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

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.