Title: Development of novel diagnostic and therapeutic techniques for functional sensory symptoms
Funder: Health Education England

Abstract: Background Functional Neurological Disorder (FND) is a common cause of disability that exists at the interface between neurology and psychiatry. Patients experience a range of symptoms including sensory disturbance, motor symptoms and dissociative seizures. It is the second most common diagnosis made in outpatient neurology clinics and often results in long-term disability. Recent years have seen substantial progress in the understanding and treatment of motor symptoms and dissociative seizures but functional sensory symptoms (FSS) remain poorly understood and largely ignored. FSS affect most patients with FND, they cause distress, contribute to disability and there are no evidence based treatments. Research is needed to improve diagnosis and treatment. Aims Explore and describe the clinical features of FSS. Develop electrophysiological techniques for diagnosis of FSS and to gain insights into mechanism. Protocolise and pilot a novel intervention for FSS.The aims will be explored in 3 work packages (WP): Methods WP1: 100 patients with FND motor symptoms will be recruited from specialist clinics at St George's Hospital, it is expected about 65% will also experience FSS. Each participant will complete a structured interview; questionnaires; quantitative sensory testing; and a 12-month online/postal follow up. Outputs will include the specificity and sensitivity of clinical signs of FSS; test-retest reliability of FSS assessment (in the proportion of participants who complete WP2); impact on disability; and 12-month outcome. WP2: 50 participants from WP1 with hemisensory loss will be invited to participate. EEG will be used to explore the electrophysiological responses to somatosensory stimulation, comparing the affected side to the unaffected side. The aim is to develop adjunctive laboratory diagnostic techniques for FSS. This study will explore: somatosensory evoked potentials (SSEPs) at a range of stimulation intensities; mismatch negativity (MMN) and P300 responses to an 'oddball' paradigm. MMN and P300 are markers of higher processing of sensory stimulation. WP3: Will protocolise and pilot a novel therapeutic approach for FSS. The treatment will exploit the process of multisensory integration, where multimodal sensory streams (somatosensation, auditory, visual) are processed simultaneously, which appears to 'boost' the cortical processing of the stimuli. Twenty participants from WP1 will be invited to take part in a randomised cross-over study. The intervention (synchronous multisensory stimulation) will be compared to a control (stimuli presented individually) with a washout period of at least one week. The therapeutic potential will be assessed by pre and post measurements using questionnaires, quantitative sensory testing, reaction times and EEG. Timeline Based on recruitment rates from previous studies, recruitment is expected to take up to 18 months. WP1 and 2 will be completed simultaneously over the first 2 years, with WP3 becoming the focus in year 3. Publication of results will occur progressively. Impact and dissemination This will be the first cohort study of FSS. Potential impact includes data to support diagnosis and treatment of a large group of patients with high-level disability. Dissemination will target high quality journals and international conferences. A lay summary will be shared with participants and disseminated publically with support from FND charities.

Lay abstract: This research will explore the common neurological symptom of functional sensory loss, which I will refer to as functional sensory symptoms, using the abbreviation FSS.Aims Define the clinical features of FSS in a large group of patients. Develop methods to assess and diagnose FSS, including use of EEG (recording of electrical activity in the brain). Develop and test a novel way to treat FSS. BackgroundFunctional neurological disorder (FND) is a problem with functioning of the nervous system that interferes with how the brain and body sends and receives signals. It can cause many different symptoms, including weakness, sensory loss (FSS), shaking and blackouts. FND is the second most common diagnosis made in outpatient neurology clinics. It can cause high levels of disability and distress that persists over many years. Many patients are unable to work and have high care needs.Recent years have seen an increase in research into FND motor symptoms (weakness, walking difficulty, etc) and blackouts (dissociative seizures). As a result new treatments are being developed and tested in large clinical trials for these specific problems. However, there has been very little research into FSS and there are no known effective treatments. FSS cause distress to patients and interfere with day-to-day limb function and mobility. Research is needed to understand the impact of FSS and how it can be treated.MethodsProject 1 will explore and describe FSS in 100 people. Participants will complete: questionnaires; sensation testing; and follow-up questionnaires after 12 months. This work is aimed to help clinicians assess and diagnose FSS and also to understand the impact on patients.Project 2 will use electroencephalography (EEG) to explore electrical activity in the brain in 50 people who have FSS on one side of their body. Adhesive electrodes will deliver a mild electrical current to the skin and the resulting brain activity will be recorded using EEG (a non-invasive procedure). Electrical 'signatures' of conscious and subconscious processing of sensory information will be analysed, comparing the affected side of the body with the unaffected side. This work aims to find a way to diagnose FSS using EEG. It will also explore what is going wrong when the brain processes sensation, and how this might be addressed with treatment.Project 3 will test a sensory retraining programme in 20 people with FSS. The idea is based on research that shows that when different types of stimulation (touch, light and sound) are presented together, the signal of the stimulation is boosted in the brain. This is called multisensory integration. The training programme will deliver bursts of electrical stimulation (touch) together with light and sound. The programme will be compared to a second programme where the same stimuli are delivered individually. Each participant will complete both programmes, in a random order with a break of at least one week in between. Participants will be assessed before and after each treatment with questionnaires, sensory testing, reaction times and EEG.Patient and public involvement (PPI) Patient collaborators with FND have highlighted mobility/movement as a priority for treatment and FSS are an important factor in normal movement. A comprehensive PPI strategy will be carried out; this includes refining the methodology, acceptability and relevance; reviewing outcome measures to ensure they are meaningful; collaborative development of participant information and outputs; and support with dissemination.Dissemination Results will be published in quality medical journals and presented at international conferences for health professionals. Participants will receive a lay summary produced with support from PPI representatives. Patient support charities will help disseminate trial outcomes. Study protocols will be published to allow replication.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL