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Introduction: Antiplatelets and oral anticoagulants are commonly used to treat patients with various cardiovascular and cerebrovascular diseases. However, the primary concern for clinicians remains the risk of bleeding, thus necessitating the development of new therapies. Milvexian is a new anticoagulant that inhibits factor XIa, preventing the pathological formation of thrombi without increasing bleeding risk., Areas Covered: This drug evaluation examines the pharmacokinetic properties of milvexian and provides information on its pharmacodynamics and clinical efficacy in treating some cerebrovascular conditions., Expert Opinion: Milvexian shows a good pharmacokinetic profile with low renal elimination rates, justifying its use in patients with a high degree of renal impairment, and without relevant drug-drug interactions. In patients affected by acute non-cardioembolic ischemic stroke or high-risk transient ischemic stroke, milvexian, in addition to dual antiplatelet therapy, seems to have a positive efficacy profile without any safety concerns, especially in terms of intracranial hemorrhage. Two phase 3 trials are ongoing to investigate the efficacy and safety of milvexian for preventing cardioembolic and non-cardioembolic ischemic stroke.

Background: Rehabilitation is currently the best available treatment for post-stroke disability. There is, however, great variability in the proportion of patients accessing rehabilitation across high-income countries suggesting that factors not explained by facilities availability or guidelines diversity may intervene in decision-making., Objectives: To evaluate which factors are associated with appropriate post-stroke rehabilitation referrals in a tertiary stroke unit setting., Methods: Retrospective single-center cohort study including patients admitted to the Stroke Unit of the "Santa Maria della Misericordia" University Hospital, Udine (IT) from January 1st to December 31st, 2019. Information regarding stroke severity (National Institute of Health Stroke Scale), functional assessment (modified Rankin scale [mRS] and Barthel index [BI]), length of hospital stay, and rehabilitation pathway was collected. Outcome was defined as referral to the appropriate rehabilitation pathway. Appropriateness was assessed comparing patient clinical information at discharge against local criteria for intensive vs. extensive rehabilitation. A mixed-linear effect model was built to explore NIHSS, mRS, and BI variation over time. Multivariable logistic regression was used to estimate the adjusted-odds ratio (OR) and 95% confidence interval (CI 95%) of appropriate assignment to rehabilitation pathways., Results: 288 patients were included in the study (age 73.1 years, males 57.9%) and in 75.7%, the rehabilitation pathway assignment was appropriate. NIHSS at discharge was lower compared to admission but no effect of rehabilitation assignment was evident, while mRS scores at discharge and at three months were 2.6 (CI 95% 2.2; 3.0) and 2.1 (CI 95% 1.8; 2.5) higher compared to admission (p < 0.0001). Rehabilitation assignment effect on mRS was time dependent, resulting in an additional - 0.6 (CI 95% - 1.0; - 0.2) lowering at discharge for those appropriately assigned (p = 0.003), with a trend for significance at three months (p = 0.08). BI score was higher at discharge (p < 0.0001), and appropriate assignment was associated with higher scores (p = 0.01). Multivariate analysis showed that the OR of appropriate rehabilitation pathway assignment were reduced by higher mRS (0.60 [CI 95% 0.48; 0.76], p < 0.0001) and increased by higher NIHSS (1.11 [CI 95% 1.04; 1.19], p = 0.001) scores at discharge. The latter finding might be explained by the rehabilitation assessment focus on post-stroke motor symptoms captured by NIHSS., Conclusions: Higher mRS and lower NIHSS levels at discharge were independent predictors for inappropriate rehabilitation assignment after stroke in our cohort. These findings may reflect a therapeutic bias toward patients with higher post-stroke disability in a rehabilitation framework heavily tilted on post-stroke motor symptoms., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double-blind, placebo-controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral hemorrhage or acute ischemic stroke were randomized to receive ESL 800 mg/d or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is the occurrence of a first unprovoked seizure within 6 months after randomization ("failure rate"). Secondary efficacy assessments include the occurrence of a first unprovoked seizure during 12 months after randomization and during the entire study; functional outcomes (Barthel Index original 10-item version; National Institutes of Health Stroke Scale); post-stroke depression (Patient Health Questionnaire-9; PHQ-9); and overall survival. Safety assessments include the evaluation of treatment-emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behavior (PHQ-9 question 9). The protocol aimed to randomize approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID-19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomized. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk., Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures., Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022., Exposures: Type of acute symptomatic seizure., Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke)., Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy., Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Non-contrast computer tomography detects the presence of hyperdense middle cerebral artery sign (HMCAS). Studies on the prognostic value of HMCAS among patients undergoing mechanical thrombectomy (MT) are conflicting. A retrospective analysis of consecutive patients with acute ischemic stroke due to middle cerebral artery occlusion, presenting with or without HMCAS, who underwent MT, was performed. We enrolled 191 patients (HMCAS +, n = 140; HMCAS -, n = 51). Prevalence of successful recanalization was significantly higher in patients with HMCAS than in those without HMCAS (92.1% versus 74.5%, p = 0.001). Patients with HMCAS had a better clinical outcome than those HMCAS - (54.3% versus 37.3%, p = 0.037, for three-month favorable outcome; 62.9% versus 39.3%, p = 0.004, for major neurological improvement at discharge; 8.6% versus 19.6%, p = 0.035, for in-hospital mortality; 14.3% versus 27.5%, p = 0.035, for intracranial hemorrhage; 2.9% versus 17.6%, p = 0.001, for symptomatic intracranial hemorrhage). Multivariate analyses confirmed that HMCAS represents an independent predictor of three-month favorable outcome (OR 2.48, 95% CI 1.10-5.58, p = 0.028), major neurological improvement at discharge (OR 2.40, 95% CI 1.09-5.20, p = 0.030), in-hospital mortality (OR 0.29, 95% CI 0.010-0.81, p = 0.018), presence of ICH (OR 0.49, 95% CI 0.25-0.97, p = 0.042) and presence of SICH (OR 0.16, 95% CI 0.04-0.63, p = 0.009). HMCAS presence predicts favorable outcome in patients undergoing MT. This result may indicate that hyperdense clots are more likely to respond to MT than isodense ones. This effect is mediated by reduction in hemorrhagic transformation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polysomnography (PSG) is a fundamental diagnostical method for the detection of Obstructive Sleep Apnea Syndrome (OSAS). Historically, trained physicians have been manually identifying OSAS episodes in individuals based on PSG recordings. Such a task is highly important for stroke patients, since in such cases OSAS is linked to higher mortality and worse neurological deficits. Unfortunately, the number of strokes per day vastly outnumbers the availability of polysomnographs and dedicated healthcare professionals. The data in this work pertains to 30 patients that were admitted to the stroke unit of the Udine University Hospital, Italy. Unlike previous studies, exclusion criteria are minimal. As a result, data are strongly affected by noise, and individuals may suffer from several comorbidities. Each patient instance is composed of overnight vital signs data deriving from multi-channel ECG, photoplethysmography and polysomnography, and related domain expert's OSAS annotations. The dataset aims to support the development of automated methods for the detection of OSAS events based on just routinely monitored vital signs, and capable of working in a real-world scenario., (© 2022. The Author(s).)

Objective: 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. ANN NEUROL 2021;90:808-820., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Acute cerebrovascular disease, particularly ischemic stroke, has emerged as a serious complication of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the Coronavirus disease-2019 (COVID-19). Accumulating data on patients with COVID-19-associated stroke have shed light on specificities concerning clinical presentation, neuroimaging findings, and outcome. Such specificities include a propensity towards large vessel occlusion, multi-territory stroke, and involvement of otherwise uncommonly affected vessels. Conversely, small-vessel brain disease, cerebral venous thrombosis, and intracerebral hemorrhage appear to be less frequent. Atypical neurovascular presentations were also described, ranging from bilateral carotid artery dissection to posterior reversible encephalopathy syndrome (PRES), and vasculitis. Cases presenting with encephalopathy or encephalitis with seizures heralding stroke were particularly challenging. The pathogenesis and optimal management of ischemic stroke associated with COVID-19 still remain uncertain, but emerging evidence suggest that cytokine storm-triggered coagulopathy and endotheliopathy represent possible targetable mechanisms. Some specific management issues in this population include the difficulty in identifying clinical signs of stroke in critically ill patients in the intensive care unit, as well as the need for a protected pathway for brain imaging, intravenous thrombolysis, and mechanical thrombectomy, keeping in mind that "time is brain" also for COVID-19 patients. In this review, we discuss the novel developments and challenges for the diagnosis and treatment of stroke in patients with COVID-19, and delineate the principles for a rational approach toward precision medicine in this emerging field., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Italy is one of the most affected countries by the coronavirus disease 2019 (COVID-19). The responsible pathogen is named severe acute respiratory syndrome coronavirus (SARS-CoV-2). The clinical spectrum ranges from asymptomatic infection to severe pneumonia, leading to intensive care unit admission. Evidence of cerebrovascular complications associated with SARS-CoV-2 is limited. We herein report six patients who developed acute stroke during COVID-19 infection., Methods: A retrospective case series of patients diagnosed with COVID-19 using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs, who developed clinical and neuroimaging evidence of acute stroke during SARS-CoV-2 infection., Results: Six patients were identified (5 men); median age was 69 years (range 57-82). Stroke subtypes were ischemic (4, 67%) and hemorrhagic (2, 33%). All patients but one had pre-existing vascular risk factors. One patient developed encephalopathy prior to stroke, characterized by focal seizures and behavioral abnormalities. COVID-19-related pneumonia was severe (i.e., requiring critical care support) in 5/6 cases (83%). Liver enzyme alteration and lactate dehydrogenase (LDH) elevation were registered in all cases. Four patients (67%) manifested acute kidney failure prior to stroke. Four patients (67%) had abnormal coagulation tests. The outcome was poor in the majority of the patients: five died (83%) and the remaining one (17%) remained severely neurologically affected (mRS: 4)., Conclusions: Both ischemic and hemorrhagic stroke can complicate the course of COVI-19 infection. In our series, stroke developed mostly in patients with severe pneumonia and multiorgan failure, liver enzymes and LDH were markedly increased in all cases, and the outcome was poor.

Aim of the Study: The aim of the study was to evaluate the clinical characteristics of patients with previous stroke (either ischemic or hemorrhagic), who developed status epilepticus (SE) mimicking a stroke relapse., Materials and Methods: We performed a retrospective cohort study of patients brought to hospital by the emergency service between December 2016 and January 2018 with a stroke code as possible candidates for intravenous thrombolysis and who had already have a previous stroke. Among them, patients admitted for negative symptoms and finally discharged with a diagnosis of SE mimicking stroke were selected and their clinical characteristics collected. All patients underwent routine blood sample analysis, head computed tomography (CT) scan and, when indicated, CT angiography and CT-perfusion imaging of the head. After admission in our stroke unit, an Electroencephalogram (EEG) was performed within 3 h in patients suspected with SE, then classified according to International League Against Epilepsy (ILAE) classification (2015). Outcome measures were SE duration, antiepileptic drugs (AEDs) administered, mortality at 12 months, Engel scale, and modified Rankin scale (m-RS) at 6 months. A second cohort included those consecutive patients discharged with a true stroke relapse in the same considered time span. Clinical characteristics of these two cohorts were compared using Mann-Whitney test or Student t-test (Confidence Interval (C.I.) 95%, p < 0.05) for continuous variable and Fisher exact test or Pearson-Chi test for dichotomic variables (p < 0.05). Survival rates were calculated, and a Log-Rank test was performed to evaluate differences in survival distribution. Only in the group with SE, m-RS at 6 months and recurrence of SE were also evaluated., Results: Eleven patients were discharged with a diagnosis of SE mimicking stroke and 65 patients with stroke relapse. Temporal lobe localization was significantly more represented in group with SE (p = 0.036) while there was no difference regarding age, sex, and National Institutes of Health Stroke Scale (NIHSS). The m-RS was significantly higher in patients with hemorrhage relapse, mainly due to the high incidence of amyloid angiopathy in this subgroup. Status epilepticus recurred in 36.4% of patients, presenting with the same clinical features, and most patients (62.5%) achieved a good seizure control at 6 months (Engel scale = 1). A difference in mortality at 12 months (all cause considered) appeared only when distinguishing strokes between ischemic and hemorrhagic (Chi-Square: 10.711, p < 0.005)., Discussion and Conclusion: Status epilepticus is not infrequent in patients with previous stroke and may present with negative neurological symptoms, thus mimicking a stroke recurrence. EEG should be considered as a potential diagnostic tool in the acute stroke setting, at least in patients with previous stroke. This article is part of the Special Issue "Seizures & Stroke"., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Sporadic small vessel disease (SVD) has high prevalence in aging population and stroke patients, but also in younger asymptomatic subjects. In this last group it can represents a prelude to stroke and cognitive impairment. Still nowadays, its pathogenesis is unclear. 35 consecutive patients with SVD at brain MRI and 35 age- and sex-matched controls, between January 2016 and February 2018, underwent an extended screening for thrombophilia, autoimmunity and evaluated levels of blood markers of inflammation and endothelial activation. Asymmetric DiMethyl Arginine (ADMA) levels proved higher in patients (70.44 ± 36.25 ng/ml vs. 46.58 ± 30.67 ng/ml; p = 0.004), also after controlling for confounding factors. ADMA levels showed positive correlation with Fazekas score (r = 0.304; p = 0.01). ROC curve analysis showed a moderate accuracy in discriminating patients and controls (AUC = 0.70; CI 0.57-0.82; p = 0.004): a cut-off of 46 ng/ml is associated with 80% sensitivity, but limited (54%) specificity. Higher ADMA levels characterize selected subjects with sporadic SVD, asymptomatic for vascular diseases and without latent inflammatory conditions or coagulopathy. This reinforces the hypothesis of the key role of endothelial dysfunction in SVD. Further studies should explore the cause-effect relationship between ADMA pathway and SVD.

Paraneoplastic cerebellar degeneration (PCD) is usually thought to have a subacute progression over several weeks. We report herein incidence and clinical features of hyperacute onset PCD, a vertebrobasilar stroke mimic. We performed a retrospective analysis of all suspected PCD cases referred to the Udine University Hospital between 2009 and 2017. Our center provides the only neuroimmunology laboratory for three provinces of the Friuli-Venezia Giulia region, Italy (983,190 people as of January 1, 2017). Inclusion criteria were (1) abrupt onset of neurological symptoms; (2) initial consideration of a vascular etiology; (3) final diagnosis of "definite PCD." We also carried out a systematic review of the literature in order to identify previous stroke-like PCD cases. Between 2009 and 2017, 24 patients received a final diagnosis of PCD. The age-standardized incidence rate of PCD was 0.22/100,000 person-years. Two cases (8.3%) had a stroke-like onset, with an incidence of 0.02/100,000 person-years. Additionally, 10 previously reported stroke-like PCD cases were identified. Among all cases (n = 12), 67% were female; median age was 51 years (range, 22-69). An associated cancer was discovered in all cases. Brain imaging was normal in most (75%) of the patients. Cerebrospinal fluid (CSF) analysis showed inflammatory alterations in 73% of the cases. Cancer treatment was more effective than immunotherapy in improving the neurological syndrome. Typical patients with hyperacute PCD are middle-aged women with normal brain imaging, inflammatory markers in CSF, and cancer. Surgery of the underlying cancer is probably the best treatment. PCD must be considered in the differential diagnosis of acute-onset ataxia and/or vertigo.

Background: Epilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy., Methods: We selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018., Results: Renin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives., Conclusions: Current evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.

Patients at short-term risk of paroxysmal atrial fibrillation (PAF) often exhibit increased RR interval variability during sinus rhythm. We studied if RR dynamic analysis, applied in the first hours after stroke unit (SU) admission, identified acute ischemic stroke patients at higher risk for subsequent PAF episodes detected within the SU hospitalization. Acute ischemic stroke patients underwent continuous cardiac monitoring (CCM) using standard bedside monitors immediately after SU admission. The CCM tracks from the first 48 h were analyzed using a telemedicine service (SRA clinic, Apoplex Medical, Germany). Based on the RR dynamics, the stroke risk analysis (SRA) algorithm stratified the risk for PAF as follows: low risk for PAF, high risk for PAF, presence of manifest AF. The subsequent presence/absence of PAF during the whole SU hospitalization was ruled out using all available CCMs, standard ECGs, or 24-h Holter ECGs. Two hundred patients (40% females, mean age 71 ± 16 years) were included. According to the initial SRA analysis, 111 patients (56%) were considered as low risk for PAF, 52 (26%) as high risk while 37 patients (18%) had manifest AF. A low-risk level SRA was associated with a reduced probability for subsequent PAF detection (1/111, 0.9%, 95% CI 0-4.3%) while a high-risk level SRA predicted an increased probability (20/52, 38.5% (95% CI 25-52%). RR dynamic analysis performed in the first hours after ischemic stroke may stratify patients into categories at low or high risk for forthcoming paroxysmal AF episodes detected within the SU hospitalization.

Background: Stroke is one of the leading causes of acquired epilepsy in adults. An instrument to predict whether people are at high risk of developing post-stroke seizures is not available. We aimed to develop and validate a prognostic model of late (>7 days) seizures after ischaemic stroke., Methods: In this multivariable prediction model development and validation study, we developed the SeLECT score based on five clinical predictors in 1200 participants who had an ischaemic stroke in Switzerland using backward elimination of a multivariable Cox proportional hazards model. We externally validated this score in 1169 participants from three independent international cohorts in Austria, Germany, and Italy, and assessed its performance with the concordance statistic and calibration plots., Findings: Data were complete for 99·2% of the predictors (99·2% for Switzerland, 100% for Austria, 97% for Germany, and 99·7% for Italy) and 100% of the outcome parameters. Overall, the risk of late seizures was 4% (95% CI 4-5) 1 year after stroke and 8% (6-9) 5 years after stroke. The final model included five variables and was named SeLECT on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). The lowest SeLECT value (0 points) was associated with a 0·7% (95% CI 0·4-1·0) risk of late seizures within 1 year after stroke (1·3% [95% CI 0·7-1·8] within 5 years), whereas the highest value (9 points) predicted a 63% (42-77) risk of late seizures within 1 year (83% [62-93] within 5 years). The model had an overall concordance statistic of 0·77 (95% CI 0·71-0·82) in the validation cohorts. Calibration plots indicated high agreement of predicted and observed outcomes., Interpretation: This easily applied instrument was shown to be a good predictor of the risk of late seizures after stroke in three external validation cohorts and is freely available as a smartphone app. The SeLECT score has the potential to identify individuals at high risk of seizures and is a step towards more personalised medicine. It can inform the selection of an enriched population for antiepileptogenic treatment trials and will guide the recruitment for biomarker studies of epileptogenesis., Funding: None., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures., Methods: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study., Results: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS., Conclusions: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation., (© 2015 S. Karger AG, Basel.)

Background: Stroke incidence in high-income countries is reported to decrease, and new data on stroke incidence and outcome are needed to design stroke services and to ameliorate stroke management., Methods: This study is part of a two-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), Friuli-Venezia Giulia region, northeast of Italy, between 1 April 2007 and 31 March 2009. Overlapping sources for case finding were used, combining hot and cold pursuit., Results: We identified 784 stroke cases, 640 (81.6%) incident. The crude overall annual incidence rate per 100,000 residents was 256 (95% confidence interval 241-271) for all strokes and 209 (95% confidence interval 195-223) for first-ever strokes. Incidence rate for first-ever strokes was 181 (95% confidence interval 155-211) after adjustment to the 2007 Italian population and 104 (95% confidence interval 88-122) compared with the European standard population. Incidence rates for first-ever strokes was 215 (196-235) for women, 202 (183-223) for men. Crude annual incidence rates per 100,000 population were 167 (153-178) for ischemic stroke, 31 (26-37) for intracerebral hemorrhage, 8.1 (5.7-11.4) for sub-arachnoid hemorrhage, and 4.6 (2.8-7.1) for undetermined stroke. Overall case fatality rates for first-ever stroke were 20.6% at 28 days and 30.2% at 180 days., Conclusions: Our study shows incidence rates higher than previously reported in our region but not supporting the view of higher incidence rates in Northern than in Southern Italy. Results contribute to time-trends analysis on epidemiology, useful for dimensioning services in Italy and show the persistence of a gap between the outcome of stroke in Italy and that of the best performing European countries, urging to adopt better stroke management plans., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background and Purpose: Long obstructive sleep apnoeas (LOSAs) can cause brain ischaemia through paradoxical embolism since they can lead to right to left shunting (RLSh) but this has never been assessed as a risk factor for stroke. We investigated whether the combination of LOSA and RLSh is associated with ischaemic stroke or transient ischaemic attack (TIA) on waking (wake-up stroke)., Methods: We prospectively considered patients aged over 18 years, admitted to 13 stroke units for acute ischaemic stroke or TIA. Patients had to be able to give consent, to specify whether the event occurred on waking, and to cooperate sufficiently to undergo contrast transcranial Doppler examination and cardiorespiratory sleep study within 10 days of the onset of symptoms. Single LOSA events, lasting 20 s or more, were considered a possible harbinger of RLSh., Results: Between April 2008 and March 2010, 335 patients (109 women; 61 TIA, mean age 64 years) were enrolled; 202 (60%) had at least one LOSA and 116 (35%) a RLSh; 69 (21%) had both. There were significantly more wake-up strokes/TIAs in subjects with RLSh plus LOSA than those without this association (27/69 vs 70/266; OR 1.91, controlled for age, sex, hypertension, diabetes, atrial fibrillation, antithrombotic therapy; 95% CI 1.08 to 3.38; p=0.03). No other risk factor was associated with an increase in the incidence of events on waking., Conclusions: The study suggests that the combination of LOSA and RLSh could be a new major, potentially treatable risk factor for cerebrovascular ischaemic events.

Background and Purpose: The importance of transient ischemic attack (TIA) lies on the short-term risk of stroke, and the ABCD2 score may improve early stroke risk prediction. However, population-based studies are still needed. We aimed to provide data on TIA incidence and to evaluate the ABCD2 predictive ability for early recurrent stroke in a population-based study., Methods: This study is part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153 312 inhabitants), Friuli Venezia Giulia region, northeast of Italy, between April 1, 2007 and March 31, 2009. Multiple overlapping sources for finding cases were used, combining hot and cold pursuit., Results: We identified 178 TIA, 161 (90.4%) of which were incident. The crude overall annual TIA incidence rate per 1000 residents was 0.52 (95% confidence interval [CI], 0.45-0.61). Incidence rate was 0.45 (95% CI, 0.31-0.65) when standardized to the 2007 Italian population and 0.25 (95% CI, 0.16-0.39) when standardized to the European standard population. Estimates of stroke risk after the index TIA within 2, 7, 30, and 90 days were, respectively, 2.5% (95% CI, 0.7-6.2), 5.6% (95% CI, 2.6-10.3), 6.2% (95% CI, 3.0-11.1), and 11.2% (95% CI, 6.8-17.1). ABCD2 score was strongly associated with stroke occurrence after index TIA: the areas under the receiver operating characteristic curve at 2, 7, 30, and 90 days were, respectively, 0.85 (95% CI, 0.72-0.97), 0.69 (95% CI, 0.56-0.82), 0.69 (95% CI, 0.56-0.85), and 0.76 (95% CI, 0.67-0.86). No patients with an ABCD2 score <4 had a stroke within the 90-day follow-up period., Conclusions: This study adds new data on TIA incidence and prognosis and it further validates the ability of the ABCD2 score to identify patients at early risk for stroke.

Background and purpose: Stroke has been described as a COVID-19 complication. However, its occurrence rate, risk factors, and causal relationships are still not well established. Methods: We describe the characteristics of confirmed COVID-19-related strokes among all cases of COVID-19 hospitalized in our health network, from November 1, 2020 to April 30, 2021. Risk factor analysis has been conducted for ischemic stroke (IS), which represents 92% of all confirmed cases of Covid-19-related strokes, and a "causal attribution to infection" classification is provided. Results: In all, 62/4105 hospitalized COVID-19 patients had an acute stroke (1.51%). Severe COVID-19 (OR 2.27--CI 1.06-4.77; p = 0.032), atrial fibrillation (OR 3.65--CI 1.63-7.98; p = 0.001), and ischemic heart disease (OR 4.590--CI 1.714-12.137; p = 0.002) proved to be independent risk factors for IS, while obesity was a protective factor (OR 0.90--CI 0.82-0.97; p = 0.012). COVID-19 had a causal role in 32.1% of IS cases, was a relevant cofactor in 28.6% of cases of IS, and was a possible trigger in 39.3% of events. Conclusion: Our stroke occurrence rate is consistent with other populationbased reports (range 0.34-2.7%). Prespecified peculiar clinical and radiological features allow the distinction between "IS caused by COVID-19" and "IS triggered by COVID-19." Clinical history of vascular diseases and risk factors is crucial in determining the risk of IS in patients with COVID-19. However, the protective effect of a BMI > 30 kg/m2 seems to suggest an obesity paradox. [ABSTRACT FROM AUTHOR]

Introduction: It is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are "disabling" or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS. Methods: We included all consecutive patients admitted for AIS at our institution fromJanuary 2015 to May 2022 who presented a baseline NIHSS score of 0-5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scoredmore than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database. Results: After the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0-1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment. Discussion: This observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS. [ABSTRACT FROM AUTHOR]

Introduction: Mechanical thrombectomy (MT) is the first line treatment in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Approximately half of patients treated with MT does not have a favorable outcome 3months after stroke. The aim of this study was to identify predictors of futile recanalization (FR) in patients with LVO treated with MT. Methods: A retrospective analysis of consecutive patients with acute ischemic stroke due to anterior circulation LVO who underwent MT. Patients with a TICI score of 2b or 3 were included. We distinguished two groups, FR and meaningful recanalization (MR), according to patients' disability three months after stroke (FR: mRS score > 2; MR: mRS score < 2). Results: We enrolled 238 patients (FR, n = 129, 54.2%; MR, n = 109, 45.8%). Age (OR 1.05, 95% CI 1.01-1.09, p = 0.012), female sex (OR 2.43, 95% CI 1.12-5.30, p = 0.025), stress hyperglycemia, as measured by the GAR index, (OR 1.17, 95% CI 1.06-1.29, p = 0.002), NIHSS at admission (OR 1.15, 95% CI 1.07-1.25, p = 0.001) and time from symptoms onset to MT (OR 1.01, 95% CI 1.00-1.01, p = 0.020) were independent predictors of FR. The AUC for the model combining age, female sex, GAR index, NIHSS at admission and time from symptoms onset to MT was 0.81 (95% CI 0.76-0.87; p < 0.001). The optimal GAR index cut-off score to predict FR was 17.9. Discussion: FR is common after MT. We recognized older age, female sex and baseline NIHSS as non-modifiable predictors of FR. On the other hand, time from symptoms onset to MT and stress hyperglycemia were modifiable pre- and post- MT factors, respectively. Any effort should be encouraged to reduce the impact of these modifiable predictors. [ABSTRACT FROM AUTHOR]

(1) Background: Stroke is one of the most frequent causes of status epilepticus (SE) in adults. Patients with stroke and SE have poorer prognosis than those with stroke alone. We described characteristics and prognosis of early- and late-onset post-stroke SE (PSSE). (2) Methods: We retrospectively analyzed consecutive stroke patients who experienced a first SE between August 2012 and April 2021, comparing clinical characteristics, stroke, and SE features between early- versus late-onset SE in relation to patients' outcome. (3) Results: Forty stroke patients experienced PSSE. Fourteen developed an early-onset SE (35%) and twenty-six a late-onset SE (65%). Early-onset SE patients had a slightly higher NIHSS score at admission (6.9 vs. 6.0; p = 0.05). Early-onset SE was more severe than late-onset, according to STESS (Status Epilepticus Severity Score) (3.5 vs. 2.8; p = 0.05) and EMSE (Epidemiology-based Mortality score in Status Epilepticus) score (97.0 vs. 69.5; p = 0.04); furthermore, it had a significant impact on disability at 3-month and 1-year follow-up (p = 0.03 and p = 0.02). SE recurrence and seizures relapse were observed mainly in cases of late-onset SE. (4) Conclusions: Early-onset SE seems to be associated with higher disability in short- and long-term follow-up as possible expression of severe acute brain damage. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19. Aim and Methods: From a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation. Results: A total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%. Discussion and Conclusions: The occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect. [ABSTRACT FROM AUTHOR]

Although a causal relationship cannot be proved, the temporal relation of the patient's motor symptoms with the infection suggests that COVID-19, a possible trigger of neurovascular injury [[8]], may have played a role in causing the spinal cord ischemia. Whole spine magnetic resonance imaging (MRI) scan revealed a weak T2-weighted anterior spinal cord hyper-intensity, extending from C6 to T1 level, without contrast enhancement. 1 Cervical and thoracic spinal cord MRI of Covid-19 related ischemic myelopathy, obtained 37 days after onset of symptoms. [Extracted from the article]

Intravenous thrombolysis (IVT) in patients with a low National Institutes of Health Stroke Scale (NIHSS) score of 0–5 remains controversial. IVT should be used in patients with mild but nevertheless disabling symptoms. We hypothesize that response to IVT of patients with "mild stroke" may depend on their level of functional dependence (FD) at hospital admission. The aims of our study were to investigate the effect of IVT and to explore the role of FD in influencing the response to IVT. This study was a retrospective analysis of a prospectively collected database, including 389 patients stratified into patients receiving IVT (IVT+) and not receiving IVT (IVT −) just because of mild symptoms. Barthel index (BI) at admission was used to assess FD, dividing subjects with BI score < 80 (FD+) and with BI score ≥ 80 (FD−). The efficacy endpoints were the rate of positive disability outcome (DO+) (3-month mRS score of 0 or 1), and the rate of positive functional outcome (FO+) (mRS score of zero or one, plus BI score of 95 or 100 at 3 months). At the multivariate analysis, IVT treatment was an independent predictor of DO+ (OR 3.12, 95% CI 1.34−7.27, p = 0.008) and FO+ (OR: 4.70, 95% CI 2.38−9.26, p = 0.001). However, FD+ IVT+ patients had a significantly higher prevalence of DO+ and FO+ than those FD+ IVT–. Differently, IVT treatment did not influence DO+ and FO+ in FD– patients. In FD+ patients, IVT treatment represented the strongest independent predictor of DO+ (OR 6.01, 95% CI 2.59–13.92, p = 0.001) and FO+ (OR 4.73, 95% CI 2.29–9.76, p = 0.001). In conclusion, alteplase seems to improve functional outcome in patients with "mild stroke". However, in our experience, this beneficial effect is strongly influenced by FD at admission. [ABSTRACT FROM AUTHOR]

Although seizures are frequently seen after cerebrovascular accidents, their effects on long-term outcome in stroke patients are still unknown. Therefore, the aim of this study was to investigate the relationship between post-stroke seizures and the risk of long-term disability and mortality in stroke patients. This study is part of a larger population-based study. All patients were prospectively followed up by a face-to-face interview or a structured telephone interview. We enrolled 635 patients with first-ever stroke and without a history of seizures. Prevalence of ischemic stroke (IS) was 85.2%, while the remaining 14.8% of patients were affected by intracerebral hemorrhage (ICH). During the study period, 51 subjects (8%) developed post-stroke seizures. Patients with post-stroke seizures were younger, had a higher prevalence of ICH, had a more severe stroke at admission, were more likely to have an IS involving the total anterior circulation, and were more likely to have a lobar ICH than patients without seizures. Moreover, subjects with seizures had more frequently hemorrhagic transformation after IS and cortical strokes. At 24 months, the risk of disability in patients with seizures was almost twice than in those without seizures. However, the negative effect of seizures disappeared in multivariate analysis. Kaplan-Meier survival curves at 12 years were not significantly different between patients with and without post-stroke seizures. Using the Cox multivariate analysis, age, NIHSS at admission, and pre-stroke mRS were independently associated with all-cause long-term mortality. In our sample, seizures did not impair long-term outcome in patients affected by cerebrovascular accidents. The not significant, slight difference in favor of a better survival for patients with seizures may be attributed to the slight age difference between the two groups. [ABSTRACT FROM AUTHOR]

Little is known about intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with pre-existing disability. Disabled patients are often excluded from IVT treatment. Previous studies investigated the role of pre-existing disability on outcomes in AIS patients after IVT. However, no studies have been conducted to date to determine whether IVT may improve clinical outcomes in AIS patients with pre-existing disability. The aim of our study was to evaluate efficacy and safety of IVT in patients with pre-existing moderate and moderately severe disability (pre-stroke modified Rankin Scale score = 3 or 4) affected by AIS. This study was based on a retrospective analysis of a prospectively collected database of consecutive patients admitted to the Udine University Hospital with AIS from January 2015 to May 2018. The efficacy endpoints were the rate of favorable outcome and rate of major neurological improvement. The safety endpoints were the rate of mortality at three months, presence of intracranial hemorrhage (ICH), and presence of symptomatic intracranial hemorrhage (sICH). The study population included 110 AIS patients with pre-existing moderate and moderately severe disability, 36 of which received (IVT+) and 74 did not receive IVT (IVT−). AIS disabled patients treated with IVT had higher rates of favorable outcome (66.7% vs. 36.5%, p = 0.003) and major neurological improvement (39.4% vs. 17.4%, p = 0.01) compared to non-treated ones. Two in three disabled patients returned to their pre-stroke functional status when treated with IVT. Prevalence of three-month mortality, ICH, and sICH did not differ in the two groups. Disabled patients affected by AIS significantly improved after IVT. Moderate and moderately severe disability alone should not be considered, per se, as a contraindication to IVT treatment. [ABSTRACT FROM AUTHOR]

Endovascular therapy (EVT) represents the gold standard treatment in patients affected by acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Prior antiplatelet (APT) therapy might increase the risk of bleeding and modify the clinical outcome of AIS patients treated with EVT. Thus, we compared effectiveness and safety of EVT in Caucasian patients with and without previous use of APT agents. We recruited consecutive patients admitted to Udine University Hospital with AIS undergoing EVT from January 2015 to December 2017. The following outcomes were documented: successful recanalization, 3-month favorable outcome, symptomatic intracranial hemorrhage (sICH), parenchymal hematoma (PH), and 3-month mortality. The study population included 100 patients (mean age 70.1 ± 11.2 years, 58% males). At time of admission, 34 patients were taking APT agents. Patients on APT pretreatment were older, had more vascular risk factors, and showed higher levels of serum creatinine than APT naïve patients. Moreover, prior APT therapy was associated with a higher rate of pre-stroke disability and a more severe stroke at admission. Patients pretreated with APT had higher rates of successful recanalization (91.2% vs. 74.2%, p = 0.04). Prevalence of 3-month unfavorable outcome and 3-month mortality was significantly higher in APT-pretreated patients than in those without APT pretreatment. However, these associations were not confirmed on multivariable analyses. Prevalence of sICH and PH did not differ in the two groups. APT pretreatment is associated to successful recanalization rate, without increasing the risk of intracranial bleeding in patients with LVO undergoing EVT. [ABSTRACT FROM AUTHOR]

The aim of this study was to prospectively investigate the occurrence of early poststroke seizures (within 7 days of stroke) in patients undergoing reperfusion therapies (intravenous rtPA [recombinant tissue plasminogen activator] and/or endovascular thrombectomy) in comparison to those not undergoing these procedures. Patients aged ≥ 18 years with acute ischemic stroke admitted in five Italian centers were prospectively recruited. Clinical data, details on stroke type and etiology, stroke treatment, and radiological data were collected. The frequency of early poststroke seizures was assessed, and predictive factors for their occurrence were evaluated. Five hundred and sixteen patients (262 in the reperfusion therapies group) were included. Stroke severity on admission and at discharge was higher among patients undergoing reperfusion therapies. Ten patients (3.8%) undergoing reperfusion therapies and 6 (2.3%) of those not receiving these treatments experienced early poststroke seizures (p = 0.45). There were no differences in any of the baseline characteristics between patients experiencing and those not experiencing early seizures. The incidence of early poststroke seizures was overall rare, and no significant differences emerged between patients receiving and those not receiving reperfusion therapies. This article is part of the Special Issue "Seizures and Stroke". • Few conflicting data exist on the risk of early seizures in stroke patients undergoing reperfusion. • This study investigated the occurrence of early post-stroke seizures in patients undergoing reperfusion procedures. • Early post-stroke seizures are rare in patients receiving reperfusion therapies. [ABSTRACT FROM AUTHOR]