Late-onset epilepsy with cognitive symptoms: Comparison of cognitive and imaging profiles with probable Alzheimer's disease.

OBJECTIVE: We aimed to (i) compare the clinical, neuropsychological, and neuroimaging characteristics of unprovoked late-onset epilepsy (LOE) patients with cognitive symptoms against probable Alzheimer's disease (AD) patients; (ii) clarify how neurodegeneration and other processes could be implicated in the cognitive symptoms of unprovoked LOE patients; and (iii) characterize the longitudinal trajectory of unprovoked LOE patients with cognitive symptoms. METHODS: Twenty-six unprovoked LOE patients with cognitive symptoms and 26 probable AD were retrospectively recruited from epilepsy and memory clinics at a single tertiary referral center. The patients underwent comprehensive clinical, neuropsychological, and 18Fluorodeoxyglucose PET-CT assessments. All LOE patients had clinical follow-up and a subset of 17 patients had repeat neuropsychological assessments. RESULTS: At baseline, 18% of LOE patients with cognitive symptoms had dementia-range cognitive impairment and one received a diagnosis of probable AD. Compared with the probable AD group, the LOE group did not perform significantly better in global measures of cognition (total ACE-III), neuropsychological tests for fluency, working memory, language, attention, or executive function, but performed better in naming, memory, and visuospatial ability. The commonest patterns of cognitive impairment in the LOE group were frontal and left temporal, whereas all AD patients exhibited parietotemporal patterns. The AD group had more 18Fluorodeoxyglucose PET-CT hypometabolism in the parietal and occipital, but not the temporal and frontal lobes. During the 3.0 ± 3.2 years follow-up, improved seizure frequency in the LOE group covaried with improved total ACE-III score, there was no further conversion to probable AD and no group-level cognitive decline. CONCLUSION: Unprovoked LOE patients with cognitive symptoms had varying severities of cognitive impairment, and different patterns of cognitive and imaging abnormalities compared with AD patients. They were rarely diagnosed with probable AD at presentation or follow-up. Cognitive outcome in LOE may be related to seizure control. Cerebral small vessel disease may play a role in LOE-associated cognitive impairment.

Integrated psychological care services within seizure settings: Key components and implementation factors among example services in four ILAE regions: A report by the ILAE Psychiatry Commission.

Mental health comorbidities are prevalent and problematic in patients with seizures but often suboptimally managed. To address common gaps in care, the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy (ILAE) Psychiatry Commission was tasked with providing education and guidance on the integration of mental health management (e.g., screening, referral, treatment) into routine seizure care. This report aims to describe a variety of established services in this area, with a specific focus on psychological care models. Services were identified by members of the ILAE Psychiatry Commission and authors of psychological intervention trials in epilepsy. A total of eight services met inclusion criteria and agreed to be showcased. They include three pediatric and five adult services located across four distinct ILAE regions (Europe, North America, Africa, Asia Oceania). The report describes the core operations, known outcomes, and implementation factors (i.e., barriers and facilitators) of these services. The report concludes with a set of practical tips for building successful psychological care services within seizure settings, including the importance of having local champions, clearly defining the scope of the service, and establishing sustainable funding models. The breadth of exemplars demonstrates how models tailored to the local environment and resources can be implemented. This report is an initial step to disseminate information regarding integrated mental health care within seizure care settings. Future work is needed to systematically examine both psychological and pharmacological care models and to further establish the evidence base in this area, especially around clinical impact, and cost-effectiveness.

How frequently is anxiety and depression identified and treated in hospital and community samples of adults with epilepsy?

While it is often stated that psychiatric co-morbidity in PWE is under-recognized and under-treated, little research has directly examined this assertion. The aims of this study were to understand the rates of confirmed diagnosis and treatment of depression and anxiety in people with epilepsy (PWE). Two samples were recruited: a hospital sample of 106 adult outpatients with epilepsy who underwent a structured psychiatric diagnostic interview and a community sample of 273 PWE who completed validated measures of depression and anxiety symptoms online. In the hospital sample, fewer participants who met criteria for an anxiety disorder had received a prior diagnosis compared to those with a depressive disorder (36% vs 67%). In the community sample, the rates of known diagnosis were comparable (65% vs. 69%). Approximately, one-third of PWE with an anxiety disorder (or clinically significant symptoms) were receiving current treatment compared to approximately half of those with depression. These findings confirm the high rates of psychiatric co-morbidity in PWE and indicate that a large proportion of anxiety diagnoses, in particular, are undetected and not receiving either pharmacological or psychological support. Future work is needed to improve the detection and management of psychiatric co-morbidity in PWE, especially for anxiety disorders.

The impact of hippocampal damage on appetitive control.

Animal data indicates the hippocampus assists appetite-regulation.  We tested this in humans, contrasting two patients (DW, JC) with hippocampal damage to controls on an appetite-regulation test conducted hungry and sated.  When hungry, controlsviewed palatable snacks and reported a desire to eat them, a memory-based judgment.  After sampling them, they reported liking their taste.  Post-lunch (DW ate little, precluding a test of our hypothesis), controls showed a large decrease in desire for the snacks, but less change in taste-liking.  JC ate like controls, but reported no change in desire across states, suggesting that the human hippocampus also contributes to appetite-regulation.

Accelerated long-term forgetting is not evident in adults with genetic generalized epilepsy irrespective of the paradigm used.

Accelerated long-term forgetting (ALF) is a recently discovered memory disorder characterized by intact acquisition and retention over short delays, followed by abnormally fast rates of forgetting. Accelerated long-term forgetting has been repeatedly found in children, but not in adults, with genetic generalized epilepsy (GGE). It is possible that this discrepancy is due to a difference in paradigms used in these studies. The current study aimed to determine whether adults with GGE displayed ALF using two paradigms, one that required complete learning and another one that did not. In addition, we explored the relationships with everyday memory difficulties, working memory, mood, and epilepsy variables. Fourteen adults with GGE were compared with 16 healthy controls on two verbal memory tests: a modified version of the California Verbal Learning Test learned to a criterion of 100% (complete learning) and Logical Memory from the Wechsler Memory Scale (Fourth Edition) presented only once (incomplete learning). Recall was tested at 2 min, 30 min, and 1 week, and recognition at 1 week only. Working memory, everyday memory, and mood were also assessed. We found no evidence of ALF on either of the two verbal memory paradigms on recall or recognition tests although patients displayed significantly poorer working memory. Moreover, patients with GGE reported significantly more memory difficulties in everyday life, and these were associated with greater mood disturbances but not with memory tests scores. Greater number of antiepileptic drugs and epilepsy severity also related to memory scores on some tests. Our study suggests that a difference in paradigms used to investigate ALF in children and adults with GGE is unlikely to explain the differences in findings. The study tentatively raises a hypothesis that developmental factors may play a role in ALF in patients with GGE; children with GGE may grow out of ALF. Nevertheless, this hypothesis would need to be tested in a longitudinal study that would follow patients from childhood to early adulthood.

Group-based cognitive behavioral therapy program for improving poor sleep quality and quality of life in people with epilepsy: A pilot study.

Sleep difficulties are commonly reported by patients with epilepsy and can have a detrimental impact on overall quality of life. The purpose of this pilot study was to assess the efficacy of a psychotherapeutic approach, namely Cognitive Behavioral Therapy for Insomnia (CBT-I), in improving sleep quality in patients with epilepsy. Twenty outpatients with epilepsy who reported poor sleep quality were randomized to either a control or CBT-I treatment group, which involved four group-based CBT-I sessions, delivered on a weekly basis. In addition to completing a range of standardized measures related to sleep quality and quality of life, participants also monitored their sleep with a self-completed sleep diary over a two-week period, on two separate occasions. Following CBT-I treatment, no between-group difference was found on any sleep or quality of life measure. However, both the treatment and control groups improved on measures of sleep quality, quality of life, sleep hygiene behaviors, and dysfunctional beliefs about sleep. These findings suggest that sleep monitoring alone may have the potential for prompting healthy behavior change in this clinical population.

Design and validation of two measures to detect anxiety disorders in epilepsy: The Epilepsy Anxiety Survey Instrument and its brief counterpart.

OBJECTIVE: The study objective was to develop and validate the first epilepsy-specific anxiety survey instrument (Epilepsy Anxiety Survey Instrument [EASI]) alongside a briefer screening instrument to detect anxiety disorders in routine clinical practice (brEASI). METHODS: The instruments were developed utilizing a mixed-methods approach in four related studies. Pilot items were developed following qualitative interviews with people with epilepsy (PWE; Study 1) and consultation with multidisciplinary experts in anxiety and epilepsy (Study 2). PWE (n = 314) then completed pilot items alongside existing measures of anxiety and depression (Study 3). Factor analysis was conducted to refine the scale and select well-performing items for a briefer diagnostic screener (brEASI). The brEASI was validated against a gold standard diagnostic interview in 106 PWE recruited from an outpatient epilepsy service (Study 4). Receiver operating characteristic analysis was conducted to determine the brEASI's diagnostic performance. RESULTS: Twenty-six pilot items were generated based on the findings of Studies 1 and 2. Analyses in Study 3 resulted in an 18-item EASI, and eight well-performing items were selected for the brEASI. The area under the curve (AUC) of brEASI was excellent (AUC = 0.89, 95% confidence interval = 0.82-0.94). At a cutoff of 7, it demonstrated a sensitivity of 76% and specificity of 84% for identifying Diagnostic and Statistical Manual of Mental Disorders, 5th edition anxiety disorders. SIGNIFICANCE: The EASI and brEASI represent the first valid and reliable epilepsy-specific anxiety instruments. The EASI has been designed to comprehensively assess anxiety in PWE, whereas the brEASI may be used within busy neurology settings to provide rapid information to aid diagnoses of anxiety disorders. Given the significant prevalence and burden of anxiety in PWE, these tools are important potential solutions to improve the understanding and detection of anxiety in epilepsy.

A qualitative examination and theoretical model of anxiety in adults with epilepsy.

OBJECTIVE: There is an elevated prevalence of anxiety disorders among people with epilepsy, and the comorbidity of anxiety in epilepsy is associated with adverse medical and psychosocial outcomes. Despite its importance, little is known about what psychosocial or epilepsy factors may be associated with the development of anxiety. The aim of this qualitative study was to determine what factors may explain why some people with epilepsy develop anxiety disorders and others do not. METHODS: Adults with epilepsy were recruited from an outpatient epilepsy service. Semistructured interviews were conducted with 26 participants, 15 of whom reported clinically significant levels of anxiety. Grounded theory analysis was used to develop a theoretical model of anxiety development in the context of epilepsy. RESULTS: Qualitative analyses revealed a number of processes that appeared to account for the development of anxiety in the context of epilepsy. These included inflated estimates regarding epilepsy-specific risks and excessive attempts to avoid these risks. Such excessive avoidance often resulted in greater interference with participants' role functioning, thus risking ongoing quality of life. A number of premorbid and contextual factors also appear to be implicated in the development of anxiety. CONCLUSION: This investigation provides a comprehensive account for the development of anxiety in epilepsy, which is consistent with existing theories of anxiety development and maintenance. Importantly, this model provides a foundation for future research and appropriate treatment strategies to address anxiety in people with epilepsy.

Accelerated Long Term Forgetting in patients with focal seizures: Incidence rate and contributing factors.

BACKGROUND: Accelerated Long Term Forgetting (ALF) is usually defined as a memory impairment that is seen only at long delays (e.g., after days or weeks) and not at shorter delays (e.g., 30min) typically used in clinical settings. Research indicates that ALF occurs in some patients with epilepsy, but the incidence rates and underlying causes have not been established. In this study, we considered these issues. METHODS: Forty-four patients with a history of focal seizures were tested at 30min and 7day delays for material from the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Test. Recently published norms from a matched group of 60 control subjects (Miller et al., 2015 ) were used to determine whether patients demonstrated ALF, impairment at 30min or intact memory performance. RESULTS: The incidence of ALF in the epilepsy patients (18%) was >3 times higher than normal on the RAVLT, but no different (7%) from the incidence in normal subjects on the Aggie Figures. A different, but again significantly high, proportion of patients (36%) showed shorter-term memory deficits on at least one task. ALF was found mainly in patients with temporal-lobe epilepsy, but also occurred in one patient with an extratemporal seizure focus. Presence of a hippocampal lesion was the main predicting factor of ALF. CONCLUSIONS: Many patients with a focal seizure disorder show memory deficits after longer delays that are not evident on standard assessment. The present study explored the factors associated with this ALF memory profile. These new findings will enhance clinical practice, particularly the management of patients with memory complaints.

Testing the importance of the Medial Temporal Lobes in human interoception: Does it matter if there is a memory component to the task?

Interoception is the ability to consciously perceive internal bodily states. Neuroimaging suggests that the insula (IC) and anterior cingulate cortex (ACC) mediate interoception, while studies involving patients/animals with brain lesions suggest the medial temporal lobe (MTL) is particularly important. One reason for these contrasting conclusions may lie in the types of interoceptive task used by these different approaches. Some tasks probably require integration of current physiological state with mnemonic information (e.g., how much one last ate), and these may be especially reliant upon MTL processing. We compared one task that probably requires integration - a water load task - with one that likely does not - a heart-rate tracking task - in two individuals with selective MTL damage (and with intact IC and ACC). A group of matched healthy individuals served as controls. The main finding was that individuals with MTL damage, relative to controls, were equally and significantly impaired on both types of interoception task. This suggests that MTL structures are involved in mediating interoception even when using a task (heart rate tracking) that does not seemingly require memory and that in neuroimaging studies activates the IC and ACC. The reasons for this apparent inconsistency with neuroimaging findings and the functional role of the MTL in interoception are discussed.

Old dogs with new tricks: Detecting accelerated long-term forgetting by extending traditional measures.

Accelerated long-term forgetting (ALF) is a condition in which normal memory performance is displayed after short delays, but significant memory loss is detected when memory is tested after several days or weeks. This condition has been reported in patients with epilepsy, but there are few normative scores available for its detection in clinical practice. In the present study, we assessed 60 healthy control subjects 18-60years of age on three memory measures [Rey Auditory Verbal Learning (RAVLT), Logical Memory (LM), and Aggie Figures] at delays of 30min and 7days. With these normative values, we determined cutoff scores to look for ALF and then categorized the performance of 15 patients with focal epilepsy on the same tasks. Seven of the patients showed ALF, and, in four of these, no other memory deficits (i.e., deficits at 30min on at least one task) were detected. Of the several demographic and epilepsy factors examined, only higher estimated IQ and older age predicted ALF (and only on one task: RAVLT). The findings provide a useful set of data to be applied in the clinic and some insight into the factors that influence retention within the first week.

Anxiety in epilepsy: a neglected disorder.

OBJECTIVE: Anxiety disorders and symptoms are highly prevalent and problematic comorbidities in people with epilepsy (PWE), yet they remain poorly understood and often go undetected. This research aimed to further our understanding about anxiety in PWE. METHODS: Study 1 assessed the effectiveness of the commonly utilised yet unvalidated measure (Hospital Anxiety Depression Scale-Anxiety subscale; HADS-A) to identify DSM-IV anxiety disorders in 147 adult epilepsy outpatients. RESULTS: This study found that although the HADS-A had reasonable specificity (75%), its poor sensitivity (61%) and inadequate area under the curve (.68) deemed it unreliable as a screener for anxiety disorders in this population. METHODS: Study 2 aimed to further our understanding of the relationship between anxiety disorders, as defined by clinical interview, and psychosocial correlates in PWE. One hundred and twenty-two participants from Study 1 completed a battery of psychosocial measures. RESULTS: Multivariate analysis revealed that the presence of an anxiety disorder was associated with unemployment, which was found to be the only independent predictor. That is, despite the fact that psychosocial factors together contributed to the variance in anxiety disorders none were revealed to be significant independent predictors. CONCLUSION: These findings add to the literature indicating that the HADS may indicate distress, but does not adequately identify people with anxiety disorders and highlights the urgent need for the development of a reliable anxiety screening measure for PWE. Further, the results suggest that anxiety disorders in PWE are likely to be multiply determined with respect to psychosocial factors and require further investigation.

Cognitive behaviour therapy to improve mood in people with epilepsy: a randomised controlled trial.

This study compared a 9-week individualised Cognitive Behaviour Therapy (CBT) programme for people with epilepsy (PWE), with a wait-list control. Fifty-nine PWE were randomised and 45 (75%) completed post-treatment outcomes. People with lower quality of life (QoL), particularly for cognitive functioning, were more likely to drop out. Analyses based on treatment completers demonstrated significant improvements on the Neurological Depressive Disorders Inventory for Epilepsy (p = .045) and Hospital Anxiety Depression Scale-Depression subscale (p = .048). Importantly, CBT significantly reduced the likelihood of clinical depressive symptoms (p = .014) and suicidal ideation (p = .005). Improvements were not observed for anxiety, QoL or maintained overtime for depression. Results suggest that CBT was effective, however, and could be improved to increase patient retention and long-term outcomes.

Accelerated long-term forgetting of verbal information in unilateral temporal lobe epilepsy: Is it related to structural hippocampal abnormalities and/or incomplete learning?

The factors contributing to accelerated long-term forgetting (ALF) are not yet clear. In this study, a 12-item word list was presented repeatedly to 23 patients with temporal lobe epilepsy (TLE) and 27 control participants (NC) until it was recalled completely on two consecutive trials or until 12 trials were undertaken. Compared to NCs, patients with hippocampal lesions and those who failed to learn the list showed ALF by one day post learning, but the alternative patient groups also showed ALF when tested after seven days. Overall, our findings suggest that in patients with TLE neither a preserved hippocampus nor intact learning protects against ALF.

Accelerated long-term forgetting: a newly identified memory impairment in epilepsy.

Recently, a pattern referred to as accelerated long-term forgetting (ALF) has been described in patients with epilepsy. In ALF, acquisition and retention over standard delayed recall intervals (up to 30 minutes) tend to be intact, but there is an abnormally rapid rate of forgetting over delays of days or weeks. ALF is associated with everyday memory complaints as well as impairments in autobiographical memory, but goes largely undetected by traditional neuropsychological measures. We consider here the characteristics of ALF and possible contributors to its underlying pathophysiology. Overall, a better understanding of this relatively newly recognised memory disorder should improve clinical treatment.

The psychosocial correlates of depressive disorders and suicide risk in people with epilepsy.

OBJECTIVE: Despite considerable effort to identify correlates of psychopathology in people with epilepsy (PWE), research has yet to identify consistent predictors. We tested the association between factors predicted by a model of adjustment to illness and psychopathology in PWE. METHODS: In 123 PWE recruited from a tertiary referral centre, we examined the cross-sectional relationship between psychosocial factors (illness representations, coping, self-illness enmeshment and self-efficacy) with depression and suicide risk, while controlling for condition-related and demographic factors. RESULTS: Multivariate analyses confirmed previous findings showing that condition-related and demographic variables did not consistently account for unique variance in depression although employment status was found to be a significant predictor of suicide risk. In multivariate analyses escape-avoidance coping and the illness consequences subscale of the illness representation questionnaire predicted unique variance in both depression and suicide risk. CONCLUSION: The results provided partial support for a model of adjustment to illness. Specifically, those who believed epilepsy was serious and coped through avoidance were more likely to be depressed and report a current level of suicide risk. These results suggest that interventions that target coping strategies and illness representations may be warranted for PWE with psychopathology.

Examining factors related to accelerated long-term forgetting in epilepsy using ambulatory EEG monitoring.

PURPOSE: Some patients with epilepsy demonstrate normal memory when this is tested at relatively short intervals (e.g., 30 min), but substantial loss over longer delay periods (e.g., days or weeks) when compared to healthy control subjects. This pattern of "accelerated long-term forgetting" (ALF) affects the everyday lives of patients, yet goes undetected by standard neuropsychological memory tests, and its pathophysiologic basis is poorly understood. By testing memory over a period of concurrent ambulatory electroencephalography (EEG), the current study aimed to investigate possible factors contributing to ALF. METHODS: Thirty-nine patients diagnosed with epilepsy or probable epilepsy underwent 5 days of continuous ambulatory EEG: 18 had normal EEG studies, 10 had focal epileptic discharges, 5 had generalized epileptic discharges, and 6 had one or more seizures. Fifteen matched healthy control subjects also participated, but did not undergo EEG. Subjects were taught 13-item word and design lists to criterion, and recall was tested at 30 min, 24 h, and 4 days. Subjects also completed questionnaires pertaining to everyday memory and mood. KEY FINDINGS: Group analyses (excluding patients who experienced seizures during monitoring) indicated that patients who experienced generalized discharges during the 24-h to 4-day delay intervals showed higher rates of forgetting for nonverbal information. Those with focal discharges showed ALF between 30 min and 4 days for verbal information, whereas those with normal EEGs over the 4 days recording had no evidence of ALF. Surprisingly, mood and epilepsy variables (such as duration of disease or number of anticonvulsant medications) showed no significant correlation with ALF. Although no aspect of nighttime sleep architecture was found to be related to recall after the first 24 h, daytime naps were associated with better retention. Self-report of everyday memory functioning was related to recall at longer delays, but not at 30 min. SIGNIFICANCE: The present findings indicated that ALF in epilepsy is associated with subclinical discharges rather than antiepileptic drugs (AEDs), mood or sleep disturbance. Measures of longer-term recall can reveal correlations with subjective everyday memory complaints that are not evident when recall is only tested at a standard (30 min) delay interval. These findings have the potential to improve treatment strategies for patients who complain of memory difficulties.

Rates of DSM-IV mood, anxiety disorders, and suicidality in Australian adult epilepsy outpatients: a comparison of well-controlled versus refractory epilepsy.

Despite recent research into the impact of seizure control on mood disorders in epilepsy, it is often assumed that rates of psychiatric disorders are higher in people with refractory rather than well-controlled epilepsy. We assessed the point prevalence of mood and anxiety disorders and suicide risk using the Mini International Neuropsychiatric Interview (MINI) in a consecutive sample of epilepsy outpatients from a tertiary referral center. One hundred and thirty patients, whose epilepsy was categorized as well-controlled versus drug-treatment-refractory epilepsy (69; 53% well-controlled epilepsy) were recruited. High rates of mood disorders (n = 34; 26%), anxiety disorders (n = 37; 29%) and suicide risk (n = 43; 33%) were found. However, there was no difference in rates of disorders or suicide risk for those with refractory versus well-controlled epilepsy. These results underscore the importance of assessment and management of psychopathology in all people with epilepsy, regardless of their seizure control.