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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Anxiety After Stroke: The Importance of Subtyping.

BACKGROUND AND PURPOSE: Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. METHODS: We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. RESULTS: Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45-0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94-9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3-5, [anxiety] 55% versus [no anxiety] 29%; P<0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10-27 versus [no anxiety] 0, 0-5; P<0.001). CONCLUSIONS: Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety.

'Cryptogenic Drop Attacks' revisited: evidence of overlap with functional neurological disorder.

OBJECTIVE: In their 1973 BMJ paper 'Cryptogenic Drop Attacks', Stevens and Matthews described 40, mostly middle-aged, female patients with drop attacks of unknown cause. Although clinically common, there has been little on this topic since. We aimed to determine clinical features, comorbidity and outcome of patients with drop attacks. METHODS: We carried out a retrospective review of patients with cryptogenic drop attacks seen consecutively by one clinician (JS) between 2006 and 2016. Demographics, phenomenology, duration and frequency of attacks, attack description and comorbid diagnoses were recorded. Patients were followed up with a notes review. RESULTS: 83 patients with cryptogenic drop attacks were predominantly female (89%, n=79), mean age 44 years. The majority (93%, n=77) could not remember the fall itself and almost half (43%, n=36) experienced prodromal dissociative symptoms. Mechanical trips or syncope preceded drop attacks, historically, in 24% (n=20) of cases. Persistent fatigue (73%, n=61), chronic pain (40%, n=33), functional limb weakness (31%,n=26) and dissociative (non-epileptic) attacks 28% (n=23) were common, with the latter usually preceding or emerging from drop attacks. At follow-up (88%, mean 38 months), 28% (n=23) had resolution of their drop attacks. Predisposing (but non-causative) disease comorbidity was found at baseline (n=12) and follow-up (n=5). CONCLUSIONS: Cryptogenic drop attacks are associated with high frequency of comorbid functional somatic and functional neurological disorders. Patients commonly have prodromal dissociative symptoms and in some there was a clear relationship with prior or subsequent dissociative (non-epileptic) attacks. Some cryptogenic drop attacks may be best understood as phenomena on the spectrum of dissociative attacks.

Cognitive behavioural therapy for depression: systematic review of imaging studies.

OBJECTIVE: Although cognitive behavioural therapy (CBT) has been shown to be an effective treatment for depression, the biological mechanisms underpinning it are less clear. This review examines if it is associated with changes identifiable with current brain imaging technologies. METHODS: To better understand the mechanisms by which CBT exerts its effects, we undertook a systematic review of studies examining brain imaging changes associated with CBT treatment of depression. RESULTS: Ten studies were identified, five applying functional magnetic resonance imaging, three positron emission tomography, one single photon emission computer tomography, and one magnetic resonance spectroscopy. No studies used structural MRI. Eight studies included a comparator group; in only one of these studies was there randomised allocation to another treatment. CBT-associated changes were most commonly observed in the anterior cingulate cortex (ACC), posterior cingulate, ventromedial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC) and amygdala/hippocampus. DISCUSSION: The evidence, such as it is, suggests resting state activity in the dorsal ACC is decreased by CBT. It has previously been suggested that treatment with CBT may result in increased efficiency of a putative 'dorsal cognitive circuit', important in cognitive control and effortful regulation of emotion. It is speculated this results in an increased capacity for 'top-down' emotion regulation, which is employed when skills taught in CBT are engaged. Though changes in activity of the dorsal ACC could be seen as in-keeping with this model, the data are currently insufficient to make definitive statements about how CBT exerts its effects. Data do support the contention that CBT is associated with biological brain changes detectable with current imaging technologies.

Somatic symptom count scores do not identify patients with symptoms unexplained by disease: a prospective cohort study of neurology outpatients.

OBJECTIVE: Somatic symptoms unexplained by disease are common in all medical settings. The process of identifying such patients requires a clinical assessment often supported by clinical tests. Such assessments are time-consuming and expensive. Consequently the observation that such patients tend to report a greater number of symptom has led to the use of self-rated somatic symptom counts as a simpler and cheaper diagnostic aid and proxy measure for epidemiological surveys. However, despite their increasing popularity there is little evidence to support their validity. METHODS: We tested the score on a commonly used self-rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus enhanced iterations including an additional 10 items on specific neurological symptoms and an additional 5 items on mental state) for diagnostic sensitivity and specificity against a medical assessment (with 18 months follow-up) in a prospective cohort study of 3781 newly attending patients at neurology clinics in Scotland, UK. RESULTS: We found 1144/3781 new outpatients had symptoms that were unexplained by disease. The patients with symptoms unexplained by disease reported higher symptoms count scores (PHQ 15: 5.6 (95% CI 5.4 to 5.8) vs 4.2 (4.1 to 4.4) p<0.0001). However, the PHQ15 performed little better than chance in its ability to identify patients with symptoms unexplained by disease. The findings with the enhanced scales were similar. CONCLUSIONS: Self-rated symptom count scores should not be used to identify patients with symptoms unexplained by disease.

'A Leg to Stand On' by Oliver Sacks: a unique autobiographical account of functional paralysis.

Oliver Sacks, the well known neurologist and writer, published his fourth book, 'A Leg to Stand On', in 1984 following an earlier essay 'The Leg' in 1982. The book described his recovery after a fall in a remote region of Norway in which he injured his leg. Following surgery to reattach his quadriceps muscle, he experienced an emotional period in which his leg no longer felt a part of his body, and he struggled to regain his ability to walk. Sacks attributed the experience to a neurologically determined disorder of body-image and bodyego induced by peripheral injury. In the first edition of his book Sacks explicitly rejected the diagnosis of 'hysterical paralysis' as it was then understood, although he approached this diagnosis more closely in subsequent revisions. In this article we propose that, in the light of better understanding of functional neurological symptoms, Sacks' experiences deserve to be reappraised as a unique insight in to a genuinely experienced functional/psychogenic leg paralysis following injury.

Functional (conversion) neurological symptoms: research since the millennium.

Functional neurological symptoms (FNS) are commonly encountered but have engendered remarkably little academic interest. 'UK-Functional Neurological Symptoms (UK-FNS)' was an informal inaugural meeting of UK based clinicians in March 2011 with a variety of research and clinical interests in the field. This narrative review reflects the content of the meeting, and our opinion of key findings in the field since the turn of the millennium.