COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol

Background The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. Methods/Design The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse events. We will include a nested qualitative study to evaluate participants’ views of the intervention and factors that acted as facilitators and barriers to participation. Discussion This study will be the first adequately powered evaluation of CBT for this patient group and offers the potential to provide an evidence base for treating this patient group. Trial registration Current Controlled Trials ISRCTN05681227 ClinicalTrials.gov NCT0232554

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

BACKGROUND: Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. METHODS: The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. DISCUSSION: The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. TRIAL REGISTRATION: ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014)

Physio4FMD: protocol for a multicentre randomised controlled trial of specialist physiotherapy for functional motor disorder

Background Patients with functional motor disorder (FMD) experience persistent and disabling neurological symptoms such as weakness, tremor, dystonia and disordered gait. Physiotherapy is usually considered an important part of treatment; however, sufficiently-powered controlled studies are lacking. Here we present the protocol of a randomised controlled trial (RCT) that aims to evaluate the clinical and cost effectiveness of a specialist physiotherapy programme for FMD. Methods/design The trial is a pragmatic, multicentre, single blind parallel arm randomised controlled trial (RCT). 264 Adults with a clinically definite diagnosis of FMD will be recruited from neurology clinics and randomised to receive either the trial intervention (a specialist physiotherapy protocol) or treatment as usual control (referral to a community physiotherapy service suitable for people with neurological symptoms). Participants will be followed up at 6 and 12 months. The primary outcome is the Physical Function domain of the Short Form 36 questionnaire at 12 months. Secondary domains of measurement will include participant perception of change, mobility, health-related quality of life, health service utilisation, anxiety and depression. Health economic analysis will evaluate the cost impact of trial and control interventions from a health and social care perspective as well as societal perspective. Discussion This trial will be the first adequately-powered RCT of physical-based rehabilitation for FMD. Trial registration International Standard Randomised Controlled Trials Number ISRCTN56136713. Registered 27 March 2018

Physio4FMD: protocol for a multicentre randomised controlled trial of specialist physiotherapy for functional motor disorder.

BACKGROUND: Patients with functional motor disorder (FMD) experience persistent and disabling neurological symptoms such as weakness, tremor, dystonia and disordered gait. Physiotherapy is usually considered an important part of treatment; however, sufficiently-powered controlled studies are lacking. Here we present the protocol of a randomised controlled trial (RCT) that aims to evaluate the clinical and cost effectiveness of a specialist physiotherapy programme for FMD. // METHODS/DESIGN: The trial is a pragmatic, multicentre, single blind parallel arm randomised controlled trial (RCT). 264 Adults with a clinically definite diagnosis of FMD will be recruited from neurology clinics and randomised to receive either the trial intervention (a specialist physiotherapy protocol) or treatment as usual control (referral to a community physiotherapy service suitable for people with neurological symptoms). Participants will be followed up at 6 and 12 months. The primary outcome is the Physical Function domain of the Short Form 36 questionnaire at 12 months. Secondary domains of measurement will include participant perception of change, mobility, health-related quality of life, health service utilisation, anxiety and depression. Health economic analysis will evaluate the cost impact of trial and control interventions from a health and social care perspective as well as societal perspective. // DISCUSSION: This trial will be the first adequately-powered RCT of physical-based rehabilitation for FMD

Unravelling the influence of affective stimulation on functional neurological symptoms: A pilot experiment examining potential mechanisms

Background: Differences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the hypotheses that highly arousing affective stimulation would result in elevated subjective functional neurological symptoms (FNS), and this would be associated with elevated autonomic reactivity. The possible influence of cognitive detachment was also explored. Method: Individuals diagnosed with FND (motor symptoms/seizures; n=14) and healthy controls (n=14) viewed Positive, Negative and Neutral images in blocks, while passively observing the stimuli ( € Watch') or detaching themselves ( € Distance'). The FND group rated their primary FNS, and all participants rated subjective physical (arousal, pain, fatigue) and psychological states (positive/negative affect, dissociation), immediately after each block. Skin conductance (SC) and heart rate (HR) were monitored continuously. Results: FNS ratings were higher after Negative compared with Positive and Neutral blocks in the FND group (p=0.002, •p2=0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, •p2=0.267). SC and/or HR correlated with FNS ratings in the Negative-Watch and Neutral-Distance conditions (r values=0.527-0.672, p values=0.006-0.035). The groups did not differ in subjective affect or perceived arousal (p values=0.541-0.919, •p2=<0.001-0.015). Conclusions: Emotionally significant events may exert an influence on FNS which is related to autonomic activation rather than altered subjective affect or perceived arousal. This influence may be modulated by cognitive detachment. Further work is needed to determine the relevance and neural bases of these processes in specific FND phenotypes

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Rotation and Spin in Physics

We delineate the role of rotation and spin in physics, discussing in order Newtonian classical physics, special relativity, quantum mechanics, quantum electrodynamics and general relativity. In the latter case, we discuss the generalization of the Kepler formula to post-Newtonian order $(c^{-2}$) including spin effects and two-body effects. Experiments which verify the theoretical results for general relativistic spin-orbit effects are discussed as well as efforts being made to verify the spin-spin effects