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Background: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown. Methods: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0–2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0–1), symptomatic intracranial hemorrhage, and early neurological deterioration. Results: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63–82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4–10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66–1.01]; P =0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95–1.43]; P =0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35–4.67]; P =0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64–3.84]; P Conclusions: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Background: Although anxiety is common in several neurological conditions, it has been poorly investigated after spontaneous intracerebral hemorrhage (ICH). Aims: In consecutive ICH survivors, we assessed the long-term prevalence of anxiety and its clinical and radiological determinants. Methods: Using the Hospital Anxiety and Depression Scale (HADS), we evaluated ICH survivors enrolled in the prospective, single-center Prognosis of Intracerebral Hemorrhage (PITCH) study. The prevalence of anxiety (defined as a HADS-anxiety subscale score >7) was evaluated at three time points (1–2, 3–5, and 6–8 years after ICH), along with neurological symptoms severity, functional disability, and cognitive impairment scores. Clinical and radiological characteristics associated with anxiety were evaluated in univariate and multivariable models. Results: Of 560 patients with spontaneous ICH, 255 were alive 1 year later, 179 of whom completed the HADS questionnaire and were included in the study. Thirty-one patients (17%; 95% confidence interval (CI) = 12–23) had anxiety 1–2 years, 38 (27%; 95% CI = 19–34) 3–5 years, and 18 (21%; 95% CI = 12–30) 6–8 years after ICH. In patients with anxiety, the prevalence of associated depressive symptoms was 48% 1–2 years, 61% 3–5 years, and 56% 6–8 years after ICH. Among clinical and radiological baseline characteristics, only lobar ICH location was significantly associated with anxiety 1–2 years after ICH (odds ratio = 2.8; 95% CI = 1.2–6.5). Anxiety was not associated with concomitant neurological symptoms severity, functional disability, or cognitive impairment. Conclusion: Anxiety is frequent in ICH survivors, often in association with depressive symptoms, even many years after the index event.

BackgroundIntravenous thrombolysis (IVT) for patients treated with mechanical thrombectomy (MT) for proximal occlusions has recently been questioned through randomized trials. However, few patients with M2 occlusions were included. We investigated the influence of prior IVT for patients presenting M2 occlusions treated with MT in comparison with MT alone.MethodsWe conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a multicenter observational study. Data from consecutive patients treated with MT for M2 occlusions between January 2015 and January 2022 at 26 comprehensive stroke centers were analyzed. The primary endpoint was 90-day modified Rankin Scale score of 0–2. Outcomes were compared using propensity score approaches. We also performed sensitivity analysis in relevant subgroups of patients.ResultsAmong 1132 patients with M2 occlusions treated with MT, 570 received prior IVT. The two groups were comparable after propensity analysis. The rate of favorable functional outcome was significantly higher in the IVT+MT group compared with the MT alone group (59.8% vs 44.7%; adjusted OR 1.38, 95% CI 1.10 to 1.75, P=0.008). Hemorrhagic and procedural complications were similar in both groups. In sensitivity analysis excluding patients with anticoagulation treatment, favorable recanalization was more frequent in the IVT+MT group (OR 1.37, 95% CI 1.11 to 1.70, P=0.004).ConclusionsIn cases of M2 occlusions, prior IVT combined with MT resulted in better functional outcome than MT alone, without increasing the rate of hemorrhagic or procedural complications. These results suggest the benefit of IVT in patients undergoing MT for M2 occlusions.

BackgroundPatients treated with acute carotid stenting (CAS) may have higher odds of a favorable outcome than those treated without CAS during thrombectomy in tandem occlusions. Antiplatelet therapy is associated with CAS to avoid stent thrombosis, which occurs in around 20% of patients and negatively impacts outcomes. In this study we compared two antiplatelet strategies in tandem occlusion strokes treated with CAS and intracranial thrombectomy in clinical practice.MethodsThe Endovascular Treatment in Ischemic Stroke Registry is an ongoing prospective observational study involving 21 comprehensive stroke centers performing thrombectomy in France. We analyzed patients with atherosclerotic tandem occlusions treated with acute CAS and intracranial thrombectomy who received at least one antiplatelet agent. Aggressive antiplatelet therapy included oral or intravenous glycoprotein (GP) IIb/IIIa or P2Y12 inhibitors. The primary outcome was cervical carotid artery patency at day 1 imaging follow-up.ResultsAmong the 187 included patients, 124 (66.3%) received aspirin alone and 63 (33.7%) received aggressive antiplatelet therapy. There was no significant difference regarding safety outcomes, especially in symptomatic intracerebral hemorrhage, parenchymal hematoma, and procedural complications. There was a significantly higher rate of carotid stent patency at day 1 in the aggressive antiplatelet therapy group (81.7% vs 97.1%, aOR 17.49, 95% CI 1.10 to 277.2, p=0.042). Odds of favorable functional outcome (90-day modified Rankin Scale score 0–2) were similar between the groups (OR 3.04, 95% CI 0.64 to 14.25, p=0.158).ConclusionsIn tandem occlusions treated with CAS plus thrombectomy, an aggressive antiplatelet regimen was associated with an increased rate of carotid stent patency at day 1 without safety concerns. Randomized trials are warranted to confirm these findings.

Background and Purpose: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

International audience; OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

Background and objectivePredictors of symptomatic haemorrhagic transformation (s-HT) of cerebral ischaemia after intravenous recombinant tissue-plasminogen activator (rt-PA) were identified in studies using CT scans. We evaluated whether MRI can identify other predictors.MethodWe analysed predictors of s-HT in a cohort of consecutive patients who received intravenous rt-PA for cerebral ischaemia after MRI at baseline. We used receiver operating characteristic curves considering an area under the curve (AUC) of 0.70 or higher as indicating acceptable discrimination.ResultsOf 944 patients, 49 patients (5.2%) developed s-HT. Clinical factors independently associated with s-HT were age (adjusted OR (adjOR) 1.03 for 1 year increase; 95% CI 1.01 to 1.05), excessive alcohol consumption (adjOR 3.13; 95% CI 1.32 to 7.42), recent transient ischaemic attack (adjOR 2.88; 95% CI 1.04 to 7.95) and baseline national institutes of health stroke scale score (adjOR 1.06 for 1 point increase; 95% CI 1.02 to 1.10). MRI predictors were vascular hyperintensities (adjOR 3.89; 95% CI 1.50 to 10.08), old infarcts (adjOR 2.01; 95% CI 1.11 to 3.66) and volume of diffusion-weighted imaging (DWI) abnormality (adjOR 1.02 for 1 cm3 increase; 95% CI 1.01 to 1.03). The only variable with an acceptable discrimination was volume of DWI abnormality (AUC 0.72; 95% CI 0.64 to 0.79), a value of 4 cm3 predicting s-HT with a 78% sensitivity and 58% specificity. Variables that can be assessed only with MRI did not predict s-HT.ConclusionAlthough the volume of DWI abnormality predicts s-HT, other imaging characteristics that can only be assessed with MRI were not significantly associated with s-HT.Trial registration numberNCT01614080

Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

ObjectiveTo test the hypothesis that remote intracerebral hemorrhages (r-ICHs) after IV thrombolysis occur in preexisting brain lesions.MethodWe prospectively collected baseline data from consecutive patients treated with IV thrombolysis for cerebral ischemia and reviewed their baseline MRI scans to identify preexisting lesions in those who developed r-ICH. We evaluated outcomes with the modified Rankin Scale (mRS) and defined good outcomes as scores of 0 to 2 or similar to the preexisting mRS score.ResultsOf 944 patients, 24 (2.5%) had r-ICH: lobar in 14, deep in 7, and both in 3. Sixteen of them (1.7% of all patients, 66.7% of those with r-ICH) were asymptomatic. Of the 41 r-ICHs found in these patients, 17 (41%) occurred within a lesion present before thrombolysis: 6 cerebral microbleeds (CMBs), 6 old and 1 recent infarct, and 4 areas of white matter hyperintensity. Patients with r-ICH were more likely to have strictly lobar CMBs (p = 0.049). They were 10 years older (p = 0.007), had a 16–mm Hg higher systolic blood pressure (p = 0.035) at baseline, and had more CMBs (p = 0.007). r-ICHs were better predicted by clinical (age, baseline systolic blood pressure) than imaging (purely lobar CMBs and having >5 CMBs) variables. r-ICHs tended to be associated with worse outcomes.ConclusionWe identified preexisting brain lesions in nearly half of the patients with r-ICH. All were of vascular origin, supporting the hypothesis that r-ICHs occur in preexisting brain lesions. Higher-field machines could help identifying preexisting lesions in those who developed r-ICH in an apparently normal area.

Objective This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage. Methods We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia. Results The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3–35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32–3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13–2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01–2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00–2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60–2.87). Conclusion Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up.

Background and Purpose— The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of 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 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]; P =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% ( P =0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% ( P =0.023). The primary outcome or intracranial hemorrhage was reduced by 25% ( P =0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P =0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875.

ObjectiveNeuropsychiatric (NP) symptoms are prominent features of cognitive decline, but they have been understudied in patients with spontaneous intracerebral haemorrhage (ICH). In ICH survivors, we aimed at assessing NP symptoms prevalence and profiles, and their influence on long-term outcomes.MethodsWe analysed data from consecutive 6-month ICH survivors enrolled in the Prognosis of Intracerebral Haemorrhage study. We performed NP evaluation using the Neuropsychiatric Inventory Questionnaire. Patients underwent long-term clinical follow-up after ICH (median follow-up time 7.2 years, IQR 4.8–8.2).ResultsOut of 560 patients with ICH, 265 survived at 6 months. NP evaluation 6 months after ICH was feasible in 202 patients. NP symptoms were present in 112 patients (55%), and in 36 out of 48 patients (75%) with post-ICH dementia. Affective symptoms were present in 77 patients (38%), followed by vegetative symptoms (52 patients, 26%) and hyperactivity (47 patients, 23%). Apathy and hyperactivity were associated with post-ICH dementia and cerebral amyloid angiopathy MRI profile (all pConclusionNP symptoms were present in more than half of 6-month ICH survivors, with higher prevalence and severity in patients with post-ICH dementia. Distinctive NP profile might be associated to cognitive status and inform on long-term dementia risk.

Background and purpose Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area. Method We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS. Results During the study period (2016–2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72–90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234–264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay. Conclusion The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay.

A stroke mimic is a situation in which a diagnosis of stroke at admission is not confirmed, and a stroke chameleon is a situation in which a stroke is revealed by clinical symptoms that are not usual in stroke. The objective of this review is to identify the most frequent clinical situations in which stroke mimics and chameleons are encountered and consequences for the patient.The safety profile of intravenous thrombolysis (IVT) in patients who have stroke mimics is excellent, and intracranial hemorrhages are rare. Modern neuroimaging techniques help identifying most mimics. For stroke chameleons the role of imaging may be less important, especially when the clinical presentation is not suggestive of a brain disorder that request immediate neuroimaging. Education of health providers to identify such situations is crucial.Stroke mimics account for up to 25% of admissions for probable strokes. The proportion of patients with stroke mimics decreases with use of MRI at baseline. Mimics cannot always be ruled out in emergency. The problem with mimics is that stroke facilities are not properly used, and patients may receive IVT. However, thrombolysis is usually well tolerated in mimics and we should not spend much time in all patients to improve diagnostic accuracy, knowing that the time lost is harmful in all patients, and will only prevent treating one mimic out of 100 patients. The problem with chameleons is more serious, because patients are not identified, and are not properly treated.

Many strokes are treatable in the acute stage, provided patients are admitted soon enough. There is evidence that stroke unit care improves outcomes, and that the benefit does not depend on age, severity, and stroke subtype. In ischaemic strokes, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and mechanical thrombectomy in case of proximal arterial occlusion, on top of thrombolysis in the absence of contraindication or alone otherwise, aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. The time window for thrombolysis or thrombectomy can be extended beyond the usual 4.5h and 6h in a few patients who are likely to have significant penumbra. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, while surgery does not seem effective to reduce death and disability.

Background Factors associated with long-term mortality after spontaneous intracerebral hemorrhage (ICH) have been poorly investigated. Aim Our objective was to identify variables associated with long-term mortality in a prospective cohort of 30-day ICH survivors. Methods We prospectively included consecutive 30-day spontaneous ICH survivors. We evaluated baseline and follow-up clinical characteristics and magnetic resonance imaging (MRI) markers of chronic brain injury as variables associated with long-term mortality using univariate and multivariable Cox proportional hazard regression models. Results Of 560 patients with spontaneous ICH, 304 (54.2%) survived more than 30 days and consented for follow-up. During a median follow-up of 10 years (interquartile range: 8.0–10.5), 176 patients died. The cumulative survival rate at 10 years was 38%. In multivariable analysis, variables independently associated with long-term mortality were age (hazard ratio (HR) per 10-year increase: 1.68, 95% confidence interval (CI): 1.45–1.95), male gender (HR: 1.41, CI: 1.02–1.95), prestroke dependency (HR: 1.66, CI: 1.15–2.39), National Institutes of Health Stroke Scale score (HR per 1-point increase: 1.03, CI: 1.01–1.04), occurrence of any stroke (HR: 2.24, CI: 1.39–3.60), and dementia (HR: 1.51, CI: 1.06–2.16) during follow-up. Among MRI markers, only cerebral atrophy (HR per 1-point increase: 1.50, CI: 1.13–2.00) was independently associated with long-term mortality. Conclusions Preexisting comorbidities, clinical severity at presentation, and significant clinical event during follow-up are associated with long-term mortality. Among MRI markers of chronic brain injury, only cerebral atrophy is associated with long-term mortality.

ObjectiveTo identify in patients who survived 6 months after a spontaneous intracerebral haemorrhage (ICH) baseline characteristics and new clinical events associated with functional decline.MethodsIn a single-centre study, we prospectively included 6-month survivors with a modified Rankin Scale (mRS) score 0–3. We defined functional decline by a transition to mRS 4–5. We evaluated associations of baseline characteristics and new clinical events with functional decline, using univariate and multivariable models.ResultsOf 560 patients, 174 (31%) had an mRS score 0–3 at 6 months. During a median follow-up of 9 years (IQR 8.1–9.5), 40 (23%) converted to mRS 4–5. Age, diabetes mellitus, ICH volume and higher mRS scores at 6 months were independently associated with functional decline. Among baseline MRI markers, presence of strictly lobar cerebral microbleeds (CMBs), and mixed lobar and deep CMBs were independently associated with functional decline. When new clinical events occurring during follow-up were added in multivariable models, age (cause-specific HR (CSHR): 1.07; 95% CI: 1.03 to 1.11), ICH volume (CSHR: 1.03; 95% CI: 1.01 to 1.06), mRS score at 6 months (CSHR per 1 point increase 1.61, 95% CI 1.07 to 2.43), occurrence of dementia (CSHR: 3.81, 95% CI: 1.78 to 8.16) and occurrence of any stroke (CSHR: 4.29, 95% CI: 1.80 to 10.22) remained independently associated with transition to mRS 4–5.InterpretationAlmost one-fourth of patients with spontaneous ICH developed a functional decline over time. Age, ICH volume, higher mRS score at 6 months and new clinical events after ICH are the major determinants.

Cerebral amyloid angiopathy (CAA) is a frequent age-related small vessel disease (SVD) with cardinal magnetic resonance imaging (MRI) signatures that are hemorrhagic in nature, and include the presence of strictly lobar (superficial) cerebral microbleeds and intracerebral hemorrhages as well as cortical superficial siderosis. When investigating a patient with suspected CAA in the context of intracranial hemorrhage (parenchymal or subarachnoid) or cognitive dysfunction, various MRI parameters influence the optimal detection and characterization (and prognostication) of this frequent SVD. The present report describes the influence of imaging techniques on the detection of the key hemorrhagic CAA imaging signatures in clinical practice, in research studies, and the imaging parameters that must be understood when encountering a CAA patient, as well as reviewing CAA literature.

Background and Purpose— We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods— We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2–4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). Results— In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09–2.07; P =0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73–5.35; P P =0.014), PH ( P =0.013), and PHr ( P 10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10–3.12; P =0.020; and odds ratio: 3.99; 95% confidence interval: 1.55–10.22; P =0.004, respectively). Conclusions— Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

Objective:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity).Methods:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2–4, 5–10, and >10 CMBs), using random effects models.Results:We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2–12.6 vs 1.1%, 95% CI 0.5–1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1–3 years): OR 3.1 (95% CI 1.4–6.8; p = 0.006), 4.3 (95% CI 1.8–10.3; p = 0.001), and 3.4 (95% CI 1.4–8.3; p = 0.007) for 2–4, 5–10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1–15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts.Conclusions:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.

Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p

Aim In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. Method Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months. The observed outcomes were then compared with the probability of good (mRS 0–1) and of catastrophic (mRS 5–6) outcomes, as predicted by the stroke-thrombolytic predictive instrument (STPI). Results Of the 1000 consecutive patients (469 male, median age 74 years, median baseline National Institutes of Health Stroke Scale 11, median onset-to-needle time 143 min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0–2 or similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%) developed symptomatic intracerebral hemorrhage according to ECASS-II (Second European–Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%) eligible for evaluation by the s-TPI, the observed rate of good outcomes was 41.3% (95% CI: 37.5–45.3%), while expected rates with and without rt-PA were 48.8% (95% CI: 44.8–52.7%) and 32.5% (95% CI: 28.8–36.2%), respectively; the observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0–19.9%), while the expected rate was 19.2% (95% CI: 16.1–22.4%) with or without rt-PA. Conclusion In clinical practice, the rate of good outcomes is slightly lower than expected, according to the s-TPI, except for the most severe cases, whereas the rate of catastrophic outcomes is roughly similar. However, the rate of good outcomes is higher than predicted without treatment. This finding suggests that rt-PA is effective for improving outcomes in clinical practice.

One in six patients admitted for stroke was previously demented. These patients have less access to appropriate stroke care, although little is known about their optimal management. Objective To determine how pre-stroke cognitive impairment can be detected, its mechanism, and influence on outcome and management. Methods Literature search. Results (i) A systematic approach with the Informant Questionnaire of Cognitive Decline in the Elderly is recommended; (ii) Pre-stroke cognitive impairment may be due to brain lesions of vascular, degenerative, or mixed origin; (iii) Patients with pre-stroke dementia, have worse outcomes, more seizures, delirium, and depression, and higher mortality rates; they often need to be institutionalised after their stroke; (iv) Although the safety profile of treatment is not as good as that of cognitively normal patients, the risk:benefit ratio is in favour of treating these patients like others. Conclusion Patients with cognitive impairment who develop a stroke have worse outcomes, but should be treated like others. RESUMO Um em cada seis pacientes internados em decorrência de acidente vascular cerebral (AVC) apresenta diagnóstico prévio de demência. Estes indivíduos têm menor acesso à assistência recomendada para pacientes com AVC, mas pouco ainda se sabe em relação aos cuidados médicos ideais que devem receber. Objetivo Determinar como o comprometimento cognitivo prévio ao AVC pode ser detectado, qual o mecanismo etiológico subjacente, e as consequências para o prognóstico e para o acompanhamento clínico. Método Pesquisa bibliográfica. Resultados (i) O rastreamento sistemático com o Informant Questionnaire of Cognitive Decline in the Elderly é recomendado; (ii) O comprometimento cognitivo preexistente pode ser devido a lesões cerebrais de origem vascular, degenerativa ou mista; (iii) Pacientes com demência prévia ao AVC têm pior prognóstico, maior frequência de crises epilépticas, de delirium e depressão, além de taxas de mortalidade mais altas; eles frequentemente são institucionalizados após o AVC; (iv) Embora a tolerabilidade às medicações não seja tão boa quanto a de pacientes com AVC sem comprometimento cognitivo, a relação risco/benefício é a favor de tratamento similar àquele oferecido aos demais pacientes. Conclusão Pacientes com comprometimento cognitivo que apresentam AVC têm pior prognóstico, porém eles devem ser tratados de modo semelhante aos demais casos.

Cerebral microbleeds (CMB)—small round or ovoid lesions detected in hyposignal on blood-sensitive MRI sequences—are promising radiological biomarkers of cerebral small vessel disease. Their relations with ischaemic or haemorragic stroke and their potential contribution to dementia have been extensively addressed. This article reviews recent research on the clinical significance of CMB that remains to be determined. The presence, burden and location of CMB allow to obtain a more accurate estimate of intracerebral haemorrhage and ischaemic stroke risk. Most studies evaluating the association between CMB and dementia are hampered by methodological limitations and show conflicting results. CMB mainly reflect the severity of the underlying small vessel disease and should not be interpreted independently of the others neuroimaging biomarkers or the clinical setting. Future large prospective longitudinal studies and randomized controlled trials in various settings are required to determine whether specific therapies are beneficial in case of incidental findings.

Background and Purpose— We aimed to determine incidences and predictors of major vascular events in intracerebral hemorrhage (ICH) survivors. Methods— We did a prospective observational cohort study in patients with spontaneous ICH from the Prognosis of Intracerebral Hemorrhage cohort in Lille, France. We studied incidences and predictors of long-term vascular events (cerebral and extracerebral, ischemic and hemorrhagic) in patients alive at 30 days with a prespecified subgroup analysis according to ICH location. We performed multivariable analyses (competing risk analyses, with death during follow-up as a competing event). Results— From the 560 patients with spontaneous ICH enrolled between November 2004 and March 2009, we included 310 patients (median age, 70 years). Eighty-two patients presented at least 1 major vascular event leading to an incidence rate of 20.0% (95% CI, 15.7–24.7) at 5 years after ICH. In the overall cohort, ischemic events were more frequent than hemorrhagic events. However, the incidence strikingly differed according to ICH location: deep ICH was associated with future ischemic events (subhazard ratio, 1.85; 95% CI, 1.01–3.40), whereas lobar ICH with hemorrhagic events (subhazard ratio, 2.38; 95% CI, 1.17–4.86). In deep ICH, the incidence of ischemic events at 5 years was 6× higher than the incidence of hemorrhagic events. Conclusions— ICH survivors are at high risk of both cerebral and extracerebral vascular events. The ischemic or hemorrhagic risk profile varies according to the index ICH location with a stronger ischemic risk in deep ICH. Secondary prevention, tailored on ICH location, should target not only cerebral recurrences but also extracerebral vascular events.

Summary Background Dementia occurs in at least 10% of patients within 1 year after stroke. However, the risk of dementia after spontaneous intracerebral haemorrhage that accounts for about 15% of all strokes has not been investigated in prospective studies. We aimed to determine the incidence of dementia and risk factors after an intracerebral haemorrhage. Methods We did a prospective observational cohort study in patients with spontaneous intracerebral haemorrhage from the Prognosis of Intracerebral Haemorrhage (PITCH) cohort who were admitted to Lille University Hospital, Lille, France. We included patients aged 18 years and older with parenchymal haemorrhage on the first CT scan. Exclusion criteria were pure intraventricular haemorrhage; intracerebral haemorrhage resulting from intracranial vascular malformation, intracranial venous thrombosis, head trauma, or tumour; haemorrhagic transformation within an infarct; and referral from other hospitals. Median follow-up was 6 years. We studied risk factors (clinical and neuroradiological [MRI] biomarkers) of new-onset dementia as per a prespecified subgroup analysis, according to intracerebral haemorrhage location. Dementia diagnosis was based on the National Institute on Aging-Alzheimer's Association criteria for all-cause dementia. We did multivariable analyses using competing risk analyses, with death during follow-up as a competing event. Findings From the 560 patients with spontaneous intracerebral haemorrhage enrolled in the PITCH cohort between Nov 3, 2004 and March 29, 2009, we included 218 patients (median age 67·5 years) without pre-existing dementia who were alive at 6 months follow-up. 63 patients developed new-onset dementia leading to an incidence rate of 14·2% (95% CI 10·0–19·3) at 1 year after intracerebral haemorrhage, and incidence reached 28·3% (22·4–34·5) at 4 years. The incidence of new-onset dementia was more than two times higher in patients with lobar intracerebral haemorrhage (incidence at 1 year 23·4%, 14·6–33·3) than for patients with non-lobar intracerebral haemorrhage (incidence at 1 year 9·2%, 5·1–14·7). Disseminated superficial siderosis (subhazard ratio [SHR] 7·45, 95% CI 4·27–12·99), cortical atrophy score (SHR per 1-point increase 2·61, 1·70–4·01), a higher number of cerebral microbleeds (SHR for >5 cerebral microbleeds 2·33, 1·38–3·94), and older age (SHR per 10-year increase 1·34, 1·00–1·79) were risk factors of new-onset dementia. Interpretation There is a substantial risk of incident dementia in dementia-free survivors of spontaneous intracerebral haemorrhage; our results suggest that underlying cerebral amyloid angiopathy is a contributing factor to the occurrence of new-onset dementia. Future clinical trials including patients with intracerebral haemorrhage should assess cognitive endpoints. Funding French Ministry of Education, Research, and Technology, Adrinord, Inserm U1171.

Background and Purpose— Orolingual angioedema (OLAE) is a life-threatening complication of intravenous thrombolysis. Our objective was to compare outcomes of patients with and without OLAE. Methods— We prospectively included consecutive patients who received intravenous thrombolysis for cerebral ischemia at Lille University Hospital. We examined tongue and lips every 15 minutes during thrombolysis and ≤30 minutes after. We evaluated the 3-month outcome with the modified Rankin scale (mRS) and compared outcomes of patients with and without OLAE. Results— Of 923 consecutive patients, 20 (2.2%) developed OLAE. None of them needed oro-tracheal intubation. They were more likely to be under angiotensin-converting enzyme inhibitors (adjusted odds ratio [adjOR], 3.9; 95% confidence interval [CI], 1.6–9.7; P =0.005) to have total insular infarcts (OR, 5.0; 95% CI, 1.5–16.5; P =0.004) and tended to develop more symptomatic intracerebral hemorrhages. Results concerning angiotensin-converting enzyme inhibitors were not modified after adjustment for propensity scores (OR, 4.4; 95% CI, 1.6–11.9; P =0.004) or matched analysis based on propensity scores (OR, 3.4; 95% CI, 1.3–8.1; P =0.010). Patients with OLAE did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1 (adjOR, 0.9; 95% CI, 0.3–2.1), mRS score of 0 to 2 (adjOR, 0.8; 95% CI, 0.1–1.8), and death (adjOR, 1.1; 95% CI, 0.3–3.8). Conclusions— OLAE occurs in 1 of 50 patients who receive intravenous thrombolysis, 1 of 10 in case of total insular infarct, and 1 of 6 if they are under angiotensin-converting enzyme inhibitors. Their long-term outcome does not differ from that of other patients.

Background and Purpose— We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones. Methods— In a multicenter IVT-register–based cohort study, we compared previously dependent (prestroke modified Rankin Scale score, 3–5) versus independent (prestroke modified Rankin Scale score, 0–2) patients. Outcome measures were poor 3-month outcome (not reaching at least prestroke modified Rankin Scale [dependent patients]; modified Rankin Scale score of 3–6 [independent patients]), death, and symptomatic intracranial hemorrhage. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (OR [95% confidence interval]) were calculated. Results— Among 7430 IVT-treated patients, 489 (6.6%) were dependent and 6941 (93.4%) were independent. Previous stroke, dementia, heart, and bone diseases were the most common causes of preexisting dependency. Dependent patients were more likely to die (OR unadjusted , 4.55 [3.74–5.53]; OR adjusted , 2.19 [1.70–2.84]). Symptomatic intracranial hemorrhage occurred equally frequent (4.8% versus 4.5%). Poor outcome was more frequent in dependent (60.5%) than in independent (39.6%) patients, but the adjusted ORs were similar (OR adjusted , 0.95 [0.75–1.21]). Among survivors, the proportion of patients with poor outcome did not differ (35.7% versus 31.3%). After adjustment for age and stroke severity, the odds of poor outcome were lower in dependent patients (OR adjusted , 0.64 [0.49–0.84]). Conclusions— IVT-treated stroke patients who were dependent on the daily help of others before stroke carry a higher mortality risk than previously independent patients. The risk of symptomatic intracranial hemorrhage and the likelihood of poor outcome were not independently influenced by previous dependency. Among survivors, poor outcome was avoided at least as effectively in previously dependent patients. Thus, withholding IVT in previously dependent patients might not be justified.

Background Nonagenarians are under-represented in thrombolytic trials for acute ischemic stroke (AIS). The effectiveness of intravenous thrombolytics in nonagenarians in terms of safety and outcome is not well established. Materials and Methods We used a multinational registry to identify patients aged 90 years or older with good baseline functional status who presented with AIS. Differences in outcomes—disability level at 90 days, frequency of symptomatic intracerebral hemorrhage (sICH), and mortality—between patients who did and did not receive thrombolytics were assessed using multivariable logistic regression, adjusted for prespecified prognostic factors. Coarsened exact matching (CEM) was utilized before evaluating outcome by balancing both groups in the sensitivity analysis. Results We identified 227 previously independent nonagenarians with AIS; 122 received intravenous thrombolytics and 105 did not. In the unmatched cohort, ordinal analysis showed a significant treatment effect (adjusted common odds ratio [OR]: .61, 95% confidence interval [CI]: .39-.96). There was an absolute difference of 8.1% in the rate of excellent outcome in favor of thrombolysis (17.4% versus 9.3%; adjusted ratio: .30, 95% CI: .12-.77). Rates of sICH and in-hospital mortality were not different. Similarly, in the matched cohort, CEM analysis showed a shift in the primary outcome distribution in favor of thrombolysis (adjusted common OR: .45, 95% CI: .26-.76). Conclusions Nonagenarians treated with thrombolytics showed lower stroke-related disability at 90 days than those not treated, without significant difference in sICH and in-hospital mortality rates. These observations cannot exclude a residual confounding effect, but provide evidence that thrombolytics should not be withheld from nonagenarians because of age alone.

ObjectiveTo study the effect of platelet count (PC) on bleeding risk and outcome in stroke patients treated with IV thrombolysis (IVT) and to explore whether withholding IVT in PC < 100 × 109/L is supported.MethodsIn this prospective multicenter, IVT register–based study, we compared PC with symptomatic intracranial hemorrhage (sICH; Second European-Australasian Acute Stroke Study [ECASS II] criteria), poor outcome (modified Rankin Scale score 3–6), and mortality at 3 months. PC was used as a continuous and categorical variable distinguishing thrombocytopenia (9/L), thrombocytosis (>450 × 109/L), and normal PC (150–450 × 109/L [reference group]). Moreover, PC < 100 × 109/L was compared to PC ≥ 100 × 109/L. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from the logistic regression models were calculated.ResultsAmong 7,533 IVT-treated stroke patients, 6,830 (90.7%) had normal PC, 595 (7.9%) had thrombocytopenia, and 108 (1.4%) had thrombocytosis. Decreasing PC (every 10 × 109/L) was associated with increasing risk of sICH (ORadjusted 1.03, 95% CI 1.02–1.05) but decreasing risk of poor outcome (ORadjusted 0.99, 95% CI 0.98–0.99) and mortality (ORadjusted 0.98, 95% CI 0.98–0.99). The risk of sICH was higher in patients with thrombocytopenic than in patients with normal PC (ORadjusted 1.73, 95% CI 1.24–2.43). However, the risk of poor outcome (ORadjusted 0.89, 95% CI 0.39–1.97) and mortality (ORadjusted 1.09, 95% CI 0.83–1.44) did not differ significantly. Thrombocytosis was associated with mortality (ORadjusted 2.02, 95% CI 1.21–3.37). Forty-four (0.3%) patients had PC < 100 × 109/L. Their risks of sICH (ORunadjusted 1.56, 95% CI 0.48–5.07), poor outcome (ORadjusted 1.63, 95% CI 0.82–3.24), and mortality (ORadjusted 1.38, 95% CI 0.64–2.98) did not differ significantly from those of patients with PC ≥ 100 × 109/L.ConclusionLower PC was associated with increased risk of sICH, while higher PC indicated increased mortality. Our data suggest that PC modifies outcome and complications in individual patients, while withholding IVT in all patients with PC < 100 × 109/L is challenged.

ObjectiveTo determine the prevalence of cortical superficial siderosis (cSS), its clinical and neuroimaging associated markers, and its influence on the risk of recurrent intracerebral hemorrhage (ICH) in a prospective observational ICH cohort.MethodsWe investigated clinical and radiologic markers associated with cSS using multivariable analysis. In survival analyses, we used Cox models to identify predictors of recurrent ICH after adjusting for potential confounders.ResultsOf the 258 patients included in the study, 49 (19%; 95% confidence interval [CI] 14%–24%) had cSS at baseline. Clinical factors independently associated with the presence of cSS were increasing age (odds ratio [OR] 1.03 per 1-year increase, 95% CI 1.001–1.06, p = 0.044), preexisting dementia (OR 2.62, 95% CI 1.05–6.51, p = 0.039), and history of ICH (OR 4.02, 95% CI 1.24–12.95, p = 0.02). Among radiologic biomarkers, factors independently associated with the presence of cSS were ICH lobar location (OR 24.841, 95% CI 3.2–14.47, p < 0.001), severe white matter hyperintensities score (OR 5.51, 95% CI 1.17–5.78, p = 0.019), and absence of lacune (OR 4.46, 95% CI 1.06–5.22, p = 0.035). During a median follow-up of 6.4 (interquartile range 2.9–8.4) years, recurrent ICH occurred in 19 patients. Only disseminated cSS (hazard ratio 4.69, 95% CI 1.49–14.71, p = 0.008), not the presence or absence of cSS or focal cSS on baseline MRI, was associated with recurrent symptomatic ICH.ConclusionIn a prospective observational cohort of spontaneous ICH, clinical and radiologic markers associated with cSS suggest the implication of underlying cerebral amyloid angiopathy. Disseminated cSS may become a key prognostic neuroimaging marker of recurrent ICH that could be monitored in future clinical trials dedicated to patients with ICH.

Objective: To determine whether higher neutrophil counts before IV recombinant tissue plasminogen activator (rtPA) administration in ischemic stroke (IS) patients are associated with symptomatic intracerebral hemorrhages (sICH) and worse outcomes at 3 months. Methods: Blood samples for leukocyte, neutrophil, and lymphocyte counts were drawn before IV rtPA administration in IS patients included in the cohorts of Lille and Helsinki. The primary endpoint was sICH (European Cooperative Acute Stroke–II definition). Secondary endpoints were death and excellent (modified Rankin Scale [mRS] score 0–1 or equal to prestroke mRS) and good (mRS score 0–2 or equal to prestroke mRS) outcomes at 3 months. Results: We included 846 patients (median age 71 years; 50.8% men). The neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with the 4 endpoints: sICH (adjusted odds ratio [ adj OR] for an increase of 1,000 neutrophils = 1.21 and adj OR 1.11, respectively), death ( adj OR 1.16 and adj OR 1.08), and excellent ( adj OR 0.87 and adj OR 0.85) and good ( adj OR 0.86 and adj OR 0.91) outcomes. The total leukocyte count was not associated with any of the 4 endpoints. The best discriminating factor for sICH was NLR ≥4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32). Patients with NLR ≥4.80 had a 3.71-fold increased risk for sICH (95% confidence interval adj OR: 1.97–6.98) compared to patients with NLR Conclusions: Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.

Intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) should be available on a 24/7 basis in hospitals admitting patients with stroke. We aimed at evaluating the influence of the number of patients previously treated with i.v. rt-PA by neurologists on patients' outcome. For each patient consecutively treated with i.v. rt-PA for cerebral ischaemia at the Lille University Hospital, we determined the number of previous treatments with rt-PA administered by the neurologist. We performed logistic regression analyses to determine the influence of the experience on the outcome evaluated by the modified Rankin scale (mRS) after 3 months, 0-1 meaning independence, and 0-2 meaning absence of handicap. We compared outcomes of patients treated by the 25% less experienced neurologists with those of trials. Forty-four neurologists treated 800 patients. The experience of the treating neurologist was independently associated with independence (adjusted odds ratio [(adj)OR] 1.062 for 10 patients more; 95% confidence interval [CI] 1.008-1.120), and absence of handicap ((adj)OR 1.076 for 10 patients more; 95%CI 1.016-1.140) at 3 months, but not with symptomatic intracerebral haemorrhage and death. The proportions of patients from the 1st quartile who were independent and without handicap at 3 months were 37.9 and 51.1%. Patients treated by less experienced neurologists, have similar outcomes than expected from trials, suggesting they benefit from thrombolysis. However, the outcome of patients treated by more experienced neurologists was slightly better. Less experienced neurologists should not be excluded from rt-PA programmes, but their practices should be evaluated and educational programmes organised.

ObjectiveTo study the association between poststroke cognitive impairment and defining a specific resting functional marker.MethodsThe resting-state functional connectivity 6 months after an ischemic stroke in 56 patients was investigated. Twenty-nine of the patients who had an impairment of one or several cognitive domains were compared to 27 without any cognitive deficit. We studied the whole-brain connectivity using 2 complementary approaches: graph theory to study the functional network organization and network-based statistics to explore connectivity between brain regions. We assessed the potential cortical atrophy using voxel-based morphometry analysis.ResultsThe overall topological organization of the functional network was not altered in cognitively impaired stroke patients, who had the same mean node degree, average clustering coefficient, and global efficiency as cognitively healthy stroke patients. Network-based statistics analysis showed that poststroke cognitive impairment was associated with dysfunction of a whole-brain network composed of 167 regions and 178 connections, and functional disconnections between superior, middle, and inferior frontal gyri and the superior and inferior temporal gyri. These regions had connections that were specifically and positively correlated with cognitive domain scores. No intergroup differences in overall gray matter thickness and ischemic infarct topography were observed. To assess the effect of prestroke white matter hyperintensities on connectivity, we included the initial Fazekas scale in the regression model for a second network-based analysis. The resulting network was associated with the same key alterations but had fewer connections.ConclusionsThe observed functional network alterations suggest that the appearance of a cognitive impairment following stroke may be associated with a particular functional alteration, shared specifically between cognitive domains.

Background: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. CAA-related ICH survivors are at substantial risk for recurrent ICH, accounting for the significant morbidity of the disease. Identifying predictors of recurrence is therefore crucial. Recent data have implicated cortical superficial siderosis (cSS) as a key hemorrhagic MRI signature of CAA, and a possible marker of increased risk for CAA-ICH recurrence. However, data remain limited. We obtained precise estimates on cSS as an independent predictor of ICH recurrence risk in CAA cohorts from a systematic review of published studies pooled with data from our centre. Methods: We included cohort studies of consecutive CAA-related ICH patients based on the original Boston criteria, with available blood-sensitive MRI sequences at baseline for cSS assessment, and adequate follow-up for recurrent symptomatic ICH. The strength of the association between cSS and recurrent ICH was quantified using random effects models. Covariate-adjusted hazard rations (adj-HR) as provided from pre-specified Cox proportional hazard models were used for a two-stage meta-analysis. Results: Three cohorts including 443 CAA-ICH patients were eligible for analysis. The pooled prevalence of cSS presence and disseminated cSS (>3 affected sulci) was 32% (95%CI: 32%-41%) and 21% (95%CI: 18%-25%) respectively. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH, a pooled risk ratio of 6.9% per year (I 2 : 63%, p=0.07). In adjusted pooled analysis, any cSS and disseminated cSS were both independently associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95%CI: 1.5-3.8; p2 : 0% and adj-HR: 4.1; 95%CI: 2.6-6.6; p2 : 47%), after adjusting for multiple strictly lobar microbleeds presence and increasing age. Conclusions: Our findings in a large population of CAA patients with ICH and a large number of recurrence events, indicate that cSS, particularly if disseminated, is the single most important prognostic risk factor on MRI for future recurrent lobar ICH. The provided estimates may help stratify future bleeding risk in CAA, with clinical implications for prognosis and treatment.

We aimed to evaluate the influence of prestroke cognitive impairment (PSCI) on outcomes in stroke patients treated with IV recombinant tissue plasminogen activator (rtPA).OPHELIE-COG was a prospective observational multicenter study conducted in French and Japanese patients treated with IV rtPA for cerebral ischemia. The preexisting cognitive status was evaluated by the short version of the Informant Questionnaire on Cognitive Decline in the Elderly. PSCI was defined as a mean score3. The primary endpoint was a favorable outcome (modified Rankin Scale [mRS] score 0-1) after 3 months. Secondary endpoints were symptomatic intracerebral hemorrhage (sICH), mRS scores 0-2, and mortality at 3 months. We performed a pooled analysis with Biostroke and Strokdem.Of 205 patients, 62 (30.2%) met criteria for PSCI. They were 11 years older (p0.001). Although they had more sICH and were less frequently independent after 3 months, they did not differ for any endpoint after adjustment for age, baseline NIH Stroke Scale score, and onset-to-needle time: sICH (odds ratio [OR] 2.78; 95% confidence interval [CI] 0.65-11.86), mRS 0-1 (OR 0.82; 95% CI 0.41-1.65), mRS 0-2 (OR 0.62; 95% CI 0.28-1.37), death (OR 0.40; 95% CI 0.08-2.03). The pooled analysis found no association of PSCI with any endpoint.Ischemic stroke patients with PSCI should receive rtPA if they are eligible. This conclusion cannot be extended to severe cognitive impairment or severe strokes.This study provides Class IV evidence that in patients with PSCI presenting with acute ischemic stroke, IV rtPA improves outcomes.

Objective:To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia.Methods:We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080.Results:We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26–10.34).Conclusions:The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.

Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12,000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In cerebral ischaemia, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5hours, mechanical thrombectomy on top of rt-PA or alone in case of contra-indication to rt-PA, in patients with proximal large-vessel occlusion, aspirin 300mg, immediately or after 24hours in case of thrombolysis, and, in a few patients, decompressive surgery.