Exploratory study of blood biomarkers in patients with post-stroke epilepsy.

INTRODUCTION: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. PATIENTS AND METHODS: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. RESULTS: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). DISCUSSION AND CONCLUSION: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

Antiseizure medication withdrawal in adult patients with idiopathic generalized epilepsy: Performance of two seizure recurrence prediction models.

PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.

Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

Risk assessment of long-term epilepsy after de novo status epilepticus with clinical and electroencephalographic biomarkers: The AFTER score.

BACKGROUND: The risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up. METHODS: The study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy. RESULTS: We included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE. A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13-4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03-4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07-3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40-5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3-84.3 %, p < 0.001). CONCLUSIONS: The AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations.

Prediction of long-term unprovoked seizures after status epilepticus.

OBJECTIVE: Possible long-term consequences of status epilepticus (SE) include cognitive and behavioral impairment and the development of chronic epilepsy. However, these aspects have not been systematically studied in clinical practice. We aimed to evaluate long-term seizure recurrence after SE and the potential risk factors for their development. METHODS: Data were obtained from a prospective registry of all SE episodes occurring in adult patients who attended our center from February 2011 to April 2022. Clinical data, electroencephalographic findings, treatment, and long-term data were prospectively recorded. We performed a cross-sectional study of consecutive SE patients without previous epilepsy diagnosis, and analyzed the development of unprovoked remote seizures. RESULTS: A total of 849 patients were registered in the database. After excluding in-hospital mortality (198/849, 23.3%) and patients with prior epilepsy history (291/849, 44.7%), 360 patients (42.4%) with a first SE episode were included. The median age was 68 years (interquartile range [IQR] = 56-79), and 176 patients (48.9%) were women. The median time to first-line treatment initiation was 2 h (IQR = .7-7.4), and it was correlated with SE duration (R = .375, p < .001). One hundred nine patients (30.3%) presented unprovoked seizures during a median follow-up of 1.8 years (IQR = .5-4.3). After adjusting for identifiable confounders in a multivariable Cox regression analysis, progressive symptomatic etiology (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.33, p = .011), time to first-line treatment initiation > 1.5 h (HR = 1.89, 95% CI = 1.25-2.87, p = .003), and superrefractory SE (HR = 2.34, 95% CI = 1.26-4.33, p = .007) were independently associated with a greater risk of unprovoked seizure recurrence. In contrast, older patients (HR = .99, 95% CI = .97-.99, p = .021) and an acute symptomatic etiology (HR = .44, 95% CI .28-.68, p < .001) were at lower risk of unprovoked seizure recurrence. SIGNIFICANCE: The etiology of SE, the delay in initiating SE treatment, and the presence of superrefractoriness have been identified as potentials factors associated with unprovoked remote seizures following a new onset SE. Therefore, prompt and appropriate management should be applied to avoid seizure recurrence.

Relationship between visuoperceptual functions and parietal structural abnormalities in temporal lobe epilepsy.

Progressive gray matter volume reductions beyond the epileptogenic area has been described in temporal lobe epilepsy. There is less evidence regarding correlations between gray and white matter volume changepres and multi-domain cognitive performance in this setting. We aimed to investigate correlations between volume changes in parietal structures and visuospatial performance in temporal lobe epilepsy patients. we performed a cross-sectional study comparing global and regional brain volume data from 34 temporal lobe epilepsy patients and 30 healthy controls. 3D T1-weighted sequences were obtained on a 3.0 T magnet, and data were analyzed using age and sex-adjusted linear regression models. Global and regional brain volumes and cortical thickness in patients were correlated with standardized visual memory, visuoperceptual, visuospatial, and visuoconstructive parameters obtained in a per-protocol neuropsychological assessment. temporal lobe epilepsy patients had smaller volume fractions of the deep gray matter structures, putamen and nucleus accumbens, and larger cerebrospinal fluid volume fraction than controls. Correlations were found between: 1) visual memory and precuneus and inferior parietal cortical thickness; 2) visuoperceptual performance and precuneus and supramarginal white matter volumes; 3) visuospatial skills and precuneus, postcentral, and inferior and superior parietal white matter volumes; 4) visuoconstructive performance and inferior parietal white matter volume. Brain volume loss is widespread in temporal lobe epilepsy. Volumetric reductions in parietal lobe structures were associated with visuoperceptual cognitive performance.

Reponse of second-line treatment in focal status epilepticus: A tertiary hospital experience.

OBJECTIVE: To investigate the response to various antiseizure medications (ASMs) in the treatment of focal status epilepticus (SE) in the established phase, and the effect of administering several ASMs prior to sedation. METHODS: All SE cases in patients aged > 16 years treated with non-BZDs ASMs were prospectively collected in our centre from February 2011 to April 2019. In total, 281 episodes were analysed. RESULTS: Median age at SE onset was 65.1 years; 47 % were focal motor and 53 % focal non-motor episodes. SE cessation was achieved in 79 % episodes with second-line drugs, whereas a third line (anesthetics) was required in 47 episodes. SE cessation was achieved in only 27 % with the first ASM, 48 % with the second, and 51 % with the third. Prompt resolution of the SE episode with a first or second ASM was associated with a better outcome than episodes requiring a larger number of drugs (p = 0.024). The first option in our sample was levetiracetam in 70 % of cases. Among the total of non-responding SE cases treated with levetiracetam as the first ASM option, 107 were subsequently given lacosamide (seizure cessation in 53.3 %) and 34 valproic acid (seizure cessation in 29.4 %) (p = 0.015). CONCLUSION: Our findings further support the notion that early termination of SE with a first or second ASM confers a better functional outcome. The large difference in response between the first ASM and consecutive ones suggests that the sum of different ASMs might be the key to resolving focal SE.

Interictal brain activity changes in temporal lobe epilepsy: A quantitative electroencephalogram analysis.

OBJECTIVES: To evaluate the usefulness of quantitative electroencephalography (qEEG) in the analysis of baseline activity in patients with temporal lobe epilepsy (TLE) and identify measures potentially associated with disease duration and drug resistance. MATERIALS AND METHODS: Cross-sectional study of adult patients with TLE and controls who underwent video-EEG monitoring. Representative artifact-free resting wakefulness baseline EEG segments were selected for quantitative analysis. The fast Fourier transform (FFT) approach was used for the power spectral analysis, with computation of FFT power ratios and alpha-delta and alpha-theta ratios for both hemispheres. The resulting measures were compared between TLE patients and controls and their values as predictors of epilepsy duration and drug resistance analyzed. RESULTS: Thirty-nine TLE patients and 23 controls were included. The TLE patients had a lower alpha-delta ratio in the posterior quadrant ipsilateral to the epileptic focus and a lower alpha-theta ratio in the ipsilateral anterior/posterior quadrants and temporal region. A younger age at onset and longer epilepsy duration correlated with a higher theta power ratio in the contralateral anterior and posterior quadrants and temporal region. No qEEG measures predicted drug resistance. CONCLUSIONS: Quantitative electroencephalography background activity may contribute to the diagnosis of TLE and provide useful information on disease duration. A lower alpha-delta and alpha-theta ratio may be reliable baseline qEEG measures for identifying patients with TLE. A higher contralateral theta power ratio may be indicative of longer epilepsy duration.

The economic burden of newly diagnosed epilepsy in Spain.

OBJECTIVE: The aim of this study was to determine the hospital burden and economic impact of epilepsy in adults in Spain and identify characteristics associated with higher direct medical costs. METHOD: Patients newly diagnosed with epilepsy at the outpatient epilepsy unit of a tertiary hospital in Spain in 2012 were included. Sociodemographic and clinical data and use of health resources were collected retrospectively from electronic medical records from the time of diagnosis to the end of follow-up (2019). Direct costs (in 2012 Euro) were estimated and linear regression models built to explore predictors of higher costs. RESULTS: We studied 110 patients with newly diagnosed epilepsy. Their mean (SD) age was 52.6 (19.6) years and 53.6% were men. Eighty-nine patients (80.9%) had focal epilepsy and 45 (40.9%) had an unknown etiology. At 6 months, 79.1% of patients were classified as responders and 17.6% as having drug-resistant epilepsy. The mean direct cost in the first year of epilepsy diagnosis was €3816.06, 49.7% of which was due to hospital admissions. The mean annual cost per patient was €2584.17, 51.4% of which was due to anti-seizure medications (ASMs). Focal epilepsy and poor response in the first 6 months of treatment predicted higher annual costs, while focal epilepsy and pre-existing comorbidities predicted higher costs in the first year. CONCLUSIONS: The direct cost of newly diagnosed epilepsy in adults in our area is €2584 per patient/year. Anti-seizure medication use is the main cost driver. Focal epilepsy, comorbidities, and poor response to ASMs are independent predictors of higher costs.

Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways.

Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases.

Effect of late-onset epilepsy on cognitive functioning in patients with small vessel disease.

RATIONALE: Late-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease. METHODS: Twenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors. RESULTS: Compared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found. CONCLUSION: Patients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.

Relationship between sleep quality and cognitive performance in patients with epilepsy.

PURPOSE: To investigate the relationship between self-reported sleep quality and cognitive function in patients with epilepsy (PWE), as well as anxiety and depressive symptoms and patient quality of life (QoL). METHODS: This multicenter cross-sectional study included PWE aged ≥12 years who were receiving ≥1 anti-seizure medication (ASM) and had not been diagnosed with a sleep disorder. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Montreal Cognitive Assessment test (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). RESULTS: The study enrolled 150 patients aged 16-83 years, mean age (standard deviation [SD]) 40.6 (15.2) years; 58.7% were female and 75.3% had focal epilepsy. Mean (SD) PSQI score was 4.71 (3.08), 44.4% of patients had impaired sleep quality (PSQI score ≥5), 19.9% had pathologic excessive daytime sleepiness (ESS score >12), and 32.7% had mild cognitive impairment (MoCA score <26). Within the PSQI, sleep disturbance (P = 0.036) and use of sleep medication (P = 0.006) scores were significantly higher in patients with mild cognitive impairment. Multiple regression analysis showed older age (regression coefficient [B], -0.086; 95% confidence interval [CI], -0.127, -0.045; P < 0.001) and the use of sleep medication component of the PSQI [B, -1.157; 95% CI, -2.064, -0.220; P = 0.013) were independently associated with lower MoCA score. Poor sleep quality was associated with probable anxiety and depression symptoms, and directly correlated with reduced QoL. CONCLUSIONS: In PWE, sleep quality was not significantly independently associated with mild cognitive impairment, although poor sleep quality had a negative effect on mood and QoL.

Medium-term effects of COVID-19 pandemic on epilepsy: A follow-up study.

OBJECTIVE: To analyze the medium-term impact of the COVID-19 pandemic on epilepsy patients, focusing on psychological effects and seizure control. METHODS: Prospective follow-up study to evaluate the medium-term effects of the COVID-19 pandemic on a cohort of epilepsy patients from a tertiary hospital previously surveyed during the first peak of the pandemic. Between July 1, 2020, and August 30, 2020, the patients answered an online 19-item questionnaire, HADS, and PSIQ scales. Short- and medium-term effects of the pandemic confinement and the perception of telemedicine were compared. RESULTS: 153 patients completed the questionnaire, mean ± SD age, 47.6 ± 19.3 years; 49.7% women. Depression was reported by 43 patients, significantly more prevalent than in the short-term analysis (29.2% vs. 19.7%; p = .038). Anxiety (38.1% vs. 36.1%; p = 0.749) and insomnia (28.9% vs. 30.9%, p = .761) remained highly prevalent. Seventeen patients reported an increase in seizure frequency (11.1% vs. 9.1%, p = .515). The three factors independently associated with an increase in seizure frequency in the medium term were drug-resistant epilepsy (odds ratio [OR] = 8.2, 95% CI 2.06-32.52), depression (OR = 6.46, 95% CI 1.80-23.11), and a reduction in income (OR = 5.47, 95% CI 1.51-19.88). A higher proportion of patients found telemedicine unsatisfactory (11.2% vs. 2.4%), and a lower percentage (44.8% vs. 56.8%) found it very satisfactory (p = .005). CONCLUSIONS: Depression rates increased significantly after the first wave. Depression, drug-resistant epilepsy, and a reduction in family income were independent risk factors for an increased seizure frequency. Perception of telemedicine worsened, indicating need for re-adaptation.

Factors associated with resistance to benzodiazepines in status epilepticus.

OBJECTIVE: To investigate factors related to benzodiazepine (BZD) resistance in status epilepticus (SE) with a focus on their relationship with the etiology of the episode. METHODS: All SE cases in patients aged >16 years treated with BZDs were prospectively collected in our center from February 2011 to April 2019. The registry included demographics, SE type and etiology, the timing and duration of BZD administration, and the outcome. In total, 371 episodes were analyzed. RESULTS: Median age at SE onset was 61.3 years; the most frequent etiology was acute symptomatic (55.8%). SE with prominent motor symptoms occurred in 63.3%. Median time to BZD administration was 2 h. We studied the correlation between two-time variables: time from SE onset to BZD administration and time from BZD administration to resolution of SE (response); we observed that timely administration correlated with a faster response in patients with prominent motor symptoms (p = 0.017), SE due to a chronic structural cerebral lesion (p = 0.004), and patients with a history of seizures (p = 0.013). In these subgroups (prominent motor symptoms or chronic structural lesion) BZD administration within the first 4.5 h was highly associated with shorter post-BZD SE duration (p < 0.001). SIGNIFICANCE: The relationship between prompt BZD administration and subsequent duration of SE was found to depend to some extent on the etiology of the episode: patients with chronic structural lesions and those with previous epilepsy responded faster to BZDs. Semiology may have also its impact, as the presence of prominent motor symptoms showed also a faster response.

Levetiracetam as first-line monotherapy for Idiopathic Generalized Epilepsy in women.

BACKGROUND: Levetiracetam (LEV) is effective in Idiopathic Generalized Epilepsy (IGE) and seems to be a good alternative to valproic acid in women of childbearing age. However, there is lack of approval for this indication as monotherapy. The aim of this study is to assess the efficacy of LEV as a first-line therapy in this population. METHODS: The study is a descriptive analysis of women aged between 16 and 45 years old diagnosed with IGE and treated with LEV as first-line monotherapy. Minimum follow-up was 24 months. RESULTS: 26 women. Mean age: 25.4 years (17-43). 14 Juvenile Myoclonic Epilepsy; 8 Tonic-Clonic Seizures Alone; 4 Juvenile Absence. Mean follow-up: 68.3 months (24-120). 11 patients (40.7%) continued to take LEV as monotherapy, of which 10 were seizure-free, and three (11.5%) continue to be seizure-free after withdrawing LEV. 12 patients (46.2%) required a change of treatment: 25% (3/12) due to lack of efficacy, 42% (5/12) due to adverse effects and 33% (4/12) due to both. Irritability was the most frequent adverse effect. At the last assessment, three patients (11.5%) continued to have seizures despite polytherapy. Estimated retention rates were 78.1% at one year (SE 7.3%) and 51% at 5 years (SE 9.8%). Estimated median retention time is 72 months (CI 95%: 50.9-93.1). CONCLUSION: LEV could be an effective drug as first-line treatment for IGE in women of childbearing potential. The adverse effects are its main limitation. Comparative studies are needed in order to establish it for this indication.

Incidence and mortality in adults with epilepsy in northern Spain.

OBJECTIVES: We aimed to determine the regional incidence and mortality of adult epilepsy, compare mortality rates with the expected in the general population, and identify predictors of shorter survival. MATERIALS AND METHODS: We included all consecutive newly diagnosed epilepsy visited at a university hospital in Spain throughout 2012. We collected all relevant clinical data up to December 2018. We analyzed the incidence of epilepsy in our catchment area, studied mortality rates, and explored factors predictive of shorter survival. RESULTS: The annual incidence of epilepsy among adults was 37.7 cases/100,000 inhabitants. We studied 110 patients with newly diagnosed epilepsy. Mean age was 52.6 years, and 53.6% were men. Eighty-nine patients (80.9%) had focal epilepsy, 50 (45.5%) had a structural etiology, and 45 (40.9%) had an unknown cause. Nineteen patients died over a median follow-up of 5.3 years. Mortality was almost four times higher than expected in general population and was increased in patients aged 40-59 years. Mortality rates were 5.5%, 12%, and 16.8% in the first, second, and third year, after which they remained stable to the end of follow-up. Independent predictors of mortality were age (p = 0.001), tumor-related epilepsy (p = 0.003), and generalized seizures (p = 0.020). CONCLUSIONS: There is a high incidence of epilepsy among adults in our geographic area, with a mortality rate quadrupling that expected for the general population. Age, generalized seizures, and tumor-related epilepsy are independently associated with a higher risk of death.

The mediating role of epileptic seizures, irritability, and depression on quality of life in people with epilepsy.

PURPOSE: Psychiatric comorbidity is common in epilepsy and has a considerable impact on patient quality of life (QoL). This study aimed to analyze the relationship between seizure frequency, irritability, and depression and describe how they mediate each other's effect on QoL in epilepsy. METHODS: This is a cross-sectional study of consecutive adults seen at an outpatient epilepsy clinic of a tertiary hospital in Barcelona, Spain. All the patients were evaluated for psychiatric comorbidity and administered the State-Trait Anger Expression Inventory-2 (STAXI-2), the Hospital Anxiety and Depression Scale (HADS), and the Quality Of Life in Epilepsy Inventory-10 (QOLIE-10). Mediation analysis with multiple linear regression followed by the Sobel test was performed. RESULTS: We studied 157 patients. Seizure frequency (R = -0.193, P = .053), irritability (R = 0.216, P = .039), and depression (R = -0.598, P < .001) had all a negative effect on QoL. In the adjusted linear regression model, depression was the only independent predictor of impaired QoL (B = -2.453 [95% confidence interval (CI): -3.161, -1.744], P < .001). The Sobel test showed that depression exerted a significant mediating effect on seizure frequency (Z = -1.984; P = .047) and irritability (Z = -3.669; P < .001) in their influence on QoL. CONCLUSION: Depression is an independent predictor of worse QoL and significantly mediated the effects of irritability and poor seizure control on QoL impairment in patients with epilepsy.

Blood biomarkers predictive of epilepsy after an acute stroke event.

OBJECTIVE: Blood biomarkers have not been widely investigated in poststroke epilepsy. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and analyze their association with the development of epilepsy at long term. METHODS: A panel of 14 blood biomarkers was evaluated in patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z-scores. Stroke and epilepsy-related variables were also assessed: stroke severity, determined by National Institutes of Health Stroke Scale (NIHSS) score, stroke type and cause, time from stroke to onset of late seizures, and type of seizure. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with epilepsy. RESULTS: From a cohort of 1115 patients, 895 patients were included. Mean ± standard deviation (SD) age was 72.0 ± 13.1 years, and 57.8% of patients were men. Fifty-one patients (5.7%) developed late seizures, with a median time to onset of 232 days (interquartile range [IQR] 86-491). NIHSS score ≥8 (P < .001, hazard ratio [HR] 4.013, 95% confidence interval [CI] 2.123-7.586) and a history of early onset seizures (P < .001, HR 4.038, 95% CI 1.802-9.045) were factors independently associated with a risk of developing epilepsy. Independent blood biomarkers predictive of epilepsy were high endostatin levels >1.203 (P = .046, HR 4.300, 95% CI 1.028-17.996) and low levels of heat shock 70 kDa protein-8 (Hsc70) <2.496 (P = .006, HR 3.795, 95% CI 1.476-9.760) and S100B <1.364 (P = .001, HR 2.955, 95% CI 1.534-5.491). The risk of epilepsy when these biomarkers were combined increased to 17%. The area under the receiver-operating characteristic (ROC) curve of the predictive model was stronger when clinical variables were combined with blood biomarkers (74.3%, 95% CI 65.2%-83.3%) than when they were used alone (68.9%, 95% CI 60.3%-77.6%). SIGNIFICANCE: Downregulated S100B and Hsc70 and upregulated endostatin may assist in prediction of poststroke epilepsy and may provide additional information to clinical risk factors. In addition, these data are hypothesis-generating for the epileptogenic process.