Investigating psychobiological causes and mechanisms in functional seizures and functional motor symptoms: Study protocol.

INTRODUCTION: Advances have been made in understanding the aetiology of functional neurological disorder (FND); however, its pathophysiological mechanisms have not been definitively demonstrated. Evidence suggests interacting roles for altered emotional processing and interoception, elevated autonomic arousal, and dissociation, but there is limited evidence demonstrating their causal influence on specific FND symptoms. Our superordinate aim is to elucidate potentially shared and distinct aetiological factors and mechanisms in two common FND subtypes, functional seizures (FS) and functional motor symptoms (FMS). METHODS: This study has a multimodal, mixed between- and within-groups design. The target sample is 50 individuals with FS, 50 with FMS, 50 clinical controls (anxiety/depression), and 50 healthy controls. Potential aetiological factors (e.g., adverse life events, physical/mental health symptoms, dissociative tendencies, interoceptive insight/sensibility) will be assessed with a detailed medical history interview and self-report questionnaires. A laboratory session will include a neurocognitive battery, psychophysiological testing, cardiac interoception and time estimation tasks and an isometric handgrip task. A subsample will undergo magnetic resonance imaging, including structural, resting-state and task-based scans combined with psychophysiological recording. Remote monitoring with ecological momentary assessment and wearables will measure variability in FND symptoms and their potential predictors/correlates for ≥2 weeks in patients' daily lives. Longitudinal follow-ups at 3, 6, and 12-months will monitor longer-term outcomes in the clinical groups. DISCUSSION: This study employs multimodal research methods to rigorously examine several putative mechanisms in FND, at subjective/experiential, behavioural, and physiological levels. The study will test causal hypotheses about the role of altered emotional processing, autonomic arousal, dissociation and interoception in the initiation or exacerbation of FND symptoms, directly comparing these processes in FS and FMS to healthy and clinical controls. This is the first study of its kind, with potential to reveal important targets for prevention and treatment of FND in future.

Psychological Therapy for Functional Neurological Disorder: Examining Impact on Dissociation, Psychological Distress and General Functioning.

Functional neurological disorder (FND) represents a broad group of motor and sensory clinical symptoms which cannot be explained by other neurological diagnoses. Dissociation is considered a key mechanism in their development and maintenance. Despite psychological therapy being the recommended choice of treatment for FND, evidence for its effectiveness is in its infancy. This study explored the dissociative profile of forty-seven patients with FND and evaluated whether individual psychological therapy improved dissociative symptoms, psychological distress and general functioning among twenty-five adults with FND. Patients completed the Multiscale Dissociation Inventory, the EuroQol five-dimensional descriptive system, the General Anxiety Disorder-7 scale and the Patient Health Questionnaire-9. Our sample showed high levels of disengagement, depersonalization and memory disturbance at baseline. Treatment was associated with significant improvements in general functioning, and symptoms of dissociation and anxiety. Improvements in dissociative experiences were found to be possibly due to reduction in anxiety. Improvements in depression were the strongest predictor of improvements in general functioning. Limitations and areas for further research are discussed.

Etiological Factors and Symptom Triggers in Functional Motor Symptoms and Functional Seizures: A Pilot Investigation.

OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functional symptoms, quality of life, and general functioning). METHODS: Seventeen participants with FMS or FS and 17 healthy control participants underwent an in-depth clinical interview and completed questionnaires assessing adverse life events, psychological and physical symptoms, alexithymia, autistic traits, illness perceptions, health-related quality of life (HRQoL), and work and social functioning. RESULTS: Participants with FMS or FS perceived various causes of the disorder, including physical symptoms (65%), emotional problems (53%), adverse life events (47%), and work-related factors (29%). Triggers of FMS and FS included physical activity or exertion (59%), stress and emotions (59%), sensory experiences (47%), and fatigue (41%). Compared with healthy control participants, participants with FMS or FS reported more adverse events during adolescence and higher levels of alexithymia, somatoform dissociation, psychological dissociation (disengagement, depersonalization, and derealization), anxiety, depression, and physical symptoms. Participants with FMS or FS had worse HRQoL than healthy control participants and impaired work and social functioning. There were inverse associations between HRQoL scores and somatoform dissociation, anxiety, and adverse life events. CONCLUSIONS: Participants with FMS or FS reported diverse biopsychosocial etiological factors and symptom triggers. Ongoing psychological symptoms and lifetime adverse experiences were associated with worse HRQoL. Future studies will examine these factors in larger samples of individuals with FMS or FS to better understand their shared and distinct etiological underpinnings.

Mental health and neurodevelopmental patient-reported outcome measures (PROMs) for children and young people with epilepsy: A systematic review.

Children and young people with epilepsy are at higher risk of mental health disorders and atypical neurodevelopmental outcomes compared to the general population. It is essential to detect such comorbidities early in children with epilepsy and provide appropriate interventions, to improve clinical outcomes. We aimed to identify and evaluate the measurement properties of Patient-Reported Outcome Measures (PROMs) that have been validated specifically to measure mental health and neurodevelopmental outcomes in children and/or young people with epilepsy. We searched Embase, Medline, and PsycINFO in May 2023 for relevant studies. Mental health was defined as psychological symptoms (e.g., anxiety, depression, psychosis) and/or behavioural difficulties (e.g., conduct disorders). Neurodevelopmental outcomes included neurodevelopmental disorder traits such as attention-deficit hyperactivity disorder (ADHD) and autistic spectrum disorders. We assessed methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidance. Twelve papers were identified that psychometrically evaluated 13 relevant PROMs (two epilepsy-specific, eleven generic). The appraisal of the PROMs was limited by the availability of only one or two published articles for each, and incomplete psychometric evaluations in some cases. The tool demonstrating the strongest evidence was The Neurological Disorders Depression Inventory-Epilepsy for Youth. The ADHD Rating Scale-IV and The Paediatric Symptom Checklist -17 demonstrated good evidence in favour of at least two measurement properties. This review identified only a small number of mental health and neurodevelopmental PROMs evaluated specifically in paediatric epilepsy. There is a need for further validation of mental health and neurodevelopmental PROMs in children with epilepsy.

Routine outcomes and evaluation of an 8-week outpatient multidisciplinary rehabilitative therapy program for functional neurological disorder.

OBJECTIVES: We report routinely collected outcome data from an 8-week outpatient rehabilitative therapy program. The aims of the intervention were to (1) reduce symptom severity and (2) improve functional mobility in adults with functional neurological disorder (FND). METHODS: The program delivered individual physiotherapy, cognitive behavioral therapy (CBT) and self-management sessions, group physiotherapy, and psychoeducation. Outcome measures included the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Work and Social Adjustment Scale (WSAS), 10-Meter Walk Test (10MWT), Timed Up and Go (TUG), and Berg Balance Scale (BBS). Data were analyzed retrospectively in accordance with routine service evaluation. Wilcoxon signed-rank tests assessed changes in outcomes between weeks 1 and 8 for all patients completing treatment (n = 45). For patients who attended the 3-month follow-up (n = 31), Friedman's ANOVA assessed overall change in outcomes over time. Post hoc Wilcoxon signed-rank tests compared pairs of time-points (Weeks 1, 8, and 3-month follow-up). RESULTS: Analyses of patients completing the program revealed significant improvements in scores between week 1 and week 8. Excluding the BBS, there were statistically significant improvements in all outcomes between weeks 1 and 8 and between weeks 1 and 3-month follow-up. DISCUSSION: This outpatient therapy program provided effective treatment for FND. Patients reported reduced anxiety, depression, and functional impairment, as well as improved performance on most physiotherapy measures.

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, ηp 2=0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, ηp 2=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, ηp 2=<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.

Objective and subjective neurocognitive functioning in functional motor symptoms and functional seizures: preliminary findings.

INTRODUCTION: This study aimed to provide a preliminary assessment of objective and subjective neurocognitive functioning in individuals with functional motor symptoms (FMS) and/or functional seizures (FS). We tested the hypotheses that the FMS/FS group would display poorer objective attentional and executive functioning, altered social cognition, and reduced metacognitive accuracy. METHOD: Individuals with FMS/FS (n = 16) and healthy controls (HCs, n = 17) completed an abbreviated CANTAB battery, and measures of intellectual functioning, subjective cognitive complaints, performance validity, and comorbid symptoms. Subjective performance ratings were obtained to assess local metacognitive accuracy. RESULTS: The groups were comparable in age (p = 0.45), sex (p = 0.62), IQ (p = 0.57), and performance validity (p-values = 0.10-0.91). We observed no impairment on any CANTAB test in this FMS/FS sample compared to HCs, although the FMS/FS group displayed shorter reaction times on the Emotional Bias task (anger) (p = 0.01, np2 = 0.20). The groups did not differ in subjective performance ratings (p-values 0.15). Whilst CANTAB attentional set-shifting performance (total trials/errors) correlated with subjective performance ratings in HCs (p-values<0.005, rs = -0.85), these correlations were non-significant in the FMS/FS sample (p-values = 0.10-0.13, rs-values = -0.46-0.50). The FMS/FS group reported more daily cognitive complaints than HCs (p = 0.006, g = 0.92), which were associated with subjective performance ratings on CANTAB sustained attention (p = 0.001, rs = -0.74) and working memory tests (p < 0.001, rs = -0.75), and with depression (p = 0.003, rs = 0.70), and somatoform (p = 0.003, rs = 0.70) and psychological dissociation (p-values<0.005, rs-values = 0.67-0.85). CONCLUSIONS: These results suggest a discordance between objective and subjective neurocognitive functioning in this FMS/FS sample, reflecting intact test performance alongside poorer subjective cognitive functioning. Further investigation of neurocognitive functioning in FND subgroups is necessary.

Interoception in functional motor symptoms and functional seizures: Preliminary evidence of intact accuracy alongside reduced insight and altered sensibility.

Altered interoception may be a pathophysiological mechanism in functional neurological disorder (FND). However, findings have been inconsistent across interoceptive dimensions in FND including functional motor symptoms (FMS) and seizures (FS). Here, individuals with FMS/FS (n = 17) and healthy controls (HC, n = 17) completed measures of interoceptive accuracy and insight (adapted heartbeat tracking task [HTT] with confidence ratings), a time estimation control task (TET) and the Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2) to assess interoceptive sensibility. The groups did not differ in interoceptive accuracy (p = 1.00, g = 0.00) or confidence (p = .99, g = 0.004), although the FMS/FS group displayed lower scores on the "Not-Distracting" (p < .001, g = 1.42) and "Trusting" (p = .005, g = 1.17) MAIA-2 subscales, relative to HCs. The groups did not differ in TET performance (p = .82, g = 0.08). There was a positive relationship between HTT accuracy and confidence (insight) in HCs (r = .61, p = .016) but not in FMS/FS (r = 0.11, p = .69). HTT confidence was positively correlated with MAIA-2 "Self-Regulation" (r = 0.77, p = .002) and negatively correlated with FND symptom severity (r = -0.84, p < .001) and impact (r = -0.86, p < .001) in FMS/FS. Impaired interoceptive accuracy may not be a core feature in FMS/FS, but reduced insight and altered sensibility may be relevant. Reduced certainty in self-evaluations of bodily experiences may contribute to the pathogenesis of FND symptoms.

MODIFI: protocol for randomised feasibility study of eye-movement desensitisation and reprocessing therapy (EMDR) for functional neurological disorder (FND).

INTRODUCTION: Functional neurological disorder (FND) refers to an involuntary loss of control over and/or aberrant perception of the body. Common presenting symptoms are functional (non-epileptic) seizures, and functional motor disorder, for example, walking difficulties, weakness or tremor. Greater access to effective treatments would lead to reduced distress and disability; and reduce unnecessary healthcare costs.This study will examine eye-movement desensitisation and reprocessing therapy (EMDR) as a treatment for FND. EMDR is an evidence-based treatment for post-traumatic stress disorder (PTSD), but its use for other conditions is growing. An FND-specific EMDR protocol will be tested, and if the intervention proves feasible with promising clinical outcomes, progression to a substantive study could take place. METHODS AND ANALYSIS: Fifty adult patients diagnosed with FND will be recruited. It will be a single-blind randomised controlled trial with two arms: EMDR (plus standard neuropsychiatric care; NPC) and standard NPC. The two groups will be compared at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). Measures of feasibility include safety, recruitment, retention, treatment adherence and acceptability. Clinical outcome measures will assess health-related functioning/quality of life, ratings of FND symptoms and severity, depression, anxiety, PTSD, dissociation, service utilisation and other costs. Improvement and satisfaction ratings will also be assessed. Feasibility outcomes will be summarised using descriptive statistics. Exploratory analyses using (linear/logistic) mixed-effect models will examine the rate of change in the groups' clinical outcome measures across the four time-points.After the intervention period, a sample of participants, and clinicians, will be invited to attend semistructured interviews. The interviews will be analysed using reflexive thematic analysis. ETHICS AND DISSEMINATION: This study has been approved by the NHS West Midlands-Edgbaston Research Ethics Committee. Study findings will be published in open access peer-reviewed journals, presented at conferences, and communicated to participants and other relevant stakeholders. TRIAL REGISTRATION: NCT05455450 (www. CLINICALTRIALS: gov).

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Views on Using Psychoactive Substances to Self-Manage Functional Neurological Disorder: Online Patient Survey Results.

Objective: Functional neurological disorder (FND) causes a high burden of disability and distress. Although it is a common disorder, there is a pressing need for improved access to evidence-based treatments. With difficulties in finding effective treatment, some people with FND may seek alternative means of symptom relief, such as legal and illicit psychoactive substances, although the prevalence and nature of such self-management strategies are currently unclear. Additionally, psychoactive substances may represent novel treatment research opportunities, particularly for those with suboptimal improvement. The investigators examined the use of self-management techniques, as well as perspectives on novel therapies, in this patient population. Methods: An online survey was created to assess self-management strategies and views on novel treatments for FND, including psychedelic therapy. The survey was accessible for 1 month, and respondents were recruited internationally through social media and patient groups. A total of 1,048 respondents from 16 countries completed the survey. Results: Almost half (46%) of 980 respondents reported having tried legal psychoactive substances for the management of their FND symptoms and, on average, nicotine, alcohol, and cannabidiol were reported as modestly effective. Additionally, 15% of respondents reported having used illicit substances, mostly cannabis, to manage FND, with the majority reporting moderate effectiveness and experiencing no or minimal physical (90%) and psychological (95%) sequelae. Many respondents (46%) reported that they would be willing to try medically supervised psychedelic therapy (with 19% of respondents ambivalent) if it were found to be safe and effective. Conclusions: Many people with FND seek alternative means of symptom management outside usual medical care, including legal and illicit psychoactive substances. Further research exploring novel treatment options, such as psychedelics, in FND may be warranted.

Dissociation and its biological and clinical associations in functional neurological disorder: systematic review and meta-analysis.

BACKGROUND: Studies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking. AIMS: To systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations. METHOD: We searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle-Ottawa criteria. The findings were synthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263). RESULTS: Seventy-five studies were eligible (FND n = 3940; control n = 3073), most commonly prospective case-control studies (k = 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy (g = 0.90, 95% CI 0.66-1.14, I2 = 70%) and neurological controls (g = 0.56, 95% CI 0.19-0.92, I2 = 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls (g = 0.94, 95% CI 0.65-1.22, I2 = 42%) and FND samples with motor symptoms (g = 0.40, 95% CI -0.18 to 1.00, I2 = 54%). Somatoform dissociation was elevated in FND versus healthy controls (g = 1.80, 95% CI 1.25-2.34, I2 = 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations. CONCLUSIONS: Our findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed.

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: Functional neurological disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with FND, suggesting that gaps remain in our systems-level neurobiological understanding. As such, other important physiological variables, including autonomic, endocrine, and inflammation findings, need to be contextualized for a more complete mechanistic picture. METHODS: The investigators conducted a systematic review and meta-analysis of available case-control and cohort studies of FND. PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1900, to September 1, 2020, that investigated autonomic, endocrine, and inflammation markers in patients with FND. Sixty-six of 2,056 screened records were included in the review, representing 1,699 patients; data from 20 articles were used in the meta-analysis. RESULTS: Findings revealed that children and adolescents with FND, compared with healthy control subjects (HCs), have increased resting heart rate (HR); there is also a tendency toward reduced resting HR variability in patients with FND across the lifespan compared with HCs. In adults, peri-ictal HR differentiated patients with functional seizures from those with epileptic seizures. Other autonomic and endocrine profiles for patients with FND were heterogeneous, with several studies highlighting the importance of individual differences. CONCLUSIONS: Inflammation research in FND remains in its early stages. Moving forward, there is a need for the use of larger sample sizes to consider the complex interplay between functional neurological symptoms and behavioral, psychological, autonomic, endocrine, inflammation, neuroimaging, and epigenetic/genetic data. More research is also needed to determine whether FND is mechanistically (and etiologically) similar or distinct across phenotypes.

International online survey of 1048 individuals with functional neurological disorder.

BACKGROUND AND PURPOSE: Functional neurological disorder (FND) is common, and symptoms can be severe. There have been no international large-scale studies of patient experiences of FND. METHODS: A patient questionnaire was created to assess FND patient characteristics, symptom comorbidities and illness perceptions. Respondents were recruited internationally through an open access questionnaire via social media and patient groups over a month-long period. RESULTS: In total, 1048 respondents from 16 countries participated. Mean age was 42 years (86% female). Median FND symptom duration was 5 years, and median time from first symptom to diagnosis was 2 years. Mean number of current symptoms (core FND and associated) was 9.9. Many respondents had associated symptoms, for example fatigue (93%), memory difficulties (80%) and headache (70%). Self-reported psychiatric comorbidities were relatively common (depression, 43%; anxiety, 51%; panic, 20%; and post-traumatic stress disorder, 22%). Most respondents reported that FND had multiple causes, including physical and psychological. CONCLUSIONS: This large survey adds further evidence that people with FND typically have high levels of multiple symptom comorbidity with resultant distress. It also supports the notion that associated physical symptoms are of particular clinical significance in FND patients. Dualistic ideas of FND were not supported by respondents, who generally preferred to conceptualize the disorder as one at the interface of mind and brain. The need for a broad approach to this poorly served patient group is highlighted. Potential selection and response biases due to distribution of the survey online, mostly via FND patient groups, are a key limitation.

Trial Of Neurostimulation In Conversion Symptoms (TONICS): a feasibility randomised controlled trial of transcranial magnetic stimulation for functional limb weakness.

OBJECTIVES: Transcranial magnetic stimulation (TMS) has been used therapeutically for functional (conversion) motor symptoms but there is limited evidence for its efficacy and the optimal protocol. We examined the feasibility of a novel randomised controlled trial (RCT) protocol of TMS to treat functional limb weakness. DESIGN: A double-blind (patient, outcome assessor) two parallel-arm, controlled RCT. SETTING: Specialist neurology and neuropsychiatry services at a large National Health Service Foundation Trust in London, UK. PARTICIPANTS: Patients with a diagnosis of functional limb weakness (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition). Exclusion criteria included comorbid neurological or major psychiatric disorder, contraindications to TMS or previous TMS treatment. INTERVENTIONS: Patients were randomised to receive either active (single-pulse TMS to primary motor cortex (M1) above resting motor threshold) or inactive treatment (single-pulse TMS to M1 below resting motor threshold). Both groups received two TMS sessions, 4 weeks apart. OUTCOME MEASURES: We assessed recruitment, randomisation and retention rates. The primary outcome was patient-rated symptom change (Clinical Global Impression-Improvement scale, CGI-I). Secondary outcomes included clinician-rated symptom change, psychosocial functioning and disability. Outcomes were assessed at baseline, both TMS visits and at 3-month follow-up. RESULTS: Twenty-two patients were recruited and 21 (96%) were successfully randomised (active=10; inactive=11). Nineteen (91%) patients were included at follow-up (active=9; inactive=10). Completion rates for most outcomes were good (80%-100%). Most patients were satisfied/very satisfied with the trial in both groups, although ratings were higher in the inactive arm (active=60%, inactive=92%). Adverse events were not more common for the active treatment. Treatment effect sizes for patient-rated CGI-I scores were small-moderate (Cliff's delta=-0.1-0.3, CIs-0.79 to 0.28), reflecting a more positive outcome for the active treatment (67% and 44% of active arm-rated symptoms as 'much improved' at session 2 and follow-up, respectively, vs 20% inactive group). Effect sizes for secondary outcomes were variable. CONCLUSIONS: Our protocol is feasible. The findings suggest that supramotor threshold TMS of M1 is safe, acceptable and potentially beneficial as a treatment for functional limb weakness. A larger RCT is warranted. TRIAL REGISTRATION NUMBER: ISRCTN51225587.

Driving a motor vehicle and psychogenic nonepileptic seizures: ILAE Report by the Task Force on Psychogenic Nonepileptic Seizures.

OBJECTIVES: This International League Against Epilepsy (ILAE) Report: (a) summarizes the literature about "driving and psychogenic nonepileptic seizures (PNES)"; (b) presents the views of international experts; and (c) proposes an approach to assessing the ability of persons with PNES (PwPNES) to drive. METHODS: Phase 1: Systematic literature review. Phase 2: Collection of international expert opinion using SurveyMonkey®. Experts included the members of the ILAE PNES Task Force and individuals with relevant publications since 2000. Phase 3: Joint analysis of the findings and refinement of conclusions by all participants using email. As an ILAE Report, the resulting text was reviewed by the Psychiatry Commission, the ILAE Task Force on Driving Guidelines, and Executive Committee. RESULTS: Eight studies identified by the systematic review process failed to provide a firm evidence base for PNES-related driving regulations, but suggest that most health professionals think restrictions are appropriate. Twenty-six experts responded to the survey. Most held the view that decisions about driving privileges should consider individual patient and PNES characteristics and take account of whether permits are sought for private or commercial driving. Most felt that those with active PNES should not be allowed to drive unless certain criteria were met and that PNES should be thought of as "active" if the last psychogenic seizure had occurred within 6 months. SIGNIFICANCE: Recommendations on whether PwPNES can drive should be made at the individual patient level. Until future research has determined the risk of accidents in PwPNES a proposed algorithm may guide decisions about driving advice.

Dissociation and interoception in functional neurological disorder.

Introduction: We aimed to examine susceptibility to dissociation and the impact of dissociation on interoceptive processing in individuals with functional neurological disorder (FND). We hypothesised that dissociative states would be elevated and interoceptive accuracy and awareness impaired at baseline in people with FND, and that such differences would be exacerbated following acute dissociation. Methods: Nineteen adults with FND were compared to 20 healthy controls. A modified heart-beat tracking task measured interoceptive accuracy and awareness (confidence) before and after a validated dissociation induction procedure. An exteroceptive processing control task was included. Mann-Whitney tests and r-values (effect size) were computed for between-group comparisons. Results: The FND group displayed elevated dissociation at baseline (p = 0.001, r = 0.528) compared to controls which increased following dissociation-induction (p < 0.001, r = 0.663). Interoceptive accuracy did not differ between groups at baseline (p = 0.967, r = 0.009); however, the FND group had lower accuracy scores post-induction (p = 0.021, r = 0.379). A negative correlation (trend) between change scores for dissociation and interoceptive accuracy was noted (rs = -0.411, p = 0.057). Confidence ratings on interoceptive and exteroceptive processing tasks were lower in the FND group (p-values < 0.05 or <0.01, r-values 0.331-0.489). Conclusions: Individuals with FND experienced greater susceptibility to dissociation, metacognitive deficits and impaired interoceptive accuracy than controls after acute dissociation.

Attentional Processing and Interpretative Bias in Functional Neurological Disorder.

OBJECTIVE: Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally. METHODS: We compared the cognitive task performance of FND, CFS, and healthy control (HC) groups. The tasks assessed attentional bias toward illness-relevant stimuli (visual probe task), attentional control (attention network task), and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue, and general health. RESULTS: Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS, and 51 HC participants were included. Although participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13, p = .002, d = 0.624), individuals with FND did not (t = -1.59, p = .118, d = 0.379). Both the FND (t = 3.08, p = .003, d = 0.759) and CFS (t = 2.74, p = .007, d = 0.548) groups displayed worse attentional control than did the HC group. Similarly, the FND (t = 3.63, p < .001, d = 0.801) and CFS groups (t = 4.58, p < .001, d = 0.909) showed more somatic interpretative bias than did the HC group. CONCLUSIONS: Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias toward somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.

Differentiating psychogenic nonepileptic from epileptic seizures: A mixed-methods, content analysis study.

BACKGROUND: Identification of clinical features that might distinguish psychogenic nonepileptic seizures (PNES) from epileptic seizures (ES) is of value for diagnosis, management, and understanding of both conditions. Previous studies have shown that patients' descriptions of their seizures reflect differences in content and delivery. We aimed to compare verbal descriptions of PNES and ES using a mixed-methods approach. METHODS: We analyzed data from semi-structured interviews in which patients with video-electroencephalography (EEG)-confirmed ES (n = 30) or PNES (n = 10) described their seizures. Two masked raters independently coded the transcripts for relevant psychological categories and discrepancies that were noted and resolved. Additional analyses were conducted using the Linguistic Inquiry and Word Count system. The identified phenomena were descriptively compared, and inferential analyses assessed group differences in frequencies. A logistic regression analysis examined the predictive power of the most distinctive phenomena for diagnosis. RESULTS: As compared with ES, PNES reported longer seizures, more preseizure negative emotions (e.g., fear), anxiety symptoms (e.g., arousal, hyperventilation), altered vision/olfaction, and automatic behaviors. During seizures, PNES reported more fear, altered breathing, and dissociative phenomena (depersonalization, impaired time perception). Epileptic seizures reported more self-injurious behavior. Postseizure, PNES reported more fear and weeping and ES more amnesia and aches. The predictive power when including these variables was 97.5%. None of the single predictor variables was significant. The few but consistent linguistic differences related to the use of some pronouns and references to family. CONCLUSIONS: Although no single clinical feature definitively distinguishes PNES from ES, several features may be suggestive of a PNES diagnosis, including longer duration, negative emotion (i.e., fear) throughout the events, preseizure anxiety, ictal dissociation, and postseizure weeping. Fewer reports of ictal self-injury and postseizure amnesia and aches may also indicate the possibility of PNES.