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.

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.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Clinical outcomes of eslicarbazepine acetate monotherapy for focal-onset seizures: A multicenter audit.

OBJECTIVE: To assess the effectiveness and tolerability of eslicarbazepine acetate (ESL) monotherapy in routine clinical practice for the treatment of focal-onset seizures. METHODS: Multicenter, retrospective, observational study conducted in patients older than 16 years treated with ESL as first-line monotherapy or converted to ESL monotherapy from polytherapy or other monotherapy. Outcomes included 1-year retention rate, seizure-free rates after 6 and 12 months of monotherapy treatment, and safety/tolerability issues. RESULTS: A total of 256 patients were included (106 first-line and 150 conversion to monotherapy; 56 patients aged >65 years). Overall, the 1-year retention rate was 79% (72.7% in the ≥65 years subgroup) and seizure-free rates at 6 and 12 months were 59.3% and 55.3% (72.2% and 67.3% in the ≥65 years subgroup), without significant differences when comparing first-line vs conversion-to-ESL monotherapy groups (P = .979). However, the conversion group was heterogeneous and included 43 (29.1%) patients that were seizure free the year prior ESL introduction. A substantially higher proportion of patients remained seizure free for the entire follow-up among those who initiated ESL due to tolerability problems compared with those treated due to inadequate seizure control (71.4% vs 37.3%). Overall, 62 of 256 (24.2%) patients reported AEs (39.3% in >65 years subgroup) and led to discontinuation in 20/256 (7.8%) patients (12.5% in >65 years subgroup). Commonly reported AEs were somnolence (6.6%), dizziness (6.3%), and headache (4.3%). Hyponatremia was recorded in five patients, the majority (4/5) of whom were older than 65 years. CONCLUSIONS: Eslicarbazepine acetate was effective and well-tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal-onset seizures.

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12-month GENERAL study.

OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SIGNIFICANCE: In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.

Control of seizures in different stages of partial epilepsy: LACO-EXP, a Spanish retrospective study of lacosamide.

Lacosamide is approved as adjunctive therapy for focal epilepsies. The number of antiepileptic drugs (AEDs) tried is associated with prognosis. This multicenter, retrospective, observational study (LACO-EXP) in Spain in 500 adult patients with focal epilepsies examined the efficacy and tolerability of add-on lacosamide. Factors associated with better efficacy/tolerability were analyzed. After 12months, the responder rate (≥50% reduction in seizure frequency) was 57.1%, and the seizure-free rate was 14.9%. Efficacy was better when lacosamide was the first or second add-on AED, although there was a small chance to be seizure-free even for patients who had received ≤10 prior AEDs. The mechanism of action of concomitant AEDs is important in all the stages, but differences are smaller in the early stages. Lacosamide was generally well tolerated. A slower dosage-titration schedule was associated with a lower adverse event rate. Further investigation of the timing of initiation of lacosamide add-on therapy and ideal combinations of AEDs is required.

Proposed Recommendations for the Management of Depression in Adults with Epilepsy: An Expert Consensus.

INTRODUCTION: Experts agree that there is a need for protocols to guide health professionals on how to best manage psychiatric comorbidities in patients with epilepsy (PWE). We aimed to develop practical recommendations for key issues in the management of depression in PWE. METHODS: This was a qualitative study conducted in four steps: (1) development of a questionnaire on the management of depression in PWE to be answered; (2) literature review and, if evidence from guidelines/consensus or systematic reviews was available, drafting initial recommendations; (3) a nominal group methodology for reviewing initial recommendations and formulating new recommendations on those issues without available evidence; and (4) drafting and approving the final recommendations. A scientific committee (one neurologist and one psychiatrist) was responsible for the development of the project and its scientific integrity. The scientific committee selected a panel of experts (nine neurologists and nine psychiatrists with experience in this field) to be involved in the nominal group meetings and to formulate final recommendations. RESULTS: Fifteen recommendations were formulated. Four on the screening and diagnosis: screening and diagnosis of depression, evaluation of the risk of suicide, and diagnosis of depression secondary to epilepsy; nine on the management of depression: referral to a psychiatrist, selection of the antiseizure medication, change of antiseizure medication, antidepressant treatment initiation, selection of antidepressant, use of antidepressants during pregnancy, use of psychotherapy, antidepressant treatment duration, and discontinuation of antidepressant treatment; two on the follow-up: duration of the follow-up under usual conditions, and follow-up of patients at risk of suicide. CONCLUSION: We provide recommendations based on expert opinion consensus to help healthcare professionals assess depression in PWE. The detection and treatment of major depressive disorders are key factors in improving epilepsy outcomes and avoiding suicide risk.

Hemicrania continua in a headache clinic: referral source and diagnostic delay in a series of 22 patients.

Hemicrania continua (HC) is a unilateral and continuous primary headache with superimposed exacerbations frequently associated with autonomic features. Diagnostic criteria of HC, according to II Edition of International Classification of Headache Disorders require complete response to indomethacin. HC is probably misdiagnosed more often than other primary headaches. We aim to analyze characteristics of a series of 22 consecutive cases of HC. We recruited patients from a headache outpatient clinic in a tertiary hospital over a 3-year period (January 2008 to January 2011). We prospectively gathered demographic and nosological characteristics and considered referral source and delay between onset of headache and diagnosis of HC. Twenty-two patients (14 females, 8 males) out of 1,150, who attended the mentioned clinic during the inclusion period (1.9 %) were diagnosed with HC. All cases responded to indomethacin. No patient received a diagnosis of HC before attending our headache office. Mean latency of diagnosis was 86.1 ± 106.5 months (range 3-360). 11 patients (50 %) were referred from primary care, with 9 (40.9 %) from other neurology clinics and 2 (9.1 %) from other specialities offices. According to our series, HC is not an infrequent diagnosis in a headache outpatient clinic. Diagnostic delay is comparable to data collected in previous studies. As HC is frequently misdiagnosed, we thing there is a need for increasing the understanding of this entity, potentially responsive to indomethacin.

High prevalence of end-stage renal disease of unknown origin in Aguascalientes Mexico: role of the registry of chronic kidney disease and renal biopsy in its approach and future directions.

BACKGROUND: Chronic kidney disease (CKD) is one of the pathologies with the greatest impact on the public health system. Over the last few decades, the relevance of CKD in Mexico has increased, with associated overwhelming costs for care of renal disease. There are no reliable CKD statistics in Mexico. METHODOLOGY: In June 2018, the government of Aguascalientes called on all Health Institutions to create a state registry of treated end-stage renal disease (ESRD). In the same system, a renal biopsy result registry included all the native kidney biopsies obtained in the state of Aguascalientes since 2012. We herein describe the prevalence, incidence and characteristics of the patients included in the CKD and renal biopsy registry in the state of Aguascalientes. RESULTS: As of April 2020, the state has documented 2827 patients on renal replacement therapy (RRT), 1877 on dialysis and 950 that have been transplanted. The prevalence of patients on dialysis is 1326 per million population (p.m.p.), and if transplanted individuals are included, it is 1997 p.m.p. The incidence of treated ESRD in 2019 was 336 p.m.p. (n = 474) in individuals with an average age of 45.6 years (standard deviation ±18), and in a higher proportion of men (61%). There is a bimodal distribution of the age at which RRT was initiated. The first and the most significant peaks are between the ages of 20 and 40 years and are usually the result of CKD of unknown cause (73%). The second peak is between 50 and 70 years of age, and CKD is usually the result of diabetes mellitus and systemic arterial hypertension (59.6%). Since January 2012, 423 biopsies have been recorded. The patient's ages were between 20 and 30 years (n = 112), and the most frequent diagnosis was focal segmental glomerulosclerosis (FSGS) (54%). CONCLUSIONS: The prevalence of treated ESRD in the state of Aguascalientes is high. The disease mostly afflicts young people between 20 and 40 years of age, and there is a clear male predominance. In this age group, the main clinical diagnosis is CKD of unknown origin, and the most frequent biopsy diagnosis was FSGS.

Effectiveness and Safety/Tolerability of Eslicarbazepine Acetate in Epilepsy Patients Aged ≥ 60 Versus < 60 Years: A Subanalysis from the Euro-Esli Study.

INTRODUCTION: Clinical practice studies help guide antiepileptic drug (AED) therapy in patient groups routinely excluded from clinical trials, such as the elderly. The Euro-Esli study investigated the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) when used in everyday clinical practice in Europe. A subanalysis of data from elderly patients (≥ 60 years) included in the Euro-Esli study was conducted to assess these aspects of ESL use in this population. METHODS: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness parameters included responder (≥ 50% seizure frequency reduction) and seizure freedom rates after 3, 6 and 12 months of treatment and at last visit. Safety and tolerability were assessed throughout the follow-up by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Data were compared for patients aged ≥ 60 versus those aged < 60 years at study entry. RESULTS: Euro-Esli included 2058 patients (mean age 44.0 years). Age at study entry was known for 2057 patients, of whom 358 (17.4%) and 1699 (82.6%) were aged ≥ 60 and < 60 years, respectively. Mean maximum ESL dose was   882.0 and 1008.2 mg/day in patients aged ≥ 60 and < 60 years, respectively  (p < 0.001). At all timepoints, responder and seizure freedom rates were significantly higher in patients aged ≥ 60 versus < 60 years; for example, at 12 months, responder rates were 83.9 and 73.7%, respectively (p = 0.002), and seizure freedom rates were 58.5 and 37.1%, respectively (p < 0.001). The incidence of AEs was significantly higher in patients aged ≥ 60 versus < 60 years (41.4 vs. 32.5%; p = 0.001), but the rate of discontinuation due to AEs was comparable between age groups (16.2 vs 13.1%; p = not significant). The safety/tolerability of ESL in patients aged ≥ 60 years was consistent with its known    profile. CONCLUSION: Eslicarbazepine acetate was efficacious and generally well tolerated when used to treat elderly patients with focal epilepsy in clinical practice, with no new or unexpected safety signals emerging in this setting. FUNDING: Eisai Ltd.

Early add-on lacosamide in a real-life setting: results of the REALLY study.

BACKGROUND AND OBJECTIVES: Many patients with epilepsy are treated with antiepileptic drug (AED) polytherapy. Several factors influence the choice of early add-on therapy, and deciding on the most appropriate drug can be difficult. This study aimed to assess the efficacy and tolerability of lacosamide as early add-on therapy in patients with partial-onset seizures. METHODS: REALLY (REtrospective study of lAcosamide as earLy add-on aLong one Year) was a multicenter, retrospective, 1-year, real-life study. Patients included were aged older than 16 years, had partial-onset seizures, and were treated with lacosamide as add-on therapy after one or two prior AEDs. Data were collected retrospectively from clinical records. The primary study objective was to assess the efficacy of lacosamide over 12 months (seizure-free and responder rates), and the secondary objective was to assess the tolerability of lacosamide at 3, 6, and 12 months [adverse events (AEs) and discontinuation]. RESULTS: One hundred and ninety-nine patients were enrolled in the study; 89 patients (44.7 %) had tried one AED and 110 patients (55.3 %) had tried two AEDs before lacosamide. At 12 months, the proportion of patients who were seizure free was 44.9 %, and 76 % of patients were responders. The seizure-free rate at 12 months for patients who had previously received one or two AEDs was 58 and 34.3 %, and the responder rate at 12 months was 83.0 and 70.4 %, respectively. The AE rate was 21.5 % at 3 months, 27.1 % at 6 months, and 31.2 % at 12 months, with 7.0 % of patients discontinuing treatment because of an AE. The most common AE reported was dizziness (11.6 %). Cryptogenic epilepsy, a higher number of prior AEDs, and the use of a sodium channel blocker at onset were associated with a worse outcome. The number of concomitant AEDs decreased over 1 year (Z = 5.89; p < 0.001). Twenty-two patients were converted to lacosamide monotherapy with at least one evaluation ≥6 months from the beginning of monotherapy conversion. CONCLUSIONS: Lacosamide was effective and well tolerated as early add-on treatment in patients who had received one or two previous AEDs.

Early clinical experience with lacosamide as adjunctive therapy in patients with refractory focal epilepsy and nocturnal seizures.

This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13-24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p>0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures.

Síndrome cardio-digital (holt-oram): a propósito de un caso: Maternidad Concepción Palacios Caracas / Cardio digital (holt-oram) syndrome: case report Maternidad Concepción Palacios

Se presenta el caso de una paciente de 33 años. IIg. Op. 1 aborto con embarazo de 30 semanas y diagnóstico ecográfico de hidropesía fetal, oligohidramnios severo e hidronefrosis bilateral. Se realizó cesárea a las 31 semanas de gestación por perfil biofísico fetal comprometido. Nace con múltiples malformaciones, peso al nacer 1400 g y talla 38 cm, se evidenció ausencia del pulgar derecho e hipoplasia marcada del antebrazo. Las características físicas, de laboratorio y el estudio genético son compatibles con un síndrome de Holt-Oram. El recién nacido fallece al 4to día de vida