Evaluating noninvasive brain stimulation to treat overactive bladder in individuals with multiple sclerosis: a randomized controlled trial protocol.
Functional MRI
Multiple sclerosis
Neurogenic overactive bladder
Transcranial magnetic stimulation
Journal
BMC urology
ISSN: 1471-2490
Titre abrégé: BMC Urol
Pays: England
ID NLM: 100968571
Informations de publication
Date de publication:
25 Jan 2024
25 Jan 2024
Historique:
received:
11
08
2023
accepted:
06
11
2023
medline:
26
1
2024
pubmed:
26
1
2024
entrez:
25
1
2024
Statut:
epublish
Résumé
Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD. By employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS. Some limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD. This trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023.
Sections du résumé
BACKGROUND
BACKGROUND
Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.
METHODS
METHODS
By employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS.
DISCUSSION
CONCLUSIONS
Some limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD.
TRIAL REGISTRATION
BACKGROUND
This trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023.
Identifiants
pubmed: 38273296
doi: 10.1186/s12894-023-01358-8
pii: 10.1186/s12894-023-01358-8
doi:
Banques de données
ClinicalTrials.gov
['NCT06072703']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20Subventions
Organisme : NIH HHS
ID : 1R01DK134340-01
Pays : United States
Organisme : NIH HHS
ID : 1R01DK134340-01
Pays : United States
Organisme : NIH HHS
ID : 1R01DK134340-01
Pays : United States
Organisme : NIH HHS
ID : 1R01DK134340-01
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61(1):37–49. https://doi.org/10.1016/s0090-4295(02)02243-4 .
doi: 10.1016/s0090-4295(02)02243-4
pubmed: 12559262
Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4–20. https://doi.org/10.1002/nau.20798 .
doi: 10.1002/nau.20798
pubmed: 19941278
Al Dandan HB, Coote S, McClurg D. Prevalence of lower urinary tract symptoms in people with multiple sclerosis: a systematic review and meta-analysis. Int J MS Care. 2020;22(2):91–9. https://doi.org/10.7224/1537-2073.2019-030 .
doi: 10.7224/1537-2073.2019-030
pubmed: 32410904
pmcid: 7204365
Nazari F, Shaygannejad V, Mohammadi Sichani M, Mansourian M, Hajhashemi V. The prevalence of lower urinary tract symptoms based on individual and clinical parameters in patients with multiple sclerosis. BMC Neurol. 2020;20(1):24. https://doi.org/10.1186/s12883-019-1582-1 .
doi: 10.1186/s12883-019-1582-1
pubmed: 31952513
pmcid: 6966887
Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 Suppl):2455–63. https://doi.org/10.1016/j.juro.2012.09.079 .
doi: 10.1016/j.juro.2012.09.079
pubmed: 23098785
Lightner DJ, Gomelsky A, Souter L, Vasavada SP. Diagnosis and treatment of overactive bladder (Non-Neurogenic) in adults: AUA/SUFU guideline amendment 2019. J Urol. 2019;202(3):558–63. https://doi.org/10.1097/JU.0000000000000309 .
doi: 10.1097/JU.0000000000000309
pubmed: 31039103
Ginsberg DA, Boone TB, Cameron AP, et al. The AUA/SUFU guideline on adult neurogenic lower urinary tract dysfunction: treatment and follow-up. J Urol. 2021;206(5):1106–13. https://doi.org/10.1097/JU.0000000000002239 .
doi: 10.1097/JU.0000000000002239
pubmed: 34495688
Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging. 2009;4:225–33. https://doi.org/10.2147/cia.s5358 .
doi: 10.2147/cia.s5358
pubmed: 19554093
pmcid: 2697587
Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis. Eur Urol. 2005;48(1):5–26. https://doi.org/10.1016/j.eururo.2005.02.024 .
doi: 10.1016/j.eururo.2005.02.024
pubmed: 15885877
Kay GG, Abou-Donia MB, Messer WS Jr, Murphy DG, Tsao JW, Ouslander JG. Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc. 2005;53(12):2195–201. https://doi.org/10.1111/j.1532-5415.2005.00537.x .
doi: 10.1111/j.1532-5415.2005.00537.x
pubmed: 16398909
Risacher SL, McDonald BC, Tallman EF, et al. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. JAMA Neurol. 2016;73(6):721–32. https://doi.org/10.1001/jamaneurol.2016.0580 .
doi: 10.1001/jamaneurol.2016.0580
pubmed: 27088965
pmcid: 5029278
Chartier-Kastler E, Rovner E, Hepp Z, Khalaf K, Ni Q, Chancellor M. Patient-reported goal achievement following onabotulinumtoxinA treatment in patients with neurogenic detrusor overactivity. Neurourol Urodyn. 2016;35(5):595–600. https://doi.org/10.1002/nau.22757 .
doi: 10.1002/nau.22757
pubmed: 25846869
Phe V, Pakzad M, Curtis C, et al. Urinary tract infections in multiple sclerosis. Mult Scler. 2016;22(7):855–61. https://doi.org/10.1177/1352458516633903 .
doi: 10.1177/1352458516633903
pubmed: 26892318
Zecca C, Digesu GA, Robshaw P, et al. Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice. Eur J Neurol. 2014;21(3):506–11. https://doi.org/10.1111/ene.12339 .
doi: 10.1111/ene.12339
pubmed: 24387787
Finazzi-Agro E, Petta F, Sciobica F, Pasqualetti P, Musco S, Bove P. Percutaneous tibial nerve stimulation effects on detrusor overactivity incontinence are not due to a placebo effect: a randomized, double-blind, placebo controlled trial. J Urol. 2010;184(5):2001–6. https://doi.org/10.1016/j.juro.2010.06.113 .
doi: 10.1016/j.juro.2010.06.113
pubmed: 20850833
Hartmann KE, McPheeters ML, Biller DH, et al. Treatment of overactive bladder in women. Evid Rep Technol Assess (Full Rep). 2009;187:1–120 ( https://www.ncbi.nlm.nih.gov/pubmed/19947666 ).
Herbison GP, Arnold EP. Sacral neuromodulation with implanted devices for urinary storage and voiding dysfunction in adults. Cochrane Database Syst Rev. 2009;2:CD004202. https://doi.org/10.1002/14651858.CD004202.pub2 .
doi: 10.1002/14651858.CD004202.pub2
Peters KM, Carrico DJ, Perez-Marrero RA, et al. Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial. J Urol. 2010;183(4):1438–43. https://doi.org/10.1016/j.juro.2009.12.036 .
doi: 10.1016/j.juro.2009.12.036
pubmed: 20171677
Sanford MT, Suskind AM. Neuromodulation in neurogenic bladder. Transl Androl Urol. 2016;5(1):117–26. https://doi.org/10.3978/j.issn.2223-4683.2015.12.01 .
doi: 10.3978/j.issn.2223-4683.2015.12.01
pubmed: 26904417
pmcid: 4739974
Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol. 2007;3(7):383–93. https://doi.org/10.1038/ncpneuro0530 .
doi: 10.1038/ncpneuro0530
pubmed: 17611487
Huerta PT, Volpe BT. Transcranial magnetic stimulation, synaptic plasticity and network oscillations. J Neuroeng Rehabil. 2009;6:7. https://doi.org/10.1186/1743-0003-6-7 .
doi: 10.1186/1743-0003-6-7
pubmed: 19254380
pmcid: 2653496
Janicak PG, Dokucu ME. Transcranial magnetic stimulation for the treatment of major depression. Neuropsychiatr Dis Treat. 2015;11:1549–60. https://doi.org/10.2147/NDT.S67477 .
doi: 10.2147/NDT.S67477
pubmed: 26170668
pmcid: 4492646
Lipton RB, Pearlman SH. Transcranial magnetic simulation in the treatment of migraine. Neurotherapeutics. 2010;7(2):204–12. https://doi.org/10.1016/j.nurt.2010.03.002 .
doi: 10.1016/j.nurt.2010.03.002
pubmed: 20430320
pmcid: 5084102
Martin JL, Barbanoj MJ, Perez V, Sacristan M. Transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder. Cochrane Database Syst Rev. 2003;3:CD003387. https://doi.org/10.1002/14651858.CD003387 .
doi: 10.1002/14651858.CD003387
Centonze D, Petta F, Versace V, et al. Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple sclerosis. Mult Scler. 2007;13(2):269–71. https://doi.org/10.1177/1352458506070729 .
doi: 10.1177/1352458506070729
pubmed: 17439897
Brusa L, Finazzi Agro E, Petta F, et al. Effects of inhibitory rTMS on bladder function in Parkinson’s disease patients. Mov Disord. 2009;24(3):445–8. https://doi.org/10.1002/mds.22434 .
doi: 10.1002/mds.22434
pubmed: 19133657
Griffiths D. Neural control of micturition in humans: a working model. Nat Rev Urol. 2015;12(12):695–705. https://doi.org/10.1038/nrurol.2015.266 .
doi: 10.1038/nrurol.2015.266
pubmed: 26620610
Tadic SD, Griffiths D, Schaefer W, Murrin A, Clarkson B, Resnick NM. Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol Urodyn. 2012;31(5):652–8. https://doi.org/10.1002/nau.21240 .
doi: 10.1002/nau.21240
pubmed: 22473921
pmcid: 3376195
Clarkson BD, Karim HT, Griffiths DJ, Resnick NM. Functional connectivity of the brain in older women with urgency urinary incontinence. Neurourol Urodyn. 2018;37(8):2763–75. https://doi.org/10.1002/nau.23766 .
doi: 10.1002/nau.23766
pubmed: 30054930
pmcid: 6469490
Elizondo RA, Karmonik C, Boone TB, Khavari R. Protocol for a prospective observational study of cortical lower urinary tract control changes following intradetrusor injection of botulinum toxin-A in patients with multiple sclerosis. BMJ Open. 2017;7(2):e013225. https://doi.org/10.1136/bmjopen-2016-013225 .
doi: 10.1136/bmjopen-2016-013225
pubmed: 28159850
pmcid: 5293986
Karmonik C, Boone T, Khavari R. Data-driven machine-learning quantifies differences in the voiding initiation network in neurogenic voiding dysfunction in women with multiple sclerosis. Int Neurourol J. 2019;23(3):195–204. https://doi.org/10.5213/inj.1938058.029 .
doi: 10.5213/inj.1938058.029
pubmed: 31607098
pmcid: 6790826
Khavari R, Chen J, Boone T, Karmonik C. Brain activation patterns of female multiple sclerosis patients with voiding dysfunction. Neurourol Urodyn. 2020;39(3):969–77. https://doi.org/10.1002/nau.24304 .
doi: 10.1002/nau.24304
pubmed: 32032447
pmcid: 7337290
Khavari R, Elias SN, Boone T, Karmonik C. Similarity of functional connectivity patterns in patients with multiple sclerosis who void spontaneously versus patients with voiding dysfunction. Neurourol Urodyn. 2019;38(1):239–47. https://doi.org/10.1002/nau.23837 .
doi: 10.1002/nau.23837
pubmed: 30311665
Khavari R, Elias SN, Pande R, Wu KM, Boone TB, Karmonik C. Higher neural correlates in patients with multiple sclerosis and neurogenic overactive bladder following treatment with intradetrusor injection of onabotulinumtoxinA. J Urol. 2019;201(1):135–40. https://doi.org/10.1016/j.juro.2018.07.066 .
doi: 10.1016/j.juro.2018.07.066
pubmed: 30076906
pmcid: 6309940
Khavari R, Karmonik C, Shy M, Fletcher S, Boone T. Functional magnetic resonance imaging with concurrent urodynamic testing identifies brain structures involved in micturition cycle in patients with multiple sclerosis. J Urol. 2017;197(2):438–44. https://doi.org/10.1016/j.juro.2016.09.077 .
doi: 10.1016/j.juro.2016.09.077
pubmed: 27664581
Khavari R, Tran K, Helekar SA, et al. Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial. J Urol 2021:101097JU0000000000002297. https://doi.org/10.1097/JU.0000000000002297 .
Shi Z, Tran K, Karmonik C, Boone T, Khavari R. High spatial correlation in brain connectivity between micturition and resting states within bladder-related networks using 7 T MRI in multiple sclerosis women with voiding dysfunction. World J Urol. 2021;39(9):3525–31. https://doi.org/10.1007/s00345-021-03599-4 .
doi: 10.1007/s00345-021-03599-4
pubmed: 33512570
pmcid: 8344374
Tran K, Hubbard L, Karmonik C, Boone TB, Khavari R. Preliminary analysis of brain footprints in multiple sclerosis females with detrusor sphincter dyssynergia: a concurrent urodynamic and functional magnetic resonance imaging study. Int Neurourol J. 2021. https://doi.org/10.5213/inj.2142012.006 .
doi: 10.5213/inj.2142012.006
pubmed: 34856727
pmcid: 8896778
Tran K, Karmonik C, Boone TB, Khavari R. Are white matter tract integrities different in multiple sclerosis women with voiding dysfunction? Female Pelvic Med Reconstr Surg. 2021;27(1):e101–5. https://doi.org/10.1097/SPV.0000000000000830 .
doi: 10.1097/SPV.0000000000000830
pubmed: 32265400
pmcid: 9744261
Tran K, Shi Z, Karmonik C, et al. Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial. Pilot Feasibility Stud. 2021;7(1):83. https://doi.org/10.1186/s40814-021-00825-z .
doi: 10.1186/s40814-021-00825-z
pubmed: 33757581
pmcid: 7989407
Mawla I, Schrepf A, Ichesco E, et al. Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP network neuroimaging Study. Sci Rep. 2020;10(1):19901. https://doi.org/10.1038/s41598-020-76857-x .
doi: 10.1038/s41598-020-76857-x
pubmed: 33199816
pmcid: 7669903
Orringer DA, Golby A, Jolesz F. Neuronavigation in the surgical management of brain tumors: current and future trends. Expert Rev Med Devices. 2012;9(5):491–500. https://doi.org/10.1586/erd.12.42 .
doi: 10.1586/erd.12.42
pubmed: 23116076
pmcid: 3563325
Noh TS, Rah YC, Kyong JS, et al. Comparison of treatment outcomes between 10 and 20 EEG electrode location system-guided and neuronavigation-guided repetitive transcranial magnetic stimulation in chronic tinnitus patients and target localization in the Asian brain. Acta Otolaryngol. 2017;137(9):945–51. https://doi.org/10.1080/00016489.2017.1316870 .
doi: 10.1080/00016489.2017.1316870
pubmed: 28471721
Sparing R, Hesse MD, Fink GR. Neuronavigation for transcranial magnetic stimulation (TMS): where we are and where we are going. Cortex. 2010;46(1):118–20. https://doi.org/10.1016/j.cortex.2009.02.018 .
doi: 10.1016/j.cortex.2009.02.018
pubmed: 19371865
Theodoroff SM, Stevens AA, McMillan G, Pettersson DR, Woodward W, Folmer RL. MRI verification of a 10–20 targeting protocol used during transcranial magnetic stimulation sessions for tinnitus. Brain Topogr. 2018;31(4):690–9. https://doi.org/10.1007/s10548-018-0636-9 .
doi: 10.1007/s10548-018-0636-9
pubmed: 29464519
pmcid: 5999188
Herwig U, Satrapi P, Schonfeldt-Lecuona C. Using the international 10–20 EEG system for positioning of transcranial magnetic stimulation. Brain Topogr. 2003;16(2):95–9. https://doi.org/10.1023/b:brat.0000006333.93597.9d .
doi: 10.1023/b:brat.0000006333.93597.9d
pubmed: 14977202
De Witte S, Klooster D, Dedoncker J, Duprat R, Remue J, Baeken C. Left prefrontal neuronavigated electrode localization in tDCS: 10–20 EEG system versus MRI-guided neuronavigation. Psychiatry Res Neuroimaging. 2018;274:1–6. https://doi.org/10.1016/j.pscychresns.2018.02.001 .
doi: 10.1016/j.pscychresns.2018.02.001
pubmed: 29429773
Collins DL, Neelin P, Peters TM, Evans AC. Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr. 1994;18(2):192–205 ( https://www.ncbi.nlm.nih.gov/pubmed/8126267 ).
doi: 10.1097/00004728-199403000-00005
pubmed: 8126267
Weissbart SJ, Bhavsar R, Rao H, et al. Specific changes in brain activity during urgency in women with overactive bladder after successful sacral neuromodulation: a functional magnetic resonance imaging study. J Urol. 2018;200(2):382–8. https://doi.org/10.1016/j.juro.2018.03.129 .
doi: 10.1016/j.juro.2018.03.129
pubmed: 29630979
Ketai LH, Komesu YM, Schrader RM, et al. Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks. Am J Obstet Gynecol. 2021;224(5):498 e1–498 e10. https://doi.org/10.1016/j.ajog.2020.10.041 .
doi: 10.1016/j.ajog.2020.10.041
pubmed: 33122028
Lefaucheur JP, Andre-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014;125(11):2150–206. https://doi.org/10.1016/j.clinph.2014.05.021 .
doi: 10.1016/j.clinph.2014.05.021
pubmed: 25034472
Aloizou AM, Pateraki G, Anargyros K, et al. Transcranial magnetic stimulation (TMS) and repetitive TMS in multiple sclerosis. Rev Neurosci. 2021;32(7):723–36. https://doi.org/10.1515/revneuro-2020-0140 .
doi: 10.1515/revneuro-2020-0140
pubmed: 33641274
Bag AK, Patel BN, Osman S, Roberson GH. Clinico-radiologic profile of spinal cord multiple sclerosis in adults. Neuroradiol J. 2011;24(4):511–8. https://doi.org/10.1177/197140091102400405 .
doi: 10.1177/197140091102400405
pubmed: 24059707
Stankiewicz JM, Neema M, Alsop DC, et al. Spinal cord lesions and clinical status in multiple sclerosis: A 1.5 T and 3 T MRI study. J Neurol Sci. 2009;279(1–2):99–105. https://doi.org/10.1016/j.jns.2008.11.009 .
doi: 10.1016/j.jns.2008.11.009
pubmed: 19178916
pmcid: 2679653
Galler S, Stellmann JP, Young KL, et al. Improved lesion detection by using axial T2-weighted MRI with full spinal cord coverage in multiple sclerosis. AJNR Am J Neuroradiol. 2016;37(5):963–9. https://doi.org/10.3174/ajnr.A4638 .
doi: 10.3174/ajnr.A4638
pubmed: 26744444
pmcid: 7960307
Rahnama’i MS. Neuromodulation for functional bladder disorders in patients with multiple sclerosis. Mult Scler. 2020;26(11):1274–80. https://doi.org/10.1177/1352458519894714 .
doi: 10.1177/1352458519894714
pubmed: 31814519