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

Abstract

ObjectivesTranscranial 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.DesignA double-blind (patient, outcome assessor) two parallel-arm, controlled RCT.SettingSpecialist neurology and neuropsychiatry services at a large National Health Service Foundation Trust in London, UK.ParticipantsPatients 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.InterventionsPatients 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 measuresWe 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.ResultsTwenty-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.ConclusionsOur 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 numberNCT51225587.

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“…It is worth noticing, however, that only one of these studies was controlled [29]; therefore, a placebo effect of rTMS cannot be excluded. This notion is further supported by other findings, such as patients' improvement with very low stimulation frequency, outside the range of plasticity-inducing rTMS protocols [30,35], in addition to strength increase with sham stimulation [31]. Along this line, it has been suggested that possible therapeutic effects of TMS on FP may rely on the demonstration of intact motor pathways to the patient in an objective way [33,34].…”

Transcranial magnetic stimulation-based closed-loop modality for activity of daily living gain in spinal cord injury: a retrospective study using propensity score matching analysis

“… 25 , 26 Some studies even report on the near-zero incidence of rTMS-relevant side effects. 27 , 28 On the other hand, as an additional approach, rTMS inevitably added to rehabilitative consumption and incidence of side effects. As a consequence, our radar chart further visually illustrated the total value of each rehabilitative strategy.…”

Functional Neurologic Disorders, disorders to be managed by neurologists, or are neurologists wandering in a dangerous field with inadequate resources?

“…The authors also summarized the effect of Transcranial Magnetic Stimulation (TMS), which can improve the clinical picture, according to several observations (162)(163)(164), but they also commented that the mechanism is still unclear, addressing methodological bias (165). Interestingly, TMS was suggested to mainly act through a cognitivebehavioral mechanism (166), rather than by cortical excitability modulation.…”