Prospective study of cenobamate on cognition, affectivity, and quality of life in focal epilepsy.

OBJECTIVE: Cenobamate is a recently approved antiseizure medication that proved to be safe and effective in randomized controlled trials. However, little is known about its impact on some areas frequently affected by epilepsy. For this reason, we explored the effects of cenobamate on cognitive performance, as well as on negative affectivity and quality of life in a sample of patients with drug-resistant epilepsy. METHODS: Two prospective cohort studies were carried out. In Study 1, 32 patients (22 men and 10 women) underwent a baseline (T0) and a short-term (T1) neuropsychological assessment after 3 months of cenobamate administration. In Study 2, 22 patients (16 men and 6 women) from the T1 sample also underwent a baseline and a follow-up evaluation (T2) 6 months after T0. RESULTS: No significant differences were found in cognitive variables, negative affectivity, and quality of life either in Study 1 or Study 2. Similarly, based on the reliable change index, it was found that most patients showed no changes in these variables. SIGNIFICANCE: These results suggest that cenobamate is a safe antiseizure medication in terms of cognition, negative affectivity, or quality of life since no adverse events have been found after 3 and 6 months of treatment. PLAIN LANGUAGE SUMMARY: Cenobamate is a new antiseizure medication. In patients with epilepsy, cenobamate seems to not affect cognition, anxiety, depression, or quality of life.

Impact of Polytherapy on Memory Functioning in Patients With Drug-Resistant Epilepsy: The Role of Attention and Executive Functions.

OBJECTIVE: The aim was to examine the effect of polytherapy (i.e., the number of administered anti-seizure medications (ASMs)) on memory, and whether the interaction between the number of ASMs and attentional/executive functioning affect presurgical memory functioning and postsurgical memory changes in patients with drug-resistant epilepsy. METHODS: Two studies were carried out. Study 1 consisted of a presurgical assessment of 125 adult patients, in which attention/executive function (EpiTrack screening tool) and memory were assessed (cross-sectional study). Of them, 72 patients underwent a second postsurgical evaluation, in which memory was assessed (Study 2). Patients were distributed into groups based on EpiTrack performance and number of ASMs. RESULTS: The interaction between the number of ASMs and the attentional/executive functioning significantly affected presurgical memory, with patients with impaired EpiTrack performance taking three-four ASMs having poorer scores than patients with intact EpiTrack performance taking three-four ASMs (for all, p < .0001). This interaction also affected postsurgical memory changes, with patients with impaired Epitrack performance taking three-four ASMs having higher postsurgical decline than those with intact Epitrack performance taking three-four ASMs (for all, p < .005). No differences were found in patients taking two ASMs. Furthermore, the number of ASMs was associated with presurgical memory performance and postsurgical memory changes only in patients with impaired EpiTrack performance (for all, p < .05). CONCLUSIONS: Our findings underline the utility of EpiTrack, together with the clinical information on the number of prescribed ASMs, to corroborate the impact of polytherapy on memory and to optimize the prediction of postsurgical memory changes.

Stress phenotypes in epilepsy: impact on cognitive functioning and quality of life.

Introduction: Drug-resistant epilepsy has been proposed as a chronic stress model. Stress can be measured in terms of chronicity (epilepsy duration) and intensity (comorbidities), with depression and anxiety among the most important comorbidities in epilepsy due to its prevalence and its relationship with cognitive functioning and quality of life. This study aims to establish phenotypes according to how patients face a stressful condition (epilepsy) and examine differences in cognition and quality of life depending on these phenotypes. We hypothesize that there will be an interrelationship between epilepsy duration and negative affectivity, and these variables will influence cognition and quality of life. Methods: 170 patients (82 men and 88 women) underwent a neuropsychological evaluation in which trait anxiety, depression, attention and executive function, verbal and visual memory, language, emotional recognition, and quality of life were assessed. Hierarchical clustering was performed using z-scores for three variables: trait anxiety; depression; and epilepsy duration. Results: Three clusters were found: vulnerable (high negative affectivity and short duration); resilient (moderate negative affectivity and long duration); and low-impact group (low negative affectivity and short duration). Results show that the vulnerable group had poorer cognitive functioning and quality of life than the other groups. Specifically, the vulnerable group had poorer scores than the low-impact group on verbal memory, visual confrontation naming, and quality of life (except seizure worry). Furthermore, resilient patients had better scores than the low-impact group on cognitive flexibility variables, but lower scores on some quality-of-life subscales (i.e., overall quality of life, emotional well-being, and energy). Finally, the vulnerable group had poorer scores than the resilient group in executive functioning, naming, and quality of life. Discussion: These results suggest that dealing with stress in patients with epilepsy is related to cognitive performance and quality of life. These findings underline the relevance of considering comorbidities in epilepsy and may be useful for detecting vulnerable or resilient profiles as risk or protective factors for cognitive and quality of life decline.

The relationship between memory and quality of life is mediated by trait anxiety in patients with temporal lobe epilepsy.

PURPOSE: Memory deficits are very frequent in patients with drug-resistant epilepsy, but they predict a small proportion of variance of their quality of life (QOL) in previous studies, possibly due to the lack of consideration of mediating factors of this relationship. This study aimed to examine whether trait anxiety mediates the relationship between memory and QOL in this population, controlling the influence of demographic and seizure-related factors. METHODS: In this cross-sectional study, 119 adults with drug-resistant temporal lobe epilepsy (TLE) underwent a neuropsychological evaluation, in which memory, anxiety, and QOL were assessed. RESULTS: In the total sample, better delayed memory had an effect on better QOL indirectly through lower trait anxiety (B = 0.13, SE = 0.06, p = 0.04, abcs = 0.13; κ2 = 0.18; PMind = 0.76). Additionally, delayed memory has not a direct association with QOL (B = 0.04, SE = 0.09, p = 0.64, Cohen's f 2 = 0.005; PMdir = 0.24), and the total effect of delayed memory on QOL tended to reach statistical significance (B = 0.17, SE = 0.10, p = 0.08). The proposed mediation model yielded excellent fit (CFI = 1.00, RMSEA = 0.0001, SRMR = 0.009, and χ2 (1) = 0.50, p = 0.48) and explained 38% of the variance of QOL. CONCLUSION: These findings suggest that trait anxiety is an important factor in understanding the relationship between memory and QOL in patients with TLE, considering the influence of demographic and seizure-related variables, and may have relevant implications for decision-making in this population.

Clinical utility of Epitrack for differentiating profiles and patterns of post-surgical change in memory and quality of life in patients with drug-resistant epilepsy.

PURPOSE: To assess whether performance in attention and executive functions evaluated with the Epitrack screening tool before surgery can differentiate memory and quality of life (QOL) profiles, and detect different post-surgical change patterns in these variables in patients with epilepsy. METHODS: This is a longitudinal study. Seventy-seven patients with drug-resistant epilepsy (mean age = 37.91) underwent a neuropsychological assessment before and one year after surgery. Epitrack, a screening tool that exclusively evaluates attention and executive functioning, was administered in the pre-surgical assessment, and verbal and visual memory and QOL were assessed before and after surgery. RESULTS: Patients with impaired Epitrack performance had poorer verbal and visual memory than those with intact Epitrack performance, regardless of the time point (for all, p < 0.0001). They also showed a post-surgical decline in immediate verbal recall (p = 0.04) and discriminability (p = 0.001). Patients with intact Epitrack performance did not exhibit this decline. Epitrack total score significantly contributed to 13 and 11% of the variance of post-surgical changes in immediate verbal recall and discriminability, respectively. Epitrack groups did not differ in QOL profiles or changes, but post-surgical immediate verbal recall improvements were related to post-surgical QOL improvements. CONCLUSION: Our findings underline the utility of Epitrack screening tool to detect different patterns of verbal and visual memory dysfunction, as well as to predict post-surgical verbal memory decline in patients with drug-resistant epilepsy. Patients with lower pre-surgical Epitrack scores appear to be at increased risk for post-surgical memory decline.

Cardiovascular response to stress in patients with drug-resistant epilepsy: preliminary data / Respuesta cardiovascular al estrés en pacientes con epilepsia farmacorresistente: datos preliminares

Stress is a risk factor for cardiovascular diseases in the general population. Epilepsy has been considered a suitable model of chronic stress with a higher incidence of cardiovascular mortality than the general population. This study provides preliminary data about cardiovascular response to a cognitive stressor and a neuropsychological assessment in patients with epilepsy. It also explores the relationship between cardiovascular response and cognitive performance, depending on the side of seizure focus. Thirty-five patients with drug-resistant epilepsy, 17 with epileptogenic area (EA) in the left hemisphere (LH) and 18 with EA in the right hemisphere (RH), underwent a cognitive stressor and a neuropsychological assessment. The cardiovascular response was recorded throughout both conditions. Results showed that a long-lasting neuropsychological assessment was capable of producing a hemisphere-modulated cardiovascular response with heart rate (HR) decreases (and R-R interval increases) more pronounced in the LH patients than in the RH patients at the post-assessment period (p = .05 and p = .01, respectively). The hemisphere of EA moderated the relationship between cardiovascular response and cognitive performance (for all, p < .03). Our findings may have clinical implications from a preventive perspective since the EA hemisphere may be a relevant factor for coping with stress in people with drug-resistant epilepsy.(AU)

El estrés es un factor de riesgo para las enfermedades cardiovasculares en la población general. La epilepsia se ha considerado un modelo adecuado de estrés crónico, con mayor incidencia de mortalidad cardiovascular que la población general. Este estudio proporciona datos preliminares sobre la respuesta cardiovascular ante un estresor cognitivo y una evaluación neuropsicológica en pacientes con epilepsia, explorando las relaciones entre la respuesta cardiovascular y el rendimiento cognitivo dependiendo del hemisferio responsable de la epilepsia. Treinta y cinco pacientes con epilepsia farmacorresistente, 17 con el área epileptógena (AE) en el hemisferio izquierdo (HI) y 18 con AE en el hemisferio derecho (HD), se sometieron a un estres cognitivo y una evaluación neuropsicológica. La respuesta cardiovascular se registró durante toda la sesión en ambas condiciones. Los resultados mostraron que una evaluación neuropsicológica de larga duración fue capaz de producir una respuesta cardiovascular modulada por el hemisferio, con disminuciones de la frecuencia cardíaca (y aumentos del intervalo RR) más pronunciadas en el período post-evaluación en pacientes con epilepsia del HI que en pacientes con epilepsia del HD (p = .05, p = .01, respectivamente). El hemisferio del AE moderó la relación entre la respuesta cardiovascular y el rendimiento cognitivo (para todos, p < .03). Nuestros hallazgos podrían tener implicaciones clínicas desde una perspectiva preventiva, ya que sugieren que el hemisferio del AE podría ser un factor relevante en el afrontamiento del estrés en personas con epilepsia farmacorresistente.(AU)

Drug load and memory during intracarotid amobarbital procedure in epilepsy.

BACKGROUND: Anti-seizure medications (ASMs) have been related to poor cognitive function, but their relationship with intracarotid amobarbital procedure (IAP) results remains unclear. AIMS OF THE STUDY: To elucidate whether the number and drug load of ASMs are associated with memory scores of the IAP and the neuropsychological assessment. METHODS: Fifty-nine adult patients with drug-resistant epilepsy (mean age = 36.1, SD = 11.6) underwent bilateral IAP (with drawings and words as memory items) and a neuropsychological assessment to assess the risk of post-surgical memory decline. Total ASM drug load was calculated by summing the daily dose/defined daily dose ratio of every ASM of each patient. Pearson's correlations and hierarchical regressions were computed. RESULTS: Total IAP memory score was associated with total ASM drug load (r = -0.30, p = 0.02) and seizure frequency (r = -0.25, p = 0.05). After controlling clinical variables, total ASM drug load explained 16% of the variance of total IAP memory score. This relationship was especially prominent in patients with left hemisphere focus (r = -0.33, p = 0.04). The number of current ASMs was not related to IAP memory score (r = -0.16, p = 0.24). The number or drug load of ASMs were not related to neuropsychological assessment results (for all, p > 0.07). CONCLUSIONS: Our findings suggest that total drug load can be a confounding variable in the IAP memory performance that could explain, at least in part, the reverse asymmetries reported in different studies.

The number of anti-seizure medications mediates the relationship between cognitive performance and quality of life in temporal lobe epilepsy.

OBJECTIVES: To assess whether cognitive performance predicts quality of life (QOL) in patients with drug-resistant temporal lobe epilepsy (TLE), using the Epitrack cognitive screening tool, while considering the mediating role of the number of anti-seizure medications (ASMs) and controlling for seizure-related, social, and emotional factors. METHODS: Seventy-five adult patients with drug-resistant TLE (mean age = 39.76 years, SD = 11.66) underwent a presurgical neuropsychological assessment. MAIN OUTCOME MEASURES: Cognitive performance (Epitrack), depression (BDI-II), trait anxiety (STAI); and QOL (QOLIE-31) were assessed. RESULTS: Adjusting for seizure-related, social, and emotional factors, the Epitrack total score significantly contributed to QOL composite score, and energy and cognitive self-rating subscales. We found a significant indirect effect of the Epitrack total score on QOL composite score and seizure worry and social functioning subscales via the number of ASMs. CONCLUSION: Our findings underline the relevance of cognitive functioning on QOL and the clinical utility of Epitrack to track cognitive side effects of ASMs and, consequently, to predict and manage QOL in this population.