Pain and functional neurological disorder: a systematic review and meta-analysis.

BACKGROUND: Functional neurological disorder (FND) is characterised by neurological symptoms, such as seizures and abnormal movements. Despite its significance to patients, the clinical features of chronic pain in people with FND, and of FND in people with chronic pain, have not been comprehensively studied. METHODS: We systematically reviewed PubMed, Embase and PsycINFO for studies of chronic pain in adults with FND and FND in patients with chronic pain. We described the proportions of patients reporting pain, pain rating and timing, pain-related diagnoses and responsiveness to treatment. We performed random effects meta-analyses of the proportions of patients with FND who reported pain or were diagnosed with pain-related disorders. RESULTS: Seven hundred and fifteen articles were screened and 64 were included in the analysis. Eight case-control studies of 3476 patients described pain symptoms in a higher proportion of patients with FND than controls with other neurological disorders. A random effects model of 30 cohorts found that an estimated 55% (95% CI 46% to 64%) of 4272 patients with FND reported pain. Random effects models estimated diagnoses of complex regional pain syndrome in 22% (95% CI 6% to 39%) of patients, irritable bowel syndrome in 16% (95% CI 9% to 24%) and fibromyalgia in 10% (95% CI 8% to 13%). Five studies of FND diagnoses among 361 patients with chronic pain were identified. Most interventions for FND did not ameliorate pain, even when other symptoms improved. CONCLUSIONS: Pain symptoms and pain-related diagnoses are common in FND. Classification systems and treatments should routinely consider pain as a comorbidity in patients with FND.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

What is brain fog?

BACKGROUND: The term 'brain fog' is increasingly used colloquially to describe difficulties in the cognitive realm. But what is brain fog? What sort of experiences do people talk about when they talk about brain fog? And, in turn, what might this tell us about potential underlying pathophysiological mechanisms? This study examined first-person descriptions in order to better understand the phenomenology of brain fog. METHODS: Posts containing 'brain fog' were scraped from the social media platform Reddit, using python, over a week in October 2021. We examined descriptions of brain fog, themes of containing subreddits (topic-specific discussion forums), and causal attributions. RESULTS: 1663 posts containing 'brain fog' were identified, 717 meeting inclusion criteria. 141 first person phenomenological descriptions depicted forgetfulness (51), difficulty concentrating (43), dissociative phenomena (34), cognitive 'slowness' and excessive effort (26), communication difficulties (22), 'fuzziness' or pressure (10) and fatigue (9). 50% (363/717) posts were in subreddits concerned with illness and disease: including COVID-19 (87), psychiatric, neurodevelopmental, autoimmune and functional disorders. 134 posts were in subreddits about drug use or discontinuation, and 44 in subreddits about abstention from masturbation. 570 posts included the poster's causal attribution, the most frequent attribution being long COVID in 60/570 (10%). CONCLUSIONS: 'Brain fog' is used on Reddit to describe heterogeneous experiences, including of dissociation, fatigue, forgetfulness and excessive cognitive effort, and in association with a range of illnesses, drugs and behaviours. Encouraging detailed description of these experiences will help us better understand pathophysiological mechanisms underlying cognitive symptoms in health and disease.

Cognitive Behavioral Therapy: Principles, Science, and Patient Selection in Neurology.

Cognitive behavioral therapy (CBT) is a widely used therapeutic modality in general psychiatric practice. In this review, we consider its application to neurological disorders. We examine the basic framework of CBT-that symptoms, emotions, thoughts, and behaviors are all interrelated and that therapeutic interventions that lead to change in thoughts or behavior may have the potential to reduce symptoms or emotional distress. We also outline specific methodological issues to consider when reading or planning studies of CBT interventions, highlighting important topics pertaining to quality control, control group selection, dropouts, and generalizability. We then review the evidence base for CBT's use across a range of neurological disorders. In doing so, we highlight where there is a clear evidence base, and where it is a technique with potential. The review is targeted at a general neurology audience as introduction to the topic not as an advanced guide for expert practitioners.

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Functional cognitive disorder: dementia's blind spot.

An increasing proportion of cognitive difficulties are recognized to have a functional cause, the chief clinical indicator of which is internal inconsistency. When these symptoms are impairing or distressing, and not better explained by other disorders, this can be conceptualized as a cognitive variant of functional neurological disorder, termed functional cognitive disorder (FCD). FCD is likely very common in clinical practice but may be under-diagnosed. Clinicians in many settings make liberal use of the descriptive term mild cognitive impairment (MCI) for those with cognitive difficulties not impairing enough to qualify as dementia. However, MCI is an aetiology-neutral description, which therefore includes patients with a wide range of underlying causes. Consequently, a proportion of MCI cases are due to non-neurodegenerative processes, including FCD. Indeed, significant numbers of patients diagnosed with MCI do not 'convert' to dementia. The lack of diagnostic specificity for MCI 'non-progressors' is a weakness inherent in framing MCI primarily within a deterministic neurodegenerative pathway. It is recognized that depression, anxiety and behavioural changes can represent a prodrome to neurodegeneration; empirical data are required to explore whether the same might hold for subsets of individuals with FCD. Clinicians and researchers can improve study efficacy and patient outcomes by viewing MCI as a descriptive term with a wide differential diagnosis, including potentially reversible components such as FCD. We present a preliminary definition of functional neurological disorder-cognitive subtype, explain its position in relation to other cognitive diagnoses and emerging biomarkers, highlight clinical features that can lead to positive diagnosis (as opposed to a diagnosis of exclusion), and red flags that should prompt consideration of alternative diagnoses. In the research setting, positive identifiers of FCD will enhance our recognition of individuals who are not in a neurodegenerative prodrome, while greater use of this diagnosis in clinical practice will facilitate personalized interventions.

Occupational therapy consensus recommendations for functional neurological disorder.

BACKGROUND: People with functional neurological disorder (FND) are commonly seen by occupational therapists; however, there are limited descriptions in the literature about the type of interventions that are likely to be helpful. This document aims to address this issue by providing consensus recommendations for occupational therapy assessment and intervention. METHODS: The recommendations were developed in four stages. Stage 1: an invitation was sent to occupational therapists with expertise in FND in different countries to complete two surveys exploring their opinions regarding best practice for assessment and interventions for FND. Stage 2: a face-to-face meeting of multidisciplinary clinical experts in FND discussed and debated the data from stage 1, aiming to achieve consensus on each issue. Stage 3: recommendations based on the meeting were drafted. Stage 4: successive drafts of recommendations were circulated among the multidisciplinary group until consensus was achieved. RESULTS: We recommend that occupational therapy treatment for FND is based on a biopsychosocial aetiological framework. Education, rehabilitation within functional activity and the use of taught self-management strategies are central to occupational therapy intervention for FND. Several aspects of occupational therapy for FND are distinct from therapy for other neurological conditions. Examples to illustrate the recommendations are included within this document. CONCLUSIONS: Occupational therapists have an integral role in the multidisciplinary management of people with FND. This document forms a starting point for research aiming to develop evidence-based occupational therapy interventions for people with FND.

Telemedicine Cognitive Behavioral Therapy for Anxiety After Stroke: Proof-of-Concept Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Disabling anxiety affects a quarter of stroke survivors but access to treatment is poor. We developed a telemedicine model for delivering guided self-help cognitive behavioral therapy (CBT) for anxiety after stroke (TASK-CBT). We aimed to evaluate the feasibility of TASK-CBT in a randomized controlled trial workflow that enabled all trial procedures to be carried out remotely. In addition, we explored the feasibility of wrist-worn actigraphy sensor as a way of measuring objective outcomes in this clinical trial. METHODS: We recruited adult community-based stroke patients (n=27) and randomly allocated them to TASK-CBT (n=14) or relaxation therapy (TASK-Relax), an active comparator (n=13). RESULTS: In our sample (mean age 65 [±10]; 56% men; 63% stroke, 37% transient ischemic attacks), remote self-enrolment, electronic signature, intervention delivery, and automated follow-up were feasible. All participants completed all TASK-CBT sessions (14/14). Lower levels of anxiety were observed in TASK-CBT when compared with TASK-Relax at both weeks 6 and 20. Mean actigraphy sensor wearing-time was 33 days (±15). CONCLUSIONS: Our preliminary feasibility data from the current study support a larger definitive clinical trial and the use of wrist-worn actigraphy sensor in anxious stroke survivors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03439813.

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.

Neurologists' experiences of participating in the CODES study-A multicentre randomised controlled trial comparing cognitive behavioural therapy vs standardised medical care for dissociative seizures.

PURPOSE: We investigated neurologists' experience of participating in the large CODES trial involving around 900 adults with dissociative seizures which subsequently evaluated the effectiveness of tailored cognitive behavioural therapy (CBT) plus standardised medical care versus standardised medical care alone in 368 patients with dissociative seizures. METHOD: We asked all neurologists referring patients with dissociative seizures to the CODES study to complete a 43-item online survey. This examined neurologists' (i) demographics, (ii) knowledge of dissociative seizures before and after their involvement in the CODES trial, (iii) clinical practice before, during and since their involvement, and (iv) their experience of the CODES trial. RESULTS: Forty-three (51%) neurologists completed the questionnaire. Only about half of neurologists could make referrals to psychological intervention specific for dissociative seizures before and after the trial. One-third of doctors reported having changed their referral practice following their involvement. The majority (>69%) agreed that patient satisfaction with different aspects of the trial was very high, and 83.7% thought that it was easy to recruit patients for the study. Over 90% agreed they would like the treatment pathway to continue. Respondents found different elements of the trial useful, in particular, the patient factsheet booklet (98%), diagnosis communication advice (93%) and the CBT package (93%). CONCLUSIONS: Neurologists participating in CODES generally found it easy to recruit patients and perceived patient satisfaction as very high. However, 46.5% of neurologists could not offer psychotherapy once the trial had finished, suggesting that problems with lack of access to psychological treatment for dissociative seizures persist.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.

The misdiagnosis of functional disorders as other neurological conditions.

BACKGROUND: Several studies have shown that when patients with functional neurological disorders are followed up, it is rare to find another neurological condition that better explains the initial symptoms in hindsight. No study has examined the reverse, studying patients with a range of neurological disease diagnoses with the aim of assessing how often a new diagnosis of functional disorder better explains the original symptoms. METHODS: A prospective multi-centre cohort study of 2637 new neurology outpatient referrals from primary care in Scotland. Neurologists provided initial diagnoses and a rating of the extent to which their symptoms were explained by an 'organic' neurological disease. Patients were followed up 19 months later with a questionnaire to their primary care physician asking about diagnostic change, and when indicated also by discussion with the original assessing neurologist and review of secondary care records. RESULTS: Valid responses were obtained for 2378 out of 2637 patients (90%) with symptoms 'largely' or 'completely' explained by organic disease at baseline. At follow-up, we found diagnostic errors in 48 patients. Of those, ten (0.4%) had a functional diagnosis and 38 patients (1.6%) had a different 'organic' diagnosis which better explained the original symptoms. CONCLUSIONS: Patients diagnosed with neurological disease sometimes have a functional diagnosis at follow-up which, with hindsight, better explains the original symptoms. This occurs at a frequency similar to the misdiagnosis of 'organic' neurological disease as functional disorder. Misdiagnosis can harm patients in either direction, especially as we enter an era of evidence-based treatment for functional neurological disorders.

Complex regional pain syndrome and functional neurological disorders - time for reconciliation.

There have been many articles highlighting differences and similarities between complex regional pain syndrome (CRPS) and functional neurological disorders (FND) but until now the discussions have often been adversarial with an erroneous focus on malingering and a view of FND as 'all in the mind'. However, understanding of the nature, frequency and treatment of FND has changed dramatically in the last 10-15 years. FND is no longer assumed to be only the result of 'conversion' of psychological conflict but is understood as a complex interplay between physiological stimulus, expectation, learning and attention mediated through a Bayesian framework, with biopsychosocial predisposing, triggering and perpetuating inputs. Building on this new 'whole brain' perspective of FND, we reframe the debate about the 'psychological versus physical' basis of CRPS. We recognise how CRPS research may inform mechanistic understanding of FND and conversely, how advances in FND, especially treatment, have implications for improving understanding and management of CRPS.

Treating anxiety after stroke (TASK): the feasibility phase of a novel web-enabled randomised controlled trial.

BACKGROUND: Anxiety affects a quarter of strokes. It can be disabling even after mild stroke and transient ischaemic attack (TIA). It is not feasible to deliver conventional psychological therapies to the large population of anxious stroke and TIA patients. We are testing the feasibility of a web-enabled randomised controlled trial (RCT) to compare an individualised telemedicine cognitive behavioural therapy (CBT)-based intervention with a self-guided web-based relaxation programme. This study aims to evaluate the feasibility of novel trial procedures and the delivery of the TASK interventions in stroke and TIA patients. METHODS: We aim to recruit 40 community-based stroke and TIA patients experiencing anxiety at least 1 month post-discharge in Lothian, Scotland. We will assess the (1) recruitment number per month; (2) percentage completion of electronic consent; (3) time taken for remote eligibility confirmation; (4) percentage completion of follow-up surveys: modified Rankin scale, EuroQol-5D5L, 7-item generalised anxiety disorder, Patient Health Questionnaire-2 and modified fear questionnaire; (5) data capture of intervention fidelity and (6) use of actigraph smartwatches to obtain continuous data of rest/activity. DISCUSSION: The current study will provide feasibility data on streamlined web-enabled trial procedures and the use of smartwatches to obtain objective measures in stroke and TIA patients, offering potential for large efficient RCTs to be conducted centrally and remotely with far fewer resources in the future. This study will inform further refinements of the TASK interventions before evaluation in a definitive RCT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03439813. Retrospectively registered on 20/2/2018.