Cognitive phenotypes in patients with drug-resistant temporal lobe epilepsy: Relationships with cortisol and affectivity.

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) is a neurological disorder characterized by cognitive deficits. This study examined whether patients with TLE and different cognitive phenotypes differ in cortisol levels and affectivity while controlling for demographic and clinical variables. Methods: In this cross-sectional study, 79 adults with TLE underwent neuropsychological evaluation in which memory, language, attention/processing speed, executive function, and affectivity were assessed. Six saliva samples were collected in the afternoon to examine the ability of the hypothalamic-pituitary-adrenal (HPA) axis to descend according to the circadian rhythm (C1 to C6). The cortisol area under the curve concerning ground (AUCg) was computed to examine global cortisol secretion. RESULTS: Three cognitive phenotypes were identified: memory impairment, generalized impairment, and no impairment. The memory-impairment phenotype showed higher cortisol levels at C4, C5, and C6 than the other groups (p = 0.03, η2 = 0.06), higher cortisol AUCg than the generalized-impairment phenotype (p = 0.004, η2 = 0.14), and a significant reduction in positive affectivity after the evaluation (p = 0.026, η2 = 0.11). Higher cortisol AUCg and reductions in positive affectivity were significant predictors of the memory-impairment phenotype (p < 0.001; Cox and Snell R2 = 0.47). CONCLUSIONS: Patients with memory impairment had a slower decline in cortisol levels in the afternoon, which could be interpreted as an inability of the HPA axis to inhibit itself. Thus, chronic stress may influence hippocampus-dependent cognitive function more than other cognitive functions in patients with TLE.

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 antiseizure medication with a very long half-life on long term video-EEG monitoring in focal epilepsy.

PURPOSE: To assess the impact of antiseizure medications (ASMs) with a very long half-life on long term video-EEG monitoring (LTM) in people with focal epilepsy (FE). METHODS: In this retrospective cohort study, we searched our local database for people with FE who underwent ASM reduction during LTM at the University Hospital of 'La Fe', Valencia, from January 2013 to December 2019. Taking into account the half-life of the ASM, people with FE were divided into two groups: Group A contained individuals who were taking at least one ASM with a very long half-life at admission, and Group B consisted of those not taking very long half-life ASMs. Using multivariable analysis to control for important confounders, we compared the following outcomes between both groups: seizure rates per day, time to first seizure, and LTM duration. RESULTS: Three hundred seventy individuals were included in the study (154 in Group A and 216 in Group B). The median recorded seizure rates (1.3 seizures/day, range 0-15.3 vs.1.3 seizures/day, range 0-9.3, p-value=0.68), median time to the first seizure (24 h, range 2-119 vs. 24 h, range 2-100, p-value=0.92), and median LTM duration (4 days, range 2-5 vs. 4 days, range 2-5, p-value=0.94) were similar in both groups. Multivariable analysis did not reveal any significant differences in the three outcomes between the two groups (all p-values>0.05). CONCLUSION: ASMs with a very long half-life taken as co-medication do not significantly affect important LTM outcomes, including recorded seizure rates, time to the first seizure, or LTM duration. Therefore, in general, there is no need to discontinue ASMs with a very long half-life prior to LTM.

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.

Real-life evidence about the use of intravenous brivaracetam in urgent seizures: The BRIV-IV study.

PURPOSE: Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice. METHODS: BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation. RESULTS: A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam. CONCLUSION: IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes.

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.

Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

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.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

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.

Outcome after resective epilepsy surgery in the elderly.

OBJECTIVE: The objective of this study was to compare complications, seizures, and neuropsychological outcomes after resective epilepsy surgery in patients ≥ 60 years of age who underwent operations to younger and matched controls. METHODS: Charts of 2243 patients were screened for operated patients in the authors' center between 2000 and 2015. Patients with available postsurgical follow-up data who were operated on at the age of 60 years or older and matched (by gender, histopathology, and side of surgery) controls who were between 20 and 40 years of age at the time of surgery were included. Outcomes regarding postoperative seizure control were scored according to the Engel classification and group comparisons were performed by using chi-square statistics. RESULTS: Data of 20 older patients were compared to those of 60 younger controls. Postoperative seizure control was favorable in the majority of the elderly patients (Engel classes I and II: 75% at 12 months, 65% at last follow-up), but the proportion of patients with favorable outcome tended to be larger in the control group (Engel classes I and II: 90% at 12 months, p = 0.092; 87% at last follow-up, p = 0.032, chi-square test). The surgical complication rate was higher in the elderly population (65% vs 27%, p = 0.002), but relevant persistent deficits occurred in 2 patients of each group only. Neuropsychological and behavioral assessments displayed considerable preoperative impairment and additional postoperative worsening, particularly of verbal skills, memory (p < 0.05), and mood in the elderly. CONCLUSIONS: The overall favorable postsurgical outcome regarding seizure control and the moderate risk of disabling persistent neurological deficits in elderly patients supports the view that advanced age should not be a barrier per se for resective epilepsy surgery and underscores the importance of an adequate presurgical evaluation and of referral of elderly patients to presurgical assessment.

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)

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

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.

Epilepsy surgery beyond 50 years: Long-term seizure and cognitive outcomes.

INTRODUCTION: Surgery is a well-demonstrated effective treatment for patients with refractory epilepsy. However, there are scarce data about the efficacy in older patients. Endpoint was to evaluate the outcome of epilepsy surgery in pharmacorresistant patients operated in middle-late adulthood. METHODS: We conducted a retrospective observational study including patients who underwent a epilepsy surgery at age ≥ 50. Presurgical clinical data, type of surgery, and postsurgical seizure outcome and neurological complications, including neuropsychological assessment were analyzed. Minimum post-surgical follow-up was 1 year. RESULTS: We identified 38 patients (22 males, 17 females) out of 350 patients who underwent a resective surgery with curative intention in our Epilepsy Unit (12%). Median age at surgery was 56 years (50-69), with median epilepsy duration of 42 years (4-67). Neuroimaging showed focal epileptogenic lesions in 37 patients, mainly mesial temporal sclerosis (21). Presurgical neuropsychological evaluation was available in 38 patients: 35 had deficits, mostly in verbal or visual memory. Twenty-eight patients underwent standard temporal lobectomy with amygdalohippocampectomy, 7 lesionectomy and 4 lobectomy. Median follow-up was 4.46 years (1-9.75). A good outcome was achieved by 86.8% (28 Engel I; 5 Engel II); 5 patients were studied with SEEG, without any complications. None had postsurgical permanent neurological complications. From 22 patients with available post-surgical neuropsychological assessment, 16 scored lower than in pre-surgical one, mainly in memory domain. CONCLUSION: Surgical treatment of long-term refractory epilepsy in patients ≥50 years can be effective and safe. Post-surgical memory decline is a frequent side effect, but with a low impact in daily life.

MONOZEB: Long-term observational study of eslicarbazepine acetate monotherapy.

AIM: The aim of the study was to evaluate the effectiveness and tolerability of eslicarbazepine acetate (ESL) when used as monotherapy for 1 year or more in routine clinical use in patients with focal seizures in epilepsy clinics in Spain. METHODS: This is a retrospective, observational, noninterventional study. Eligible patients were aged ≥18 years, had focal seizures, and started on ESL ≥1 year before database closure. Primary endpoint was the following: proportion seizure-free for ≥6 months at 1 and 2 years. Secondary endpoints included retention on ESL monotherapy at 1 and 2 years, seizure frequency change, seizure worsening, and side effects. Other analyses included seizure freedom from baseline to 1 and 2 years and outcomes in special populations. RESULTS: Four hundred thirty-five patients were included (127 on first-line monotherapy and 308 converting to ESL monotherapy): median daily dose was 800 mg at all time points; 63.2% were seizure-free at 1 year, 65.1% at 2 years, and 50.3% for the entire follow-up. Mean duration of ESL monotherapy was 66.7 months; retention was 88.0% at 1 year and 81.9% at 2 years. Mean reduction in seizure frequency was 75.5% at last visit. Over the entire follow-up, seizure worsening was seen in 22 patients (5.1%), side effects in 28.0%, considered severe in 1.8%, and leading to discontinuation in 5.7%. Dizziness, hyponatremia (sodium <135 mEq/l), and somnolence were the most frequent side effects. Outcomes in special populations (patients aged ≥65 years and those with psychiatric history or learning difficulty) were consistent with the overall population. CONCLUSIONS: Patients with focal seizures taking ESL monotherapy had excellent retention, high seizure-free rates, and good tolerability up to 2 years.

Blood Pressure in Seizures and Epilepsy.

In this narrative review, we summarize the current knowledge of neurally mediated blood pressure (BP) control and discuss how recently described epilepsy- and seizure-related BP alterations may contribute to premature mortality and sudden unexpected death in epilepsy (SUDEP). Although people with epilepsy display disturbed interictal autonomic function with a shift toward predominant sympathetic activity, prevalence of arterial hypertension is similar in people with and without epilepsy. BP is transiently increased in association with most types of epileptic seizures but may also decrease in some, illustrating that seizure activity can cause both a decrease and increase of BP, probably because of stimulation or inhibition of distinct central autonomic function by epileptic activity that propagates into different neuronal networks of the central autonomic nervous system. The principal regulatory neural loop for short-term BP control is termed baroreflex, mainly involving peripheral sensors and brain stem nuclei. The baroreflex sensitivity (BRS, expressed as change of interbeat interval per change in BP) is intact after focal seizures, whereas BRS is markedly impaired in the early postictal period following generalized convulsive seizures (GCS), possibly due to metabolically mediated muscular hyperemia in skeletal muscles, a massive release of catecholamines and compromised brain stem function. Whilst most SUDEP cases are probably caused by a cardiorespiratory failure during the early postictal period following GCS, a profoundly disturbed BRS may allow a life-threatening drop of systemic BP in the aftermath of GCS, as recently reported in a patient as a plausible cause of SUDEP in a few patients.

Desafíos diagnósticos en epilepsia / Diagnostic challenges in epilepsy

Introducción. Las crisis epilépticas y la epilepsia son parte de la práctica clínica diaria en neurología. No obstante, el número de diagnósticos falsos positivos es sorprendentemente alto. Casi uno de cada cinco pacientes tratado por epilepsia en realidad no tiene ese diagnóstico, un porcentaje elevado teniendo en cuenta las consecuencias sociomédicas que conlleva el diagnóstico de epilepsia. Objetivos. Resumir los desafíos diagnósticos más importantes en epilepsia, describir posibles fuentes de error en el diagnóstico y proporcionar consejos sobre cómo evitarlos. Desarrollo. La epilepsia se caracteriza por una tendencia a sufrir crisis epilépticas no provocadas. El mayor obstáculo al diagnosticar una epilepsia radica en que las crisis epilépticas son fenómenos transitorios que ocurren relativamente con poca frecuencia y el médico que realiza el diagnóstico raramente llega a verlas. Además, existen otros eventos clínicos, como por ejemplo síncopes o crisis no epilépticas, que pueden tener una apariencia similar a las crisis epilépticas y, en consecuencia, confundirse con ellas. Finalmente, al interpretar las dos técnicas diagnósticas complementarias más importantes en epileptología, el electroencefalograma y la resonancia magnética cerebral, deben tenerse en cuenta los errores más comunes para prevenir diagnósticos erróneos. Conclusiones. El diagnóstico de una epilepsia es un reto y debe basarse en una historia clínica detallada y específica. Si desde el inicio existen dudas razonables sobre el diagnóstico de epilepsia o si el paciente no responde bien al tratamiento antiepiléptico, recomendamos derivar al paciente a un centro especializado que establezca un diagnóstico definitivo

Introduction. Epileptic seizures and epilepsy are part of daily clinical practice in neurology. Yet, the number of false positive diagnoses is surprisingly high. Almost one out of every five patients treated for epilepsy does not really have this diagnosis, which is a high percentage bearing in mind the social and medical consequences that being diagnosed with epilepsy entails. Aims. To summarise the most important diagnostic challenges in epilepsy, to describe possible sources of diagnostic error and to offer advice on how to avoid them. Development. Epilepsy is characterised by a tendency to suffer unprovoked epileptic seizures. The greatest obstacle when it comes to diagnosing a case of epilepsy is the fact that epileptic seizures are transient phenomena that occur relatively infrequently and the physician who must carry out the diagnosis will rarely see them. Moreover, there are other clinical events, such as syncopes or non-epileptic seizures, that may be similar to epileptic seizures in appearance and, consequently, can be mistaken for them. Finally, when interpreting the two most important complementary diagnostic techniques in epileptology, the electroencephalogram and magnetic resonance imaging of the brain, the most common errors must be taken into account in order to prevent mistaken diagnoses. Conclusions. The diagnosis of epilepsy is a challenge and must be based on a detailed and specific medical record. If there are any reasonable doubts, from the outset, about the diagnosis of epilepsy or if the patient does not respond well to the antiepileptic treatment, we recommend referring the patient to a specialised centre to establish a definitive diagnosis