Psychological and demographic characteristics of 368 patients with dissociative seizures: data from the CODES cohort.

BACKGROUND: We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology. METHODS: Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic). RESULTS: Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men. CONCLUSIONS: Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort.

Characteristics of 698 patients with dissociative seizures: A UK multicenter study.

OBJECTIVE: We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. METHODS: We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non-Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. RESULTS: In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self-reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two-thirds were unemployed. SIGNIFICANCE: Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

Implicit attentional bias for facial emotion in dissociative seizures: Additional evidence.

This study sought to extend knowledge about the previously reported preconscious attentional bias (AB) for facial emotion in patients with dissociative seizures (DS) by exploring whether the finding could be replicated, while controlling for concurrent anxiety, depression, and potentially relevant cognitive impairments. Patients diagnosed with DS (n=38) were compared with healthy controls (n=43) on a pictorial emotional Stroop test, in which backwardly masked emotional faces (angry, happy, neutral) were processed implicitly. The group with DS displayed a significantly greater AB to facial emotion relative to controls; however, the bias was not specific to negative or positive emotions. The group effect could not be explained by performance on standardized cognitive tests or self-reported depression/anxiety. The study provides additional evidence of a disproportionate and automatic allocation of attention to facial affect in patients with DS, including both positive and negative facial expressions. Such a tendency could act as a predisposing factor for developing DS initially, or may contribute to triggering individuals' seizures on an ongoing basis. Psychological interventions such as Cognitive Behavioral Therapy (CBT) or AB modification might be suitable approaches to target this bias in clinical practice.

Explicit Facial Emotion Processing in Patients With Dissociative Seizures.

OBJECTIVE: There have, as yet, been few experimental studies of explicit facial affect recognition in patients with dissociative seizures (DS). The aim of the study was to examine explicit recognition and physiological responses to facial expressions in this group, relative to healthy controls. METHODS: Forty patients with DS and 43 controls completed a computerized test of facial affect recognition, including five basic expressions (happiness, anger, disgust, fear, neutral). Recognition accuracy, emotional intensity judgements, and skin conductance levels and responses were dependent measures. Analyses controlled for a range of potentially confounding variables, including anxiety, depression, and medication effects. RESULTS: The DS group was less accurate at identifying facial expressions than controls (p = .005, ηp = 0.10). No group difference emerged for intensity judgements (p = .72, ηp = 0.002). Mean skin conductance levels were higher in the DS group relative to controls (p = .046, ηp = 0.053). However, a subgroup of DS patients showed attenuated skin conductance responses to the facial stimuli, compared with controls (p = .015, ηp = 0.18). These differences could not be accounted for by possible confounding variables. Recognition accuracy for neutral faces correlated negatively with trauma scores (r = -0.486, p = .002) and abandonment concerns (r = -0.493, p = .002) in the DS group. CONCLUSIONS: Patients with DS showed reduced recognition accuracy for facial affect, despite accurately perceiving its intensity. Elevated autonomic arousal may characterize patients with DS in general, alongside reduced phasic autonomic responses to facial expressions in some patients with the disorder.

Emotion and dissociative seizures: A phenomenological analysis of patients' perspectives.

Quantitative research has indicated that patients with dissociative seizures (DS) show altered responses to emotional stimuli, in addition to considerable emotional distress and dysregulation. The present study sought to further explore emotional processes in this population, to extend previous findings, and to provide a phenomenological insight into patients' perspectives on these issues. Semistructured interviews were carried out with 15 patients with DS, and the principles of interpretative phenomenological analysis (IPA) were adopted in data analysis. Key themes elicited included: i) general emotional functioning; ii) adverse (stressful/traumatic) life experiences; iii) the role of emotions in DS; iv) relating to others; and v) resilience, protective factors, and coping mechanisms. The clinical and theoretical implications of the findings are discussed.

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

BACKGROUND: The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. METHODS/DESIGN: The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse events. We will include a nested qualitative study to evaluate participants' views of the intervention and factors that acted as facilitators and barriers to participation. DISCUSSION: This study will be the first adequately powered evaluation of CBT for this patient group and offers the potential to provide an evidence base for treating this patient group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05681227 ClinicalTrials.gov NCT02325544.

Recent developments in our understanding of the semiology and treatment of psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) pose clinical challenges in terms of diagnosis and management. Recent studies have thrown further light on the extent to which features of PNES semiology may distinguish PNES patients from those with epilepsy. Management of this patient group will include discussion of the diagnosis, withdrawal of antiepileptic drugs, and psychological intervention when PNES persist. However, the evidence base for these different stages remains limited, although recent studies are beginning to provide guidance for clinicians and future research.

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme.

Autonomic and subjective responsivity to emotional images in people with dissociative seizures.

People with dissociative seizures (DS) report a range of difficulties in emotional functioning and exhibit altered responding to emotional facial expressions in experimental tasks. We extended this research by investigating subjective and autonomic reactivity (ratings of emotional valence, arousal and skin conductance responses [SCRs]) to general emotional images in 39 people with DS relative to 42 healthy control participants, whilst controlling for anxiety, depression, cognitive functioning and, where relevant, medication use. It was predicted that greater subjective negativity and arousal and increased SCRs in response to the affective pictures would be observed in the DS group. The DS group as a whole did not differ from controls in their subjective responses of valence and arousal. However, SCR amplitudes were greater in 'autonomic responders' with DS relative to 'autonomic responders' in the control group. A positive correlation was also observed between SCRs for highly arousing negative pictures and self-reported ictal autonomic arousal, in DS 'autonomic responders'. In the DS subgroup of autonomic 'non-responders', differences in subjective responses were observed for some conditions, compared to control 'non-responders'. The findings indicate unaffected subjective responses to emotional images in people with DS overall. However, within the group of people with DS, there may be subgroups characterized by differences in emotional responding. One subgroup (i.e., 'autonomic responders') exhibit heightened autonomic responses but intact subjective emotional experience, whilst another subgroup (i.e., 'autonomic non-responders') seem to experience greater subjective negativity and arousal for some emotional stimuli, despite less frequent autonomic reactions. The current results suggest that therapeutic interventions targeting awareness and regulation of physiological arousal and subjective emotional experience could be of value in some people with this disorder.

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

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

Illness representations, coping styles and mood in adults with epilepsy.

It has been generally accepted that psychosocial well-being in people with epilepsy may show an association with the type of coping strategies they adopt. However, relatively little attention has been paid to the way people with epilepsy perceive their illness (illness representations) in determining their well-being and whether these representations are related to coping strategies in determining psychological outcome. We administered the Illness Perception Questionnaire and the Ways of Coping scale and examined their relationship with anxiety and depression scores in 43 adults with chronic epilepsy. Within multiple regression analyses, whilst epilepsy variables were not significantly related to mood, after also adjusting for patients' gender, anxiety scores were best predicted by an increased relative use of escape-avoidance and a decreased relative use of distancing as coping strategies; increased depression scores were best predicted by greater relative use of escape-avoidant and self-controlling coping. Once coping factors had been accounted for, Illness Identity scores independently predicted anxiety scores, indicating that coping was not acting simply to mediate the impact of illness representations on patients' mood. However, illness representations did not independently predict depression, suggesting that in the case of negative affect, coping was acting as a mediating factor. Findings indicate the importance of aspects of epilepsy patients' cognitive representations of their illness, as well as of their coping styles in determining psychological well-being.

Nonepileptic seizures following general anesthetics: a report of five cases.

Five patients who developed seizures following a general anesthetic are described. It is not possible to determine retrospectively whether or not the initial attacks were definitely epileptic, but these patients all subsequently received a diagnosis of psychological nonepileptic convulsions/seizures (also known as pseudoseizures, psychogenic nonepileptic seizures, and nonepileptic attack disorder) established by video/EEG telemetry or ictal EEG recordings. In two cases there was evidence of concurrent epilepsy. We suggest that nonepileptic seizures may develop following postanesthetic seizures and that a psychogenic basis for seizures occurring after general anesthetics needs to be considered.

An evaluation of cognitive behavioral therapy as a treatment for dissociative seizures: a pilot study.

OBJECTIVE: To evaluate in an open trial the effectiveness of cognitive behavioral therapy as a treatment of adults with dissociative seizures (i.e., "pseudoseizures"). BACKGROUND: Although suggestions have been made concerning the management of patients with dissociative seizures, no studies have previously evaluated the systematic use of cognitive behavioral therapy in the treatment of this disorder. METHOD: Twenty patients diagnosed with dissociative seizures were offered treatment comprising 12 sessions of cognitive behavioral therapy. Principal outcome measures were dissociative seizure frequency and psychosocial functioning, including improvement in employment status and mood. Measures were administered before treatment, at the end of treatment, and at a 6-month follow-up. RESULTS: Treatment was completed by 16 patients (questionnaire measures were not available for 4 patients who discontinued treatment). Following treatment, there was a highly significant reduction in seizure frequency and an improvement in self-rated psychosocial functioning. These improvements were maintained at the 6-month follow-up. There was also a tendency for patients to have improved their employment status between the start of treatment and the 6-month follow-up period. CONCLUSIONS: In this open prospective trial, cognitive behavioral therapy was associated with a reduction in dissociative seizure frequency and an improvement in psychosocial functioning in adults with dissociative seizures.