Publications by authors named "Norbert Nighoghossian"

172 Publications

Predictors of Outcome After Mechanical Thrombectomy in Stroke Patients Aged ≥85 Years.

Can J Neurol Sci 2021 Mar 9:1-6. Epub 2021 Mar 9.

Department of Medicine (Neurology), Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.

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.
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http://dx.doi.org/10.1017/cjn.2021.37DOI Listing
March 2021

Large vessel cardioembolic stroke and embolic stroke of undetermined source share a common profile of matrix metalloproteinase-9 level and susceptibility vessel sign length.

Eur J Neurol 2021 Mar 7. Epub 2021 Mar 7.

Stroke Center, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, France.

Background: Embolic stroke of undetermined source (ESUS) accounts for up to 25% of ischemic strokes. Identification of biomarkers that could improve the prediction of stroke subtype and subsequently of stroke prevention still remains a major issue.

Methods: The HIBISCUS-STROKE cohort includes ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. Presence and length of susceptibility vessel sign (SVS) were assessed by gradient-recalled echo T2*-weighted imaging. Matrix metalloproteinase-9 (MMP-9) was measured on sera collected at admission. A multiple logistic regression model was performed to detect independent markers distinguishing cardioembolic (CE) from large-artery atherosclerosis (LAA) subtype.

Results: A total of 147 patients were included, of them the etiology was distributed as follows: 86 (58.5%) CE, 26 (17.7%) LAA, and 35 (23.8%) ESUS. The optimal cutoff for differentiating CE from LAA subtype was 14.5 mm for SVS length (sensitivity, 79.7%; specificity, 72.7%) and 1110 ng/ml for admission MMP-9 level (sensitivity, 85.3%; specificity, 52.2%). Multivariate analysis revealed that current smoking (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.93), tandem occlusion (OR 0.01, 95% CI 0.01-0.21), SVS length (OR 0.78, 95% CI 0.63-0.97), and admission MMP-9 level (OR 0.99, 95% CI 0.99-1.00) were inversely associated with CE subtype. SVS length and MMP-9 level did not differ between ESUS and CE subtypes.

Conclusion: SVS length and admission MMP-9 level may improve the prediction of CE subtype whose profile is close to ESUS, thus suggesting a common cardiac embolic source.
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http://dx.doi.org/10.1111/ene.14806DOI Listing
March 2021

Quantitative Assessment of Motor Neglect.

Stroke 2021 Mar 4:STROKEAHA120031949. Epub 2021 Mar 4.

Sorbonne Université, Inserm U 1127, CNRS UMR 7225, Paris Brain Institute, ICM, Hôpital de la Pitié-Salpêtrière, France (M.N.T., R.M., P.B.).

Background And Purpose: We used differential actigraphy as a novel, objective method to quantify motor neglect (a clinical condition whereby patients mimic hemiplegia even in the absence of sensorimotor deficits), whose diagnosis is at present highly subjective, based on the clinical observation of patients' spontaneous motor behavior.

Methods: Patients wear wristwatch-like accelerometers, which record spontaneous motor activity of their upper limbs during 24 hours. Asymmetries of motor behavior are then automatically computed offline. On the basis of normal participants' performance, we calculated cutoff scores of left/right motor asymmetry.

Results: Differential actigraphy showed contralesional motor neglect in 9 of 35 patients with unilateral strokes, consistent with clinical assessment. An additional patient with clinical signs of motor neglect obtained a borderline asymmetry score. Lesion location in a subgroup of 25 patients was highly variable, suggesting that motor neglect is a heterogenous condition.

Conclusions: Differential actigraphy provides an ecological measure of spontaneous motor behavior, and can assess upper limb motricity in an objective and quantitative manner. It thus offers a convenient, cost-effective, and relatively automatized procedure for following-up motor behavior in neurological patients and to assess the effects of rehabilitation.
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http://dx.doi.org/10.1161/STROKEAHA.120.031949DOI Listing
March 2021

Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.

Eur J Neurol 2021 Mar 3. Epub 2021 Mar 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background And Purpose: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD.

Methods: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale.

Results: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS.

Conclusions: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.
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http://dx.doi.org/10.1111/ene.14797DOI Listing
March 2021

Extent of FLAIR Hyperintense Vessels May Modify Treatment Effect of Thrombolysis: A Analysis of the WAKE-UP Trial.

Front Neurol 2020 4;11:623881. Epub 2021 Feb 4.

Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Here, 85% of all patients ( = 140) and 95% of middle cerebral artery (MCA) occlusion patients ( = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth ( = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), -value for interaction was 0.11. While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012.
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http://dx.doi.org/10.3389/fneur.2020.623881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890254PMC
February 2021

Impact of the reperfusion status for predicting the final stroke infarct using deep learning.

Neuroimage Clin 2021 25;29:102548. Epub 2020 Dec 25.

CREATIS, CNRS, UMR-5220, INSERM U1206, Université Lyon 1, INSA Lyon, Villeurbanne, France. Electronic address:

Background: Predictive maps of the final infarct may help therapeutic decisions in acute ischemic stroke patients. Our objectives were to assess whether integrating the reperfusion status into deep learning models would improve their performance, and to compare them to current clinical prediction methods.

Methods: We trained and tested convolutional neural networks (CNNs) to predict the final infarct in acute ischemic stroke patients treated by thrombectomy in our center. When training the CNNs, non-reperfused patients from a non-thrombectomized cohort were added to the training set to increase the size of this group. Baseline diffusion and perfusion-weighted magnetic resonance imaging (MRI) were used as inputs, and the lesion segmented on day-6 MRI served as the ground truth for the final infarct. The cohort was dichotomized into two subsets, reperfused and non-reperfused patients, from which reperfusion status specific CNNs were developed and compared to one another, and to the clinically-used perfusion-diffusion mismatch model. Evaluation metrics included the Dice similarity coefficient (DSC), precision, recall, volumetric similarity, Hausdorff distance and area-under-the-curve (AUC).

Results: We analyzed 109 patients, including 35 without reperfusion. The highest DSC were achieved in both reperfused and non-reperfused patients (DSC = 0.44 ± 0.25 and 0.47 ± 0.17, respectively) when using the corresponding reperfusion status-specific CNN. CNN-based models achieved higher DSC and AUC values compared to those of perfusion-diffusion mismatch models (reperfused patients: AUC = 0.87 ± 0.13 vs 0.79 ± 0.17, P < 0.001; non-reperfused patients: AUC = 0.81 ± 0.13 vs 0.73 ± 0.14, P < 0.01, in CNN vs perfusion-diffusion mismatch models, respectively).

Conclusion: The performance of deep learning models improved when the reperfusion status was incorporated in their training. CNN-based models outperformed the clinically-used perfusion-diffusion mismatch model. Comparing the predicted infarct in case of successful vs failed reperfusion may help in estimating the treatment effect and guiding therapeutic decisions in selected patients.
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http://dx.doi.org/10.1016/j.nicl.2020.102548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810765PMC
December 2020

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial.

Neurol Res Pract 2020 20;2:40. Epub 2020 Nov 20.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.

Methods: WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.

Results: Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years,  <  0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%,  = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome ( = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236).

Conclusions: Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.
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http://dx.doi.org/10.1186/s42466-020-00087-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678217PMC
November 2020

Symptoms and probabilistic anatomical mapping of lacunar infarcts.

Neurol Res Pract 2020 3;2:21. Epub 2020 Aug 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: The anatomical distribution of acute lacunar infarcts has mainly been studied for supratentorial lesions. In addition, little is known about the association with distinct stroke symptoms, not summarized as classical lacunar syndromes. We aimed to describe the spatial lesion distribution of acute supra- and infratentorial lacunar infarcts and their association with stroke symptoms in patients eligible for thrombolysis.

Methods: All patients enrolled in the WAKE-UP trial (efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in wake-up stroke) were screened for lacunar infarcts on diffusion-weighted imaging (DWI). The relationship between the anatomical distribution of supra- and infratentorial lacunar infarcts, their demographic characteristics and acute stroke symptoms, defined by the National Institutes of Health Stroke Scale (NIHSS) score, were correlated and compared.

Results: Maps of lesion distribution from 224 lacunar infarct patients (76 [33.9%] females, mean age [standard deviation] of 63.4 [11.5] years) were generated using computational image mapping methods. Median infarct volume was 0.73 ml (interquartile range [IQR] 0.37-1.15 ml). Median NIHSS sum score on hospital arrival was 4 (IQR 3-6). 165 (73.7%) patients had lacunar infarcts in the supratentorial deep white or grey matter, while 59 (26.3%) patients had infratentorial lacunar infarcts. Patients with supratentorial lacunar infarcts presented with a significantly lower occurrence of deficits in the NIHSS items gaze ( < 0.001) and dysarthria ( = 0.008), but had more often a paresis of the left arm ( = 0.009) and left leg ( = 0.068) compared to patients with infratentorial infarcts.

Conclusions: The anatomical lesion distribution of lacunar infarcts reveals a distinct pattern and supports an association of localization with different stroke symptoms.

Trial Registration: NCT01525290.
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http://dx.doi.org/10.1186/s42466-020-00068-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650076PMC
August 2020

PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

Brain Commun 2020 11;2(2):fcaa193. Epub 2020 Nov 11.

Univ Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, 69000 Lyon, France.

In an acute ischaemic stroke, understanding the dynamics of blood-brain barrier injury is of particular importance for the prevention of symptomatic haemorrhagic transformation. However, the available techniques assessing blood-brain barrier permeability are not quantitative and are little used in the context of acute reperfusion therapy. Nanoparticles cross the healthy or impaired blood-brain barrier through combined passive and active processes. Imaging and quantifying their transfer rate could better characterize blood-brain barrier damage and refine the delivery of neuroprotective agents. We previously developed an original endovascular stroke model of acute ischaemic stroke treated by mechanical thrombectomy followed by positron emission tomography-magnetic resonance imaging. Cerebral capillary permeability was quantified for two molecule sizes: small clinical gadolinium Gd-DOTA (<1 nm) and AGuIX nanoparticles (∼5 nm) used for brain theranostics. On dynamic contrast-enhanced magnetic resonance imaging, the baseline transfer constant was 0.94 [0.48, 1.72] and 0.16 [0.08, 0.33] ×10min, respectively, in the normal brain parenchyma, consistent with their respective sizes, and 1.90 [1.23, 3.95] and 2.86 [1.39, 4.52] ×10min in choroid plexus, confirming higher permeability than brain parenchyma. At early reperfusion, for both Gd-DOTA and AGuIX nanoparticles was significantly higher within the ischaemic area compared to the contralateral hemisphere; 2.23 [1.17, 4.13] and 0.82 [0.46, 1.87] ×10min for Gd-DOTA and AGuIX nanoparticles, respectively. With AGuIX nanoparticles, also increased within the ischaemic growth areas, suggesting added value for AGuIX. Finally, was significantly lower in both the lesion and the choroid plexus in a drug-treated group (ciclosporin A,  = 7) compared to placebo ( = 5). quantification with AGuIX nanoparticles can monitor early blood-brain barrier damage and treatment effect in ischaemic stroke after reperfusion.
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http://dx.doi.org/10.1093/braincomms/fcaa193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716090PMC
November 2020

Association of Interleukin-6 Levels and Futile Reperfusion After Mechanical Thrombectomy.

Neurology 2021 02 1;96(5):e752-e757. Epub 2020 Dec 1.

From the Stroke Center (L.M., L.D., E.O., T.-H.C., N.N.), Cardiac Intensive Care Unit (T.B.), Clinical Investigation Center (M.B., C.A., N.M., M.O.), INSERM 1407, Neuroradiology Department (Y.B., O.F.E.), and NeuroBioTec (N.D.), CRB, Hospices Civils de Lyon; and INSERM U1060 (L.M., T.B., A.P., C.C.D.S., E.O., M.O., T.-H.C., N.N.), CarMeN Laboratory, and CREATIS (Y.B.), CNRS UMR 5220, INSERM U1044, University Lyon 1, France.

Objective: To 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).

Methods: The 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.

Results: One 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.

Conclusions: IL-6 is a marker of futile reperfusion in the setting of MT.
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http://dx.doi.org/10.1212/WNL.0000000000011268DOI Listing
February 2021

Impact of a theory-informed and user-centered stroke information campaign on the public's behaviors, attitudes, and knowledge when facing acute stroke: a controlled before-and-after study.

BMC Public Health 2020 Nov 16;20(1):1712. Epub 2020 Nov 16.

Université de Lyon, Université Claude Bernard Lyon 1 - HESPER EA 7425, Lyon, France.

Background: Public awareness of stroke symptoms is a key factor to ensure access to reperfusion strategies in due time. We designed and launched a regional theory-informed and user-centered information campaign and assessed its impact on emergency medical services (EMS) calls for stroke suspicion, time-to-call, and public attitudes and awareness concerning stroke.

Methods: A controlled before-and-after study was conducted during 3 sequential time-periods in 2 separate counties. Key messages of the campaign were underpinned by stroke representations and the theory of planned behavior, and focused on recognition of stroke warning signs and the need to call EMS urgently. The campaign included posters, leaflets, adverts and films displayed in bus and subway stations, internet, social networks, and local radio. Outcome measures on behavior, attitudes, and knowledge were assessed before the launch of the campaign, at 3 months, and 12 months.

Results: The number of EMS calls for stroke suspicion increased by 21% at 12 months in the intervention county and this change was significantly different to that observed in the control county (p = 0.02). No significant changes were observed regarding self-reported attitudes in case of stroke. An 8% significant increase in recognizing at least 2 stroke warning signs was observed in the intervention county (p = 0.04) at 3 months, while it did not change significantly in the control county (p = 0.6). However, there was no significant difference in warning sign recognition between both counties (p = 0.16).

Conclusion: The campaign significantly improved public's behavior of calling EMS, although stroke knowledge was not improved as much as expected. Repeating these campaigns over time might further help improve timeliness and access to reperfusion strategies.

Trial Registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT02846363 .
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http://dx.doi.org/10.1186/s12889-020-09795-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667807PMC
November 2020

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid F-NaF PET/MRI.

J Nucl Cardiol 2020 Nov 3. Epub 2020 Nov 3.

Stroke Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, 59 Boulevard Pinel, 69677, Bron, France.

Background: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using F-sodium fluoride (F-NaF) to check simultaneously F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability.

Methods And Results: We included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent F-NaF PET/MRI. F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients.

Conclusions: F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.
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http://dx.doi.org/10.1007/s12350-020-02400-0DOI Listing
November 2020

Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke: a preclinical two-centre study.

Sci Rep 2020 10 9;10(1):16874. Epub 2020 Oct 9.

The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.

Reperfusion is the only existing strategy for patients with acute ischemic stroke, however it causes further brain damage itself. A feasible therapy targeting reperfusion injury is remote ischemic conditioning (RIC). This was a two-centre, randomized, blinded international study, using translational imaging endpoints, aimed to examine the neuroprotective effects of RIC in ischemic stroke model. 80 male rats underwent 90-min middle cerebral artery occlusion. RIC consisted of 4 × 5 min cycles of left hind limb ischemia. The primary endpoint was infarct size measured on T2-weighted MRI at 24 h, expressed as percentage of the area-at-risk. Secondary endpoints were: hemispheric space-modifying edema, infarct growth between per-occlusion and 24 h MRI, neurofunctional outcome measured by neuroscores. 47 rats were included in the analysis after applying pre-defined inclusion criteria. RIC significantly reduced infarct size (median, interquartile range: 19% [8%; 32%] vs control: 40% [17%; 59%], p = 0.028). This effect was still significant after adjustment for apparent diffusion coefficient lesion size in multivariate analysis. RIC also improved neuroscores (6 [3; 8] vs control: 9 [7; 11], p = 0.032). Other secondary endpoints were not statistically different between groups. We conclude that RIC in the setting of acute ischemic stroke in rats is safe, reduces infarct size and improves functional recovery.
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http://dx.doi.org/10.1038/s41598-020-74046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547701PMC
October 2020

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Front Neurol 2020 28;11:957. Epub 2020 Aug 28.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. We performed a analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.
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http://dx.doi.org/10.3389/fneur.2020.00957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483750PMC
August 2020

Multiprofessional intervention to improve adherence to medication in stroke patients: a study protocol for a randomised controlled trial (ADMED AVC study).

Eur J Hosp Pharm 2020 Sep 25. Epub 2020 Sep 25.

Department of Pharmacy, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.

Introduction: Adherence to secondary preventive medications is often suboptimal in patients with stroke, exposing them to an increased risk of recurrent cerebral and/or cardiovascular events. Effective actions in the long term to improve adherence to medication are needed. The study will evaluate the efficacy of a collaborative multiprofessional patient-centred intervention conducted by a pharmacist on adherence to secondary preventive medication in stroke survivors.

Methods And Analysis: This is a multicentre cluster-randomised controlled trial. Two groups of 91 patients (intervention vs standard care) will be recruited. The clinical pharmacist intervention targeting secondary preventive medication will consist of three parts over 1 year: (1) an individual semi-structured interview at hospital discharge; (2) follow-up telephone interviews at 3, 6 and 9 months after discharge; and (3) a final individual semi-structured interview 1 year after discharge. Information on patient follow-up will be shared with the general practitioner and the community pharmacist by sending a report of each interview. The primary outcome is adherence to medication during the 12 months after hospital discharge, assessed using a composite endpoint: the medication possession ratio associated with a self-administered questionnaire.

Ethics And Dissemination: The local ethics committee, the national committee for use of personal data in medical research and the national data protection agency approved the study. The sponsor has no role in study design; collection, analysis and interpretation of data; or report writing.

Discussion: This pharmacist-led educational programme has the potential to significantly improve adherence to medication in stroke survivors which could lead to a decrease in recurrent cerebral and/or cardiovascular events.

Trial Registration Number: NCT02611440.
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http://dx.doi.org/10.1136/ejhpharm-2020-002425DOI Listing
September 2020

Effect of the COVID-19 pandemic on acute stroke reperfusion therapy: data from the Lyon Stroke Center Network.

J Neurol 2020 Sep 9. Epub 2020 Sep 9.

Department of Neurology, Stroke Center, Hospices Civils de Lyon, Lyon, France.

Background: The 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.

Methods: We 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.

Results: A 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]. 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]; p < 0.01). The daily number of Emergency Medical Dispatch calls considerably increased (1502 [1133-2238] vs 1023 [960-1410]; p < 0.01).

Conclusions: Our study showed a decrease in 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.
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http://dx.doi.org/10.1007/s00415-020-10199-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479751PMC
September 2020

Letter by Nighoghossian and Mechtouff Regarding Article, "Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease".

Stroke 2020 08 10;51(8):e165. Epub 2020 Jul 10.

Stroke Department, Hospices Civils de Lyon, Claude Bernard University Lyon 1, France.

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http://dx.doi.org/10.1161/STROKEAHA.120.030322DOI Listing
August 2020

Recognition of musical emotions and their perceived intensity after unilateral brain damage.

Cortex 2020 09 12;130:78-93. Epub 2020 Jun 12.

Lyon Neuroscience Research Center; CNRS, UMR5292; INSERM, U1028; Lyon, France; University Lyon 1, Lyon, France.

For the hemispheric laterality of emotion processing in the brain, two competing hypotheses are currently still debated. The first hypothesis suggests a greater involvement of the right hemisphere in emotion perception whereas the second hypothesis suggests different involvements of each hemisphere as a function of the valence of the emotion. These hypotheses are based on findings for facial and prosodic emotion perception. Investigating emotion perception for other stimuli, such as music, should provide further insight and potentially help to disentangle between these two hypotheses. The present study investigated musical emotion perception in patients with unilateral right brain damage (RBD, n = 16) or left brain damage (LBD, n = 16), as well as in matched healthy comparison participants (n = 28). The experimental task required explicit recognition of musical emotions as well as ratings on the perceived intensity of the emotion. Compared to matched comparison participants, musical emotion recognition was impaired only in LBD participants, suggesting a potential specificity of the left hemisphere for explicit emotion recognition in musical material. In contrast, intensity ratings of musical emotions revealed that RBD patients underestimated the intensity of negative emotions compared to positive emotions, while LBD patients and comparisons did not show this pattern. To control for a potential generalized emotion deficit for other types of stimuli, we also tested facial emotion recognition in the same patients and their matched healthy comparisons. This revealed that emotion recognition after brain damage might depend on the stimulus category or modality used. These results are in line with the hypothesis of a deficit of emotion perception depending on lesion laterality and valence in brain-damaged participants. The present findings provide critical information to disentangle the currently debated competing hypotheses and thus allow for a better characterization of the involvement of each hemisphere for explicit emotion recognition and their perceived intensity.
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http://dx.doi.org/10.1016/j.cortex.2020.05.015DOI Listing
September 2020

Prevalence and Outcome of Potential Candidates for Left Atrial Appendage Closure After Stroke With Atrial Fibrillation: WATCH-AF Registry.

Stroke 2020 08 9;51(8):2355-2363. Epub 2020 Jul 9.

APHP, Department of Neurology and Stroke center, Bichat Hospital, INSERM LVTS-U1148, DHU FIRE, Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France (E.O., E.M., C.G., C.H., P.C.L., H.C., L.C., A.M.-B., R.R., P.A.).

Background And Purpose: As a result of contraindications (eg, frailty, cognitive impairment, comorbidities) or patient refusal, many patients with stroke and atrial fibrillation cannot be discharged on oral anticoagulant. Among them, the proportion of potential candidates for left atrial appendage closure (LAAC) and their 12-month outcome is not well known.

Methods: The prospective WATCH-AF registry (Warfarin Aspirin Ten-A Inhibitors and Cerebral Infarction and Hemorrhage and Atrial Fibrillation) enrolled consecutive patients admitted within 72 hours of an acute stroke associated with atrial fibrillation in 2 stroke centers. Scales to evaluate stroke severity, disability, functional independence, risk of fall, cognition, ischemic and hemorrhagic risk-stratification, and comorbidities were systematically collected at admission, discharge, 3, 12 months poststroke. The 2 main end points were death or dependency (modified Rankin Scale score >3) and recurrent stroke (brain infarction and brain hemorrhage).

Results: Among 400 enrolled patients (370 with brain infarction, 30 with brain hemorrhage), 31 died before discharge and 57 (14.3%) were possible European Heart Rhythm Association/European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society candidates for LAAC. At 12 months, the rate of death or dependency was 17.9%, and the rate of stroke recurrence was 9.8% in the 274/400 (68.5%) patients discharged on a long-term oral anticoagulant strategy, as compared with 17.5% and 24.7%, respectively, in 57 patients candidate for LAAC. As compared with patients on a long-term oral anticoagulant strategy, there was a 2-fold increase in the risk of stroke recurrence in the group with an indication for LAAC (adjusted hazard ratio, 2.58 [95% CI, 1.40-4.76]; P=0.002).

Conclusions: Fourteen percent of patients with stroke associated with atrial fibrillation were potential candidates for LAAC. The 12-month stroke risk of these candidates was 3-fold the risk of anticoagulated patients.
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http://dx.doi.org/10.1161/STROKEAHA.120.029267DOI Listing
August 2020

Matrix Metalloproteinase-9 Relationship With Infarct Growth and Hemorrhagic Transformation in the Era of Thrombectomy.

Front Neurol 2020 9;11:473. Epub 2020 Jun 9.

Stroke Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, France.

To assess the relationship between matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and infarct growth and hemorrhagic transformation in acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the era of mechanical thrombectomy (MT) using the kinetics of MMP-9 and sequential magnetic resonance imaging (MRI). HIBISCUS-STROKE is a cohort study including AIS patients with LVO treated with MT following admission MRI. Patients underwent sequential assessment of MMP-9, follow-up CT at day 1, and MRI at day 6. The CT scan at day 1 classified any hemorrhagic transformation according to the European Co-operative Acute Stroke Study-II (ECASS II) classification. Infarct growth was defined as the difference between final Fluid-Attenuated Inversion Recovery volume and baseline diffusion-weighted imaging volume. Conditional logistic regression analyses were adjusted for main confounding variables including reperfusion status. One hundred and forty-eight patients represent the study population. A high MMP-9 level at 6 h from admission (H6) ( = 0.02), a high glucose level ( = 0.01), a high temperature ( = 0.04), and lack of reperfusion ( = 0.02) were associated with infarct growth. A high MMP-9 level at H6 ( = 0.03), a high glucose level ( = 0.03) and a long delay from symptom onset to groin puncture ( = 0.01) were associated with hemorrhagic transformation. In this MT cohort study, MMP-9 level at H6 predicts infarct growth and hemorrhagic transformation.
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http://dx.doi.org/10.3389/fneur.2020.00473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296118PMC
June 2020

Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion.

Stroke 2020 07 17;51(7):2232-2235. Epub 2020 Jun 17.

Stroke Department (L.M., L.D., E.O., T.-H.C., N.N.), Hospices Civils de Lyon, France.

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 (=0.01), high MCP-1 levels (<0.01), a low National Institute of Health Stroke Score (=0.046), a high diastolic blood pressure (=0.049), the absence of tandem occlusion (=0.046), a high Alberta Stroke Program Early CT Score (<0.01) and a low volume on the diffusion-weighted imaging (<0.01) were associated with good collateral status. Following multivariate analysis, low MMP-9 levels (=0.02) and high MCP-1 levels (<0.01) remained associated with good collateral status.

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.
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http://dx.doi.org/10.1161/STROKEAHA.120.029395DOI Listing
July 2020

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.

J Cereb Blood Flow Metab 2021 Apr 19;41(4):745-760. Epub 2020 May 19.

CREATIS, CNRS UMR-5220, INSERM U1206, Université Lyon 1, INSA Lyon Bât. Blaise Pascal, Villeurbanne, France.

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia () based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.
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http://dx.doi.org/10.1177/0271678X20921310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983495PMC
April 2021

Myocardial infarction: Economic, health, and social impacts on informal caregivers.

Int J Technol Assess Health Care 2020 Jun 21;36(3):245-251. Epub 2020 Apr 21.

Hospices Civils de Lyon, Pôle de Santé Publique, Lyon, France.

Objectives: The aim of the study was to measure the economic impact of informal care (IC) on caregivers assisting myocardial infarction (MI) survivors in France. Health and social impacts were also described.

Methods: Data from the prospective 2008 Health and Disabilities Households Survey (Enquête Handicap-Santé), carried out among the French general population, were used to obtain information about patients with MI and their informal caregivers. To estimate the approximate monetary value of IC, three methods were used: the proxy good method, opportunity cost method (OCM), and contingent valuation method (CVM). A multivariate analysis was performed to determine the associations of the IC duration and the existence of professional care with the health indicators stated by caregivers.

Results: The analysis included data from 147 caregivers. The mean value of IC ranged from €9,679 per year using the CVM to €11,288 per year using the OCM (p > .05). The mean willingness to pay for an additional hour of IC was €10.9 (SD = 8.3). A total of 46.2 percent of caregivers reported that IC negatively affected theirs physical condition, and 46.3 percent reported that it negatively affected their psychological health. In addition, 40.1 percent declared that caregiving activity made them anxious and 38.8 percent stated they felt alone. Associations were identified between the duration of IC and feeling the need to be replaced, feeling alone and making sacrifices (p < .05).

Conclusions: Informal caregiver burden may be recognized in health technology assessment in order not to underestimate the cost of strategies and to facilitate the comparability of cost-effectiveness outcomes between studies.
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http://dx.doi.org/10.1017/S0266462320000148DOI Listing
June 2020

Different Mismatch Concepts for Magnetic Resonance Imaging-Guided Thrombolysis in Unknown Onset Stroke.

Ann Neurol 2020 06 20;87(6):931-938. Epub 2020 Apr 20.

Department of Neurology, University Hospitals Leuven, Leuven, Belgium.

Objective: To explore the prevalence of the perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch and response to intravenous thrombolysis in the WAKE-UP trial.

Methods: We performed a prespecified post hoc analysis of ischemic stroke patients screened for DWI-fluid-attenuated inversion recovery (FLAIR) mismatch in WAKE-UP who underwent PWI. We defined PWI-DWI mismatch as ischemic core volume < 70ml, mismatch volume > 10ml, and mismatch ratio > 1.2. Primary efficacy end point was a modified Rankin Scale score of 0-1 at 90 days, adjusted for age and symptom severity.

Results: Of 1,362 magnetic resonance imaging-screened patients, 431 underwent PWI. Of these, 57 (13%) had a double mismatch, 151 (35%) only a DWI-FLAIR mismatch, and 54 (13%) only a PWI-DWI mismatch. DWI-FLAIR mismatch was more prevalent than PWI-DWI mismatch (48%, 95% confidence interval [CI] = 43-53% vs 26%, 95% CI = 22-30%; p < 0.0001). Screening for either one of the mismatch profiles resulted in a yield of 61% (95% CI = 56-65%). Prevalence of PWI-DWI mismatch was similar in patients with (27%) or without (24%) DWI-FLAIR mismatch (p = 0.52). In an exploratory analysis in the small subgroup of 208 randomized patients with PWI, PWI-DWI mismatch status did not modify the treatment response (p for interaction = 0.73).

Interpretation: Evaluating both the DWI-FLAIR and PWI-DWI mismatch patterns in patients with unknown time of stroke onset will result in the highest yield of thrombolysis treatment. The treatment benefit of alteplase in patients with a DWI-FLAIR mismatch seems to be driven not merely by the presence of a PWI-DWI mismatch, although this analysis was underpowered. ANN NEUROL 2020;87:931-938.
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http://dx.doi.org/10.1002/ana.25730DOI Listing
June 2020

Choice of Initial Brain Imaging in Patients with Suspected Acute Stroke: STROKE69, a Population-Based Study.

Cerebrovasc Dis 2020 25;49(1):110-118. Epub 2020 Feb 25.

Université de Lyon, Université Claude Bernard Lyon 1, HESPER EA 7425, Lyon, France,

Background: In patients with suspected stroke, brain imaging is recommended in the acute phase for appropriate management and treatment. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered reasonable choices for initial brain imaging. When both techniques are available, choosing one or the other might be associated with specific factors related either to patients, stroke symptoms, and severity or management organization.

Methods: The study was performed within the STROKE 69 database, a population-based cohort of all adult patients with suspected stroke admitted in one of the emergency departments (ED), primary stroke center, or stroke center of the Rhône County, from November 2015 to December 2016. Patients were included if they were admitted within 24 h following either symptom onset or last known normal. To identify factors potentially associated with the choice of initial brain imaging, a multivariate logistic regression was performed.

Results: Among the 3,244 patients with suspected stroke enrolled in the STROKE69 cohort, 3,107 (95.8%) underwent brain imaging within the first 24 h after admission. Among those 74.6% underwent CT as initial imaging while 25.4% had an MRI. In multivariate analyses, several factors were associated with a lower probability of having an MRI as initial brain imaging versus CT. These were either patient characteristics: older age (>80 years old, OR 0.39 [95% CI 0.28-0.54]), preexisting disability (OR 0.55 [95% CI 0.36-0.84]), use of anticoagulants (OR 0.52 [95% CI 0.33-0.81]), stroke characteristics: stroke of unknown onset (OR 0.42 [95% CI 0.31-0.58]) or factors associated with overall management: onset-to-door time (>6 h, OR 0.38 [95% CI 0.23-0.60]), initial admission to ED (OR 0.02 [95% CI 0.02-0.04]) or intensive care unit (OR 0.01 [95% CI 0.001-0.08]), personal transport (OR 0.66 [95% CI 0.45-0.96]), and admission during working hours (OR 0.65 [95% CI 0.51-0.84]).

Conclusions: Besides CT or MRI availability, a number of other parameters could influence the choice of first imaging in case of stroke suspicion. These are related to patient characteristics, type of stroke symptoms, and type of organization.
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http://dx.doi.org/10.1159/000505960DOI Listing
September 2020

Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke.

Stroke 2020 04 20;51(4):1231-1239. Epub 2020 Feb 20.

APHP, Department of Endocrinology, Pitié-Salpêtrière hospital, Sorbonne University, Paris, France (E.B.).

Background and Purpose- The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of <70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque >4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods- One thousand seventy-three French patients were assigned to <70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90-110 mg/dL, 2.3-2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results- After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57-0.94]; =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% (=0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% (=0.023). The primary outcome or intracranial hemorrhage was reduced by 25% (=0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53-2.62]; =0.70). Conclusions- After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of <70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.
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http://dx.doi.org/10.1161/STROKEAHA.119.028718DOI Listing
April 2020

Atrial premature activity detected after an ischaemic stroke unveils atrial myopathy.

Arch Cardiovasc Dis 2020 Apr 29;113(4):227-236. Epub 2020 Jan 29.

Service d'explorations fonctionnelles cardiovasculaires, groupement hospitalier Est, hospices civils de Lyon, hôpital Louis Pradel, 28, avenue Doyen-Lépine, 69677 Bron, France. Electronic address:

Background: Recent publications suggest that left atrial (LA) myopathy is a potential source of thromboembolism, independent of atrial fibrillation.

Aims: We sought to investigate whether the presence of atrial premature activity after an ischaemic stroke is associated with LA remodelling and dysfunction, and might be a surrogate marker of LA myopathy.

Methods: After an ischaemic stroke or a transient ischaemic attack, patients without known atrial fibrillation or overt heart disease were included prospectively in the study. All patients had a standard workup, including ambulatory Holter electrocardiogram monitoring and transthoracic echocardiography. In some patients, transoesophageal echocardiography was also performed. Anatomical and functional LA remodelling were assessed using minimal and maximal volumes and LA emptying fraction in two-dimensional and three-dimensional echocardiography. Patients were separated into two groups according to the burden of atrial premature complexes (APCs), measured by Holter electrocardiography.

Results: Among 148 eligible patients recruited from October 2015 to May 2016, 93 were included in the group with non-frequent APCs (nf-APC:<100 APCs/24hours) and 43 in the group with frequent APCs (f-APC:>100 APCs/24hours). Twelve patients had paroxysmal atrial fibrillation, and were not included in the statistical analysis. Maximal and minimal indexed LA volumes were significantly higher in the f-APC group than in the nf-APC group (P<0.01). LA emptying fraction was worse in the f-APC group than in the nf-APC group. In addition, LA appendage emptying velocity was impaired in the f-APC group, and was correlated with LA remodelling variables, especially LA emptying fraction (r=0.621).

Conclusions: After an ischaemic stroke or a transient ischaemic attack, excessive APCs are associated with LA remodelling. Thus, LA dilatation and dysfunction reflect early LA myopathy, which might itself be responsible for cardioembolic stroke.
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http://dx.doi.org/10.1016/j.acvd.2019.12.002DOI Listing
April 2020

Correction to: A case of verbal and emotional prosody processing dissociation after a right temporal venous infarct.

Neurol Sci 2020 Mar;41(3):737

Stroke Department, Hôpital Neurologique Pierre Wertheimer, 69677, Bron, France.

The above article was published online with missing authors.
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http://dx.doi.org/10.1007/s10072-020-04259-yDOI Listing
March 2020