4, L5-S5, S1-S1, S1-S2, S1-S3, S1-S4, S1-S5, S2-S2, S2-S3, S2-S4, S2-S5, S3-S3, S3-S4, S3-S5, S4-S4, S4-S5, and S5-S6.",
    "18. The method of claim 1, wherein said magnetic stimulation is applied over a region between T11 and L4.",
    "19. The method of claim 18, wherein said magnetic stimulation is applied over L1 L2 and/or over T11-T12.",
    "20. The method of claim 1, wherein said magnetic stimulation produces a magnetic field of at least 1 tesla, or at least 2 tesla, or at least 3 tesla, or at least 4 tesla, or at least 5 tesla.",
    "21. The method of claim 1, wherein said subject is administered at least one monoaminergic agonist.",
    "22. The method of claim 1, wherein: said subject has a spinal cord injury; or said subject has an ischemic brain injury; or said subject has a neurodegenerative pathology.",
    "23. The method of claim 1, wherein said volitional voiding or control of bladder and/or bowel improves over a period ranging from 4 to 16 weeks after initiating said treatments.",
    "24. The method of claim 23, wherein said treatment frequency is weekly for at least 16 weeks.",
    "25. The method of claim 1, wherein said subject has sustained voluntary bladder contraction with increased detrusor pressure during micturition, in the absence of magnetic stimulation.",
    "26. The method of claim 1, wherein said subject has reduced urethral pressure that stays below bladder pressure during entire course of micturition without magnetic stimulation.",
    "27. The method of claim 1, wherein said subject retains volitional bladder control for at least 2 weeks without magnetic stimulation."
  ],
  "description_excerpt": "This invention was made with government support under Grant Number TR000124, awarded by the National Institutes of Health, and Grant Number W81XWH-14-2-0129, awarded by the U.S. Army, Medical Research and Materiel Command. The Government has certain rights in the invention.\n\nSpinal cord injury is a serious condition that frequently leads to long-term disabilities and significant social and economic consequences. The incidence annually is approximately 12.7 to 52.2 per 1 million (Oteir et al. (2014) Prehospital and Disaster Med., 29: 399-402). The annual total cost in the US is estimated to be approximately 10 billion dollars (Ma et al. (2014) Arch. Phys. Med. Rehab., 95: 986-995). Currently, there are more than 250,000 spinal cord injured individuals living in the US. Multiple studies have shown that bladder function, along with sexual function, consistently rank as the top health and quality of life priorities in these individuals (Simpson et al. (2012) J. Neurotrauma, 29: 1548-1555; Bloemen-Vrencken et al. (2005) Disabil. Rehab. 27: 1381-1389).\n\nIndividuals with spinal cord injuries must catheterize the bladder to empty it, and as a consequence, they experience high rates of urinary tract infections, obstructive uropathies and significantly reduced quality of life (Manack et al. (2011) Neurourol. Urodynam., 30: 395-401; Anderson (2004) J. Neurotrauma, 21: 1371-1383; Nicolle (2014) Curr. Infect. Dis. Rep. 16: 390). Direct muscle stimulation (Bartley et al. (2013) Nat. Rev., Urol., 10: 513-521) or stimulation of peripheral nerves (Brindley (1974) J. Physiol., 237: 15p-16p) or rhizotomy (Van Kerrebroeck et al. (1996) J.",
  "cpc": [
    "A61N 2/006",
    "A61N 1/0456",
    "A61N 1/36003",
    "A61N 1/36007",
    "A61N 1/36017",
    "A61N 1/36034",
    "A61N 1/40",
    "A61N 2/004",
    "A61N 2/02"
  ],
  "ipc": [
    "A61N 1/04",
    "A61N 1/36",
    "A61N 2/00",
    "A61N 2/02"
  ],
  "assignees": [
    "University of California San Diego UCSD"
  ],
  "inventors": [
    "Daniel C. Lu"
  ],
  "filing_date": "2016-11-04",
  "publication_date": "2021-08-24",
  "grant_date": "2021-08-24",
  "priority_date": "2015-11-04",
  "application_number": "US-201615344381-A",
  "family_id": "59019039",
  "cited_by_count": 21,
  "citations": [
    "US3543761A",
    "US3662758A",
    "US3724467A",
    "US4044774A",
    "US4102344A",
    "US4141365A",
    "US4285347A",
    "US4340063A",
    "US4379462A",
    "US4414986A",
    "US4538624A",
    "US4549556A",
    "US4800898A",
    "US4559948A",
    "US4573481A",
    "US4934368A",
    "US4969452A",
    "US5081989A",
    "US5002053A",
    "JPH0326620A",
    "US5031618A",
    "US5066272A",
    "US5121754A",
    "US5354320A",
    "US5374285A",
    "US5344439A",
    "US5417719A",
    "US5476441A",
    "US5643330A",
    "US5562718A",
    "US5733322A",
    "US6066163A",
    "US20020055779A1",
    "US6988006B2",
    "US7127297B2",
    "WO1997047357A1",
    "US5983141A",
    "US6500110B1",
    "RU2130326C1",
    "RU2141851C1",
    "US6122548A",
    "US6319241B1",
    "US20020111661A1",
    "US6503231B1",
    "US6463327B1",
    "WO2005051306A2",
    "US7209787B2",
    "US6819956B2",
    "US6104957A",
    "US6505074B2",
    "US6470213B1",
    "RU2178319C2",
    "US7496404B2",
    "US20070276450A1",
    "US6895280B2",
    "US6516227B1",
    "US6666831B1",
    "US6308103B1",
    "RU2160127C1",
    "US7949395B2",
    "US6551849B1",
    "RU2192897C2",
    "US6587724B2",
    "US7877146B2",
    "US20060111754A1",
    "US7096070B1",
    "US20120165899A1",
    "US6895283B2",
    "US6662053B2",
    "US8214048B1",
    "US20050119713A1",
    "US6871099B1",
    "US6862479B1",
    "US20040111118A1",
    "US20020193843A1",
    "US20070208381A1",
    "US20020115945A1",
    "US7065408B2",
    "RU2001102533A",
    "US6839594B2",
    "US20050102007A1",
    "US7324853B2",
    "US20030100933A1",
    "US7628750B2",
    "US6892098B2",
    "US7381192B2",
    "US7153242B2",
    "US6685729B2",
    "US20050125045A1",
    "US20090281599A1",
    "US20030032992A1",
    "US20080021513A1",
    "US20140046407A1",
    "WO2003026735A2",
    "US20030078633A1",
    "US7024247B2",
    "US7536226B2",
    "US7127296B2",
    "US6975907B2",
    "US20040122483A1",
    "US20050209655A1",
    "US20070265679A1",
    "US20080071325A1",
    "US7110820B2",
    "US7127287B2",
    "US7239920B1",
    "US20030158583A1",
    "US7697995B2",
    "US6950706B2",
    "US6937891B2",
    "WO2003092795A1",
    "US20030220679A1",
    "US20040039425A1",
    "US7251529B2",
    "US20070016266A1",
    "US20030233137A1",
    "US7584000B2",
    "US7228179B2",
    "US20040044380A1",
    "US20100114239A1",
    "US20040127954A1",
    "US7544185B2",
    "US20040133248A1",
    "US20040138518A1",
    "US7797057B2",
    "RU2226114C1",
    "US7020521B1",
    "US7035690B2",
    "US7047084B2",
    "US20060149333A1",
    "US20040111126A1",
    "US20060142822A1",
    "US20070016097A1",
    "WO2004087116A2",
    "US20070156179A1",
    "US7493170B1",
    "US7463928B2",
    "US20070083240A1",
    "US6999820B2",
    "US20050004622A1",
    "RU2258496C2",
    "US7184837B2",
    "US7252090B2",
    "US20050070982A1",
    "US20050075669A1",
    "US7200443B2",
    "US20050075678A1",
    "US20110288609A1",
    "US8260436B2",
    "US20050113882A1",
    "WO2005065768A1",
    "JP2007526798A",
    "US7502652B2",
    "WO2005087307A2",
    "US7590454B2",
    "US7330760B2",
    "US7313440B2",
    "US20050246004A1",
    "US20060003090A1",
    "US8750957B2",
    "US20070060980A1",
    "US20050278000A1",
    "US7813809B2",
    "US8195304B2",
    "US20060041295A1",
    "US9205261B2",
    "US20120283697A1",
    "US20130165991A1",
    "US8712546B2",
    "US7337005B2",
    "US9205259B2",
    "US7337006B2",
    "US9205260B2",
    "US8229565B2",
    "US20080154329A1",
    "US20120259380A1",
    "US20060122678A1",
    "US20060089696A1",
    "US20070168008A1",
    "US20060100671A1",
    "US7734340B2",
    "US20060142816A1",
    "US20060149337A1",
    "US8190262B2",
    "US20100145428A1",
    "US20070060954A1",
    "US20110166546A1",
    "US8295936B2",
    "US20060282127A1",
    "US20060239482A1",
    "US7603178B2",
    "US7813803B2",
    "US20140114374A1",
    "US20070073357A1",
    "WO2006138069A1",
    "JP2008543429A",
    "US20080200749A1",
    "US20070276449A1",
    "US20130013041A1",
    "US8332029B2",
    "US20100198298A1",
    "US7991465B2",
    "WO2007007058A1",
    "US7415309B2",
    "US20070055337A1",
    "US20070049814A1",
    "US7856264B2",
    "US20070179534A1",
    "US20110276107A1",
    "US20140107398A1",
    "US20140213842A1",
    "US20160121116A1",
    "US20140107397A1",
    "US20150165226A1",
    "US20140081071A1",
    "US20130304159A1",
    "US20140100633A1",
    "US20120126392A1",
    "US7660636B2",
    "US20090299167A1",
    "US20130030501A1",
    "US7467016B2",
    "US7801601B2",
    "US20070191709A1",
    "US20070233204A1",
    "US20090012436A1",
    "US7729781B2",
    "WO2007107831A2",
    "US20120109251A1",
    "US20070265691A1",
    "US20120006793A1",
    "US20070255372A1",
    "US20090198305A1",
    "US8369961B2",
    "US20110245734A1",
    "US20100152811A1",
    "US20080046049A1",
    "US20080051851A1",
    "US20090299166A1",
    "US20080103579A1",
    "US8355791B2",
    "US8019427B2",
    "US20080140152A1",
    "US20080140169A1",
    "US20080147143A1",
    "US7734351B2",
    "US20100241191A1",
    "US8346366B2",
    "US20080234791A1",
    "US20080183224A1",
    "US20080215113A1",
    "US20080202940A1",
    "US20080207985A1",
    "US20100268299A1",
    "US7949403B2",
    "US20110224753A1",
    "US20080221653A1",
    "WO2008109862A2",
    "US20080228241A1",
    "US8428728B2",
    "US20110184488A1",
    "US20120283797A1",
    "US20080228250A1",
    "WO2008121891A1",
    "US8364273B2",
    "US20080279896A1",
    "US8311644B2",
    "US20130012853A1",
    "US7769463B2",
    "RU2361631C2",
    "US20110184489A1",
    "WO2009042217A1",
    "US20090093854A1",
    "US20090157141A1",
    "US20090112281A1",
    "US20100217355A1",
    "US20090204173A1",
    "US20090118365A1",
    "US8170660B2",
    "WO2009111142A2",
    "US20090270960A1",
    "US7890182B2",
    "RU2368401C1",
    "US8108052B2",
    "US20090306491A1",
    "US20120277824A1",
    "US8700145B2",
    "US20100004715A1",
    "RU2396995C2",
    "US8155750B2",
    "US8131358B2",
    "US20120179222A1",
    "US20100042193A1",
    "US20100023103A1",
    "US20110224752A1",
    "US7987000B2",
    "US8442655B2",
    "US20100070007A1",
    "US8050773B2",
    "US20100137938A1",
    "WO2010055421A1",
    "US20110224757A1",
    "US20100125313A1",
    "RU2387467C1",
    "RU2397788C2",
    "US8352036B2",
    "US20100185253A1",
    "US20120035684A1",
    "US8355797B2",
    "US20100228310A1",
    "US20120310315A1",
    "US20110230701A1",
    "US20110125203A1",
    "US20160045731A1",
    "US20160121114A1",
    "US20120101326A1",
    "US20120185020A1",
    "US20130066392A1",
    "US20140357936A1",
    "US20110152967A1",
    "US8271099B1",
    "WO2010114998A1",
    "US20100274312A1",
    "US20130110196A1",
    "WO2010124128A1",
    "US20100305660A1",
    "US20100318168A1",
    "US20100331925A1",
    "US20140031893A1",
    "US20110029040A1",
    "US20110040349A1",
    "US20110054579A1",
    "US20110054567A1",
    "US20110054568A1",
    "US20120221073A1",
    "US20130053922A1",
    "US20120302821A1",
    "US8412345B2",
    "US20150065559A1",
    "US20120252874A1",
    "US20130281890A1",
    "US20110130804A1",
    "US20120277834A1",
    "US20110160810A1",
    "US20110218594A1",
    "US20110224665A1",
    "US20110230702A1",
    "US8588884B2",
    "US20110295100A1",
    "US20130303873A1",
    "US20130123568A1",
    "US20120029528A1",
    "US20140066950A1",
    "US8452406B2",
    "US20130197408A1",
    "US8239038B2",
    "US20120109295A1",
    "US20120123293A1",
    "RU2445990C1",
    "US20120172946A1",
    "US20140163640A1",
    "EP2661307A2",
    "WO2012094346A2",
    "CA2823592A1",
    "AU2012204526A1",
    "US9101769B2",
    "US20160030748A1",
    "US20130310911A1",
    "US20170157389A1",
    "WO2012100260A2",
    "US8805542B2",
    "US20140316503A1",
    "US20120197338A1",
    "US20120232615A1",
    "US20150265830A1",
    "US20140330067A1",
    "RU2471518C2",
    "US20150231396A1",
    "US20140180361A1",
    "WO2012129574A2",
    "RU2475283C2",
    "US20140236257A1",
    "US20120310305A1",
    "US20120330391A1",
    "US20130030319A1",
    "US20130053734A1",
    "US20150182784A1",
    "US20130204324A1",
    "US20130085317A1",
    "US20130123659A1",
    "CA2856202A1",
    "US20140316484A1",
    "US20140296752A1",
    "WO2013071307A1",
    "US9393409B2",
    "WO2013071309A1",
    "US20160220813A1",
    "US20170007831A1",
    "US20160121109A1",
    "CA2864473A1",
    "US10806927B2",
    "US9415218B2",
    "US20130253299A1",
    "US20130253611A1",
    "US20130268021A1",
    "US20130268016A1",
    "US20130289446A1",
    "WO2013188965A1",
    "US20140058490A1",
    "US20140067007A1",
    "US20140067354A1",
    "US20140330335A1",
    "US20160045727A1",
    "US9993642B2",
    "US20160030737A1",
    "EP2968940A1",
    "WO2014144785A1",
    "US20180361146A1",
    "US20140303901A1",
    "US20140324118A1",
    "US20140336722A1",
    "US9072891B1",
    "US20150005840A1",
    "US10137299B2",
    "US20190167987A1",
    "US20160235977A1",
    "WO2015048563A2",
    "US9283391B2",
    "US20150190634A1",
    "US9272143B2",
    "US20170161454A1",
    "US10751533B2",
    "WO2016029159A2",
    "US20170274209A1",
    "US10773074B2",
    "WO2016033369A1",
    "US20170246450A1",
    "US20170246452A1",
    "WO2016033372A1",
    "US20160074663A1",
    "US20160175586A1",
    "US20160271413A1",
    "US20160339239A1",
    "US9610442B2",
    "US20180185642A1",
    "WO2017011410A1",
    "US20190022371A1",
    "WO2017024276A1",
    "WO2017035512A1",
    "US20180280693A1",
    "US20180256906A1",
    "WO2017044904A1",
    "US20170296837A1",
    "WO2018106843A1",
    "US20190381313A1",
    "WO2018140531A1",
    "US20200155865A1",
    "WO2018217791A1",
    "WO2020041502A1",
    "WO2020041633A1",
    "WO2020236946A1"
  ]
}