Hypoperfusion intensity ratio correlates with collaterals and predicts outcome and infarct volume in acute ischemic stroke patients.

BACKGROUND: Hypoperfusion Intensity Ratio (HIR) is associated with collaterals and outcome in acute ischemic stroke (AIS). We investigated whether a combined assessment of HIR and collaterals could provide an added value. METHODS: Retrospective single-center study, including AIS patients with large vessel occlusion and endovascular treatment 0-24 h from onset. Predictors of FIV and outcome (90 days modified Rankin Scale 0-1) were investigated with linear and logistic regression respectively. Subjects were stratified in three groups: poor collaterals (grade 0-3) with poor HIR (≥.4), good collaterals (grade 4-5) with poor HIR/poor collaterals with good HIR (<.4) and good collaterals with good HIR. RESULTS: We included 337 patients (median age 77, 53.1% males), of whom 100 (29.7%) had excellent outcome. One hundred and forty five patients with favourable collateral and HIR profiles had smaller infarct (median poor collaterals with poor HIR 41 mL, good collaterals with poor HIR/poor collaterals with good HIR 21 mL and good collaterals with good HIR 11 mL, p <.001) and higher rates of excellent outcome (poor collaterals with poor HIR 15.7%, good collaterals with poor HIR/poor collaterals with good HIR 26.2% and good collaterals with good HIR 39.3% p =.001). Logistic regression showed that patients with favourable collateral and HIR profiles had the highest odds of good outcome (OR: 3.83, 95% CI 1.62-9.08, p =.002). CONCLUSION: Collaterals and HIR are independent predictors of final infarct lesion and outcome in stroke patients and their integration provides an added value. These findings might inform clinical practice and future trials.

Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI.

BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Multi-phase CT-Angiography outperforms angiographic careggi collateral score and predicts functional outcome in acute ischemic stroke.

BACKGROUND: Collaterals are a strong determinant of clinical outcome in acute ischemic stroke (AIS) patients undergoing Endovascular Treatment (EVT). Careggi Collateral Score (CCS) is an angiographic score that demonstrated to be superior to the widely suggested ASITN/SIR score. Multi-phase CT-Angiography (mCTA) could be alternatively adopted for collateral assessment. We investigated whether mCTA had an equivalent predictive performance for functional outcome compared to CCS. METHODS: Consecutive AIS patients undergoing EVT for large vessel occlusion within 24 h from onset were analyzed. Receiver operating characteristic curves and multivariable logistic regression were investigated to evaluate the predictive performance of mCTA collateral score (range 0-5) and CCS (range 0-4) for good functional outcome (three-months modified Rankin Scale 0-2). RESULTS: We included 201 subjects (59.7% females, mean age 75), of whom 96 (47.7%) had good outcome at three-months. Both CCS (OR = 14.4, 95% CI = 6.3-33.8) and mCTA (OR = 23.8, 95% CI = 10.1-56.4) collateral scores were independent predictors of outcome. The AUC of CCS was 0.80 (95% CI 0.73-0.86) and the best cut-off was ≥ 3 (87% sensitivity, 71% specificity), while the AUC of mCTA collateral score was 0.84 (95% CI 0.78-0.90) with an optimal cut-off of ≥ 4 (85% sensitivity, 87% specificity). Patients with good mCTA collaterals experienced smaller (16.6 vs. 63.7 mL, p < 0.001) infarct lesion as compared to those with mCTA poor collaterals. CONCLUSION: mCTA discriminative ability for three-months 0-2 mRS was found to be comparable to CCS. mCTA appears a valid, non-invasive imaging modality for evaluating collaterals of AIS patients potentially eligible for EVT.

Thrombectomy in ischemic stroke patients with tandem occlusion in the posterior versus anterior circulation.

BACKGROUND: Mechanical thrombectomy (MT) was found to be beneficial in acute ischemic stroke patients with anterior tandem occlusion (a-TO). Instead, little is known about the effectiveness of MT in stroke patients with posterior tandem occlusion (p-TO). We aimed to compare MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO. METHODS: We conducted a cohort study on prospectively collected data of patients registered in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) who were treated with MT within 24 h from last known well time for acute ischemic stroke with p-TO (n = 275) or a-TO (n = 1853). RESULTS: After adjustment for unbalanced pre-procedure variables (year 2015-2021, age, sex, NIHSS score, ASPECTS, and time strata for puncture groin) and pre-stroke mRS score as pre-defined predictor, p-TO was significantly associated with lower probability of mRS score 0-2 (OR 0.415, 95% CI 0.268-0.644) and with higher risk of death (OR 2.813, 95% CI 2.080-3.805) at 3 months. After adjustment for unbalanced procedural and post-procedure variables (IVT, general anesthesia, TICI 3, and 24-h HT) and pre-stroke mRS score as pre-defined predictor, association between p-TO and lower probability of mRS score 0-2 (OR 0.444, 95% CI 0.304-0.649) and association between p-TO and with higher risk of death (OR 2.971, 95% CI 1.993-4.429) remained significant. CONCLUSIONS: MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO was associated with worse outcomes at 3 months.

Predictors and Prognostic Impact of Hematoma Expansion in Infratentorial Cerebral Hemorrhage.

BACKGROUND: Hematoma expansion (HE) is common and predicts poor outcome in patients with supratentorial intracerebral hemorrhage (ICH). We investigated the predictors and prognostic impact of HE in infratentorial ICH. METHODS: We conducted a retrospective analysis of patients with brainstem and cerebellar ICH admitted at seven sites. Noncontrast computed tomography images were analyzed for the presence of hypodensities according to validated criteria, defined as any hypodense region strictly encapsulated within the hemorrhage with any shape, size, and density. Occurrence of HE (defined as > 33% and/or > 6-mL growth) and mortality at 90 days were the outcomes of interest. Their predictors were investigated using logistic regression with backward elimination at p < 0.1. Logistic regression models for HE were adjusted for baseline ICH volume, antiplatelet and anticoagulant treatment, onset to computed tomography time, and presence of hypodensities. The logistic regression model for mortality accounted for the ICH score and HE. RESULTS: A total of 175 patients were included (median age 75 years, 40.0% male), of whom 38 (21.7%) had HE and 43 (24.6%) died within 90 days. Study participants with HE had a higher frequency of hypodensities (44.7 vs. 24.1%, p = 0.013), presentation within 3 h from onset (39.5 vs. 24.8%, p = 0.029), and 90-day mortality (44.7 vs. 19.0%, p = 0.001). Hypodensities remained independently associated with HE after adjustment for confounders (odds ratio 2.44, 95% confidence interval 1.13-5.25, p = 0.023). The association between HE and mortality remained significant in logistic regression (odds ratio 3.68, 95% confidence interval 1.65-8.23, p = 0.001). CONCLUSION: Early presentation and presence of noncontrast computed tomography hypodensities were independent predictors of HE in infratentorial ICH, and the occurrence of HE had an independent prognostic impact in this population.

Using Noncontrast Computed Tomography to Improve Prediction of Intracerebral Hemorrhage Expansion.

BACKGROUND: Noncontrast computed tomography hypodensities are a validated predictor of hematoma expansion (HE) in intracerebral hemorrhage and a possible alternative to the computed tomography angiography (CTA) spot sign but their added value to available prediction models remains unclear. We investigated whether the inclusion of hypodensities improves prediction of HE and compared their added value over the spot sign. METHODS: Retrospective analysis of patients admitted for primary spontaneous intracerebral hemorrhage at the following 8 university hospitals in Boston, US (1994-2015, prospective), Hamilton, Canada (2010-2016, retrospective), Berlin, Germany (2014-2019, retrospective), Chongqing, China (2011-2015, retrospective), Pavia, Italy (2017-2019, prospective), Ferrara, Italy (2010-2019, retrospective), Brescia, Italy (2020-2021, retrospective), and Bologna, Italy (2015-2019, retrospective). Predictors of HE (hematoma growth >6 mL and/or >33% from baseline to follow-up imaging) were explored with logistic regression. We compared the discrimination of a simple prediction model for HE based on 4 predictors (antitplatelet and anticoagulant treatment, baseline intracerebral hemorrhage volume, and onset-to-imaging time) before and after the inclusion of noncontrast computed tomography hypodensities, using receiver operating characteristic curve and De Long test for area under the curve comparison. RESULTS: A total of 2465 subjects were included, of whom 664 (26.9%) had HE and 1085 (44.0%) had hypodensities. Hypodensities were independently associated with HE after adjustment for confounders in logistic regression (odds ratio, 3.11 [95% CI, 2.55-3.80]; P<0.001). The inclusion of noncontrast computed tomography hypodensities improved the discrimination of the 4 predictors model (area under the curve, 0.67 [95% CI, 0.64-0.69] versus 0.71 [95% CI, 0.69-0.74]; P=0.025). In the subgroup of patients with a CTA available (n=895, 36.3%), the added value of hypodensities remained statistically significant (area under the curve, 0.68 [95% CI, 0.64-0.73] versus 0.74 [95% CI, 0.70-0.78]; P=0.041) whereas the addition of the CTA spot sign did not provide significant discrimination improvement (area under the curve, 0.74 [95% CI, 0.70-0.78]). CONCLUSIONS: Noncontrast computed tomography hypodensities provided a significant added value in the prediction of HE and appear a valuable alternative to the CTA spot sign. Our findings might inform future studies and suggest the possibility to stratify the risk of HE with good discrimination without CTA.

Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

OBJECTIVE: The objective of this paper was to explore the utility of time to maximum concentration (Tmax )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT). METHODS: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves. RESULTS: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). Tmax  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A Tmax  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73). INTERPRETATION: Tmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888.

Secondary prevention after intracerebral haemorrhage.

BACKGROUND: Intracerebral haemorrhage (ICH) has high mortality in the acute phase and poor functional outcome in the majority of survivors. ICH recurrence is a major determinant of long-term prognosis and is the most feared complication of antithrombotic treatment. On the other hand, ICH patients are at high risk of future ischaemic vascular events. METHODS: This narrative review provides a critical analysis of the current knowledge on the topic. We performed a Pubmed search with the following terms 'intracerebral haemorrhage', 'stroke', 'outcome', 'secondary prevention', 'anticoagulation' and 'atrial fibrillation', including only English written studies with no time restrictions. RESULTS: Blood pressure management is the cornerstone of secondary ICH prevention, regardless of ICH location or underlying cerebral small vessel disease. Resumption of antiplatelet and anticoagulation therapy is often challenging, with limited evidence from randomized trials. Clinical and imaging predictors can inform the stratification of ICH recurrence risk and might identify patients at very high probability of future haemorrhagic events. This narrative review provides a summary of the main diagnostic tools and therapeutic strategies available for secondary prevention in ICH survivors. CONCLUSION: Appropriate recognition and treatment of modifiable risk factors for ICH recurrence might improve outcomes in ICH survivors. Ongoing randomized trials might provide novel insights and improve long-term management.

Added value of non-contrast CT and CT perfusion markers for prediction of intracerebral hemorrhage expansion and outcome.

OBJECTIVES: To test the hypothesis that the combined analysis of non-contrast CT (NCCT) and CT perfusion (CTP) imaging markers improves prediction of hematoma expansion (HE) and outcome in intracerebral hemorrhage (ICH). METHODS: Retrospective, single-center analysis of patients with primary ICH undergoing NCCT and CTP within 6 h from onset. NCCT images were assessed for the presence of intrahematomal hypodensity and shape irregularity. Perihematomal cerebral blood volume and spot sign were assessed on CTP. The main outcomes of the analysis were HE (growth > 6 mL and/or > 33%) and poor functional prognosis (90 days modified Rankin Scale 3-6). Predictors of HE and outcome were explored with logistic regression. RESULTS: A total of 150 subjects were included (median age 68, 47.1% males) of whom 54 (36%) had HE and 52 (34.7%) had poor outcome. The number of imaging markers on baseline imaging was independently associated with HE (odds ratio 2.66, 95% confidence interval 1.70-4.17, p < 0.001) and outcome (odds ratio 1.64, 95% CI 1.06-2.56, p = 0.027). Patients with the simultaneous presence of all the four markers had the highest risk of HE and unfavorable prognosis (mean predicted probability of 91% and 79% respectively). The combined-markers analysis outperformed the sensitivity of the single markers analyzed separately. In particular, the presence of at least one marker identified patients with HE and poor outcome with 91% and 87% sensitivity respectively. CONCLUSION: NCCT and CTP markers provide additional yield in the prediction of HE and ICH outcome. KEY POINTS: • Perihematomal hypoperfusion is associated with hematoma expansion and poor outcome in acute intracerebral hemorrhage. • Non-contrast CT and CT perfusion markers improve prediction of hematoma expansion and unfavorable prognosis. • A multimodal CT protocol including CT perfusion will help the identification of patients at high risk of clinical deterioration and poor outcome.

Effect of the COVID-19 pandemic on disease activity in multiple sclerosis patients treated with hematopoietic stem cell transplantation.

BACKGROUND AND PURPOSE: It is still debated whether the COVID-19 pandemic affected disease activity in people with autoimmune diseases, including multiple sclerosis (MS). The aim of this study, therefore, was to explore the impact of COVID-19 in people with MS (pwMS) not receiving continuative disease-modifying therapy (DMT) after previous treatment with autologous hematopoietic stem cell transplantation (AHSCT). MATERIALS AND METHODS: We included pwMS treated with AHSCT who were in disease remission without receiving DMTs during the pandemic and who were followed up at our centre during the study period. Data on SARS-CoV-2 infection and vaccination were recorded, with details of adverse events and clinical-radiological disease activity. RESULTS: A total of 36 pwMS (31 females; 86%) were included, of whom 23 (64%) had relapsing-remitting (RR-MS) and 13 had secondary progressive MS (SP-MS). Thirty-three pwMS (92%) received anti-SARS-CoV-2 mRNA vaccines. Thirteen patients (36%) developed mild to moderate COVID-19 a median (range) of 58 (4-224) months after AHSCT; seven (54%) of these patients were not yet vaccinated. Transient neurological symptoms after vaccination or infection were reported in 9% and 36% of the patients, respectively. The rate of new inflammatory events (relapses or asymptomatic magnetic resonance imaging [MRI] activity) after AHSCT increased from 0.006 (one asymptomatic new lesion/159 patient-years) before the pandemic to 0.083 (five relapses plus two cases of asymptomatic MRI activity/84 patient-years) since the pandemic start (p = 0.004). CONCLUSIONS: People with MS with a history of highly active disease, who are untreated or receiving moderate-efficacy DMTs might be more vulnerable to disease reactivation, possibly elicited by exogenous triggers. Careful monitoring and further investigation are warranted to ascertain whether special precautions are needed in these cases.

Cognitive phenotypes and factors associated with cognitive decline in a cohort of older patients with atrial fibrillation: The Strat-AF study.

BACKGROUND AND PURPOSE: The multifactorial relationship between atrial fibrillation (AF) and cognitive impairment needs to be elucidated. The aim of this study was to assess, in AF patients on oral anticoagulants (OACs), the prevalence of cognitive impairment, defined according to clinical criteria or data-driven phenotypes, the prevalence of cognitive worsening, and factors associated with cognitive outcomes. METHODS: The observational prospective Strat-AF study enrolled AF patients aged ≥ 65 years who were receiving OACs. The baseline and 18-month protocol included clinical, functional, and cognitive assessment, and brain magnetic resonance imaging. Cognitive outcomes were: empirically derived cognitive phenotypes; clinical diagnosis of cognitive impairment; and longitudinal cognitive worsening. RESULTS: Out of 182 patients (mean age 77.7 ± 6.7 years, 63% males), 82 (45%) received a cognitive impairment diagnosis, which was associated with lower education level and functional status, and higher level of atrophy. Cluster analysis identified three cognitive profiles: dysexecutive (17%); amnestic (25%); and normal (58%). Compared to the normal group, the dysexecutive group was older, and had higher CHA2 DS2 -VASc scores, while the amnestic group had worse cognitive and functional abilities, and medial temporal lobe atrophy (MTA). Out of 128 followed-up patients, 35 (27%) had cognitive worsening that was associated with lower education level, worse cognitive efficiency, CHA2 DS2 -VASc score, timing of OAC intake, history of stroke, diabetes, non-lacunar infarcts, white matter hyperintensities and MTA. In multivariate models, belonging to the dysexecutive or amnestic group was a main predictor of cognitive worsening. CONCLUSIONS: In our cohort of older AF patients, CHA2 DS2 -VASc score, timing of OAC intake, and history of stroke influenced presence, type and progression of cognitive impairment. Empirically derived cognitive classification identified three groups with different clinical profiles and better predictive ability for cognitive worsening compared to conventional clinical diagnosis.

Predictors for clinical and functional outcomes in stroke patients with first-pass complete recanalization after thrombectomy.

BACKGROUND AND PURPOSE: The aim was to identify baseline clinical and radiological/procedural predictors and 24-h radiological predictors for clinical and functional outcomes in stroke patients obtaining complete recanalization in one pass of mechanical thrombectomy (MT) in an optimal baseline and procedural setting. METHODS: A retrospective analysis was conducted of prospectively collected data from 924 stroke patients with anterior large vessel occlusion, Alberta Stroke Program Early Computed Tomography (ASPECT) score ≥6 and pre-stroke modified Rankin Scale score 0, who started MT ≤6 h from symptom onset and obtained first-pass complete recanalization. A first logistic regression model was performed to identify baseline clinical predictors and a second model to identify baseline radiological/procedural predictors. A third model including baseline clinical and radiological/procedural predictors was performed, and a fourth model including independent baseline predictors from the third model plus 24-h radiological variables (hemorrhagic transformation [HT] and cerebral edema [CED]). RESULTS: In the fourth model, higher National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.089) and higher ASPECT score (OR 1.292) were predictors of early neurological improvement (ENI) (NIHSS score ≤4 points from baseline or NIHSS score of 0 at 24 h), whereas older age (OR 0.973), longer procedure time (OR 0.990), HT (OR 0.272) and CED (OR 0.569) were inversely associated with ENI. Older age (OR 0.970), diabetes mellitus (OR 0.456), higher NIHSS score (OR 0.886), general anesthesia (OR 0.454), longer onset-to-groin time (OR 0.996), HT (OR 0.340) and CED (OR 0.361) were inversely associated with 3-month excellent functional outcome (mRS score 0-1), whereas higher ASPECT score (OR 1.294) was a predictor of excellent outcome. CONCLUSIONS: Higher NIHSS score was a predictor of ENI but inversely associated with 3-month excellent outcome. Older age, HT and CED were inversely associated with both good outcomes.

Mechanical thrombectomy in young patients with large vessel occlusion-related ischemic stroke: Data from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND AND PURPOSE: The weight of outcome predictors in acute ischemic stroke (AIS) patients older than 60 years is not necessarily mirrored in the younger population, posing the question of whether outcome determinants specific for the latter might vary. Very few data are available on predictors of outcome in young AIS patients receiving endovascular treatment (EVT). METHODS: We analyzed data for patients aged between 16 and 55 years from the Italian Registry of Endovascular Treatment in Acute Stroke. We divided our population into patients <45 years old and patients aged between 45 and 55 years. After testing the differences between groups in terms of 90-day modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage, we looked for predictors of poor outcome (mRS 3-6), death, and symptomatic intracerebral hemorrhage in the two groups. RESULTS: A total of 438 patients younger than 45 years and 817 aged 45-55 years were included; 284 (34.8%) patients aged 45-55 years and 112 (25.6%) patients younger than 45 years old showed poor 90-day functional outcome (p = 0.001). Predictors of poor outcome in the older group were baseline National Institutes of Health Stroke Scale (NIHSS; p < 0.001), diabetes (p = 0.027), poor collateral status (p = 0.036), and groin puncture-to-recanalization time (p = 0.010), whereas Thrombolysis in Cerebral Infarction (TICI) 2b-3 had an inverse association (p < 0.001). Predictors of poor outcome in patients younger than 45 years were baseline NIHSS (p < 0.001) and groin puncture-to-recanalization time (p = 0.015), whereas an inverse association was found for baseline Alberta Stroke Program Early CT Score (p = 0.010) and TICI 2b-3 (p < 0.001). CONCLUSIONS: Approximately one third of young adults treated with EVT do not reach a good functional outcome. Fast and successful recanalization, rather than common risk factors, has a major role in determining clinical outcome.

Stroke with large vessel occlusion in the posterior circulation: IV thrombolysis plus thrombectomy versus IV thrombolysis alone.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014-15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524-1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215-14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064-6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095-0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009-0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006-0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011-0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395-89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

IV thrombolysis plus thrombectomy versus IV thrombolysis alone for minor stroke with anterior circulation large vessel occlusion from the IRETAS and Italian SITS-ISTR cohorts.

INTRODUCTION: The aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation. PATIENTS AND METHODS: Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed. RESULTS: Among the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173-3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579-12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378-22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310-11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0-1 (72.1% versus 69.1%), mRS score 0-2 (79.6% versus 79%), and death (6.2% versus 6.1%). CONCLUSIONS: Compared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

Pivotal role of multiphase computed tomography angiography for collateral assessment in patients with acute ischemic stroke.

The cerebral collateral circulation is the main compensatory mechanism that maintains the ischemic penumbra viable, the tissue at risk for infarction that can be saved if blood flow is restored by reperfusion therapies. In clinical practice, the extent of collateral vessels recruited after vessel occlusion can be easily assessed with computed tomography angiography (CTA) using two different techniques: single-phase CTA (sCTA) and multi-phase CTA (mCTA). Both these methodologies have demonstrated a high prognostic predictive value for prognosis due to the strong association between the presence of good collaterals and favorable radiological and clinical outcomes in patients with acute ischemic stroke (AIS). However, mCTA seems to be superior to sCTA in the evaluation of collaterals and a promising tool for identifying AIS patients who can benefit from reperfusion therapies. In particular, it has recently been proposed the use of mCTA eligibility criteria has been recently proposed for the selection of AIS patients suitable for endovascular treatment instead of the current accepted criteria based on CT perfusion. In this review, we analyzed the characteristics, advantages and disadvantages of sCTA and mCTA to better understand their fields of application and the potential of mCTA in becoming the method of choice to assess collateral extent in AIS patients.

Clinical Features, Non-Contrast CT Radiomic and Radiological Signs in Models for the Prediction of Hematoma Expansion in Intracerebral Hemorrhage.

PURPOSE: Rapid identification of hematoma expansion (HE) risk at baseline is a priority in intracerebral hemorrhage (ICH) patients and may impact clinical decision making. Predictive scores using clinical features and Non-Contract Computed Tomography (NCCT)-based features exist, however, the extent to which each feature set contributes to identification is limited. This paper aims to investigate the relative value of clinical, radiological, and radiomics features in HE prediction. METHODS: Original data was retrospectively obtained from three major prospective clinical trials ["Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy (SPOTLIGHT)NCT01359202; The Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT)NCT00810888] Patients baseline and follow-up scans following ICH were included. Clinical, NCCT radiological, and radiomics features were extracted, and multivariate modeling was conducted on each feature set. RESULTS: 317 patients from 38 sites met inclusion criteria. Warfarin use (p=0.001) and GCS score (p=0.046) were significant clinical predictors of HE. The best performing model for HE prediction included clinical, radiological, and radiomic features with an area under the curve (AUC) of 87.7%. NCCT radiological features improved upon clinical benchmark model AUC by 6.5% and a clinical & radiomic combination model by 6.4%. Addition of radiomics features improved goodness of fit of both clinical (p=0.012) and clinical & NCCT radiological (p=0.007) models, with marginal improvements on AUC. Inclusion of NCCT radiological signs was best for ruling out HE whereas the radiomic features were best for ruling in HE. CONCLUSION: NCCT-based radiological and radiomics features can improve HE prediction when added to clinical features.

Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke.

BACKGROUND AND PURPOSE: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. METHODS: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b-3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. RESULTS: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P=0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P=0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality (Pinteraction=0.003) and symptomatic intracranial hemorrhage (Pinteraction=0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. CONCLUSIONS: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.

Delayed perihematomal hypoperfusion is associated with poor outcome in intracerebral haemorrhage.

BACKGROUND: The aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH). METHODS: A single-centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6 h from onset (T0) and at 7 days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. Poor functional prognosis (modified Rankin Scale 3-6) at 90 days was the outcome of interest, and predictors were explored with multivariable logistic regression. RESULTS: A total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3-6 at 90 days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change -7.8 vs. -6.0 ml/100 g/min, p < .001, and median CBV change -0.5 vs. -0.4 ml/100 g, p = .010, respectively). This finding remained significant after adjustment for confounders (odds ratio [OR] for 1 ml/100 g/min CBF reduction: 1.33, 95% confidence interval [CI] (1.15-1.55), p < .001; OR for 0.1 ml/100 g CBV reduction: 1.67, 95% CI 1.18-2.35, p = .004). The presence of CBF < 20 ml/100 g/min at T7 was then demonstrated as an independent predictor of poor functional outcome (adjusted OR: 2.45, 95% CI 1.08-5-54, p = .032). CONCLUSION: Perihaemorrhagic hypoperfusion becomes more severe in the days following acute ICH and is independently associated with poorer outcome. Understanding the underlying biological mechanisms responsible for delayed decrease in perihematomal perfusion is a necessary step towards outcome improvement in patients with ICH.