{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T01:07:04Z","timestamp":1773191224267,"version":"3.50.1"},"reference-count":33,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"unspecified","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Transcranial magnetic stimulation (TMS) has been used therapeutically for functional (conversion) motor symptoms but there is limited evidence for its efficacy and the optimal protocol. We examined the feasibility of a novel randomised controlled trial (RCT) protocol of TMS to treat functional limb weakness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A double-blind (patient, outcome assessor) two parallel-arm, controlled RCT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Specialist neurology and neuropsychiatry services at a large National Health Service Foundation Trust in London, UK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>Patients with a diagnosis of functional limb weakness (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition). Exclusion criteria included comorbid neurological or major psychiatric disorder, contraindications to TMS or previous TMS treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Patients were randomised to receive either active (single-pulse TMS to primary motor cortex (M1) above resting motor threshold) or inactive treatment (single-pulse TMS to M1 below resting motor threshold). Both groups received two TMS sessions, 4\u2009weeks apart.<\/jats:p><\/jats:sec><jats:sec><jats:title>Outcome measures<\/jats:title><jats:p>We assessed recruitment, randomisation and retention rates. The primary outcome was patient-rated symptom change (Clinical Global Impression\u2013Improvement scale, CGI-I). Secondary outcomes included clinician-rated symptom change, psychosocial functioning and disability. Outcomes were assessed at baseline, both TMS visits and at 3-month follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-two patients were recruited and 21 (96%) were successfully randomised (active=10; inactive=11). Nineteen (91%) patients were included at follow-up (active=9; inactive=10). Completion rates for most outcomes were good (80%\u2013100%). Most patients were satisfied\/very satisfied with the trial in both groups, although ratings were higher in the inactive arm (active=60%, inactive=92%). Adverse events were not more common for the active treatment. Treatment effect sizes for patient-rated CGI-I scores were small-moderate (Cliff\u2019s delta=\u22120.1\u20130.3, CIs\u22120.79 to 0.28), reflecting a more positive outcome for the active treatment (67% and 44% of active arm-rated symptoms as \u2018much improved\u2019 at session 2 and follow-up, respectively, vs 20% inactive group). Effect sizes for secondary outcomes were variable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our protocol is feasible. The findings suggest that supramotor threshold TMS of M1 is safe, acceptable and potentially beneficial as a treatment for functional limb weakness. A larger RCT is warranted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial results\" xlink:href=\"NCT51225587\">NCT51225587<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2020-037198","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T17:44:12Z","timestamp":1680716652000},"page":"e037198","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Trial Of Neurostimulation In Conversion Symptoms (TONICS): a feasibility randomised controlled trial of transcranial magnetic stimulation for functional limb weakness"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct51225587","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-6723","authenticated-orcid":false,"given":"Susannah","family":"Pick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-9901","authenticated-orcid":false,"given":"John","family":"Hodsoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-9109","authenticated-orcid":false,"given":"Biba","family":"Stanton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-9801","authenticated-orcid":false,"given":"Amy","family":"Eskander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-1826","authenticated-orcid":false,"given":"Ioannis","family":"Stavropoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3105-7099","authenticated-orcid":false,"given":"Kiran","family":"Samra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Bottini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hena","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0967-774X","authenticated-orcid":false,"given":"Anthony S","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-4417","authenticated-orcid":false,"given":"Alistair","family":"Purves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-4417","authenticated-orcid":false,"given":"Timothy R","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"2023040221341712000_10.10.e037198.1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association . Diagnostic and statistical manual of mental disorders (DSM-5). 5th edn. Washington: American Psychiatric Association, 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"2023040221341712000_10.10.e037198.2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305321"},{"key":"2023040221341712000_10.10.e037198.3","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21687"},{"key":"2023040221341712000_10.10.e037198.4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.35302.x"},{"key":"2023040221341712000_10.10.e037198.5","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1001\/jamaneurol.2018.1264","article-title":"Current concepts in diagnosis and treatment of functional neurological disorders","volume":"75","author":"Espay","year":"2018","journal-title":"JAMA Neurol"},{"key":"2023040221341712000_10.10.e037198.6","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1001\/jamapsychiatry.2014.817","article-title":"Multicenter pilot treatment trial for psychogenic nonepileptic seizures: a randomized clinical trial","volume":"71","author":"LaFrance","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"2023040221341712000_10.10.e037198.7","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e39658"},{"key":"2023040221341712000_10.10.e037198.8","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2016-314408"},{"key":"2023040221341712000_10.10.e037198.9","doi-asserted-by":"publisher","DOI":"10.2340\/16501977-1246"},{"key":"2023040221341712000_10.10.e037198.10","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304181"},{"key":"2023040221341712000_10.10.e037198.11","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/ene.12684","article-title":"Can repetitive transcranial magnetic stimulation increase muscle strength in functional neurological paresis? A proof-of-principle study","volume":"22","author":"Broersma","year":"2015","journal-title":"Eur J Neurol"},{"key":"2023040221341712000_10.10.e037198.12","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2017.00338","article-title":"Impact of transcranial magnetic stimulation on functional movement disorders: cortical modulation or a behavioral effect?","volume":"8","author":"Garcin","year":"2017","journal-title":"Front Neurol"},{"key":"2023040221341712000_10.10.e037198.13","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304062"},{"key":"2023040221341712000_10.10.e037198.14","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/mds.27727","article-title":"Repetitive transcranial magnetic stimulation for functional tremor: a randomized, double-blind, controlled study","volume":"34","author":"Taib","year":"2019","journal-title":"Mov Disord"},{"key":"2023040221341712000_10.10.e037198.15","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jpsychores.2016.08.010","article-title":"Transcranial magnetic stimulation as a treatment for functional (psychogenic) upper limb weakness","volume":"89","author":"McWhirter","year":"2016","journal-title":"J Psychosom Res"},{"key":"2023040221341712000_10.10.e037198.16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1176\/appi.neuropsych.19060128","article-title":"Outcome measures for functional neurological disorder: a review of the theoretical complexities","volume":"32","author":"Nicholson","year":"2020","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"2023040221341712000_10.10.e037198.17","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322180"},{"key":"2023040221341712000_10.10.e037198.18","first-page":"22","article-title":"The Mini-International neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10","volume":"59 Suppl 20","author":"Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"2023040221341712000_10.10.e037198.19","doi-asserted-by":"publisher","DOI":"10.1002\/pmh.34"},{"key":"2023040221341712000_10.10.e037198.20","unstructured":"Nelson HE . National adult reading test (NART): for the assessment of premorbid intelligence in patients with dementia: test manual. Nfer-Nelson 1982."},{"key":"2023040221341712000_10.10.e037198.21","doi-asserted-by":"publisher","DOI":"10.1348\/014466505X35344"},{"key":"2023040221341712000_10.10.e037198.22","doi-asserted-by":"crossref","unstructured":"Mills KR . Magnetic stimulation of the human nervous system. Oxford University Press: Oxford, 1999.","DOI":"10.1093\/oso\/9780192629869.001.0001"},{"key":"2023040221341712000_10.10.e037198.23","doi-asserted-by":"crossref","unstructured":"Guy W . ECDEU assessment manual for psychopharmacology. Rockville, MD, US: Department of Health, Education, and Welfare, 1976.","DOI":"10.1037\/e591322011-001"},{"key":"2023040221341712000_10.10.e037198.24","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-200203000-00008"},{"key":"2023040221341712000_10.10.e037198.25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1497.2001.016009606.x"},{"key":"2023040221341712000_10.10.e037198.26","doi-asserted-by":"publisher","DOI":"10.1080\/14733145.2012.729069"},{"key":"2023040221341712000_10.10.e037198.27","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-199206000-00002"},{"key":"2023040221341712000_10.10.e037198.28","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.166.10.1092"},{"key":"2023040221341712000_10.10.e037198.29","first-page":"61","article-title":"Functional evaluation: the Barthel index: a simple index of independence useful in scoring improvement in the rehabilitation of the chronically ill","volume":"14","author":"Mahoney","year":"1965","journal-title":"Md State Med J"},{"key":"2023040221341712000_10.10.e037198.30","doi-asserted-by":"publisher","DOI":"10.1191\/026921599676896799"},{"key":"2023040221341712000_10.10.e037198.31","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.180.5.461"},{"key":"2023040221341712000_10.10.e037198.32","unstructured":"Beecham J , Knapp M . Costing psychiatric interventions. In: Measuring mental health needs. London: Gaskell, 2001: 200\u201324."},{"key":"2023040221341712000_10.10.e037198.33","unstructured":"Romano J , Kromrey JD , Coraggio J , et al . Exploring methods for evaluating group differences on the NSSE and other surveys: Are the t-test and Cohen\u2019sd indices the most appropriate choices. Annual Meeting of the Southern Association for Institutional Research, 2006:1\u201351."}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2020-037198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T07:26:14Z","timestamp":1702193174000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2020-037198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10,6]]},"published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1136\/bmjopen-2020-037198"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2020-037198","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}