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Background:The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT.Methods:Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0–3 or equal to pre-stroke mRS at 3 months.Results:Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36–0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83–0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32–10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08–0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization.Conclusions:Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

ObjectiveTo assess whether interleukin-6 (IL-6) level is a marker of futile reperfusion in patients with acute ischemic stroke (AIS) with large vessel occlusion treated with mechanical thrombectomy (MT).MethodsThe Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke (HIBISCUS-STROKE) includes patients with AIS treated with MT after MRI. We performed a sequential assessment of IL-6 (admission, 6 hours, 24 hours, 48 hours and 3 months from admission). Among patients with successful reperfusion (Thrombolysis in Cerebral Infarction scale 2b/3), reperfusion was considered effective if 3-month modified Rankin Scale (mRS) score was 0 to 2 and futile if 3-month mRS score was 3 to 6. Our model was adjusted for the main confounding variables.ResultsOne hundred sixty-four patients represent the study population. One hundred thirty-three patients had successful reperfusion (81.1%), while in 46 (34.6%), reperfusion was classified as futile. In single-variable analyses, high IL-6 levels at 6, 24, and 48 hours in combination with a higher age, a prestroke mRS score >2, a history of hypertension or diabetes, lack of current smoking, a higher baseline NIH Stroke Scale score, the absence of associated intravenous thrombolysis, an intracranial internal carotid artery or a tandem occlusion, and an increased infarct growth were associated with futile reperfusion. After multivariable analyses, a high IL-6 level at 24 hours (odds ratio 6.15, 95% confidence interval 1.71–22.10) remained associated with futile reperfusion.ConclusionsIL-6 is a marker of futile reperfusion in the setting of MT.

Background and Purpose: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy. Methods: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0–2) and good (Higashida score, 3–4). A multiple logistic regression model was performed to detect independent markers of good collateral status. Results: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels ( P =0.01), high MCP-1 levels ( P P =0.046), a high diastolic blood pressure ( P =0.049), the absence of tandem occlusion ( P =0.046), a high Alberta Stroke Program Early CT Score ( P P P =0.02) and high MCP-1 levels ( P Conclusions: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.

Purpose Intracranial plaque gadolinium enhancement revealed by high-resolution MRI imaging (HR MRI) is considered as a marker of plaque inflammation, a contributing factor of plaque unstability. The aim of the present study was to assess the distribution of gadolinium enhancement in intracranial atherosclerosis. Methods Single center analysis of ischemic stroke patients with intracranial atherosclerotic stenosis of M1 or M2 segments of middle cerebral artery, or terminal internal carotid artery (ICA) based on CT-angio or MR-angio. High-resolution MRI imaging (HRMRI) was performed within 6 first weeks following the index event, with 3DT2 BB (black-blood) and 3D T1 BB MR sequences pre and post-contrast administration. Results We identified 8 patients with 14 plaques, 4 were deemed non-culprit and 10 culprit. All culprit plaques (10/10 plaques) and 3 out of 4 non-culprit plaques showed a gadolinium enhancement. Conclusion At the acute/subacute stage of stroke, a gadolinium enhancement may affect multiple asymptomatic intracranial plaques and may reflect a global inflammatory state.

IntroductionThe relevance of the brush-sign remained poorly documented in large vessel occlusion (LVO). We aimed to assess the relationship between the brush-sign and collateral status and its potential impact on baseline diffusion-weighted imaging–Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) in acute ischemic stroke (AIS) patients eligible to mechanical thrombectomy (MT).MethodsConsecutive patients admitted in the Lyon Stroke Center with anterior circulation AIS due to intracranial internal carotid artery (ICA) and/or M1 or M2 segment of the middle cerebral artery (MCA) occlusion eligible for MT were included. The brush-sign was assessed on T2-gradient-echo MRI. Collateral status was assessed on digital subtraction angiography according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) score.ResultsIn this study, 504 patients were included, among which 171 (33.9%) patients had a brush-sign. Patients with a brush-sign more frequently had a poor collateral status [72 (42.1%) vs. 103 (30.9%); p = 0.017]. In univariable analysis, a DWI-ASPECTS < 7 was associated with a brush sign. Following multivariable analysis, the brush-sign no longer affected DWI-ASPECTS < 7 while the latter remained associated with younger age [odds ratio (OR) 0.97, 95% CI.96–0.99], male sex (OR 1.79, 95% CI 1.08–2.99), a higher National Institutes of Health Stroke Scale (NIHSS) score (OR 1.16, 95% CI 1.1–1.21), a poor collateral status (OR 9.35, 95% CI 5.59-16.02), MCA segment (OR 2.54, 95% CI 1.25–5.38), and intracranial ICA (OR 3.01, 95% CI 1.16–8) occlusion.Conclusions and RelevanceThe brush-sign may be a marker of poor collateral status but did not independently predict a lower DWI-ASPECTS.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04620642.

International audience; BACKGROUND: The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage. METHODS: The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding. FINDINGS: Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group. INTERPRETATION: Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage. FUNDING: French Ministry of Health.

As diffusion tensor imaging (DTI) is able to assess tissue integrity, authors used diffusion to detect abnormalities in trigeminal nerves (TGN) in patients with trigeminal neuralgia (TN) caused by neurovascular compression (NVC) who had undergone microvascular decompression (MVD). The authors also studied anatomical TGN parameters (cross-sectional area [CSA] and volume [V]). The study compared pre- and postoperative findings.Using DTI sequencing on a 3-T MRI scanner, we measured the fraction of anisotropy (FA) and apparent diffusion coefficient (ADC) of the TGN in 10 patients who had undergone MVD for TN and in 6 normal subjects. We compared data between affected and unaffected nerves in patients and both nerves in normal subjects (controls). We then correlated these data with CSA and V. Data from the affected side and the unaffected side before and 4 years after MVD were compared.Before MVD, the FA of the affected side (0.37 ± 0.03) was significantly lower (p 0.05) compared to the unaffected side in patients (0.48 ± 0.03) and controls (0.52 ± 0.02), and the ADC in the affected side (5.6 ± 0.34 mmDTI revealed a loss of anisotropy and an increase in diffusivity in affected nerves before surgery. Diffusion alterations correlated with atrophic changes in patients with TN caused by NVC. After removal of the compression, the loss of FA remained, but ADC normalized in the affected nerves, suggesting improvement in the diffusion of the trigeminal root.

In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-thrombolysis recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following intravenous thrombolysis administration in LVO patients. From a multicenter registry, we identified 218 thrombolysed LVO patients referred for thrombectomy with both (i) pre-thrombolysis MRI, including diffusion-weighted imaging (DWI), T2*-imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and (ii) evaluation of recanalization on first angiographic run or non-invasive imaging ≤ 3 h from thrombolysis start. Infarct core volume on DWI, PWI-DWI mismatch volume and hypoperfusion intensity ratio (HIR; defined as Tmax ≥ 10 s volume/ Tmax ≥ 6 s volume, low HIR indicating milder hypoperfusion) were determined using a commercially available software. Early recanalization occurred in 34 (16%) patients, and multivariable analysis was associated with lower HIR ( P = 0.006), shorter thrombus on T2*-imaging ( P

BackgroundFirst-pass effect (FPE) defined as a complete or near-complete reperfusion achieved after a single thrombectomy pass is predictive of favorable outcome in acute ischemic stroke (AIS) patients. We aimed to assess whether admission levels of inflammatory markers are associated with FPE.MethodsHIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes AIS patients with large vessel occlusion treated with mechanical thrombectomy following brain MRI. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2, matrix metalloproteinase-9 (MMP-9), soluble P-selectin, and vascular cellular adhesion molecule-1 were measured in admission sera using an ELISA assay. FPE was defined as a complete or near-complete reperfusion (thrombolysis in cerebral infarction scale (TICI) 2c or 3) after the first pass. A multivariate logistic regression analysis was performed to assess independent factors associated with FPE.ResultsA total of 151 patients were included. Among them, 43 (28.5%) patients had FPE. FPE was associated with low admission levels of IL-6, MMP-9, and platelet count, an older age, lack of hypertension, lack of tandem occlusion, a shorter thrombus length, and a reduced procedural time. Following multivariate analysis, a low admission level of IL-6 was associated with FPE (OR 0.66, 95% CI 0.46 to 0.94). Optimal cut-off of IL-6 level for distinguishing FPE from non-FPE was 3.0 pg/mL (sensitivity 92.3%, specificity 42.3%).ConclusionA lower admission level of IL-6 is associated with FPE.

Importance The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy. Objective To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO. Design, Setting, and Participants This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019. Main Outcomes and Measures ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause. Results Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively. Conclusions and Relevance The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic would have particularly affected acute stroke care. However, its impact is clearly inherent to the local stroke network conditions. We aimed to assess the impact of COVID-19 pandemic on acute stroke care in the Lyon comprehensive stroke center during this period.MethodsWe conducted a prospective data collection of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) during the COVID-19 period (from 29/02/2020 to 10/05/2020) and a control period (from 29/02/2019 to 10/05/2019). The volume of reperfusion therapies and pre and intra-hospital delays were compared during both periods.ResultsA total of 208 patients were included. The volume of IVT significantly decreased during the COVID-period (55 (54.5%) vs 74 (69.2%); p=0.03) and was mainly due to time delay among patients treated with MT. The volume of MT remains stable over the two periods (72 (71.3%) vs 65 (60.8%); p=0.14) but the door-to-groin puncture time increased in patients transferred for MT (237 [187-339] vs 210 [163-260]; pConclusionsOur study showed a decrease of the volume of IVT, whereas the volume of MT remained stable although intra-hospital delays increased for transferred patients during the COVID-19 pandemic. These results contrast in part with the national surveys and suggest that the impact of the pandemic may depend on local stroke care networks.

Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis.To analyze the radiological presentation and natural history of adult IDH-wildtype astrocytomas with TERTp.We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas.Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged50 yr (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥8 mm/yr but 7 cases displayed a slow growth (VDE8 mm/yr) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 mo.IDH-wildtype TERTp-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged50 yr. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.

Objectives: The aim of the present study was to assess the association between collateral status and DWI-FLAIR mismatch in patients with acute ischemic stroke within the 4.5 h time-window. Methods: We analysed DWI, FLAIR, and PWI data in patients within 4.5 h after symptom onset from the I-KNOW European database. Collateral flow maps were graded by analyzing contrast ‘staining’ extent over the early, mid and late perfusion phases. ADC values, DWI lesion volume, and normalised perfusion parameters (CBV,Tmax) within DWI lesions were determined. Visibility of parenchymal hyperintensivty on FLAIR was evaluated (“FLAIR positive”), and DWI-FLAIR mismatch was assessed. Spontaneously reperfused regions were defined as voxels with Tmax

We report a case of multiple cervical artery dissections that occurred 4 days after a first course of alemtuzumab in a woman with relapsing–remitting multiple sclerosis and discuss its potential relationship and mechanisms of action. In particular, an arterial inflammatory process, secondary to cytokine release, could potentially lead to intimal thickening, luminal irregularities, stenosis, and ultimately occlusion. Occurrence of an unexpected serious adverse event, in our case, multiple cervical artery dissections, especially in a close time window after drug administration, questions a potential causal relationship with the drug or a simple coincidence.

Background and purpose Transient ischemic attack may rarely reveal an intracranial artery occlusion. We analyzed acute magnetic resonance imaging (MRI) patterns and early outcome after reperfusion therapy in these cases. Method Clinical and imaging data were taken retrospectively from our comprehensive stroke center registry. Two MRI patterns were determined. Pattern A: full mismatch with negative diffusion-weighted imaging (DWI) and perfusion defect. Pattern B: large mismatch with positive DWI and perfusion defect. MRI-derived collateral flow maps were automatically generated from the raw of dynamic susceptibility contrast MRI. Patients were treated either by recombinant tissue plasminogen activator (rtPA) alone or in combination with mechanical thrombectomy. Results From October 1, 2010 to May 15, 2016, 1,019 patients were admitted and treated by t-PA within 4.5 hours of stroke onset of them; 14 had a transient ischemic attack (TIA) within the 6 hours preceding MRI. Perfusion imaging was performed in 11 patients. An arterial occlusion was found in all of them, 11 patients had a distal anterior circulation occlusion, whereas 3 patients (21%) had a proximal occlusion. According to MRI, 6 patients showed pattern A, whereas 5 patients had pattern B. Good collaterals were observed in 10 patients (6 patients with grade 3 and 4 patients with grade 4), whereas 1 patient had poor collaterals (grade 2). The day 1 National Institutes of Health Stroke Scale median was 0. Modified Rankin Scale median at 3 months was 0. Conclusion TIAs may reveal acute intracranial artery occlusion. Acute MRI may able to assist in therapeutic decision.

INTRODUCTION Currently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination. MATERIAL AND METHODS We reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n=59) or a Psp (n=24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI. RESULTS In univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (

The significance of white matter hyperintensities (WMHs) in the setting of mechanical thrombectomy (MT) remains poorly documented. We assessed whether pre-existing WMHs burden was associated with baseline clinical and imaging factors and neurological outcome in patients undergoing MT. This retrospective single-center study included consecutive acute ischemic stroke (AIS) patients with stroke due to large vessel occlusion treated with MT. WMHs were assessed on baseline T2 fluid-attenuated inversion recovery magnetic resonance imaging. Neurological outcome was assessed at day 90 by the modified Rankin Scale (mRS). We analyzed the association between WMH burden and clinical and imaging factors by univariate and multivariate logistic regression analyses. Between July 2013 and June 2019, 293 patients with anterior circulation AIS met the inclusion criteria. WMHs burden was not associated to baseline NIHSS score severity (OR 0.89, 95% CI 0.54–1.49, p = 0.66), poor collateral status, Higashida score

Background and Purpose— The development of leptomeningeal collateral artery network might be adversely affected by small vessel wall alteration. We sought to determine whether small vessel disease (SVD) burden may impact collateral development in patients treated by mechanical thrombectomy for anterior circulation acute ischemic stroke. Methods— The patients admitted in our center for anterior circulation acute ischemic stroke and (1) treated by mechanical thrombectomy with or without thrombolysis and (2) who underwent a baseline magnetic resonance imaging were included in the study. The SVD burden and the pial collaterality were assessed through the cerebral SVD score (severe when ≥1) and the Higashida score (favorable when ≥ 3) on magnetic resonance imaging and digital subtraction angiography, respectively. Any association between the cerebral SVD score and the collaterality were assessed through comparative and regression analyses. Results— Between January 2013 and March 2018, 240 patients met the inclusion criteria (68.7±16.1 years old; 49.2 % female). The cerebral SVD scores were of 0 in 125 (52.1%), 1 in 74 (30.8%), 2 in 30 (12.5%), and 3 in 11 (4.6%) patients. Hundred and thirty-six patients (58.1%) presented a favorable collaterality score. The favorable collaterality subgroup presented a significantly higher proportion of female (79%), lower baseline National Institutes of Health Stroke Scale ( P P P =0.51). Conclusions— In patients with anterior circulation acute ischemic stroke, collateral flow status does not seem to be influenced by SVD burden.

Background and purpose Hemodynamic and metabolic impairment in intracranial atherosclerotic stenosis (ICAS) may promote stroke vulnerability particularly in borderzone areas. Perfusion and oxygen mapping magnetic resonance imaging (MRI) may provide useful information in this setting. Methods In this pilot study, patients with symptomatic atherosclerotic anterior circulation stenosis ≥60%, without other sources of ischemic stroke, were included. High-resolution vessel wall MRI quantified the stenosis degree, and hemodynamic and metabolic impairment was assessed at baseline using dynamic susceptibility contrast perfusion and multiparametric quantitative blood-oxygen-level-dependent (mqBOLD) oxygenation MRI. All parameters were assessed within both hemispheres and in borderzone areas. Results Forty-three subjects with intracranial artery narrowing were screened from November 2014 to January 2016. Eleven patients met the study criteria (mean ± standard deviation age = 64.4 ± 10.6 years, the mean degree of stenosis was 76.9 ± 23.4%). No interhemispheric differences were observed across oxygen (cerebral metabolic rate of oxygen and tissular saturation of oxygen) or perfusion (mean transit time, time to maximum, Tmax , normalized cerebral blood volume [nCBV], and normalized cerebral blood flow) parameters. A positive correlation was observed between the stenosis degree and ipsilateral nCBV (R = .77, P = .008). In addition, a significant increase in CBV was observed in anterior cortical borderzones ipsilateral to stenosis (nCBV = 7.20 ± 1.81 vs. 5.45 ± 1.40 mL/100 g, P = .02). Conclusion Symptomatic ICAS had no global impact on perfusion and oxygen mapping MRI at resting state. A significant increase in nCBV was found within anterior borderzone areas.

Background and Purpose— In acute stroke patients with large vessel occlusion, the goal of intravenous thrombolysis (IVT) is to achieve early recanalization (ER). Apart from occlusion site and thrombus length, predictors of early post-IVT recanalization are poorly known. Better collaterals might also facilitate ER, for instance, by improving delivery of the thrombolytic agent to both ends of the thrombus. In this proof-of-concept study, we tested the hypothesis that good collaterals independently predict post-IVT recanalization before thrombectomy. Methods— Patients from the registries of 6 French stroke centers with the following criteria were included: (1) acute stroke with large vessel occlusion treated with IVT and referred for thrombectomy between May 2015 and March 2017; (2) pre-IVT brain magnetic resonance imaging, including diffusion-weighted imaging, T2*, MR angiography, and dynamic susceptibility contrast perfusion-weighted imaging; and (3) ER evaluated ≤3 hours from IVT start on either first angiographic run or noninvasive imaging. A collateral flow map derived from perfusion-weighted imaging source data was automatically generated, replicating a previously validated method. Thrombus length was measured on T2*-based susceptibility vessel sign. Results— Of 224 eligible patients, 37 (16%) experienced ER. ER occurred in 10 of 83 (12%), 17 of 116 (15%), and 10 of 25 (40%) patients with poor/moderate, good, and excellent collaterals, respectively. In multivariable analysis, better collaterals were independently associated with ER ( P =0.029), together with shorter thrombus ( P P =0.010). Conclusions— In our sample of patients with stroke imaged with perfusion-weighted imaging before IVT and intended for thrombectomy, better collaterals were independently associated with post-IVT recanalization, supporting our hypothesis. These findings strengthen the idea that advanced imaging may play a key role for personalized medicine in identifying patients with large vessel occlusion most likely to benefit from IVT in the thrombectomy era.

Background and Purpose— Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)—a surrogate marker of poor outcome. Methods— From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results— Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2–4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4–13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21–1.92; P Conclusions— ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Severity of vascular damage of white matter may predict hemorrhagic transformation (HT). We assess the relationship between leukoaraiosis (LA) severity and the type of hemorrhagic transformation in elderly patients treated with thrombolysis. We retrospectively analyzed the clinical data and pretreatment magnetic resonance imaging (MRI) of 180 consecutive ischemic stroke patients aged over 75 years. LA severity was graded according to the Fazekas scale, and acute diffusion-weighted-imaging (DWI) lesion volumes were semi-automatically outlined. Predictors of hemorrhagic infarction (HI) and parenchymal hemorrhage (PH) were identified using logistic regression analysis and exact multinomial logistic analysis. HT occurred in 31 patients (17 %). Baseline National Institute of Health Stroke Score (NIHSS; p = 0.008), severe LA (p = 0.02), and diffusion lesion volume (p = 0.02) were predictors of HT in univariable logistic regression. Adjusted to lesion volume and baseline NIHSS score, exact multinomial logistic analysis showed that severe LA was the only independent predictor of parenchymal hemorrhage (p = 0.03). In elderly patients, LA severity better predicts parenchymal hemorrhage than infarct size.

Objective: To identify the clinical and radiologic features that should raise suspicion for the pseudotumoral presentation of cerebral amyloid angiopathy–related inflammation (CAA-I). Methods: We retrospectively reviewed the characteristics of 5 newly diagnosed and 23 previously reported patients in whom the CAA-I imaging findings were initially interpreted as CNS neoplasms. Results: Most cases (85%) occurred in patients >60 years old. The clinical characteristics at presentation included subacute cognitive decline (50%), confusion (32%), focal deficits (32%), seizures (25%), and headaches (21%). Brain MRI demonstrated infiltrative white matter lesions that exhibited a loco-regional mass effect without parenchymal enhancement (93%). In general, these findings were interpreted as low-grade glioma or lymphoma. Eighteen patients (64%) underwent a biopsy, which was nondiagnostic in 4 patients (14%), and 6 patients (21%) underwent a surgical resection. The primary reason for the misinterpretation of the imaging findings was the absence of T2*-weighted gradient recalled echo (T2*-GRE) sequences on initial imaging (89%). When subsequently performed (39%), the T2*-GRE sequences demonstrated multiple characteristic cortical and subcortical microhemorrhages in all cases. Perfusion MRI and magnetic resonance spectroscopy (MRS), which were performed on a subset of patients, indicated markedly reduced relative cerebral blood flow and a normal metabolic ratio. Conclusion: The identification of one or several nonenhancing space-occupying lesions, especially in elderly patients presenting with cognitive impairment, should raise suspicion for the pseudotumoral presentation of CAA-I and lead to T2*-GRE sequences. Perfusion MRI and MRS appear to be useful techniques for the differential diagnosis of this entity.

Revue Neurologique - In Press.Proof corrected by the author Available online since samedi 6 mai 2017

Background and Purpose: The immediate decrease of the apparent diffusion coefficient (ADC) is the main characteristic change of water diffusion in acute ischemic stroke. There is only limited information on the time course of diffusion parameters in different tissue compartments of cerebral ischemia. Materials and Methods: In a longitudinal study, we examined 21 patients with acute ischemic stroke by diffusion tensor imaging within 5 h after symptom onset, 3 h later, 2 days, and 1 month after symptom onset. Acute diffusion lesion and the fluid-attenuated inversion recovery (FLAIR) after 2 days were used as volumes of interest to define persistent core, lesion growth, and reversible acute diffusion lesion. For all diffusion parameters ratios between the stroke lesion VOIs and the mirror VOIs were calculated for each time point. ADC ratio, fractional anisotropy ratios, and eigenvalues ratios were measured in these volumes of interest and in contralateral mirror regions at each time points. Results: In the persistent core, ADC ratio (0.772) and all eigenvalues ratios were reduced on admission up to 1 day after stroke and increased after 1 month (ADC ratio 1.067). Within the region of infarct growth time course of diffusion parameter changes was similar, but delayed. In the brain area with reversible diffusion lesion, a partial normalization of diffusion parameters over the time was observed, while after 1 month diffusion parameters did not show the signature of healthy brain tissue. There were significantly different trends for all parameters over time between the three tissue compartments. Conclusion: Diffusion tensor imaging displays characteristic changes of water diffusion in different tissue compartments over time in acute ischemic stroke. Even regions with reversible diffusion lesion show diffusion signatures of persisting tissue alterations.

BACKGROUND: Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis. The aim of the present study was to analyze their radiological presentation and natural history. MATERIAL AND METHODS: We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n=19, grade III n=21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas and of 15 IDH-wildtype TERTp-wildtype astrocytomas. RESULTS: Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged >50 years (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥ 8 mm/year but 7 cases displayed a slow growth (VDE < 8 mm/year) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 months. CONCLUSION: IDH-wildtype TERTp-mutant astrocytomas typically present as non-enhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged >50 years. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.

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PURPOSE Susceptibility vessel sign (SVS) may likely influence recanalization after thrombolysis. We assessed, through the European sequential MRI database “I-KNOW,” the relationship between the presence of SVS on T2-weighted gradient echo imaging, its angiographic counterpart on magnetic resonance angiography and its subsequent impact on recanalization after thrombolysis. MATERIALS AND METHODS Initial clinical and MRI characteristics and early follow up were analyzed in acute ischemic stroke patients treated with rt-Pa within 4.5 hours. Patients underwent multimodal MRI at admission. Sequential imaging performed 3 hours, 2 days and 1 month later allowed the analysis of SVS changes and recanalization. RESULTS Fifty patients were included in the study. SVS was observed in 54% of cases at admission. SVS was still present in 46% patients at 3 hours, 16% at 2 days, and 0% at 1 month. It was an independent predictor of no recanalization after thrombolysis (P = .04). After 3 hours, SVS disappeared in only 4 cases, and was not linked with recanalization on MRA. Conversely, when SVS persisted, a partial or complete recanalization was observed in 9 and 6 cases, respectively. CONCLUSIONS SVS is a predictor of lower recanalization rate. Its disappearance is not necessarily correlated with recanalization.

BACKGROUND AND PURPOSE Though still debated, early reperfusion is increasingly used as a biomarker for clinical outcome. However, the lack of a standard definition hinders the assessment of reperfusion therapies and study comparisons. The objective was to determine the optimal early reperfusion criteria that predicts clinical outcome in ischemic stroke. METHODS Early reperfusion was assessed voxel-wise in 57 patients within 6 hours of symptom onset. The performance of the time to peak (TTP), the mean transit time (MTT), and the time to maximum of residue function (Tmax) at various delays thresholds in predicting the neurological response (based on the National Institutes of Health Stroke Scale) and the functional outcome (modified Rankin scale ≤1) at 1 month were compared. A receiver operating characteristics (ROC) analysis determined the optimal extent of reperfusion. A novel unsupervised classification of reperfusion using group-based trajectory modeling (GBTM) was evaluated. RESULTS MTT had a lower performance than TTP and Tmax in predicting the neurological response (P = .008 vs. TTP and P = .006 vs. Tmax) or the functional outcome (P = .0006 vs. TTP; P = .002 vs. Tmax). No delay threshold had a significantly higher predictive value than another. The optimal percentage of reperfusion was dependent on the outcome scale (P < .001). The GBTM-based classification of reperfusion was closely associated with the clinical outcome and had a similar accuracy compared to ROC-based classification. CONCLUSIONS TTP and Tmax should be preferred to MTT in defining early reperfusion. GBTM provided a clinically relevant reperfusion classification that does not require prespecified delay thresholds or clinical outcomes.

Pineal tumors are rare and include a large variety of entities. Germ cell tumors are relatively frequent and often secreting lesions. Pineal parenchymal tumors include pineocytomas, pineal parenchymal tumor of intermediate differentiation, pineoblastomas and papillary tumors of the pineal region. Other lesions including astrocytomas and meningiomas as well as congenital malformations i.e. benign cysts, lipomas, epidermoid and dermoid cysts, which can also arise from the pineal region. Imagery is often non-specific but detailed analysis of the images compared with the hormone profile can narrow the spectrum of possible diagnosis.

BACKGROUND AND PURPOSE We sought to identify MRI factors associated with BBB changes at the acute stage of ischemic stroke. METHODS We analyzed BBB changes on admission and within 3 hours after the first scan. BBB changes was defined as the presence of leptomeningeal and parenchymal contrast enhancement on T1-weighted imaging. Tmax, CBV, and DWI lesion volume were assessed on baseline MRI. Clinical and MRI factors associated with BBB changes were assessed by univariate and multivariate logistic regressions analyses. RESULTS Forty-four patients were included. BBB changes on baseline MRI was observed in 2 of 44 patients (3%). BBB disruption on H3-MRI was present in 19 of 44 patients (43%). Hemodynamic status and baseline ischemic core size were not different between patients with or without BBB changes. BBB alteration on H3 MRI was strongly associated with FLAIR MRI sequence positivity, 16/19 patients (83%) P = .001. CONCLUSION BBB changes are exceptional during the first 3 hours after stroke onset. Delayed BBB alteration was associated with FLAIR positivity mainly reflecting vasogenic edema.

International audience; Acute reperfusion despite persistent arterial occlusion may occur in up to 30% of ischemic stroke patients. Recruitment of leptomeningeal collaterals may explain this phenomenon. Using dynamic susceptibility-contrast perfusion imaging (DSC-PI), we assessed acute changes in collateral flow among patients without recanalization. From a multicenter prospective database (I-KNOW), 46 patients with magnetic resonance angiography visible occlusion in whom both reperfusion and recanalization were assessed within 6 h of onset were identified. Maps of collateral flow at arterial, capillary and late venous phases were generated from DSC-PI through inter-frame registration, baseline signal subtraction and temporal summation, and graded blind to all other relevant clinical and radiological data using the Higashida scale. Flow direction and the acute evolution of collaterals were evaluated against the reperfusion status. Among patients without recanalization ( n = 33), flow direction remained retrograde. Collateral grades significantly improved between admission and acute follow-up in patients who reperfused (OR: 4.57; 95% CI: 1.1–22.7; p = 0.048), but not in those without reperfusion (OR: 1.34; 95% CI: 0.4–4.5; p = 0.623). Our study confirmed that acute reperfusion without recanalization is associated with a significant improvement of retrograde collateral flow. DSC-PI can detect acute changes in collateral flow, and may help evaluate novel treatments targeting leptomeningeal collaterals.

Background: Brain atrophy has shown a protective effect on the risk of early neurological deterioration (END) related to malignant edema in patients with hemispheric infarction but could be deleterious on the outcome. Aims: We aimed to assess whether brain atrophy has an impact on the risk of END and on the outcome in severe ischemic strokes after intravenous (IV) thrombolysis. Methods: From a prospective thrombolysis registry, 137 patients who had a National Institutes of Health Stroke Scale (NIHSS) ≥15, MRI at admission, and IV thrombolysis were included. Relative cerebral volume was calculated. END was defined as a ≥2-points deterioration 72-h NIHSS and a good outcome as a modified Rankin Scale (mRS) ≤2 at 3 months. A multiple logistic regression analysis with a stepwise backward procedure was performed. Results: END and a good outcome were observed, respectively, in 20 (14.6%) and 48 (37.5%) patients. In univariate analysis, predictors of END included age (p = 0.049), diabetes (p = 0.041), and parenchymal hemorrhage (p = 0.039). In multivariate analysis, age (p = 0.018) was significantly associated with END. Brain atrophy was not associated with END even in subgroup analysis according to the baseline infarct size. In univariate analysis, age (p = 0.003), prestroke mRS (p = 0.002), hypertension (p = 0.006), baseline NIHSS (p = 0.002), END (p = 0.002), proximal occlusion (p = 0.006), and recanalization at 24 h (p < 0.001) were associated with a good outcome. Only baseline NIHSS (p = 0.006) was associated with a good outcome after adjustment. Conclusions: We did not find any impact of brain atrophy on the risk of END and the outcome at 3 months in severe ischemic strokes after IV thrombolysis.

Background and Purpose— Regional brain oxygen saturation (rSO 2 ) changes, assessed by cerebral near-infrared spectroscopy, are likely influenced by cerebral hemodynamic fluctuations induced by thrombectomy of acute proximal occlusion. We studied the correlations between rSO 2 and baseline magnetic resonance imaging perfusion parameters and the relationship between rSO 2 changes, recanalization, and clinical outcome. Methods— Seventeen acute ischemic stroke patients, treated with mechanical thrombectomy, were monitored using bilateral near-infrared spectroscopy before, during, and continuously for 24 hours after the procedure. All patients had baseline brain magnetic resonance imaging with perfusion weighted imaging. Results— rSO 2 was only correlated with baseline Tmax (ρ=−0.42; P P 2 difference was noted, and this diminished over time when recanalization had occurred (median [interquartile range], −8 [−12 to −5] to 3 [−3 to 7]; P =0.01). rSO 2 changes were not correlated with clinical outcome. Conclusions— rSO 2 was merely correlated with baseline Tmax and mean transit time magnetic resonance imaging perfusion parameters. Multiple sites recording beyond frontal pole explored areas may provide more relevant correlation with hemodynamic parameters.

Introduction Du fait que l’imagerie en tenseur de diffusion (DTI) est capable de verifier l’integrite tissulaire, nous avons decide d’utiliser cette technique pour la detection des anomalies structurelles des nerfs trijumeaux (T) chez des patients souffrant de nevralgie trigeminale (NT) provoquee par compression neurovasculaire (CNV) et qui ont beneficie d’une decompression vasculaire microchirurgicale (DVMC). Ces donnees ont ete couplees aux parametres anatomiques des nerfs (surface de section au niveau de la root-entry-zone [SS] et volume du nerf [V]). Materiel et methodes En utilisant la sequence DTI-3 T nous avons mesure la fraction d’anisotropie (FA) et le coefficient apparent de diffusion (ADC) chez 10 patients soumis a la DVMC et 6 sujets normaux. Nous avons compare les resultats entre les nerfs affectes (groupe ipsilateralNT, n = 10), les nerfs non-affectes (groupe contralateralNT, n = 10) et les nerfs des sujets normaux (groupe controle, n = 12). Les resultats ont ete correles aux valeurs de SS et V. Nous avons compare aussi et surtout les resultats des groupes ipsilateralNT et contralateralNT avant et 4 ans apres la DVMC. Resultats Avant la DVMC, la FA du groupe ipsilateralNT (0,37 ± 0,08) etait significativement reduite (p 0,05) a celui du groupe contralateralNT (4,01 ± 0,33 mm2/s). Conclusion La DTI a mis en evidence des alterations de la FA et d’ADC des T affectes. Ces alterations etaient correlees avec l’atrophie des T affectes. Apres la decompression du nerf, la reduction de la FA se maintenait, tandis que l’ADC se normalisait au niveau des nerfs affectes. Ceci suggere la persistance des lesions axonales, une reduction de l’œdeme de la racine et la recuperation de la conduction sensitive.

International audience; High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffu-sion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

Background: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI. Methods: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.2 or more. Six lesion compartments were outlined: initial DWI (b = 1,000 s/mm2) lesion, initial PWI-DWI mismatch (Tmax >4 s and DWI-negative), final infarct mapped on 1-month fluid-attenuated inversion recovery (FLAIR) imaging, lesion growth between acute DWI and 1-month FLAIR, DWI lesion reversal at 1 month and salvaged mismatch. The WM and GM were segmented on T1-weighted images, and all images were co-registered within subjects to the baseline MRI. WM and GM proportions were calculated for each compartment. Results: Fifty patients were eligible for the study. Median delay between symptom onset and baseline MRI was 140 min. The percentage of WM was significantly greater in the following compartments: initial mismatch (52.5 vs. 47.5%, p = 0.003), final infarct (56.7 vs. 43.3%, p < 0.001) and lesion growth (58.9 vs. 41.2%, p < 0.001). No significant difference was found between GM and WM percentages within the initial DWI lesion, DWI reversal and salvaged mismatch compartments. Conclusions: Ischemic lesions may extend preferentially within the WM. Specific therapeutic strategies targeting WM ischemic processes may deserve further investigation.

Background and Purpose— MR signal changes after intravenous ultrasmall superparamagnetic iron oxide (USPIO) injection are related to inflammatory cells at the subacute stages after focal cerebral injury. However, at the early stages, the interpretation of USPIO-related MR signal alterations remains controversial. Here, we compared MR signal changes after intravenous USPIO injection with the histological iron and macrophage distribution during the first 24 hours in a rodent model of acute stroke. Methods— Multiparametric MRI at 7T and histological USPIO distribution were confronted from 6 to 24 hours after permanent middle cerebral artery occlusion in mice. Blood–brain barrier disruption was assessed using gadolinium MRI and immunoglobulin staining. Prussian blue staining was performed to depict the USPIO brain distribution. USPIO uptake by phagocytes was assessed by immunochemistry on brain tissue, peripheral blood cells, and monocyte cells derived from bone marrow culture. Results— After USPIO injection, 4 areas of early signal change were observed on every MRI. In all these areas, iron particles were mostly free whether detected in the vascular and cerebrospinal fluid compartments or in the interstitium. Within the first 24 hours, USPIO-loaded cells were not detected in the blood of injured mice or in cultured monocytic cells incubated with USPIO at plasmatic concentration. Conclusions— These results suggest that, in this model, early reproducible USPIO-related MR signal changes are mainly caused by passive diffusion of free USPIO after blood–brain barrier leakage and by intravascular trapping rather than by peripheral phagocyte infiltration.

Background and Purpose— Our aim was to explore whether the mismatch in lesion visibility between b1000 and b0 images is an alternative to mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery imaging as a surrogate marker of stroke age. Methods— We analyzed patients from the European multicenter I-KNOW database. Independent readers assessed the visibility of ischemic lesions of the anterior circulation on b0 and fluid-attenuated inversion recovery imaging images. The signal-intensity ratio for b0 and fluid-attenuated inversion recovery imaging images was also measured from the segmented stroke lesion volume on b1000 images. Results— This study included 112 patients (68 men; mean age, 67.4 years) with stroke onset within (n=85) or longer than (n=27) 4.5 hours. b1000–b0 mismatch identified patients within 4.5 hours of stroke onset with moderate sensitivity (72.9%; 95% confidence interval [CI], 63.5–82.4) and specificity (70.4%; 95% CI, 53.2–87.6), high positive predictive value (88.6%; 95% CI, 81.1–96.0), and low negative predictive value (45.2%; 95% CI, 30.2–60.3). Global comparison of b1000–b0 mismatch with diffusion-weighted imaging–fluid-attenuated inversion recovery imaging mismatch (considered the imaging gold standard) indicated high sensitivity (85.9%; 95% CI, 78.2–93.6), specificity (91.2%; 95% CI, 76.3–98.1), and positive predictive value (96.7%; 95% CI, 88.0–99.1) and moderate negative predictive value (73.8%; 95% CI, 60.5–87.1) of this new approach. b0 signal-intensity ratio ( r =0.251; 95% CI, 0.069–0.417; P =0.008) was significantly although weakly correlated with delay between stroke onset and magnetic resonance imaging. Conclusions— b1000–b0 mismatch may identify patients with ischemic stroke of the within 4.5 hours of onset with high positive predictive value, perhaps constituting an alternative imaging tissue clock.

Background and Purpose— The relative merits of reperfusion versus recanalization to predict tissue and clinical outcomes in anterior circulation stroke have been previously assessed using data acquired >12 hours postonset. To avoid late-occurring confounders such as non-nutritional reperfusion, futile recanalization and no-reflow phenomenon, we performed ultraearly assessment of reperfusion and recanalization. Methods— From a multicenter prospective database, 46 patients with acute magnetic resonance angiography–visible occlusion and in whom both reperfusion and recanalization were assessed on follow-up magnetic resonance imaging ≤6 hours of symptom onset were identified. Multiple linear regressions modeled salvaged penumbra, diffusion-weighted imaging lesion growth, and final infarct at 1 month using baseline clinical and imaging parameters and acute reperfusion or recanalization. Best predictors were determined with the Akaike information criterion. Univariate and multivariate logistic regressions identified the clinical and imaging predictors of clinical outcome. Results— Admission magnetic resonance imaging showed M1 occlusion in 15 (33%) patients; median penumbra volume was 13.4 mL. Acute reperfusion was observed in 27 (59%) patients; 42% of nonrecanalized patients demonstrated reperfusion. The dichotomized classification of reperfusion and recanalization was discordant ( P =0.0002). Reperfusion ≤6 hours was a significant ( P Conclusions— Reperfusion ≤6 hours was consistently superior to recanalization in predicting tissue and clinical outcome. Reperfusion without recanalization was frequent and probably related to retrograde reperfusion through leptomeningeal collaterals. Acute reperfusion was the strongest predictor of, and may therefore, represent a reliable surrogate for, clinical outcome.

International audience; OBJECTIVES: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size. METHODS: Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis. RESULTS: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009). CONCLUSIONS: Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone.

Background and Purpose— Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization. Methods— The volume of cerebral tissue with CBV ≤2.5th percentile of the normal hemisphere was calculated within the acute diffusion-weighted imaging lesion. Hemorrhagic transformation was assessed on day 2 MRI according to the European Cooperative Acute Stroke Study II criteria. Recanalization and reperfusion were assessed on 3-hour follow-up MRI. Results— Of the 110 patients, hemorrhagic transformation occurred in 59 patients, including 7 PH. In univariate analysis, the acute National Institutes of Health Stroke Scale score ( P =0.002), acute diffusion-weighted imaging lesion volume ( P =0.02), and thrombolysis ( P =0.03), but not very low CBV ( P =0.52), were associated with hemorrhagic transformation. The volume of very low CBV was the only predictor of PH ( P =0.007). Early reperfusion and recanalization had no influence on either hemorrhagic transformation or PH. Conclusion— Very low CBV was the only independent predictor of PH in patients with acute stroke.