Aspectos radiológicos, clínicos, ultrasonográficos y bioquímicos en pacientes con ictus y foramen oval permeable, y su relación con la recurrencia de ictus

Consultable des del TDXTítol obtingut de la portada digitalitzadaCada año más de 30000 españoles quedan discapacitados tras sufrir un infarto cerebral. A esta cifra hay que sumar una muy cercana de familiares que cambian radicalmente de vida y se dedican en cuerpo y alma a cuidar de estas personas. En la actualidad, más de 150000 personas necesitan de otra que les cuide el resto de sus vidas. El estudio Isedic (Impacto social de los enfermos dependientes por ictus) demuestra que el 45 % de las personas que sobreviven a un ictus sufre secuelas físicas y mentales importantes (Informe ISEDIC, 2004). La incidencia anual de ictus es de entre 150-200 casos por cada 100000 habitantes con una prevalencia de entre 500 y 600 casos / 100000. Esto implica que en una ciudad como Barcelona de 10 a 12 personas sufren un ictus por primera vez, lo que representa unos 4000 nuevos ictus al año. En la actualidad en España el ictus constituye la segunda causa de muerte en los varones y la primera en las mujeres, representando el 11,5 % del total de fallecimientos en nuestro país. Además representa la primera causa de incapacidad física en las personas adultas. Todo esto conlleva un importante porcentaje del gasto sanitario, sin tener en cuenta el coste económico que supone para una familia un enfermo con ictus (Vázquez, Revista española de la economía de la salud, 2005). El ictus es un trastorno, transitorio o permanente, en una zona del parénquima encefálico secundario a una alteración de los vasos sanguíneros. Según la naturaleza de la lesión encefálica se distinguen dos grandes tipos de ictus (Álvarez Sabín, Patología cerebrovascular isquémica, 2000): Isquémico: debido a una falta de aporte a una determinada zona del parénquima encefálico. Hemorrágico: causado por la rotura de un vaso sanguíneo encefálico con extravasación de sangre fuera del torrente vascular

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

Effectiveness; Focal epilepsy; PerampanelEficacia; Epilepsia focal; PerampanelEfectivitat; Epilèpsia focal; PerampanelIntroduction: The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. Methods: This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results: The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). Discussion: This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.The study received funding from Eisai Ltd. Editorial assistance was provided by John Scopes of mXm Medical Communications and funded Eisai Ltd

PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice

Effectiveness; Focal epilepsy; TolerabilityEficacia; Epilepsia focal; TolerabilidadEficàcia; Epilèpsia focal; TolerabilitatThe PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness assessments included 50% responder rate (≥ 50% reduction in seizure frequency from baseline) and seizure freedom rate (no seizures since at least the prior visit); in PWE with status epilepticus, response was defined as seizures under control. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 5193 PWE. Retention, effectiveness and safety/tolerability were assessed in 4721, 4392 and 4617, respectively. Retention on PER treatment at 3, 6, and 12 months was 90.5%, 79.8%, and 64.2%, respectively. Mean retention time on PER treatment was 10.8 months. The 50% responder rate was 58.3% at 12 months and 50.0% at the last visit, and the corresponding seizure freedom rates were 23.2% and 20.5%, respectively; 52.7% of PWE with status epilepticus responded to PER treatment. Overall, 49.9% of PWE reported AEs and the most frequently reported AEs (≥ 5% of PWE) were dizziness/vertigo (15.2%), somnolence (10.6%), irritability (8.4%), and behavioral disorders (5.4%). At 12 months, 17.6% of PWEs had discontinued due to AEs. PERMIT demonstrated that PER is effective and generally well tolerated when used to treat people with focal and/or generalized epilepsy in everyday clinical practice.This study was funded by Eisai Ltd. Editorial assistance in the preparation of this manuscript was funded by Eisai Ltd

Long-Term Treatment with Citicoline Prevents Cognitive Decline and Predicts a Better Quality of Life after a First Ischemic Stroke

Stroke, as the leading cause of physical disability and cognitive impairment, has a very significant impact on patients' quality of life (QoL). The objective of this study is to know the effect of citicoline treatment in Qol and cognitive performance in the long-term in patients with a first ischemic stroke. This is an open-label, randomized, parallel study of citicoline vs. Usual treatment. All subjects were selected 6 weeks after suffering a first ischemic stroke and randomized into parallel arms. Neuropsychological evaluation was performed at 1 month, 6 months, 1 year and 2 years after stroke, and QoL was measured using the EuroQoL-5D questionnaire at 2 years. 163 patients were followed during 2 years. The mean age was 67.5 years-old, and 50.9% were women. Age and absence of citicoline treatment were independent predictors of both utility and poor quality of life. Patients with cognitive impairment had a poorer QoL at 2 years (0.55 vs. 0.66 in utility, p = 0.015). Citicoline treatment improved significantly cognitive status during follow-up (p = 0.005). In conclusion, treatment with long-term citicoline is associated with a better QoL and improves cognitive status 2 years after a first ischemic stroke

Onset of efficacy and adverse events during Cenobamate titration period

Cenobamate; Drug-resistant epilepsy; SeizuresCenobamato; Epilepsia resistente a los medicamentos; ConvulsionesCenobamat; Epilèpsia resistent a medicaments; ConvulsionsObjectives Cenobamate is an antiseizure medication (ASM) approved in Europe as adjunctive therapy for adults with inadequately controlled focal seizures. This post hoc analysis reports onset of efficacy and characterizes time to onset, duration, and severity of the most common treatment-emergent adverse events (TEAEs) during cenobamate titration. Materials & Methods Adult patients with uncontrolled focal seizures taking 1 to 3 concomitant ASMs were randomized to receive adjunctive cenobamate or placebo (double-blind studies C013 and C017) or cenobamate (open-label study C021). Outcome assessments included efficacy (median percentage change in seizure frequency and onset [studies C013 and C017]) and safety (onset, duration, and severity of TEAEs [all studies]). Results Onset of efficacy was observed by Weeks 1 to 4 of titration in studies C013 and C017 which used a faster titration schedule than study CO21. In study C013, the median percentage seizure frequency reduction was 36.7% in patients receiving cenobamate versus 16.3% in those taking placebo (p = .002); in study C017, significant differences in seizure frequency emerged in Week 1 and continued throughout titration between all cenobamate groups and placebo (p < .001). The most commonly reported TEAEs were somnolence, dizziness, fatigue, and headache, with first onset of each reported as early as Week 1; however, the majority resolved. Conclusions Reductions in seizure frequency occurred during titration with initial efficacy observed prior to reaching the target dose. These reductions were regarded as clinically meaningful because they may indicate early efficacy at lower doses than previously expected and had a considerable impact on patient quality of life. Long-term treatment with adjunctive cenobamate was generally safe and well-tolerated.The double-blind studies and open-label study were funded by SK Life Science, Inc. (Paramus, NJ, USA). Study data were pooled and analyzed by Angelini S.p.a. Nicole Day, PhD, of MedVal Scientific Information Services, LLC (Princeton, NJ, USA) provided medical writing assistance, funded by Angelini S.p.a. The manuscript was prepared according to the International Society for Medical Publication Professionals' “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

Psychosocial Factors and Antiepileptic Drug Use Related to Delayed Diagnosis of Refractory Psychogenic Nonepileptic Seizures

OBJECTIVE: We analyzed clinical and psychosocial factors in patients with refractory psychogenic nonepileptic seizures, seeking characteristics that could hasten diagnosis. BACKGROUND: Psychogenic nonepileptic seizures remain a diagnostic challenge. Prognosis is best if patients are treated within 2 years of symptom onset. Psychosocial factors have been shown to provide important information for differential diagnosis. METHODS: Over a year and 1132 consecutive patients, our hospital's Epilepsy Unit suspected 93 patients of having psychogenic nonepileptic seizures and confirmed refractory psychogenic nonepileptic seizures in 67. We referred these patients to our psychiatric consultation unit for detailed diagnostic interviews, and 53 of the patients followed through. Two months after the psychiatric evaluation we gave them a psychiatric intervention, explaining the diagnosis and treating their comorbidities. We also tracked the patients' use of antiepileptic drugs for 3 months, from just before the psychiatric evaluation until a month after they started the intervention. RESULTS: Women, patients with an inadequate primary support group, and patients who had tried many antiepileptic drugs were most likely to have their diagnosis of psychogenic nonepileptic seizures delayed by >2 years after onset. A stepwise logistic regression showed that the 2 best predictors of late diagnosis were lack of availability of a primary support group and patients trying many antiepileptic drugs. CONCLUSIONS: Clinicians evaluating patients with questionable seizures should raise their suspicion of psychogenic nonepileptic seizures especially in female patients with an insufficient primary support group and a history of taking multiple antiepileptic drugs

Overnight switch from levetiracetam to brivaracetam: safety and tolerability

Brivaracetam; Epilepsy; TolerabilityBrivaracetam; Epilepsia; TolerabilidadBrivaracetam; Epilèpsia; TolerabilitatBrivaracetam is a newer antiseizure medication than levetiracetam. It has a more selective action on the synaptic vesicle glycoprotein 2A binding site, and it seems to provide a more favorable neuropsychiatric profile. The aim of this study was to assess the safety and tolerability of an overnight switch from levetiracetam to brivaracetam. This was a retrospective descriptive study including patients with epilepsy treated with levetiracetam, who switched due to inefficacy or previous adverse events (AEs). In total, forty-one patients were included (mean age 40.9 ± 17.8 years, women 48.8%). Focal epilepsy represented 75.6% (n = 31) of patients (structural cause [n = 25], unknown cause [n = 6]). Four patients had idiopathic generalized epilepsy, two had developmental and epileptic encephalopathy and four patients were unclassified. The reason to start brivaracetam was inefficacy in 53.7% (n = 22), AEs in 65.9% (25/27 neuropsychiatric) and both in 19.5% (n = 8). Brivaracetam-related AEs were reported in 24.4%. Neuropsychological AEs associated with the previous use of levetiracetam improved in 76% of patients. Treatment was discontinued in 19.5% patients. Patients’ reported seizure frequency improved, worsened and remained stable in 26.8%, 12.2%, and 61.0% of the cases, respectively. An overnight switching to brivaracetam is safe and well tolerated. This treatment can improve levetiracetam-related neuropsychiatric AEs

Seizures after Ischemic Stroke: A Matched Multicenter Study

Accidente cerebrovascular isquémico; Tratamiento de reperfusión; Factores de riesgoIschemic Stroke; Reperfusion treatment; Risk factorsAccident cerebrovascular isquèmic; Tractament de reperfusió; Factor de riscObjective The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. Methods We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. Results In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. Interpretation Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy

Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke

Biomarcador; Endostatina; Accident cerebrovascular isquèmicBiomarcador; Endostatina; Accidente cerebrovascular isquémicoBiomarker; Endostatin; Ischemic strokeStroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke.This work has been funded by Instituto de Salud Carlos III (PI18/00804) and by La Fundació La Marató (Reg. 84/240 proj. 201702). Neurovascular Research Laboratory takes part in the Spanish stroke research network INVICTUS+ (RD16/0019/0021). L.R. is supported by a pre-doctoral fellowship from the Instituto de Salud Carlos III (IFI17/00012)

L'ús dels biomarcadors plasmàtics (CKMB i BNP) facilita la detecció de patologies embòliques en l'ictus isquèmic agut

Per avaluar la utilitat dels biomarcadors en el diagnòstic etiològic de l'ictus agut, es van estudiar pacients amb ictus isquèmic agut no lacunar, en els quals es va fer una exploració cardiològica i es van determinar els biomarcadors plasmàtics seleccionats (CKMB, pèptid natriurètic cerebral(BNP), D-dímer, mioglobina i troponina I). Els pacients amb fibril·lació auricular i els pacients amb patologia embòlica en l'estudi amb ecocardiograma transtoràcic(ETT) van mostrar nivells més elevats de CKMB i BNP respecte els pacients amb ritme sinusal i estudi ETT normal, respectivament. Després de la regressió logística, CKMB i BNP es mantenien com a predictors independents de font embòlica