Neuropsychological function in psychosis of epilepsy.

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.

Influence of comorbidity on mortality in patients with epilepsy and psychogenic nonepileptic seizures.

OBJECTIVE: This study aims to determine the contribution of comorbidities to excess psychogenic nonepileptic seizures (PNES) mortality. METHODS: A retrospective cohort study was conducted of tertiary epilepsy outpatients from St. Vincent's Hospital Melbourne, Australia with an 8:1 comparison cohort, matched by age, sex, and socioeconomic status (SES) to national administrative databases between 2007 and 2017. Privacy-preserving data linkage was undertaken with the national prescription, National Death Index, and National Coronial Information System. Forty-five comorbid disease classes were derived by applying the Australian validated RxRisk-V to all dispensed prescriptions. We fitted Cox proportional hazard models controlling for age, sex, SES, comorbidity, disease duration, and number of concomitant antiseizure medications, as a marker of disease severity. We also performed a parallel forward-selection change in estimate strategy to explore which specific comorbidities contributed to the largest changes in the hazard ratio. RESULTS: A total of 13 488 participants were followed for a median 3.2 years (interquartile range = 2.4-4.0 years), including 1628 tertiary epilepsy outpatients, 1384 patients with epilepsy, 176 with PNES, and 59 with both. Eighty-two percent of epileptic seizures and 92% of typical PNES events were captured in an epilepsy monitoring unit. The age-/sex-/SES-adjusted hazard ratio was elevated for epilepsy (4.74, 95% confidence interval [CI] = 3.36-6.68) and PNES (3.46, 95% CI = 1.38-8.68) and remained elevated for epilepsy (3.21, 95% CI = 2.22-4.63) but not PNES (2.15, 95% CI = .77-6.04) after comorbidity adjustment. PNES had more pre-existing comorbidities (p = .0007), with a three times greater median weighted Rx-RiskV score. Psychotic illness, opioid analgesia, malignancies, and nonopioid analgesia had the greatest influence on PNES comorbid risk. SIGNIFICANCE: Higher comorbidity appears to explain the excess PNES mortality and may represent either a wider underrecognized somatoform disorder or a psychological response to physical illness. Better understanding and management of the bidirectional relationship of these wider somatic treatments in PNES could potentially reduce the risk of death.

A cross-sectional investigation of cognition and epileptiform discharges in juvenile absence epilepsy.

OBJECTIVES: Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24-h epileptiform discharge load. METHOD: Forty-four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24-h ambulatory EEG monitoring. Generalized epileptiform discharges of any length, and prolonged generalized discharges ≥3 s were quantified across wakefulness and sleep. The relationship between standardized cognitive scores and epileptiform discharges was assessed through regression models. RESULTS: Cognitive performances in overall intellectual ability, acquired comprehension-knowledge, processing speed, long-term memory storage and retrieval, and executive processes were 0.63-1.07 standard deviation (SD) units lower in the JAE group compared to the population reference mean, adjusted for educational attainment. Prolonged discharges (≥3 s) were recorded in 20 patients (47.6%) from 42 available electroencephalography (EEG) studies and were largely unreported. Duration and number of prolonged discharges were associated with reduced processing speed and long-term memory storage and retrieval. SIGNIFICANCE: Cognitive dysfunction is seen in patients with JAE across various cognitive abilities, including those representing more stable processes like general intellect. During 24-h EEG, prolonged epileptiform discharges are common yet underreported in JAE despite treatment, and they show moderate effects on cognitive abilities. If epileptiform burden is a modifiable predictor of cognitive dysfunction, therapeutic interventions should consider quantitative 24-h EEG with routine neuropsychological screening. The growing recognition of the spectrum of neuropsychological comorbidities of IGE highlights the value of multidisciplinary approaches to explore the causes and consequences of cognitive deficits in epilepsy.

Adherence patterns in antiseizure medications influencing risk of sudden unexplained death in epilepsy: A data linkage study using dispensed prescriptions.

OBJECTIVE: Medication adherence is considered an important risk factor for sudden unexpected death in epilepsy (SUDEP), although measurement accuracy is difficult. Using prescription dispensations, this study aims to estimate antiseizure medication (ASM) adherence and identify adherence patterns that influence epilepsy mortality. METHODS: This is a retrospective cohort study of tertiary epilepsy outpatients seen at St Vincent's Hospital Melbourne, Victoria, Australia, from January 1, 2012 until December 31, 2017. Privacy-preserving data linkage with the Australian national prescription, death, and coroner's databases was performed. We fitted a four-cluster longitudinal group-based trajectory model for ASM adherence from recurring 90-day windows of prescription dispensations during a 3-year "landmark period" from January 1, 2012 to December 31, 2014, using the AdhereR package. We estimated the risk of SUDEP and all-cause death for each adherence pattern during an "observation period" from January 1, 2015 to December 31, 2017. The Cox proportional hazards and logistic regression models were adjusted for age, sex, socioeconomic status, epilepsy duration, comorbidity, drug resistance, and inadequate seizure control. RESULTS: One thousand one hundred eighty-seven participants were observed for a median of 3.2 years (interquartile range = 2.4-4.0 years). We observed 66 deaths with 10 SUDEP cases during the observation period. We identified four patterns of ASM adherence: good, 51%; declining, 24%; poor, 16%; and very poor, 9%. Declining adherence was associated with an increased risk for SUDEP, with hazard ratio (HR) = 8.43 (95% confidence interval [CI] = 1.10-64.45) at 1 year and HR = 9.17 (95% CI = 1.16-72.21) at 3 years. Compared to no ASM therapeutic change, the addition of a second to fourth ASM offered increased protection against SUDEP in patients with continuing drug-resistant epilepsy. SIGNIFICANCE: ASM nonadherence was observed in half of outpatients with epilepsy. A declining pattern of adherence, observed in a quarter of patients, was associated with more than eight times increased risk of SUDEP. Any ongoing medication interventions must include strategies to maintain and improve ASM adherence if we are to reduce the risk of SUDEP.

Sleep and seizure risk in epilepsy: bed and wake times are more important than sleep duration.

Sleep duration, sleep deprivation and the sleep-wake cycle are thought to play an important role in the generation of epileptic activity and may also influence seizure risk. Hence, people diagnosed with epilepsy are commonly asked to maintain consistent sleep routines. However, emerging evidence paints a more nuanced picture of the relationship between seizures and sleep, with bidirectional effects between changes in sleep and seizure risk in addition to modulation by sleep stages and transitions between stages. We conducted a longitudinal study investigating sleep parameters and self-reported seizure occurrence in an ambulatory at-home setting using mobile and wearable monitoring. Sixty subjects wore a Fitbit smartwatch for at least 28 days while reporting their seizure activity in a mobile app. Multiple sleep features were investigated, including duration, oversleep and undersleep, and sleep onset and offset times. Sleep features in participants with epilepsy were compared to a large (n = 37 921) representative population of Fitbit users, each with 28 days of data. For participants with at least 10 seizure days (n = 34), sleep features were analysed for significant changes prior to seizure days. A total of 4956 reported seizures (mean = 83, standard deviation = 130) and 30 485 recorded sleep nights (mean = 508, standard deviation = 445) were included in the study. There was a trend for participants with epilepsy to sleep longer than the general population, although this difference was not significant. Just 5 of 34 participants showed a significant difference in sleep duration the night before seizure days compared to seizure-free days. However, 14 of 34 subjects showed significant differences between their sleep onset (bed) and/or offset (wake) times before seizure occurrence. In contrast to previous studies, the current study found undersleeping was associated with a marginal 2% decrease in seizure risk in the following 48 h (P < 0.01). Nocturnal seizures were associated with both significantly longer sleep durations and increased risk of a seizure occurring in the following 48 h. Overall, the presented results demonstrated that day-to-day changes in sleep duration had a minimal effect on reported seizures, while patient-specific changes in bed and wake times were more important for identifying seizure risk the following day. Nocturnal seizures were the only factor that significantly increased the risk of seizures in the following 48 h on a group level. Wearables can be used to identify these sleep-seizure relationships and guide clinical recommendations or improve seizure forecasting algorithms.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

Increased cortical thickness in nodes of the cognitive control and default mode networks in psychosis of 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.

Exploring the Semantic Structure of WMS-IV Verbal Paired Associates using the Hub-and-Spoke Model.

OBJECTIVES: This study aimed to identify a well-fitting and theoretically justified item-level latent factor structure for the Wechsler Memory Scales (WMS)-IV verbal paired associates (VerbalPA) subtest to facilitate the ease and accuracy of score interpretations for patients with lateralized temporal lobe epilepsy (TLE). METHODS: Archival data were used from 250 heterogeneous neurosciences patients who were administered the WMS-IV as part of a standard neuropsychological assessment. Three theoretically motivated models for the latent structure of VerbalPA were tested using confirmatory factor analysis. The first model, based on cognitive principles of semantic processing from hub-and-spoke theory, tested whether performance is related to specific semantic features of target words. The second, motivated by the Cattell-Horn-Carroll (CHC) model of cognitive abilities, investigated whether the associative properties of items influence performance. A third, Hybrid model tested whether performance is related to both semantic and associative properties of items. The best-fitting model was tested for diagnostic group effects contrasting the heterogeneous neuroscience patients with subsets of left and right TLE (n = 51, n = 26, respectively) patients. RESULTS: The Hybrid model was found to have the best fit. Patients with left TLE scored significantly less well than the heterogeneous neurosciences sample on selected semantic factor scores, although the effect size was small. CONCLUSIONS: Future editions of the WMS may consider implementing a semantic scoring structure for the VerbalPA to facilitate test score interpretation. Additionally, these results suggest that principles of hub-and-spoke theory may be integrated into CHC cognitive ability taxonomy.

Latent Semantic Structure of the WMS-III Verbal Paired-Associates.

OBJECTIVE: To investigate the factor structure of the verbal paired-associates (VPA) subtest in the WMS-III using a theoretically driven model of semantic processing previously found to be well-fitting for the WMS-IV version of the test. METHOD: Archival data were used from 267 heterogeneous neurosciences patients and 223 seizure disorder patients who completed the WMS-III as part of a standard neuropsychological evaluation. Confirmatory factor analysis was used to test theoretically driven models for VPA based on principles of semantic processing. Four nested models of different complexities were examined and compared for goodness-of-fit using chi-squared difference testing. Measurement invariance testing was conducted across heterogeneous neuroscience and seizure disorder samples to test generality of the factor model. RESULTS: After removing items with limited variability (very easy or very hard; 12 of 40 items), a four-factor model was found to be best-fitting in the present patient samples. The four factors were "recreational", "functional", "material", and "symbolic", each representing semantic knowledge associated with the function of the target word referent. This model subsequently met the criteria for the strict measurement invariance, showing good overall fit when factor loadings, thresholds, and residuals were held to equality across samples. CONCLUSIONS: The results of this study provide further evidence that "arbitrary" associations between word pairs in VPA items have an underlying semantic structure, challenging the idea that unrelated hard-pairs are semantic-free. These results suggest that a semantic-structure model may be implemented as an alternative scoring in future editions of the WMS to facilitate interpretation.

Source data from a systematic review and meta-analysis of EEG and MEG studies investigating functional connectivity in idiopathic generalized epilepsy.

This article describes source data from a systematic review and meta-analysis of electroencephalography (EEG) and magnetoencephalography (MEG) studies investigating functional connectivity in idiopathic generalized epilepsy. Data selection, analysis and reporting was performed according to PRISMA guidelines. Eligible studies for review were identified from human case-control, and cohort studies. Twenty-two studies were included in the review. Extracted descriptive data included sample characteristics, acquisition of EEG or MEG recordings and network construction. Reported differences between IGE and control groups in functional connectivity or network metrics were extracted as the main outcome measure. Qualitative group differences in functional connectivity were synthesized through narrative review. Meta-analysis was performed for group-level, quantitative estimates of common network metrics clustering coefficient, path length, mean degree and nodal strength. Six studies were included in the meta-analysis. Risk of bias was assessed across all studies. Raw and synthesized data for included studies are reported, alongside effect size and heterogeneity statistics from meta-analyses. Network neurosciences is a rapidly expanding area of research, with significant potential for clinical applications in epilepsy. This data article provides novel, statistical estimates of brain network differences from patients with IGE relative to healthy controls, across the existing literature. Increasing data accessibility supports study replication and improves study comparability for future reviews, enabling a better understanding of network characteristics in IGE.

Pre-hospital benzodiazepines associated with improved outcomes in out-of-hospital status epilepticus: A 10-year retrospective cohort study.

Outcomes of status epilepticus have not substantially changed over the last decade. Given onset is most often in the community, early termination strategies that are implementable outside of hospitals are of public health importance. This 10-year retrospective single-centre cohort study aimed to determine whether pre-hospital benzodiazepine administration is associated with improved health outcomes in patients with out-of-hospital onset status epilepticus. METHODS: We reviewed the medical records of all patients admitted with status epilepticus between 2008 and 2018 at St Vincent's Hospital Melbourne. Data regarding onset setting, medical history, management and outcomes were extracted. RESULTS: 72 patients meeting inclusion criteria were identified. Onset of status epilepticus was out-of-hospital for 74% (53/72) of patients, 66% (35/53) of whom were administered a benzodiazepine before reaching hospital, most often by ambulance officers (30/35, 86%). Pre-hospital benzodiazepine administration was associated with a 90% reduction in duration time to seizure cessation (0.65 vs 5.8 days, p = 0.012) and 50% reduction in length of hospital stay (7.6 vs 15.8 days, p = 0.045). In-hospital onset status epilepticus was associated with higher mortality than out-of-hospital onset (26% vs 4%, RR 6.5, p = 0.004). CONCLUSION: Pre-hospital benzodiazepines shorten the time to seizure control and length of hospital stay in patients with out-of-hospital status epilepticus, although is under-utilised by both ambulance staff and home carers. Health policy measures to improve ambulance officer and home carer administration skills and confidence may address these issues.

Resting-state functional connectivity in the idiopathic generalized epilepsies: A systematic review and meta-analysis of EEG and MEG studies.

For idiopathic generalized epilepsies (IGE), brain network analysis is emerging as a biomarker for potential use in clinical care. To determine whether people with IGE show alterations in resting-state brain connectivity compared to healthy controls, and to quantify these differences, we conducted a systematic review and meta-analysis of EEG and magnetoencephalography (MEG) functional connectivity and network studies. The review was conducted according to PRISMA guidelines. Twenty-two studies were eligible for inclusion. Outcomes from individual studies supported hypotheses for interictal, resting-state brain connectivity alterations in IGE patients compared to healthy controls. In contrast, meta-analysis from six studies of common network metrics clustering coefficient, path length, mean degree and nodal strength showed no significant differences between IGE and control groups (effect sizes ranged from -0.151 -1.78). The null findings of the meta-analysis and the heterogeneity of the included studies highlights the importance of developing standardized, validated methodologies for future research. Network neuroscience has significant potential as both a diagnostic and prognostic biomarker in epilepsy, though individual variability in network dynamics needs to be better understood and accounted for.

Spatiotemporal Patterns of High-Frequency Activity (80-170 Hz) in Long-Term Intracranial EEG.

OBJECTIVE: To determine the utility of high-frequency activity (HFA) and epileptiform spikes as biomarkers for epilepsy, we examined the variability in their rates and locations using long-term ambulatory intracranial EEG (iEEG) recordings. METHODS: This study used continuous iEEG recordings obtained over an average of 1.4 years from 15 patients with drug-resistant focal epilepsy. HFA was defined as 80- to 170-Hz events with amplitudes clearly larger than the background, which was automatically detected with a custom algorithm. The automatically detected HFA was compared with visually annotated high-frequency oscillations (HFOs). The variations of HFA rates were compared with spikes and seizures on patient-specific and electrode-specific bases. RESULTS: HFA included manually annotated HFOs and high-amplitude events occurring in the 80- to 170-Hz range without observable oscillatory behavior. HFA and spike rates had high amounts of intrapatient and interpatient variability. Rates of HFA and spikes had large variability after electrode implantation in most of the patients. Locations of HFA and spikes varied up to weeks in more than one-third of the patients. Both HFA and spike rates showed strong circadian rhythms in all patients, and some also showed multiday cycles. Furthermore, the circadian patterns of HFA and spike rates had patient-specific correlations with seizures, which tended to vary across electrodes. CONCLUSION: Analysis of HFA and epileptiform spikes should consider postimplantation variability. HFA and epileptiform spikes, like seizures, show circadian rhythms. However, the circadian profiles can vary spatially within patients, and their correlations to seizures are patient-specific.

Quality of life and its association with comorbidities and adverse events from antiepileptic medications: Online survey of patients with epilepsy in Australia.

OBJECTIVE: This study aimed to explore the quality of life (QoL) of adult patients with epilepsy (PwE) in Australia and its relationship with comorbidities and adverse events (AEs) from antiepileptic drugs (AEDs). METHODS: Cross-sectional surveys were completed by PwE, or carer proxies, recruited via the online pharmacy application MedAdvisor and Australian PwE Facebook groups from May to August 2018. Data were collected on demographics, epilepsy severity and management, AEs, comorbidities, and QoL (using the Patient-Weighted Quality of Life in Epilepsy Inventory [QOLIE-10-P] total score). Two linear regression models were constructed to explore associations between AEs or comorbidities and QOLIE-10-P score, with possible confounders determined using stepwise selection. RESULTS: Nine hundred and seventy-eight of 1267 responses were eligible (mean age of respondents: 44.5 years, 64% female, 52% employed). Recent AED use was reported by 97%; 47% were on AED monotherapy, 35% had ≤2 lifetime AEDs, and 55% were seizure-free for >1 year. After stepwise selection, control variables included in both models were time since diagnosis, employment status, seizure frequency, number of currently prescribed AEDs, and number of general practitioner (GP) visits per year. In the model for comorbidities, "psychiatric disorders" was associated with the largest QOLIE-10-P score decrease (-23.14, p < 0.001). In the model for AEs, which additionally controlled for depression and anxiety disorder, self-reported "memory problems" was associated with the largest decrease in QOLIE-10-P score (-14.27, p < 0.001). CONCLUSIONS: In this survey of Australian PwE, many of whom had relatively well-controlled epilepsy, psychiatric and self-reported memory problems were common and associated with the greatest detrimental impact on QoL. Further research is needed to better understand the underlying causes of impaired QoL and thereby improve its management.

Default mode network dysfunction in idiopathic generalised epilepsy.

In order for fMRI findings to be valid and replicable, they must first adhere to quality standardisation. Currently, fMRI literature investigating idiopathic generalised epilepsy is heterogeneous in terms of design, acquisition, processing, and analysis. The present study reported the quality, methods, and functional connectivity findings of fMRI research investigating idiopathic generalised epilepsies, targeting studies that best represent valid and replicable methodologies. Twenty-four studies were identified in the present systematic review. The default mode network showed more significantly altered connectivity than other resting state networks. These networks and associated regions of interest were frequently deactivated at rest amongst all idiopathic generalised epilepsy subtypes compared to controls. This review highlights the need for standardization in acquisition techniques and parameters, processing steps, and analysis techniques, if research in this field is to be replicable. There is also a need for further investigation into default mode network connectivity in the juvenile absence epilepsy population, as a common subtype of idiopathic generalized epilepsy.

Single-subject manual independent component analysis and resting state fMRI connectivity outcomes in patients with juvenile absence epilepsy.

The quality of fMRI data impacts functional connectivity measures and consequently, the decisions that clinicians and researchers make regarding functional connectivity interpretation. The present study used resting state fMRI to investigate resting state network connectivity in a sample of patients with Juvenile Absence Epilepsy. Single-subject manual independent component analysis was used in two levels, whereby all noise components were removed, and cerebrospinal fluid pulsation components only were isolated and removed. Improved temporal signal to noise ratios and functional connectivity metrics were observed in each of the cleaning levels for both epilepsy and control cohorts. Results showed full, single-subject manual independent component analysis reduced the number of functional connectivity correlations and increased the strength of these correlations. Similar effects were also observed for the cerebrospinal fluid pulsation only cleaned data relative to the uncleaned, and fully cleaned data. Single-subject manual independent component analysis coupled with short TR multiband acquisition can significantly improve the validity of findings derived from fMRI data sets.

Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy.

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.

Risk factors for injury in a community-treated cohort of patients with epilepsy in Australia.

OBJECTIVE: There remains a paucity of knowledge regarding specific epilepsy-related risk factors for accidents and injuries in people with epilepsy. Injury studies in people with epilepsy are overrepresented, with tertiary based populations that are prone to bias from severe disease. This study aims to assess the contribution of epilepsy-related risk factors to injuries in a community-based cohort. METHODS: We performed a retrospective nested case-control study on patients recruited into the Tasmanian Epilepsy Register (TER) from July 1, 2001 to June 30, 2002. The TER is a community-based cohort of patients with epilepsy in Tasmania, Australia, recruited from the national prescription database and interviewed for epilepsy diagnosis, injuries, and risk factors using validated questionnaires with diagnosis made by an epilepsy specialist. The primary outcome measures were lifetime and recent 12-month injury. Multivariate logistic regression with multiple imputation modeling responder nondisclosure was performed, adjusting for age, gender, region, socioeconomic status, seizure frequency, and epilepsy duration. RESULTS: A total of 819 patients with epilepsy were included in this study. Ten percent of patients experienced an injury in the preceding year. Before adjusting for seizure frequency, any seizure over the past 12 months was associated with recent injury (adjusted odds ratio [OR] = 7.90, 95% confidence interval [CI] = 4.17-14.96). Impaired awareness, cluster seizures, sleep-only seizures, and convulsive seizure were characteristics found to significantly influence injuries irrespective of seizure frequency. Although a warning appeared initially protective for recent injuries (OR = 0.39, 95% CI = 0.22-0.69), this was entirely explained by seizure frequency, with the effect becoming nonsignificant. SIGNIFICANCE: Likely due to their unpredictable nature, seizures expose patients with epilepsy to a high risk of life-threatening injury. These findings emphasize the importance of seizure freedom for maximizing the safety of patients with epilepsy.

Preictal autonomic dynamics in psychogenic nonepileptic seizures.

OBJECTIVES: Psychogenic nonepileptic seizures (PNES) resemble seizures but are psychological in origin. The etiology of PNES remains poorly understood, yet several theories argue for the importance of autonomic dysregulation in its pathophysiology. We therefore conducted a retrospective study to investigate autonomic dynamics leading up to a seizure to inform their mechanistic relevance. METHODS: One hundred one patients with PNES and 45 patients with epileptic seizure (ES) were analyzed for preictal heart rate (HR) and respiratory rate (RR) at baseline and at minute intervals from 5 min to onset. RESULTS: Patients with PNES showed rising HR (p < 0.001, repeated-measures analysis of variance (ANOVA)) and rising RR (p = 0.012, repeated-measures ANOVA) from baseline to the onset of their seizures. Patients with ES did not exhibit significant preictal HR or RR increase. Patients with PNES had nonsignificantly higher preictal HR and RR than patients with ES. SIGNIFICANCE: Patients with PNES exhibit increasing autonomic arousal prior to seizure events unlike patients with epilepsy. This may reflect increasing levels of preictal anxiety, and future studies could study patients' subjective experiences of the preictal period, and more definitive measures of ventilation to see if this supported a model of PNES as "panic without panic".