Heterogeneity of patients with functional/dissociative seizures: Three multidimensional profiles.

OBJECTIVE: Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis. METHODS: We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests. RESULTS: Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics: A "No/Single Trauma" group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology; A "Cumulative Lifetime Traumas" group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and A "Childhood Traumas" group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation. SIGNIFICANCE: Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile.

Anticipatory anxiety of seizures is associated with ictal emotional distress and amygdala onset seizures.

OBJECTIVE: Anxiety disorders are a frequent psychiatric condition in patients with epilepsy. Anticipatory anxiety of seizures (AAS) is described as a daily persistent fear or excessive worry of having a seizure. AAS seems to be related to "subjective ictal anxiety" reported by patients. The current study aimed to assess the association between objective ictal features and the presence of AAS. METHODS: Ninety-one patients with drug-resistant focal epilepsy underwent a standardized psychiatric assessment, specific for epilepsy, and presurgical long-term video-electroencephalography (EEG) or stereo-EEG (SEEG). We compared seizure semiology and epilepsy features of patients with AAS (n = 41) to those of patients without AAS (n = 50). We analyzed emotional and motor behavior ictal signs as well as ictal consciousness. We further assessed amygdala ictal involvement in seizures recorded with SEEG (n = 28). RESULTS: AAS was significantly associated with the presence of ictal emotional distress; negative emotional behavior (p < .01) and negative emotion were explicitly reported to the examiner during recording (p = .015), regardless of the ictal level of consciousness. Among the patients recorded with SEEG, we found a significant involvement of amygdala within the seizure onset zone (p < .01) for patients with AAS. SIGNIFICANCE: Higher risk of developing AAS is associated with seizures expressing negative emotional symptoms, independently of ictal consciousness level. Persistent interictal fear of seizures might be viewed as the consequence of a reinforcement of the emotional networks secondary to amygdala involvement in seizures of temporal origin. Physicians should screen for AAS not only to assess the impact of epilepsy on daily life, but also as an interictal biomarker of ictal semiology and emotional network involvement at seizure onset.

Postictal psychosis, a cause of secondary affective psychosis: A clinical description study of 77 patients.

OBJECTIVE: Postictal psychosis (PIP) is a severe complication occurring at least in 2% of patients with epilepsy. Since the 19th century, psychiatrists have reported the specificity of PIP presentation, but descriptions did not clearly distinguish PIP from after-seizure delirium. This study aimed to provide a precise description of psychiatric signs occurring during PIP, and improve recognition of PIP. METHODS: We performed a review of clinical descriptions available in literature (48 patients), that we gathered with a retrospective multicentric case series of patients from three French epilepsy units (29 patients). For each patient, we collected retrospectively the psychiatric signs, and epilepsy features. RESULTS: We found a high prevalence of persecutory (67.5%) and religious (55.8%) delusions, with almost systematic hallucinations (83.1%) and frequent mood disturbances (76.6%), especially euphoria. Severe consequences were not negligible (other-directed assault in 20.8%, self-directed in 13.0%). The type of delusion was associated with mood symptoms (p = 0.017). Episode onset was mainly sudden/rapid (90.9%), its duration was mostly between one and 14 days (64.9%) and the response to antipsychotic medication was good. Disorder was recurrent in more than a half of the sample (57.1% of patients with at least 2 episodes). CONCLUSION: Considering our findings, PIP resembles more an affective psychosis, than a purely psychotic disorder. The presence of affective signs differentiates PIP from other psychotic comorbidities in epilepsy. Additionally, resemblance between PIP and psychotic manic episode might help to discuss links between epilepsy and bipolar disorder.

An international study of the effects of the COVID-19 pandemic on characteristics of functional seizures.

OBJECTIVE: We investigated whether the COVID-19 pandemic has affected the clinical characteristics of patients with functional seizure (FS) (at the time of diagnosis) in a large multicenter international study. METHODS: This was a retrospective study. We investigated all patients with FS, who were admitted at the epilepsy monitoring units at six centers in the world: 1. Shiraz, Iran; 2. Salzburg, Austria; 3. Nancy, France; 4. Atlanta, USA; 5. Kuwait City, Kuwait; and 6. Cairo, Egypt. Patients were studied during two time periods: admitted in 2018-2019 (pre-COVID era) and 2020-2021 (COVID era). RESULTS: Three hundred and twenty-six patients were studied. Two hundred and twenty-four (68.7%) patients were diagnosed before and 102 (31.3%) persons during the COVID-19 pandemic. Only, a history of family dysfunction was significantly associated with the COVID-19 pandemic era (Odds Ratio: 1.925, 95% Confidence Interval: 1.099-3.371; p = 0.022). A low level of education might also be associated with FS during the COVID-19 pandemic, at least in some cultures (e.g., the Middle-East). CONCLUSION: The COVID-19 pandemic has not affected the clinical characteristics of patients with FS (at the time of diagnosis). However, a history of family dysfunction was significantly more frequently associated with FS during the COVID-19 pandemic. Multiagency integration of law enforcement responses, social services, and social awareness is recommended to address family dysfunction and domestic violence and support the victims during this pandemic.

Functional (psychogenic non-epileptic/dissociative) seizures: why and how?

Functional seizures (FS) known also as psychogenic non-epileptic seizures or dissociative seizures, present with ictal semiological manifestations, along with various comorbid neurological and psychological disorders. Terminology inconsistencies and discrepancies in nomenclatures of FS may reflect limitations in understanding the neuropsychiatric intricacies of this disorder. Psychological and neurobiological processes of FS are incompletely understood. Nevertheless, important advances have been made on underlying neuropsychopathophysiological mechanisms of FS. These advances provide valuable information about the underlying mechanisms of mind-body interactions. From this perspective, this narrative review summarises recent studies about aetiopathogenesis of FS at two levels: possible risk factors (why) and different aetiopathogenic models of FS (how). We divided possible risk factors for FS into three categories, namely neurobiological, psychological and cognitive risk factors. We also presented different models of FS based on psychological and neuroanatomical understanding, multilevel models and integrative understanding of FS. This work should help professionals to better understand current views on the multifactorial mechanisms involved in the development of FS. Shedding light on the different FS profiles in terms of aetiopathogenesis will help guide how best to direct therapy, based on these different underlying mechanisms.

Functional neurologic disorders in an adult with propionic acidemia: a case report.

BACKGROUND: Inborn errors of metabolism are often characterized by various psychiatric syndromes. Previous studies tend to classify psychiatric manifestations into clinical entities. Among inborn errors of metabolism, propionic acidemia (PA) is a rare inherited organic aciduria that leads to neurologic disabilities. Several studies in children with PA demonstrated that psychiatric disorders are associated to neurological symptoms. To our knowledge, no psychopathological description in adult with propionic acidemia is available. CASE PRESENTATION: We aimed to compare the case of a 53-year-old woman with PA, to the previous psychiatric descriptions in children with PA and in adults with other inborn errors of metabolism. Our patient presented a large variety of signs: functional neurologic disorders, borderline personality traits (emotional dyregulation, dissociative and alexithymic trends, obsessive-compulsive disorders), occurring in a context of neurodevelopmental disorder. CONCLUSION: Clinical and paraclinical examinations are in favor of a mild mental retardation since childhood and disorders of behavior and personality without any definite psychiatric syndrome, as already described in other metabolic diseases (group 3). Nonetheless, further studies are needed to clarify the psychiatric alterations within adult patients with PA.

Anxiety and Depression in Newly Diagnosed Epilepsy: A Matter of Psychological History?

Purpose: Anxiety and depression are highly prevalent in patients with epilepsy (PWE), and these symptoms can even precede the onset of the pathology. We aimed to define the prevalence of anxiety and depressive symptoms at the time of the epilepsy diagnosis and the factors related to their presence in newly diagnosed adult patients. Methods: One hundred and twelve newly diagnosed patients were assessed, usually in the week after diagnosis. Patients were untreated at this time. We used the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E, cut-off ≥15) and the Generalized Anxiety Disorder 7-Item scale (GAD-7, cut-off >7). A semi-structured interview was conducted to collect sociodemographic and epilepsy data and patients' psychiatric history. We first compared patients with and without anxiety symptoms, then patients with and without depressive symptoms. Results: According to the GAD-7 scale, the prevalence of anxiety symptoms at the time of diagnosis was 35%. Patients with anxiety symptoms had significantly more psychiatric history (26%, p = 0.001) and more history of psychological trauma (51%, p = 0.003) than patients with no anxiety symptoms. According to the NDDI-E scores, the prevalence of depressive symptoms at the time of the diagnosis was 11%. Patients with depressive symptoms had significantly more psychiatric history (43%, p < 0.001) and more history of psychological trauma (65%, p = 0.007) than patients with no depressive symptoms. No difference between groups was found for other sociodemographic variables (age and gender), epilepsy characteristics (number of seizures prior to diagnosis, time from first seizure to diagnosis, type of epilepsy, and localization in focal epilepsy), or neurological comorbidities. Conclusions: Anxiety symptoms are common whereas depressive symptoms are less prevalent at the time of diagnosis. It appears essential to be aware of anxiety and depression in newly diagnosed epileptic patients. They should be screened and routinely monitored, especially those patients with a history of psychological trauma and/or psychiatric disorders. Longitudinal follow-up is required to identify whether these factors and anxiety and depression themselves have an impact on the future course of care.

Past Trauma Is Associated With a Higher Risk of Experiencing an Epileptic Seizure as Traumatic in Patients With Pharmacoresistant Focal Epilepsy.

Objective: The present study aimed to evaluate the prevalence of traumatic experienced seizures (TES) and of postepileptic seizure PTSD (PS-PTSD) in patients with pharmacoresistant focal epilepsy and to explore the determining factors of TES. Methods: We conducted an observational study enrolling 107 adult refractory epilepsy patients. We used the DSM-5 criteria of traumatic events and PTSD to define TES and PS-PTSD. We assessed all traumatic life events unrelated to epilepsy, general and specific psychiatric comorbidities, and quality of life. Results: Nearly half (n = 48) of the 107 participants reported at least one TES (44.85%). Among these, one-third (n = 16) developed PS-PTSD. The TES group was more likely to experience traumatic events unrelated to epilepsy (p < 0.001), to have generalized anxiety disorder (p = 0.019), and to have specific psychiatric comorbidities [e.g., interictal dysphoric disorder (p = 0.024) or anticipatory anxiety of seizures (p = 0.005)]. They reported a severe impact of epilepsy on their life (p = 0.01). The determining factors of TES according to the multifactorial model were the experience of trauma (p = 0.008), a history of at least one psychiatric disorder (p = 0.03), and a strong tendency toward dissociation (p = 0.03). Significance: Epileptic seizures may be a traumatic experience in some patients who suffer from pharmacoresistant epilepsy and may be the source of the development of PS-PTSD. Previous trauma unrelated to epilepsy and psychiatric history are determining factors of TES. These clinical entities should be explored systematically.

Working toward the ideal situation: A pragmatic Epi-Psy approach for the diagnosis and treatment of psychogenic nonepileptic seizures.

Medical international guidelines recommend regular psychiatric consultations for patients with epilepsy, in order to detect comorbidities. However, there is a lack of guidance about PNES that constitute both a differential diagnosis and a comorbidity of epilepsy. While waiting for the ideal collaboration between neurologists and psychiatrists, we develop a pragmatic approach. Wrong diagnosis between epilepsy and Psychogenic nonepileptic seizures (PNES) is frequent and may lead to iatrogenic consequences for patients. To limit the risk of misdiagnosis, psychiatrists and neurologists should collaborate and be more trained about epilepsy, PNES, and their comorbidities. We illustrate the aim of this collaboration through the case of a patient, initially diagnosed with epilepsy, then with PNES only and finally with comorbid epilepsy and PNES. The correct final diagnosis would not have been performed without the collaboration of psychiatrists and neurologists, trained in "Epi-Psy" approach.

Social aspects of life in patients with functional (psychogenic nonepileptic) seizures: An international study.

PURPOSE: To explore various social aspects of life (i.e., employment, education, and driving) in a large sample of patients with functional seizures (FS) living in seven countries from four continents. METHODS: In this retrospective study, we investigated adult patients with FS, who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We studied the social aspects of life in the whole cohort. Then, we compared the social aspects of life between different world regions. RESULTS: Four hundred and forty patients were included (241 from Iran, 56 from Qatar, 52 from France, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia). One hundred and twenty six people (30%) had college education, 142 (33%) were employed, and 101 (28%) drove a motor vehicle in their routine daily lives. People with FS and college education were more likely to report a history of sexual abuse compared with those with a lower education. Patients with no loss of responsiveness with their FS were more likely to be employed. Male patients and patients without aura were more likely to drive a motor vehicle in their routine daily lives. None of the social characteristics of the patients with FS showed significant differences among the two large culturally different groups (Muslim nations vs. Christian nations). CONCLUSION: It appears that patients with FS across cultures have significant problems in their social aspects of life.

Marital status in patients with functional (psychogenic nonepileptic) seizures: An international study.

PURPOSE: The study aimed to investigate the marital status in a cohort of patients with functional seizures from seven countries in four continents. Factors associated with marital status were also explored. METHODS: Adult patients with functional seizures who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE) were retrospectively identified. Marital status was assessed in the whole cohort. RESULTS: Four hundred thirty-two patients were included (241 from Iran, 52 from France, 48 from Qatar, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia); 302 were women and 130 were men. One hundred fifty (35%) subjects were single, 245 (57%) were married, and 37 (8%) were separated (31 divorced, 7%; 6 widowed, 1%). Auras with functional seizures were less frequently reported by single people in comparison with that by married patients (54% vs. 61%) [odds ratio (OR) = 0.58]. Separated people compared with those who were married less often had auras with their functional seizures (27% vs. 61%; OR = 0.26) and more often reported a history of sexual abuse (49% vs. 12%; OR = 6.14). CONCLUSION: The marital status has significant associations with the semiology of functional seizures. A history of sexual abuse is significantly associated with being separated and should be inquired and tackled appropriately during the management process of patients with functional seizures.

Skin conductance response and emotional response in women with psychogenic non-epileptic seizures.

PURPOSE: Recent etiopathogenic models place emotional dysregulation at the core of psychogenic nonepileptic seizure (PNES). Our purpose was to assess physiological, cognitive, and behavioral emotional responses of PNES patients. METHODS: This study compared three types of emotional responses to visual emotional stimuli between 34 female PNES group and 34 matched healthy controls: physiological response measured by skin conductance response (SCR) (rate, amplitude and latency) and heart rate deceleration; cognitive response measured by valence and arousal elicited by the images; and behavioural response measured by latency of ratings. The groups were characterized on psychiatric comorbidities, traumatic history, alexithymia, and dissociation. RESULTS: Compared to controls, PNES group displayed lower SCR for all images (p = 0.038), shorter amplitude of heart rate deceleration (p = 0.024) and faster arousal rating for all images (p = 0.019), but no difference on cognitive rating of images. Within-groups analyses showed only in PNES subjects increased rate (+19.35%, p = 0.046) SCR for negative stimuli with strong arousal compared to negative with low arousal. PNES physiological response (SCR and heart rate deceleration) was negatively correlated to dissociation tendency (r=-0.48, p = 0.0083) and alexithymia (r=-0.44, p = 0.012)). For cognitive response, no correlation was found. CONCLUSION: These results are in favour of a lower physiological emotional response but with an over-reactivity at behavioral level contrasting with similar cognitive assessment. For strong aversive stimuli, PNES might present a trend to overreact at physiological and behavioural levels. Our results suggest that dissociation and difficulty in describing feelings are associated with an altered physiological response in PNES women only.

Clinical characteristics of functional (psychogenic nonepileptic) seizures: An international retrospective study.

PURPOSE: We conducted a multicenter international cross-cultural comparative study to investigate clinical semiology and predisposing factors of functional seizures in a large cohort of patients living in different countries around the world. We hypothesized that semiology and predisposing factors of functional seizures differ between various world regions. METHODS: We conducted this retrospective observational study in adults with functional seizures admitted to epilepsy centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We assessed and compared the demographic and clinical seizure characteristics of these patients, according to the patients' reports and review of the ictal recordings during video-electroencephalogram (EEG) monitoring. RESULTS: Five hundred nine patients were included (270 from Iran, 74 from Qatar, 63 from France, 43 from the USA, 22 from Egypt, 20 from UAE, and 17 from Georgia). Although all major manifestations of functional seizures (e.g., aura, loss of responsiveness, generalized motor seizures, ictal injury) were seen in all world regions, seizure semiology differed significantly across countries. Auras, ictal urinary incontinence, and ictal injury were more commonly reported by the American patients than patients from other world regions, whereas loss of responsiveness and generalized motor seizures were more frequently observed in the Iranian and American patients than the European and Arab patients. CONCLUSION: Semiology of functional seizures seems to vary across various regions of the world; socioeconomic, cultural, ethnic, and religious differences may play an essential role in the modulation of functional seizures semiology across different nations and cultures.

Epileptic psychoses are underrecognized by French neurologists and psychiatrists.

This study evaluates the knowledge about psychotic disorders associated with epilepsy among medical practitioners in France. A self-report questionnaire was sent, and responses of 486 participants were collected. Results showed the rate of correct responses being higher among neurologists compared to psychiatrists, respectively 70.6% and 58.3% (p < 10-11). The highest rate of correct responses was found for the participants trained in epileptology (71%), and a regression analysis confirmed that epilepsy-training was the most influential variable. However, we found that knowledge about epileptic psychosis was imprecise among all participants: current classification was not known to most participants (77%), there were false beliefs concerning postictal confusion and psychosis (41%), and both prevalence and duration of postictal psychosis were not well-known. There is the first survey to highlight such gaps of knowledge, and hopefully lead to measures to remedy this, especially specialists such as psychiatrists, neurologists, and epileptologists who may be called upon to treat such patients.