Marie Tisserand

Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion

Background and Purpose— It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion. Methods— We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ⩽6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ⩽10%. Results— Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0–40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77–82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ⩽10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively. Conclusions— Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset.

Can DWI-ASPECTS Substitute for Lesion Volume in Acute Stroke?

Background and Purpose— The extent of diffusion lesion on pretreatment imaging is a risk factor for poor outcome and hemorrhagic transformation after thrombolysis, and volumes of 70 to 100 mL have been advocated as cut-offs. However, estimating diffusion-weighted imaging (DWI) lesion volume (VolDWI) in the acute setting may be cumbersome. We aimed to determine whether the DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS) can substitute for VolDWI. Methods— DWI-ASPECTS and VolDWI were measured retrospectively on pretreatment MRI (median onset-to-MRI delay=122 minutes) in 330 consecutively treated patients with middle cerebral artery stroke. Results— DWI-ASPECTS and VolDWI were strongly correlated (&rgr;=−0.82), but each DWI-ASPECTS point corresponded to a wide range of VolDWI. All patients with DWI-ASPECTS ≥7 (n=207) had VolDWI <70 mL, whereas 32 of the 34 patients with DWI-ASPECTS <4 had VolDWI >100 mL. However, intermediate DWI-ASPECTS (4–6; n=89) corresponded to highly variable VolDWI (median, 66 mL; interquartile range, 40–98). Conclusions— Although each DWI-ASPECTS point corresponds to a wide range of volumes, DWI-ASPECTS <4 or ≥7 may be used as reliable surrogates of VolDWI >100 or <70 mL, respectively.

Microbleed Status and 3-Month Outcome After Intravenous Thrombolysis in 717 Patients With Acute Ischemic Stroke

Background and Purpose— Whether cerebral microbleeds (CMBs) detected on pretreatment magnetic resonance imaging increase the risks of symptomatic intracranial hemorrhage (sICH) and, most importantly, poor outcome in patients treated by intravenous thrombolysis for acute ischemic stroke is still debated. We assessed the effect of CMB presence and burden on 3-month modified Rankin Scale and sICH in a multicentric cohort. Methods— We analyzed prospectively collected data of consecutive patients solely treated by intravenous thrombolysis for acute ischemic stroke, in 2 centers where magnetic resonance imaging is the first-line pretreatment imaging. Neuroradiologists blinded to clinical data rated CMBs on T2* sequence using a validated scale. Logistic regressions were used to assess relationships between CMBs and 3-month modified Rankin Scale or sICH. Results— Among 717 patients, 150 (20.9%) had ≥1 CMBs. CMB burden was associated with worse modified Rankin Scale in univariable shift analysis (odds ratio, 1.07; 95% confidence interval, 1.00–1.15 per 1-CMB increase; P=0.049), but significance was lost after adjustment for age, hypertension, and atrial fibrillation (odds ratio, 1.03; 95% confidence interval, 0.96–1.11 per 1-CMB increase; P=0.37). Results remained nonsignificant when taking into account CMB location or presumed underlying vasculopathy. The incidence of sICH ranged from 3.8% to 9.1%, depending on the definition. Neither CMB presence, burden, location, nor presumed underlying vasculopathy was independently associated with sICH. Conclusions— Poor outcome or sICH was not associated with CMB presence or burden on pre–intravenous thrombolysis magnetic resonance imaging after adjustment for confounding factors. An individual patient data meta-analysis is needed to determine whether a subgroup of patients with CMBs carries an independent risk of poor outcome that might outweigh the expected benefit of intravenous thrombolysis.

Unexplained Early Neurological Deterioration After Intravenous Thrombolysis: Incidence, Predictors, and Associated Factors

Background and Purpose— Early neurological deterioration (END) after anterior circulation stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 hours of intravenous recombinant tissue-type plasminogen activator, apart from definite causes such as symptomatic intracranial hemorrhage and malignant edema whose incidence, predictors, and clinical management are well established, little is known about END without clear mechanism (ENDunexplained). Methods— We analyzed 309 consecutive patients thrombolysed intravenously ⩽4.5 hours from onset of anterior circulation stroke. ENDunexplained was defined as a ≥4-point deterioration on 24-hour National Institutes of Health Stroke Scale, without definite mechanism on concomitant imaging. ENDunexplained and no-END patients were compared for pretreatment clinical and imaging (including magnetic resonance diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post-treatment clinical (including blood pressure and glycemic changes) and imaging (24-hour recanalization) data, using univariate logistic regression. Exploratory multivariate analysis was also performed after variable reduction, with bootstrap analysis for internal validation. Results— Among 33 END patients, 23 (7% of whole sample) had ENDunexplained. ENDunexplained was associated with poor 3-month outcome (P<0.01). In univariate analysis, admission predictors of ENDunexplained included no prior use of antiplatelets (P=0.02), lower National Institutes of Health Stroke Scale score (P<0.01), higher glycemia (P=0.03), larger mismatch volume (P=0.03), and proximal occlusion (P=0.01), with consistent results from the multivariate analysis. Among factors recorded during the first 24 hours, only no recanalization was associated with ENDunexplained in multivariate analysis (P=0.02). Conclusions— ENDunexplained affected 7% of patients and accounted for most cases of END. Several predictors and associated factors were identified, with important implications regarding underlying mechanisms and potential prevention of this ominous event.

Susceptibility vessel sign on T2* magnetic resonance imaging and recanalization results of mechanical thrombectomy with stent retrievers: A multicentre cohort study

The susceptibility vessel sign (SVS) on T2*‐weighted magnetic resonance imaging has been reported in several studies as a negative predictor of early recanalization after intravenous thrombolysis. The meaning of SVS regarding the results of mechanical thrombectomy with stent retrievers was investigated.

How Sustained Is 24-Hour Diffusion-Weighted Imaging Lesion Reversal? : Serial Magnetic Resonance Imaging in a Patient Cohort Thrombolyzed Within 4.5 Hours of Stroke Onset

Background and Purpose— Here, we assessed how sustained is reversal of the acute diffusion lesion (RAD) observed 24 hours after intravenous thrombolysis, and the relationships between RAD fate and early neurological improvement. Methods— We analyzed 155 consecutive patients thrombolyzed intravenously 152 minutes (median) after stroke onset and who underwent 3 MR sessions: 1 before and 2 after treatment (median times from onset, 25.6 and 54.3 hours, respectively). Using voxel-based analysis of diffusion-weighted imaging (DWI)1, DWI2, and DWI3 lesions on coregistered image data sets, we assessed the outcome of RAD voxels (hyperintense on DWI1 but not on DWI2) as transient or sustained on DWI3, and their relationships with early neurological improvement, defined as &Dgr;National Institutes of Health Stroke Scale ≥8 or National Institutes of Health Stroke Scale ⩽1 at 24 hours. Tmax and apparent diffusion coefficient values were compared between sustained and transient RAD voxels. Results— The median (interquartile range) baseline National Institutes of Health Stroke Scale and DWI1 lesion volume were 11 (7–18) mL and 15.6 (6.0–50.9) mL, respectively. The median (interquartile range) RAD volume on DWI2 was 2.8 (1.1–6.6) mL, of which 70% was sustained on DWI3. Sixteen (10.3%) patients had sustained RAD ≥10 mL. As compared with transient RAD voxels, sustained RAD voxels had nonsignificantly higher baseline apparent diffusion coefficient values (median [interquartile range], 793 [717–887] versus 777 [705–869]×10−6 mm2·s −1, respectively; P=0.08) and significantly better perfusion (Tmax, mean±SD, 6.3±3.2 versus 7.8±4.0 s; P<0.001). At variance with transient RAD, the volume of sustained RAD was associated with early neurological improvement in multivariate analysis (odds ratio, 1.08; 95% confidence interval, [1.01–1.17], per 1-mL increase; P=0.03). Conclusions— After thrombolysis, over two-thirds of the DWI lesion reversal captured on 24-hour follow-up MR is sustained. Sustained DWI lesion reversal volume is a strong imaging correlate of early neurological improvement.

Does Diffusion Lesion Volume Above 70 mL Preclude Favorable Outcome Despite Post-Thrombolysis Recanalization?

Background and Purpose— Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ⩽4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal. Methods— We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ⩽2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes. Results— Median (interquartile range) DWI lesion volume was 22 mL (10–60), and median onset time to imaging was 116 minutes (86–151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09–20.32]; P=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2–47.6] versus 8.5 mL [4.3–31.1]; P=0.17; and 19.6% [10.9–62.8] versus 8.7% [3.9–16.5], respectively; P=0.049). Conclusions— Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal.

An update on brain imaging in transient ischemic attack

Neuroimaging is critical in the evaluation of patients with transient ischemic attack (TIA) and MRI is the recommended modality to image an ischemic lesion. The presence of a diffusion (DWI) lesion in a patient with transient neurological symptoms confirms the vascular origin of the deficit and is predictive of a high risk of stroke. Refinement of MR studies including high resolution DWI and perfusion imaging using either MRI or CT further improve the detection of ischemic lesions. Rapid etiological work-up includes non-invasive imaging of cervical and intracranial arteries to search for symptomatic stenosis/occlusion associated with an increased risk of stroke.

Is White Matter More Prone to Diffusion Lesion Reversal After Thrombolysis

Background and Purpose— In acute ischemic stroke, white matter (WM) is considered more resistant to infarction than gray matter (GM). To test this hypothesis, we compared the fate of WM and GM voxels belonging to the acute diffusion-weighted imaging (DWI) lesion, expecting WM voxels to be more prone to reversal after thrombolysis. Methods— Reversible acute DWI (RAD) lesion was defined voxel-wise as an acute lesion on initial DWI (DWI1) with no visible lesion on 24-hour DWI (DWI2). Only patients with RAD lesions >10 mL and >10% of DWI1 from our previously reported cohort were eligible. The core was defined as voxels hyperintense on DWI1 and DWI2. Semiautomated segmentation of DWI1, core, and RAD lesions, normalization into standard space, and WM/GM segmentation allowed calculations of WM/GM proportions in each region of interest using a voxel-counting algorithm. Results— Thirty patients were eligible (RAD lesion median volume [interquartile range], 23.3 mL [19.1–35.0 mL]; onset-to-treatment time, 134 minutes [105–185 minutes]). WM voxels fraction was greater in RAD lesions than in the core (59.4% [52.8%–68.9%] versus 49.6% [43.0%–57.5%]; P=0.011). The proportion of reversibility was greater for WM than for GM voxels (60.8% [25.5%–88.7%] versus 53.5% [21.1%–77.3%]; P=0.02). The percentage of RAD lesions increased with the proportion of WM present in the acute DWI lesion (P<0.0001; R=0.67). Conclusions— Acute DWI lesions predominantly involving WM may be more prone to reversal and, hence, to respond to therapy than their GM counterparts.

Clinical and Magnetic Resonance Imaging Predictors of Very Early Neurological Response to Intravenous Thrombolysis in Patients With Middle Cerebral Artery Occlusion

Background The early identification of patients who are unlikely to respond to intravenous recombinant tissue plasminogen activator (IV‐tPA) could help select candidates for additional intra‐arterial therapy or add‐on antithrombotic drugs during the acute stage of stroke. Given that very early neurological improvement (VENI) is a reliable surrogate of early recanalization, we assessed the clinical and magnetic resonance imaging predictors of lack of VENI. Methods and Results We reviewed consecutive ischemic stroke patients with middle cerebral artery occlusion and treated within 4.5 hours by IV‐tPA between 2003 and 2012 in our center, where magnetic resonance imaging is systematically implemented as first‐line diagnostic workup. Lack of VENI was defined as a <40% decrease in baseline National Institutes of Health Stroke Scale (NIHSS) score 1 hour after start of IV‐tPA. Poor outcome was defined as a 3‐month modified Rankin scale ≥2. Associations between lack of VENI and potential determinants were assessed in logistic regression models. In all, 186 patients were included (median baseline NIHSS score, 16; median onset to treatment time, 155 minutes). One hundred forty‐three patients (77%) had no VENI. The variables significantly associated with lack of VENI in multivariable analysis were baseline NIHSS (OR, 1.08; 95% CI, 1.01 to 1.16 per 1‐point increase; P=0.03), onset to treatment time >120 minutes (OR, 2.94; 95% CI, 1.31 to 6.63; P=0.009) and diffusion weighted imaging—Alberta Stroke Programme Early CT Score ≤5 (OR, 3.60; 95% CI, 1.14 to 11.35; P=0.03). Patients without VENI were more likely to have a modified Rankin Scale ≥2 than those without VENI (68% versus 24%; OR, 5.01; 95% CI, 2.12 to 11.82) and less likely to have recanalization after 24 hours (OR, 0.41; 95% CI, 0.19 to 0.88). Conclusions Lack of VENI provides an early estimate of 3‐month outcome and recanalization after IV‐tPA. Baseline NIHSS, onset to treatment time, and diffusion weighted imaging—Alberta Stroke Programme Early CT Score could help to predict lack of VENI and, in turn, might help early selection of candidates for complementary reperfusion strategies.