Title: Non-invasive brain stimulation in the treatment of conversion disorder: studies of efficacy and mechanism
Funder: Department of Health and Social Care

Abstract: Background: Conversion disorder (CD) is defined as neurological symptoms (e.g. paralysis) that occur in the absence of neurological disease and are presumed psychological in origin. It is common, accounting for up to 16% of neurology outpatient referrals1 with a community prevalence estimated at 50/100,0002. Outcomes are poor and chronic severe symptoms are common with high levels of disability and attendant health and social care costs3. Despite this it has been neglected by research and consequently there are no established evidence based treatments4 although there is encouraging evidence for Cognitive Behavioural Therapy for those presenting with seizures. However, there have been recent reports that Transcranial Magnetic Stimulation (TMS) might be effective for those presenting with weakness or movement disorders (motor CD)5 but there have been no randomised controlled trials (RCTs) to confirm this and the mechanism by which it might work is unclear. The lack of high quality trials of any treatments for motor CD means that the optimal outcome measure(s) for RCTs remain to be established as those currently in use were not designed for CD and have not been validated in the condition. Aims:Main aim: to perform the preliminary studies to enable later rigorous assessment of whether TMS is an effective treatment for motor CD. Other key aims: i) Optimise outcome measures for trials of motor CD, by understanding currently available measures in this population and develop new measure(s). ii) Understand mechanism(s) of action of TMS for motor CD at the neurophysiological level in order to optimise treatment strategy and investigate predictors and markers of change. Plan of investigation:Summary: an initial feasibility study will be followed by a pilot RCT of single pulse TMS to the motor cortex. In the active' treatment TMS pulses will be sufficient to create movement in affected limb(s) but in the control' treatment the pulses will not be sufficient to induce movement. Linked neurophysiology and neuroimaging studies will investigate the mechanism(s) of action of TMS in this context. Detail: - Feasibility study: 20 patients will be complete the RCT to assess recruitment rates and the percentage of subjects not completing the trial (due non-acceptance of randomisation or non-completion of the trial). It will also begin investigation of the performance of existing outcome measures and the development of a measure specifically designed for CD. - Pilot study: 60 patients will complete the RCT to allow preliminary assessments of efficacy of the interventions and the performance of items from the outcome measures. - Neurophysiology studies: will assess motor cortex thresholds in all 80 patients from the feasibility and pilot study. Cortical inhibition will be assessed in those undergoing the active treatment. - Neuroimaging studies: high resolution structural scans and functional imaging paradigms (resting state and implicit emotion tasks) will assess for predictors of response in all 20 patients from the feasibility study and a subgroup of 20 patients from the pilot study. Summary of benefits to patients/NHS: this research will lay the groundwork to the possible identification of a cheap, safe and well tolerated treatment for CD that could be delivered with existing equipment in neurophysiology laboratories across the UK within 5 years of the end of this study. CD is a common, and often severe and chronic condition, with attendant high health and social care costs, for which there are currently no evidence based treatments. Improving symptoms would generate a large saving in the health and social care costs required for this patient group.

Lay abstract: Conversion Disorder (CD) is where neurological symptoms, such as paralysis, aren't caused by neurological disease. It is presumed to be psychological in origin. Little is known about how these disabling symptoms are produced and there are few treatments. Recent reports suggest that Transcranial Magnetic Stimulation (TMS), where a magnet is placed over the scalp to stimulate nerves to the affected limb, can be effective. This project will initially do the groundwork enabling the design of a thorough trial of TMS. A trial will then test whether TMS is effective in treating CD. Simultaneous studies will investigate how TMS actually works.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: MENTAL HEALTH