Paternal exposure to antiseizure medications and offspring outcomes: a systematic review.

BACKGROUND: Concerns have recently been raised about risks to the fetus resulting from paternal exposure to antiseizure medications (ASMs). To address these concerns, we conducted a systematic review of the literature to assess neurodevelopmental and anatomical outcomes in offspring born to fathers taking ASMs at the time of conception. METHODS: Electronic searches of MEDLINE, PsycINFO, and Embase were conducted to identify human studies published in English that reported on outcomes, comprising neurodevelopmental disorders, major congenital malformations, small-for-gestational age or low birth weight, in offspring of fathers taking ASMs at conception. Quality analysis of included studies was undertaken using the Newcastle-Ottawa Scale. A narrative synthesis was used to report study findings. RESULTS: Of 923 studies identified by the search and screened by title and abstract, 26 underwent full-text review and 10 met eligibility criteria. There was limited evidence available, but there appeared to be no clear evidence for an adverse impact of paternal ASM use on offspring outcomes. Few isolated adverse findings were not replicated by other investigations. Several methodological limitations prevented meta-analysis, including failure by most studies to report outcomes separately for each individual ASM, heterogeneity in measurement and outcome reporting, and small numbers of monotherapy exposures. CONCLUSIONS: Although there were limited data available, this systematic review provides reassuring evidence that paternal exposure to ASMs at conception is unlikely to pose any major risk of adverse outcomes for the offspring. Further research is needed to examine the relationship between preconception ASM use in males and offspring outcomes at birth and postnatally.

Re-PROGRAM: The evaluation of a brief intervention program for patients with functional seizures in an outpatient hospital setting.

OBJECTIVE: Functional seizures (FS) account for 20%-25% of referrals to specialist epilepsy clinics. They are associated with major disability, increased mortality, and frequent and costly health care use. Current guidelines emphasize the importance of implementing clinical pathways to coordinate and deliver effective treatment, but there are few targeted evidence-based interventions that reliably improve patient outcomes, and treatment resources are limited. We conducted a retrospective evaluation of Re-PROGRAM, a novel, brief intervention for functional seizure patients, to assess its feasibility in an outpatient setting. METHODS: Twenty-nine patients with FS undertook Re-PROGRAM between August 2020 and January 2022 at the Alfred Hospital Functional Seizures Clinic, Melbourne, Australia. The intervention comprised five 60-90-min consecutive weekly appointments via telehealth, where psychologists engaged patients in a structured program of seizure management skills, lifestyle modification, and behavioral activation strategies. Following the intervention, patient feedback was collected in routine clinical follow-up as well as with a 24-item self-report pre-/postintervention comparison questionnaire. RESULTS: All 29 patients who enrolled in Re-PROGRAM completed the scheduled sessions. Of those who returned the postintervention questionnaire (n = 16), 15 reported a reduction in seizure frequency. Four patients were lost to follow-up. Of the remaining nine, eight reported seizure frequency reduction during clinical follow-up. Qualitative analysis of the feedback revealed the majority of patients reported reduced seizure duration, intensity, and bothersomeness, and patients felt improvements in their sense of control over seizures, confidence to use seizure control strategies, assertive communication, problem solving, coping skills, relationships with others, and their day-to-day functioning. SIGNIFICANCE: This retrospective evaluation demonstrates the feasibility and acceptability of Re-PROGRAM as a brief intervention for individuals diagnosed with FS delivered in a clinical outpatient setting and warrants further investigation in larger scale, randomized controlled studies.

"What are your seizures telling you?": A therapeutic tool for functional seizures.

BACKGROUND: Understanding illness representations is considered important for improving health outcomes, yet how people with functional seizures reflect on the possible psychological function of their seizures has not been studied. METHODS: A semi-structured interview comprising open and closed questions was administered to 99 participants with a documented diagnosis of functional seizures. One item, 'What do you think your functional seizure symptoms are telling you?" sought to explore how individuals reflect on the possible function of their seizures. Qualitative analysis using NVivo comprised thematic content analysis of responses to the question, and pattern analysis, to determine association with diagnosis acceptance, and openness to a possible psychological aetiology. RESULTS: Most patients (88 %) readily interpreted their seizures in response to this question. We identified one major theme, with the majority of participants interpreting seizure symptoms as an enforced hiatus. Two minor themes were identified: personal growth and contempt. Subthemes were identified within both the enforced hiatus (stop, slow down, relax) and personal growth (self-care, self-development, acceptance) themes. Individuals who did not accept the diagnosis of functional seizures referenced seizures with contempt towards the self or answered, 'don't know'. Respondents who did not know also tended to reject a psychological basis for their seizures in contrast to those who discussed themes of enforced hiatus, personal growth, and contempt. CONCLUSIONS: Responses provide valuable insight into how individuals reflect on their condition in a non-acute setting. Themes can serve as a foundation for future therapeutic discussions and patient-centred communication strategies to build a mutual understanding of the potential function of physical symptoms regardless of whether a psychological basis for them is accepted or not. What is already known on this topic: Outcomes for functional seizures are generally poor and often attributed to patients rejecting psychiatric care or not accepting the diagnosis. WHAT THIS STUDY ADDS: This study is the first to explore patient conceptualisations of the possible function of their functional seizures as a therapeutic tool for understanding the condition. How this study might affect research, practice, or policy: Findings may provide a basis for improved clinician-patient relationships, treatment engagement, and more targeted interventions for people with functional seizures.

The "make or break" impact of family dynamics on psychological outcomes in focal epilepsy.

OBJECTIVE: Living with epilepsy can shape the dynamics of the whole family unit. The first objective of this study was to establish the reliability and validity of our purpose-built online family mapping tool: "Living with Epilepsy." Our second objective was to identify distinct patterns of emotional closeness between family members (family typologies), and to explore (1) whether family typologies are shaped by epilepsy-related factors, and (2) which typologies confer optimal psychological outcomes to people with epilepsy. METHODS: Ninety-one adults with chronic epilepsy and their caregivers (n = 56) participated and 70 similarly aged healthy controls and 36 caregiver controls (N = 253). Purpose-built software assessed a range of epilepsy-specific psychosocial issues, including family mapping. Questionnaires validated for epilepsy evaluated mood and quality of life (QOL). RESULTS: The reliability and validity of the family mapping tool was established. Family maps revealed three typologies varying in emotional closeness, each with distinct patterns of healthy vs maladaptive family behavior: Extremely Close (32%), Close (54%), and Fractured (14%). There was no difference in the frequency of typology between epilepsy and control families (p > .05). Within the epilepsy cohort, however, patients with seizure onset in childhood largely belonged to the extreme typologies: Extremely Close (47%) or Fractured (42%). In comparison, those with adolescent or adult onset commonly belonged to the moderate typology: Close (53%). People with epilepsy from Extremely Close families reported significantly higher QOL (p = .013) and lower mood symptoms (p = .008) relative to other typologies; no such association was found for controls or caregivers (p > .05). SIGNIFICANCE: These findings suggest that adults whose epilepsy commenced in childhood are likely to have extreme family dynamics characterized by either being brought closer together or driven apart. Extremely close families appear highly adaptive for people with epilepsy, bringing benefits for mood and QOL not seen in their caregivers or controls. The results provide strong empirical support for the value of an emotionally supportive family when living with epilepsy and suggest that fostering healthy connections within epilepsy families can optimize long-term patient well-being.

Childhood trauma in patients with epileptic vs nonepileptic seizures.

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 (nRetrospective  = 203; nProspective  = 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.

Body image dissatisfaction: A novel predictor of poor quality of life in epilepsy.

OBJECTIVE: People with epilepsy have long reported reduced quality of life (QoL) compared to healthy peers. This initial study seeks to broaden our understanding of QoL in adults with epilepsy, by examining the adverse impact of body image dissatisfaction for the first time. This aim stems from the observation that both seizures and their medical treatment can cause unwanted changes to physical appearances, such as weight change, hirsutism, and acne. METHOD: Sixty-three adults with epilepsy and 48 age- and gender-matched healthy controls were recruited from a tertiary epilepsy program and targeted social media. Participants completed an online suite of well-validated questionnaires canvassing state (current) and trait (long-term) aspects of body image dissatisfaction, mood, QoL, and medical history. RESULTS: People with epilepsy reported significantly elevated levels of trait body image dissatisfaction compared to controls across the dimensions of appearance evaluation, body areas satisfaction, and self-classified weight (p = 0.02); but did not differ from controls on state body image dissatisfaction (p > 0.05). All facets of body image dissatisfaction in participants with epilepsy were strongly associated with reduced QoL, together with heavier body weight, depressive symptoms, medical comorbidities, and a belief that epilepsy hindered their ability to attain a healthier physique. Multiple regression revealed that body image dissatisfaction was the strongest unique contributor to poor QoL in the epilepsy group (ß = 0.46, p ≤ 0.001), above and beyond the contribution of current depressive symptoms (ß = 0.34, p ≤ 0.01). SIGNIFICANCE: This is the first study to highlight the high rates of body image dissatisfaction among adults with epilepsy, and the significantly detrimental impact it has on patient well-being. It also opens novel avenues for psychological interventions in epilepsy, that focus on enhancing positive body image as a means of holistically improving the often-poor psychological outcomes for people with this condition.

Improving the treatment of functional seizures through a public specialist outpatient clinic.

OBJECTIVES: We performed an audit of the first 12 months of clinical operations to assess the feasibility of a newly established public outpatient clinic for the assessment and treatment of functional (psychogenic nonepileptic) seizures (FS). METHOD: Clinical notes for the first 12 months of the FSclinic weresystematicallyreviewed with data compiled onreferral pathways, clinic attendance, clinical features, treatments, and outcomes. RESULTS: Of eighty-two new FS patients referred to the clinic, over 90% attended. Patients were diagnosed with FS after comprehensive epileptological and neuropsychiatric review, mostly with typical seizure-like episodes captured during video-EEG monitoring, and most accepted the diagnosis. Most had FS at least weekly, with little sense of control and significant impairment. The majority of individuals had significant psychiatric and medical comorbidity. Predisposing, precipitating, and perpetuating factors were readily identified in >90% of cases. Of 52 patients with follow-up data within12 months, 88% were either stable or improved in terms of the control of their FS. CONCLUSION: The Alfred functional seizure clinic model, the first dedicated public outpatient clinic for FS in Australia, provides a feasible and potentially effective treatment pathway for this underserved and disabled patient group.

Principles for delivering improved care of people with functional seizures: Closing the treatment gap.

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.

Postictal Psychosis in Epilepsy: A Clinicogenetic Study.

OBJECTIVE: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation. METHODS: We conducted a case-control cohort study including patients diagnosed with postictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile, and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis; 49 had postictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with postictal psychosis; univariate associations with a p value < 0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated. RESULTS: Cases were more likely to have seizure clustering (odds ratio [OR] = 7.59, p < 0.001), seizures with a recollected aura (OR = 2.49, p = 0.013), and a family history of psychiatric disease (OR = 5.17, p = 0.022). Cases showed predominance of right temporal epileptiform discharges (OR = 4.87, p = 0.007). There was no difference in epilepsy duration, neuroimaging findings, or antiseizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of postictal psychosis cases (n = 58) were significantly higher than in 1,366 epilepsy controls (R2  = 3%, p = 6 × 10-3 ), but not significantly different from 945 independent patients with schizophrenia (R2  = 0.1%, p = 0.775). INTERPRETATION: Postictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (postictal psychosis) in a common disease. ANN NEUROL 2021;90:464-476.

Multidimensional psychopathological profile differences between patients with psychogenic nonepileptic seizures and epileptic seizure disorders.

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 (η2p = 0.05) and group by measure interaction (η2p = 0.03). Simple effects analysis indicated that the PNES group had particularly elevated scores for childhood trauma (ß = 0.78), dissociation (ß = 0.70), and depression (ß = 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 (ß = 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.

Understanding long-term changes in patient identity 15-20 years after surgery for temporal lobe epilepsy.

OBJECTIVE: Following epilepsy surgery, patients can experience complex psychosocial changes. We recently described a longer term adjustment and reframing ("meaning-making") process 15-20 years following surgery for temporal lobe epilepsy, which could involve an ongoing sense of being a "different" person for some patients. Here, we quantitatively examine identity at long-term follow-up and how this relates to meaning-making and postoperative seizure outcome. METHODS: Eighty-seven participants were included: 39 who underwent anterior temporal lobectomy (ATL) 15-20 years ago (59% female; median age = 49.2 years, interquartile range [IQR] = 10; median follow-up = 18.4 years, IQR = 4.4) and 48 surgically naïve focal epilepsy patients (56% female; median age = 34.5 years, IQR = 19). We captured approach to meaning-making by coding for key narrative features identified in our previous qualitative work. Nonparametric tests and correspondence analysis were then used to explore relationships between a quantitative measure of identity and meaning-making, as well as seizure outcome, mood, and health-related quality of life (HRQOL). RESULTS: Patients 15-20 years post-ATL demonstrated a shift toward increasing identity commitment and exploration compared to the surgically naïve cohort, with this shift significantly linked to seizure outcome. Examining the relationship between identity and meaning-making also revealed three groups: (1) those who embraced self-change (29%), (2) those who continued to struggle with this process (60.5%), and (3) those who showed minimal engagement (10.5%). Those who "embraced change" were significantly younger at regular seizure onset and demonstrated a trend toward higher HRQOL. SIGNIFICANCE: Findings suggest that ATL patients show a more developed identity profile compared to surgically naïve controls; however, the majority still struggled with postoperative identity change at long-term follow-up. Approximately one third of patients demonstrated positive psychological growth following surgery, reflected in the ability to embrace change. Findings highlight the importance of understanding the impact of surgery on patient identity to maximize the psychosocial benefits.

Clinical predictors of discordance between screening tests and psychiatric assessment for depressive and anxiety disorders among patients being evaluated for seizure disorders.

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.

Prenatal valproate exposure and adverse neurodevelopmental outcomes: Does sex matter?

OBJECTIVE: Prenatal exposure to the antiepileptic drug (AED) valproic acid (VPA) is associated with an increased risk of impaired postnatal neurodevelopment, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We aimed to evaluate the influence of sex and drug dosage on the association between prenatal VPA exposure and postnatal behavioral outcomes. METHODS: The Australian Pregnancy Register of AEDs was interrogated to identify children aged 4-11 years prenatally exposed to AEDs. Parents reported on their child's behavior using the Autism Spectrum Quotient-Children's Version and the National Institute for Children's Health Quality Vanderbilt Assessment Scale for ADHD. General linear mixed-effects models were used to investigate the relationship between clinicodemographic variables and psychometric scores. RESULTS: A total of 121 children were studied: 54 prenatally exposed to VPA (28 males, 26 females; mean dose ± SD: 644 ± 310 mg/day) and 67 exposed to other AEDs. There was a main effect of sex showing higher ASD scores in males compared to females (p = .006). An interaction between sex and VPA exposure revealed that males had higher ASD symptoms among children exposed to AEDs other than VPA (p = .01); however, this typical sex dynamic was not evident in VPA-exposed children. There was no evidence of any dose-response relationship between VPA exposure and ASD symptoms. Males had higher ADHD scores compared to females, but there was no evidence for a link between ADHD symptoms and VPA exposure. SIGNIFICANCE: Prenatal VPA exposure seems to negate the usual male sex-related predominance in the incidence of ASD. These initial findings deepen the concept of VPA as a "behavioral teratogen" by indicating that its effect might be influenced by sex, with females appearing particularly sensitive to the effects of VPA. No association between VPA doses and adverse postnatal behavioral outcomes was detected, possibly related to the low VPA doses used in this study.

Does continuous positive airways pressure treatment improve clinical depression in obstructive sleep apnea? A randomized wait-list controlled study.

BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with a range of adverse daytime sequelae, including significantly higher rates of clinical depression than is seen in the general community. Improvements in depressive symptoms occur after treatment of the primary sleep disorder, suggesting that comorbid depression might be an intrinsic feature of OSA. However, there are limited data on whether treatment for OSA in patients diagnosed with clinical depression improves mood symptoms meaningfully enough to lead to the remission of the psychiatric diagnosis. METHODS: N = 121 untreated OSA patients were randomized to either continuous positive airway pressure (CPAP) treatment or waitlist control, and depressive symptoms, sleepiness and clinical depression (using a structured clinical interview) were assessed at baseline and 4 months. Linear and logistic regression analyses were conducted, controlling for baseline scores, stratification factors and antidepressant use. RESULTS: Depressive symptoms (odds ratio [OR] = -4.19; 95% confidence interval [CI] = -7.25, -1.13; p = .008) and sleepiness (OR = -4.71; 95% CI = -6.26, -3.17; p < .001) were significantly lower at 4 months in the CPAP group compared to waitlist. At 4 months, there was a significant reduction in the proportion of participants in the CPAP group meeting criteria for clinical depression, compared to the waitlist controls (OR = 0.06, 95% CI = 0.01, 0.37; p = .002). CONCLUSION: Treatment of OSA may be a novel approach for the management and treatment of clinical depression in those with comorbid sleep disordered breathing. Larger trials of individuals with clinical depression and comorbid OSA are needed.

Psychiatric and cognitive characteristics of older adults admitted to a Video-EEG monitoring (VEM) unit.

OBJECTIVE: To compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Adverse events related to antiepileptic drugs.

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.

Positive illusions determine quality of life in drug-resistant epilepsy.

OBJECTIVE: Humans use a complex system of protective cognitive biases or "positive illusions" that foster emotional well-being and subjective quality of life. This study examined the role of positive illusions in patient adjustment to drug-resistant epilepsy and its surgical treatment. METHODS: One hundred fifty people participated, including 93 focal epilepsy patients being evaluated for surgery and 57 sociodemographically matched healthy controls. We purpose-built computer software, "Living With Epilepsy," to assess the impact of positive illusions on patient perceptions of their current life, and administered well-validated questionnaires of depression (Neurological Disorders Depression Inventory for Epilepsy), anxiety (Patient Health Questionnaire for Generalized Anxiety Disorder-7 items), and health-related quality of life (HRQOL; Epilepsy Surgery Inventory-55) before and at 3 and 12 months after surgery. RESULTS: We identified two patient groups: those with "high positive illusions" (53%) about their epilepsy and those with "low positive illusions" (47%), with no differences between sociodemographic or epilepsy variables (all P > .05). Before epilepsy surgery, patients with high positive illusions exhibited fewer symptoms of depression (P < .001) and anxiety (P = .002) and higher HRQOL (P ≥ .002 ≤ 0.046) than those with low positive illusions. A subset of patients proceeded with surgery (n = 34 at 3 months; n = 26 at 12 months). They showed that the beneficial impact of having high positive illusions re-emerged 12 months postsurgery, with patients reporting lower depression and anxiety (P = .006) and elevated HRQOL (P = .036) compared to low positive illusions patients, independent of seizure outcome (P > .05). SIGNIFICANCE: These findings point to an active psychological process in drug-resistant patients, where approximately half generate strong positive illusions about their life with epilepsy, maintaining their mood and subjective well-being. Those who use this psychological mechanism show better adjustment 12 months postsurgery independent of seizure outcome, providing a potential new target for psychological treatment in patients with epilepsy.

Contribution of autobiographic memory impairment to subjective memory complaints in focal epilepsy.

"My memory is terrible!" is a common refrain among people with epilepsy, but such complaints are not reliably linked to poor performances on standard tests of memory. Negative affect like depression and anxiety are the most robust predictor of these complaints; however, neither do they entirely account for the phenomenon. The contribution of autobiographic memory impairment to subjective memory complaints in focal epilepsy has not been well-explored despite autobiographic memory impairments being common in patients with epilepsy, and the face validity of relating day-to-day memory failings to such a personally relevant form of memory. The current study sought to clarify whether autobiographic memory dysfunction contributes to subjective complaints in epilepsy, above and beyond negative affect, objective memory impairment, and epileptological factors in a large sample of patients with drug-resistant focal epilepsy relative to healthy controls (N = 135). Patients were stratified into groups with mesial temporal (MT; n = 40) versus nonmesial temporal (NMT; n = 46) foci. Compared to controls (n = 46), both patient groups reported more bitter subjective memory complaints (p < 0.001, large effect size), demonstrated poorer episodic (p = 0.001, large effect size) and semantic autobiographical recall (p = 0.004, medium effect size), and had higher levels of depressive symptomatology (p = 0.011, medium effect size), and trait neuroticism (p = 0.015, medium effect size). Contrary to expectations, multiple regression analyses revealed that autobiographic memory function was not an independent predictor of subjective memory complaints in either group with epilepsy. In people with epilepsy with MT foci, objective verbal memory dysfunction, neuroticism, and female gender predicted memory complaints (R2 = 0.70, p = 0.015), whereas only neuroticism predicted memory complaints in people with epilepsy with NMT foci (R2 = 0.21, p = 0.001). Although patients' poor recall of their autobiographical memories did not contribute to their concerns about their day-to-day memory function, the findings indicate that the location of the epileptogenic focus can provide clues as to the underlying contributors to subjective memory complaints in focal epilepsy. Important clinical implications to stem from these findings include the need for clinicians to adopt a patient-tailored, multifactorial lens when managing memory complaints in people with epilepsy, taking into account both psychological and cognitive factors.

Affective, neurocognitive and psychosocial disorders associated with traumatic brain injury and post-traumatic epilepsy.

Survivors of traumatic brain injury (TBI) often develop chronic neurological, neurocognitive, psychological, and psychosocial deficits that can have a profound impact on an individual's wellbeing and quality of life. TBI is also a common cause of acquired epilepsy, which is itself associated with significant behavioral morbidity. This review considers the clinical and preclinical evidence that post-traumatic epilepsy (PTE) acts as a 'second-hit' insult to worsen chronic behavioral outcomes for brain-injured patients, across the domains of emotional, cognitive, and psychosocial functioning. Surprisingly, few well-designed studies have specifically examined the relationship between seizures and behavioral outcomes after TBI. The complex mechanisms underlying these comorbidities remain incompletely understood, although many of the biological processes that precipitate seizure occurrence and epileptogenesis may also contribute to the development of chronic behavioral deficits. Further, the relationship between PTE and behavioral dysfunction is increasingly recognized to be a bidirectional one, whereby premorbid conditions are a risk factor for PTE. Clinical studies in this arena are often challenged by the confounding effects of anti-seizure medications, while preclinical studies have rarely examined an adequately extended time course to fully capture the time course of epilepsy development after a TBI. To drive the field forward towards improved treatment strategies, it is imperative that both seizures and neurobehavioral outcomes are assessed in parallel after TBI, both in patient populations and preclinical models.

Autobiographical Memory From Different Life Stages in Individuals With Obstructive Sleep Apnea.

OBJECTIVES: Autobiographical memory dysfunction is a marker of vulnerability to depression. Patients with obstructive sleep apnea (OSA) experience high rates of depression and memory impairment, and autobiographical memory impairments have been observed compared to healthy controls; however, these groups were not age-matched. This study aimed to determine whether individuals with untreated OSA have impaired autobiographical memory when compared to age-matched controls, and to assess the quality of autobiographical memories from three broad time points. METHODS: A total of 44 participants with OSA (M age=49.4±13.0) and 44 age-matched controls (M age=50.0±13.1) completed the Autobiographical Memory Interview (AMI) to assess semantic and episodic memories from three different life stages, and 44 OSA participants and 37 controls completed the Autobiographical Memory Test (AMT) to assess overgeneral memory recall (an inability to retrieve specific memories). RESULTS: OSA participants had significantly poorer semantic recall of early adult life on the AMI (p<.001), and more overgeneral autobiographical memories recalled on the AMT (=.001), than controls. Poor semantic recall from early adult life was significantly correlated with more depressive symptoms (p=0.006) and lower education (p<0.02), while higher overgeneral memory recall was significantly associated with older age (p=.001). CONCLUSIONS: A specific deficit in semantic autobiographical recall was observed in individuals with OSA. OSA patients recalled more overgeneral memories, suggesting that aspects of the sleep disorder affect their ability to recollect specific details of events from their life. These cognitive features of OSA may contribute to the high incidence of depression in this population. (JINS 2019, 25, 266-274).