Wagih Ben Hassen

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.

Intracranial Aneurysms: Recurrences More than 10 Years after Endovascular Treatment—A Prospective Cohort Study, Systematic Review, and Meta-Analysis

PURPOSE To assess the efficacy of endovascular treatment (EVT) of intracranial aneurysms for recurrence, bleeding, and de novo aneurysm formation at long-term follow-up (> 10 years after treatment) with magnetic resonance (MR) angiography and to identify risk factors for recurrence through a prospective study and a systematic review of the literature. MATERIALS AND METHODS Clinical examinations and 3-T MR angiography were performed prospectively 10 years after EVT of intracranial aneurysms in a single institution. Ethics committee approval and informed consent were obtained. PubMed, EMBASE, and Cochrane databases were searched to identify studies in which authors reported bleeding and/or aneurysm recurrence rates in patients who received follow-up more than 10 years after EVT. Univariate and multivariate subgroup analyses were performed to identify risk factors (midterm MR angiographic results, aneurysm characteristics, retreatment within 5 years). RESULTS In the prospective study, sac recanalization occurred between midterm and long-term MR angiography in 16 of 129 (12.4%) aneurysms. Grade 2 classification on the Raymond scale at midterm MR angiography (relative risk [RR], 4.16; 99% confidence interval [CI]: 2.12, 8.14) and retreatment within 5 years (RR, 4.67; 99% CI: 1.55, 14.03) were risk factors for late recurrence. In the systematic review (15 cohorts, 2773 patients, 2902 aneurysms), bleeding, aneurysm recurrence, and de novo lesion formation rates were, respectively, 0.7% (99% CI: 0.2%, 2.7%; I(2), 0%; one of 694 patients), 11.4% (99% CI: 7.0%, 18.0%; I(2), 21.6%), and 4.1% (99% CI: 1.7, 9.4%; I(2), 54.1%). Raymond grade 2 initial result (RR, 7.08; 99% CI: 1.24, 40.37; I(2), 82.6%) and aneurysm size greater than 10 mm (RR, 4.37; 99% CI: 1.83, 10.44; I(2), 0%) were risk factors for late recurrence. CONCLUSION EVT of intracranial aneurysm is effective for prevention of long-term bleeding, but recurrences occur in a clinically relevant percentage of patients, a finding that may justify follow-up of selected patients for 10 years or more, such as patients with aneurysms larger than 10 mm or classified as Raymond grade 2 at midterm MR angiography.

Circumferential Thick Enhancement at Vessel Wall MRI Has High Specificity for Intracranial Aneurysm Instability

Purpose To identify wall enhancement patterns on vessel wall MRI that discriminate between stable and unstable unruptured intracranial aneurysm (UIA). Materials and Methods Patients were included from November 2012 through January 2016. Vessel wall MR images were acquired at 3 T in patients with stable (incidental and nonchanging over 6 months) or unstable (symptomatic or changing over 6 months) UIA. Each aneurysm was evaluated by using a four-grade classification of enhancement: 0, none; 1, focal; 2, thin circumferential; and 3, thick (>1 mm) circumferential. Inter- and intrareader agreement for the presence and the grade of enhancement were assessed by using κ statistics and 95% confidence interval (CI). The sensitivity, specificity, and negative and positive predictive values of each enhancement grade for differentiating stable from unstable aneurysms was compared. Results The study included 263 patients with 333 aneurysms. Inter- and intrareader agreement was excellent for both the presence of enhancement (κ values, 0.82 [95% CI: 0.67, 0.99] and 0.87 [95% CI: 0.7, 1.0], respectively) and enhancement grade (κ = 0.92 [95% CI: 0.87, 0.95]). In unruptured aneurysms (n = 307), grade 3 enhancement exhibited the highest specificity (84.4%; 233 of 276; 95% CI: 80.1%, 88.7%; P = .02) and negative predictive value (94.3%; 233 of 247) for differentiating between stable and unstable lesions. There was a significant association between grade 3 enhancement and aneurysm instability (P < .0001). Conclusion In patients with intracranial aneurysm, a thick (>1 mm) circumferential pattern of wall enhancement demonstrated the highest specificity for differentiating between stable and unstable aneurysms.

Inter- and intraobserver reliability for angiographic leptomeningeal collateral flow assessment by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale

Background The adequacy of leptomeningeal collateral flow has a pivotal role in determining clinical outcome in acute ischemic stroke. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral score is among the most commonly used scales for measuring this flow. It is based on the extent and rate of retrograde collateral flow to the impaired territory on angiography. Objective To evaluate inter- and intraobserver agreementin angiographic leptomeningeal collateral flow assessment. Materials and methods Thirty pretreatment angiogram video loops (frontal and lateral view), chosen from the randomized controlled trial THRombectomie des Artères CErebrales (THRACE), were sent for grading in an electronic file. 19 readers participated, including eight who had access to a training set before the first grading. 13 readers made a double evaluation, 3 months apart. Results Overall agreement among the 19 observers was poor (κ = 0,16 ± 6,5.10 -3), and not improved with prior training (κ = 0,14 ± 0,016). Grade 4 showed the poorest interobserver agreement (κ=0.18±0.002) while grades 0 and 1 were associated with the best results (κ=0.52±0.001 and κ=0.43±0.004, respectively). Interobserver agreement increased (κ = 0,27± 0,014) when a dichotomized score, ‘poor collaterals’ (score of 0, 1 or 2) versus ‘good collaterals’ (score of 3 or 4) was used. The intraobserver agreements varied between slight (κ=0.18±0.13) and substantial (κ=0.74±0.1), and were slightly improved with the dichotomized score (from κ=0.19±0.2 to κ=0.79±0.11). Conclusion Inter- and intraobserver agreement of collateral circulation grading using the ASITN/SIR score was poor, raising concerns about comparisons among publications. A simplified dichotomized judgment may be a more reproducible assessment when images are rated by the same observer(s) in randomized trials.

Design and Methodology of a Pilot Randomized Controlled Trial of Transcranial Direct Current Stimulation in Acute Middle Cerebral Artery Stroke (STICA)

Background: Stroke is a major cause of death and disability worldwide. The related burden is expected to further increase due to aging populations, calling for more efficient treatment. Ischemic stroke results from a focal reduction in cerebral blood flow due to the sudden occlusion of a brain artery. Ischemic brain injury results from a sequence of pathophysiological events that evolve over time and space. This cascade includes excitotoxicity and peri-infarct depolarizations (PIDs). Focal impairment of cerebral blood flow restricts the delivery of energetics substrates and impairs ionic gradients. Membrane potential is eventually lost, and neurons depolarize. Although recanalization therapies target the ischemic penumbra, they can only rescue the penumbra still present at the time of reperfusion. A promising novel approach is to “freeze” the penumbra until reperfusion occurs. Transcranial direct current stimulation (tDCS) is a non-invasive method of neuromodulation. Based on preclinical evidence, we propose to test the penumbra freezing concept in a clinical phase IIa trial assessing whether cathodal tDCS—shown in rodents to reduce infarction volume—prevents early infarct growth in human acute Middle Cerebral Artery (MCA) stroke, in adjunction to conventional revascularization methods. Methods: This is a monocentric randomized, double-blind, and placebo-controlled trial performed in patients with acute MCA stroke eligible to revascularization procedures. Primary outcome is infarct volume growth on diffusion weighted imaging (DWI) at day 1 relative to baseline. Secondary outcomes include safety and clinical efficacy. Significance: Results from this clinical trial are expected to provide rationale for a phase III study. Clinical trial registration—EUDRACT: 2016-A00160-51