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The 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.

Haemorrhagic transformation (HT) of ischaemic infarction occurs when an area of brain infarction is stained with blood products, mainly red blood cells. An abnormally permeable blood–brain barrier resulting from ischaemia of the capillary endothelium allows this extravasation of blood products. HT is part of the natural history of some forms of ischaemic infarction, especially cerebral embolism, but it can be precipitated or enhanced by therapeutic interventions used in the acute phase of ischaemic stroke. The old view of HT after cerebral embolism as a generally asymptomatic change in a tissue that is already necrotic has been challenged by observations from therapeutic thrombolysis that suggest that HT can have a negative effect on patients' outcomes. Understanding of the risk factors for and the underlying mechanisms and clinical variability of HT in the context of acute therapeutic interventions in ischaemic stroke could help in the early detection of this complication, in determining the safety of recanalisation approaches, and in setting the stage for future research into the prevention or treatment of HT in patients with acute ischaemic stroke.

Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

Stroke 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 < 0.001). Moreover, endostatin > 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.

Objective. Nocturnal seizures are usually underestimated and represent a major problem in adult patients with epilepsy. Our aim was to study the effectiveness of perampanel for the treatment of nocturnal seizures in adult patients with epilepsy. Methods. Observational study of a prospectively acquired sample of adult patients with focal and generalized epilepsy in which perampanel was started from January to October 2021 in a specialized epilepsy unit in a tertiary hospital. Demographic and clinical characteristics were recorded. All patients completed a follow-up period of at least 3 months. Seizure frequency during the 6-month period before the patient started treatment was obtained from medical records. Retention and responder rates (considered as a nocturnal seizure frequency reduction of ≥50%) and improvement of subjective sleep disturbances were analyzed as outcome measures. Results. Forty-eight patients were included (mean age 39.8±17.4; 60.4% men), and 38 of them had a 6-month follow-up. Focal epilepsy was the most common diagnosis (81.3%), and most patients had a structural etiology (56.3%). Thirty-four (70.8%) patients had drug-resistant epilepsy. The mean nocturnal seizure frequency per month at baseline was 13.2±35.9. Fifteen (31.3%) patients had subjective sleep disturbances at baseline, of which insomnia was the most frequent complaint (16.7%). Perampanel was started at a median dose of 4 mg/day (range=2-14). At 3-month follow-up, the retention rate was 74.6%; 64.6% were considered responders (54.2% were seizure-free). Monthly nocturnal seizures decreased significantly at 3 months (8.2±26.7 vs. 13.2±35.9 seizures/month; p=0.044) and 6 months (5.3±18.2 vs. 13.2±35.9 seizures/month; p=0.006). Subjective sleep disturbances improved at 3-month follow-up (10.4% vs. 31.3%; p=0.002) and 6-month follow-up (10.5% vs. 31.3%; p=0.022). Significance. Perampanel can be a suitable treatment option in adult patients with both focal and generalized epilepsy with nocturnal seizures and can reduce the presence of sleep complaints.

Objective Drug‐resistant epilepsy (DRE) leads to a range of medical and social consequences, which contribute to a high disease burden. We aimed to describe factors associated with an increased medical burden in DRE. Methods We designed a longitudinal prospective study including adult people with epilepsy (PWE) who visited at least once in an outpatient clinic of a tertiary hospital during 2023. Demographic and clinical data were collected. Emergency department (ED) consultations and antiseizure medications (ASM) were documented at each visit. Information comes from a structured data warehouse integrated into an electronic health record designed for the follow‐up of PWE and used systematically in clinical practice. Patients were categorized into drug‐responsive or drug‐resistant epilepsy (DRE) according to the ILAE criteria. Results Of 2835 patients (51% men) and 4935 outpatient visits, 785 (27.7%) had DRE. Drug resistance was more common in focal epilepsy (29.7% vs. 19.6% in generalized epilepsy; p < 0.001), in younger patients (44.1 ± 17.8 vs. 51.1 ± 20.7 years; p < 0.001), and with a younger onset (24.3 ± 22.4 vs. 42.4 ± 26 years; p < 0.001). DRE accounted for a higher rate of outpatient consultations [median per patient/year: 2 (1–3) vs. 1 (1, 2); p < 0.001], ED consultations (25.5% vs. 16.9%; p < 0.001) and traumatic injury resulting from seizures (1.7% vs. 0.5%; p = 0.01). ASM changes were more frequent in DRE (61.1% vs. 32.2, %; p < 0.001). Significance Systematic data collection using electronic health records enables comprehensive identification of epidemiological and clinical factors associated with DRE. Earlier age at onset and focal epilepsy contribute to a higher disease burden, along with more frequent follow‐up visits and increased adjustments in ASM.

Data from 44 pooled clinical practice studies were compared for epilepsy patients with focal-onset and/or generalised-onset seizures treated with perampanel (PER) as early (n=632) versus late add-on therapy (n=1900). Retention was assessed after 3, 6 and 12 months of PER treatment. Effectiveness assess- ments comprised responder rate (≥50% seizure frequency reduction), seizure freedom rate and rate of unchanged or worsening seizure frequency. Adverse events (AEs) and discontinuation due to AEs were evaluated. Retention was significantly higher with early versus late add-on therapy at all timepoints. At last visit, seizure freedom rate was significantly higher with early versus late add-on therapy (40.1% vs. 8.7%; p<0.001), as was responder rate (73.0% vs. 36.4%; p<0.001); and the proportion of patients with unchanged seizure frequency was significantly lower in the early versus late add-on group (10.2% vs. 31.8%; p<0.001), as was worsening seizure frequency (6.1% vs. 13.6%; p<0.001). Patients treated with early versus late add-on therapy had a significantly lower incidence of AEs (41.8% vs. 54.5%; p<0.001), psychi- atric AEs (18.3% vs. 22.2%; p=0.046), and discontinuation rates due to AEs at 12 months (15.0% vs.18.7%; p=0.045). In conclusion, PER was significantly more effective and better-tolerated as early add-on therapy in everyday clinical practice.Supported by Eisai.

Cryptogenic stroke represents a diagnostic challenge. Several conditions have been found to be more frequent in patients with cryptogenic stroke. Aortic arch atheroma (AAA) and patent foramen ovale (PFO) have been shown to be highly prevalent in the adult population, especially in patients with ischemic cerebrovascular events, particularly cryptogenic strokes. In both conditions, clinical relevance and stroke risk are related to age, with AAA being more frequent and severer in patients >55 years, and the relationship between stroke and PFO being stronger in those <55 years of age. This review is focused on the prevalence, risk of stroke and therapeutic strategies in patients with cryptogenic stroke related to AAA or PFO.

BackgroundIn addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke.MethodsWe analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs.ResultsSeizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0–6 points) had low COSY (0.7%–11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3–13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7–13 points) had the highest risk (14%–92%).ConclusionsPersonalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Purpose. Brivaracetam (BRV), an antiseizure medication indicated for focal-onset seizures, has shown efficacy in the treatment of focal to bilateral tonic-clonic seizures (FBTCS). We aimed to determine the effectiveness and safety of BRV in patients with FBTCS and generalized tonic-clonic seizures (GTCS). Methods. We performed a multicenter, retrospective, longitudinal study in adult patients with epilepsy who experienced at least one FBTCS or GTCS before starting BRV (baseline visit). Data were collected from consecutive outpatient visits over a 4-year period. All patients had been followed for at least 3 months before the baseline visit and completed a minimum follow-up of 3 months after starting BRV. Response (≥50% reduction in FBTCS/GTCS frequency) and retention rates, as well as seizure freedom and presence of adverse events at 3, 6, and 12 months, were recorded as outcome measures. Results. 114 patients were included (mean age 36.3±18.0 years, 52% male, 36.6% genetic generalized epilepsy); 94 had a 12-month follow-up period. At 12 months’ follow-up, the response rate was 83%, and 73.4% of patients were FBTCS/GTCS-free. Retention was 79% at 12 months. Adverse events occurred in 29.8% of patients, the most common being drowsiness (14.9%). No significant differences were found in response rates between FBTCS and GTCS. Drug resistance was independently associated with lower response and seizure freedom rates at follow-up. The absence of a titration period predicted seizure freedom and response at 3 months. Conclusions. BRV is an effective and well-tolerated treatment in patients with focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures.