Arterial Recanalization During Interhospital Transfer for Thrombectomy.

BACKGROUND: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes. METHODS: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis. RESULTS: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization. CONCLUSIONS: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

Clinical change during inter-hospital transfer for thrombectomy: Incidence, associated factors, and relationship with outcome.

BACKGROUND: Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome. METHODS: We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately. RESULTS: A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59-3.71; p < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37-0.98; p = 0.044). CONCLUSION: Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request.

Using Epidemiological Data to Inform Clinical Trial Feasibility Assessments: A Case Study.

BACKGROUND: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed. METHODS: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan. RESULTS: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0-2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to <6), the number predicted to be eligible for the trial increased to 4%. At the time of trial conclusion, 57% of the enrolled patients qualified only by the modified criteria, and the trial was stopped at an interim analysis that demonstrated efficacy. We estimated that the Wilcoxon rank-sum value for the unadjusted predicted enrollment would not have crossed the threshold for efficacy and the trial not stopped. CONCLUSIONS: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

Precision Care in Cardiac Arrest: ICECAP (PRECICECAP) Study Protocol and Informatics Approach.

BACKGROUND: Most trials in critical care have been neutral, in part because between-patient heterogeneity means not all patients respond identically to the same treatment. The Precision Care in Cardiac Arrest: Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (PRECICECAP) study will apply machine learning to high-resolution, multimodality data collected from patients resuscitated from out-of-hospital cardiac arrest. We aim to discover novel biomarker signatures to predict the optimal duration of therapeutic hypothermia and 90-day functional outcomes. In parallel, we are developing a freely available software platform for standardized curation of intensive care unit-acquired data for machine learning applications. METHODS: The Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) study is a response-adaptive, dose-finding trial testing different durations of therapeutic hypothermia. Twelve ICECAP sites will collect data for PRECICECAP from multiple modalities routinely used after out-of-hospital cardiac arrest, including ICECAP case report forms, detailed medication data, cardiopulmonary and electroencephalographic waveforms, and digital imaging and communications in medicine files (DICOMs). We partnered with Moberg Analytics to develop a freely available software platform to allow high-resolution critical care data to be used efficiently and effectively. We will use an autoencoder neural network to create low-dimensional representations of all raw waveforms and derivative features, censored at rewarming to ensure clinical usability to guide optimal duration of hypothermia. We will also consider simple features that are historically considered to be important. Finally, we will create a supervised deep learning neural network algorithm to directly predict 90-day functional outcome from large sets of novel features. RESULTS: PRECICECAP is currently enrolling and will be completed in late 2025. CONCLUSIONS: Cardiac arrest is a heterogeneous disease that causes substantial morbidity and mortality. PRECICECAP will advance the overarching goal of titrating personalized neurocritical care on the basis of robust measures of individual need and treatment responsiveness. The software platform we develop will be broadly applicable to hospital-based research after acute illness or injury.

Home-based virtual reality therapy for hand recovery after stroke.

BACKGROUND: Many stroke survivors experience arm and hand weakness, but there are only limited efficacious options for arm therapy available. OBJECTIVE: To assess the feasibility of unsupervised home-based use of a virtual reality device (Smart Glove) for hand rehabilitation post stroke. DESIGN: Prospective single-arm study consisting of a 2-week run-in phase with no device use followed by an 8-week intervention period. SETTING: Participants were recruited at the Stanford Neuroscience Outpatient Clinic. PARTICIPANTS: Twenty chronic stroke patients with upper extremity impairment. INTERVENTIONS: Participants were instructed to use the Smart Glove 50 minutes per day, 5 days per week for 8 weeks. MAIN OUTCOME MEASURES: The following outcomes were measured: (1) compliance, (2) patients' impression of the intervention, and (3) efficacy using the upper extremity Fugl-Meyer (UE-FM), the Jebsen-Taylor hand function test (JTHFT), and the Stroke Impact Scale (SIS). RESULTS: Of 20 participants, seven (35%) met target compliance of 40 days use, and six (30%) used the device for 20-39 days. Eighty-five percent of participants were satisfied with the therapy, with 80% reporting improvement in hand function. During the run-in phase there were no improvements in hand function. During the intervention, patients improved by a mean of 26.6 ± 48.8 seconds on the JTHFT (P = .03), by 16.1 ± 15.3 points on the hand-domain of the SIS (P < .01) and there was a trend toward improvement on the UE-FM (2.2 ± 5.5 points, P = .10). CONCLUSIONS: Unsupervised use of the Smart Glove in the home environment may improve hand/arm function in subacute/chronic stroke patients. A randomized controlled trial is needed to confirm these results.

Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis.

BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.

Perfusion Imaging Collateral Scores Predict Infarct Growth in Non-Reperfused DEFUSE 3 Patients.

OBJECTIVE: This study evaluated the associations of perfusion imaging collateral profiles with radiographic and clinical outcome in late presenting, non-reperfused patients in the DEFUSE 3 clinical trial. METHODS: Non-reperfused patients in both treatment arms were included. Baseline ischemic core, Tmax >6s, and Tmax >10s perfusion volumes were calculated with RAPID software; infarct volumes obtained 24 hours after randomization were manually determined from DWI or CT. Substantial infarct growth was defined as a >25mL increase between baseline and 24-hour follow-up. Hypoperfusion Intensity Ratio (HIR) was defined as the proportion of the Tmax >6s lesion with Tmax >10s delay; CBV index was calculated by RAPID from mean CBV values within the Tmax >6s lesion compared to regions of normal CBV. RESULTS: Eighty-four patients were included. ROC analysis showed HIR ≥0.34 (AUC=0.68) and CBV index ≤0.74 (AUC=0.72) optimally predicted substantial infarct growth in follow-up. Median growth was 23.4 versus 73.2mL with HIR threshold of 0.34 (p=0.005), and 24.3 versus 58.7mL with CBV index threshold of 0.74 (p=0.004). If baseline HIR and CBV index were both favorable, median growth was 21.7mL, 40.9mL if one was favorable, and 108.2mL if both were unfavorable (p<0.001). Baseline perfusion profile was not associated with 90-day functional outcome. CONCLUSIONS: Perfusion collateral scores forecast infarct growth in late presenting, non-reperfused ischemic stroke patients. These parameters may be useful for guiding transfer decisions, such as need for repeat imaging upon thrombectomy center arrival, and may help identify slow progressing patients more likely to have persistent salvageable ischemic tissue beyond 24 hours.

Predictors of Early and Late Infarct Growth in DEFUSE 3.

Introduction: The goal of this study is to explore the impact of reperfusion and collateral status on infarct growth in the early and late time windows. Materials and Methods: Seventy patients from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with baseline, 24-h, and late follow-up scans were evaluated. Scans were taken with DWI or CTP at time of enrollment (Baseline), with DWI or CT 24-h after enrollment (24-h), and with DWI or CT 5 days after enrollment (Late). Early infarct growth (between baseline and 24-h scans) and late infarct growth (between 24-h and late scans) was assessed for each patient. The impact of collateral and reperfusion status on infarct growth was assessed in univariate and multivariate regression. Results: The median early infarct growth was 30.3 ml (IQR 16.4-74.5) and the median late infarct growth was 6.7 ml (IQR -3.5-21.6) in the overall sample. Patients with poor collaterals showed greater early infarct growth (Median 58.5 ml; IQR 18.6-125.6) compared to patients with good collaterals (Median 28.4 ml; IQR 15.8-49.3, unadjusted p = 0.04, adjusted p = 0.06) but showed no difference in late infarct growth. In contrast, patients who reperfused showed no reduction in early infarct growth but showed reduced late infarct growth (Median 1.9 ml; IQR -6.1-8.5) compared to patients without reperfusion (Median 11.2 ml; IQR -1.1-27.2, unadjusted p < 0.01, adjusted p = 0.04). Discussion: In the DEFUSE 3 population, poor collaterals predict early infarct growth and absence of reperfusion predicts late infarct growth. These results highlight the need for timely reperfusion therapy, particularly in patients with poor collaterals and indicate that the 24-h timepoint is too early to assess the full impact of reperfusion therapy on infarct growth. Clinical Trial Registration: http://www.clinicaltrials.gov, Unique identifier [NCT02586415].

Quality of Life in Physical, Social, and Cognitive Domains Improves With Endovascular Therapy in the DEFUSE 3 Trial.

BACKGROUND AND PURPOSE: The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes. METHODS: Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool. RESULTS: Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression (P<0.01 for all). Variables other than endovascular therapy that were independently associated with better QoL included lower baseline National Institutes of Health Stroke Scale, younger age, and male sex. The degree to which the modified Rankin Scale captures differences in QoL between patients varied by domain; the modified Rankin Scale score accounted for a high proportion of the variability in mobility (Rs2=0.82), a moderate proportion in social participation (Rs2=0.62), and a low proportion in cognition (Rs2=0.31) and depression (Rs2=0.19). CONCLUSIONS: Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients' outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02586415.

Comparison of Tmax values between full- and half-dose gadolinium perfusion studies.

AHA guidelines recommend use of perfusion imaging for patient selection in the 6-24 h window. Recently, the safety of gadolinium-based contrast agents for MR perfusion imaging has been questioned based on findings that gadolinium accumulates in brain tissue. Regulatory bodies have recommended to limit the use of gadolinium-based contrast agents where possible. Focusing specifically on the time to maximum of the tissue residue function (Tmax) parameter, used in DAWN and DEFUSE 3, we hypothesized that half-dose scans would yield a similar Tmax delay pattern to full-dose scans. We prospectively recruited 10 acute ischemic stroke patients imaged with two perfusion scans at their follow-up visit, one with a standard dose gadolinium followed by a half-dose injection a median of 7 min apart. The brain was parcellated into a grid of 3 × 3 regions and the mean of the difference in Tmax between the 3 × 3 regions on the half- and full-dose Tmax maps was 0.1 s (iqr 0.38 s). The fraction of brain tissue that differed by no more than ±1 s was 93.7%. In patients with normal or modest Tmax delays, half-dose gadolinium appears to provide comparable Tmax measurements to those of full-dose scans.

What predicts poor outcome after successful thrombectomy in late time windows?

BACKGROUND: Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b-3) with an emphasis on modifiable factors. METHODS: Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b-3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3-6). RESULTS: 70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P<0.001), and had poor cerebral perfusion collaterals (hypoperfusion intensity ratio) (median 0.45 vs 0.38; P=0.03). Following thrombectomy, poor outcome patients had larger 24 hour' core infarctions (median 59.5 vs 29.9 mL; P=0.01), more core infarction growth (median 33.6 vs 13.4 mL; P<0.001), and more mild (65% vs 50%; P=0.02) and severe (18% vs 0%; P=0.01) reperfusion hemorrhage. In a logistic regression analysis, the presence of any reperfusion hemorrhage (OR 3.3 [95% CI, 1.67 to 5]; P=0.001), age (OR 1.1 [95% CI, 1.03 to 1.11], P=0.004), higher NIHSS (OR 1.25 [95% CI, 1.07 to 1.41], P=0.002), and time from imaging to femoral artery puncture (OR 5 [95% CI, 1.16 to 16.67], P=0.03) independently predicted poor outcomes. CONCLUSIONS: In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02586415.

Renal Safety of Multimodal Brain Imaging Followed by Endovascular Therapy.

BACKGROUND AND PURPOSE: Contrast-enhanced noninvasive angiography and perfusion imaging are recommended to identify eligible patients for endovascular therapy (EVT) in extended time windows (>6 hours or wake-up). If eligible, additional intraarterial contrast exposure will occur during EVT. We aimed to study the renal safety in the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) population, selected with contrast-enhanced multimodal Imaging and randomized to EVT versus medical management. METHODS: In the randomized DEFUSE 3 trial population, we compared changes in serum creatinine between baseline (before randomization) and 24 hours later. The primary outcome was the relative change in creatinine level between baseline and 24 hours in the EVT versus medical arm. The secondary outcome was a comparison between computed tomography (CT) versus magnetic resonance imaging selection in the EVT arm. The safety outcome was a comparison of the proportion of patients with criteria for contrast-associated kidney injury in the EVT versus medical arm and a comparison between CT versus magnetic resonance imaging selection in the EVT arm. RESULTS: In the DEFUSE 3 population (n=182, age 69±13, 51% female), mean creatinine decreased from a baseline of 0.98±0.33 mg/dL to 0.88±0.28 mg/dL at 24 hours (P<0.001). There was no difference in change between treatment groups: relative to baseline, there was a 6.3% reduction in the EVT group versus 9.2% in the medical group, P=0.294. Absolute decrease -0.08±0.18 in EVT versus -0.12±0.18 in medical, P=0.135; Among patients treated with EVT, there was no difference in 24-hour creatinine level changes between patients who were selected with CT angiography/CT perfusion (-0.08±0.18) versus magnetic resonance imaging (-0.07±0.19), P=0.808 or 6.8% reduction versus 4.8%, P=0.696. In the EVT arm, contrast-associated kidney injury was encountered in 4 out of 91 (4.4%) versus 2/90 (2.2%) in the medical arm P=0.682. In the EVT arm, contrast-associated kidney injury was evenly distributed between magnetic resonance imaging (1/22, 4.6%) versus CT 3 out of 69 (4.4%), P=1.0. CONCLUSIONS: Perfusion imaging before EVT was not associated with evidence of decline in renal function. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3.

We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax > 6 s perfusion lesion predicts the infarct volume at 24 h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24 h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32, p = 0.006; CBV Index 0.78 vs. 0.85, p = 0.001) and 24 h (HIR 0.56 vs. 0.07, p = 0.004; CBV Index 0.47 vs. 0.73, p = 0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73, p = 0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24 h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24 h.

Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma.

OBJECTIVE: To validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest. METHODS: Consecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest. RESULTS: Ninety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC <650 ×10-6 mm2/s was highly predictive for poor outcome with a sensitivity of 0.63 (95% confidence interval [CI] 0.42-0.80), a specificity of 0.96 (95% CI 0.77-0.998), and a positive predictive value (PPV) of 0.94 (95% CI 0.71-0.997). The mean whole-brain ADC was higher among patients with good outcomes. Receiver operating characteristic curve analysis showed that ADC <650 ×10-6 mm2/s had an area under the curve of 0.79 (95% CI 0.65-0.93, p < 0.001). Quantitative DWI MRI data improved prognostication of both good and poor outcomes. CONCLUSIONS: This prospective, clinician-blinded study validates previous research showing that an ADC <650 ×10-6 mm2/s in >10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.

Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.

Thrombectomy Results in Reduced Hospital Stay, More Home-Time, and More Favorable Living Situations in DEFUSE 3.

Background and Purpose- The DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) demonstrated that endovascular thrombectomy in the 6- to 16-hour time window improves functional outcomes of patients with evidence of salvageable tissue on baseline computed tomography or magnetic resonance imaging. The purpose of this study is to assess the effect of endovascular therapy on length of hospital stay, home-time during the first 3 months poststroke, and living situation poststroke in DEFUSE 3. Methods- Duration of hospital stay and home-time (number of days during the 90-day poststroke period that the patient resides in their own home or in that of a relative) were compared between treatment groups using the Wilcoxon rank-sum test. Patient living situation was assessed at discharge, 30 days, and 90 days on an ordinal 4-point scale (home, acute rehabilitation unit, institutionalized care, or hospice/death) and differences between groups were analyzed using the Cochran-Armitage trend test. Results- Median length of hospital stay was 9.1 (interquartile range, 6.2-15.0) days in the medical group versus 6.5 (interquartile range, 3.7-9.3) days in the endovascular group (P<0.001). Median home-time during the first 90 days after stroke was 0 (interquartile range, 0-53) days in the medical group versus 55 (interquartile range, 0-83) days in the endovascular group (P<0.001). The endovascular group had more favorable living situations at time of discharge (P<0.001), 30 days (P<0.001), and 90 days (P<0.001) poststroke. Conclusions- Endovascular thrombectomy resulted in reduced hospital stay, more home-time, and more desirable living situations in the 90 days after stroke. These results provide evidence that endovascular therapy in the delayed time window can improve quality of life for stroke patients and reduce healthcare costs. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.