Laurence Legrand

Clot Burden Score on Admission T2*-MRI Predicts Recanalization in Acute Stroke

Background and Purpose— To propose a T2*-MR adaptation of the computed tomography angiography-clot burden score (CBS), and assess its value as predictor of 24-hour recanalization and clinical outcome in anterior circulation stroke treated by intravenous thrombolysis ⩽4.5 hours from onset. Methods— Two independent observers retrospectively analyzed pretreatment T2* images for evaluation of clot burden, using a 10-point scale T2*-CBS. Three points are subtracted for susceptibility vessel sign in the supraclinoid internal carotid artery, 2 points each for susceptibility vessel sign in the proximal and distal part of middle cerebral artery, and 1 point each for susceptibility vessel sign in middle cerebral artery branches (with a maximum of 2 points) and for susceptibility vessel sign in anterior cerebral artery. Associations with 24-hour recanalization and favorable outcome (3-month modified Rankin Scale score, ⩽2) were assessed in multivariate analyses. Results— We analyzed 184 consecutive patients (mean age, 67 years) with median (interquartile range) admission National Institutes of Health Stroke Scale score and onset-to-treatment time of 15 (9–19) and 151 (120–185) minutes, respectively. The intraclass correlation for T2*-CBS between observers was 0.97 (95% confidence interval, 0.97–0.98). In multivariate analyses, T2*-CBS >6 was significantly associated with 24-hour recanalization (adjusted odds ratio, 5.1 [1.9–13.5]; P=0.001) or with favorable outcome (adjusted odds ratio, 4.2 [1.7–10.8]; P=0.003). Conclusions— T2*-CBS, a new reproducible semiquantitative score adapted from the computed tomography angiography-CBS, is associated with 24-hour recanalization and 3-month outcome after intravenous thrombolysis. This score needs external validation and could be useful to identify poor responders to intravenous thrombolysis.

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.

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.

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.

Do FLAIR Vascular Hyperintensities beyond the DWI Lesion Represent the Ischemic Penumbra

FLAIR images from over 140 patients with acute MCA infarctions were analyzed and compared with images used to estimate the ischemic penumbra. A FLAIR-DWI mismatch was seen in 72% of patients and the authors concluded that this may be used to identify the ischemic penumbra. BACKGROUND AND PURPOSE: In acute stroke with proximal artery occlusion, FLAIR vascular hyperintensities observed beyond the boundaries of the cortical lesion on DWI (newly defined “FLAIR vascular hyperintensity–DWI mismatch”) may be a marker of tissue at risk of infarction. Our aim was to compare the occurrence of FLAIR vascular hyperintensity–DWI mismatch relative to that of perfusion-weighted imaging–DWI mismatch in patients with proximal MCA occlusion before IV thrombolysis. MATERIALS AND METHODS: In 141 consecutive patients with proximal MCA occlusion, 2 independent observers analyzed FLAIR images for the presence of FLAIR vascular hyperintensity–DWI mismatch before IV thrombolysis. PWI-DWI mismatch was defined as Volumehypoperfusion > 1.8 × VolumeDWI, with Volumehypoperfusion > 6 seconds on time to maximum value of the residue function maps in the 94 patients with available PWI. The presence of FLAIR vascular hyperintensity–DWI mismatch, PWI-DWI mismatch, and infarct growth on 24-hour follow-up DWI was compared. RESULTS: A FLAIR vascular hyperintensity–DWI mismatch was present in 102/141 (72%) patients, with an excellent interobserver reliability (κ = 0.91), and a PWI-DWI mismatch, in 61 of the 94 (65%) patients with available PWI. FLAIR vascular hyperintensity–DWI mismatch predicted PWI-DWI mismatch with a sensitivity of 92% (95% CI, 85%–99%) and a specificity of 64% (95% CI, 47%–80%). Patients with FLAIR vascular hyperintensity–DWI mismatch had smaller initial DWI lesion and larger infarct growth (P < .001) than patients without FLAIR vascular hyperintensity–DWI mismatch, even though their final infarcts remained smaller (P < .001). CONCLUSIONS: Albeit being moderately specific, probably due to inclusion of oligemic tissue, the FLAIR vascular hyperintensity–DWI mismatch identifies large PWI-DWI mismatch with high sensitivity.

Non-invasive diagnosis of intracranial aneurysms

Patients need to be examined for intracranial aneurysms if they have had a subarachnoid hemorrhage. The preferred technique in this situation is CT angiography. Screening can be done for familial forms or for elastic tissue disorders, for which the first line investigation is magnetic resonance angiography. These non-invasive methods have now taken over from conventional angiography that was reserved for the pretreatment phase. A good technical knowledge of these imaging methods, their artifacts and misleading images enables reliable detection of intracranial aneurysms and for an accurate report to be returned to clinicians.

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.

Comparison between voxel-based and subtraction methods for measuring diffusion-weighted imaging lesion growth after thrombolysis

Background Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal. Aim To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction. Methods We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57–80), National Institute of Health Stroke Score at admission 14 (8–19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24 h (DWI2) after IV-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score. Results Infarct growth volume metrics were strongly correlated (ρ = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23–38.9) vs. 16.98 (4.4–45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82–0.90) vs. 0.82 (0.78–0.87), P = 0.003). Conclusion At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensities-Diffusion-Weighted Imaging Mismatch Identifies Acute Stroke Patients Most Likely to Benefit From Recanalization.

Background and Purpose— Fluid-attenuated inversion recovery vascular hyperintensities (FVH) beyond the boundaries of diffusion-weighted imaging (DWI) lesion (FVH-DWI mismatch) have been proposed as an alternative to perfusion-weighted imaging (PWI)-DWI mismatch. We aimed to establish whether FVH-DWI mismatch can identify patients most likely to benefit from recanalization. Methods— FVH-DWI mismatch was assessed in 164 patients with proximal middle cerebral artery occlusion before intravenous thrombolysis. PWI-DWI mismatch (PWITmax>6sec/DWI>1.8) was assessed in the 104 patients with available PWI data. We tested the associations between 24-hours complete recanalization on magnetic resonance angiography and 3-month favorable outcome (modified Rankin Scale score ⩽2), stratified on FVH-DWI (or PWI-DWI) status. Results— FVH-DWI mismatch was present in 121/164 (74%) patients and recanalization in 50/164 (30%) patients. The odds ratio for favorable outcome with recanalization was 16.2 (95% confidence interval, 5.7–46.5; P<0.0001) in patients with FVH-DWI mismatch and 2.6 (95% confidence interval, 0.6–12.1; P=0.22) in those without FVH-DWI mismatch (P=0.048 for interaction). Recanalization was associated with favorable outcome in patients with PWI-DWI mismatch (odds ratios, 9.9; 95% confidence interval, 3.1–31.3; P=0.0001) and in patients without PWI-DWI mismatch (odds ratios, 7.0; 95% confidence interval, 1.1–44.1; P=0.047), P=0.76 for interaction. Conclusion— The FVH-DWI mismatch may rapidly identify patients with proximal occlusion most likely to benefit from recanalization.