Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study.

INTRODUCTION: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes. METHODS: In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance imaging (MRI)-based SVD markers (lacunes, white matter hyperintensities, microbleeds, perivascular spaces) and explored associations with 6- and 12-month cognitive (battery of 15 neuropsychological tests) and functional (modified Rankin scale) outcomes. RESULTS: A global SVD score (range 0-4) was associated with cognitive impairment; worse performance in executive function, attention, language, and visuospatial ability; and worse functional outcome across a 12-month follow-up. Although the global SVD score did not improve prediction, individual SVD markers, assessed across their severity range, improved the calibration, discrimination, and reclassification of predictive models including demographic, clinical, and other imaging factors. DISCUSSION: SVD presence and severity are associated with worse cognitive and functional outcomes 12 months after stroke. Assessing SVD severity may aid prognostication for stroke patients. HIGHLIGHTS: In a multi-center cohort, we explored associations of small vessel disease (SVD) burden with stroke outcomes. SVD burden associates with post-stroke cognitive and functional outcomes. A currently used score of SVD burden does not improve the prediction of poor outcomes. Assessing the severity of SVD lesions adds predictive value beyond known predictors. To add predictive value in assessing SVD in stroke patients, SVD burden scores should integrate lesion severity.

Simulation-based training improves process times in acute stroke care (STREAM).

BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.

Stroke Etiology Modifies the Effect of Endovascular Treatment in Acute Stroke.

Background and Purpose- Stroke etiology drives thrombus composition. We thus hypothesized that endovascular treatment shows different efficacy in cardioembolic versus noncardioembolic large-vessel occlusions (LVOs). Methods- Procedural characteristics, grade of reperfusion, and functional outcome at discharge and 90 days were compared between patients with cardioembolic versus noncardioembolic LVO from the GSR-ET (German Stroke Registry-Endovascular Treatment; n=2589). To determine associations with functional outcome, adjusted odds ratios and 95% CIs were calculated using ordinal multivariable logistic regression models adjusting for potential baseline confounder variables. Results- Endovascular treatment of cardioembolic LVO had a higher rate of successful reperfusion (85.6% versus 81.0%; P=0.002) and a higher rate of complete reperfusion after a single thrombectomy pass (45.7% versus 38.1%; P<0.001) compared with noncardioembolic LVO. Cardioembolic LVO was associated with better functional outcome at discharge (adjusted odds ratio, 1.61 [95% CI, 1.37-1.88]) and 90 days (adjusted odds ratio, 1.29 [95% CI, 1.09-1.53]). In mediation analysis, reperfusion explained 47% of the effect of etiology on functional outcome at discharge. Conclusions- These results provide evidence for higher efficacy of endovascular treatment in cardioembolic LVO compared with noncardioembolic LVO.

Clinical and Imaging Parameters Associated With Hyperacute Infarction Growth in Large Vessel Occlusion Stroke.

Background and Purpose- Large vessel occlusion stroke leads to highly variable hyperacute infarction growth. Our aim was to identify clinical and imaging parameters associated with hyperacute infarction growth in patients with an large vessel occlusion stroke of the anterior circulation. Methods- Seven hundred twenty-two consecutive patients with acute stroke were prospectively included in our monocentric stroke registry between 2009 and 2017. We selected all patients with a large vessel occlusion stroke of the anterior circulation, documented times from symptom onset, and CT perfusion on admission for our analysis (N=178). Ischemic core volume was determined with CT perfusion using automated thresholds. Hyperacute infarction growth was defined as ischemic core volume divided by times from symptom onset, assuming linear progression during times from symptom onset to imaging on admission. For collateral assessment, the regional leptomeningeal collateral score (rLMC) was used. Clinical data included the National Institutes of Health Stroke Scale score on admission and cardiovascular risk factors. Regression analysis was performed to adjust for confounders. Results- Median ischemic core volume was 34.4 mL, and median hyperacute infarction growth was 0.27 mL/min. In regression analysis including age, sex, National Institutes of Health Stroke Scale, clot burden score, diabetes mellitus, smoking, hypercholesteremia, hypertension, Alberta Stroke Program Early CT Score, and rLMC scores, only the rLMC score had a significant, independent association with hyperacute infarction growth (adjusted ß=-0.35; P<0.001). Trichotomizing patients by rLMC scores yielded 65 patients with good (rLMC >15), 67 with intermediate (rLMC 11-15) and 46 with poor collaterals (rLMC <11) with an infarction growth of 0.17 mL/min, 0.26 mL/min, and 0.41 mL/min, respectively. Conclusions- Hyperacute infarction growth strongly depends on collaterals. In primary stroke centers, hyperacute infarction growth may be extrapolated to estimate the stroke progression during transfer times to thrombectomy centers and to support decisions on which patients to transfer.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Thalamic Diaschisis in Acute Ischemic Stroke: Occurrence, Perfusion Characteristics, and Impact on Outcome.

BACKGROUND AND PURPOSE: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. METHODS: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. RESULTS: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P<0.001). In the ITD+ group, larger cerebral blood flow (P=0.002) and cerebral blood volume (P<0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch (P=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P>0.05). ITD had no influence on the development of subacute stroke complications. CONCLUSIONS: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials.

Reversible cerebral vasoconstriction syndrome with concurrent bilateral carotid artery dissection.

BACKGROUND: The pathophysiological basis of reversible cerebral vasoconstriction syndrome is poorly understood but carotid artery dissection has been discussed as a rare possible cause. So far, only single cases of unilateral carotid artery dissection and reversible cerebral vasoconstriction syndrome have been reported. CASE: Here, we describe the case of a 54-year old patient presenting to the emergency department with right hemiparesis, hypaesthesia and dysarthria. Furthermore, he reported two episodes of thunderclap headache after autosexual activity. Cerebral imaging showed ischaemic infarcts, slight cortical subarachnoid haemorrhage, bilateral carotid artery dissection and fluctuating intracranial vessel irregularities, compatible with reversible cerebral vasoconstriction syndrome. An extensive diagnostic work-up was normal. No typical trigger factors of reversible cerebral vasoconstriction syndrome could be found. The patient received intravenous heparin and the calcium channel blocker nimodipine. Follow-up imaging revealed no vessel irregularities, the left internal carotid artery was still occluded. CONCLUSION: This case supports the assumption that carotid artery dissection should be considered as a potential trigger of reversible cerebral vasoconstriction syndrome, possibly by altering sympathetic vascular tone.

The carotid plaque imaging in acute stroke (CAPIAS) study: protocol and initial baseline data.

BACKGROUND: In up to 30% of patients with ischemic stroke no definite etiology can be established. A significant proportion of cryptogenic stroke cases may be due to non-stenosing atherosclerotic plaques or low grade carotid artery stenosis not fulfilling common criteria for atherothrombotic stroke. The aim of the CAPIAS study is to determine the frequency, characteristics, clinical and radiological long-term consequences of ipsilateral complicated American Heart Association lesion type VI (AHA-LT VI) carotid artery plaques in patients with cryptogenic stroke. METHODS/DESIGN: 300 patients (age >49 years) with unilateral DWI-positive lesions in the anterior circulation and non- or moderately stenosing (<70% NASCET) internal carotid artery plaques will be enrolled in the prospective multicenter study CAPIAS. Carotid plaque characteristics will be determined by high-resolution black-blood carotid MRI at baseline and 12 month follow up. Primary outcome is the prevalence of complicated AHA-LT VI plaques in cryptogenic stroke patients ipsilateral to the ischemic stroke compared to the contralateral side and to patients with defined stroke etiology. Secondary outcomes include the association of AHA-LT VI plaques with the recurrence rates of ischemic events up to 36 months, rates of new ischemic lesions on cerebral MRI (including clinically silent lesions) after 12 months and the influence of specific AHA-LT VI plaque features on the progression of atherosclerotic disease burden, on specific infarct patterns, biomarkers and aortic arch plaques. DISCUSSION: CAPIAS will provide important insights into the role of non-stenosing carotid artery plaques in cryptogenic stroke. The results might have implications for our understanding of stroke mechanism, offer new diagnostic options and provide the basis for the planning of targeted interventional studies. TRIAL REGISTRATION: NCT01284933.

White matter volume loss drives cortical reshaping after thalamic infarcts.

OBJECTIVE: The integration of somatosensory, ocular motor and vestibular signals is necessary for self-location in space and goal-directed action. We aimed to detect remote changes in the cerebral cortex after thalamic infarcts to reveal the thalamo-cortical connections necessary for multisensory processing and ocular motor control. METHODS: Thirteen patients with unilateral ischemic thalamic infarcts presenting with vestibular, somatosensory, and ocular motor symptoms were examined longitudinally in the acute phase and after six months. Voxel- and surface-based morphometry were used to detect changes in vestibular and multisensory cortical areas and known hubs of central ocular motor processing. The results were compared with functional connectivity data in 50 healthy volunteers. RESULTS: Patients with paramedian infarcts showed impaired saccades and vestibular perception, i.e., tilts of the subjective visual vertical (SVV). The most common complaint in these patients was double vision or vertigo / dizziness. Posterolateral thalamic infarcts led to tilts of the SVV and somatosensory deficits without vertigo. Tilts of the SVV were higher in paramedian compared to posterolateral infarcts (median 11.2° vs 3.8°). Vestibular and ocular motor symptoms recovered within six months. Somatosensory deficits persisted. Structural longitudinal imaging showed significant volume reduction in subcortical structures connected to the infarcted thalamic nuclei (vestibular nuclei region, dentate nucleus region, trigeminal root entry zone, medial lemniscus, superior colliculi). Volume loss was evident in connections to the frontal, parietal and cingulate lobes. Changes were larger in the ipsilesional hemisphere but were also detected in homotopical regions contralesionally. The white matter volume reduction led to deformation of the cortical projection zones of the infarcted nuclei. CONCLUSIONS: White matter volume loss after thalamic infarcts reflects sensory input from the brainstem as well the cortical projections of the main affected nuclei for sensory and ocular motor processing. Changes in the cortical geometry seem not to reflect gray matter atrophy but rather reshaping of the cortical surface due to the underlying white matter atrophy.

Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA.

BACKGROUND: Complicated nonstenosing carotid artery plaques (CAPs) are an under-recognized cause of stroke. OBJECTIVES: The purpose of this study was to determine whether complicated CAP ipsilateral to acute ischemic anterior circulation stroke (icCAP) are associated with recurrent ischemic stroke or transient ischemic attack (TIA). METHODS: The CAPIAS (Carotid Plaque Imaging in Acute Stroke) multicenter study prospectively recruited patients with ischemic stroke restricted to the territory of a single carotid artery. Complicated (AHA-lesion type VI) CAP were defined by multisequence, contrast-enhanced carotid magnetic resonance imaging obtained within 10 days from stroke onset. Recurrent events were assessed after 3, 12, 24, and 36 months. The primary outcome was recurrent ischemic stroke or TIA. RESULTS: Among 196 patients enrolled, 104 patients had cryptogenic stroke and nonstenosing CAP. During a mean follow-up of 30 months, recurrent ischemic stroke or TIA occurred in 21 patients. Recurrent events were significantly more frequent in patients with icCAP than in patients without icCAP, both in the overall cohort (incidence rate [3-year interval]: 9.50 vs 3.61 per 100 patient-years; P = 0.025, log-rank test) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years; P = 0.003). The results were driven by ipsilateral events. A ruptured fibrous cap (HR: 4.91; 95% CI: 1.31-18.45; P = 0.018) and intraplaque hemorrhage (HR: 4.37; 95% CI: 1.20-15.97; P = 0.026) were associated with a significantly increased risk of recurrent events in patients with cryptogenic stroke. CONCLUSIONS: Complicated CAP ipsilateral to acute ischemic anterior circulation stroke are associated with an increased risk of recurrent ischemic stroke or TIA. Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933).

The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid ß in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484).

Late Thrombectomy in Clinical Practice : Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry.

BACKGROUND AND PURPOSE: To provide real-world data on outcome and procedural factors of late thrombectomy patients. METHODS: We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). RESULTS: Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6-24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. CONCLUSION: In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6-24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.

Within-lesion heterogeneity of subcortical DWI lesion evolution, and stroke outcome: A voxel-based analysis.

The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline (n = 45), six months (n = 45), and three years (n = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, p = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.

Impact of Collateral Filling Delay on the Development of Subacute Complications After Acute Ischemic Stroke.

PURPOSE: Leptomeningeal collaterals play a pivotal role in acute ischemic stroke. While most collateral scores rely on subjective visual analysis, an objective quantification is possible using dynamic computed tomography (CT) angiography (dynCTA). The aim was to determine the value of collateral filling delay (CFD) as assessed by dynCTA for predicting subacute stroke complications. METHODS: All subjects with isolated prebifurcation middle cerebral artery M1 occlusions were selected from an initial cohort of 2635 patients who underwent multiparametric CT for suspected stroke. The CFD was defined as the difference in time to peak enhancement between M2 segments of both hemispheres. Logistic regression analysis of CFD for space-occupying infarction (≥5 mm shift of brain tissue over the midline), parenchymal hematoma, and hemorrhagic transformation on follow-up imaging was performed. RESULTS: In this study 78 patients (47 female, median age 74 years) were included. The median CFD was 6.31 s (interquartile range [IQR] 4.00-8.64). The CFD values were correlated with qualitative collateral scores (p < 0.05). Higher CFD was associated with the development of space-occupying infarction in univariable (odds ratio, OR = 1.28; p = 0.002) and multivariable regression analysis (OR = 1.48; p = 0.004). The CFD had no association with parenchymal hematoma or hemorrhagic transformation (p > 0.05). CONCLUSION: A high CFD may serve as reproducible measure for collateralization and indicate development of increased risk of space-occupying infarction.

Differential Benefit of Collaterals for Stroke Patients Treated with Thrombolysis or Supportive Care : A Propensity Score Matched Analysis.

PURPOSE: Leptomeningeal collaterals can slow down infarction growth; however, despite good collaterals in the DAWN and DEFUSE 3 trials, outcomes were devastating if reperfusion was not attempted. The aim of this study was to compare the influence of collaterals on morphological and functional outcome in patients with acute middle cerebral artery (MCA) stroke undergoing intravenous thrombolysis (IVT) vs. supportive care (non-IVT). METHODS: Out of 1639 consecutive patients examined with multiparametric computed tomography (CT) for suspected ischemic stroke, all patients with confirmed MCA stroke who did not undergo endovascular thrombectomy were selected. Propensity score matching (PSM) was used to match IVT and non-IVT treated patients for potential confounders including age, sex, National Institutes of Health Stroke Scale (NIHSS) score on admission, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion site. Regression analysis after PSM was performed to identify independent associations. RESULTS: After PSM, 90 IVT patients were matched with 90 non-IVT patients. In multivariable regression analysis, a high regional leptomeningeal collateral (rLMC) score was independently associated with lower final infarction volume (FIV) in the IVT group (b = -0.472, p < 0.001) but not in the non-IVT group (b = -0.116, p = 0.327). The trichotomized rLMC scores predicted functional outcome in IVT treated patients (adjusted odds ratio, aOR = 4.57, 95% confidence interval, CI, 1.03-20.32, p = 0.046) but showed no independent association with outcome in the non-IVT group (aOR = 0.69, 95% CI 0.07-6.80, p = 0.753). CONCLUSION: Good collaterals favored smaller FIV and good functional outcome in IVT treated patients but not in non-IVT treated patients. Good collateral flow may have limited prognostic value if IVT is not administered to attempt reperfusion.

Ischemic Core Volume Combined with the Relative Perfusion Ratio for Stroke Outcome Prediction after Endovascular Thrombectomy.

BACKGROUND AND PURPOSE: Imaging-based selection of stroke patients for endovascular thrombectomy (EVT) remains an ongoing challenge. Our aim was to determine the value of a combined parameter of ischemic core volume (ICV) and the relative degree of cerebral blood flow in the penumbra for morphologic and clinical outcome prediction. METHODS: In this Institutional Review Board (IRB)-approved prospective observational study, 221 consecutive patients with large vessel occlusion anterior circulation stroke within 6 hours of symptom onset and subsequent EVT were included between June 2015 and August 2017. Admission computed tomography perfusion was analyzed using automated threshold-based algorithms. Perfusion-weighted ICV (pw-ICV) was calculated by multiplying ICV with the relative cerebral blood flow reduction within the penumbra. Functional outcome was assessed by standardized assessment of the modified Rankin scale (mRS) after 3 months. RESULTS: In multivariate analyses, pw-ICV was significantly associated with final infarction volume (FIV) (ß = .38, P < .001) after adjustment for penumbra volume, age, sex and time from symptom onset. In separate multivariate analysis with either pw-ICV or ICV, pw-ICV outperformed ICV for the prediction of FIV (Akaike's information criterion: 1,072 vs. 1,089; conditional variable importance: 1,494 vs. 955). There was also a highly significant association between FIV and clinical outcome as measured by an mRS score of 2 or less (odds ratio per 10 mL = .78, P < .001). Both pw-ICV and ICV were significantly associated with NIHSS improvement (both P<.05). CONCLUSION: In EVT-treated stroke patients, pw-ICV outperforms the more commonly used ICV in the prediction of morphological and functional outcome.