Search

Patients diagnosed with functional (psychogenic nonepileptic) seizures have similar or greater levels of disability, morbidity and mortality than people with epilepsy, but there are far fewer treatment services. In contrast to epilepsy, the current understanding of pathophysiological mechanisms and the development of evidence-based treatments for functional seizures is rudimentary. This leads to high direct healthcare costs and high indirect costs to the patient, family and wider society. There are many patient, clinician and system-level barriers to improving outcomes for functional seizures. At a patient level, these include the heterogeneity of symptoms, diagnostic uncertainty, family factors and difficulty in perceiving psychological aspects of illness and potential benefits of treatment. Clinician-level barriers include sub-specialism, poor knowledge, skills and attitudes and stigma. System-level barriers include the siloed nature of healthcare, the high prevalence of functional seizures and funding models relying on individual medical practitioners. Through the examination of international examples and expert recommendations, several themes emerge that may address some of these barriers. These include (1) stepped care with low-level, brief generalised interventions, proceeding to higher level, extended and individualised treatments; (2) active triage of complexity, acuity and treatment readiness; (3) integrated interdisciplinary teams that individualise formulation, triage, and treatment planning and (4) shared care with primary, emergency and community providers and secondary consultation. Consideration of the application of these principles to the Australian and New Zealand context is proposed as a significant opportunity to meet an urgent need., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The neuropsychological profile of patients with psychosis of epilepsy (POE) has received limited research attention. Recent neuroimaging work in POE has identified structural network pathology in the default mode network and the cognitive control network. This study examined the neuropsychological profile of POE focusing on cognitive domains subserved by these networks., Methods: Twelve consecutive patients with a diagnosis of POE were prospectively recruited from the Comprehensive Epilepsy Programmes at The Royal Melbourne, Austin and St Vincent's Hospitals, Melbourne, Australia between January 2015 and February 2017. They were compared to 12 matched patients with epilepsy but no psychosis and 42 healthy controls on standardised neuropsychological tests of memory and executive functioning in a case-control design., Results: Mean scores across all cognitive tasks showed a graded pattern of impairment, with the POE group showing the poorest performance, followed by the epilepsy without psychosis and the healthy control groups. This was associated with significant group-level differences on measures of working memory (p = < 0.01); immediate (p = < 0.01) and delayed verbal recall (p = < 0.01); visual memory (p < 0.001); and verbal fluency (p = 0.02). In particular, patients with POE performed significantly worse than the healthy control group on measures of both cognitive control (p = .005) and memory (p < .001), whereas the epilepsy without psychosis group showed only memory difficulties (delayed verbal recall) compared to healthy controls (p = .001)., Conclusion: People with POE show reduced performance in neuropsychological functions supported by the default mode and cognitive control networks, when compared to both healthy participants and people with epilepsy without psychosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Childhood trauma has been implicated as a risk factor for the etiology of psychogenic nonepileptic seizures (PNES). Relatively little attention has been paid to whether profiles of specific trauma types differ between patients with epilepsy and PNES. Investigating childhood trauma profiles in these patient groups may identify psychological vulnerabilities that predispose to developing PNES, and aid early diagnoses, prevention, and treatment., Methods: Data were collected from two cohorts (n Retrospective  = 203; n Prospective  = 209) admitted to video-electroencephalography (EEG) monitoring units in Melbourne Australia. The differences in Childhood Trauma Questionnaire domain score between patient groups were investigated using standardized effect sizes and general linear mixed-effects models (GLMMs). Receiver-operating characteristic curves were used to investigate classification accuracy., Results: In the retrospective cohort, patients diagnosed with PNES reported greater childhood emotional abuse, emotional neglect, physical abuse, sexual abuse, and physical neglect relative to patients with epilepsy. These differences were replicated in the prospective cohort, except for physical abuse. GLMMs revealed significant main effects for group in both cohorts, but no evidence for any group by domain interactions. Reported sexual abuse showed the best screening performance of PNES, although no psychometric scores were adequate as isolated measures., Significance: Patients with PNES report a greater frequency of childhood trauma than patients with epilepsy. This effect appears to hold across all trauma types, with no strong evidence emerging for a particular trauma type that is more prevalent in PNES. From a practical perspective, inquiry regarding a history of sexual abuse shows the most promise as a screening measure., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: To explore the cortical morphological associations of the psychoses of epilepsy., Methods: Psychosis of epilepsy (POE) has two main subtypes - postictal psychosis and interictal psychosis. We used automated surface-based analysis of magnetic resonance images to compare cortical thickness, area, and volume across the whole brain between: (i) all patients with POE (n = 23) relative to epilepsy-without psychosis controls (EC; n = 23), (ii) patients with interictal psychosis (n = 10) or postictal psychosis (n = 13) relative to EC, and (iii) patients with postictal psychosis (n = 13) relative to patients with interictal psychosis (n = 10)., Results: POE is characterised by cortical thickening relative to EC, occurring primarily in nodes of the cognitive control network; (rostral anterior cingulate, caudal anterior cingulate, middle frontal gyrus), and the default mode network (posterior cingulate, medial paracentral gyrus, and precuneus). Patients with interictal psychosis displayed cortical thickening in the left hemisphere in occipital and temporal regions relative to EC (lateral occipital cortex, lingual, fusiform, and inferior temporal gyri), which was evident to a lesser extent in postictal psychosis patients. There were no significant differences in cortical thickness, area, or volume between the postictal psychosis and EC groups, or between the postictal psychosis and interictal psychosis groups. However, prior to correction for multiple comparisons, both the interictal psychosis and postictal psychosis groups displayed cortical thickening relative to EC in highly similar regions to those identified in the POE group overall., Significance: The results show cortical thickening in POE overall, primarily in nodes of the cognitive control and default mode networks, compared to patients with epilepsy without psychosis. Additional thickening in temporal and occipital neocortex implicated in the dorsal and ventral visual pathways may differentiate interictal psychosis from postictal psychosis. A novel mechanism for cortical thickening in POE is proposed whereby normal synaptic pruning processes are interrupted by seizure onset., Competing Interests: Conflicts of interest None of the authors have any conflict of interest to disclose., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Early differential diagnosis of psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) remains difficult. Self-reported psychopathology is often elevated in patients with PNES, although relatively few studies have examined multiple measures of psychopathology simultaneously. This study aimed to identify differences in multidimensional psychopathology profiles between PNES and ES patient groups., Method: This was a retrospective case-control study involving patients admitted for video-EEG monitoring (VEM) over a two-year period. Clinicodemographic variables and psychometric measures of depression, anxiety, dissociation, childhood trauma, maladaptive personality traits, and cognition were recorded. Diagnosis of PNES or ES was determined by multidisciplinary assessment and consensus opinion. General linear mixed models (GLMMs) were used to investigate profile differences between diagnostic groups across psychometric measures. A general psychopathology factor was then computed using principal components analysis (PCA) and differences between groups in this 'p' factor were investigated., Results: 261 patients (77 % with ES and 23 % with PNES) were included in the study. The PNES group endorsed greater symptomatology with GLMM demonstrating a significant main effect of group (η 2 p  = 0.05) and group by measure interaction (η 2 p  = 0.03). Simple effects analysis indicated that the PNES group had particularly elevated scores for childhood trauma (β = 0.78), dissociation (β = 0.70), and depression (β = 0.60). There was a high correlation between psychopathology measures, with a single p factor generated to explain 60 % variance in the psychometric scores. The p factor was elevated in the PNES group (β = 0.61). ROC curve analysis indicated that these psychometric measures had limited usefulness when considered individually (AUC range = 0.63-0.69)., Conclusion: Multidimensional psychopathological profile differences exist between patients with PNES and ES. Patients with PNES report more psychopathology overall, with particular elevations in childhood trauma, dissociation, and depression. Although not suitable to be used as a standalone screening tool to differentiate PNES and ES, understanding of these profiles at a construct level might help triage patients and guide further psychiatric examination and enquiry., Competing Interests: Declaration of Competing Interest Dr Michael Lloyd reports no disclosures. Dr Winton-Brown reports no disclosures. Dr Anthony Hew reports no disclosures. Dr Rayner is supported in part by the Australian Epilepsy Research Fund; this funding is unrelated to this study. Dr Foster is supported by the National Health and Medical Research Council (NHMRC) of Australia, The Royal Australian College of Physicians Research Entry Scholarship and AVANT Doctors in Training Scholarship. This research funding is unrelated to this study. Ms Rychkova reports no disclosures. Ms Ali reports no disclosures. Professor Velakoulis reports no disclosures. Professor O’Brien reports grants and advisory board support from Eisai Pharmaceuticals, Teva Pharmaceuticals, UCB Pharma, Zynerba Pharmaceuticals, LivaNova and Praxis Pharmaceuticals, as well as grants from the NHMRC and NINDS. This funding is unrelated to this study. Professor Kwan reports grants and non-financial support from UCB Pharma, during the conduct of the study; grants from Biscayne, grants and personal fees from Eisai, grants from GW Pharmaceuticals, grants and personal fees from LivaNova, grants and personal fees from UCB Pharma, grants from Zynerba. He is also supported by a Medical Research Future Fund Practitioner Fellowship (MRF1136427). This funding is unrelated to this study. Dr Malpas reports no disclosures., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood-brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

Objective: This cross-sectional study aimed to determine the effect of psychiatric comorbidity and neurocognitive deficits on the quality of life in a cohort of patients admitted for Video-EEG Monitoring (VEM) for investigation into a presumed seizure disorder., Methods: Patients were recruited from an inpatient VEM unit between January 2009 and December 2016. All patients had formal neuropsychiatric assessment. All patients completed questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-89), and cognition (NUCOG)., Results: A total of 451 patients were enrolled. Upon discharge, 204 patients were diagnosed to have epilepsy, 118 psychogenic nonepileptic seizures (PNES), and 29 both epilepsy and PNES, while the diagnosis was uncertain diagnosis in 100. Diagnosis (p = .002), HADS Depression score (p < .001), SCL-90-R positive symptoms total (p < .001), and NUCOG total score (p < .001) were found to be significant predictors of QOLIE-89 total scores, together explaining 65.4% of variance in quality of life. Seizure frequency was not a significant predictor of quality of life (p = .082). Patients with PNES had significantly worse quality of life, and scored higher on measures of psychiatricsymptomatology, compared to patients with epilepsy alone. The prevalence of psychiatric comorbidity was significantly higher in patients with PNES (70.3%) or both PNES and epilepsy (62.1%) compared to patients with epilepsy alone (41.2%) (p < .001)., Significance: Psychiatric symptomatology, depression, and cognition were stronger determinants of quality of life than seizure frequency in this study population of patients with drug-resistant epilepsy and PNES. Patients with PNES with or without comorbid epilepsy had similar neuropsychiatric profiles., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Adverse events (AEs) related to antiepileptic drugs (AEDs) may interfere with adequate dosing and patient adherence, leading to suboptimal seizure control, and relatedly, increased injuries, hospitalizations, and mortality. This study investigated the clinicodemographic factors associated with AEs related to AEDs as reported by the Liverpool Adverse Events Profile (LAEP), and explored the ability of LAEP to discriminate between epilepsy and psychogenic nonepileptic seizures (PNES). We hypothesized that female sex, mood disorders, AED-polytherapy, duration, and severity of epilepsy are associated with increased endorsement of AEs related to AEDs, and that endorsement of AEs related to AEDs would significantly differ between epilepsy and PNES patients., Methods: We prospectively enrolled adult patients admitted to two inpatient video-electroencephalogram monitoring units. Clinicodemographic variables and psychometric measures of depression, anxiety, and cognitive function were recorded. Patient-reported AE endorsement was obtained using the LAEP, which was reduced to four latent domains using exploratory structural equation modeling. General linear models identified variables associated with each domain. Logistic regression determined the ability of LAEP scores to differentiate between epilepsy and PNES., Results: 311 patients met inclusion criteria. Mean age was 38 years and 56% of patients were female. Network analysis demonstrated strong relationships between depression and anxiety with physical, sleep, psychiatric, and dermatological AE endorsement. Depression, female sex, and AED polytherapy were associated with greater AE endorsement. Epilepsy, compared to PNES, was associated with lower AE endorsement. Fewer prescribed AEDs and greater reported physical AE endorsement were associated with PNES diagnosis., Significance: There is a strong relationship between patient-reported AEs and psychiatric symptomatology. Those with PNES paradoxically endorse greater physical AEs despite receiving fewer AEDs. Patients who endorse AEs in clinical practice should be screened for comorbid depression or anxiety and treated accordingly., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There is a need for the development of brief tools to screen for cognitive impairments in epilepsy patients in order to prioritize and direct formal comprehensive cognitive testing. Yet, shorter cognitive screening tools are limited in their breadth of cognitive domains or have not been intensively studied on an epilepsy population. This study used a brief cognitive screening tool in order to compare cognitive profiles between patients with epilepsy and those with nonepileptic seizures., Methods: Patients admitted to the Royal Melbourne Hospital video-EEG monitoring unit between 2005 and 2017 were included. Patients were categorized according to seizure etiology (epileptic, psychogenic or other nonepileptic seizures), epilepsy syndrome (focal or generalized; temporal lobe (TLE) or extra-temporal lobe epilepsy (ETLE)), seizure frequency, and anti-seizure medications (ASMs). Attention, visuoconstructional, memory, executive, and language functioning were assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). General linear mixed models were computed to investigate cognitive profiles according to diagnostic group and other clinicodemographic variables., Results: 800 patients were included in the analysis (61% female and 39 % male, median age 36 years). Patients with both epileptic seizures and psychogenic seizures (n = 25) had the lowest total scores on NUCOG, followed by patients with epileptic seizures (n = 411), psychogenic seizures (n = 185), and nonepileptic seizures (n = 179, p = 0.002). Specifically, patients with epileptic seizures performed worse than those with nonepileptic seizures in the executive, language, and memory domain, and had lower language domain scores than those with psychogenic seizures. Patients with bilateral TLE had poorer performance than those with unilateral TLE, particularly for memory function. Specific ASMs and polypharmacy but not seizure frequency had a negative effect on cognition (p < 0.001). NUCOG scores did not differ between focal and generalized epilepsies, or between TLE and ETLE., Conclusion: The NUCOG differentiated cognitive profiles in patients with uncontrolled seizures due to different etiologies. Bilateral TLE and medication adversely affected cognitive performance, and overall patients with epilepsy performed worse than those with nonepileptic seizures. These results provide further evidence for sensitivity of the NUCOG for detecting cognitive impairment in patients with seizure disorders., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Psychosis of epilepsy (POE) can be a devastating condition, and its neurobiological basis remains unclear. In a previous study, we identified reduced posterior hippocampal volumes in patients with POE. The hippocampus can be further subdivided into anatomically and functionally distinct subfields that, along with the hippocampal fissure, have been shown to be selectively affected in other psychotic disorders and are not captured by gross measures of hippocampal volume. Therefore, in this study, we compared the volume of selected hippocampal subfields and the hippocampal fissure in 31 patients with POE with 31 patients with epilepsy without psychosis. Cortical reconstruction, volumetric segmentation, and calculation of hippocampal subfields and the hippocampal fissure were performed using FreeSurfer. The group with POE had larger hippocampal fissures bilaterally compared with controls with epilepsy, which was significant on the right. There were no significant differences in the volumes of the hippocampal subfields between the two groups. Our findings suggest abnormal development of the hippocampus in POE. They support and expand the neurodevelopmental model of psychosis, which holds that early life stressors lead to abnormal neurodevelopmental processes, which underpin the onset of psychosis in later life. In line with this model, the findings of the present study suggest that enlarged hippocampal fissures may be a biomarker of abnormal neurodevelopment and risk for psychosis in patients with epilepsy., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To identify factors associated with subjective cognitive complaints in people with presumed seizure disorders referred for video electroencephalogram monitoring (VEM)., Methods: Adult patients admitted for inpatient VEM were recruited. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Screening Tool, subjective cognitive function with the Quality of Life in Epilepsy Inventory-89 subscales, and anxiety and depressive symptoms with the Hospital Anxiety and Depression Scale. Multivariate Bayesian general linear models were used to identify predictors of subjective cognitive function., Results: 331 patients met inclusion criteria. Mean age was 39.3 years and 61.9 % patients were female. Diagnoses included epilepsy, psychogenic non-epileptic seizures (PNES) or both conditions. Depression, anxiety and objective cognitive function were predictors of subjective cognitive function across all domains. Depression was the strongest predictor of subjective memory and attention, whilst objective cognition was the strongest predictor of subjective language function. Mood also mediated the relationship between objective function and subjective function across all domains to varying extents; depression exerted the strongest effect of 22 % for the memory domain; conversely, language domain was least influenced by mood, with depression mediating 11 % and anxiety mediating only 9% of the subjective-objective relationship., Significance: Mood and objective cognitive function are both important contributors to subjective cognitive function for patients undergoing VEM. Clinicians should consider referring patients with cognitive complaints for both neurocognitive workup and neuropsychiatric evaluation. Future work may examine the effects of treating concomitant mood disorders on subjective cognitive function., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To test the hypothesis that individual antiepileptic drugs (AEDs) are not associated with cognitive impairment beyond other clinically relevant factors, we performed a cross-sectional study of patients admitted to an inpatient video-EEG monitoring unit., Methods: We prospectively enrolled patients admitted to an inpatient specialist epilepsy program between 2009 and 2016. Assessments included objective cognitive function, quality of life subscales for subjective cognitive function, and questionnaires for anxiety and depressive symptoms. Bayesian model averaging identified predictors of cognitive function. Bayesian model selection approach investigated effect of individual AEDs on cognition. Conventional frequentist analyses were also performed., Results: A total of 331 patients met inclusion criteria. Mean age was 39.3 years and 61.9% of patients were women. A total of 45.0% of patients were prescribed AED polypharmacy, 25.1% AED monotherapy, and 29.9% no AED. Age, seizure frequency, and a diagnosis of concomitant epilepsy and psychogenic nonepileptic seizure were predictors of objective cognitive function. Depression, anxiety, and seizure frequency were predictors of subjective cognitive function. Individual AEDs were not independently associated with impaired cognitive function beyond other clinically relevant variables., Conclusions: This study found that no AED was independently associated with cognitive dysfunction. Significant determinants of objective and subjective cognitive dysfunction included seizure frequency and depression, respectively. These findings suggest that optimizing therapy to prevent seizures is not likely to occur at the expense of cognitive function., (© 2020 American Academy of Neurology.)

Background: People with epilepsy (PWE) have high rates of comorbid anxiety disorders and depressive disorders, from 25% in general population cohorts to rates of 55% in people with treatment resistant epilepsy. High rates are also seen in patients with psychogenic nonepileptic seizures (PNES). Depressive disorders and anxiety disorders in PWE are associated with decreased quality of life measures and are the strongest risk factors for increased suicidality, rates of which are markedly elevated in PWE, at 12%, compared to the general Australian population (1.8%). The Hospital Anxiety and Depression Scale (HADS) is one of the more commonly used screening tools in medical populations. Past studies of the HADS in general outpatient populations with epilepsy have demonstrated promising validity for detecting depression., Objectives: The following were the objectives of the study: 1. To examine the validity of HADS in detecting depressive disorders and anxiety disorders in an inpatient population of patients admitted for video monitoring. 2. To investigate the measurement structure of the HADS across the diagnosis groups of epilepsy subtypes and PNES., Methods: This was a retrospective cohort study of 485 patients admitted to a tertiary epilepsy video electroencephalography (EEG) monitoring unit. All patients received clinical neurological, neuropsychiatric, and neuroimaging assessments to arrive at consensus epilepsy and psychiatric diagnoses. Clinical psychiatric diagnosis of depressive disorders and anxiety disorders, based on the assessment of a neuropsychiatrist, were compared to accepted HADS cutoff scores for these conditions., Findings: Of the 485 patients, 229 patients were with epilepsy, 28 had both epilepsy and PNES, and 121 had PNES. In 107 cases, no definite diagnosis could be made. At a cutoff score of 7 HADS was able to significantly classify patients with depression (area under the curve [AUC] = 0.79, 95% confidence interval [CI] = 0.72-0.82) with a sensitivity of 70% and a specificity of 83%. A similar result was observed for anxiety disorders; a cutoff score of 7 (AUC = 0.75, 95% CI = 0.72-0.81) was able to significantly classify anxiety disorders in patients with a sensitivity of 88% and specificity of 54%., Conclusions: This study has found that HADS measures two separate, yet correlated, constructs of anxiety disorders and depressive disorders. Our results indicate that while the HADS is sensitive to distress in this population, relatively low cutoff scores would be required to achieve highly sensitive screening. This sample includes patients with a diagnosis of epilepsy and/or PNES, and thus, the findings have clinical applicability to screening in tertiary epilepsy video-EEG monitoring units where both these conditions frequently co-occur., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research., Methods: In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP)., Results: Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups., Conclusion: Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the prevalence and risk factors of sleep-disordered breathing (SDB) in individuals with epilepsy and psychogenic nonepileptic seizures (PNES)., Methods: We conducted a cross-sectional study of consecutive patients admitted for inpatient video-EEG monitoring at The Royal Melbourne Hospital, Australia, between December 1, 2011, and July 31, 2017. Participants underwent routine clinical investigations during their monitoring period including polysomnography, neurocognitive testing, and screening instruments of daytime somnolence, sleep quality, and quality of life., Results: Our study population consisted of 370 participants who received a diagnosis of epilepsy (n = 255), PNES (n = 93), or both disorders (n = 22). Moderate to severe SDB (defined by an apnea-hypopnea index ≥15) was observed in 26.5% (98/370) of individuals, and did not differ across subgroups: epilepsy 26.3% (67/255), PNES 29.0% (27/93), or both disorders 18.2% (4/22; p = 0.610). Following adjustment for confounders, pathologic daytime sleepiness predicted moderate to severe SDB in epilepsy (odds ratio [OR] 10.35, 95% confidence interval [CI] 2.09-51.39; p = 0.004). In multivariable analysis, independent predictors for moderate to severe SDB in epilepsy were older age (OR 1.07, 95% CI 1.04-1.10; p < 0.001) and higher body mass index (OR 1.06, 95% CI 1.01-1.11; p = 0.029), and in PNES older age (OR 1.10, 95% CI 1.03-1.16; p = 0.002)., Conclusion: Polysomnography during inpatient video-EEG monitoring identified a substantial number of patients with undiagnosed SDB. This was remarkable in the subgroup with PNES, who were often female and obese. Identification of risk factors may improve management of SDB in these populations. The association with pathologic daytime sleepiness suggests that SDB may be an important contributor to these common and disabling symptoms in patients with epilepsy., (© 2018 American Academy of Neurology.)

Epilepsy is a group of neurological conditions in which there is a pathological and enduring predisposition to generate recurrent seizures. Evidence over the last few decades suggests that epilepsy may be associated with increased sleep-disordered breathing, which may contribute towards sleep fragmentation, daytime somnolence, reduced seizure control, and cardiovascular-related morbidity and mortality. Chronic sleep-disordered breathing can result in loss of gray matter and cause deficits to memory and global cognitive function. Sleep-disordered breathing is a novel and independent predictor of sudden cardiac death and, as such, may be involved in the mechanisms leading to sudden unexpected death in epilepsy. Despite this, the long-term consequences of sleep-disordered breathing in epilepsy remain unknown, and there are no guidelines for screening or treating this population. There is currently insufficient evidence to indicate continuous positive airway pressure (CPAP) for the primary or secondary prevention of cardiovascular disease, and recent evidence has failed to show any reduction of fatal or nonfatal cardiovascular endpoints. Treatment of sleep-disordered breathing may potentially improve seizure control, daytime somnolence, and neurocognitive outcomes, but few studies have examined this relationship. In this review, we examine sleep-disordered breathing in epilepsy, and discuss the potential effect of epilepsy treatments. We consider the role of CPAP and other interventions for sleep-disordered breathing and discuss their implications for epilepsy management.

Epilepsy is a common group of neurological diseases. Acquired epilepsy can be caused by brain insults, such as trauma, infection or tumour, and followed by a latent period from several months to years before the emergence of recurrent spontaneous seizures. More than 50% of epilepsy cases will develop chronic neurodegenerative, neurocognitive and neuropsychiatric comorbidities. It is important to understand the mechanisms by which a brain insult results in acquired epilepsy and comorbidities in order to identify targets for novel therapeutic interventions that may mitigate these outcomes. Recent studies have implicated the hyperphosphorylated tubulin-associated protein (tau) in rodent models of epilepsy and Alzheimer's disease, and in experimental and clinical studies of traumatic brain injury. This potentially represents a novel target to mitigate epilepsy and associated neurocognitive and psychiatric disorders post-brain injury. This article reviews the potential role of tau-based mechanisms in the pathophysiology of acquired epilepsy and its neurocognitive and neuropsychiatric comorbidities, and the potential to target these for novel disease-modifying treatments.

We aimed to develop and validate a Chinese version of the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG) for use in Chinese-speaking subjects internationally. Patients and healthy controls were recruited from two hospitals between July and October 2012. Receiver operating characteristic (ROC) curves were utilized to test criterion validity. Convergent validity was assessed via correlations between NUCOG and the Mini-Mental State Examination (MMSE). Reliability was measured by internal consistency (Cronbach's α). Patients with epilepsy (n=144), neurological diseases (n=81), dementia (n=44), and controls (n=260) completed the NUCOG and the MMSE. Overall, both NUCOG and MMSE scores differed significantly across the four groups with the highest scores in the control group and the lowest in the dementia group (p<0.0001). The NUCOG scores could differentiate between patients with certain seizure types, stroke and transient ischemic attack. Compared to the MMSE, the NUCOG exhibited a higher area under the ROC curve. The convergent validity was substantially correlated, and internal consistency was very high (0.922). The Chinese version of NUCOG was demonstrated to be a sensitive and reliable screening tool for cognitive impairment in a Chinese-speaking population not only in China, but also in countries where there is a sizeable population of ethnic Chinese. Additionally, our study also showed the NUCOG could better differentiate cognitive function in patients with certain seizure types, stroke and transient ischemic attack than the MMSE. This potentially expands the clinical usefulness of NUCOG, enabling clinicians to measure the cognitive profile of patients with epilepsy and ischemic cerebrovascular diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Cognitive impairment is not uncommon in patients with epilepsy, and may relate to the underlying pathophysiology of epilepsy, the effects of seizures, or epilepsy treatment. Formal neuropsychological testing is not available in many centers, and few cognitive screening tools have been validated in an epilepsy population. We aimed to ascertain the reliability and validity of a multidimensional cognitive screening instrument, the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), in a mixed epilepsy population., Methods: One hundred sixty-one of 177 consecutive patients admitted to a video telemetry unit were assessed with the NUCOG and classified with respect to seizure semiology, and a subset (n=33) were formally neuropsychologically assessed., Results: Scores did not differ between patients with epileptiform, those with nonepileptiform, and those with mixed EEGs on the NUCOG, nor between patients with focal and those with generalized epilepsies. Patients with a temporal lobe focus performed more poorly in general, and in memory specifically, than patients with an extratemporal focus. Scores on the NUCOG subscales Memory, Attention, and Executive Functioning correlated significantly with neuropsychological testing of these same domains, although patients were not impaired on measures of language or spatial function., Conclusion: The NUCOG appears to correlate strongly with neuropsychological functioning in a number of key cognitive areas affected in patients with epilepsy, and appears to robustly detect memory impairment in patients with temporal lobe epilepsy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Imaging studies of epilepsy patients with comorbid affective disturbance demonstrate morphometric changes in limbic brain regions implicated in psychiatric disease. Genetic Absence Epilepsy Rats from Strasbourg (GAERS), specifically bred for their epilepsy phenotype, also exhibit elevated anxiety-like behaviors suggesting a common causality. Here we examined whether relevant cerebral morphological alterations exist in this rat strain using volumetric measurements and large deformation high dimensional mapping (HDM-LD), a tool recently validated to produce accurate three-dimensional surface representations of the hippocampus., Methods: Volumetric MRI and the Open Field test of anxiety were performed in adult female GAERS (n=12) and Non-Epileptic Controls (NEC; n=11). The volumes of selected brain regions, including cortex, hippocampus, amygdala, thalamus, hypothalamus and lateral ventricles, were measured using Region-Of-Interest analysis from the MRI data and total volumes compared between the two strains., Results: GAERS had increased amygdala (right: p=0.003; left p<0.001), cortices (right: p=0.006; left p=0.012) and ventricular volumes (p=0.002) when compared with NEC rats. Further, HDM-LD showed GAERS to have hippocampal volume loss in two regions: the medial hippocampal surface immediately caudal to the hippocampal commissure, and the lateral hippocampal surface over the mid-portion of the septotemporal axis. GAERS exhibited increased anxiety in the Open Field compared with NEC rats: reduced distance traveled (p<0.001) and reduced time in the centre area (p=0.042)., Conclusions: Morphometric brain changes in GAERS could be relevant to their hyperanxious and epileptic phenotypes. This model may be useful in illuminating the pathogenesis of affective disorders generally, as well as modeling psychiatric comorbidities of epilepsy.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P

Objective: This study was undertaken to identify factors that predict discordance between the screening instruments Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E) and Generalized Anxiety Disorder scale (GAD‐7), and diagnoses made by qualified psychiatrists among patients with seizure disorders. Importantly, this is not a validation study; rather, it investigates clinicodemographic predictors of discordance between screening tests and psychiatric assessment. Methods: Adult patients admitted for inpatient video‐electroencephalographic monitoring completed eight psychometric instruments, including the NDDI‐E and GAD‐7, and psychiatric assessment. Patients were grouped according to agreement between the screening instrument and psychiatrists' diagnoses. Screening was "discordant" if the outcome differed from the psychiatrist's diagnosis, including both false positive and false negative results. Bayesian statistical analyses were used to identify factors associated with discordance. Results: A total of 411 patients met inclusion criteria; mean age was 39.6 years, and 55.5% (n = 228) were female. Depression screening was discordant in 33% of cases (n = 136/411), driven by false positives (n = 76/136, 56%) rather than false negatives (n = 60/136, 44%). Likewise, anxiety screening was discordant in one third of cases (n = 121/411, 29%) due to false positives (n = 60/121, 50%) and false negatives (n = 61/121, 50%). Seven clinical factors were predictive of discordant screening for both depression and anxiety: greater dissociative symptoms, greater patient‐reported adverse events, subjective cognitive impairment, negative affect, detachment, disinhibition, and psychoticism. When the analyses were restricted to only patients with psychogenic nonepileptic seizures (PNES) or epilepsy, the rate of discordant depression screening was higher in the PNES group (n = 29, 47%) compared to the epilepsy group (n = 70, 30%, Bayes factor for the alternative hypothesis = 4.65). Significance: Patients with seizure disorders who self‐report a variety of psychiatric and other symptoms should be evaluated more thoroughly for depression and anxiety, regardless of screening test results, especially if they have PNES and not epilepsy. Clinical assessment by a qualified psychiatrist remains essential in diagnosing depressive and anxiety disorders among such patients. [ABSTRACT FROM AUTHOR]

Objective: People with neurocognitive disorders (NCDs) have an increased risk of epilepsy. However, most studies investigating the risk of seizures in people with NCDs are limited to those with Alzheimer's disease (AD) and vascular dementia (VD), and those who developed dementia after age 65 years. A knowledge gap exists regarding factors associated with development of epilepsy in people with younger-onset NCD, and those with non-AD and non-VD dementia subtypes. In this study, we aimed to identify the factors associated with the development of epilepsy in people with younger-onset NCDs of varied etiologies, the majority of whom had symptom onset prior to age 65 years. Participants and Methods: This was a retrospective study reviewing the medical records of consecutive people admitted with cognitive impairment to a tertiary neuropsychiatry unit between 1 January 2004 and 30 April 2019. People diagnosed with primary NCDs were included in the analysis. The prevalence and characteristics of epilepsy were described. The factors associated with developing epilepsy were identified in a binary logistic regression model. Results: A total of 427 people were included. One hundred fourteen had Alzheimer's disease, 104 frontotemporal dementia, 51 vascular dementia, 69 movement disorder-associated dementia, and 89 unspecified NCD. The median age on admission was 59 years (range 33–86) and 75.2% (n = 321/427) had young-onset NCD with onset before 65 years of age. 40/427 (9.4%) people had epilepsy, and epilepsy onset clustered between 2 years before and 6 years after the onset of cognitive decline in 80% (n = 32/40). The most frequent seizure type was focal to bilateral tonic-clonic seizure (35%, n = 14/40). Most of the people (94.7%, n = 36/38) achieved seizure freedom with one or two antiseizure medications. People with unspecified NCD (compared to frontotemporal dementia and movement disorder-associated dementia, age of onset of NCDs ≤50 years, and current smoking status were independently associated with higher risk of developing epilepsy. Conclusion: Epilepsy is common in people with younger-onset NCDs, and a high index of suspicion is warranted particularly for those with unspecified subtype and smoking status. Smoking reduction or cessation should be further investigated as a potentially modifiable factor for risk reduction. [ABSTRACT FROM AUTHOR]

• Treatment-resistant temporal lobe epilepsy patients may have hippocampal surgery. • Pre-surgery MRI measurements of hippocampal shape & volume can quantify morphology. • Contralateral shape inflation of the left hippocampus in right-sided TLE was found. • This inflation may result from functional compensation &/or abnormal tissue. • Right-sided TLE hippocampal structure is correlated with visuospatial function. We sought to quantify the morphology in vivo of hippocampi in patients with drug resistant temporal lobe epilepsy (TLE) via magnetic resonance imaging (MRI), prior to temporal lobe resection, and the correlation of surface-based shape analysis of morphology and clinical cognitive function. Thirty patients with drug-resistant TLE and twenty healthy controls underwent clinical neuropsychological testing, and brain MRI at Lund University Hospital prior to hippocampal resection. A neuroradiologist categorised radiological findings into normal hippocampus, subtle changes or definite hippocampal sclerosis. We manually segmented MRI of the hippocampus of participants using ANALYZE 11.0 software; and analysed hippocampal shape using SPHARM-PDM software. For radiologist visual-ratings of definite left hippocampal sclerosis in those with left-sided TLE, hippocampal volumes were significantly smaller compared to normal controls. In right-sided TLE we found contralateral shape inflation of the left hippocampus, partially confirming previous shape analytic studies of the hippocampus in TLE. We found significant correlation of volume and surface deflation of the right hippocampus in right-sided TLE with reduced performance on the two right-lateralised visuospatial memory tests, the Rey Complex Figure Test (Immediate and Delayed recall) and the Recognition Memory Test for faces. Decreased hippocampal volume was correlated with poorer performance on these tasks. The morphology of the hippocampus can be quantified via neuroimaging shape analysis in TLE. Contralateral shape inflation of the left hippocampus in right-sided TLE is intriguing, and may result from functional compensation and/or abnormal tissue. In right-sided TLE, hippocampal structural integrity, quantified as hippocampal shape, is correlated with lateralised visuospatial function. [ABSTRACT FROM AUTHOR]

Objective Exposure to early life childhood trauma has been implicated as resulting in a vulnerability to epileptic and psychogenic nonepileptic seizures (PNES), hippocampal atrophy, and psychiatric disorders. This study aimed to explore the relationships between childhood trauma, epilepsy, PNES, and hippocampal volume in patients admitted to a video-electroencephalogram monitoring (VEM) unit. Methods One hundred thirty-one patients were recruited from the Royal Melbourne Hospital VEM unit. The diagnostic breakdown of this group was: temporal lobe epilepsy (TLE) (32), other epilepsy syndromes (35), PNES (47), other nonepileptic syndromes (5), both epilepsy and PNES (6), and uncertain diagnosis (6). All patients completed a questionnaire assessing exposure to childhood trauma, the Childhood Trauma Questionnaire (CTQ), as well as questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-98) and cognition (NUCOG). Volumetric coronal T1 MRI scans were available for 84 patients. Hippocampal volumes were manually traced by a blinded operator. Results The prevalence of childhood trauma in patients with PNES was higher than in patients with other diagnoses (p = 0.005), and the group with PNES overall scored significantly higher on the CTQ (p = 0.002). No association was found between CTQ scores and hippocampal volumes; however, patients with a history of sexual abuse were found to have smaller left hippocampal volumes than patients who had not (p = 0.043). Patients reporting having experienced childhood trauma scored lower on measures of quality of life and higher on measures of psychiatric symptomatology. Significance Patients with PNES report having experienced significantly more childhood trauma than those with epileptic seizures, and in both groups there was a relationship between a history of having experienced sexual abuse and reduced left hippocampal volume. Patients with PNES and those with epilepsy who have a history of childhood trauma have overall worse quality of life and more psychiatric symptomatology. [ABSTRACT FROM AUTHOR]

Antiepileptic drug treatment can induce psychosis in some patients. However, there are no agreed definitions or diagnostic criteria for antiepileptic drug-induced psychotic disorder in the classification systems of either epileptology or psychiatry. In this study we investigated the clinical spectrum of antiepileptic drug-induced psychotic disorder in patients with epilepsy. The medical records of all patients with epilepsy who were diagnosed by a neuropsychiatrist as having a psychotic disorder at the Royal Melbourne Hospital from January 1993 to June 2015 were reviewed. Data were extracted regarding epilepsy and its treatment, psychotic symptoms profile and outcome. The diagnosis of epilepsy was established in accordance to the classification system of the International League Against Epilepsy while that of psychotic disorder was made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposal on neuropsychiatric disorders in epilepsy. Patients with antiepileptic drug-induced psychotic disorder were compared to those with psychotic disorders unrelated to antiepileptic drugs assessed over the same period (non-antiepileptic drug induced psychotic disorder group). Univariate comparisons were performed and variables with a value of P < 0.1 were selected for the multivariate logistic regression analysis. The records of 2630 in-patients and outpatients with epilepsy were screened, from which 98 (3.7%) with psychotic disorders were identified. Among these, 14 (14.3%) were diagnosed to have antiepileptic drug-induced psychotic disorder. Excluding one patient who developed psychosis after valproate withdrawal, 76.9% in the antiepileptic drug induced psychotic disorder group were female and the percentage of temporal lobe involvement was higher in the antiepileptic drug induced psychotic disorder group (69.2% versus 38.1%, P < 0.05). Current use of levetiracetam was higher in antiepileptic drug-induced psychotic disorder group (84.6% versus 20.2%, P < 0.01) while use of carbamazepine was higher in the comparator group (15.4% versus 44.0%, P < 0.05). Multivariate logistic regression confirmed four factors associated with antiepileptic drug-induced psychotic disorder: female gender, temporal lobe involvement and use of levetiracetam, and a negative association with carbamazepine. Disorganized behaviours and thinking were more common in the antiepileptic drug-induced psychotic disorder group (100% versus 72.6% and 76.9% versus 38.1%, respectively; P < 0.05). The percentage of continuous treatment with antipsychotic drugs was lower in the antiepileptic drug-induced psychotic disorder group (15.4% versus 66.7%, P50.01). No patients experienced a chronic course in antiepileptic drug-induced psychotic disorder group whereas 40.5% did in non-antiepileptic drug induced psychotic disorder (P < 0.05). Our findings indicated that one in seven patients with epilepsy who developed psychosis had antiepileptic drug-induced psychotic disorder. In these patients, female gender, temporal lobe involvement and current use of levetiracetam were significantly associated with antiepileptic drug induced psychotic disorder compared to other types of psychosis, while carbamazepine had a negative association. Disorganized behaviours and thinking were predominant in antiepileptic drug-induced psychotic disorder. Patients with antiepileptic drug-induced psychotic disorder differed from non-antiepileptic drug-induced psychotic disorders in having better outcome. [ABSTRACT FROM AUTHOR]

Background: Previous work has identified elevated prevalence rates for psychiatric disorders in individuals with medically refractory focal epilepsy, particularly temporal lobe epilepsy. Many studies were undertaken before the advent of video electroencephalogram monitoring (VEM) and magnetic resonance imaging (MRI).Aims: To investigate which characteristics of the focal epilepsy syndromes are associated with the presence of depression or psychosis.Method: Three hundred and nineteen individuals with focal epilepsy admitted for VEM were seen over an 11-year period. The lifetime history of depression and psychosis, epileptic site, laterality and type of lesion were determined by clinical assessment, VEM and MRI scan.Results: There was a significant association between the prevalence of depressive symptoms and non-lesional focal epilepsy. There were no significant differences in prevalence of neuropsychiatric disorders between the groups with temporal lobe epilepsy and those with extratemporal lobe epilepsy.Conclusions: These findings contrast with previous findings in smaller cohorts. The association between non-lesional focal epilepsy and depression may be due to the effects of a more diffuse epileptogenic area. [ABSTRACT FROM AUTHOR]

Background: We describe the presentation of a young woman with long-standing complex partial seizures with occasional secondary generalization, who presented with complex visual hallucinations (CVHs) and delusions. Methods: Routine biological workup including magnetic resonance imaging revealed an area of significant left-sided occipital gliosis. Video telemetry monitoring revealed a left occipital focus for the origin of the electrographic seizure discharge. Conclusion: CVHs occur in a range of organic states, including epilepsy, and can be understood in terms of the underpinning neuroanatomy and neurotransmitter systems of the visual system. [ABSTRACT FROM AUTHOR]

Abstract: We present a case of tuberous sclerosis complex (TSC) diagnosed in adulthood in a man initially referred for specialist neuropsychiatric assessment with psychosis and obsessive-compulsive symptoms (OCS) on a background of epilepsy and intellectual disability. To our knowledge, this is the first reported patient with TSC featuring both psychosis and OCS. This patient highlights the importance of comprehensive re-evaluation of atypical presentations of intellectual disability, epilepsy and associated neuropsychiatric symptoms, even in adulthood. This is particularly relevant in the context of significant advances in genetics, neuroscience, imaging and treatments for heritable neurogenetic disorders. [Copyright &y& Elsevier]

Background: Copy number variants have made important contributions to understanding neuropsychiatric disorders, including schizophrenia. Deletions in genes encoding neuronal cell adhesion molecules have identified widely varied neurodevelopmental phenotypes.Case Summary: A 27-year old woman presented with schizophrenia, borderline intellectual functioning and shortened metacarpal bones. Subsequent electroencephalogram confirmed genetic generalised epilepsy and microarray analysis found a 0.2 megabase deletion of chromosome 3p26.3.Conclusions: We report the first case of schizophrenia in a proband with a CNTN6 deletion. Schizophrenia has been reported in relatives of probands with this deletion but not in probands themselves. This finding further contributes to the evolving literature regarding schizophrenia pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Tau hyperphosphorylation has been implicated in the pathogenesis of a variety of forms of human epilepsy. Here we investigated whether treatment with sodium selenate, a drug which reduces pathological hyperphosphorylated tau by enhancement of PP2A activity, would inhibit seizures in rodent models. In vitro, sodium selenate reduced tau phosphorylation in human neuroblastoma cells and reversed the increase in tau phosphorylation induced by the PP2A inhibitor, okadaic acid. Sodium selenate treatment was then tested against three different rodent seizure models. Firstly the propensity of 6-Hz electrical corneal stimulation to induce seizures in adult mice was assessed following acute treatment with different doses of sodium selenate. Secondly, the number of seizures induced by pentylenetetrazole (PTZ) was quantified in rats following chronic sodium selenate treatment via drinking water. Finally, amygdala kindled rats were chronically treated with sodium selenate in drinking water and the length and the severity of the seizures evoked by stimulation of the amygdala recorded. The results demonstrated a dose-dependent protection of sodium selenate against 6-Hz stimulation induced seizures, and significant reduction in the total number of seizures following PTZ injection. Amygdala kindled rats chronically treated with sodium selenate had significantly shorter seizure duration compared controls, with more pronounced effects observed as the duration of treatment increased. The results of this study indicate that targeting hyperphosphorylated tau by treatment with sodium selenate has anti-seizure effects in a broad range of rodent models, and may represent a novel approach to treatment of patients with epilepsy. [Copyright &y& Elsevier]

• Psychiatric comorbidities are common among older adults admitted for VEM. • PNES is not as frequently diagnosed in older adults compared to younger adults. • Risk factors for PNES in younger adults are also applicable to older adults. • Older adults presenting for VEM had more cognitive impairment than younger adults. To compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit. This was a retrospective case–control study involving patients admitted for VEM over a two-year period (from April 2018 to April 2020) at two comprehensive epilepsy units. Patients were categorized into an older (≥60 years) and a younger (<60 years) group. Younger patients were individually matched to older adults to form a matched younger group. Diagnosis was determined by a consensus opinion of epileptologists, neurologists, and neuropsychiatrists. The main diagnostic categories were epilepsy, psychogenic nonepileptic seizures (PNES), and 'other' diagnosis (non-diagnostic and other nonepileptic diagnoses). Clinical psychiatric diagnoses were obtained from neuropsychiatric reports. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Subjective cognitive function was assessed using the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) cognitive subscales. Five-hundred and thirty three patients (71 older, 462 younger) aged 16–91 years were admitted to the VEM unit during the study period. There was a diagnosis of focal epilepsy in 55% of the older group and 48% of the younger group, generalized epilepsy in 3% of the older group and 10% of the younger group, and 'other' in 32% of the older group and 19% of the younger group. Ten percent (2 males and 5 females) of the older group were diagnosed with PNES compared to 22% of the younger group (p = 0.016). A depressive disorder was diagnosed in 34% of the older group and 24% of the younger group (p = 0.20). An anxiety disorder was diagnosed in 15% of the older group and 25% of the younger group (p = 0.15). Mild neurocognitive disorder was more common in the older group (34%) compared to the matched younger group (34% vs 3%, p < 0.001). The older group had lower mean NUCOG scores compared to the matched younger group (79.49 vs 87.73, p = <0.001). There was no evidence for a relationship between mean NUCOG score and overall subjective cognitive difficulties for the older group (r = 0.03, p = 0.83). Among older adults, those diagnosed with PNES had more experiences of childhood trauma. Measures of dissociation, depression, or general anxiety did not differ between PNES and non-PNES diagnoses in the older group. Psychiatric comorbidities are common among older adults admitted for VEM. The psychological impact of epilepsy and risk factors for PNES seen in younger patients are also applicable in the older group. The older group demonstrated more cognitive impairments than the younger group, although these were usually unrecognized by individuals. Older adults admitted to VEM will benefit from psychiatric and neuropsychological input to ensure a comprehensive care approach to evaluation and management. [ABSTRACT FROM AUTHOR]

Seizure-induced cardiorespiratory and autonomic dysfunction has long been recognized, and growing evidence points to its implication in sudden unexpected death in epilepsy (SUDEP). However, a comprehensive understanding of cardiorespiratory function in the preictal, ictal, and postictal periods are lacking. We examined continuous cardiorespiratory and autonomic function in 157 seizures (18 convulsive and 139 nonconvulsive) from 70 consecutive patients who had a seizure captured on concurrent video-encephalogram (EEG) monitoring and polysomnography between February 1, 2012 and May 31, 2017. Heart and respiratory rates, heart rate variability (HRV), and oxygen saturation were assessed across four distinct periods: baseline (120 s), preictal (60 s), ictal, and postictal (300 s). Heart and respiratory rates were further followed for up to 60 min after seizure termination to assess return to baseline. Ictal tachycardia occurred during both convulsive and nonconvulsive seizures, but the maximum rate was higher for convulsive seizures (mean: 138.8 beats/min, 95% confidence interval (CI): 125.3–152.4) compared with nonconvulsive seizures (mean: 105.4 beats/min, 95% CI: 101.2–109.6; p < 0.001). Convulsive seizures were associated with a lower ictal minimum respiratory rate (mean: 0 breaths/min, 95% CI: 0–0) compared with nonconvulsive seizures (mean: 11.0 breaths/min, 95% CI: 9.5–12.6; p < 0.001). Ictal obstructive apnea was associated with convulsive compared with nonconvulsive seizures. The low-frequency (LF) power band of ictal HRV was higher among convulsive seizures than nonconvulsive seizures (ratio of means (ROM): 2.97, 95% CI: 1.34–6.60; p = 0.008). Postictal tachycardia was substantially prolonged, characterized by a longer return to baseline for convulsive seizures (median: 60.0 min, interquartile range (IQR): 46.5–60.0) than nonconvulsive seizures (median: 0.26 min, IQR: 0.008–0.9; p < 0.001). For postictal hyperventilation, the return to baseline was longer in convulsive seizures (median: 25.3 min, IQR: 8.1–60) than nonconvulsive seizures (median: 1.0 min, IQR: 0.07–3.2; p < 0.001). The LF power band of postictal HRV was lower in convulsive seizures than nonconvulsive seizures (ROM: 0.33, 95% CI: 0.11–0.96; p = 0.043). Convulsive seizures with postictal generalized EEG suppression (PGES; n = 12) were associated with lower postictal heart and respiratory rate, and increased HRV, compared with those without (n = 6). Profound cardiorespiratory and autonomic dysfunction associated with convulsive seizures may explain why these seizures carry the greatest risk of SUDEP. • Convulsive and nonconvulsive seizures alter cardiorespiratory function. • Cardiorespiratory function is substantially altered in convulsive seizures. • Ictal apnea duration was longer in convulsive seizures, and commonly obstructive. • Convulsive seizures have prolonged postictal tachycardia and hyperventilation. [ABSTRACT FROM AUTHOR]

• Epilepsy and psychogenic seizures are associated with elevated psychopathology. • Somatisation, and general and phobic anxiety are particular markers of psychogenic seizures. • Machine learning produced a SCL-90-R subset maximising PNES classification accuracy. • PNES classification accuracy was not sufficient for diagnostic use. Similarities in clinical presentations between epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) produces a risk of misdiagnosis. Video-EEG monitoring (VEM) is the diagnostic gold standard, but involves significant cost and time commitment, suggesting a need for efficient screening tools. 628 patients were recruited from an inpatient VEM unit; 293 patients with ES, 158 with PNES, 31 both ES and PNES, and 146 non-diagnostic. Patients completed the SCL-90-R, a standardised 90-item psychopathology instrument. Bayesian linear models were computed to investigate whether SCL-90-R domain scores or the overall psychopathology factor p differed between groups. Receiver operating characteristic (ROC) curves were computed to investigate the PNES classification accuracy of each domain score and p. A machine learning algorithm was also used to determine which subset of SCL-90-R items produced the greatest classification accuracy. Evidence was found for elevated scores in PNES compared to ES groups in the symptom domains of anxiety (b = 0.47, 95%HDI = [0.10, 0.80]), phobic anxiety (b = 1.32, 95%HDI = [0.98, 1.69]), somatisation (b = 0.84, 95%HDI = [0.49, 1.20]), and the general psychopathology factor p (b = 1.35, 95%HDI = [0.86, 1.82]). Of the SCL-90-R domain scores, somatisation produced the highest classification accuracy (AUC = 0.74, 95%CI = [0.69, 0.79]). The genetic algorithm produced a 6-item subset from the SCL-90-R, which produced comparable classification accuracy to the somatisation scores (AUC = 0.73, 95%CI = [0.64, 0.82]). Compared to patients with ES, patients with PNES report greater symptoms of somatisation, general anxiety, and phobic anxiety against a background of generally elevated psychopathology. While self-reported psychopathology scores are not accurate enough for diagnosis in isolation, elevated psychopathology in these domains should raise the suspicion of PNES in clinical settings. [ABSTRACT FROM AUTHOR]

Psychopathology is common in patients undergoing investigation for seizure-related disorders. Psychometric examination using self-report instruments, such as the Symptom Checklist 90 – Revised (SCL-90-R), can assist diagnosis. The SCL-90-R, however, is a lengthy instrument and might not be tolerated by all patients. We assessed several abbreviated forms of the SCL-90-R in patients undergoing video encephalographic monitoring (VEM). Six hundred eighty-seven patients completed the SCL-90-R, and scores were computed for the full SCL-90-R and five abbreviated forms. Correlations and mean differences were computed between different forms. Classification accuracy was assessed via receiver operating characteristic (ROC) curves, and measurements models were examined using confirmatory factor analysis (CFA). All abbreviated forms were strongly correlated with the SCL-90-R for general psychopathology (r = 0.93–0.99), depression (r = 0.89–0.95), anxiety (r = 0.97–0.98), psychosis (r = 0.95–0.99), and obsessive–compulsive symptoms (r = 0.97). Classification performance was similar across forms for depression and anxiety, with high negative predictive values (0.90–0.94) and lower positive predictive values (0.34–0.38). Classification performance for psychotic and obsessive–compulsive disorders was poor. Differences were observed between the full SCL-90-R and its abbreviated forms across most domains (d = 0.00–0.65). The published measurement model was most strongly validated for the SCL-27, SCL-14, and the SCL-K-9. These five SCL-90-R abbreviated forms show high convergent validity with the full version. In patients undergoing investigation for seizure-related disorders, the Brief Symptom Inventory full form (BSI) or short form (BSI-18) is most appropriate where screening for both depression and anxiety is required. The SCL-K-9 is appropriate when only a single measure of global psychological distress is required. None of the instruments were able to detect psychotic or obsessive–compulsive symptoms with great accuracy. Caution should be exercised when making direct comparisons across the different forms. • Rates of psychopathology are high in patients undergoing investigation for epilepsy and related disorders. • The Symptom Checklist 90 – Revised (SCL-90-R) is sensitive to depression, anxiety, and general psychopathology in epilepsy. • None of the SCL-90-R forms were able to detect psychosis or obsessive–compulsive disorder with great accuracy. • The abbreviated forms of the SCL-90-R show high convergent validity with the full-version and can be used in clinical situations where time is limited. • The Brief Symptom Inventory full form (BSI) or short form (BSI-18) are most appropriate when rapid screening for depression and anxiety is required. [ABSTRACT FROM AUTHOR]