Keeping prior anticoagulation treatment in the acute phase of ischaemic stroke: the REKOALA study.

INTRODUCTION: A consensus on the management of anticoagulated patients in the acute phase of ischaemic stroke has not yet been established. We aimed to evaluate clinical outcomes in such patients based on the continuation or discontinuation of anticoagulation. METHODS: Retrospective study of patients with acute ischaemic stroke and cardioembolic source receiving anticoagulant therapy is done. Patients were classified based on the continuation or discontinuation of anticoagulation at admission. Clinical outcomes, haemorrhagic and ischaemic events were assessed. Multivariate logistic regression analysis, propensity score matching (PSM) analysis and a sub-analysis of patients with severe ischaemic stroke at admission (NIHSS score ≥ 15) were performed. RESULTS: Anticoagulation was continued in 147 (78.8%) of 186 patients. Patients continuing anticoagulant had lower NIHSS (median 5 vs 18, p < 0.001). There were no differences in haemorrhagic or ischaemic events. In the multivariate analysis, good functional outcome at discharge was higher in the continuation group, OR (CI95%) 3.77 (1.2-11.2). PSM analysis adjusted for potential confounders such as NIHSS had higher rates of good functional outcomes at discharge (80% vs 36%, p = 0.004) and at 90 days (76% vs 44%, p = 0.042) in the continuation group. Patients with severe stroke in this group had lower 90-day mortality (34.6% vs 62.5%, p = 0.045) and higher rates of good clinical outcome at discharge (33.3% vs 8.3%, p = 0.032). No differences were observed in 90-day haemorrhagic or ischaemic events. CONCLUSION: Continuation of anticoagulation in patients with acute ischaemic stroke and cardioembolic source did not increase the risk of intracranial haemorrhage and may be associated with better functional outcomes.

Impact of post-stroke aphasia on functional communication, quality of life, perception of health and depression: A case-control study.

BACKGROUND AND PURPOSE: Post-stroke aphasia is associated with a reduced quality of life (QoL) and higher risk of depression. Few studies have addressed the effect of coping with aphasia. Our aim is to evaluate the impact of post-stroke aphasia on self-reported QoL and symptoms of depression. METHODS: This was a cross-sectional prospective case-control study. Cases involved patients with post-stroke aphasia included in the DULCINEA trial (NCT04289493). Healthy controls were recruited using snowball sampling. All subjects completed the following questionnaires: General Health Questionnaire (GHQ-12), Stroke Aphasia Quality of Life Scale (SAQOL-39), Communicative Activity Log (CAL) and Stroke Aphasic Depression Questionnaire (SADQ-10). RESULTS: Twenty-three patients (eight women; mean age 62.9 years) and 73 controls (42 women; mean age 53.7 years) were included. Cases scored lower than controls in perception of health (GHQ-12: median 3 [IQR 1; 6] vs. 0 [IQR 0; 2]) and perception of QoL (SAQOL-39: median 3.6 [IQR 3.3; 40] vs. 4.6 [IQR 4.2; 4.8]). Functional communication (CAL: median 135 [IQR 122; 148] vs. 94 [IQR 74; 103]) and SAQOL-39 communication subscale (median 2.7 [IQR 2.1; 3.2] vs. 4.8 [IQR 4.6; 5.0]) were also significantly lower in the case group. Notably, cases reported fewer depressive symptoms than controls (SADQ-10: median 11 [IQR 9; 15] vs. 13 [IQR 11; 16]; p = 0.016). A mediational analysis revealed that the relationship between post-stroke aphasia and depression was not mediated by functional communication. CONCLUSIONS: Although communication difficulties impact the QoL of patients with post-stroke aphasia, such patients report fewer depressive symptoms on the SADQ-10 scale than healthy people, with no differences in scores related to social participation.

Abordaje y tratamiento del ictus isquémico en la fase aguda / Management of acute ischemic stroke

El ictus isquémico es una enfermedad neurológica grave que precisa una atención urgente. Al ser una enfermedad dependiente del tiempo, la asistencia debe ser coordinada y eficaz para que ofrezca el tratamiento adecuado de la forma más precoz posible. El tratamiento de la fase aguda incluye unas medidas generales para garantizar la estabilidad hemodinámica del paciente, el uso de terapias de reperfusión (trombolíticos intravenosos y tratamiento endovascular mediante trombectomía mecánica) y la contribución a la protección cerebral mediante el control de presión arterial, glucemia, temperatura y oxigenación, así como prevenir complicaciones cerebrales y sistémicas. Se debe planificar de manera precoz el tratamiento rehabilitador del paciente. Para evitar las recurrencias precoces se recomienda tratamiento antitrombótico según la etiología del ictus y el control de los factores de riesgo vascular. Todas estas medidas tienen como objetivo revertir los síntomas iniciales, evitar que progrese la lesión, mejorar la situación funcional del paciente y evitar recurrencias (AU)

Ischemic stroke is a serious neurological condition that requires urgent attention. As a time-dependent disease, acute stroke management must be coordinated and effective to provide the best treatment as early as possible. The treatment of the acute phase of ischemic stroke includes general measures to ensure patient hemodynamic stability, the use of reperfusion therapies (intravenous thrombolytics and mechanical thrombectomy), improving cerebral protection by monitoring the homeostasis of certain variables as blood pressure, glycemia, temperature, or oxygenation, as well as preventing cerebral and systemic complications. Also, it is necessary an early planning of comprehensive rehabilitation. To prevent early recurrences, control of vascular risk factors and antithrombotic treatment is recommended. The management of patients with acute ischemic stroke aims to reverse initial symptoms, to prevent further brain damage, improve functional outcomes and avoid ischemic recurrences (AU)

Critical illness-associated cerebral microbleeds: What we learned after the COVID-19 pandemic. A systematic review.

BACKGROUND: Cerebral microbleeds in critically ill patients have been a reported complication of COVID-19. However, they have also been described in patients with other respiratory infections and conditions requiring intensive care unit (ICU) admission. Here, we aim to describe the clinical characteristics of critical illness-associated cerebral microbleeds and compare COVID-19 cases with those related to other conditions. METHODS: We performed a systematic literature review in PubMed and Embase for Critical Illness-Associated Cerebral Microbleeds to describe the clinical characteristics of this entity, in both COVID-19 and non-COVID-19 patients. RESULTS: Of 157 manuscripts screened, 23 were included, totalling 143 cases (median age 61, interquartile range [IQR] 54-66), 104 (73 %) men. SARS-CoV2-associated pneumonia was found in 105 (73 %) cases. The median ICU stay was 34 (IQR 26-42) days and the median mechanical ventilation time was 24 (IQR 14-35) days. Cerebral microbleeds were more frequently juxtacortical (79 %) or located in the corpus callosum (75 %) and deep white matter (71 %) for both COVID-19 and non-COVID-19 individuals, whilst brainstem location was more frequent in non-COVID-19 patients (37 % vs 13 %; p = 0.02). Non-COVID-19 patients were younger (median age 42, IQR 30-54 years) than COVID-19 patients (median age 62, IQR 57-67 years; p < 0.001), and the median platelet count was significantly higher (200,000; IQR 116,000-284,000 ng/dL) in COVID-19 patients than non-COVID-19 patients (50,000; IQR 39,000-61,000 ng/mL; (p < 0.001). CONCLUSIONS: In this systematic review, most patients presented respiratory failure with prolonged mechanical ventilation and ICU stay. Juxtacortical white matter and corpus callosum are characteristic locations of critical illness-associated microbleeds.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

[Management of acute ischemic stroke]. / Abordaje y tratamiento del ictus isquémico en la fase aguda.

Ischemic stroke is a serious neurological condition that requires urgent attention. As a time-dependent disease, acute stroke management must be coordinated and effective to provide the best treatment as early as possible. The treatment of the acute phase of ischemic stroke includes general measures to ensure patient hemodynamic stability, the use of reperfusion therapies (intravenous thrombolytics and mechanical thrombectomy), improving cerebral protection by monitoring the homeostasis of certain variables as blood pressure, glycemia, temperature, or oxygenation, as well as preventing cerebral and systemic complications. Also, it is necessary an early planning of comprehensive rehabilitation. To prevent early recurrences, control of vascular risk factors and antithrombotic treatment is recommended. The management of patients with acute ischemic stroke aims to reverse initial symptoms, to prevent further brain damage, improve functional outcomes and avoid ischemic recurrences.

Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes. PURPOSE: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. RESULTS: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen ß chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. CONCLUSION: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MS for reflecting the disease state.

Neurodata Tracker: Software for computational assessment of hand motor skills based on optical motion capture in a virtual environment.

Objectives: Deficits affecting hand motor skills negatively impact the quality of life of patients. The NeuroData Tracker platform has been developed for the objective and precise evaluation of hand motor deficits. We describe the design and development of the platform and analyse the technological feasibility and usability in a relevant clinical setting. Methods: A software application was developed in Unity (C#) to obtain kinematic data from hand movement tracking by a portable device with two cameras and three infrared sensors (leap motion®). Four exercises were implemented: (a) wrist flexion-extension (b) finger-grip opening-closing (c) finger spread (d) fist opening-closing. The most representative kinematic parameters were selected for each exercise. A script in Python was integrated in the platform to transform real-time kinematic data into relevant information for the clinician. The application was tested in a pilot study comparing the data provided by the tool from ten healthy subjects without any motor impairment and ten patients diagnosed with a stroke with mild to moderate hand motor deficit. Results: The NeuroData Tracker allowed the parameterization of kinematics of hand movement and the issuance of a report with the results. The comparison of the data obtained suggests the feasibility of the tool for detecting differences between patients and healthy subjects. Conclusions: This new platform based on optical motion capturing provides objective measurement of hand movement allowing quantification of motor deficits. These findings require further validation of the tool in larger trials to verify its usefulness in the clinical setting.

European Stroke Organisation (ESO) Guidelines on Moyamoya angiopathy Endorsed by Vascular European Reference Network (VASCERN).

The European Stroke Organisation (ESO) guidelines on Moyamoya Angiopathy (MMA), developed according to ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, were compiled to assist clinicians in managing patients with MMA in their decision making. A working group involving neurologists, neurosurgeons, a geneticist and methodologists identified nine relevant clinical questions, performed systematic literature reviews and, whenever possible, meta-analyses. Quality assessment of the available evidence was made with specific recommendations. In the absence of sufficient evidence to provide recommendations, Expert Consensus Statements were formulated. Based on low quality evidence from one RCT, we recommend direct bypass surgery in adult patients with haemorrhagic presentation. For ischaemic adult patients and children, we suggest revascularization surgery using direct or combined technique rather than indirect, in the presence of haemodynamic impairment and with an interval of 6-12 weeks between the last cerebrovascular event and surgery. In the absence of robust trial, an Expert Consensus was reached recommending long-term antiplatelet therapy in non-haemorrhagic MMA, as it may reduce risk of embolic stroke. We also agreed on the utility of performing pre- and post- operative haemodynamic and posterior cerebral artery assessment. There were insufficient data to recommend systematic variant screening of RNF213 p.R4810K. Additionally, we suggest that long-term MMA neuroimaging follow up may guide therapeutic decision making by assessing the disease progression. We believe that this guideline, which is the first comprehensive European guideline on MMA management using GRADE methods will assist clinicians to choose the most effective management strategy for MMA.

Circulating extracellular vesicles promote recovery in a preclinical model of intracerebral hemorrhage.

Circulating extracellular vesicles (EVs) are proposed to participate in enhancing pathways of recovery after stroke through paracrine signaling. To verify this hypothesis in a proof-of-concept study, blood-derived allogenic EVs from rats and xenogenic EVs from humans who experienced spontaneous good recovery after an intracerebral hemorrhage (ICH) were administered intravenously to rats at 24 h after a subcortical ICH. At 28 days, both treatments improved the motor function assessment scales score, showed greater fiber preservation in the perilesional zone (diffusion tensor-fractional anisotropy MRI), increased immunofluorescence markers of myelin (MOG), and decreased astrocyte markers (GFAP) compared with controls. Comparison of the protein cargo of circulating EVs at 28 days from animals with good vs. poor recovery showed down-expression of immune system activation pathways (CO4, KLKB1, PROC, FA9, and C1QA) and of restorative processes such as axon guidance (RAC1), myelination (MBP), and synaptic vesicle trafficking (SYN1), which is in line with better tissue preservation. Up-expression of PCSK9 (neuron differentiation) in xenogenic EVs-treated animals suggests enhancement of repair pathways. In conclusion, the administration of blood-derived EVs improved recovery after ICH. These findings open a new and promising opportunity for further development of restorative therapies to improve the outcomes after an ICH.

Neck CT angiography in acute stroke: An open window for fast detection of COVID-19 lung involvement? Applicability in telemedicine.

BACKGROUND: Chest CT has been proposed as a screening test to rule out SARS-CoV-2 lung infection in acute stroke. Our objectives are to analyze the predictive value of neck CT angiography (CTA) source images compared with conventional chest CT, the interobserver concordance and the reliability of the diagnosis using a mobile app. METHODS: A retrospective observational study that included acute stroke patients admitted to a stroke center. Two raters blinded to the clinical data evaluated and classified the pulmonary findings in chest CT and neck CTA source images according to the COVID-19 Reporting and Data System (CO-RADS). CTA findings were evaluated using a conventional workstation and the JOIN mobile app. Scores of 3-5 were grouped as appearing typical or indeterminate for COVID-19 lung involvement and 0-2 as appearing atypical or negative for pneumonia. SARS-CoV-2 infection was confirmed by polymerase chain reaction (PCR). RESULTS: A total of 242 patients were included (42 with PCR-confirmed COVID-19). In the cohort of 43 patients with both neck CTA and chest CT, the predictive value for COVID-19 was equivalent (sensitivity, 53.8%; specificity, 92.9%). The interobserver agreement in the classification into CO-RADS 3-5 or 1-2 in CTA was good (K = 0.694; standard error, 0.107). In the cohort of 242 patients with neck CTA, the intraobserver agreement between the workstation and the JOIN app was perfect (K = 1.000; standard error 0.000). CONCLUSIONS: Neck CTA enables the accurate identification of COVID-19-associated lung abnormalities in acute stroke. CO-RADS evaluations through mobile applications have a predictive value similar to the usual platforms.

The use of a smartphone application to improve stroke code workflow metrics: A pilot study in a comprehensive stroke centre.

Background: Timely coordination between stroke team members is of relevance for stroke code management. We explore the feasibility and potential utility of a smartphone application for clinical and neuroimaging data sharing for improving workflow metrics of stroke code pathways, and professionals' opinions about its use. Methods: We performed an observational pilot study including stroke code activations at La Paz University Hospital in Madrid, from June 2019 to March 2020. Patients were classified according to the activation or not of the JOIN app by the attending physician. Clinical data and time-to-procedures were retrieved from the app or from the hospital records and the Madrid regional stroke registry as appropriate and compared between both groups. An anonymous survey collected professionals' opinions about the app and its use. Results: A total of 282 stroke code activations were registered. The JOIN app was activated in 111 (39%) cases. They had a significant reduction in imaging-to-thrombolysis (31 vs 20 min, p = .026) and in door-to-thrombolysis times (51 vs 36 min, p = .004), with more patients achieving a door-to-needle time below 45 min (68.8% vs 37.8%, p = .016). About 50% of the users found the app useful for facilitating the diagnosis and decision-making; interoperability with clinical files was considered an opportunity for improvement. Conclusions: This pilot study suggests that JOIN helps improve and document workflow metrics in acute stroke management in a comprehensive stroke centre. These results support testing JOIN in a prospective randomised study to confirm its usefulness and the general applicability of the results.

Final Results of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial.

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8-20) were randomized (1:1) to receive intravenous adipose tissue-derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3-5.5] vs 7 [0-8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up.

Connectomic-genetic signatures in the cerebral small vessel disease.

Small vessel disease (SVD) is a disorder that causes vascular lesions in the entire parenchyma of the human brain. At present, it is not well understood how primary and secondary damage interact to give rise to the complex scenario of white matter (WM) and grey matter (GM) lesions. Using novel cross-sectional and longitudinal connectomic approaches, we unveil the bidirectional nature of GM and WM changes, that is, primary cortical neurodegeneration that leads to secondary alterations in vascular border zones, and WM lesions that lead to secondary neurodegeneration in cortical projecting areas. We found this GM-WM interaction to be essential for executive cognitive performance. Moreover, we also observed that the interlocked degeneration of GM and WM over time associates with prototypical expression levels of genes potentially linked to SVD. Among these connectomic-genetic intersections, we found that the Androgen Receptor (AR) gene, is a particularly central candidate gene that might confer key vulnerability for brain lesion development in SVD. In conclusion, this study advances in the understanding of the bidirectional relationships between GM and WM lesions, primary and secondary vascular neurodegeneration, and sheds light on the genetic signatures of SVD.

DUbbing Language-therapy CINEma-based in Aphasia post-Stroke (DULCINEA): study protocol for a randomized crossover pilot trial.

BACKGROUND: Communication is one of the most important predictors of social reintegration after stroke. Approximately 15-42% of stroke survivors experience post-stroke aphasia. Helping people recover from aphasia is one of the research priorities after a stroke. Our aim is to develop and validate a new therapy integrating dubbing techniques to improve functional communication. METHODS: The research project is structured as three work packages (WP). WP1: development of the dubbed language cinema-based therapy: Two research assistants (a speech therapist and a dubbing actor) will select the clips, mute specific words/sentences in progressive speech difficulty, and guide patients to dub them across sessions. Words to be dubbed will be those considered to be functionally meaningful by a representative sample of aphasic patients and relatives through an online survey. WP2: a randomized, crossover, interventional pilot study with the inclusion of 54 patients with post-stroke non-fluent aphasia. Patients will be treated individually in 40-min sessions twice per week for 8 weeks. Primary outcomes will be significant pre/post differences in scores in the Communicative Activity Log (CAL) questionnaire and Boston Diagnostic Aphasia Examination (BDAE) administered by a psychologist blinded to the patients' clinical characteristics. SECONDARY OUTCOMES: General Health Questionnaire (GHQ)-12, Stroke Aphasia Quality of Life Scale (SAQOL-39), Western Aphasia Battery Revised (WAB-R), and the Stroke Aphasic Depression Questionnaire (SADQ10). WP3: educational activities and dissemination of results. WP3 includes educational activities to improve public knowledge of aphasia and dissemination of the results, with the participation of the Spanish patients' association Afasia Activa. DISCUSSION: This pilot clinical trial will explore the efficacy of a new therapeutic tool based on dubbing techniques and computer technology to improve functional communication of patients suffering from post-stroke aphasia with the use of standardized test assessment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04289493 . Registered on 28 February 2020.

Protein content of blood-derived extracellular vesicles: An approach to the pathophysiology of cerebral hemorrhage.

Introduction: Extracellular vesicles (EVs) participate in cell-to-cell paracrine signaling and can be biomarkers of the pathophysiological processes underlying disease. In intracerebral hemorrhage, the study of the number and molecular content of circulating EVs may help elucidate the biological mechanisms involved in damage and repair, contributing valuable information to the identification of new therapeutic targets. Methods: The objective of this study was to describe the number and protein content of blood-derived EVs following an intracerebral hemorrhage (ICH). For this purpose, an experimental ICH was induced in the striatum of Sprague-Dawley rats and EVs were isolated and characterized from blood at baseline, 24 h and 28 days. The protein content in the EVs was analyzed by mass spectrometric data-dependent acquisition; protein quantification was obtained by sequential window acquisition of all theoretical mass spectra data and compared at pre-defined time points. Results: Although no differences were found in the number of EVs, the proteomic study revealed that proteins related to the response to cellular damage such as deubiquitination, regulation of MAP kinase activity (UCHL1) and signal transduction (NDGR3), were up-expressed at 24 h compared to baseline; and that at 28 days, the protein expression profile was characterized by a higher content of the proteins involved in healing and repair processes such as cytoskeleton organization and response to growth factors (COR1B) and the regulation of autophagy (PI42B). Discussion: The protein content of circulating EVs at different time points following an ICH may reflect evolutionary changes in the pathophysiology of the disease.

Transient Focal Neurological Events in Cerebral Amyloid Angiopathy and the Long-term Risk of Intracerebral Hemorrhage and Death: A Systematic Review and Meta-analysis.

Importance: Transient focal neurological episodes (TFNEs) are a frequently overlooked presentation of cerebral amyloid angiopathy (CAA), a condition with prognostic implications that are still not well described. Objective: To perform a systematic review and meta-analysis to examine the factors associated with incident lobar intracerebral hemorrhage (ICH) and death in patients with CAA presenting with TFNEs. Data Sources: A systematic review and individual participant meta-analysis including (1) a hospital-based cohort and (2) the results obtained from a systematic search performed in MEDLINE and Embase completed in December 2019. Study Selection: Included studies were observational reports of TFNEs. Patient-level clinical, imaging, and prognostic data were required for inclusion. For aggregate data studies, patient-level data were requested. Disagreements were resolved by consensus. Data Extraction and Synthesis: Data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines by 4 independent reviewers. The quality of reports was determined based on the modified Pearson Case Report Quality Scale. Main Outcomes and Measures: The clinical characteristics of TFNEs, neuroimaging features, and use of antithrombotics during follow-up were considered exposures. The predefined main outcomes were lobar ICH and risk of death during follow-up. Results: Forty-two studies and 222 CAA-associated TFNE cases were included from the initial 1612 records produced by the systematic search; 26 additional patients (11 men [42.3%]; mean [SD] age, 77 [8] years) were provided by the hospital-based cohort. A total of 108 TFNEs (43.5%) consisted of motor symptoms. Convexity subarachnoid hemorrhage and cortical superficial siderosis were detected in 193 individuals (77.8%) and 156 individuals (62.9%) in the systematic search and hospital-based cohort, respectively. Follow-up duration could be obtained in 185 patients (median duration, 1 year [IQR, 0.8-2.5 years]). During follow-up, symptomatic lobar ICH occurred in 76 patients (39.4%). Motor symptoms (odds ratio, 2.08 [95% CI, 1.16-3.70]) at baseline and antithrombotic use during follow-up (odds ratio, 3.61 [95% CI, 1.67-7.84]) were associated with an increase in risk of lobar ICH. A total of 31 patients (16.5%) died during follow-up; lobar ICH during follow-up and cortical superficial siderosis were the main risk factors for death (odds ratio, 3.01 [95% CI, 1.36-6.69]; odds ratio, 3.20 [95% CI, 1.16-8.91], respectively). Conclusions and Relevance: Patients presenting with CAA-associated TFNEs are at high risk of lobar ICH and death. Motor TFNEs and use of antithrombotics after a TFNE, in many cases because of misdiagnosis, are risk factors for ICH, and therefore accurate diagnosis and distinguishing this condition from transient ischemic attacks is critical.

Concurrent Cerebral, Splenic, and Renal Infarction in a Patient With COVID-19 Infection.

INTRODUCTION: Thrombotic events are potentially devastating complications of coronavirus disease 2019 (COVID-19) infection. Although less common than venous thromboembolism, arterial thrombosis has been reported in COVID-19 cohorts in almost 3% of patients. We describe a patient with COVID-19 infection and concurrent cerebral and noncerebral infarction. CASE REPORT: A 53-year-old man with history of COVID-19 pneumonia was admitted to a primary stroke center for speech disturbances and left hemiplegia. Urgent laboratory tests showed a great increase of inflammatory and coagulation parameters as D-dimer, ferritin, interleukin-6 and C-reactive protein. Neuroimaging found occlusion of the M1 segment of the right middle cerebral artery with early signs of ischemic stroke. He received intravenous thrombolysis and mechanical thrombectomy. Abdominal computed tomography discovered a splenic infarction with hemorrhagic transformation and bilateral renal infarction. Urgent angiography showed an associated splenic pseudoaneurysm, which was embolized without complications. He was treated with intermediate-dose anticoagulation (1 mg subcutaneous enoxaparin/kg/24 h), acetylsalicylic acid 100 mg and 5 days of intravenous corticosteroids. In the following days, inflammatory markers decreased so anticoagulant treatment was stopped and acetylsalicylic acid 300 mg was prescribed. His condition improved and he was discharged to a rehabilitation facility on hospital day 30. CONCLUSION: In this case, a patient with multiple thrombotic events in the acute phase of COVID-19 infection, the delimitation of the inflammatory state through analytical markers as D-dimer helped to individualize the antithrombotic treatment (full anticoagulation or anticoagulation at intermediate doses plus antiplatelet treatment as used in our patient) and its duration. However, more data are needed to better understand the mechanisms and treatment of stroke in patients with COVID-19 infection.

The Role of Ultrasound as a Diagnostic and Therapeutic Tool in Experimental Animal Models of Stroke: A Review.

Ultrasound is a noninvasive technique that provides real-time imaging with excellent resolution, and several studies demonstrated the potential of ultrasound in acute ischemic stroke monitoring. However, only a few studies were performed using animal models, of which many showed ultrasound to be a safe and effective tool also in therapeutic applications. The full potential of ultrasound application in experimental stroke is yet to be explored to further determine the limitations of this technique and to ensure the accuracy of translational research. This review covers the current status of ultrasound applied to monitoring and treatment in experimental animal models of stroke and examines the safety, limitations, and future perspectives.