Background: Determining the size of infarct extent is crucial to elect patients for reperfusion therapies. Computed tomography perfusion (CTP) based on cerebral blood volume may overestimate infarct core on admission and consequently include ghost infarct core (GIC) in a definitive lesional area. Purpose: Our goal was to confirm and better characterize the GIC phenomenon using CTP cerebral blood flow (CBF) as the reference parameter to determine infarct core. Methods: We performed a retrospective, single-center analysis of consecutive thrombectomies of middle cerebral or intracranial internal carotid artery occlusions considering noncontrast CT Alberta Stroke Program Early CT Score ≥6 in patients with pretreatment CTP. We used the RAPID® software to measure admission infarct core based on initial CBF. The final infarct was extracted from follow-up CT. GIC was defined as initial core minus final infarct > 10 mL. Results: A total of 123 patients were included. The median National Institutes of Health Stroke Scale score was 18 (13–20), the median time from symptoms to CTP was 188 (67–288) min, and the recanalization rate (Thrombolysis in Cerebral Infarction score 2b, 2c, or 3) was 83%. Twenty patients (16%) presented with GIC. GIC was associated with shorter time to recanalization (150 [105–291] vs. 255 [163–367] min, p = 0.05) and larger initial CBF core volume (38 [26–59] vs. 6 [0–27] mL, p < 0.001). An adjusted logistic regression model identified time to recanalization < 302 min (OR 4.598, 95% CI 1.143–18.495, p = 0.032) and initial infarct volume (OR 1.01, 95% CI 1.001–1.019, p = 0.032) as independent predictors of GIC. At 24 h, clinical improvement was more frequent in patients with GIC (80 vs. 49%, p = 0.01). Conclusions: CTP CBF < 30% may overestimate infarct core volume, especially in patients imaged in the very early time window and with fast complete reperfusion. Therefore, the CTP CBF technique may exclude patients who would benefit from endovascular treatment.

Background and Purpose— Time to reperfusion is fundamental in reducing morbidity and mortality in acute stroke. We aimed to demonstrate that direct transfer to angio-suite (DTAS) of patients with suspected large vessel occlusion stroke improves workflow times and outcomes. Methods— A case-control matched study of the first 79 DTAS patients with confirmed large vessel occlusion (cases) and 145 no-DTAS patients (controls). DTAS protocol included a cone beam computed tomography in the angio-suite to rule out intracerebral hemorrhage for those patients with no prior neuroimaging in a referring center. Cases and controls were matched by location of vessel occlusion, age, baseline National Institutes of Health Stroke Scale (NIHSS) score and time from symptoms onset to Comprehensive Stroke Center arrival. Dramatic clinical improvement was defined as a decrease in NIHSS score of >10 points or final NIHSS score of ≤2. Favorable outcome was defined as modified Rankin Scale score of ≤2 at 90 days. Results— During an 18 months period a total of 97 patients were directly transferred to the angio-suite after admission: 11 (11.6%) showed an intracerebral hemorrhage on cone beam computed tomography, 7 (7.2%) did not have a large vessel occlusion on initial angiogram, and 79 (76.3%) had a large vessel occlusion and received endovascular treatment (cases). There were no differences in age, baseline NIHSS score, level of occlusion and time from onset-to-door between cases and controls. The median door-to-groin time (16 [12–20] versus 70 [45–105] minutes; P <0.01) and onset-to-groin times (222 [152–282] versus 259 [190–345] minutes; P <0.01) were shorter in the DTAS group. At 24 hours, DTAS patients presented lower NIHSS score (7 [4–16] versus 14 [4–20]; P =0.01), higher rate of dramatic improvement (50.6% Vs. 31.7%; P =0.04), and higher rate of favorable clinical outcome at 90 days (41% versus 28%; P =0.05). A logistic regression model adjusting for all matching variables showed that DTAS protocol was independently associated with 3 months favorable outcome (odds ratio, 2.5; 95% CI, 1.2–5.3; P =0.01). Conclusions— DTAS is an effective strategy to reduce workflow time which may significantly increase the odds of achieving a favorable outcome.

We aimed to provide practical recommendations for the screening of subclinical atrial fibrillation (AF) in patients with ischaemic stroke or transient ischaemic attack (TIA) of undetermined origin. These guidelines are based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Five relevant Population, Intervention, Comparator, Outcome questions were defined by a multidisciplinary module working group (MWG). Longer duration of cardiac rhythm monitoring increases the detection of subclinical AF, but the optimal monitoring length is yet to be defined. We advise longer monitoring to increase the rate of anticoagulation, but whether longer monitoring improves clinical outcomes needs to be addressed. AF detection does not differ from in- or out-patient ECG-monitoring with similar monitoring duration, so we consider it reasonable to initiate in-hospital monitoring as soon as possible and continue with outpatient monitoring for more than 48h. Although insertable loop recorders (ILR) increase AF detection based on their longer monitoring duration, comparison with non-implantable ECG devices for similar monitoring time is lacking. We suggest the use of implantable devices, if feasible, for AF detection instead of non- implantable devices to increase the detection of subclinical AF. There is weak evidence of a useful role for blood, ECG, and brain imaging biomarkers for the identification of patients at high risk of AF. In patients with patent foramen ovale, we found insufficient evidence from RCT, but prolonged cardiac monitoring in patients >55 years is advisable for subclinical AF detection. To conclude, in adult patients with ischaemic stroke or TIA of undetermined origin, we recommend longer duration of cardiac rhythm monitoring of more than 48h and if feasible with IRL to increase the detection of subclinical AF.

Background: Stroke is reported as a consequence of SARS-CoV-2 infection. However, there is a lack of regarding comprehensive stroke phenotype and characteristics Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) among SARS-CoV-2 infected patients. We further investigated the association of demographics, clinical data, geographical regions, and countrie's health expenditure among AIS patients with the risk of large vessel occlusion (LVO), stroke severity as measured by National Institute of Health stroke scale (NIHSS), and stroke subtype as measured by the TOAST criteria. Additionally, we applied unsupervised machine learning algorithms to uncover possible similarities among stroke patients. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least one eligible stroke patient. Out of 432 patients included, 323(74.8%) had AIS, 91(21.1%) ICH, and 18(4.2%) CVST. Among 23 patients with subarachnoid hemorrhage, 16(69.5%) had no evidence of aneurysm. A total of 183(42.4%) patients were women, 104(24.1%) patients were younger than 55 years, and 105(24.4%) patients had no identifiable vascular risk factors. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144(37.8%) presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or undiagnosed SARS-CoV-2 infection. Among AIS patients 44.5% had LVO; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median NIHSS (8[3-17], versus 11[5-17]; p=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; p<0.001) in countries with middle to high-health expenditure when compared to countries with lower health expenditure. The unsupervised machine learning identified 4 subgroups, with a relatively large group with no or limited comorbidities. Conclusions: We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients. Among hospitalized patients, the stroke severity was lower and rate of mechanical thrombectomy was higher among countries with middle to high-health expenditure.

Introduction: Multiple sclerosis is a chronic inflammatory disease, in which a diagnostic delay could reduce the available therapeutic options. Therefore, it is important to monitor the time to diagnosis and understand factors that may potentially reduce it. The objective of this study was to determine the time between the first symptoms and the diagnosis of multiple sclerosis and which factors may contribute to a diagnostic delay.Material and Methods: Cross-sectional multicenter study, with retrospective data analysis, conducted in five tertiary Portuguese hospitals. Patients were consecutively selected from each local multiple sclerosis patients´ database. Sociodemographic and initial clinical data were collected through a questionnaire. Date of final diagnosis and multiple sclerosis classification was obtained from clinical files.Results: A total of 285 patients were included with mean age at diagnosis of 36 years. The median time between first clinical manifestation and multiple sclerosis diagnosis was nine months (IQR 2 - 38). Diagnostic delay was associated with an older age (p < 0.001; r = 0.35), motor deficit at onset [26.5 months (IQR 4.5 - 56.5); p = 0.0005], higher number of relapses before diagnosis (p < 0.001; r = 0,626), first observation by other medical specialty [11 months (IQR 2 - 48); p < 0.001], prior alternative diagnosis [20 months (IQR 4 - 67.5); p < 0.001] and primary progressive subtype [37 months (IQR 25 - 64.5); p < 0.001]. The most significant delay occurred between the initial symptom and neurological observation.Discussion: A significant delay occurred between initial symptoms and the diagnosis of multiple sclerosis, reflecting the need toincrease awareness of this entity and its diverse symptom presentation.

Background Early outcome prediction after acute ischemic stroke (AIS) might be improved with blood‐based biomarkers. We investigated whether the longitudinal profile of a multi‐marker panel could predict the outcome of successfully recanalized AIS patients. Methods We used ultrasensitive single‐molecule array (Simoa) to measure glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total‐tau (t‐tau) and ELISA for brevican in a prospective study of AIS patients with anterior circulation large vessel occlusion successfully submitted to thrombectomy. Plasma was obtained at admission, upon treatment, 24 h and 72 h after treatment. Clinical and neuroimaging outcomes were assessed independently. Results Thirty‐five patients (64.8%) had good early clinical or neuroimaging outcome. Baseline biomarker levels did not distinguish between outcomes. However, longitudinal intra‐individual biomarker changes followed different dynamic profiles with time and according to outcome. GFAP levels exhibited an early and prominent increase between admission and just after treatment. NfL increase was less pronounced between admission and up to 24 h. T‐tau increased between treatment and 24 h. Interestingly, GFAP rate‐of‐change (pg/ml/h) between admission and immediately after recanalization had a good discriminative capacity between clinical outcomes (AUC = 0.88, p < 0.001), which was higher than admission CT‐ASPECTS (AUC = 0.75, p < 0.01). T‐tau rate‐of‐change provided moderate discriminative capacity (AUC = 0.71, p < 0.05). Moreover, in AIS patients with admission CT‐ASPECTS <9 both GFAP and NfL rate‐of‐change were good outcome predictors (AUC = 0.82 and 0.77, p < 0.05). Conclusion Early GFAP, t‐tau and NfL rate‐of‐change in plasma can predict AIS clinical and neuroimaging outcome after successful recanalization. Such dynamic measures match and anticipate neuroimaging predictive capacity, potentially improving AIS patient stratification for treatment, and targeting individualized stroke care.

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Background and Purpose: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale. Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2–infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries’ health expenditure on outcomes. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were <55 years of age, and 105 (24.4%) patients had no identifiable vascular risk factors. Among acute ischemic stroke patients, 44.5% (126 of 283 patients) had large vessel occlusion; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median National Institutes of Health Stroke Scale (8 [3–17] versus 11 [5–17]; P =0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; P <0.001) in countries with middle-to-high health expenditure when compared with countries with lower health expenditure. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144 (37.8%) were asymptomatic at the time of admission for SARS-CoV-2 infection. Conclusions: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.