TAGE Score for Symptomatic Intracranial Hemorrhage Prediction After Successful Endovascular Treatment in Acute Ischemic Stroke.

BACKGROUND: Determine if early venous filling (EVF) after complete successful recanalization with mechanical thrombectomy in acute ischemic stroke is an independent predictor of symptomatic intracranial hemorrhage (sICH) and integrate EVF into a risk score for sICH prediction. METHODS: Consecutive patients with anterior acute ischemic stroke treated by mechanical thrombectomy issued from patients enrolled in the THRACE trial (Thrombectomie des Artères Cérébrales) and from 2 prospective registries were included and divided into a derivation (Center I; n=402) and validation cohorts (THRACE and center 2; n=507). EVF was evaluated by 2 blinded readers. sICH was defined according to the modified European cooperative acute stroke study II. Clinical and radiological data were analyzed in the derivation cohort (C1) to identify independent predictors of sICH and construct a predictive score test on the validation cohort (THRACE + C2). RESULTS: Symptomatic ICH rate was similar between the two cohorts (9.9% and 8.9% respectively, P=0.9). Time from onset-to-successful recanalization >270 minutes (odds ratio [OR], 7.8 [95% CI, 2.5-24]), Alberta Stroke Program Early CT Score (≤5 [OR, 2.49 (95% CI, 1.8-8.1) or 6-7 [OR, 1.15 (95% CI, 1.03-4.46)]), glucose blood level >7 mmol/L (OR, 2.92 [95% CI, 1.26-6.7]), and EVF presence (OR, 11.9 [95% CI, 3.8-37.5]) were independent predictors of sICH and constituted the Time-Alberta Stroke Program Early CT-Glycemia-EVF score. Time-Alberta Stroke Program Early CT-Glycemia-EVF score was associated with an increased risk of sICH in the derivation cohort (OR increase per unit, 1.99 [95% CI, 1.53-2.59]; P<0.001) with area under the curve, 0.832 [95% CI, 0.767-0.898]. The score had good performance in the validation cohort (area under the curve, 0.801 [95% CI, 0.69-0.91]). CONCLUSIONS: Time-Alberta Stroke Program Early CT-Glycemia-EVF score is a simple tool with readily available clinical variables with good performances for sICH prediction after mechanical thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01062698.

Synthetic FLAIR as a Substitute for FLAIR Sequence in Acute Ischemic Stroke.

Background In acute ischemic stroke (AIS), fluid-attenuated inversion recovery (FLAIR) is used for treatment decisions when onset time is unknown. Synthetic FLAIR could be generated with deep learning from information embedded in diffusion-weighted imaging (DWI) and could replace acquired FLAIR sequence (real FLAIR) and shorten MRI duration. Purpose To compare performance of synthetic and real FLAIR for DWI-FLAIR mismatch estimation and identification of patients presenting within 4.5 hours from symptom onset. Materials and Methods In this retrospective study, all pretreatment and early follow-up (<48 hours after symptom onset) MRI data sets including DWI (b = 0-1000 sec/mm2) and FLAIR sequences obtained in consecutive patients with AIS referred for reperfusion therapies between January 2002 and May 2019 were included. On the training set (80%), a generative adversarial network was trained to produce synthetic FLAIR with DWI as input. On the test set (20%), synthetic FLAIR was computed without real FLAIR knowledge. The DWI-FLAIR mismatch was evaluated on both FLAIR data sets by four independent readers. Interobserver reproducibility and DWI-FLAIR mismatch concordance between synthetic and real FLAIR were evaluated with κ statistics. Sensitivity and specificity for identification of AIS within 4.5 hours were compared in patients with known onset time by using McNemar test. Results The study included 1416 MRI scans (861 patients; median age, 71 years [interquartile range, 57-81 years]; 375 men), yielding 1134 and 282 scans for training and test sets, respectively. Regarding DWI-FLAIR mismatch, interobserver reproducibility was substantial for real and synthetic FLAIR (κ = 0.80 [95% CI: 0.74, 0.87] and 0.80 [95% CI: 0.74, 0.87], respectively). After consensus, concordance between real and synthetic FLAIR was almost perfect (κ = 0.88; 95% CI: 0.82, 0.93). Diagnostic value for identifying AIS within 4.5 hours did not differ between real and synthetic FLAIR (sensitivity: 107 of 131 [82%] vs 111 of 131 [85%], P = .2; specificity: 96 of 104 [92%] vs 96 of 104 [92%], respectively, P > .99). Conclusion Synthetic fluid-attenuated inversion recovery (FLAIR) had diagnostic performances similar to real FLAIR in depicting diffusion-weighted imaging-FLAIR mismatch and in helping to identify early acute ischemic stroke, and it may accelerate MRI protocols. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Carroll and Hurley in this issue.

Perfusion Imaging and Clinical Outcome in Acute Ischemic Stroke with Large Core.

OBJECTIVE: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. METHODS: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). RESULTS: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7-27.0] vs 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio. INTERPRETATION: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417-427.

Meningioma in patients exposed to progestin drugs: results from a real-life screening program.

PURPOSE: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate). METHODS: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening. RESULTS: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up. CONCLUSION: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

Increased Wall Enhancement During Follow-Up as a Predictor of Subsequent Aneurysmal Growth.

Background and Purpose- Absence of arterial wall enhancement (AWE) of unruptured intracranial aneurysms (UIA) has shown promise at predicting which aneurysms will not rupture. We here tested the hypothesis that increased enhancement during follow-up (increased intensity, extension, or thickness or appearance of de novo enhancement), assessed using vessel wall magnetic resonance imaging, was associated with higher rates of subsequent growth. Methods- Patients with UIA were included between 2012 and 2018. Two readers independently rated AWE modification on 3T vessel wall magnetic resonance imaging, and morphological changes on time-of-flight magnetic resonance angiography during follow-up. Results- A total of 129 patients harboring 145 UIA (mean size 4.1 mm) met study criteria, of which 12 (8.3%) displayed morphological growth at 2 years. Of them, 8 demonstrated increased AWE during follow-up before or concurrently to morphological growth, and 4 had preexisting AWE that remained stable before growth. In the remaining 133 (nongrowing) UIAs, no AWE modifications were found. In multivariable analysis, increased AWE, not size, was associated with UIA growth (relative risk, 26.1 [95% CI, 7.4-91.7], P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for UIA growth of increased AWE during follow-up were, respectively, of 67%, 100%, 96%, and 100%. Conclusions- Increased AWE during follow-up of conservatively managed UIAs predicts aneurysm growth over a 2-year period. This may impact UIA management towards closer monitoring or preventive treatment. Replication in a different setting is warranted.

Accelerated MR Evaluation of Patients with Suspected Large Arterial Vessel Occlusion: Diagnostic Performances of the FLAIR Vessel Hyperintensities.

BACKGROUND: Fluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) document slowed vascular flow at the level and after the occlusion site patients with acute ischemic stroke (AIS). We aimed to assess the accuracy of FVH for the confirmation and location of a large vessel occlusion (LVO). METHODS: Three radiologists reviewed the FLAIR sequence of the admission MRI exam of patients with suspected AIS at a single academic center. Readers were provided with the main clinical deficit with National Institute of Health Stroke Severity score and were asked to identify and locate an LVO when appropriate. Kappa coefficients were calculated for agreement along with diagnosis performances of FVH to recognize and locate an LVO with digital subtracted angiography (DSA) as gold standard. RESULTS: Among 125 patients screened with MRI for a suspected AIS, 96 (81%) were diagnosed with AIS and 47 (38%) patients had an anterior LVO of whom 25 (20%) had a DSA for mechanical thrombectomy. Kappa coefficients for intra- and inter-readers were good to excellent. Overall, the sensitivity and the specificity of the FVH to predict an anterior LVO was 0.98 (95% confidence interval [CI]: 0.94-1) and 0.86 (95% CI: 0.79-0.96), respectively, while PPV and NPV were 0.87 (95% CI: 0.85-0.95) and 0.98 (0.97-1), respectively. FVH also showed good to excellent accuracy for identifying M1 and M2 versus internal carotid artery occlusion site. CONCLUSION: We found that FVH demonstrated excellent diagnostic performances for the identification of LVO and its level with good to excellent reproducibility. This MRI radio marker of occlusion provides additional arguments and may speed-up the detection of potential candidates for MT.

Magnetic Resonance Imaging or Computed Tomography Before Treatment in Acute Ischemic Stroke.

Background and Purpose- The acute management of stroke patients requires a fast and efficient screening imaging modality. We compared workflow and functional outcome in acute ischemic stroke patients screened by magnetic resonance imaging (MRI) or computed tomography (CT) before treatment in the THRACE trial (Thrombectomie des Artères Cérébrales), with the emphasis on the duration of the imaging step. Methods- The THRACE randomized trial (June 2010 to February 2015) evaluated the efficacy of mechanical thrombectomy after intravenous tPA (tissue-type plasminogen activator) in ischemic stroke patients with proximal occlusion. The choice of screening imaging modality was left to each enrolling center. Differences between MRI and CT groups were assessed using univariable analysis and the impact of imaging modality on favorable 3-month functional outcome (modified Rankin Scale score of ≤2) was tested using multivariable logistic regression. Results- Four hundred one patients were included (25 centers), comprising 299 MRI-selected and 102 CT-selected patients. Median baseline National Institutes of Health Stroke Scale score was 18 in both groups. MRI scan duration (median [interquartile range]) was longer than CT (MRI: 13 minutes [10-16]; CT: 9 minutes [7-12]; P<0.001). Stroke-onset-to-imaging time (MRI: median 114 minutes [interquartile range, 89-138]; CT: 107 minutes [88-139]; P=0.19), onset-to-intravenous tPA time (MRI: 150 minutes [124-179]; CT: 150 minutes [123-180]; P=0.38) and onset-to-angiography-suite time (MRI: 200 minutes [170-250]; CT: 213 minutes [180-246]; P=0.57) did not differ between groups. Imaging modality was not significantly associated with functional outcome in the multivariable analysis. Conclusions- Although MRI scan duration is slightly longer than CT, MRI-based selection for acute ischemic stroke patients is accomplished within a timeframe similar to CT-based selection, without delaying treatment or impacting functional outcome. This should help to promote wider use of MRI, which has inherent imaging advantages over CT. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01062698.

Better Collaterals Are Independently Associated With Post-Thrombolysis Recanalization Before Thrombectomy.

Background and Purpose- In acute stroke patients with large vessel occlusion, the goal of intravenous thrombolysis (IVT) is to achieve early recanalization (ER). Apart from occlusion site and thrombus length, predictors of early post-IVT recanalization are poorly known. Better collaterals might also facilitate ER, for instance, by improving delivery of the thrombolytic agent to both ends of the thrombus. In this proof-of-concept study, we tested the hypothesis that good collaterals independently predict post-IVT recanalization before thrombectomy. Methods- Patients from the registries of 6 French stroke centers with the following criteria were included: (1) acute stroke with large vessel occlusion treated with IVT and referred for thrombectomy between May 2015 and March 2017; (2) pre-IVT brain magnetic resonance imaging, including diffusion-weighted imaging, T2*, MR angiography, and dynamic susceptibility contrast perfusion-weighted imaging; and (3) ER evaluated ≤3 hours from IVT start on either first angiographic run or noninvasive imaging. A collateral flow map derived from perfusion-weighted imaging source data was automatically generated, replicating a previously validated method. Thrombus length was measured on T2*-based susceptibility vessel sign. Results- Of 224 eligible patients, 37 (16%) experienced ER. ER occurred in 10 of 83 (12%), 17 of 116 (15%), and 10 of 25 (40%) patients with poor/moderate, good, and excellent collaterals, respectively. In multivariable analysis, better collaterals were independently associated with ER ( P=0.029), together with shorter thrombus ( P<0.001) and more distal occlusion site ( P=0.010). Conclusions- In our sample of patients with stroke imaged with perfusion-weighted imaging before IVT and intended for thrombectomy, better collaterals were independently associated with post-IVT recanalization, supporting our hypothesis. These findings strengthen the idea that advanced imaging may play a key role for personalized medicine in identifying patients with large vessel occlusion most likely to benefit from IVT in the thrombectomy era.

Thrombus Length Predicts Lack of Post-Thrombolysis Early Recanalization in Minor Stroke With Large Vessel Occlusion.

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Validation of overestimation ratio and TL-SVS as imaging biomarker of cardioembolic stroke and time from onset to MRI.

OBJECTIVE: We aimed to determine in the "THRACE" trial, the clinical and MRI technical parameters associated with the two-layered susceptibility vessel sign (TL-SVS) and the overestimation ratio (overR). MATERIALS AND METHODS: Patients with pre-treatment brain gradient echo (GRE) sequence and an etiological work-up were identified. Two readers reviewed TL-SVS, i.e., a SVS with a linear low-intense signal core surrounded by a higher intensity and measured the overR as the width of SVS divided by the width of the artery. Binomial and ordinal logistic regression respectively tested the association between TL-SVS and quartiles of overR with patient characteristics, cardioembolic stroke (CES), time from onset to imaging, and GRE sequence parameters (inter slice gap, slice thickness, echo time, flip angle, voxel size, and field strength). RESULTS: Among 258 included patients, 102 patients were examined by 3 Tesla MRI and 156 by 1.5 Tesla MRI. Intra- and inter-reader agreements for quartiles of overR and TL-SVS were good to excellent. The median overR was 1.59 (IQR, 1.30 to 1.86). TL-SVS was present in 101 patients (39.2%, 95%CI, 33.1 to 45.1%). In multivariate analysis, only CES was associated with overR quartiles (OR, 1.83; 95%CI, 1.11 to 2.99), and every 60 min increase from onset to MRI time was associated with TL-SVS (OR, 1.72; 95%CI, 1.10 to 2.67). MRI technical parameters were statistically associated with neither overR nor TL-SVS. CONCLUSION: Independent of GRE sequence parameters, an increased overR was associated to CES, while the TL-SVS is independently related to a longer time from onset to MRI. KEY POINTS: • An imaging biomarker would be useful to predict the etiology of stroke in order to adapt secondary prevention of stroke. • The two-layered susceptibility vessel sign and the overestimation ratio are paramagnetic effect derived markers that vary according to the MRI machines and sequence parameters. • Independent of sequence parameters, an increased overestimation ratio was associated to cardioembolic stroke, while the two-layered susceptibility vessel sign is independently related to a longer time from onset to MRI.

Benefit from revascularization after thrombectomy according to FLAIR vascular hyperintensities-DWI mismatch.

OBJECTIVES: We tested whether FLAIR vascular hyperintensities (FVH)-DWI mismatch could identify candidates for thrombectomy most likely to benefit from revascularization. METHODS: We retrospectively reviewed 100 patients with proximal MCA occlusion from 18 stroke centers randomized in the IV-thrombolysis plus mechanical thrombectomy arm of the THRACE trial (2010-2015). We tested the associations between successful revascularization on digital subtraction angiography (modified Thrombolysis in Cerebral Infarction 2b/3) and 3-month favorable outcome (modified Rankin Scale score ≤ 2), stratified on FVH-DWI mismatch status, with secondary analyses adjusted on National Institutes of Health Stroke Scale (NIHSS) and DWI lesion volume. RESULTS: FVH-DWI mismatch was present in 79% of patients, with a similar prevalence at 1.5 T (80%) and 3 T (78%). Successful revascularization (74%) was more frequent in patients with FVH-DWI mismatch (63/79, 80%) than in patients without (11/21, 52%), p = 0.01. The OR of favorable outcome for revascularization were 15.05 (95% CI 3.12-72.61, p < 0.001) in patients with FVH-DWI mismatch and 0.83 (95% CI 0.15-4.64, p = 0.84) in patients without FVH-DWI mismatch (p = 0.011 for interaction). Similar results were observed after adjustment for NIHSS (OR = 12.73 [95% CI 2.69-60.41, p = 0.001] and 0.96 [95% CI 0.15-6.30, p = 0.96]) or for DWI volume (OR = 12.37 [95% CI 2.76-55.44, p = 0.001] and 0.91 [95% CI 0.16-5.33, p = 0.92]) in patients with and without FVH-DWI mismatch, respectively. CONCLUSIONS: The FVH-DWI mismatch identifies patients likeliest to benefit from revascularization, irrespective of initial DWI lesion volume and clinical stroke severity, and could serve as a useful surrogate marker for penumbral evaluation. KEY POINTS: • The FVH-DWI mismatch, defined by FLAIR vascular hyperintensities (FVH) located beyond the boundaries of the DWI lesion, is associated with large penumbra. • Among stroke patients with proximal middle cerebral artery occlusion referred for thrombectomy, those with FVH-DWI mismatch are most likely to benefit from revascularization. • FVH-DWI mismatch provides an alternative to PWI-DWI mismatch in order to select patients who are candidates for thrombectomy.

Terrorist explosive belt attacks: specific patterns of bone traumas.

In cases of terrorist bomb attacks, the issue of victim identification is the principal aim. For investigators and justice, terrorists must also be identified in a timely manner. The fragmentation of bodies caused by explosive devices however makes this operation difficult. The cases presented correspond to six autopsies of perpetrators carrying explosives. Their explosive belts produced different body sections on areas correlated with the location on the body of carrying explosive charges. Indeed, cross-sectional areas are the signature of the level of explosive devices on the body, and some fracture features through the damage of certain areas of constitutional weaknesses are specific elements to consider. These elements can allow a quick distinction between victims and terrorists, in order to assist in the medico-legal process of identification.

Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy: Incidence, Predictors, and Prediction Scores.

Background and Purpose­Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods­Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance­ or computed tomography­based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results­In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography­based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions­The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

Cerebellar high-grade gliomas do not present the same molecular alterations as supratentorial high-grade gliomas and may show histone H3 gene mutations.

Numerous molecular alterations have been described in supratentorial high-grade gliomas (1p19q co-deletion, IDH1/2, histone H3, hTERT promotor mutations, loss of ATRX) which have led to a new histomolecular classification of diffuse gliomas. We aimed at describing these alterations in a series of 19 adults with pure cerebellar high-grade gliomas. Systematic immunohistochemical analyses, including that of IDH1R132H, ATRX, p53, PTEN, EGFR, p16, FGFR3, BRAFV600E, mismatch repair proteins, H3K27me3, H3K36me3, and H3K27M; molecular analyses of IDH1/2, hTERT, BRAF, H3F3A, and HIST1H3B mutation hotspots; and EGFR, PTEN FISH were retrospectively performed in a multicentric study. We histopathologically identified 14 glioblastomas, 4 grade III astrocytomas and 1 gliosarcoma. Two cases showed a H3F3A K27M mutation. Only one case harbored a classical profile of glioblastoma with hTERT mutation, EGFR gain and 10q loss. The most frequent alteration was the absence of p16 immunoexpression. We report a histomolecular analysis of pure cerebellar high grade gliomas. The histomolecular profile appears to be different from that of supratentorial gliomas, with no IDH1/2 gene mutations and only 1 case with a classic profile of de novo glioblastoma. In 2 cases, we identified H3F3A K27M mutation, classically described in pediatric midline gliomas.
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Is Unexplained Early Neurological Deterioration After Intravenous Thrombolysis Associated With Thrombus Extension?

BACKGROUND AND PURPOSE: Early neurological deterioration (END) after anterior circulation stroke is strongly associated with poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END occurring after intravenous thrombolysis remains unclear in most instances. We tested the hypothesis that unexplained END is associated with thrombus extension. METHODS: From our database of consecutively thrombolysed patients, we identified anterior circulation stroke patients who had both admission and 24-hour T2* magnetic resonance imaging, visible occlusion on admission magnetic resonance angiography and no recanalization on 24-hour magnetic resonance angiography. END was defined as ≥4 National Institutes of Health Stroke Scale-point deterioration on 24-hour clinical assessment and unexplained END as END without clear cause. The incidence of susceptibility vessel sign extension on T2* imaging, defined as any new occurrence or extension of susceptibility vessel sign from admission to 24-hour follow-up magnetic resonance, was compared between patients with unexplained END and those without END. RESULTS: Of 120 eligible patients for the present study, 22 experienced unexplained END. Susceptibility vessel sign extension was present in 41 (34%) patients and was significantly more frequent in the unexplained END than in the no-END group (59% versus 29%, respectively; adjusted odds ratio=3.96; 95% confidence interval, 1.25-12.53; P=0.02). CONCLUSIONS: In this study, unexplained END occurring after thrombolysis was independently associated with susceptibility vessel sign extension, suggesting in situ thrombus extension or re-embolization. These findings strengthen the need to further investigate early post-thrombolysis administration of antithrombotics to reduce the risk of this ominous clinical event.

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.

ASPECTS (Alberta Stroke Program Early CT Score) Assessment of the Perfusion-Diffusion Mismatch.

BACKGROUND AND PURPOSE: Rapid and reliable assessment of the perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch is required to promote its wider application in both acute stroke clinical routine and trials. We tested whether an evaluation based on the Alberta Stroke Program Early CT Score (ASPECTS) reliably identifies the PWI/DWI mismatch. METHODS: A total of 232 consecutive patients with acute middle cerebral artery stroke who underwent pretreatment magnetic resonance imaging (PWI and DWI) were retrospectively evaluated. PWI-ASPECTS and DWI-ASPECTS were determined blind from manually segmented PWI and DWI volumes. Mismatch-ASPECTS was defined as the difference between PWI-ASPECTS and DWI-ASPECTS (a high score indicates a large mismatch). We determined the mismatch-ASPECTS cutoff that best identified the volumetric mismatch, defined as VolumeTmax>6s/VolumeDWI≥1.8, a volume difference≥15 mL, and a VolumeDWI<70 mL. RESULTS: Inter-reader agreement was almost perfect for PWI-ASPECTS (κ=0.95 [95% confidence interval, 0.90-1]), and DWI-ASPECTS (κ=0.96 [95% confidence interval, 0.91-1]). There were strong negative correlations between volumetric and ASPECTS-based assessments of DWI lesions (ρ=-0.84, P<0.01) and PWI lesions (ρ=-0.90, P<0.01). Receiver operating characteristic curve analysis showed that a mismatch-ASPECTS ≥2 best identified a volumetric mismatch, with a sensitivity of 0.93 (95% confidence interval, 0.89-0.98) and a specificity of 0.82 (95% confidence interval, 0.74-0.89). CONCLUSIONS: The mismatch-ASPECTS method can detect a true mismatch in patients with acute middle cerebral artery stroke. It could be used for rapid screening of patients with eligible mismatch, in centers not equipped with ultrafast postprocessing software.

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.

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 ΔNational 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) mm(2)·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.

Pancreatic adenocarcinoma: MRI conspicuity and pathologic correlations.

PURPOSE: To identify the MRI sequences producing the greatest pancreatic adenocarcinoma conspicuity and to assess correlations linking MRI signal intensity and apparent diffusion coefficient to histopathological findings. METHODS: We retrospectively included 22 patients with pancreatic adenocarcinoma who underwent MRI (1.5 or 3 T) before surgical resection. Fat-suppressed (FS) T1- and T2-weighted sequences; 3D FS dynamic T1-weighted gadolinium-enhanced gradient-echo (GRE) imaging at the arterial, portal, and delayed phases; and diffusion-weighted imaging (DWI) with b values of 600-800 s/mm(2) were reviewed. On each sequence, we assessed tumor conspicuity both qualitatively (3-point scale) and quantitatively (tumor-to-proximal and -distal pancreas contrast ratios), and we performed paired Wilcoxon tests to compare these data across sequences. We evaluated correlations between histopathological characteristics and MRI features. RESULTS: 21/22 (95%) tumors were hypointense by 3D FS T1 GRE arterial phase imaging, which produced the greatest tumor conspicuity (p ≤ 0.02). By DWI, 5/20 (25%) of tumors were isointense. The correlation between size by histology and MRI was strongest with DWI. A progressive enhancement pattern was associated with extensive and dense fibrous stroma (p ≤ 0.03). CONCLUSIONS: 3D FS T1 GRE arterial phase imaging produces greater pancreatic adenocarcinoma conspicuity compared to DWI but underestimates tumor size. DWI provides the best size evaluation but fails to delineate the tumor in one-fourth of cases.