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Trial Of Neurostimulation In Conversion Symptoms (‘TONICS’): a feasibility randomised controlled trial of transcranial magnetic stimulation for functional limb weakness

Research output: Contribution to journalArticle

Susannah Pick, John Hodsoll, Biba Stanton, Amy Eskander, Ioannis Stavropoulos, Kiran Samra, Julia Bottini, Hena Ahmad, Anthony S David, Alistair Purves, Timothy Nicholson

Original languageEnglish
JournalBMJ Open
Publication statusAccepted/In press - 20 Jul 2020


  • Pick et al._Accepted

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    Accepted author manuscript

King's Authors


Objectives: 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.
Design: A double-blind (patient, outcome assessor) two parallel-arm, controlled RCT.
Setting: Specialist neurology and neuropsychiatry services at a large National Health Service Foundation Trust in London, UK.
Participants: Patients with DSM-5 diagnosis of functional limb weakness. Exclusion criteria included comorbid neurological or major psychiatric disorder, contraindications to TMS, or previous TMS treatment.
Interventions: 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, four weeks apart.
Outcome measures: We assessed recruitment, randomisation, and retention rates. The primary outcome was patient-rated symptom change (Clinical Global Impression–Improvement 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.
Results: Twenty-two patients were recruited and twenty-one (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 (80-100%). 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’s delta= -0.1-0.3, CIs= -0.79-0.28), reflecting a more positive outcome for the active treatment (67% and 44% of active arm rated symptoms as ‘much improved’ at session 2 and follow-up respectively, versus 20% inactive group). Effect sizes for secondary outcomes were variable.
Conclusions: Our protocol is feasible. The findings suggest that supra-motor threshold TMS of M1 is safe, acceptable and potentially beneficial as a treatment for functional limb weakness. A larger RCT is warranted.

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