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OBJECTIVE: To describe a case of dissection of the postero-inferior cerebellar artery (PICA) after cervical manipulation. Clinical Features: After cervical manipulation, a 42-year-old woman had a cerebellar syndrome related to an infarct in the area supplied by the PICA, confirmed by computed tomography of the brain. Cerebral angiography showed a normal appearance of the vertebral artery, a cervical extradural origin of PICA, and a dissection of the latter at the C1-C2 level. Intervention and Outcome: Anticoagulant treatment with heparin was implemented. A positive outcome was achieved after 3 weeks. CONCLUSION: Anatomical variations of the vertebral arteries and their branches are not infrequent and may constitute a predisposing factor to complications after neck manipulation. [ABSTRACT FROM AUTHOR]

Background: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated., Methods: The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. 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 to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event., Results: Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P <0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; P =0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; P =0.75)., Conclusions: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57., Competing Interests: Disclosures Dr Amarenco reports receipt of research grant support from Pfizer, Sanofi, Bristol-Myers-Squibb (BMS), Merck, AstraZeneca, Boston Scientific, Althera Pharmaceutical, from the French government and consulting fees from Pfizer, BMS, AstraZeneca, Bayer, Janssen, Kowa, Amgen, Portola, Novartis, and lecture fees from Amgen, Pfizer, and Sanofi. Dr Kim reports the following relationships: Dong-A, Pfizer, Servier, Daiichi-Sankyo, and Shin-Poong. Dr Giroud reports the following relationships: Sanofi, Bayer, Boehringer-Ingelheim, Pfizer, AstraZeneca, BMS, Daiichi-Sankyo. Dr Lee reports the following relationships: Boehringer-Ingelheim, Bayer, Daiichi-Sankyo, Esai, and AstraZeneca. Dr Steg discloses the following relationships: Research grant from Bayer, Merck, Sanofi, and Servier; speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer-Ingelheim, BMS, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, Novo Nordisk, Idorsia, PhaseBio; and patent for use of alirocumab use to reduce cardiovascular risk (patent assigned to Sanofi). Dr Vicaut reports Consulting/speaking honoraria from Abbott, Amgen, BMS, Fresenius, GSK, Medtronic, Pfizer, Sanofi, Stallergenes, Novartis. Dr Bruckert reports having received grants from Pfizer and AstraZeneca, honorarium for Consulting/presentation from Amryt Pharma Holdings Ltd, Novartis, Merck, AstraZeneca, Amarin Pharma Inc, Silence Therapeutics, AMGEN, Genfit, Sanofi and Regeneron, Aegerion, Mylan, AKCEA, Danone, and Servier. The other authors report no conflicts.

Background: In atherosclerotic stroke, lipid-lowering treatment with a target LDL (low-density lipoprotein) cholesterol of <70 compared with 100±10 mg/dL reduced the risk of subsequent cardiovascular events. This post hoc analysis explored the relative effects of the combination of statin and ezetimibe (dual therapy) and statin monotherapy in achieving the lower LDL cholesterol target and in reducing the risk of major vascular events, as compared with the higher target group., 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 to a target LDL cholesterol of <70 or 100±10 mg/dL, using statin and/or ezetimibe as needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event., Results: Among 2860 patients enrolled, patients who were on dual therapy during the trial in the lower target group had a higher baseline LDL cholesterol as compared to patients on statin monotherapy (141±38 versus 131±36, respectively, P <0.001). In patients on dual therapy and on statin monotherapy, the achieved LDL cholesterol was 66.2 and 64.1 mg/dL respectively, and the primary outcome was reduced during dual therapy as compared with the higher target group (HR, 0.60 [95% CI, 0.39-0.91]; P =0.016) but not during statin monotherapy (HR, 0.92 [95% CI, 0.70-1.20]; P =0.52), with no significant increase in intracranial bleeding., Conclusions: In the TST trial (Treat Stroke to Target), targeting an LDL cholesterol of < 70 mg/dL with a combination of statin and ezetimibe compared with 100±10 mg/dL consistently reduced the risk of subsequent stroke., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01252875. URL: clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

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 <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe., 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 <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

After an ischemic stroke with evidence of atherosclerosis, lipid-lowering treatment with a target LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL reduced the risk of subsequent cardiovascular events. In this analysis, we explored the effect in the subgroup of patients with diabetes compared with the subgroup without, as well as in those with newly diagnosed diabetes. 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 at a 1:1 ratio to a target LDL cholesterol of <70 mg/dL or 100 ± 10 mg/dL using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and death resulting from vascular disease. We performed a prespecified analysis to evaluate the effect in patients with diabetes. Of 2,860 patients enrolled, 643 had diabetes at baseline, with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL, and were followed for a median of 3 years. The primary composite end point occurred in 27 (8.2%) of 328 patients in the lower-target group and in 44 (14.0%) of 315 patients in the higher-target group (adjusted hazard ratio [HR] 0.56; 95% CI 0.34-0.89; P = 0.016). In patients without diabetes, the HR was 0.87 (95% CI 0.66-1.14; P = 0.31; interaction P = 0.15). In those with diabetes, there were three intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98 (9.2%) of 1,070 and in 80 (7.4%) of 1,085 patients in the lower- and higher-target groups, respectively (HR 1.27; 95% CI 0.94-1.71; P = 0.11), and baseline higher HbA 1c was the unique multivariable predictor. In conclusion, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in patients with and without diabetes, but the higher risk in those with diabetes yielded a higher absolute risk reduction, with number needed to treat of 17., (© 2021 by the American Diabetes Association.)

Objectives: Admission hyperglycemia is a penumbra-modifying factor that is associated with poor functional outcome in acute ischemic stroke (AIS) patients treated with intravenous rt-PA and/or mechanical thrombectomy (MT). Insulin therapy has failed to demonstrate a clinical benefit and the question of the patient selection remains under debate. We assessed the relationship between admission glycemia (AG) and functional outcome in AIS patients treated by MT according to both penumbra characteristics and reperfusion status., Patients and Methods: We performed a retrospective analysis of a multi-center registry of consecutive AIS (NIHSS ≥ 10) due to middle cerebral artery occlusion treated by MT (± tissue Plasminogen Activator (tPA)). To evaluate the association between AG and the 3-month functional outcome (modified Rankin Scale (mRS) ≤2), univariable and multivariable analyses were used. Subgroup analyses were performed according to both clinical-ASPECTS Mismatch (CAM2) and the complete recanalization (CR) status defined by a mTICI scale (modified Thrombolysis in Cerebral Infarction) 2b/3., Results: 216 AIS patients were included (Median Age: 68.43[58.12-77.95], median NIHSS: 18[15-21]). 104/216 (48.15%) patients had mRS≤2 at 3 months. AG was an independent predictor of functional outcome (/1 g/L OR: 0.10[0.03-0.37]) after adjusting for potential cofounders. Among subgroups formed by combining CAM2 and CR, AG was found to be predictor of functional outcome only in CAM2 + /CR + and specifically when recanalization was early., Conclusion: This study highlights the fact that the relationship between AG and prognosis is not homogeneous for all patients and indicates that AG has a deleterious effect on the ischemic penumbra, thus explaining its statistical association with functional outcome. Stroke neuroprotection by targeting hyperglycemia should be considered in acute stroke patients with mismatch and early complete recanalization. More prospective randomized trials are needed to generalize the conclusions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

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]; 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 <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.

Current guidelines recommend performing laboratory tests aimed at monitoring unfractionated heparin (UFH) treatments within a delay not exceeding 1 to 2 h(s) after sampling when blood is collected into citrated tubes. As such a short delay could be an issue, we evaluated the potential impact of longer delays. For that purpose, two citrated tubes were obtained from patients on UFH: one was centrifuged and tested for anti-Xa activity and aPTT within 1 h after collection (T1 h) and one was stored for 4 h at room temperature (T4 h) before being processed. A total of 123 paired tubes were investigated. Anti-Xa activity was significantly lower at T4 h than at T1 h, with a mean bias, calculated according to Bland-Altman, of 0.05 IU/mL. Considering 0.30 to 0.70 IU/mL as the therapeutic range, there were 12 cases of discrepant test results (9.8%). Most of them being around the lower limit of the therapeutic range had no impact on patients' management. APTT was significantly shortened (p < 0.0001) at T4 h vs. T1 h, with a mean bias of -7.9 s. Considering anti-Xa correlated aPTT therapeutic range, 29 cases of discrepant test results (23.6%) were found, 10% would have induce dosage changes. The concordance between anti-Xa activities measured at T4 h and T1 h was excellent (kappa = 0.813) and good for aPTT (kappa = 0.661). In conclusion, extending the delay between blood collection and measurement of tests prescribed for monitoring UFH therapy up to 4 h was found to lead to a systematic reduction in both anti-Xa activity and aPTT in unspun citrated tubes. As changes at T4 h were limited and had few clinically relevance than the ones observed with aPTT testing, a 4 h-delay was found to be acceptable for anti-Xa activity. The maximum delay for aPTT should remain around 1-2 h as changes were more relevant., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied., Methods: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes., Results: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups., Conclusions: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: In patients with non-cardio-embolic stroke, atorvastatin 80 mg/day reduced the relative risk of recurrent stroke by 16%, and a post hoc analysis showed that achieving an LDL-c of less than 70 mg/dL reduced the relative risk by 28% as compared to an on-treatment LDL of 100 mg/dL or more. Current guidelines from the French drug agency recommend treating with a statin after an ischaemic stroke to a target of less than 100 mg/dL, but no study directly tested LDL-c targets. The Treat Stroke to Target (TST) trial will compare the efficacy of achieving an LDL-c of less than 70 mg/dL versus an achieved LDL-c of 100 ± 10 mg/dL for secondary prevention in patients with recent ischaemic stroke of atherosclerotic origin.Main hypothesis: An achieved on-treatment LDL-c of less than 70 mg/dL will reduce by 25% the risk of recurrent ischaemic stroke, myocardial infarction, urgent coronary or carotid revascularisation following new symptoms requiring hospitalisation, and vascular death compared with on-treatment LDL-c of 100 ± 10 mg/dL., Design: Patients are randomised to either LDL-c levels, and the investigator who is not blinded can use the lipid-lowering agent of his/her choice available on the market (including statins and ezetimibe), in order to achieve the assigned LDL-c level. To be eligible for enrolment, patients have a recent ischaemic stroke or TIA of atherosclerotic origin with at least one arterial stenosis of a cerebral artery, enrolled between acute phase of the qualifying stroke (once the neurological deficit is stabilised) and three months. The initial planned sample size of 3760 participants followed three years was amended to allow follow-up of all enrolled patients until 385 primary efficacy outcome events have occurred, and no later than 31 December 2019. Patients will be recruited in 76 sites in two countries (France and South Korea) between March 2010 and December 2018 (last included patient followed up to one year). Safety outcomes will include haemorrhagic strokes and new onset diabetes. All primary endpoints will be adjudicated by an endpoint committee, blinded to the assigned LDL-c level. Two sub-studies assess (1) the relative effect of assigned LDL-c levels on occurrence of new atherosclerotic plaque as detected by carotid ultrasound during follow-up, using M'ATH software for repositioning and (2) the genetic and biomarker drivers of recurrent primary endpoints according to assigned LDL-c lowering arm, in atherosclerotic strokes., Summary: The TST trial is evaluating the benefits of achieving an LDL-c less than 70 mg/dL for secondary stroke prevention in ischaemic stroke patients of atherosclerotic origin. Main results are anticipated in 2020 or earlier (ClinicalTrials.gov NCT01252875)., (© European Stroke Organisation 2019.)

Objectives: Diagnosis of occult atrial fibrillation (AF) in stroke patients remains challenging. Several scores predictive of occult AF in stroke patients have been proposed, all based on the positive predictive value of clinical, biological, and radiological parameters, but they failed to modify the management of AF detection after stroke. The aim of this study was to identify a group of Stroke patients with Underlying Risk of Atrial Fibrillation (SURF) excluding stroke patients with low risk of AF., Patients and Methods: We enrolled consecutive AF-naive stroke patients without indication of long-term anticoagulation. AF was adjudicated after prolonged Holter ECG and 2 years of follow-up. The negative predictive value (NPV) was determined for each relevant parameter in the acute phase. Firstly, clinico-radiological parameters with NPV > 95% defined the initial exclusion criteria of SURF. Secondly, the ultimate exclusion criterion of SURF was defined by a composite criterion constructed using the beta-coefficient of independent predictive parameters of AF determined by logistic regression., Results: Among 773 AF-naïve patients without indication of anticoagulation, 111(14.4%) AFs were found. Initial SURF exclusion criteria, determined by NPV ≥ 95%, are: symptomatic atherosclerotic stenosis ≥50%, symptomatic arterial dissection or lacunar stroke. The SURF definition was completed by a composite exclusion criterion [Age*10+BNP< = 700] (NPV: 96.8%[92.6-98.9]). In the SURF group, 93/195(47.7%) AFs were diagnosed., Conclusions: In the SURF group, nearly half of the stroke patients had AF. The criteria used to define such a group are easily obtained in all stroke units, in the acute phase. SURF is a new concept proposal, which aims to improve the effectiveness of AF diagnosis after stroke., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Most of the time, watershed infarcts (WIs) involve steno-occlusive carotid disease. The pathophysiological mechanism could be predicted by their pattern: internal WIs (IWIs) are thought to be due to hemodynamic impairment in contrast to cortical WIs (CWIs), which are more likely to be caused by microembolic phenomena. We used a 3D time-of-flight (TOF) magnetic resonance angiography (MRA) study to assess this hypothesis., Methods: In 45 consecutive patients with a recent WI and ipsilateral cervical carotid stenosis, clinical and radiological data were obtained retrospectively. 3D TOF MRA were analyzed both qualitatively and quantitatively (internal carotid and anterior, middle and posterior cerebral arteries). Then, 2 groups were determined depending on their radiological patterns: WIs with (IWI+) or without (IWI-) an internal watershed., Results: Thirty-two of the 45 patients (71%) had IWIs that were or were not associated with CWIs (IWI+), while 13 patients (29%) had only CWIs (IWI-). There was no significant relationship between the radiological pattern and the demographic data, the cardiovascular risk factors, or the degree of stenosis. However, IWI+ patients more frequently had motor weakness (P = .03) than CWI patients. An ipsilateral reduced middle cerebral artery intensity on 3D TOF MRA in both qualitative and quantitative analyses was significantly associated with IWI+. Instead within IWI-, no significantly reduced signal intensity was found., Conclusion: These findings originally support the view that IWIs are mainly caused by a hemodynamic impairment related to carotid stenosis, whereas CWIs are mostly due to a microembolic mechanism. 3D TOF MRA, which gives pertinent information on pathophysiology on IWIs, can help in decision making., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Thrombin-activatable fibrinolysis inhibitor (TAFI) activation following thrombolysis may affect thrombolysis effectiveness in acute ischemic stroke (AIS). To support this hypothesis, we propose to study the relationship between TAFI consumption, activated/inactivated TAFI (TAFIa/ai) and stroke severity and outcome in 2 groups of AIS patients, one treated and one untreated with intravenous recombinant tissue type plasminogen activator (rt-PA)., Methods: In this prospective, longitudinal, multicenter, observational study, we aimed to study the association between TAFIa/ai and stroke outcome. TAFI levels were sequentially measured in patients treated with intravenous rt-PA thrombolysis (T), and in patients not given any thrombolytic therapy (NT). Baseline reference values were established in healthy subjects matched for age and gender. The National Institutes of Health Stroke Scale (NIHSS) score assessed at baseline and on day 2 was dichotomized into 2 severity groups (0-7 vs. >7). The modified Rankin Scale (mRS) score at day 90 was dichotomized for favorable (0-1) and unfavorable (2-6) outcomes., Results: A total of 109 patients were included, with 41 receiving rt-PA. At admission, patients had higher TAFIa/ai levels than reference. A significant increase in TAFIa/ai levels was observed at the end of thrombolysis (mean change from baseline of 963%) and lasted up to 4 h (191%). Higher TAFIa/ai levels were associated with a more severe day 2 NIHSS score (p = 0.0098 at T2h post thrombolysis) and an unfavorable mRS score from T48h (p = 0.0417) to day 90 (p = 0.0046). In NT patients, higher TAFIa/ai levels at admission were associated with a more severe stroke, as assessed by day 2 NIHSS score (p = 0.0026) and mRS score (p = 0.0003)., Conclusion: These data demonstrate a consistent relationship between TAFI levels and early clinical severity during rt-PA treatment., (© 2016 S. Karger AG, Basel.)

Objectives: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size., Methods: Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis., Results: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009)., Conclusions: Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization., Classification of Evidence: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone., (© 2015 American Academy of Neurology.)

Apixaban is a direct inhibitor of coagulation factor Xa. Superior efficacy over aspirin and antivitamin K has been shown in the prevention of stroke and systemic embolism during non-valvular atrial fibrillation with a more favorable safety profile, even though the risk of hemorrhage cannot be ignored, considering its mechanism of action. The recommended dose is 5mg twice daily which can be reduced to 2.5mg depending on the individual risk. Apixaban is also indicated for the treatment of venous thromboembolism but reimbursement has not yet been accepted in France for this indication. As with all direct oral anticoagulants, no routine biological monitoring is required, nevertheless their use may have an impact on all coagulation tests, eventually hampering interpretation. In particular clinical circumstances where a measure of anticoagulant efficacy is deemed necessary, specific assay of anti-Xa activity is appropriate, the result being expressed as concentration of the anticoagulant used. It is therefore necessary to state the name of the medicine for which the assay is requested. With these new anticoagulants, management of hemorrhagic events can be more difficult due to the lack of a specific antidote. Pro-hemostatic substances have exhibited efficacy in animal models but results are still insufficiently documented in clinical practice. Local or locoregional hemostasis measurements, when possible, are an essential factor in the treatment of hemorrhagic events., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: We aimed at comparing the long-term benefit-risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis., Methods: Long-term follow-up study of patients included in Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S), a randomized, controlled trial of carotid stenting versus endarterectomy in 527 patients with recently symptomatic severe carotid stenosis, conducted in 30 centers in France. The main end point was a composite of any ipsilateral stroke after randomization or any procedural stroke or death., Results: During a median follow-up of 7.1 years (interquartile range, 5.1-8.8 years; maximum 12.4 years), the primary end point occurred in 30 patients in the stenting group compared with 18 patients in the endarterectomy group. Cumulative probabilities of this outcome were 11.0% (95% confidence interval, 7.9-15.2) versus 6.3% (4.0-9.8) in the endarterectomy group at the 5-year follow-up (hazard ratio, 1.85; 1.00-3.40; P=0.04) and 11.5% (8.2-15.9) versus 7.6% (4.9-11.8; hazard ratio, 1.70; 0.95-3.06; P=0.07) at the 10-year follow-up. No difference was observed between treatment groups in the rates of ipsilateral stroke beyond the procedural period, severe carotid restenosis (≥70%) or occlusion, death, myocardial infarction, and revascularization procedures., Conclusions: The long-term benefit-risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis favored endarterectomy, a difference driven by a lower risk of procedural stroke after endarterectomy. Both techniques were associated with low and similar long-term risks of recurrent ipsilateral stroke beyond the procedural period., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00190398., (© 2014 American Heart Association, Inc.)

Background: Tracking down atrial fibrillation (AF) in the stroke unit is a relevant challenge for the prevention of recurrent AF-related stroke. The optimal terms of use of continuous ECG monitoring (CEM) are unknown. We compared 24-hour routine Holter ECG with two different CEM analysis strategies for AF detection., Methods: We prospectively enrolled consecutive ischemic stroke patients. All AF-naïve patients received CEM during hospitalization. Two methods for reading CEM data were compared: manual analysis using the Holter function (hCEM) and semiautomated analysis using software (aCEM). The McNemar test was used to compare AF detection rates., Results: Of the 362 patients included, 58 (16.0%) were non-AF-naïve patients and 304 were AF-naïve patients. AF-Naïve patients underwent CEM with a median duration of 5.3 days (3.4-9.7). We detected 22 new AF cases (7.2%) with first-24-hour hCEM, 31 (10.2%) with aCEM, and 42 (13.8%) with hCEM. hCEM and aCEM both significantly increased the AF detection rate compared to first-24-hour hCEM. hCEM detected more new AF cases than aCEM (+3.6%, p = 0.003)., Conclusions: In stroke patients, early and prolonged aCEM and hCEM both increase the AF detection rate compared to first-24-hour hCEM. hCEM gives the best AF detection rate. We suggest that in aCEM, detection based only on the ventricular rhythm analysis explains its lower specificity and sensitivity., (© 2014 S. Karger AG, Basel.)

Objectives: Relationship between low-level air pollution and stroke is conflicting. This study was conducted to document the relationship between outdoor air pollution and ischaemic stroke occurrence., Design: Time-stratified case-crossover analysis., Setting: University Hospital of Nice, France., Participants: All consecutive patients with ischaemic stroke living in Nice admitted in the University Hospital of Nice (France) between January 2007 and December 2011., Main Outcome Measure: Association (adjusted OR) between daily levels of outdoor pollutants (ozone (O3), nitrogen dioxide (NO2), particulate matter (PM10) and sulfur dioxide (SO2)) and ischaemic stroke occurrence., Results: 1729 patients with ischaemic stroke (mean age: 76.1±14.0 years; men: 46.7%) were enrolled. No significant association was found between stroke occurrence and short-term effects of all pollutants tested. In stratified analysis, we observed significant associations only between recurrent (n=280) and large artery ischaemic stroke (n=578) onset and short-term effect of O3 exposure. For an increase of 10 µg/m(3) of O3 level, recurrent stroke risk (mean D-1, D-2 and D-3 lag) was increased by 12.1% (95% CI 1.5% to 23.9%) and large artery stroke risk (mean D-3 and D-4 lag) was increased by 8% (95% CI 2.0% to 16.6%). Linear dose-response relationship for both subgroups was found., Conclusions: Our results confirm the relationship between low-level O3 exposure and ischaemic stroke in high vascular risk subgroup with linear exposure-response relation, independently of other pollutants and meteorological parameters. The physiopathological processes underlying this association between ischaemic stroke and O3 exposure remain to be investigated.

Background: Several studies have suggested that after ischemic stroke, continuous electrocardiographic (ECG) monitoring (CEM) increases the atrial fibrillation (AF) detection rate. However, optimal CEM terms of use are not clear. The aim of our study was to evaluate the usefulness of CEM in detecting AF and define optimal terms of the use of CEM., Methods: We prospectively enrolled consecutive patients with acute ischemic stroke who were admitted to the stroke unit without AF on baseline ECG. We compared 2 strategies of AF detection: the first using CEM and the second with routine clinical practice (24-hour Holter ECG and additional ECGs). Adjusted odds ratios for the association between AF diagnosis and the use of CEM stratified by monitoring duration were calculated using multivariate logistic regression analysis., Results: Of the 1166 patients included, 220 (18.87%) had AF on baseline ECG and were excluded. Of the 946 remaining patients, 592 underwent CEM. The prevalence of AF using CEM was 12.50% compared 2.26% using the routine strategy. After adjustment (demographic data, vascular risk factors, and National Institutes of Health Stroke Scale scores), using CEM increased 5.29 fold the odds of finding AF (95% confidence interval [CI] 2.43-11.55) compared to the routine strategy. The adjusted odds ratio (9.82; 95% CI 3.01-32.07) was maximum for the first day of monitoring and decreased later. Beyond 5 days, CEM usefulness was not significantly higher than the routine strategy., Conclusions: We suggest that in order to enhance the detection rate of AF, CEM could be generalized in the stroke unit. It must be started early in patients with acute stroke and prolonged over a minimum of 4 days., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Detection of new atrial fibrillation (AF) after ischemic stroke is challenging. The aim of the TARGET-AF study was to identify relevant markers for ruling out delayed AF in stroke patients. Early and prolonged Holter electrocardiography (ECG) monitoring during hospitalization was performed systematically in consecutive acute stroke patients naive to AF (no history of AF or no AF on baseline ECG). All clinical and paraclinical data for routine etiologic assessment were collected. The diagnostic value of all parameters significantly associated with AF was assessed by comparison of area under the receiver operating characteristic curve (AUC). Of the 300 stroke patients enrolled (mean age, 62.5 ± 15.5 years; sex ratio: 1.7; mean National Institutes of Health Stroke Scale score, 7.1 ± 7.9, median duration of Holter ECG monitoring, 6.8 days), 52 (17.3%) had newly diagnosed AF. Parameters significantly associated with AF were classified by increasing AUC: anterior circulation localization (AUC, 0.604; 95% confidence interval [CI], 0.546-0.660), P-wave initial force (AUC, 0.608; 95% CI, 0.545-0.669), left atrial dilatation (AUC, 0.657; 95% CI, 0.600-0.711), National Institutes of Health Stroke Scale score (AUC, 0.667; 95% CI, 0.611-0.720), sex (AUC, 0.683; 95% CI, 0.627-0.736), age (AUC, 0.755; 95% CI, 0.707-0.797), CHA2DS2-VASc score (AUC, 0.796; 95% CI, 0.746-0.841), STAF (score for the targeting of AF) score (AUC, 0.842; 95% CI, 0.796-0.882), and plasma brain natriuretic peptide (BNP) level (AUC, 0.868; 95% CI, 0.825-0.904). The use of all parameters combined (AUC, 0.910; 95% CI, 0.872-0.940) was not significantly more efficient in diagnosing AF than BNP alone (P = .248). At the Youden plot, the diagnostic properties for BNP >131 pg/mL were sensitivity, 98.1% (95% CI, 89.7-99.7); specificity, 71.4% (95% CI, 65.3-76.9); and negative predictive value, 99.4% (95% CI, 96.9-99.9). Our data indicate that a BNP level ≤ 131 pg/mL might rule out delayed AF in stroke survivors and could be included in algorithms for AF detection., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prognostic value of cerebral border-zone infarctions (watershed infarctions) on the early postoperative outcomes of patients undergoing carotid endarterectomy (CEA) after acute ischemic stroke (AIS)., Methods: Sixty-six (66) patients with symptomatic carotid stenosis (SCS) that underwent ipsilateral CEA after AIS from January 2007 to March 2012 were included in this study. They were divided into two groups according to the topographic patterns of the stroke: group 1, Territorial Cerebral Ischemic Strokes (TCIS) caused by emboli of carotid origin; group 2, cerebral border-zone infarctions (CBZI) related to an SCS associated with hemodynamic impairment. All data was collected in a prospective database and analyzed. Outcome measures included postoperative neurological morbidity and 30-day mortality., Results: Forty-three (43) patients (65.15%) experienced TCIS and were included in group 1, 23 patients (34.85%) had a CBZI and were included in group 2. There were no postoperative deaths. The postoperative neurologic morbidity rate was significantly higher in the CBZI group (22% vs. 2%, p = 0.02). Multivariate analysis demonstrates that CBZI was the only independent predictive factor of neurologic morbidity after CEA for AIS related to an SCS. Furthermore, the risk of postoperative neurologic morbidity remained significantly higher for patients with CBZI after adjustment for age, sex, initial NHISS scores, and associated contralateral carotid occlusion (HR: 0.059, 95% CI 0.004-0.85; p = 0.03)., Conclusion: CBZIs, compared to TCIS, were associated with a higher neurological complication rate during the postoperative period after CEA for SCS in cases of AIS. Further studies are required to better define the timing and the best treatment modality for patients with CBZI related to an SCS in order to reduce associated procedural complications., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Detecting paroxysmal atrial fibrillation (PAF) after ischaemic stroke is challenging. There are several methods to increase the detection rate of PAF, but it is first necessary to identify subgroups of patients at risk. In a previous study, we established a clinicoradiologic score that predicts atrial fibrillation (AF) in stroke patients. The purpose of the present study is to validate this score specifically for PAF patients., Methods: 500 consecutive ischaemic stroke patients were examined in our stroke unit. A blind evaluation of the STAF (score for the targeting of atrial fibrillation) was performed for each patient with or without AF. Firstly, we established the reproducibility of the STAF performance by comparing areas under the receiver operating characteristic curves in the preliminary and present studies. Secondly, to validate the predictive value of the STAF in occult AF, areas under the receiver operating characteristic curves were compared for each type of AF. Thirdly, the best threshold value was calculated., Results: AF was detected in 145 cases including 45% of paroxysmal forms. There is no significant score performance difference (p = 0.192) between the preliminary and prospective cohort areas under the receiver operating characteristic curves. This confirms the reproducibility of STAF performance. The area under the receiver operating characteristic curve for the PAF group was 0.907 versus 0.911 for the permanent AF group (p = 0.906). The diagnostic value of the STAF is as good in permanent as paroxysmal AF. In PAF, a STAF ≥ 5 has a sensitivity of 91% and a specificity of 77%., Conclusions: Due to its reproducibility and predictive value, the STAF can be used by neurologists as part of a novel diagnostic strategy for occult AF., (Copyright © 2011 S. Karger AG, Basel.)

Introduction: Various clinical manifestations can occur in syphilis, especially meningovascular syphilis. We report three cases of ischemic stroke related to meningovascular syphilis and HIV infection., Case Reports: Three men, aged 30, 31 and 41, presented typical neurologic deficit leading to the diagnosis of ischemic stroke. Radiographic investigations showed internal carotid thrombosis in two patients, and a basilar stenosis in the third. CSF analysis and blood samples revealed meningovascular syphilis associated with HIV infection. The other explorations were normal., Conclusion: Due to the reemergence of syphilis, search for Treponema pallidum infection should be systematic in young stroke victims., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Introduction: Intravenous thrombolysis with rt-Pa in stroke has been approved in France since 2002. We report an evaluation of our practice. We have tried to identify predictive factors of dependence and death, and to compare our results with the data of the literature., Patients and Method: All patients treated with intravenous rt-PA within the first 270min after the stroke onset were included. Univariate, then multivariate analyses were performed to determine the variables influencing the functional outcome at 3 months follow-up, according to a dichotomy established from the modified Rankin scale., Results: One hundred and forty-two patients were included in this study (mean initial National Institute of Health Stroke Scale [NIHSS]: 15). Fifty percent had a Rankin score higher than 2 at 3 months follow-up. NIHSS above 12, glycemia of at least 120mg/l, and systolic blood pressure above 160mmHg at admission were identified as independent predictive factors of poor functional outcome. Less than 4 points decrease of NIHSS proved to be a simple and early predictor of poor functional outcome at 3 months follow-up., Conclusions: In terms of safety and efficacy the data issuing from the daily activity of our stroke unit are comparable with those of clinical trials.

Summary: A case of multiple cerebral aneurysms caused by left atrial myxoma is reported.We present the details of this case and discuss the hypothetical pathogenesis, radiological aspects and treatment of these neoplastic aneurysms.

Background: A spontaneous mobilization of Peripheral Blood-Mononuclear CD34+ Cells (PB-MNC-CD34+) has recently been reported in human myocardial infarction and found to be related to improved heart function and survival. However, nothing is known regarding a possible relation between PB-MNC-CD34+ mobilization and neurological recovery in human acute cerebral ischemia., Methods and Results: PB-MNC-CD34+ were determined daily after an acute cerebral ischemic attack for 14 days in 25 patients with acute ischemic stroke and compared with controls. Results indicated that stroke was followed by large and bursting mobilizations of PB-MNC-CD34+. The amplitude of the mobilizations was similar to those observed in Granulocyte Colony Stimulating Factor (G-CSF) conditioned aplastic patients following myeloablative therapy before leukapheresis and autologous bone graft. The extent of PB-MNC-CD34+ mobilization in each patient was directly related to neurological and functional recoveries as assessed by NIH Stroke Scale, and modified Rankin Scale respectively., Conclusions: The mobilization of PB-MNC-CD34+ cells might be predictive of neurological and functional recovery.

Background and Purpose: Spontaneous isolated posteroinferior cerebellar artery (PICA) dissection is very rare. The aim of the study was to investigate the clinical manifestations, the neuroradiological aspects and the treatment of 5 cases collected in 5 years., Methods and Results: From 1999 to 2003, five patients (40-71 years old) were hospitalized for PICA dissection. Two patients presented symptoms after cervical manipulation. No predisposing factor or traumatic cause was described in the other cases. The diagnosis was carried out by cerebral angiography in all the cases: in 4, angiography showed focal stenosis with saccular or fusiform dilatation of the artery at the site of the dissection; in 1 a double lumen aspect was described. One patient presented ischemic manifestations; he was treated with heparin. The others presented subarachnoid hemorrhage (SAH) and were treated by embolization (endovascular sacrifice of the PICA). No ischemic complication and no rebleeding were observed after sacrifice of the PICA. Three patients presented acute hydrocephalus and were treated with surgical derivation. The angiographic and clinical follow-up lasted more than 3 years. We assessed the long-term results with the Glasgow Outcome Score and the modified Rankin Score. A good recovery was achieved for 4 patients (modified Rankin Score 0); one patient who presented SAH and who was in bad clinical state on admission had a Glasgow Outcome Score of 3 and a modified Rankin Score of 4 three years later., Conclusion: Clinical course and prognosis are variable in PICA dissections. The treatment depends on the existence of a hemorrhagic event. In the group of patients presenting SAH, endovascular treatment was safe and effective. The long-term clinical results depend mainly on the clinical status on admission.

Stroke is a medical emergency. Intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) within three hours of stroke onset is the only pharmacological treatment proven effective in ischemic stroke. Its efficacy is time dependent. Patients must be carefully selected and treated in dedicated stroke units to reduce the risk of hemorrhage. Early treatment in dedicated stroke units reduces mortality and disability, independent of any specific treatment. Secondary prevention includes antiplatelet therapy and successful control of all risk factors (hypertension, diabetes, tobacco use, and hyperlipidemia). Carotid endarterectomy may be considered if the residual disability is not serious. Lowering blood pressure is beneficial even when initial blood pressure is normal. Lowering LDL-C with statins after ischemic stroke reduces the risk of recurrent stroke and coronary events.

Background and Purpose: When performed soon after stroke onset, single-photon emission computed tomography (SPFCT) with hexamethylpropylenamine oxime or Tc 99m L,L-ethyl cysteinate dimer (ECD) has significant added predictive value compared to neurological scores. With ECD SPECT, the degree of tracer uptake reduction predicts neurological recovery, and using a 40% threshold to characterize irreversibly damaged tissue (IDT), significant correlations have been observed. However, correlations between this uptake threshold and tissue outcomes have not been assessed. The purpose of this study was to validate the 40% ECD uptake threshold for the probabilistic mapping of IDT using an automatic, voxel-based approach., Methods: In 10 acute stroke patients, the authors first compared early ECD SPECT and late coregistered magnetic resonance imaging (MRI) data and assessed for IDT and "tissue at risk" (i.e., tissue with ECD uptake below and above 40%) the percentage of voxels ultimately infarcted and noninfarcted on late brain MRI. They then assessed the correlations between the volumes of brain tissue compartments and subsequent neurological recovery. Finally, to assess whether visual SPECT analysis is reliable compared to the more complex voxel-based approach, the authors compared the predictive value of the 2 methods for neurological recovery., Results: The majority of IDT voxels (average = 84%), defined by ECD uptake < 40%, evolved toward infarction, and 51.8% to 100% of at-risk voxels (average = 89%) escaped infarction. The extent of IDT correlated significantly with neurological recovery (P = .0009). There was good agreement between visual and voxel-based analyses (P = .0004)., Conclusion: The results support the validity of the ECD uptake thresholds chosen, suggesting that ECD uptake can reflect neuronal viability and that ECD SPECT can be useful for the early detection of potentially salvageable tissue and irreversible damage. These preliminary results encourage the use of this method in a clinical setting for fast decision making in choosing acute therapy.

Objectives: Accurate prediction of outcome in acute stroke would help in identifying subgroups of patients for therapeutic trials and intravenous thrombolysis. The purpose of this study was to prospectively test the hypothesis that brain SPECT, with (99m)Tc-L, L-ethylcysteinate dimer (ECD), a tracer sensitive to cell function, performed in the first hours after stroke onset, adds predictive power to concomitant neurological evaluation., Methods: Twenty-four patients with a first-ever middle cerebral artery stroke were prospectively studied with ECD-SPECT within 12 h after stroke onset. Neurological evaluation was performed using Orgogozo's scale at admission and 3 months later in order to calculate the percent Martinez-Vila evolution indices (EI%). Semiquantitative visual analysis of SPECT images was performed in 6 cortical regions relevant for carotid artery territory. Both the extent and the intensity of cortical reduced ECD uptake were calculated, leading to an 'ischemia' score, corresponding to the sum of regions of interest (ROI) where ECD uptake was between 40 and 80% of the contralateral healthy hemisphere, and an 'irreversibly damaged tissue' (IDT) score, corresponding to an uptake below 40%, and a total score (ischemia + IDT). Each patient was assigned to one of three patterns: (1) pattern I with severe ECD cortical uptake reduction defined by at least one ROI with uptake under 40%, (2) pattern II with moderate ECD cortical uptake reduction (40-80%) only and (3) pattern III with normal ECD uptake., Results: There were 11 patients (46%) with pattern I ECD-SPECT. This group had almost invariably (10/11 patients) a poor outcome. The 12 patients (50%) classified in pattern II had a variable clinical outcome, ranging from improvement to deterioration. The single patient with a normal SPECT (pattern III) had a full clinical recovery. Both total score and IDT score were strongly significantly correlated with neurological recovery EI% (respectively p = 0.006 and 0.004). Their predictive value was significantly higher than, and independent of, day 0 neurological evaluation. No patient had an increased ECD uptake., Conclusion: Our results show that the degree of ECD cortical uptake reduction, measured on early brain SPECT, is a strong predictor of neurological recovery. ECD-SPECT data have a higher predictive value than day 0 neurological evaluation. The apparently better predictive value of ECD over hexamethylpropyleneamine oxime may reflect this tracer's brain retention mechanisms which are weighted more towards cell function than towards perfusion. ECD-SPECT is easily obtainable and may help in selecting out from therapy those patients who are likely to have either very good or very poor spontaneous outcome, and thus improve the assessment of acute stroke and the choice of therapeutic strategy., (Copyright 2000 S. Karger AG, Basel)

We describe a new cause of spinal cord ischemia illustrated by two cases--compression by the diaphragmatic crus of a lumbar artery giving rise to a spinal artery. The diagnosis has been established by dynamic spinal angiography, showing complete occlusion of the lumbar artery. Surgical section of the diaphragmatic crus prevents irreversible infarction.

Background and Purpose: It is not yet known which end points are the most suitable for evaluation of the effects of acute stroke intervention. The European Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The study was powered to detect a 15% improvement of the median of each primary end point. The study failed to show this effect and was negative in the intention-to-treat analysis. The National Institute of Neurological Disorders and Stroke (NINDS) study used 4 dichotomized end points and applied a global end-point analysis. This study was positive and led to FDA approval of thrombolytic therapy for acute ischemic stroke. This study was undertaken to answer the question of whether a different statistical design may have shown a positive results of the ECASS I trial., Methods: We performed a retrospective analysis of the ECASS I intention-to-treat data set (615 randomized and treated patients, rtPA treatment versus placebo) and post hoc application of the NINDS trial statistical methodology (global end-point analysis). The scores of the modified Rankin Scale (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale (NIHSS) were dichotomized according to the criteria used in the NINDS trial. Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100 on BI, and a score of 0 or 1 on NIHSS., Results: The number of patients reaching favorable outcome were higher in all 3 end points in the rtPA-treated group. The effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The differences are statistically significant for the mRS (P=0.044; odds ratio [OR], 1. 4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS (P=0.001; OR, 1.9; 95% CI, 1.4 to 2.8), while for the BI significance was missed (P=0.102; OR, 1.3; 95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a significant increase (P=0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome in the rtPA-treated patient group., Conclusions: Using the global end-point analysis, ECASS is positive in the intention-to-treat analysis. This may indicate that the time window for thrombolysis may be as long as 6 hours. Looking at the 3 dichotomized end points, the effect sizes for 2 end points, mRS and BI, are smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial all 3 end points reveal statistically significant results, in ECASS only 2 of the 3 corresponding end points, mRS and NIHSS, were statistically significant. This finding underlines an important difference of a global end-point approach: it may show a positive overall result although one of the end points is not positive.

Elevated homocysteine (HCY) levels in tissues and blood are associated with premature occlusive diseases. A number of techniques have been developed to assay HCY, including high-performance liquid chromatography (HPLC) with fluorimetric or electrochemical detection, and radioenzymatic methods. The present study evaluated the adaptation of a liquid chromatographic, ion-exchange technique with postcolumn derivatization using ninhydrin. Fasting and moreover post-methionine load total plasma HCY were assayed in 50 patients three months after a stroke and in 20 age-matched controls. Ion-exchange liquid chromatography was performed on an amino acid analyzer using a modified procedure to improve methionine and HCY separation. HCY values in the fasting state were moderately but significantly increased (P<0.05) in the patients compared to the controls: 10.5+/-3.4 versus 9.3+/-2.3 micromol/l. The difference between the two groups was amplified in post-load HCY results, which were significantly increased (P<0.05) in the patients: 41.6+/-17.8 versus 29.2+/-5.5 micromol/l in controls. The relationship between cerebrovascular disease and impaired HCY metabolism has previously been emphasized by other investigators. Our findings suggest that certain inherited and/or acquired HCY disorders observed in the fasting state (14%) and especially in post-methionine load conditions (32%) may occur during acute disease, and that total plasma HCY can be determined by ion-exchange chromatography even after oral methionine loading.

Objectives: We conducted this study to evaluate the role of transoesophageal echocardiography in the aetiologic diagnosis of ischaemic cerebral vascular events in young subjects., Methods: Over a 16-month period, 70 consecutive patients under 55 (mean age 49 years; range 32-55; 34 females, 36 males) underwent transoesophageal echocardiography as part of a complete work-up after a recent (< 1 month) cerebral event considered to be ischaemic in nature. Exclusion criteria were age over 55, vascular stenosis or ulcerated plaque, embologenic heart disease and valve prosthesis. 24-h Holter recordings were also obtained in all patients., Results: The cerebral event was temporary in 11 subjects and permanent in the other 59. The ischaemic nature of the event was confirmed in all patients with computed tomography or magnetic resonance imagery. All patients were in sinus rhythm at examination and supraventricular paroxysmal arrhythmia was observed in 7 during the Holter recordings. The transoesophageal echocardiography was normal in 37 patients (52%) and pathologic in 33 (48%). The source of the embolus was identified in 4 cases (6%) and the probable cause of the cerebral event was found in 29 (42%). Among the abnormal structures observed were permeable oval foramens, inter-atrial septum aneurysms and plaques on the ascending aorta., Conclusions: In our selected population of patients under 55 years of age, transoesophageal echocardiography detected the certain or probable source of the ischaemic cerebral event in 48% of the cases, a diagnostic yield better than most other methods. Nevertheless, there is no known therapeutic response to several of the potential sources of embolus observed.