Comparison of rescue intracranial stenting versus best medical treatment alone in acute refractory large vessel occlusion: study protocol for the PISTAR multicenter randomized trial.

BACKGROUND: Mechanical thrombectomy (MT) has become a standard treatment for acute ischemic strokes (AIS). However, MT failure occurs in approximately 10-30% of cases, leading to severe repercussions (with mortality rates up to 40% according to observational data). Among the available rescue techniques, rescue intracranial stenting (RIS) appears as a promising option. OBJECTIVE: This trial is poised to demonstrate the superiority of RIS in addition to the best medical treatment (BMT) in comparison with BMT alone, in improving the functional outcomes at 3 months for patients experiencing an AIS due to a large vessel occlusion refractory to MT (rLVO). METHODS: Permanent Intracranial STenting for Acute Refractory large vessel occlusions (PISTAR) is a multicenter prospective randomized open, blinded endpoint trial conducted across 11 French University hospitals. Adult patients (≥18 years) with an acute intracranial occlusion refractory to standard MT techniques will be randomized 1:1 during the procedure to receive either RIS+BMT (intervention arm) or BMT alone (control arm). RESULTS: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin Scale score ≤2 and evaluated by an independent assessor blinded to the randomization arm. Secondary outcomes include hemorrhagic complications, all adverse events, and death. The number of patients to be included is 346. Two interim analyses are planned with predefined stopping rules. CONCLUSION: The PISTAR trial is the first randomized controlled trial focusing on the benefit of RIS in rLVOs. If positive, this study will open new insights into the management of AIS. TRIAL REGISTRATION NUMBER: NCT06071091.

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial.

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial.

BACKGROUND: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.

Infarct Volume Before Hemicraniectomy in Large Middle Cerebral Artery Infarcts Poorly Predicts Catastrophic Outcome.

BACKGROUND AND PURPOSE: Infarct volumes predict malignant infarcts in patients undergoing decompressive hemicraniectomy (DH) for large middle cerebral artery territory infarcts. The aim of the study was to determine the optimal magnetic resonance imaging infarct volume threshold that predicts a catastrophic outcome at 1 year (modified Rankin Scale score of 5 or death). METHODS: We included consecutive patients who underwent DH for large middle cerebral artery infarcts. We analyzed infarct volumes before DH with semi-automated methods on b1000 diffusion-weighted imaging sequences and apparent diffusion coefficient maps. We studied infarct volume thresholds for prediction of catastrophic outcomes, and analyzed sensitivity, specificity, and the area under the curve, a value ≥0.70 indicating an acceptable prediction. RESULTS: Of 173 patients (109 men, 63%; median age 53 years), 42 (24.3%) had catastrophic outcomes. Magnetic resonance imaging b1000 diffusion-weighted imaging and apparent diffusion coefficient infarct volumes were associated to the occurrence of 1-year catastrophic outcome (adjusted odds ratio, 9.17 [95% CI, 2.00-42.04] and odds ratio, 4.18 [95% CI, 1.33-13.19], respectively, per 1 log increase). The optimal volume cutoff of were 211 mL on b1000 diffusion-weighted imaging and 181 mL on apparent diffusion coefficient maps. The 2 methods showed similar sensitivities and specificities and overlapping area under the curve of 0.64 (95% CI, 0.54-0.74). CONCLUSIONS: In patients with large middle cerebral artery infarcts, optimal magnetic resonance imaging infarct volume thresholds showed poor accuracy and low specificity to predict 1-year catastrophic outcome, with different b1000 diffusion-weighted imaging and apparent diffusion coefficient thresholds. In the setting of DH, optimal infarct volumes alone should not be used to deny DH, irrespectively of the method used.

MT-DRAGON score for outcome prediction in acute ischemic stroke treated by mechanical thrombectomy within 8 hours.

OBJECTIVES: The MRI-DRAGON score includes clinical and MRI parameters and demonstrates a high specificity in predicting 3 month outcome in patients with acute ischemic stroke (AIS) treated with intravenous tissue plasminogen activator (IV tPA). The aim of this study was to adapt this score to mechanical thrombectomy (MT) in a large multicenter cohort. METHODS: Consecutive cases of AIS treated by MT between January 2015 and December 2017 from three stroke centers were reviewed (n=1077). We derived the MT-DRAGON score by keeping all variables of the MRI-DRAGON score (age, initial National Institutes of Health Stroke Scale score, glucose level, pre-stroke modified Rankin Scale (mRS) score, diffusion weighted imaging-Alberta Stroke Program Early CT score ≤5) and considering the following variables: time to groin puncture instead of onset to IV tPA time and occlusion site. Unfavorable 3 month outcome was defined as a mRS score >2. Score performance was evaluated by c statistics and an external validation was performed. RESULTS: Among 679 included patients (derivation and validation cohorts, n=431 and 248, respectively), an unfavorable outcome was similar between the derivation (51.5%) and validation (58.1%, P=0.7) cohorts, and was significantly associated with all MT-DRAGON parameters in the multivariable analysis. The c statistics for unfavorable outcome prediction was 0.83 (95%CI 0.79 to 0.88) in the derivation and 0.8 (95%CI 0.75 to 0.86) in the validation cohort. All patients (n=55) with an MT-DRAGONscore ≥11 had an unfavorable outcome and 60/63 (95%) patients with an MT-DRAGON score ≤2 points had a favorable outcome. CONCLUSION: The MT-DRAGON score is a simple tool, combining admission clinical and radiological parameters that can reliably predict 3 month outcome after MT.

Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups.

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.

Influence of Medication on Fatigue Six Months after Stroke.

Poststroke fatigue (PSF) is frequent and affects patients' quality of life. Medication use was hypothesized as being responsible for PSF. Our objective was to evaluate potential relationships between 6-month PSF and medication use at discharge and 6 months after an ischemic stroke. This study is part of STROKDEM, an ongoing longitudinal cohort study, whose main aim is to determine predictors of poststroke dementia. Patients were included within 72 hours after an ischemic stroke and followed up with standardized evaluations. Medication use 7 days and 6 months after stroke was rated, and polypharmacy was defined as the number of categories of treatments received by a patient. PSF was evaluated using the Chalder Fatigue Scale. Medical history, vascular risk factors, depression, anxiety, and sleep disturbances were evaluated. One hundred and fifty-three patients were included: 52.9% presented PSF. PSF at 6 months was not predicted by medication use at discharge nor associated with medication use at month 6. We found severity of PSF to be increased in patients with polypharmacy. Our results suggest that PSF is not a side effect of drugs use, which more reflects presence of disturbances frequently observed after stroke such as depression, anxiety, or sleep disturbances. Clinical study is registered on clinicaltrials.gov (NCT01330160).

Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study.

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.

A very early neurological improvement after intravenous thrombolysis for acute cerebral ischaemia does not necessarily predict a favourable outcome.

In patients treated by intravenous (i.v.) thrombolytic therapy for cerebral ischaemia, a very early neurological improvement (VENI) [National Institutes of Health Stroke Scale score (NIHSSS) 0, or early improvement ≥5 points], predicts a favourable outcome. VENI patients are usually excluded from trials testing complementary strategies, but a few of them have bad outcomes. To determine why VENI patients may have bad outcomes, we analysed the reasons for bad outcomes [modified Rankin Scale (mRS) score 2-6 at 3 months] in consecutive VENI patients. Of 365 consecutive patients with a pre-stroke mRS 0-1 (185 men, median age 69 years, median NIHSSS 12, median onset-to-needle time 147 min), 71 (19.5 %) had VENI. They were more likely to have had recent transient ischaemic attacks (OR 3.64, 95 % CI 1.08-12.27), higher baseline NIHSSS (median 14 vs. 11, p = 0.003) and shorter onset-to-needle times (median 135 min vs. 151, p = 0.01), and they were less likely to develop pneumonia (OR 0.27, 95 % CI 0.09-0.76) or malignant infarction (p = 0.045). In the 21 VENI patients (29.6 %) with a mRS 2-6 at 3-months, bad outcomes were due to the residual deficit in 14, secondary worsening of ischaemia in 4, intracranial haemorrhage in 2, and death from cancer in 1. One-third of VENI patients have bad outcomes, due to the residual neurological deficit in most of them. This finding suggests that VENI patients who still have a significant neurological deficit 1 h after thrombolysis should not be excluded from trials testing complementary strategies.

Decompressive surgery for malignant middle cerebral artery infarcts: the results of randomized trials can be reproduced in daily practice.

BACKGROUND: In clinical randomized controlled trials (RCTs), decompressive surgery (DS) for malignant middle cerebral artery (MMCA) infarcts leads to a 50% absolute risk reduction in mortality, and improves the 1-year functional outcome. The reproducibility of these results in routine practice has never been evaluated. The purpose of this study was to test the hypothesis that the results of DS for MMCA in practice are similar to those observed in the surgical group of RCTs. METHODS: We prospectively included the first 31 patients who underwent DS for MMCA. They were screened based on similar criteria as in the meta-analysis. The primary outcome was a modified Rankin Scale (mRS) score of ≤4, and secondary outcomes were mRS of ≤3 and death at 1 year. RESULTS: Thirty-one patients underwent DS for MMCA. The 1-year mRS was ≤4 in 22 patients (71.0%) and ≤3 in 16 (51.6%). Seven patients died (22.6%). CONCLUSION: This observational study showed that DS for MMCA in a center without previous experience provides similar results as those obtained in the surgical arm of RCTs.

Influence of differences in case mix on the better outcome of smokers after intravenous thrombolysis for acute cerebral ischemia.

BACKGROUND/AIMS: Thrombolysis for myocardial infarction is more effective in smokers. Our aim was to determine whether smokers treated by intravenous (i.v.) rt-PA for acute cerebral ischemia have better outcomes. METHOD: Comparison of smokers and non-smokers for baseline characteristics and month-3 outcome in patients treated by i.v. rt-PA for cerebral ischemia in Lille, France, and Belgrade, Serbia. The primary outcome was a modified Rankin scale (mRS) 0-1 or similar to the pre-stroke mRS. Secondary outcomes were an mRS 0-2 and death. RESULTS: We included 459 patients (255 men; median age 65 years, interquartile range 52-76; 135 smokers). Smokers were younger (median 53 vs. 70 years, p < 0.0001) and had less severe strokes (median NIHSS 10 vs. 14, p < 0.0001). At month 3, they were more likely to have an mRS 0-1 [odds ratio (OR) 1.75; 95% confidence interval (CI) 1.17-2.62], or an mRS 0-2 (OR 2.90; 95% CI 1.86-4.52) and less likely to be dead (OR 0.28; 95% CI 0.13-0.61). Smoking was not independently associated with outcome after adjustment for case mix [adjusted OR ((adj)OR) 0.86; 95% CI 0.52-1.43]. CONCLUSION: Smoking does not independently influence the outcome in patients treated by rt-PA for cerebral ischemia. The better outcome in smokers is the consequence of differences in case mix.

Relationships between recent intraplaque hemorrhage and stroke risk factors in patients with carotid stenosis: the HIRISC study.

OBJECTIVE: Intraplaque hemorrhage (IPH) is an emerging marker of plaque instability. However, little is known about the relationships between IPH and traditional risk factors and whether these relationships differ between symptomatic and asymptomatic disease. METHODS AND RESULTS: Two hundred thirty-four patients with symptomatic (n=114) or asymptomatic (n=120) carotid stenosis underwent high-resolution plaque magnetic resonance imaging. Seventy-five patients had recent IPH (symptomatic, 33%; asymptomatic, 31%). In symptomatic stenosis, recent IPH was independently associated with degree of stenosis (odds ratio [OR]=4.21, 1.61-10.98 for North American Symptomatic Carotid Endarterectomy Trial >35%; OR=2.92, 1.18-7.24 for European Carotid Surgery Trial >60%), qualifying event (OR=4.13; 1.11-15.32 for stroke or hemispheric transient ischemic attack ≥1 hour versus transient ischemic attack <1 hour or ocular symptoms), time from ischemic event (OR=6.65, 1.56-28.35 for ≤2 weeks; OR=2.24, 0.87-5.81 for 2-12 weeks versus >12 weeks; P for trend=0.03). In asymptomatic stenosis, IPH was only associated with stenosis severity >70% by ECST (OR=6.65; 1.95-22.73) but not by the NASCET method. CONCLUSIONS: Our findings support the potential link between recent IPH and risk of ipsilateral stroke in symptomatic disease but also imply that prognostic studies should adjust for known stroke risk factors in multivariate analyses. In asymptomatic stenosis, the potential predictive value of recent IPH is less likely to be confounded by stroke risk factors.

Neurosurgical treatment for aneurysm remnants or recurrences after coil occlusion.

OBJECTIVE: Neurosurgical management of residual aneurysms (RA) after coiling remains a challenging issue. We present a consecutive series of 21 patients who underwent microsurgical treatment of a previously coiled aneurysm. METHODS: We retrospectively reviewed a consecutive series of 21 patients who underwent operations for an RA after coiling between 1997 and 2007. Postcoiling follow-up imaging included brain magnetic resonance angiography and digital subtraction angiography. The decision for surgical treatment was made when an RA was significant and unsuitable for re-embolization. Data related to the RA and to the surgical technique were analyzed. Postoperative outcome was evaluated with the Glasgow Outcome Scale. RESULTS: Twenty aneurysms were initially ruptured. Twelve had undergone complete coil occlusion, whereas 6 had a residual neck, 2 had a residual lobule, and 1 had a residual sac. The aneurysms were in the anterior circulation in 18 cases and in the posterior circulation in 3 cases. Twenty RAs were excluded with the apposition of 1 clip beneath the coils, 2 required a temporary occlusion, 2 required extraction of the coils, and 1 presented with an operative rupture. All aneurysms, except 2 that had their residual neck wrapped, were completely occluded. The postoperative Glasgow Outcome Scale score was unchanged in 90% of patients, and 2 patients sustained a moderate disability. CONCLUSION: Microsurgical treatment of RA after endovascular treatment is effective, provided that patients are selected appropriately. The surgical treatment of recanalized aneurysms after coiling is challenging but can result in a good outcome with low morbidity and no mortality.

Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial.

BACKGROUND: Carotid stenting is a potential alternative to carotid endarterectomy but whether this technique is as safe as surgery and whether the long-term protection against stroke is similar to that of surgery are unclear. We previously reported that in patients in the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the rate of any stroke or death within 30 days after the procedure was higher with stenting than with endarterectomy. We now report the results up to 4 years. METHODS: In this follow-up study of a multicentre, randomised, open, assessor-blinded, non-inferiority trial, we compared outcome after stenting with outcome after endarterectomy in 527 patients who had carotid stenosis of at least 60% that had recently become symptomatic. The primary endpoint of the EVA-3S trial was the rate of any periprocedural stroke or death (ie, within 30 days after the procedure). The prespecified main secondary endpoint was a composite of any periprocedural stroke or death and any non-procedural ipsilateral stroke during up to 4 years of follow-up. Other trial outcomes were any stroke or periprocedural death, any stroke or death, and the above endpoints restricted to disabling or fatal strokes. This trial is registered with ClinicalTrials.gov, number NCT00190398. FINDINGS: 262 patients were randomly assigned to endarterectomy and 265 to stenting. The cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke after 4 years of follow-up was higher with stenting than with endarterectomy (11.1%vs 6.2%, hazard ratio [HR] 1.97, 95% CI 1.06-3.67; p=0.03). The HR for periprocedural disabling stroke or death and non-procedural fatal or disabling ipsilateral stroke was 2.00 (0.75-5.33; p=0.17). A hazard function analysis showed the 4-year differences in the cumulative probabilities of outcomes between stenting and endarterectomy were largely accounted for by the higher periprocedural (within 30 days of the procedure) risk of stenting compared with endarterectomy. After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups. For any stroke or periprocedural death, the HR was 1.77 (1.03-3.02; p=0.04). For any stroke or death, the HR was 1.39 (0.96-2.00; p=0.08). INTERPRETATION: The results of this study suggest that carotid stenting is as effective as carotid endarterectomy for middle-term prevention of ipsilateral stroke, but the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy in patients with symptomatic carotid stenosis.

Secondary prevention after ischemic stroke. Evolution over time in practice.

BACKGROUND AND OBJECTIVE: An optimal management of vascular risk factors, associated with antithrombotic drugs and carotid surgery when appropriate, reduces the risk of a new vascular event after stroke. Although secondary prevention is not optimal in many patients in practice, the question of whether there is an improvement over time remains unanswered. The aim of our study was to test the hypothesis that secondary prevention measures after cerebral ischemia improve over time. METHOD: We included 123 consecutive patients in 1994, and 125 consecutive patients in 2002, who were admitted to a neurological department for any reason and had had an episode of cerebral ischemia less than 6 years earlier. We compared the groups for the management of arterial hypertension, hypercholesterolemia, diabetes mellitus and smoking. We recorded the values of blood pressure, biological parameters, and presence of antithrombotic therapy, lipid-lowering and anti-hypertensive drugs. Whether patients were properly treated or not, was determined by a comparison between their current treatment and guidelines available when recruited. RESULTS: Prevention was not optimal in 96 of 123 (78%) patients in 1994, and in 77 of 125 (62 %) in 2002. Vascular risk factors were better identified and managed in 2002 than in 1994, especially for hypercholesterolemia. Antithrombotic therapies, statins and antihypertensive drugs, except calcium channel blockers, were more often used in 2002. The proportion of patients in whom arterial hypertension and hypercholesterolemia were identified was higher in 2002, but the proportion of patients identified as diabetics remained stable. However, the proportion of patients with blood pressure >140/90 mmHg, glycemia >or = 126 mg/dl, total cholesterol level > or = 240 mg/dl, or being current smokers, were significantly lower in 2002 than in 1994. CONCLUSION: Although most of patients with previous cerebral ischemia did not receive an optimal management of their risk factors in 2002, there was an improvement over an 8-year period.

Diffusion/perfusion-weighted magnetic resonance imaging after carotid angioplasty and stenting.

BACKGROUND AND PURPOSE: Carotid angioplasty and stenting, a so far non-validated procedure, may be an alternative to surgery in patients with a high surgical risk. However, it carries also a risk of cerebral embolic events. The purpose of this study was to evaluate tissue signal abnormalities in the brain before and after carotid angioplasty and stenting by means of diffusion- (DWI) and perfusion (PWI) weighted magnetic resonance imaging (MRI). METHODS: We performed cerebral MRI before and after carotid angioplasty in 22 consecutive patients, with 23 treated high-grade carotid stenoses. The lesions were located at the origin of the internal carotid artery (ICA) in 20 patients, and at the origin of the common carotid artery (CCA) in 2. MRI was performed the day before, and repeated within 24 hours after the procedure, and examined by two neuroradiologists. RESULTS: All stent implantations were successful but 4 patients developed an acute neurological deficit within 24 hours after carotid angioplasty. On PWI, Time To Peak (TTP) values ipsilateral to the carotid stenosis were increased before the procedure in 15 patients, and had remained normal in 6 and were not assessable in 1. After the procedure, TTP values were normal in 12 patients, increased in 8 and not assessable in 2. On DWI, new ipsilateral lesions were detected in 2 patients: 1 with an acute neurological deficit and 1 symptom free. CONCLUSION: Perfusion deficits may be present in severe carotid stenosis and be improved within 24 hours by carotid angioplasty and stenting. Asymptomatic infarcts may occur.