Trial Of Neurostimulation In Conversion Symptoms (TONICS): a feasibility randomised controlled trial of transcranial magnetic stimulation for functional limb weakness. Issue 10 (6th October 2020)

• Record Type: Journal Article
• Authors: Pick, Susannah; Hodsoll, John; Stanton, Biba; Eskander, Amy; Stavropoulos, Ioannis; Samra, Kiran; Bottini, Julia; Ahmad, Hena; David, Anthony S; Purves, Alistair; Nicholson, Timothy R
• Is Part Of: BMJ open. Volume 10:Issue 10(2020)
• Publication Date: 2020-10-06
• Subjects: adult neurology -- adult psychiatry -- clinical trials; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2020-037198
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : 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 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. 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, 4 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 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%–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 to 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, vs 20% inactive group). Effect sizes for secondary outcomes were variable. Conclusions: 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. Trial registration number: ISRCTN51225587 .