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Thrombolysis for acute ischemic stroke has predominantly been with alteplase for over a quarter of a century. In recent years, with trials showing evidence of higher rates of successful reperfusion, similar safety profile and efficacy of tenecteplase (TNK) as compared to alteplase, TNK has now emerged as another potential choice for thrombolysis in acute ischemic stroke. In this review, we will focus on these recent advances, aiming: (1) to provide a brief overview of thrombolysis in stroke; (2) to provide comparisons between alteplase and TNK for clinical, imaging, and safety outcomes; (3) to focus on key subgroups of interest to understand if there is an advantage of using TNK over alteplase or vice-versa, to review available evidence on role of TNK in intra-arterial thrombolysis, as bridging therapy and in mobile stroke units; and (4) to summarize what to expect in the near future from recently completed trials and propose areas for future research on this evolving topic. We present compelling data from several trials regarding the safety and efficacy of TNK in acute ischemic stroke along with completed yet unpublished trials that will help provide insight into these unanswered questions.

Background and purposeWe evaluate whether non-haemorrhagic imaging markers (NHIM) (white matter hyperintensity patterns, lacunes and enlarged perivascular spaces (EPVS)) can discriminate cerebral amyloid angiopathy (CAA) from hypertensive cerebral small vessel disease (HTN-cSVD) among patients with isolated lobar intracerebral haemorrhage (isolated-LICH).MethodsIn patients with isolated-LICH, four cSVD aetiologic groups were created by incorporating the presence/distribution of NHIM: HTN-cSVD pattern, CAA pattern, mixed NHIM and no NHIM. CAA pattern consisted of patients with any combination of severe centrum semiovale EPVS, lobar lacunes or multiple subcortical spots pattern. HTN-cSVD pattern consisted of any HTN-cSVD markers: severe basal ganglia PVS, deep lacunes or peribasal ganglia white matter hyperintensity pattern. Mixed NHIM consisted of at least one imaging marker from either pattern. Our hypothesis was that patients with HTN-cSVD pattern/mixed NHIM would have a higher frequency of left ventricular hypertrophy (LVH), which is associated with HTN-cSVD.ResultsIn 261 patients with isolated-LICH, CAA pattern was diagnosed in 93 patients, HTN-cSVD pattern in 53 patients, mixed NHIM in 19 patients and no NHIM in 96 patients. The frequency of LVH was similar among those with HTN-cSVD pattern and mixed NHIM (50% vs 39%, p=0.418) but was more frequent in HTN-cSVD pattern compared with CAA pattern (50% vs 20%, pConclusionAmong patients with isolated-LICH, NHIM may help differentiate HTN-cSVD from CAA, using LVH as a marker for HTN-cSVD.

Introduction: Predicting individual outcomes post-stroke with the highest possible accuracy is a crucial steppingstone in the realization of precision medicine. We here evaluated various types of lesion information in their capacity to predict stroke severity in a large cohort of patients with acute ischemic stroke. Methods: A total of 1,075 patients of the MRI-GENIE study [age: 64.2(14.7), 38% women] contributed to analyses (N=792 as train and N=283 as test sample). We employed ridge regression with hyperparameter optimization and nested five-fold cross-validation to predict acute NIHSS-based stroke severity. Our baseline model considered DWI lesion volume. Further models tested structural lesion location, indirect structural and functional lesion connectivity, individually and combined with lesion volume. Data was preprocessed by principal component analysis (PCA), retaining 95% of the variance of the original data. Model performance was compared in terms of explained variance (R-squared) and 95% confidence intervals in the outer loop of the training set and the test set. Results: Structural lesion connectivity enabled the highest prediction performance in the test set ( Figure 1 ). Prediction performance did not change notably with inclusion of lesion volume information. This contrasted with the combination of functional lesion connectivity and lesion volume that achieved a substantially higher prediction performance compared to functional lesion connectivity or lesion volume in isolation. Lesion location resulted in a prediction performance that was in the range of lesion volume alone and significantly lower than the ones of structural or functional connectivity with lesion volume. Conclusions: Structural connectivity facilitated the most convincing prediction of stroke severity. The capacity of functional lesion connectivity was substantially improved by the inclusion of lesion volume, indicating both represent complementary information.

Introduction: Patients with baseline disability account for up to one-third of stroke presentations. Despite growing evidence supporting their benefit from endovascular thrombectomy (EVT), there remains controversy in treatment selection. We compared the long-term outcomes and the likelihood of comfort care for large vessel occlusion (LVO) stroke patients who presented with severe baseline disability treated with EVT versus medical management. Methods: Individuals who presented with LVO were identified from a prospectively maintained database from January 2017 to December 2020. Severe baseline disability was defined as modified Rankin Scale (mRS) 3-5. Delta mRS was defined as the difference between baseline and 90-day mRS. Logistic and ordinal regressions were performed to evaluate the relationships between EVT and outcomes. Results: A total of 175/1007 (17%) patients were identified with severe baseline disability. The median age was 82 (IQR 70-89), and 59% were female. Thirty-two (18%) patients with severe baseline disability were treated with EVT. EVT was independently associated with improved delta mRS (B=-1.048; 95%CI=-1.777,-0.318; p=0.005) when accounting for age and NIHSS. However, EVT did not reduce the odds of transitioning to comfort care (aOR=0.794; 95%CI=0.347,1.818; p=0.585) when accounting for age and NIHSS. Seventy-six (43%) patients with severe baseline disability were transitioned to comfort care. Of the 99 patients who were not transitioned to comfort care, 18 were treated with EVT. In this subgroup not transitioned to comfort care, EVT was independently associated with improved delta mRS (B=-2.794; 95%CI=-4.002,-1.586; p Conclusions: Among patients with severe baseline disability, EVT is associated with less post-stroke accumulated disability without limiting transitions to comfort care. EVT is compatible with goal-concordant care in patients with severe baseline disability; it should not be routinely withheld on the sole basis of baseline disability.

Introduction: Deep learning (DL) has allowed for substantial progress in many, often machine vision-focused medical scenarios. Since DL models typically require 10 5 -10 7 examples, it is currently unknown whether DL can also enhance predictions of outcomes post-stroke in real-world samples of stroke patients that are several magnitudes smaller. We here compared the capacities of linear and DL algorithms regarding their prediction of stroke severity. Methods: Our analyses relied on a total of 1435 patients assembled from the MRI-GENIE study and a Massachusetts General Hospital-based study. The primary outcome was acute NIHSS-based stroke severity, which we predicted by means of lesion location. We automatically derived lesion segmentations from DWI scans, performed spatial normalization and principal component analysis (PCA), retaining 95% of the variance of the original data. We then separated a train, validation, and test set, of sizes 918, 230, and 287 respectively. We downsampled the train set to 100, 300, and 900 and learned to predict the NIHSS score for each sample size with regularized linear regression and an 8-layered neural network. We selected hyperparameters on the validation set and conducted 500 dataset splits. We here report explained variance (R-squared) in the test set. Results: While linear regression performed favorably for a sample size of 100 patients (R-squared=0.28), DL started to significantly outperform linear regression when trained on 900 patients (R-squared=0.34, Figure 1 ). Average prediction performance improved by ~20% when increasing the sample size 9x. Conclusions: For sample sizes of ~1000 patients, DL showed a more convincing prediction performance for stroke severity than typically employed linear methods. Our findings suggest the existence of non-linear relationships between lesion location and outcome post-stroke that can be utilized for an improved prediction performance once samples are reasonably large.

Introduction: Coma is an unresponsive state of disordered consciousness characterized by impaired arousal and awareness. While coma has been studied in the context of traumatic brain injury, the epidemiology and pathophysiology of coma in ischemic stroke has been underexplored. We sought to characterize the incidence and clinical features of coma as a presentation of large vessel occlusion (LVO) stroke. Methods: Individuals who presented with LVO were identified from July 2018 to December 2020. Coma was defined as an unresponsive state of impaired arousal and awareness, operationalized as a score of 3 on NIHSS item 1a: responds only with reflex motor or autonomic effects or totally unresponsive, flaccid, and areflexic. Results: A total of 28/638 (4.4%) patients with large vessel occlusion stroke were identified as presenting with coma. The median age was 65 (IQR 48-78), and 57% were female. The median NIHSS was 32 (IQR 29-34). Occlusion locations included basilar (10), vertebral (2), P1 posterior cerebral (2), internal carotid (4), M1 middle cerebral (6), and M2 middle cerebral arteries (4). In all 14 patients with anterior LVO, the acute LVO was unilateral. Of these 14, 6 had evidence of acute or chronic stroke involving the contralateral hemisphere; 1 experienced seizure; 1 experienced cardiac arrest; and 1 had chronic occlusion of the contralateral ICA. Overall, 20/28 died during the admission. Of those who died, 9 presented with anterior LVO and 11 with posterior LVO. Eight patients were treated with EVT. For those not treated, reasons included established infarct with ASPECTS Conclusions: It is not uncommon for patients with LVO stroke to present with coma, and 65% of patients not treated with EVT had delayed presentations or large established infarcts, emphasizing the need for maintaining a high index of suspicion. While more commonly thought to result from posterior LVO, coma in our cohort was similarly likely to result from anterior LVO. Further study of these patients may shed light on the pathophysiology of coma. Efforts to improve early diagnosis and care are crucial given their poor outcomes.

Introduction: With continued expansion in indications for endovascular thrombectomy (EVT), understanding the pathophysiology of reperfusion injury and the risks of hemorrhagic transformation (HT) becomes increasingly important. Pre-EVT infarct topography may have implications for treatment decisions acutely (e.g. stenting), and with post EVT care (e.g. antithrombotics). We sought to quantify region-specific volumes of infarcted tissue on pre-EVT MRI, understand their importance for HT, and identify associations with clinical and imaging characteristics. Methods: Patients with pre-EVT MRI were identified from a prospectively maintained database. Each patient’s diffusion weighted sequence underwent manual infarct delineation and was registered to a standard space for overlay with cortical, subcortical, and white matter atlases. HT was defined as ECASS PH1 or PH2. Variables with p Results: A total of 165 participants [median age 69 (IQR 56-79), 56% women] were identified. Intravenous alteplase was administered to 52%; 70% achieved TICI 2b-3 reperfusion. HT occurred in 8%. The distribution of pre-EVT infarcts was 48% (38-60%) white matter, 23% (6-47%) cortex, and 15% (4-28%) basal ganglia. Pre-EVT infarct volumes [median (IQR)] were 22 cc (12-43 cc) for total, 11 cc (6-19 cc) for white matter, 5 cc (1-19 cc) for cortex, and 3 cc (1-6 cc) for basal ganglia infarct. Paramagnetic sequences showed 3% had petechial hemorrhage and 40% had susceptibility vessel sign. Basal ganglia infarct volume was independently associated with HT (OR=1.342, 95%CI=1.002,1.797) in a model including white matter infarct volume, cortex infarct volume, smoking, and puncture-to-recanalization time. Basal ganglia infarct volume was linked to susceptibility vessel sign (Beta=0.233, p=0.006) and NIHSS (Beta=0.220, p=0.012), when controlling for total infarct volume. Conclusions: Greater basal ganglia infarct volume was associated with a higher risk of HT when accounting for infarct volumes in other regions. Susceptibility vessel sign was associated with basal ganglia infarct volume, which may be related to acute middle cerebral artery perforator occlusion.

Several studies have shown promising outcomes of the Woven EndoBridge (WEB) device for the treatment of wide-necked intracranial bifurcation aneurysms. This is a multicenter study attempts to explore the changes in trends and treatment outcomes over time for WEB embolization of intracranial aneurysms. The WorldWideWEB consortium is a retrospective multicenter collaboration of data from international centers spanning from January 2011 and June 2021, with no limitations on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. These patients were stratified based on treatment year into five treatment intervals: 2011-2015 (N = 66), 2016-2017 (N = 77), 2018 (N = 66), 2019 (N = 300), and 2020-2021 (N = 173). Patient characteristics and angiographic and clinical outcomes were compared between these time intervals. This study comprised 671 patients (median age 61.4 years; 71.2% female) with 682 intracranial aneurysms. Over time, we observed an increasing tendency to treat patients presenting with ruptured aneurysms and aneurysms with smaller neck, diameter, and dome widths. Furthermore, we observed a trend towards more off-label use of the WEB for sidewall aneurysms and increased adoption of transradial access for WEB deployment. Moreover, the proportion of patients with adequate WEB occlusion immediately and at last follow-up was significantly higher in more recent year cohorts, as well as lower rates of compaction and retreatment. Mortality and complications did not differ over time. This learning curve study suggests improved experience using the WEB for the treatment of intracranial aneurysms and has yielded higher rates of adequate occlusion over time.

The Woven EndoBridge (WEB) can be used to treat wide-necked aneurysms without antiplatelet medications, suggesting it may have advantages in the setting of aneurysmal subarachnoid hemorrhage (aSAH). The goal was assessment of safety and efficacy of WEB in aSAH given the delayed nature of aneurysmal thrombosis. An international retrospective analysis of patients with aSAH treated with WEB was conducted at 7 tertiary centers from 2016 to 2020. Outcomes included rates of rebleeding, retreatment, complications, and complete occlusion. Furthermore, a systematic review and meta-analysis was conducted from 2011 to 2020 assessing the same outcomes. All pooled event rates were calculated using a random effect model. Consecutive patients with aSAH harbored 25 aneurysms that were treated with 29 WEB devices. The mean age was 53 years, and 65% were female. Zero experienced rebleeding, 2 were retreated, 2 experienced complications, 16 were completely occluded at 3 months, and 21 were completed occluded at 9–12 months. Meta-analysis of 309 WEB treatments for aSAH from 7 case series revealed 2.5% (95% CI 1–5%) had rebleeding, 9% (95% CI 4–17%) were retreated, 17% (95% CI 10–30%) had complications, and 61% (95% CI 51–71%) were completely occluded at 3–6 months. WEB embolization in the setting of aSAH provides similar protection against rebleeding with comparable retreatment rates to traditional approaches. However, there is a higher rate of incomplete radiographic occlusion and operative complications compared to WEB embolization of unruptured aneurysms. Long-term prospective studies are needed to fully delineate the role of WEB embolization in aSAH.

The relevance of impaired microvascular tissue reperfusion despite successful macrovascular angiographic reperfusion (no-reflow) in acute ischemic stroke (AIS) remains controversial. In this study, we aimed to investigate the impact of tissue optimal reperfusion (TOR) and its influencing factors. From December 1, 2020 to December 1, 2021, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score [mTICI] ≥ 2b) after mechanical thrombectomy (MT) were retrospectively reviewed. Computed tomography perfusion was performed before and after MT. Successful reperfusion was assessed by TOR, defined as 90% reduction of the Tmax 6 s lesion volumes between baseline and early follow-up perfusion profiles. The impact of TOR on functional outcomes after successful recanalization and influencing factors for TOR were both investigated. Sixty-three patients were included, including 44 cases in the TOR group and 19 cases in the non-TOR group. The TOR group had a higher rate of favorable outcome (aOR 4.366, 95%CI 1.159-16.445, p = 0.030) and NIHSS improvement (aOR 5.089, 95%CI 1.340-19.322, p = 0.017) than the non-TOR group. Multivariable logistic regression showed baseline glucose (OR 0.648, 95%CI 0.492-0.854, p = 0.002) and mTICI 2c/3 (OR 10.984, 95%CI 2.220-54.343, p = 0.003) predicted TOR in model 1; in model 2, postoperative glucose (OR 0.468, 95%CI 0.278-0.787, p = 0.004) and mTICI 2c/3 (OR 9.436, 95%CI 1.889-47.144, p = 0.006) were predictive. TOR was strongly associated with good functional outcomes after successful recanalization of MT. Higher mTICI grade and lower perioperative glucose level may predict microvascular tissue reperfusion.

Introduction: The utility of intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is controversial. Low early recanalization (ER) rates and potential delays to MT may support bypassing IVT before MT. Recent trials suggest MT alone is reasonable for LVO patients presenting directly to MT-capable centers. However, bypassing IVT has not been evaluated for patients first presenting to “spoke” hospitals capable of administering IVT but requiring transfer to a “hub” hospital for MT. Here we examined how spoke IVT influences LVO ER and spoke-to-hub transfer time (TT) within our hub-and-spoke network. Methods: Patients presenting to 25 spoke hospitals before hub transfer from 2018 to 2020 who were considered possible EVT candidates with pre-transfer CTA-defined LVO and ASPECTS ≥6 were identified from a prospectively maintained database. ER was determined by chart review of vessel imaging on hub arrival. TT was prospectively recorded. Statistics were performed using permutation resampling and linear regression in R. Results: Of 177 patients included, 76 received IVT. Baseline characteristics, NIHSS, and intracerebral hemorrhage were similar between groups. Spoke IVT improved ER frequency [12/76 (15.8%) vs. 3/101 (3.0%), P Conclusion: Within our network, IVT significantly increases ER and decreases TT, which may contribute to improved 90-day outcomes. This retrospective study supports following current recommendations that IVT be given to all eligible patients at spoke hospitals prior to transfer for MT consideration.

Objective: The objective of this study is to assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications following endoluminal flow diversion with a single flow diverting stent. Methods: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and >12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. Results: A total of 205 patients underwent flow diversion with a single pipeline embolization device. During the study period, 12.7% of treated aneurysms remained non-occluded. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and non-occluded groups. Non-occluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 mo, p=0.016) with ANOVA demonstrating a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202)=4.2, p=0.016). An exploratory analysis demonstrated the optimum DAPT discontinuation time to minimize aneurysm non-occlusion rates was 7.9 months (95% CI: 6-11 months). There was no significant difference in the rate of complications or delayed ischemic strokes observed between patients receiving short (6 mo) DAPT (7.9% vs 9.3%, p=0.76). Conclusions: Following endovascular flow-diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing delayed thromboembolic complications.

Introduction: Endovascular thrombectomy (EVT) has revolutionized the care of emergent large vessel occlusion (ELVO) stroke patients. It is, therefore, crucial to optimize its delivery to eligible candidates. Within hub-and-spoke hospital system models, some patients first present to distant spoke hospitals and require transfer to hub hospitals for EVT. We sought to understand changes in EVT eligibility during transfer. Methods: Consecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pre-transfer CTA-defined ELVO and Alberta Stroke Program Early CT Score ≥6 were identified from a prospectively maintained database. Outcomes of interest included hub EVT, reasons for EVT ineligibility, and 90-day functional independence (modified Rankin Scale, mRS ≤2). Results: Among 258 patients, the median age was 70 years (IQR 60-81) and 50% were female. Forty-four percent underwent EVT upon hub arrival, of which 87% achieved Thrombolysis in Cerebral Infarction 2b-3 reperfusion. Compared to EVT-eligible patients, ineligible patients were older (73 vs 68 years, p=0.04), had lower NIH Stroke Scale (NIHSS, 10 vs 16, p Conclusions: These data support that approaches to increase EVT eligibility among ELVO transfers may improve long term outcomes. Infarct growth represents the primary reason for ineligibility. Possible interventions include direct field triage to the hub when feasible, improving inter-hospital transfer times, supporting ischemic penumbra before EVT, and developing novel agents to slow infarct growth.

Direct carotid-cavernous fistulas are high-flow abnormal connections between the carotid artery and cavernous sinus, which are associated with significant morbidity and mortality if left untreated. In addition to endovascular coil embolization, there is an evolving role for alternative stand-alone or adjunctive treatment approaches. We describe a case of flow diversion as an adjunctive treatment approach in a treatment-resistant direct carotid-cavernous fistula and review the literature on the use of flow diversion in this clinical context.We describe the clinical course, imaging findings, and outcome of a patient who developed a traumatic carotid-cavernous fistula requiring multiple interventions. We also performed an updated literature review of all published cases of flow diversion use in the treatment of direct CCFs.Our patient achieved angiographic cure and significant improvement in symptoms at 6-month follow-up. A total of 53 cases of flow diversion use in direct carotid-cavernous fistulas were identified from a literature search. In one third of cases, flow diversion was used as a stand-alone treatment modality. Angiographic resolution was achieved in 90% of cases at a median follow-up duration of 6 months. One half of reported cases had complete resolution of symptoms and a further third noted clinical improvement in at least some of their symptoms.There is an emerging role for flow diversion as a safe and effective stand-alone or adjunctive treatment option for direct carotid-cavernous fistulas. Our case further supports a role for flow diversion in treatment-resistant fistulas with high-risk features. As treatment approaches continue to evolve, prospective, randomized data will be needed to establish the role of flow divertors in the hierarchy of available treatments for carotid-cavernous fistulas.

The aim of this study is to explore the clinical features associated with neurological complications of infective endocarditis (IE) and to assess the impact of neurological complications on clinical outcomes.The frequency of relevant clinical features was compared in a case series of IE patients with and without neurological complications admitted to a single health care system from 2015 to 2019. Variables with significant differences (p ≤ 0.05) in baseline characteristics in univariate logistic regression models were entered into multivariable models along with age to determine associations with neurological complications, unfavorable discharge outcomes (modified Rankin score ≥ 3), and in-hospital mortality.260 patients with a mean age of 51 (±18) years and 103 (40%) females were included. Neurological complications occurred in 165 (63%) patients, with the most common being septic emboli (66 patients, 25%). In the regression analyses, antiplatelet usage (aOR 1.87, 95% CI [1.05-3.32]) and mitral valve vegetations (aOR 2.66, 95% CI [1.22-5.79]) were independently associated with neurological complications. Territorial infarction (aOR 4.13, 95% CI [1.89-9.06]) and encephalopathy (aOR 3.95, 95% CI [1.19-13.05]) were associated with an increased risk of unfavorable outcome, while cardiac surgery was associated with a lower risk of both unfavorable outcome (aOR 0.40, 95% CI [0.22-0.71]) and in-hospital mortality (aOR 0.18, 95% CI [0.09-0.35]).Neurological complications are common in IE patients and are associated with mitral valve endocarditis and antiplatelet usage. Of the neurological complications, territorial infarcts and encephalopathy are associated with unfavorable discharge outcomes.

Background Acute ischemic stroke (AIS) in the context of COVID‐19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. Methods and Results A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS‐CoV‐2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID‐19 who were diagnosed with AIS, the median age was 63 years (range, 27–94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, ( P =0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P =0.047). After multivariable adjustment for possible confounders, a 1‐year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90–0.99; P =0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02–1.10; P =0.007). Conclusions AIS in the context of COVID‐19 affects young patients at much greater rates than pre‐pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

Introduction: Endovascular thrombectomy (EVT) has revolutionized large vessel occlusion (LVO) stroke care. However, over half remain functionally disabled or die despite treatment. Understanding outcomes may influence EVT selection, novel therapies, and prognostication. We sought to identify associations between outcomes and brain regions involved in ischemic lesions. Methods: For consecutive LVO patients with post-EVT MRI, acute ischemic lesions were manually segmented from DWI and spatially normalized. Individual lesion volumes were automatically parcellated (atlas-defined 94 cortical regions, 14 subcortical nuclei, 20 white matter tracts) and then reduced to ten anatomically plausible lesion patterns using unsupervised dimensionality reduction techniques. Ninety-day modified Rankin Scale (mRS) was modeled via Bayesian regression, taking the ten lesion patterns as inputs and controlling for lesion size, age, sex, acute NIH Stroke Scale, alteplase, and TICI 2b-3 reperfusion. Results: We identified 153 LVO patients with mean age 68±15 years and 51% female. Median NIHSS was 16 (IQR 13-20), 56% received alteplase, and 84% achieved TICI2b-3. The lesion patterns predictive of 90-day mRS involved bilateral subcortical nuclei, pre- and postcentral gyri, insular and opercular cortex, as well as left-sided inferior frontal and angular gyri ( Figure 1A ). Lesions affecting white matter tracts had the highest relevance predicting 90-day mRS ( Figure 1B ). Conclusions: These data describe the significance for outcomes of specific brain regions involved in ischemic lesions on MRI after EVT. Future work in additional datasets is needed to confirm these granular findings.

Objectives Despite the proven efficacy of endovascular thrombectomy (EVT) for large vessel occlusion stroke, over half treated remain functionally disabled or die. Infarct topography may have implications for prognostication, patient selection, and the development of tissue-specific neuroprotective agents. We sought to quantify white matter injury in anterior circulation acute infarcts post-EVT to understand its significance and identify its determinants. Materials and Methods Demographics, history, presentations, and outcomes for consecutive patients treated with EVT were recorded in a prospectively maintained database at a single center. Acute infarct masks were coregistered to standard space. Standard atlases of white matter, cortex, and basal ganglia were used to determine region-specific infarct volumes. Results 167 individuals were identified with median age 69 years and 53% women. 85% achieved adequate reperfusion (TICI 2b-3) after EVT; 43% achieved 90-day functional independence (mRS 0-2). Median infarct volumes were 45cc (IQR 18-122) for total, 17cc (6-49) for white matter, 21cc (4-53) for cortex, and 5cc (1-8) for basal ganglia. The odds of 90-day mRS 0-2 were reduced in patients with larger white matter infarct volume (cc, OR=0.89, 95%CI=0.81-0.96), independent of cortex infarct volume, basal ganglia infarct volume, age, NIHSS, and TICI 2b-3 reperfusion. Reperfusion-to-MRI time was associated with white matter infarct volume (hr, β=0.119, p=0.017), but not cortical or basal ganglia infarct volume. Conclusions These data quantitatively describe region-specific infarct volumes after EVT and suggest the clinical relevance of white matter infarct volume as a predictor of long-term outcomes. Further study is warranted to examine delayed white matter infarction and the significance of specific white matter tracts.

Introduction: Telestroke (TS) networks provide an important function in community hospitals by supporting thrombolytic use and screening for patients with large vessel occlusion (LVO) who may be eligible for endovascular thrombectomy (EVT). The expansion of treatment to 24 hours from last known well has dramatically increased the pool of patients to screen. Idealized triage processes within TS networks remain uncertain. We sought to characterize the impact of the implementation of a routine spoke hospital (SH) CTA protocol in our integrated TS network. Methods: We introduced protocol-driven CTA process at 25 SH in November 2017. We retrospectively identified patients who presented to a SH with an NIHSS ≥ 6 between 3/1/2016-3/1/2017 (pre-CTA) and 3/1/2018-3/1/2019 (post-CTA). We characterized baseline demographics, transfer patterns, and rates of CTA utilization, LVO, and EVT. Differences were assessed using Wilcoxon rank-sum for continuous variables and χ2 tests for categorical variables. Results: There were 167 patients pre-CTA and 207 post-CTA. The rate of CTA at SHs increased from 13% to 70% (p4.5 hr from last known well time, the rates of transfer out of SHs did not increase (56% vs 54%, p=0.83). The rate of transfer to our CSC for EVT increased non-significantly (26% vs 35%, p=0.12) but the proportion of patients transferred >4.5 hr increased ~5-fold (7% vs 34%, p Conclusions: Implementation of a CTA protocol at SHs in our TS network was feasible, and effective in improving the efficiency of interhospital triage of candidates for EVT. In the era of late-window EVT, introducing CTA into PSC enhances the stroke system of care and keeps care local whenever possible. Replication of these findings in other TS networks is needed.

Background and Purpose— Current guidelines for endovascular thrombectomy (EVT) used to select patients for transfer to thrombectomy-capable stroke centers (TSC) may result in unnecessary transfers. We sought to determine the impact of simulated baseline vascular imaging on reducing unnecessary transfers and clinical-imaging factors associated with receiving EVT after transfer. Methods— We identified patients with stroke transferred for EVT from 30 referring hospitals between 2010 and 2016 who had a referring hospitals brain computed tomography and repeat imaging on TSC arrival available for review. Initial Alberta Stroke Program Early CT scores and TSC vascular occlusion level were assessed. The main outcome variable was receiving EVT at TSC. Models were simulated to derive optimal triaging parameters for EVT. Results— A total of 508 patients were included in the analysis (mean age, 69±14 years; 42% women). Application at referring hospitals of current guidelines for EVT yielded sensitivity of 92% (95% confidence interval, 0.84–0.96) and specificity of 53% (95% confidence interval, 0.48–0.57) for receiving EVT at TSC. Repeated simulations identified optimal selection criteria for transfer as National Institute of Health Stroke Scale >8 plus baseline vascular imaging (sensitivity=91%; 95% confidence interval, 0.83–0.95; and specificity=80%; 95% confidence interval, 0.75–0.83). Conclusions— Our findings provide quantitative estimates of the claim that implementing vascular imaging at the referring hospitals would result in significantly fewer futile transfers for EVT and a data-driven framework to inform transfer policies.

Since the term “lacune” was adopted in the 1800s to describe infarctions from cerebral small vessels, their underlying pathophysiological basis remained obscure until the 1960s when Charles Miller Fisher performed several autopsy studies of stroke patients. He observed that the vessels displayed segmental arteriolar disorganization that was associated with vessel enlargement, hemorrhage, and fibrinoid deposition. He coined the term “lipohyalinosis” to describe the microvascular mechanism that engenders small subcortical infarcts in the absence of a compelling embolic source. Since Fisher’s early descriptions of lipohyalinosis and lacunar stroke, there have been many advancements in the understanding of this pathological phenomenon. Herein, we review lipohyalinosis as it relates to modern concepts of cerebral small vessel disease. We discuss clinical classifications of lacunar stroke as well as radiologic definitions based on modern neuroimaging techniques. We provide a broad and comprehensive overview of lacunar stroke pathophysiology both at the vessel and parenchymal levels. We also comment on the role of biomarkers, the possibility of systemic disease processes, and advancements in the genetics of cerebral small vessel disease. Lastly, we assess preclinical models that can aid in studying lacunar stroke disease pathogenesis. Enhanced understanding of this highly prevalent disease will allow for the generation of specific molecular targets capable of mitigating disease sequalae.

Introduction: Early changes in NIH stroke scale (NIHSS) within the first days after ischemic stroke have been associated with clinical outcomes, however association with patient-centered outcomes is unknown. Predicting outcomes is important for decisions after the acute period. We sought to characterize the magnitude of early NIHSS change and identify its impact on 90-day Stroke Impact Scale-16 (SIS). Methods: Data were collected as part of an ongoing single-center study of recovery for patients with upper extremity weakness. NIHSS at time of presentation (presentation NIHSS) was obtained by chart review and NIHSS at time of enrollment (enrollment NIHSS) was assessed prior to acute hospital discharge. We collected demographic, treatment, imaging, and 90-day outcomes. We used a linear regression to determine the relationship of early NIHSS improvement (presentation-enrollment NIHSS) with 90-day SIS and dichotomized the dataset (early NIHSS improvement ≥3 vs not) to compare predefined clinical variables hypothesized to be early improvement predictors. Results: Study participants (n=72) had median presentation NIHSS of 6 (IQR4-13) and median enrollment NIHSS of 6 (IQR4-10) with a mean of 2.7+/-2.5 days between timepoints. Seventeen subjects improved by ≥3 and 16 worsened by ≥3. Acute treatments were endovascular therapy (ET, n=10) and thrombolysis (tPA, n=16). Early NIHSS improvement was associated with better 90-day SIS (p=0.012). This association remained when subjects who underwent ET or tPA were excluded (p=0.046). Subjects with early NIHSS improvement ≥3 were less likely to have hypertension (15 vs 85%, p=0.039) and more likely to have undergone ET (60 vs 40%, p=0.010), but there were no differences in tPA treatment, infarct volume, days between timepoints, age, or other medical history. Conclusion: This analysis confirms that there are substantial changes in NIHSS in the first days after stroke. Early NIHSS improvement was associated with better 90-day SIS, even when excluding subjects who underwent treatment with ET or tPA suggesting this association also exists for subjects with spontaneous improvement. Early NIHSS improvement may be a useful prognostic tool for patient-centered outcomes after stroke.

Introduction: Cerebral amyloid angiopathy-related inflammation (CAAri) is characterized by altered cognition, headaches, and seizures and is associated with vasogenic edema and an anti-amyloid immune response on imaging and histology. Optimal treatments are poorly understood. Our objective was to analyze clinical features and treatment strategies in CAAri to identify predictors of outcome. Methods: We retrospectively reviewed the records of 56 consecutive patients with pathologically or radiographically diagnosed CAAri at Massachusetts General Hospital. Clinical, laboratory, pathology, and treatment data were collected for analysis. Inflammatory events were defined by previously described clinical and radiographic parameters. Chi-Square analyses were used to determine if treatment with immunotherapy was associated with outcomes. Results: Of the 56 subjects, 8 had vessel wall inflammation on pathology, 21 had perivascular inflammation on pathology, and 48 had probable CAAri by validated imaging criteria. Thirty-five were female, 49 presented with an inflammatory event, and the mean age at first event was 69.3+/-10.2 years. First events included headache (n=21), cognitive/behavioral change (29), focal deficit (9), seizure (20), and other (6). CSF was examined in 26 subjects after first event (6 with WBC>5, 24 with protein>45, 1 without abnormality). Treatments included steroids (33), cyclophosphamide (6), mycophenolate (2), and no treatment (14). After first event, clinical improvement (n=39) was more likely if treated with any immunotherapy than not (32/34 vs 7/14, p=0.001). Radiographic improvement (28) was more likely if treated than not (24/28 vs 4/14, p Conclusion: This study of the largest CAAri patient population to-date suggests treatment with immunosuppression is associated with improved clinical and radiographic outcomes and decreased recurrence of events.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p=0.003), less atrial fibrillation (13% vs 40%, p

Introduction: Interfacility transfer of patients with suspected large vessel occlusion for endovascular intervention is increasingly common. Eligibility depends on stroke severity (NIHSS), yet changes in NIHSS during transfer have not been well-described. Objective: to characterize changes in NIHSS during transfer, and identify factors associated with early rapid improvement. Methods: Using prospectively collected data from our institution’s Get with the Guidelines-Stroke registry and telestroke network portal, we identified all stroke patients transferred to our hospital from 01/01/10-01/01/16. We calculated change in NIHSS (arrival score minus telestroke score at transferring outside hospital, OSH). Logistic regression identified factors associated with early rapid improvement, controlling for patient characteristics available on arrival, including tPA use. Results: Among the 505 patients included, median NIHSS at OSH was 11 (IQR 5-18) and on arrival was 9 (IQR 3-17); median change of 0 (IQR -3-0). Scores increased by ≥4 points among 7%, and decreased by ≥4 among 19%. In bivariate analysis, early rapid improvement was more likely in patients who were ambulatory at baseline, had higher NIHSS at OSH, and were treated with tPA, and less likely among patients with history of hypertension (Table). In multivariable modeling, early rapid improvement was associated with history of coronary artery disease (CAD) and higher NIHSS at OSH (Table). Patients with early rapid improvement were more likely to be discharged home in bivariate (OR 1.58, 95%CI 1.01-2.50) and multivariable analyses (OR 4.07, 95%CI 1.58-10.49). Conclusion: In this cohort of transferred patients, NIHSS scores were frequently unchanged or decreased during transfer. History of CAD and higher baseline NIHSS were associated with early rapid improvement during transfer. If confirmed in a larger sample, these results may be useful for triage and intervention planning for transferred patients.

Background and Purpose— For suspected large vessel occlusion patients efficient transfer to centers that provide endovascular therapy (ET) is critical to maximizing treatment opportunity. Our objective was to examine associations between transfer time, modes of transfer, ET, and outcomes within a hub-and-spoke telestroke network. Methods— Patients with ischemic stroke were included if transferred to a single hub hospital between January 2011 and October 2015 with National Institutes of Health Stroke Scale>6, onset Results— Of 234 patients that met inclusion criteria, 51% were transferred by ambulance and 49% by helicopter; 27% underwent ET (36% achieved modified Rankin Scale score of 0–2 at 90 days). Median actual transfer time was 132 minutes (interquartile range, 103–165), compared with median ideal transfer time at 102 minutes (interquartile range, 96–123). Longer transfer time was associated with decreased likelihood of undergoing ET (odds ratio, 0.990; P =0.003). Nocturnal transfer (18:00 to 06:00 hours) was associated with significantly longer delay (β=20.5; P Conclusions— Within a large telestroke network, there was an association between longer transfer time and decreased likelihood of undergoing ET. Nocturnal transfers were associated with a substantial delay relative to daytime transfers. In contrast, delivery of tPA was not associated with delays, underscoring the impact of effective protocols at spoke hospitals. More efficient transfer may enable higher ET treatment rates. Metrics and protocols for transfer, especially at night, may improve transfer times.

Introduction: When transferred from a referring hospital (RH) to a thrombectomy capable stroke center (TCSC), patients with initially favorable imaging profile (ASPECT score ≥6) often demonstrate infarct progression significant enough to make them ineligible at arrival. We sought to determine the clinical and imaging factors associated with this phenomenon in transferred ischemic stroke patients. Methods: We identified adult stroke patients transferred from one of 30 RH between 2010 and 2016 for which (1) a RH computed tomography (CT) and (2) a CT Angiography (CTA) at arrival were available for review. ASPECT scores were evaluated by 2 raters. The adequacy of leptomeningeal collateral flow was rated as none/poor, decreased, adequate or augmented per the Maas et al (Stroke 2009), modified scale. ASPECTS decay was defined as an ASPECT initial score ≥6 worsening between RH and TCSC CTs to a score Results: A total of 330 patients were included in the analysis (mean age 70.2 ± 14.2, 43.3% females). Univariable subgroup analyses showed that patients with ASPECTs decay were more likely to be females (55% vs 40%, p=0.02), not on anticoagulants (4% vs 15%, p=0.01), and with higher initial NIHSS (Median [IQR] 19 [15.3-22] vs 11 [6-17], p Conclusion: In ischemic stroke patients transferred for thrombectomy, poor collateral flow, stroke severity and proximal vascular occlusion, but not time interval, are the main determinants of ASPECTs decay.

Introduction: Guideline-based eligibility criteria for endovascular thrombectomy (EVT) are commonly used as criteria to select patients for transfer from referring hospitals (RH) to thrombectomy capable stroke centers (TCSC), resulting in a large amount of futile transfers. We sought to determine the baseline clinical and imaging factors associated with greater likelihood of receiving EVT after transfer, and explored the impact of simulated vascular imaging availability at RH on reducing the number of futile transfers for EVT. Methods: We identified stroke patients transferred from 30 RH between 2010 and 2016 for which (1) the RH computed tomography (CT) and (2) either CT/CT angiography or MRI at arrival were available for review. Initial ASPECT scores and baseline imaging characteristics were evaluated by 2 raters. The main outcome variable was pre-defined as receiving EVT at the TCSC after transfer. To analyze different options for improving triaging criteria for EVT at the RH, we generated various data-based situations accounting for the presumed vascular occlusion status based first on data available only at the RH and then by imputing vascular imaging information gathered at the TCSC presuming it could have been captured at the RH. The predictive ability of each situation, using varying NIHSS thresholds, was evaluated to find an optimal sensitivity (Se) - specificity (Sp) threshold. Results: A total of 508 patients were included in the analysis (mean age 69.7 ± 14.8, 41.9% females). Application of current guidelines for EVT eligibility (NIHSS >6, ASPECTs≥6, Time Conclusion: Implementation of vascular imaging at RH would result in significantly fewer futile transfers for EVT. The optimal trade-off between time, cost and imaging will impact the number needed to transfer and will depend on local resources and capabilities.