The proteomic signature of circulating extracellular vesicles following intracerebral hemorrhage: Novel insights into mechanisms underlying recovery.

Circulating extracellular vesicles (EVs) can participate in innate repair processes triggered after intracerebral hemorrhage (ICH). We aimed to describe changes in the proteomic profile of circulating EVs between the acute and subacute phases of ICH and to compare the findings depending on outcomes, as an approach to unraveling such repair mechanisms. This was a prospective observational study including patients with non-traumatic supratentorial ICH. Exclusion criteria were previous disability, signs of herniation on baseline computed tomography, or limited life expectancy. EVs were isolated from blood samples at 24 h and 7 days after symptom onset. After 6-months' follow-up, patients were dichotomized into poor and good outcomes, defining good as an improvement of >10 points or > 50 % on the National Institutes of Health Stroke Scale and a modified Rankin Scale of 0-2. The protein cargo was analyzed by quantitative mass spectrometry and compared according to outcomes. Forty-four patients completed follow-up, 16 (35.5 %) having good outcomes. We identified 1321 proteins in EVs, 37 with differential abundance. In patients with good outcomes, proteins related to stress response (DERA, VNN2, TOMM34) and angiogenesis (RHG01) had increased abundance at 7 days. EVs from patients with poor outcomes showed higher levels of acute-phase reactants (CRP, SAA2) at 7 days compared with 24 h. In conclusion, the protein content of circulating EVs in patients with ICH changes over time, the changes varying depending on the clinical outcome, with greater abundance of proteins potentially involved in the repair processes of patients with good outcomes.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol.

INTRODUCTION: Poststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality at 3 months. This study aims to evaluate the association between glucose levels during cerebral reperfusion with MT and functional recovery at 3 months, measured by subcutaneous continuous glucose monitoring (CGM) devices. METHODS: This prospective observational study aims to recruit 100 patients with ischaemic stroke and large anterior circulation vessel occlusion, in whom MT is indicated. CGM will be performed using a Freestyle Libre ProIQ device (FSL-CGM, Abbott Diabetes Care, Alameda, California, USA), which will be implanted on admission to the emergency department, to monitor glucose levels before, during and after reperfusion. The study's primary endpoint will be the functional status at 3 months, as measured by the dichotomised modified Rankin Scale (0-2 indicating good recovery and 3-6 indicating dependency or death). We will analyse expression profiles of microRNA (miRNA) at the time of reperfusion and 24 hours later, as potential biomarkers of ischaemic-reperfusion injury. The most promising miRNAs include miR-100, miR-29b, miR-339, miR-15a and miR-424. All patients will undergo treatment according to current international recommendations and local protocols for the treatment of stroke, including intravenous thrombolysis if indicated. ETHICS AND DISSEMINATION: This study (protocol V.1.1, dated 29 October 2021, code 6017) has been approved by the Clinical Research Ethics Committee of La Paz University Hospital (Madrid, Spain) and has been registered in ClinicalTrials.gov (NCT05871502). Study results will be disseminated through peer-reviewed publications in Open Access format and at conference presentations. TRIAL REGISTRATION NUMBER: NCT05871502.

Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke: The ARIES Study.

BACKGROUND: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes. METHODS AND RESULTS: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P<0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P=0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P<0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P<0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups. CONCLUSIONS: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.

Prevalence and Factors Associated with Carotid Stenosis in Acute Ischemic Stroke Patients with Atrial Fibrillation.

INTRODUCTION: Among stroke patients with atrial fibrillation (AF), it is not uncommon to identify carotid atherosclerosis. This study aimed to estimate the prevalence of, and factors associated with, carotid atherosclerosis among patients with AF and acute ischemic stroke. PATIENTS AND METHODS: Prospectively collected data from consecutive patients with anterior ischemic stroke and AF who underwent carotid imaging from 10 stroke registries were categorized retrospectively according to the degree of stenosis in: no atherosclerosis, stenosis <50%, stenosis ≥50%, and occlusion. Logistic regression analysis was used to identify factors associated with ipsilateral carotid atherosclerosis. RESULTS: Among 2,955 patients with ischemic stroke and AF, carotid atherosclerosis was evident in 1,022 (34.6%) patients, while carotid stenosis ≥50% and occlusion were identified in 204 (6.9%) and 168 (5.7%) patients, respectively. Ipsilateral carotid stenosis ≥50% or occlusion was associated with higher age (OR: 1.15, 95% CI: 1.01-1.32, per decade), previous ischemic stroke or transient ischemic attack (OR: 1.70, 95% CI: 1.29-2.25), peripheral artery disease (OR: 1.85, 95% CI: 1.23-2.78), coronary artery disease (OR: 1.53, 95% CI: 1.16-2.04), and statin treatment on admission (OR: 1.30, 95% CI: 1.01-1.67). Patients with lacunar stroke had a lower likelihood of stenosis ≥50% or occlusion (OR: 0.29, 95% CI: 0.13-0.68). Compared to the absence of atherosclerotic disease, atherosclerosis in one and two arterial beds was associated with the identification of ipsilateral carotid stenosis (OR: 1.49, 95% CI: 1.22-2.98 and OR: 3.18, 95% CI: 1.85-5.49, respectively). CONCLUSION: Among acute ischemic stroke patients with AF, 1 out of 3 had ipsilateral carotid atherosclerosis, and 1 out of 8 had ipsilateral carotid stenosis ≥50% or occlusion. Atherosclerosis in two arterial beds was the most important predictor for the identification of ipsilateral carotid stenosis. Among ischemic stroke patients with AF, carotid atherosclerosis is common, while carotid imaging should not be overlooked, especially in those with coronary or/and peripheral artery disease.

Early automated cerebral edema assessment following endovascular therapy: impact on stroke outcome.

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

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.

Immunosuppression withdrawal in living-donor renal transplant recipients following induction with antithymocyte globulin and rituximab: Results of a prospective clinical trial.

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin D+CD27--naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.

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.

Acute In Vivo Administration of Compound 21 Stimulates Akt and ERK1/2 Phosphorylation in Mouse Heart and Adipose Tissue.

The angiotensin II type 2 (AT2) receptor has a role in promoting insulin sensitivity. However, the mechanisms underlying the AT2 receptor-induced facilitation of insulin are still not completely understood. Therefore, we investigated whether acute in vivo administration of AT2 receptor agonist compound 21 (C21) could activate insulin signaling molecules in insulin-target tissues. We report that, in male C57BL/6 mice, an acute (5 min, 0.25 mg/kg; i.v.) injection of C21 induces the phosphorylation of Akt and ERK1/2 at activating residues (Ser473 and Thr202/Tyr204, respectively) in both epididymal white adipose tissue (WAT) and heart tissue. In WAT, the extent of phosphorylation (p) of Akt and ERK1/2 induced by C21 was approximately 65% of the level detected after a bolus injection of a dose of insulin known to induce maximal activation of the insulin receptor (IR). In the heart, C21 stimulated p-Akt to a lesser extent than in WAT and stimulated p-ERK1/2 to similar levels to those attained by insulin administration. C21 did not modify p-IR levels in either tissue. We conclude that in vivo injection of the AT2 receptor agonist C21 activates Akt and ERK1/2 through a mechanism that does not involve the IR, indicating the participation of these enzymes in AT2R-mediated signaling.

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.

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.

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.

The COVID-19 pandemic effect on the prehospital Madrid stroke code metrics and diagnostic accuracy.

BACKGROUND: Only very few studies have investigated the effect of the COVID-19 pandemic on the pre-hospital stroke code protocol. During the first wave, Spain was one of the most affected countries by the SARS-CoV-2 coronavirus disease pandemic. This health catastrophe overshadowed other pathologies, such as acute stroke, the leading cause of death among women and the leading cause of disability among adults. Any interference in the stroke code protocol can delay the administration of reperfusion treatment for acute ischemic strokes, leading to a worse patient prognosis. We aimed to compare the performance of the stroke code during the first wave of the pandemic with the same period of the previous year. METHODS: This was a multicentre interrupted time-series observational study of the cohort of stroke codes of SUMMA 112 and of the ten hospitals with a stroke unit in the Community of Madrid. We established two groups according to the date on which they were attended: the first during the dates with the highest daily cumulative incidence of the first wave of the COVID-19 (from February 27 to June 15, 2020), and the second, the same period of the previous year (from February 27 to June 15, 2019). To assess the performance of the stroke code, we compared each of the pre-hospital emergency service time periods, the diagnostic accuracy (proportion of stroke codes with a final diagnosis of acute stroke out of the total), the proportion of patients treated with reperfusion therapies, and the in-hospital mortality. RESULTS: SUMMA 112 activated the stroke code in 966 patients (514 in the pre-pandemic group and 452 pandemic). The call management time increased by 9% (95% CI: -0.11; 0.91; p value = 0.02), and the time on scene increased by 12% (95% CI: 2.49; 5.93; p value = <0.01). Diagnostic accuracy, and the proportion of patients treated with reperfusion therapies remained stable. In-hospital mortality decreased by 4% (p = 0.05). CONCLUSIONS: During the first wave, a prolongation of the time "on the scene" of the management of the 112 calls, and of the hospital admission was observed. Prehospital diagnostic accuracy and the proportion of patients treated at the hospital level with intravenous thrombolysis or mechanical thrombectomy were not altered with respect to the previous year, showing the resilience of the stroke network and the emergency medical service.

Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke.

OBJECTIVE: We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. PATIENTS AND METHODS: The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. RESULTS: Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. CONCLUSIONS: In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding.KEY MESSAGESInitiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term.Patients starting antidepressants after IS should be followed up more closely in case of recurrent events.Future studies are needed to verify the results and to further study the nature of this finding.

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.

Learning to control a BMI-driven wheelchair for people with severe tetraplegia.

Mind-controlled wheelchairs are an intriguing assistive mobility solution applicable in complete paralysis. Despite progress in brain-machine interface (BMI) technology, its translation remains elusive. The primary objective of this study is to probe the hypothesis that BMI skill acquisition by end-users is fundamental to control a non-invasive brain-actuated intelligent wheelchair in real-world settings. We demonstrate that three tetraplegic spinal-cord injury users could be trained to operate a non-invasive, self-paced thought-controlled wheelchair and execute complex navigation tasks. However, only the two users exhibiting increasing decoding performance and feature discriminancy, significant neuroplasticity changes and improved BMI command latency, achieved high navigation performance. In addition, we show that dexterous, continuous control of robots is possible through low-degree of freedom, discrete and uncertain control channels like a motor imagery BMI, by blending human and artificial intelligence through shared-control methodologies. We posit that subject learning and shared-control are the key components paving the way for translational non-invasive BMI.

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.

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.