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.

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.

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.

Stroke Acute Management and Outcomes During the COVID-19 Outbreak: A Cohort Study From the Madrid Stroke Network.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.

Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

Glycemic variability: prognostic impact on acute ischemic stroke and the impact of corrective treatment for hyperglycemia. The GLIAS-III translational study.

INTRODUCTION: Glycemic variability (GV) represents the amplitude of oscillations in glucose levels over time and is associated with higher mortality in critically ill patients. Our aim is to evaluate the impact of GV on acute ischemic stroke (IS) outcomes in humans and explore the impact of two different insulin administration routes on GV in an animal model. METHODS: This translational study consists of two studies conducted in parallel: The first study is an observational, multicenter, prospective clinical study in which 340 patients with acute IS will be subcutaneously implanted a sensor to continuously monitor blood glucose levels for 96 h. The second study is a basic experimental study using an animal model (rats) with permanent occlusion of the middle cerebral artery and induced hyperglycemia (through an intraperitoneal injection of nicotinamide and streptozotocin). The animal study will include the following 6 groups (10 animals per group): sham; hyperglycemia without IS; IS without hyperglycemia; IS and hyperglycemia without treatment; IS and hyperglycemia and intravenous insulin; and IS and hyperglycemia and subcutaneous insulin. The endpoint for the first study is mortality at 3 months, while the endpoints for the animal model study are GV, functional recovery and biomarkers. DISCUSSION: The GLIAS-III study will be the first translational approach analyzing the prognostic influence of GV, evaluated by the use of subcutaneous glucose monitors, in acute stroke. Trial registration https://www.clinicaltrials.gov (NCT04001049).

Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

Occipital Condyle Syndrome: A Red Flag for Malignancy. Comprehensive Literature Review and New Case Report.

OBJECTIVE: To perform a literature review of the epidemiology, clinical presentation, diagnostic evaluation, and clinical course of occipital condyle syndrome, including a new case report. BACKGROUND: Occipital condyle syndrome (OCS) is a rare clinical syndrome, consisting of unilateral occipital headache accompanied by ipsilateral hypoglossal palsy. This headache typically radiates to the temporal region, and is triggered by contralateral head rotation. It is usually associated with skull base metastasis, often unrevealed in basic neuroimaging studies. OCS might be the first manifestation of malignancy, and its unfamiliarity can lead to a delay in the diagnosis. METHODS: We performed a systematic literature review using PubMed and Embase for OCS, along with a new case report. RESULTS: A total of 35 cases (mean age 59 years, range 25-77), 24 (70%) men, presented typical unilateral headache followed by ipsilateral hypoglossal palsy from 0 to 150 days after headache presentation. In 16 patients (46%), initial neuroimaging studies were normal. OCS was due to skull base metastasis in 32 cases (91%). In 18 patients (51%), OCS was the first symptom of disease. CONCLUSIONS: OCS represents a warning sign and requires an exhaustive search for underlying neoplasm. An appropriate clinical evaluation can lead to an earlier diagnosis in patients with consistent headache.

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.

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.

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.

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.

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.

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.

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.

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.

Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study.

OBJECTIVE: Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. METHODS: Helsinki Young Stroke Registry includes patients aged 15-49 years with first-ever IS, 1994-2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1 year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. RESULTS: We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100 days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48-4.31) and during later follow-up among those with silent infarcts (2.04; 1.27-3.28), prior use of antidepressants (2.09; 1.26-3.46) and moderate versus mild stroke (2.06; 1.18-3.58). The relative difference in the hazard rate for moderate-severe limb paresis persisted both within the first 100 days (3.84, 2.12-6.97) and during later follow-up (4.54; 2.51-8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11-1.97) as well as lower (1.78; 1.25-2.54) and upper white-collar workers (2.00; 1.24-3.23) compared to blue-collar workers. CONCLUSION: One-fourth of young adults started PSADs within 1 year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up.

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.