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.

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.

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.

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.

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.

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 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.

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.

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.

How Does Migraine Change After 10 Years? A Clinical Cohort Follow-Up Analysis.

OBJECTIVE: To describe the 10-year evolution of a cohort of migraine patients, focusing on prognostic factors of improvement. BACKGROUND: Migraine is one of the most prevalent and disabling diseases and migraineurs often want to know about the evolutionary timeline of their condition. Yet, data from longitudinal studies with a long-term follow-up is scarce. METHODS: This is a 10-year longitudinal study. In 2008, we recruited 1109 consecutive migraine patients who answered an initial survey. In 2018, we did a follow-up. We compared initial and final (after 10 years) data. A reduction ≥50% in Headache days/month was considered as improvement. A comparative study was carried out to identify predictors of improvement or no improvement. RESULTS: After 10 years, 380 patients completed the survey (34.3% of the initial cohort), 77.1% (293/380) were women; mean age 41.0 ± 10.6 years and 73.7% (280/380) had an initial diagnosis of episodic migraine (EM). After 10 years, 48.2% (183/380) of patients did not have a medical follow-up of their migraine; 47.4% (180/380) decreased ≥50% in frequency, which increased the proportion of EM (73.7% vs 87.4%) (P < .001) as compared to the initial results. Factors independently associated with improvement were: a baseline frequency >10 days/month (OR[95%]: 3.04 [1.89, 4.89]; P < .001), nonsmoking (2.13 [1.23, 3.67]; P = .006) and a medical follow-up for migraine (2.45 [1.54, 3.90]; P < .001). Additionally, after 10 years, we observed a reduction in the use of preventive treatment (48.7% vs 23.5%) and an increase in monotherapy (42.2% vs 72.7%) (P < .001). CONCLUSION: After 10 years, in almost half of the patients who answered the survey, migraine improved. Other than the natural pathophysiology of migraine, having a medical follow-up and healthy habits such as nonsmoking were independent factors associated with improvement.

Epilepsy in time of COVID-19: A survey-based study.

OBJECTIVES: Collateral damage may occur in epilepsy management during the coronavirus (COVID-19) pandemic. We aimed to establish the impact of this pandemic on epilepsy patients in terms of patient-reported seizure control and emerging symptoms. MATERIALS & METHODS: This is a cross-sectional study including consecutive patients assessed by telephone contact in an epilepsy clinic during the first month of confinement. Demographic and clinical characteristics were recorded, and a 19-item questionnaire was systematically completed. Data regarding the impact of confinement, economic effects of the pandemic, and subjective perception of telemedicine were recorded. Additional clinical data were obtained in patients with a COVID-19 diagnosis. RESULTS: Two hundred and fifty-five patients were recruited: mean age 48.2 ± 19.8 years, 121 (47.5%) women. An increase in seizure frequency was reported by 25 (9.8%) patients. Sixty-eight (26.7%) patients reported confinement-related anxiety, 22 (8.6%) depression, 31 (12.2%) both, and 72 (28.2%) insomnia. Seventy-three (28.6%) patients reported a reduction in economic income. Logistic regression analysis showed that tumor-related epilepsy etiology [OR = 7.36 (95% CI 2.17-24.96)], drug-resistant epilepsy [OR = 3.44 (95% CI 1.19-9.95)], insomnia [OR = 3.25 (95% CI 1.18-8.96)], fear of epilepsy [OR = 3.26 (95% CI 1.09-9.74)], and income reduction [OR = 3.65 (95% CI 1.21-10.95)] were associated with a higher risk of increased seizure frequency. Telemedicine was considered satisfactory by 214 (83.9%) patients. Five patients were diagnosed with COVID-19, with no changes in seizure frequency. CONCLUSIONS: The COVID-19 pandemic has effects in epilepsy patients. Patients with tumor-related, drug-resistant epilepsy, insomnia, and economic difficulties are at a higher risk of increased seizure frequency. Telemedicine represents a suitable tool in this setting.

Efficacy, retention, and safety of brivaracetam in adult patients with genetic generalized epilepsy.

OBJECTIVE: The aim of this study was to evaluate the efficacy, tolerability, and retention of brivaracetam (BRV) in genetic generalized epilepsy (GGE) in real-life practice. METHODS: This is a retrospective cohort study of adult patients with GGE in whom BRV was started between 2016 and 2018, completing a follow-up period of ≥6 months. Clinical and electroencephalogram (EEG) characteristics were analyzed at baseline and at follow-up as outcome measures. RESULTS: Brivaracetam was started in 37 patients (mean age: 29.9 ±â€¯12.3 years; 73% women). Juvenile myoclonic epilepsy was the most common syndrome (43.2%). The primary indications for starting BRV were lack of efficacy (51.4%) and adverse events (AEs) (27%) of other antiepileptic drugs (AEDs). In total, 32.4% of patients received BRV monotherapy. Retention rate at 6 months was 81.1%; 83.8% of patients were considered responders, and 62.2% achieved seizure freedom. The primary reasons for withdrawal were treatment-emergent adverse events (TEAEs, 57.1%) and lack of efficacy (42.9%). The higher number of prior AED use was a risk factor for a lack of response [median = 4 (interquartile range (IQR): 3-4) vs 2 (IQR: 1-3); p < 0.05]. Patients with a previous response to valproic acid tended to have a higher response rate to BRV (86.7% vs 50%, p = 0.169). Eighty-three point eight percent (83.8%) of previous levetiracetam (LEV) responders also showed a good response to BRV. In terms of patients who presented LEV-related AEs, AE resolution was observed in 79.8%, particularly with regard to psychiatric AEs. Follow-up EEGs were compared with baseline EEGs in 25 patients (67.6%) during follow-up. Most patients showed a reduction (52%) or no change (36%) in interictal epileptiform discharge (IED) frequency. SIGNIFICANCE: Brivaracetam shows good responder and retention rates in GGE and is generally well tolerated. It is an appropriate alternative treatment for GGE, especially in refractory epilepsy and when other AEDs are not tolerated.

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.

Vascular risk factors as independent predictors of neurocognitive impairments in patients with late-onset epilepsy who have small-vessel disease.

RATIONALE: Late-onset epilepsy is often accompanied by underlying cerebrovascular disease and has been associated with neurocognitive deficits even dementia, but the interrelation between them remains unknown. In this study, we aimed to explore the contribution of vascular-related and epilepsy-related factors on neurocognitive outcomes in a sample of late-onset epilepsy with history of cerebral small vessel disease. METHODS: In this retrospective cross-sectional study, a comprehensive neurocognitive assessment was performed in 25 patients aged >60 years with one or more unprovoked seizures and history of small-vessel disease. Raw scores of cognitive tests were transformed in T-scores and were grouped in 6 cognitive domains. Regression models were performed to explore the contribution of vascular risk factors (diabetes mellitus, arterial hypertension, dyslipidemia, and smoking habit) and epilepsy-related factors (drug-resistance, number of antiepileptic drugs, age at epilepsy onset, and epileptic focus localization). RESULTS: Diabetes (p = 0.03) and smoking habit (p = 0.05) were the best independent factors to predict attention performance; diabetes also predicted visual memory function (p = 0.02); gender was related to verbal memory performance (p = 0.04) and speed processing (p = 0.02). Age at onset predicted that executive function (p = 0.05); age (p = 0.01) and gender (p = 0.03) were the major contributors to language performance. Epilepsy-related variables did not predict any cognitive outcomes. CONCLUSIONS: Vascular risk factors and sociodemographic characteristics were the best predictors of cognitive outcomes in a sample of late-onset epilepsy with cerebral small-vessel disease. Epilepsy did not show influence on cognitive function. Longitudinal studies are necessary to clarify the relationship between vascular risk factors and epilepsy on progression of cognitive deterioration in patients with late-onset epilepsy. This article is part of the Special Issue "Seizures & Stroke".

Tumor-associated status epilepticus: A prospective cohort in a tertiary hospital.

INTRODUCTION: Tumor-associated status epilepticus (TASE) follows a relatively benign course compared with SE in the general population. Little, however, is known about associated prognostic factors. METHODS: We conducted a prospective, observational study of all cases of TASE treated at a tertiary hospital in Barcelona, Spain between May 2011 and May 2019. We collected data on tumor and SE characteristics and baseline functional status and analyzed associations with outcomes at discharge and 1-year follow-up. RESULTS: Eighty-two patients were studied; 58.5% (n = 48) had an aggressive tumor (glioblastoma or brain metastasis). Fifty-one patients (62.2%) had a favorable outcome at discharge compared with just 30 patients (25.8%) at 1-year follow-up. Fourteen patients (17.1%) died during hospitalization. Lateralized period discharges (LPDs) on the baseline electroencephalography (EEG), presence of metastasis, and SE severity were significantly associated with a worse outcome at discharge. The independent predictors of poor prognosis at 1-year follow-up were SE duration of at least 21 h, an aggressive brain tumor, and a nonsurgical treatment before SE onset. Lateralized period discharges, super-refractory SE, and an aggressive tumor type were independently associated with increased mortality. CONCLUSIONS: Status epilepticus duration is the main modifiable factor associated with poor prognosis at 1-year follow-up. Accordingly, patients with TASE, like those with SE of any etiology, should receive early, aggressive treatment.

Varicella-zoster meningovasculitis in a multiple sclerosis patient treated with natalizumab.

BACKGROUND: Natalizumab is associated with the occasional occurrence of progressive multifocal leukoencephalopathy (PML). While natalizumab-associated PML is well described in multiple sclerosis (MS) patients, herpes and other infections have rarely been reported. OBJECTIVE: To report a case of varicella-zoster (VZV) meningovasculitis in a MS patient treated with natalizumab. METHODS: Case report. RESULTS: A 48-year-old woman diagnosed with MS in treatment with natalizumab (Expanded Disability Status Scale (EDSS): 4.0). After 72 infusions, she complained of a holocraneal headache and a new unsteady gait with diplopia (EDSS: 5.0). A brain and spinal cord magnetic resonance (MR) scan showed a multifocal leptomeningeal enhancing nodular lesions and an angiography revealed irregularity of the proximal segments of cerebral arteries. Testing for VZV DNA by polymerase chain reaction (PCR) amplification was positive in cerebrospinal fluid. Treatment with endovenous acyclovir was started. After clinical improvement (EDSS: 4.5), treatment with natalizumab was restarted associated with oral acyclovir as prophylaxis. CONCLUSION: Neurologists should be aware of other possible neuroinfections besides PML in MS patients under natalizumab.

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.