Screening for epilepsy-specific anxiety symptoms: French validation of the EASI.

OBJECTIVES: (1) To translate and validate the Epilepsy Anxiety Survey Instrument (EASI) in French people with epilepsy (PWE); (2) to further investigate the screening properties of each dimension of the EASI in terms of Diagnostic and Statistical Manual of Mental Disorders (DSM) anxiety disorders and of epilepsy-specific anxiety disorders, namely, anticipatory anxiety of seizures (AAS) and epileptic social phobia. METHODS: Following back-translation, the French EASI was tested in PWE > 18 years using the Mini-International Neuropsychiatric Interview (MINI) as gold standard for DSM anxiety disorders. We added 3 original questions to explore epilepsy-specific anxiety symptoms. The Generalized Anxiety Disorders-7 (GAD-7), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and Adverse Events Profile were performed for external validity. Receiver operator characteristics (ROC) were analyzed. RESULTS: One hundred and forty nine native French speakers with epilepsy were included. Concerning DSM disorders, around 25% had GAD, 18% Agoraphobia, and <10% Social Phobia or Panic Disorder. Concerning possible epilepsy-specific anxiety disorder, 35% had AAS and 38% had epileptic social phobia. Bi-dimensional structure of the EASI was confirmed. Internal and external validity was satisfactory. ROC analysis showed AUC of 0.83 for detection of GAD and AUC 0.79 for other DSM anxiety disorders. ROC analysis of the 8-item French brEASI showed good performance for detection of GAD (AUC 0.83) and other DSM anxiety disorders (AUC 0.76) but not for epilepsy-specific anxiety symptoms (AUC 0.63). Conversely, dimension 2 of the French EASI (=10 items) allowed good detection of epilepsy-specific anxiety symptoms (AUC 0.78); cutoff > 4, sensitivity 82.4, specificity 66.7. CONCLUSION: Epilepsy-specific anxiety symptoms were prevalent, in around 60%. The French version of the EASI showed robust performance. The French 8-item brEASI allows screening for all DSM anxiety disorders with superior performance than the GAD-7, but is less suited to screening for epilepsy-specific anxiety. We propose the "Epilepsy-Specific Anxiety" (ESA) 10-item screening instrument, based on dimension 2 of the EASI, as a complementary clinical and research tool.

Post-traumatic stress disorder (PTSD) in patients with epilepsy.

Anxiety and depression in epilepsy are strongly documented but post-traumatic stress disorder (PTSD) is underestimated and poorly known. We studied the links between psycho-traumagenic events (TE), onset of epilepsy, and severity of PTSD symptoms in patients with epilepsy. The study included 54 patients with epilepsy and 61 controls. We used validated questionnaires to screen for anxiety, depression, and PTSD symptoms and we conducted an interview to measure the prevalence of TE. We developed an original exploratory questionnaire to assess the presence of PTSD during interictal and peri-ictal periods. The results show that patients reported more exposure to a TE and presented significantly more severe PTSD symptoms than controls. Seventy-eight percent of patients (vs. 52% of controls) had been exposed to a TE, and 26% (vs. 7%) had a score above the diagnostic threshold of the PTSD scale. In addition, 18.6% of patients reported that their epilepsy began at the same time as they began to experience PTSD symptoms following a TE. Patients with high PTSD scores (above the threshold, n = 14) reported significantly more depression symptoms than patients without PTSD and reported PTSD symptoms both during the ictal and peri-ictal periods. Within the whole group of patients, anxiety (72%) and depression (33%) symptoms significantly correlated with PTSD symptoms reported by the scale. This study shows that patients with epilepsy have increased prevalence of self-reported PTSD symptoms. We describe the clinical picture specific to patients with epilepsy, which may include classical PTSD symptoms but also specific peri-ictal symptoms.

The Relationship Between Epilepsy and Anxiety Disorders.

PURPOSE OF REVIEW: The current review aims at providing an overview of relevant aspects of anxiety symptoms and anxiety disorders (AD) in adults patients with epilepsy (PWE). RECENT FINDINGS: Firstly, the appropriate diagnosis of type of anxiety symptoms and AD in PWE will be presented. Anxiety symptoms are often peri-ictal and classified in relation to their temporal occurrence to seizures. Anxiety symptoms are of three types: preictal (preceding a seizure), ictal (presenting as part of the seizure symptoms and signs), and postictal (occurring within 72 h of a seizure). AD are diagnosed in the interictal period and occur independently of seizures. Four specific AD in PWE can be objectified: anticipatory anxiety of epileptic seizures (AAS), seizure phobia, epileptic social phobia, and epileptic panic disorder. Secondly, the bidirectional pathophysiological relationship between anxiety and epilepsy will be described. Anxiety is a trigger for seizures in some patients, and the notion of stress and arousal is essential to understand the relationship between anxiety and seizure. Moreover, seizures arising from the limbic network especially involving amygdala, which may express fear-related semiology, provide insight into the pathophysiology of AD comorbidities. Thirdly, the methods of screening for AD and anxiety symptoms will be detailed. Fourthly, the pharmacological and psychobehavioral management of anxiety symptoms and AD in PWE will be presented. Arousal-based approaches for preictal and ictal symptoms and anxiety-based approaches for postictal and interictal symptoms will be presented. Despite lack of evidence-based approaches, it is recognized that management of epilepsy is not only about controlling seizures, but also depends heavily on detecting, correctly diagnosing, and appropriately managing anxiety symptoms and AD comorbidities, in order to maximize quality of life. Improving self-control and self-efficacy is of fundamental importance in the management of PWE. Further rigorously designed studies focusing on anxiety symptoms and AD are essential to improve the overall care of PWE.

Stress regulation in drug-resistant epilepsy.

The prevalence of psychological distress, especially depressive and anxiety disorders, is higher in epilepsy than in other chronic health conditions. These comorbid conditions contribute even more than epileptic seizures themselves to impaired quality of life in patients with epilepsy (PWE). The link between these comorbidities and epilepsy appears to have a neurobiological basis, which is at least partly mediated by stress through psychological and pathophysiological pathways. The impact of stress in PWE is also particularly important because it is the most frequently reported seizure trigger. It is therefore crucial for clinicians to take stress-related conditions and psychiatric comorbidities into account when managing PWE and to propose clinical support to enhance self-control of stress. Screening tools have been specially designed and validated in PWE for depressive disorders and anxiety disorders (e.g. NDDI-E, GAD-7). Other instruments are useful for measuring stress-related variables (e.g. SRRS, PSS, SCS, MHLCS, DSR-15, ERP-R, QOLIE-31) in order to help characterize the individual "stress profile" and thus orientate patients towards the most appropriate treatment. Management includes both pharmacological treatment and nonpharmacological methods for enhancing self-management of stress (e.g. mindfulness-based therapies, yoga, cognitive-behavioral therapies, biofeedback), which may not only protect against psychiatric comorbidities but also reduce seizure frequency.

Self-control of epileptic seizures by nonpharmacological strategies.

Despite the unpredictability of epileptic seizures, many patients report that they can anticipate seizure occurrence. Using certain alert symptoms (i.e., auras, prodromes, precipitant factors), patients can adopt behaviors to avoid injury during and after the seizure or may implement spontaneous cognitive and emotional strategies to try to control the seizure itself. From the patient's view point, potential means of enhancing seizure prediction and developing seizure control supports are seen as very important issues, especially when the epilepsy is drug-resistant. In this review, we first describe how some patients anticipate their seizures and whether this is effective in terms of seizure prediction. Secondly, we examine how these anticipatory elements might help patients to prevent or control their seizures and how the patient's neuropsychological profile, specifically parameters of perceived self-control (PSC) and locus of control (LOC), might impact these strategies and quality of life (QOL). Thirdly, we review the external supports that can help patients to better predict seizures. Finally, we look at nonpharmacological means of increasing perceived self-control and achieving potential reduction of seizure frequency (i.e., stress-based and arousal-based strategies). In the past few years, various approaches for detection and control of seizures have gained greater interest, but more research is needed to confirm a positive effect on seizure frequency as well as on QOL.

Skin conductance biofeedback training in adults with drug-resistant temporal lobe epilepsy and stress-triggered seizures: a proof-of-concept study.

The present proof-of-concept study investigated the feasibility of skin conductance biofeedback training in reducing seizures in adults with drug-resistant temporal lobe epilepsy (TLE), whose seizures are triggered by stress. Skin conductance biofeedback aims to increase levels of peripheral sympathetic arousal in order to reduce cortical excitability. This might seem somewhat counterintuitive, since such autonomic arousal may also be associated with increased stress and anxiety. Thus, this sought to verify that patients with TLE and stress-triggered seizures are not worsened in terms of stress, anxiety, and negative emotional response to this nonpharmacological treatment. Eleven patients with drug-resistant TLE with seizures triggered by stress were treated with 12 sessions of biofeedback. Patients did not worsen on cognitive evaluation of attentional biases towards negative emotional stimuli (P>.05) or on psychometric evaluation with state anxiety inventory (P = .059); in addition, a significant improvement was found in the Negative Affect Schedule (P = .014) and in the Beck Depression Inventory (P = .009). Biofeedback training significantly reduced seizure frequency with a mean reduction of -48.61% (SD = 27.79) (P = .005). There was a correlation between the mean change in skin conductance activity over the biofeedback treatment and the reduction of seizure frequency (r(11) = .62, P = .042). Thus, the skin conductance biofeedback used in the present study, which teaches patients to achieve an increased level of peripheral sympathetic arousal, was a well-tolerated nonpharmacological treatment. Further, well-controlled studies are needed to confirm the therapeutic value of this nonpharmacological treatment in reducing seizures in adults with drug-resistant TLE with seizures triggered by stress.

Stress and Epilepsy: Towards Understanding of Neurobiological Mechanisms for Better Management.

Stress has been identified as a major contributor to human disease and is postulated to play a substantial role in epileptogenesis. In a significant proportion of individuals with epilepsy, sensitivity to stressful events contributes to dynamic symptomatic burden, notably seizure occurrence and frequency, and presence and severity of psychiatric comorbidities [anxiety, depression, posttraumatic stress disorder (PTSD)]. Here, we review this complex relationship between stress and epilepsy using clinical data and highlight key neurobiological mechanisms including the hypothalamic-pituitary-adrenal (HPA) axis dysfunction, altered neuroplasticity within limbic system structures, and alterations in neurochemical pathways such as brain-derived neurotrophic factor (BNDF) linking epilepsy and stress. We discuss current clinical management approaches of stress that help optimize seizure control and prevention, as well as psychiatric comorbidities associated with epilepsy. We propose that various shared mechanisms of stress and epilepsy present multiple avenues for the development of new symptomatic and preventative treatments, including disease modifying therapies aimed at reducing epileptogenesis. This would require close collaborations between clinicians and basic scientists to integrate data across multiple scales, from genetics to systems biology, from clinical observations to fundamental mechanistic insights. In future, advances in machine learning approaches and neuromodulation strategies will enable personalized and targeted interventions to manage and ultimately treat stress-related epileptogenesis.

Is beta band desynchronization related to skin conductance biofeedback effectiveness in drug resistant focal epilepsy?

Skin Conductance Biofeedback (SCB) is a non-invasive behavioral treatment for epilepsy based on modulation of Galvanic Skin Response (GSR). We evaluated changes in functional connectivity occurring after SCB. Six patients with drug-resistant temporal lobe epilepsy underwent monthly SCB sessions. For each patient, 10 min of resting-state magnetoencephalographic (MEG) recording were acquired before and after the first and the last SCB session. For each recording we computed the mean weighted phase lag index (WPLI) across all pair of MEG sensors. After SCB, two patients had consistent reduction of seizure frequency (>50 %). Connectivity analysis revealed a decrease of WPLI-beta band in the two responders and an increase of WPLI-alpha connectivity in all patients regardless of the clinical effect. Results suggest that reduction of WPLI-beta-low connectivity is related to the clinical response after SCB.

Subjective and physiological response to emotions in temporal lobe epilepsy and psychogenic non-epileptic seizures.

BACKGROUND: Temporal lobe epilepsy (TLE) and psychogenic non-epileptic seizures (PNES) are conditions frequently associated with dysfunction in emotional regulation leading to increased risk of affective disorders. This study investigates emotional processing with an objective measure of emotional reactivity in patients with TLE and patients with PNES. METHODS: 34 patients with TLE and 14 patients with PNES were evaluated on skin conductance responses (SCR) to emotions induced by short films and compared to 34 healthy controls. An attention and a suppression condition were performed while viewing the films. RESULTS: The both groups of patients disclosed lower SCR to emotions compared to controls, mainly in suppression condition. While TLE patients had lower SCR in attention condition than controls for fear, sadness and happiness, PNES had lower SCR only for happiness. In suppression condition, both had lower SCR than controls except for peacefulness in both groups and sadness in PNES. Subjective evaluations revealed that both patient's groups scored a higher intensity for sadness than controls in attention and lower for in fear and disgust in suppression only in TLE. LIMITATIONS: The sample size in the PNES group and the lack of a control group with similar levels of mood symptoms limited the interpretation of our results. CONCLUSION: As no correlation were found between SCR to emotions and scores of affective disorders, this pattern of responses might be underpinned by specific pathophysiological and cognitive mechanisms related to TLE and to PNES. Thus, therapeutic approaches targeting emotional autonomic responses can be of interest in the management of these conditions.

A case-control study of skin conductance biofeedback on seizure frequency and emotion regulation in drug-resistant temporal lobe epilepsy.

This study investigates the physiological basis of effects of skin conductance biofeedback on anxiety disorders, depressive disorders and stress in drug-resistant temporal lobe epilepsy (TLE). This method presents an interest in seizure reduction and improvement in psychiatric comorbidities frequently associated with TLE. Our goal was to better understand the impact of biofeedback on seizure control and on emotional regulation. Fifteen patients with TLE were treated with 12 skin conductance biofeedback sessions and compared with 15 control TLE patients on a waiting list. They were evaluated in terms of seizure frequency, clinical evaluations of anxiety and depression and skin conductance responses (SCR) to five emotions: fear, disgust, sadness, happiness and peacefulness induced by short films. Biofeedback training significantly reduced seizure frequency with a mean reduction of -47.42% in the biofeedback group, while the control group did not differ at the two time measures. A significant improvement was found for depression and trait-anxiety in the biofeedback group but not in the control group. There were no differences on SCR on any emotion after biofeedback treatment. A correlation was found between mean change in SCR over the biofeedback treatment and the reduction of seizure frequency, but not between SCR changes and scores on psychiatric comorbidities. These results show independent effect of biofeedback on mood and seizure control. Improvements in anxiety and depressive symptoms were not related to SCR, whereas improved seizure control was, suggesting differential mechanisms underlying these two phenomena.