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Background: Noncontrast computed tomography hypodensities are a validated predictor of hematoma expansion (HE) in intracerebral hemorrhage and a possible alternative to the computed tomography angiography (CTA) spot sign but their added value to available prediction models remains unclear. We investigated whether the inclusion of hypodensities improves prediction of HE and compared their added value over the spot sign. Methods: Retrospective analysis of patients admitted for primary spontaneous intracerebral hemorrhage at the following 8 university hospitals in Boston, US (1994–2015, prospective), Hamilton, Canada (2010–2016, retrospective), Berlin, Germany (2014–2019, retrospective), Chongqing, China (2011–2015, retrospective), Pavia, Italy (2017–2019, prospective), Ferrara, Italy (2010–2019, retrospective), Brescia, Italy (2020–2021, retrospective), and Bologna, Italy (2015–2019, retrospective). Predictors of HE (hematoma growth >6 mL and/or >33% from baseline to follow-up imaging) were explored with logistic regression. We compared the discrimination of a simple prediction model for HE based on 4 predictors (antitplatelet and anticoagulant treatment, baseline intracerebral hemorrhage volume, and onset-to-imaging time) before and after the inclusion of noncontrast computed tomography hypodensities, using receiver operating characteristic curve and De Long test for area under the curve comparison. Results: A total of 2465 subjects were included, of whom 664 (26.9%) had HE and 1085 (44.0%) had hypodensities. Hypodensities were independently associated with HE after adjustment for confounders in logistic regression (odds ratio, 3.11 [95% CI, 2.55–3.80]; P P =0.025). In the subgroup of patients with a CTA available (n=895, 36.3%), the added value of hypodensities remained statistically significant (area under the curve, 0.68 [95% CI, 0.64–0.73] versus 0.74 [95% CI, 0.70–0.78]; P =0.041) whereas the addition of the CTA spot sign did not provide significant discrimination improvement (area under the curve, 0.74 [95% CI, 0.70–0.78]). Conclusions: Noncontrast computed tomography hypodensities provided a significant added value in the prediction of HE and appear a valuable alternative to the CTA spot sign. Our findings might inform future studies and suggest the possibility to stratify the risk of HE with good discrimination without CTA.

Background and Purpose: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. Methods: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. Results: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8–13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%–99.1%) and 79.0% (95% CI, 54.4%–94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912–1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. Conclusions: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: 3618210420, 2217698.

Perihaematomal oedema is a potential therapeutic target to improve outcome of patients with intracerebral haemorrhage, but its pathophysiology remains poorly elucidated. We investigated the longitudinal changes of cerebral perfusion and their influence on perihaematomal oedema development in 150 patients with intracerebral haemorrhage who underwent computed tomography perfusion within 6 h from onset, at 24 h and at 7 days. Perfusion parameters were measured in haemorrhagic core, perihaematomal rim, surrounding normal appearing and contralateral brain tissue. Computed tomography perfusion parameters gradually improved from the core to the periphery in each time interval with an early increase at 24 h followed by a delayed decline at 7 days compared with admission values (P < 0.001). Multivariable linear regression analysis showed that haematoma volume and cerebral blood flow gradient between normal appearing and perihaematomal rim were independently associated with absolute perihaematomal oedema volume in the different time points (within 6 h, B = 0.128, P = 0.032; at 24 h, B = 0.133, P = 0.016; at 7 days, B = 0.218, P < 0.001). In a secondary analysis with relative perihaematomal oedema as the outcome of interest, cerebral blood flow gradient between normal appearing and perihaematomal rim was an independent predictor of perihaematomal oedema only at 7 days (B = 0.239, P = 0.002). Our findings raise the intriguing hypothesis that perfusion gradients promote perihaematomal oedema development in the subacute phase after intracerebral haemorrhage.

BackgroundScientific data on the safety and efficacy of flow diverter stents (FDS) for the treatment of unruptured internal carotid artery (ICA) aneurysms with compressive neuro-ophthalmological symptoms are scarce. We studied this subject in a retrospective international multicenter series, pooling data of 9 tertiary care neurointerventional departments.ObjectiveTo investigate, in a retrospective, multicentric cohort of patients presenting with visual or oculomotor symptoms attributed to a compressive carotid artery in an unruptured intracranial aneurysm, the safety and efficacy profiles of FDS, by analyzing neuro-opthalmologic symptom evolution following FDS placement, complications, and aneurysm obliteration rates.MethodsAll patients treated since 2015 with a FDS for an unruptured aneurysm of the ICA with signs of compressive cranial nerve symptoms (CN II, III, IV, VI) were included.ResultsWe treated 55 patients with 55 aneurysms; 21 (38.2%) patients had oculomotor and 15 (27.3%) visual symptoms only; 19 (34.5%) presented with a combination of both. Treatment-related morbidity/mortality occurred in 7.2% and 3.6%, respectively. At last imaging follow-up (13.1±10.5 months) rates of complete aneurysm occlusion, neck remnant, and aneurysm remnant were 72%, 14%, and 14%, respectively. At last clinical follow-up after 13±10.5 months, 19/51 (37.3%) patients had recovered completely and 18/51 (35.3%) had recovered at least partially from their neuro-ophthalmological symptoms. In multivariable models, a longer delay between symptom onset and treatment was associated with higher odds for incomplete recovery and lower odds for any improvement (aOR 1.03 (95% CI 1.01 to 1.07), p=0.047 and 0.04 (0–0.81), p=0.020). Incomplete recovery was independently associated with older age and fusiform aneurysms.ConclusionFDS are effective to treat patients with compressive aneurysms of the ICA causing neuro-ophthalmological symptoms, especially when treatment is initiated early after symptom onset, and aneurysm occlusion is adequate. However, serious complications are not rare.

BACKGROUND AND PURPOSE: Intracranial stents for the treatment of aneurysms can be responsible for parent artery straightening, a phenomenon with potential consequences for aneurysmal occlusion. We aimed to evaluate parent artery straightening following flow-diverter stent placement in patients with intracranial aneurysms and explored the association between parent artery straightening and subsequent aneurysm occlusion. MATERIALS AND METHODS: All patients treated with flow-diverter stents for anterior circulation aneurysms located downstream from the carotid siphon between January 2009 and January 2018 were screened for inclusion. Parent artery straightening was defined as the difference (α–β) in the parent artery angle at the neck level before (α angle) and after flow-diverter stent deployment (β angle). We analyzed the procedural and imaging factors associated with parent artery straightening and the associations between parent artery straightening and aneurysmal occlusion. RESULTS: Ninety-five patients met the inclusion criteria (n = 64/95 women, 67.4%; mean age, 54.1 [SD, 11.2] years) with 97 flow-diverter stents deployed for 99 aneurysms. Aneurysms were predominantly located at the MCA bifurcation (n = 44/95, 44.4%). Parent artery straightening was found to be more pronounced in patients treated with cobalt chromium stents than with nitinol stents (P = .02). In multivariate analysis, parent artery straightening (P = .04) was independently associated with aneurysm occlusion after flow-diverter stent deployment. CONCLUSIONS: The use of flow-diverter stents for distal aneurysms induces a measurable parent artery straightening, which is associated with higher occlusion rates. Parent artery straightening, in our sample, appeared to be more prominent with cobalt chromium stents than with nitinol stents. This work highlights the necessary trade-off between navigability and parent artery straightening and may help tailor the selection of flow-diverter stents to aneurysms and parent artery characteristics.

Background: The Boston criteria are used widely for the noninvasive diagnosis of sporadic cerebral amyloid angiopathy (CAA) and hence clinical decision-making, as well as research in the field. Yet, their exact diagnostic accuracy and validity remain (paradoxically) poorly studied. We performed a meta-analysis to synthesize evidence on the value and accuracy of the Boston criteria in diagnosing probable CAA patients. Methods: In a systematic literature search, we identified studies with extractable data relevant for sensitivity and specificity of probable CAA diagnosis per the magnetic resonance imaging Boston criteria and neuropathological CAA verification. We included studies that have classified patients according to any version of the Boston criteria, based on available brain magnetic resonance imaging blood-sensitive sequences (index test) and had neuropathologic evaluation for CAA presence from brain tissue samples (diagnostic reference standard). Using a hierarchical (multilevel) logistic regression model, we calculated pooled diagnostic test accuracy for probable CAA diagnosis. Results: Seven studies, including 193 patients, 121 with neuropathologically verified CAA versus 72 non-CAA based on neuropathology definition, were included in the meta-analysis. The studies were of low-to-moderate quality and varied in several methodological aspects. The overall pooled sensitivity for probable CAA diagnosis was 66.7% (95% CI, 45.9%–82.6%) and specificity was 88.2% (95% CI, 68.5%–96.3%). A predefined subgroup analysis of 4 studies on Boston criteria v.1.0 (n=151) demonstrated a pooled sensitivity and specificity of 60% (95% CI, 45.1%–72.9%) and 93.1% (95% CI, 81.8%–97.6%), respectively. Five studies had data on Boston criteria v.1.5 (n=123): the pooled sensitivity and specificity for probable CAA diagnosis was 73.1% (95% CI, 45%–90.1%) and 86% (95% CI, 41.4%–98.1%), respectively. Conclusions: The Boston criteria v.1.0 and v.1.5 appear to have moderate-to-good diagnostic accuracy for probable CAA in symptomatic patients, with high specificity but low-to-moderate sensitivity. Data are based on limited retrospective studies of overall low quality and at high risk of bias.

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments. MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (α(K)) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests. RESULTS: Interrater agreement was substantial (α(K) = 0.63; 95% CI, 0.55–0.70); results were slightly better for MRA results of coiling (α(K) = 0.69; 95% CI, 0.56–0.76) than for CTA results of clipping (α(K) = 0.58; 95% CI, 0.44–0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (α(K) = 0.49; 95% CI, 0.32–0.61) and coiled subgroups (α(K) = 0.47; 95% CI, 0.34–0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01). CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.

Machine Learning (ML) has been proposed for tissue fate prediction after acute ischemic stroke (AIS), with the aim to help treatment decision and patient management. We compared three different ML models to the clinical method based on diffusion-perfusion thresholding for the voxel-based prediction of final infarct, using a large MRI dataset obtained in a cohort of AIS patients prior to recanalization treatment. Baseline MRI (MRI0), including diffusion-weighted sequence (DWI) and Tmax maps from perfusion-weighted sequence, and 24-hr follow-up MRI (MRI24h) were retrospectively collected in consecutive 394 patients AIS patients (median age = 70 years; final infarct volume = 28mL). Manually segmented DWI24h lesion was considered the final infarct. Gradient Boosting, Random Forests and U-Net were trained using DWI, apparent diffusion coefficient (ADC) and Tmax maps on MRI0 as inputs to predict final infarct. Tissue outcome predictions were compared to final infarct using Dice score. Gradient Boosting had significantly better predictive performance (median [IQR] Dice Score as for median age, maybe you can replace the comma with an equal sign for consistency 0.53 [0.29–0.68]) than U-Net (0.48 [0.18–0.68]), Random Forests (0.51 [0.27–0.66]), and clinical thresholding method (0.45 [0.25–0.62]) ( P

Background and purpose Recent clinical trials demonstrated the benefit of thrombectomy beyond 6 h based on the automated measurement of infarct volume exclusively with the RAPID software. We aimed to compare eight tools commonly used for the measurement of infarct volume and see whether they would lead to similar thrombectomy decisions based on the Diffusion-weighted-imaging or computerized-tomography-perfusion Assessment with clinical mismatch in the triage of Wake-up and late-presenting strokes undergoing Neurointervention with Trevo (DAWN) trial imaging inclusion criteria. Materials and Methods The diffusion-weighted-imaging (DWI) infarct volume of 36 patients was measured with 3 automated tools (including RAPID) and 5 non-automated tools. The agreement for the measurements of DWI infarct volume and the resulting thrombectomy decisions were assessed with intraclass correlation coefficient (ICC) and Fleiss’ Kappa (K) statistics. Results The correlation for the measurement of DWI infarct volume between all 9 tools was excellent (ICC > 0.8). After dichotomization, agreement was substantial for any of the cut-points used in DAWN trial. Discrepancies involving at least one of the tools for thrombectomy decisions based on DAWN criteria occurred in one third of cases. Compared with RAPID, the use of any other tool for treatment decision based on DAWN criteria would have led to contradictory decisions in 6% to 19% of cases. Conclusion There are several currently available tools for the measurement of DWI infarct volume with excellent correlation. Despite the high agreement demonstrated in our study, frequent discrepancies between measurements in some dichotomized configurations led to frequent diverging thrombectomy decisions when applying DAWN criteria.

Background and Purpose: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children. Methods: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King’s Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5. Results: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; P =0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04–217]; P =0.048). sHE was independently associated with poor outcome (King’s Outcome Scale for Childhood Head Injury P =0.043). Conclusions: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.

Although the left ventricular assist device is an important bridge to heart transplantation for patients with end-stage heart failure, it can also be a source of embolic stroke. We present a case of late intracranial mechanical thrombectomy performed for embolic stroke beyond the recommended 6 h, thus allowing for heart transplantation 4 days after intracranial mechanical thrombectomy. (Level of Difficulty: Advanced.), Central Illustration

No controlled pharmacological studies are available in the field of pediatric stroke, except for sickle cell disease. Therefore, while pharmacological and mechanical recanalization treatments have repeatedly shown clinical benefit in adults with arterial ischemic stroke, pediatric strokologists still cannot base their therapeutic management (including hyperacute strategies) on high-level evidence. Once again, pediatricians face the same dichotomic choice: adapting adult procedures now versus waiting—for a long time—for the corresponding pediatric trials. One way out is building a compromise based on observational studies with large, longitudinal, comprehensive, real-life, and multisource dataset. Two recent high-quality observational studies have delivered promising conclusions on recanalization treatments in pediatric arterial ischemic stroke. TIPSTER (Thrombolysis in Pediatric Stroke Extended Results) showed that the risk of severe intracranial hemorrhage after intravenous thrombolysis is low; the Save Childs Study reported encouraging data about pediatric thrombectomy. Beyond the conclusion of a satisfactory global safety profile, a thorough analysis of the methods, populations, results, and therapeutic complications of these studies helps us to refine indications/contraindications and highlights the safeguards we need to rely on when discussing thrombolysis and thrombectomy in children. In conclusion, pediatric strokologists should not refrain from using clot lysis/retrieval tools in selected children with arterial ischemic stroke. But the implementation of hyperacute care is only feasible if the right candidate is identified through the sharing of common adult/pediatric protocols and ward collaboration, formalized well before the child’s arrival. These anticipated protocols should never undervalue contraindications from adult guidelines and must involve the necessary pediatric expertise when facing specific causes of stroke, such as focal cerebral arteriopathy of childhood.

International audience; Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.

In patients undergoing mechanical thrombectomy, achieving complete (Thrombolysis in Cerebral Infarction 3) rather than incomplete successful reperfusion (Thrombolysis in Cerebral Infarction 2b) is associated with better functional outcome. Despite technical improvements, incomplete reperfusion remains the final angiographic result in 40% of patients according to recent trials. As most incomplete reperfusions are caused by distal vessel occlusions, they are potentially amenable to rescue strategies. While observational data suggest a net benefit of up to 20% in functional independence of incomplete versus complete reperfusions, the net benefit of secondary improvement from Thrombolysis in Cerebral Infarction 2b to 3 reperfusion might differ due to lengthier procedures and delayed reperfusion. Current strategies to tackle distal vessel occlusions consist of distal (microcatheter) aspiration, small adjustable stent retrievers, and administration of intra-arterial thrombolytics. While there are promising reports evaluating those techniques, all available studies show relevant limitations in terms of selection bias, single-center design, or nonconsecutive patient inclusion. Besides an assessment of risks associated with rescue maneuvers, we advocate that the decision-making process should also include a consideration of potential outcomes if complete reperfusion would successfully be achieved. These include (1) a futile angiographic improvement (hypoperfused territory is already infarcted), (2) an unnecessary angiographic improvement (the patient would not have developed infarction if no rescue maneuver was performed), and (3) a successful rescue maneuver with clinical benefit. Currently there is paucity of data on how these scenarios can be predicted and the decision whether to treat or to stop in a patient with incomplete reperfusion involves many unknowns. To advance the status quo, we outline current knowledge gaps and avenues of potential research regarding this clinically important question.

Points essentiels Les acouphenes pulsatiles sont a distinguer des acouphenes continus non pulsatiles car ils sont dans la plupart des cas d’origine vasculaire et curables. Un bilan ORL est essentiel dans la prise en charge d’un acouphene mais un acouphene pulsatile necessite egalement un bilan d’imagerie vasculaire et l’avis d’un neuroradiologue interventionnel. Lorsque la manœuvre de compression vasculaire cervicale modifie l’acouphene pulsatile, elle prouve l’origine vasculaire de l’acouphene. L’arteriographie cerebrale n’est plus l’examen d’imagerie a realiser en premiere intention pour un bilan d’acouphene pulsatile. Elle reste neanmoins necessaire lorsque l’on envisage un geste therapeutique. Le retentissement fonctionnel de l’acouphene est determinant pour poser l’indication d’un geste endovasculaire.

BACKGROUND AND PURPOSE: Whether architectural characteristics of ruptured brain AVMs vary across the life span is unknown. We aimed to identify angioarchitectural features associated with brain AVMs ruptured early in life. MATERIALS AND METHODS: Patients with ruptured brain AVMs referred to 2 distinct academic centers between 2000 and 2018 were pooled and retrospectively analyzed. Imaging was retrospectively reviewed for angioarchitectural characteristics, including nidus size, location, Spetzler-Martin grade, venous drainage, and arterial or nidal aneurysm. Angioarchitecture variations across age groups were analyzed using uni- and multivariable models; then cohorts were pooled and analyzed using Kaplan-Meier and Cox models to determine factors associated with earlier rupture. RESULTS: Among 320 included patients, 122 children (mean age, 9.8 ± 3.8 years) and 198 adults (mean age, 43.3 ± 15.7 years) were analyzed. Pediatric brain AVMs were more frequently deeply located (56.3% versus 21.2%, P

ObjectiveTo determine whether MRI-based cerebral small vessel disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous intracerebral hemorrhage (ICH).MethodsWe analyzed data from ICH survivors enrolled in a single-center prospective study. We employed 3 validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)–specific, and hypertensive arteriopathy (HTNA)–specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores' cutoffs to maximize predictive performance for dementia diagnosis.ResultsWe enrolled 612 ICH survivors, and followed them for a median of 46.3 months (interquartile range 35.5–58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (coefficient −0.25, standard error [SE] 0.02) and dementia risk (sub–hazard ratio 1.35, 95% confidence interval 1.10–1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all p < 0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (area under the curve [AUC] 0.89, SE 0.02 vs AUC 0.81, SE 0.03, p = 0.008 for comparison). Global CSVD scores ≥2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis.ConclusionsA validated MRI-based CSVD score is associated with cognitive performance after ICH and improved diagnostic accuracy for predicting new onset of dementia.

Supplemental Digital Content is available in the text., Background and Purpose: Post hoc analyses of randomized controlled clinical trials evaluating mechanical thrombectomy have suggested that admission-to-groin-puncture (ATG) delays are associated with reduced reperfusion rates. Purpose of this analysis was to validate this association in a real-world cohort and to find associated factors and confounders for prolonged ATG intervals. Methods: Patients included into the BEYOND-SWIFT cohort (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the Solitaire FR With the Intention for Thrombectomy; https://www.clinicaltrials.gov; Unique identifier: NCT03496064) were analyzed (n=2386). Association between baseline characteristics and ATG was evaluated using mixed linear regression analysis. The effect of increasing symptom-onset-to-admission and ATG intervals on successful reperfusion (defined as Thrombolysis in Cerebral Infarction [TICI] 2b-3) was evaluated using logistic regression analysis adjusting for potential confounders. Results: Median ATG was 73 minutes. Prolonged ATG intervals were associated with the use of magnetic resonance imaging (+19.1 [95% CI, +9.1 to +29.1] minutes), general anesthesia (+12.1 [95% CI, +3.7 to +20.4] minutes), and borderline indication criteria, such as lower National Institutes of Health Stroke Scale, late presentations, or not meeting top-tier early time window eligibility criteria (+13.8 [95% CI, +6.1 to +21.6] minutes). There was a 13% relative odds reduction for TICI 2b-3 (adjusted odds ratio [aOR], 0.87 [95% CI, 0.79–0.96]) and TICI 2c/3 (aOR, 0.87 [95% CI, 0.79–0.95]) per hour ATG delay, while the reduction of TICI 2b-3 per hour increase symptom-onset-to-admission was minor (aOR, 0.97 [95% CI, 0.94–0.99]) and inconsistent regarding TICI 2c/3 (aOR, 0.99 [95% CI, 0.97–1.02]). After adjusting for identified factors associated with prolonged ATG intervals, the association of ATG delay and lower rates of TICI 2b-3 remained tangible (aOR, 0.87 [95% CI, 0.76–0.99]). Conclusions: There is a great potential to reduce ATG, and potential targets for improvement can be deduced from observational data. The association between in-hospital delay and reduced reperfusion rates is evident in real-world clinical data, underscoring the need to optimize in-hospital workflows. Given the only minor association between symptom-onset-to-admission intervals and reperfusion rates, the causal relationship of this association warrants further research. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064.

Background and Purpose Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0–3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusions In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations.METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy.FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard.INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations.FUNDING: US National Institutes of Health (R01 AG26484).

The aim was to assess the occurrence of magnetic susceptibility artifacts (MSA) following endovascular treatment of intracranial aneurysm by stent using susceptibility weighted imaging (SWI). Imaging and clinical data of 46 patients who underwent stent placement in the case of intracranial aneurysm endovascular treatment (S-Group) were retrospectively analyzed and compared to a control group (C-Group) in which 46 patients had coiling alone. The mean number of MSA was higher in the S-group than in the C-group on postprocedural SWI sequence (8.76, 95%CI [5.76, 11.76] vs. 0.78 [0.32, 1.25], respectively, p &lt, 0.001) with a higher frequency of the appearance of MSA also in the S-group (78.26% vs. 21.74% in the C-group, p &lt, 0.001). In the S-group, in the vascular territory of the treated artery, there was a higher number of MSA than in other vascular territories (mean of 5.18 [3.43, 6.92] vs. 3.08 [1.79, 4.36], p = 0.001). An odds ratio (OR) of 20.98 [5.24, 83.95] suggested a higher proportion of onset of MSA in the S-group than in the C-group (p &lt, 0.001). The appearance of MSA after a treatment by stenting for intracranial aneurysm in patients under antiplatelet therapy was common, particularly in the treated artery territory.

The benefit of acute ischemic stroke (AIS) treatment is highly time dependent. Although studies on workflow improvement in AIS are increasingly gaining attention, there is a lack of consensus and consistency regarding the definition, measurement, and reporting of AIS workflow times. We discuss the challenges related to defining and measuring workflow times in AIS and propose a basic set of time intervals that should be reported in AIS workflow studies. We particularly focus on patients undergoing mechanical thrombectomy. Importantly, endovascular treatment workflow times should always be reported in conjunction with reperfusion quality because one is not informative without the other. We further suggest standardized reporting of workflow times that includes the 90th percentile in addition to medians and interquartile ranges, means, and SDs. The proposed methodology serves as a framework for AIS studies and aids further discussion on workflow‐related AIS research.

BACKGROUND The aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH). METHODS A single-centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6 h from onset (T0) and at 7 days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. Poor functional prognosis (modified Rankin Scale 3-6) at 90 days was the outcome of interest, and predictors were explored with multivariable logistic regression. RESULTS A total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3-6 at 90 days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change -7.8 vs. -6.0 ml/100 g/min, p

International audience; No abstract available

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Background Diagnosing probable cerebral amyloid angiopathy (CAA) after lobar intra-cerebral hemorrhage (l-ICH) currently relies on the MR-based modified Boston criteria (mBC). However, MRI has limited availability and the mBC have moderate sensitivity, with isolated l-ICH being classified as “possible CAA”. A recent autopsy-based study reported potential value of finger-like projections (FLP) and subarachnoid hemorrhage (SAH) on acute CT. Here we assessed these markers’ performance in a cohort most of whom survived the index episode. Methods We included all patients from a prospective pathology database with non-traumatic l-ICH, admission CT and available tissue sample showing no alternative cause. CT was assessed by two blinded independent neuroradiologists. Interobserver reproducibility was almost perfect for SAH and substantial for FLP. Results Sixteen patients were eligible [age 65.8 ± 7.2 yrs; hematoma volume: 39(26, 71)mls; hematoma evacuation sample 15 patients; autopsy one patient]. MRI was available in 11 patients. ICH-related death affected six patients. Aβ40–42 immunohistochemistry revealed CAA in seven patients (44%). SAH and FLP were present in 12/16 (75%) and 10/16 (62%) patients, respectively. SAH had 100% sensitivity for CAA but low specificity; FLP had lower performance. Using either pathology or MRI as reference standard yielded essentially similar results. All patients with possible CAA on MRI but CAA on pathology had SAH. Conclusions In patients with moderate-size l-ICH who mostly survived the index event, SAH had perfect sensitivity and better performance than FLP. In addition, SAH appeared to add onto MRI in possible CAA, the clinically most relevant scenario. Studies in larger samples are however warranted.

Background and Purpose— Hematoma location within the cerebellum may help identify the dominant small vessel disease type (cerebral amyloid angiopathy [CAA] versus nonamyloid small vessel disease). However, it is unknown whether this holds true for cerebral microbleeds (CMBs) within the cerebellum. We tested the hypothesis that cerebellar CMBs restricted to the cortex and vermis (defined as superficial regions) are associated with clinically diagnosed and pathology-verified CAA. Methods— Three hundred and seven consecutive spontaneous intracerebral hemorrhage (ICH) patients with a baseline magnetic resonance imaging that included susceptibility-weighted imaging or angiography were enrolled. Using a topographical template, cerebellar CMB patterns were defined as strictly superficial versus deep (cerebellar gray nuclei and white matter) or mixed (both regions involved). Thirty-six ICH patients with cerebellar CMBs and neuropathology data available were evaluated for the presence of CAA. Results— One hundred and thirty-five (44%) ICH patients had CMBs in the cerebellum. In the patient group with cerebellar CMBs, 85 (63%) showed a superficial pattern, and 50 (37%) had a deep/mixed pattern. Strictly superficial cerebellar CMBs were independently associated with a supratentorial pattern of probable CAA-ICH according to the Boston criteria (odds ratio, 1.6; CI, 1.03–2.5) and deep/mixed cerebellar CMBs with a pattern of deep/mixed ICH (odds ratio, 1.8; CI, 1.2–2.7). Pathologically verified CAA was present in 23 of 24 (96%) patients with superficial cerebellar CMBs versus 3 of 12 (25%) patients with deep/mixed cerebellar CMBs ( P Conclusions— In ICH patients, cerebellar CMBs are relatively common and often restricted to superficial regions. A strictly superficial distribution of cerebellar CMBs is associated with clinically diagnosed and pathologically verified CAA.

Background and Purpose— Mechanisms contributing to acute hematoma growth in intracerebral hemorrhage are not well understood. Neuropathological studies suggest that the initial hematoma may create mass effect that can tear vessels in the vicinity by shearing, causing further bleeding and hematoma growth. Methods— To test this in mice, we simulated initial intracerebral hemorrhage by intrastriatal injection of a liquid polymer that coagulates upon contact with tissue and measured the presence and volume of bleeding secondary to the mass effect using Hemoglobin ELISA 15 minutes after injection. Results— Secondary hemorrhage occurred in a volume-dependent (4, 7.5, or 15 μL of polymer) and rate-dependent (0.05, 0.5, or 5 μL/s) manner. Anticoagulation (warfarin or dabigatran) exacerbated the secondary hemorrhage volume. In a second model of hematoma expansion, we confirmed that intrastriatal whole blood injection (15 μL, 0.5 μL/s) also caused secondary bleeding, using acute Evans blue extravasation as a surrogate. Anticoagulation once again exacerbated secondary hemorrhage after intrastriatal whole blood injection. Secondary hemorrhage directly and significantly correlated with arterial blood pressures in both nonanticoagulated and anticoagulated mice, when modulated by phenylephrine or labetalol. Conclusions— Our study provides the first proof of concept for secondary vessel rupture and bleeding as a potential mechanism for intracerebral hematoma growth.

Background and Purpose— We investigated cortical superficial siderosis (cSS) progression and its clinical relevance for incident lobar intracerebral hemorrhage (ICH) risk, in probable cerebral amyloid angiopathy presenting with neurological symptoms and without ICH at baseline. Methods— Consecutive patients meeting modified Boston criteria for probable cerebral amyloid angiopathy from a single-center cohort who underwent magnetic resonance imaging (MRI) at baseline and during follow-up were analyzed. cSS progression was assessed by comparison of the baseline and follow-up images. Patients were followed prospectively for incident symptomatic ICH. cSS progression and first-ever ICH risk were investigated in Cox proportional hazard models adjusting for confounders. Results— The cohort included 118 probable cerebral amyloid angiopathy patients: 72 (61%) presented with transient focal neurological episodes and 46 (39%) with cognitive complaints prompting the baseline MRI investigation. Fifty-two patients (44.1%) had cSS at baseline. During a median scan interval of 2.2 years (interquartile range, 1.2–4.4 years) between the baseline (ie, first) MRI and the latest MRI, cSS progression was detected in 33 (28%) patients. In multivariable logistic regression, baseline cSS presence (odds ratio, 4.04; 95% CI, 1.53–10.70; P =0.005), especially disseminated cSS (odds ratio, 9.12; 95% CI, 2.85–29.18; P P =0.017) were independent predictors of cSS progression. For patients without an ICH during the interscan interval (n=105) and subsequent follow-up (median postfinal MRI time, 1.34; interquartile range, 0.3–3 years), cSS progression independently predicted increased symptomatic ICH risk (hazard ratio, 3.76; 95% CI, 1.37–10.35; P =0.010). Conclusions— Our results suggest that cSS evolution may be a useful biomarker for assessing disease progression and ICH risk in cerebral amyloid angiopathy patients and a candidate biomarker for clinical studies and trials.

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

OBJECTIVE Rupture of brain arteriovenous malformation (AVM) is the main etiology of intracerebral hemorrhage (ICH) in children. Ensuing intracranial hypertension is among the modifiable prognosis factors and sometimes requires emergency hemorrhage evacuation (HE). The authors aimed to analyze variables associated with HE in children with ruptured AVM. METHODS This study was a single-center retrospective analysis of children treated for ruptured AVM. The authors evaluated the occurrence of HE, its association with other acute surgical procedures (e.g., nidal excision, decompressive hemicraniectomy), and clinical outcome. Variables associated with each intervention were analyzed using univariable and multivariable models. Clinical outcome was assessed at 18 months using the ordinal King’s Outcome Scale for Childhood Head Injury. RESULTS A total of 104 patients were treated for 112 episodes of ruptured AVM between 2002 and 2018. In the 51 children (45.5% of cases) who underwent HE, 37 procedures were performed early (i.e., within 24 hours after initial cerebral imaging) and 14 late. Determinants of HE were a lower initial Glasgow Coma Scale score (adjusted odds ratio [aOR] 0.83, 95% CI 0.71–0.97 per point increase); higher ICH/brain volume ratio (aOR 18.6, 95% CI 13–26.5 per percent increase); superficial AVM location; and the presence of a brain herniation (aOR 3.7, 95% CI 1.3–10.4). Concurrent nidal surgery was acutely performed in 69% of Spetzler-Martin grade I–II ruptured AVMs and in 25% of Spetzler-Martin grade III lesions. Factors associated with nidal surgery were superficial AVMs, late HE, and absent alteration of consciousness at presentation. Only 8 cases required additional surgery due to intracranial hypertension. At 18 months, overall mortality was less than 4%, 58% of patients had a favorable outcome regardless of surgical intervention, and 87% were functioning independently. CONCLUSIONS HE is a lifesaving procedure performed in approximately half of the children who suffer AVM rupture. The good overall outcome justifies intensive initial management.

International audience; Background and purpose: Collateral status and thrombus length have been independently associated with functional outcome in patients with acute ischemic stroke. It has been suggested that thrombus length would influence functional outcome via interaction with the collateral circulation. We investigated the individual and combined effects of thrombus length assessed by the clot burden score and collateral status assessed by a FLAIR vascular hyperintensity-ASPECTS rating system on functional outcome (mRS).Materials and methods: Patients with anterior circulation acute ischemic stroke due to large-vessel occlusion from the ASTER and THRACE trials treated with endovascular thrombectomy were pooled. The clot burden score and FLAIR vascular hyperintensity score were determined on MR imaging obtained before endovascular thrombectomy. Favorable outcome was defined as an mRS score of 0-2 at 90 days. Association of the clot burden score and the FLAIR vascular hyperintensity score with favorable outcome (individual effect and interaction) was examined using logistic regression models.Results: Of the 326 patients treated by endovascular thrombectomy with both the clot burden score and FLAIR vascular hyperintensity assessment, favorable outcome was observed in 165 (51%). The rate of favorable outcome increased with clot burden score (smaller clots) and FLAIR vascular hyperintensity (better collaterals) values. The association between clot burden score and functional outcome was significantly modified by the FLAIR vascular hyperintensity score, and this association was stronger in patients with good collaterals, with an adjusted OR = 6.15 (95% CI, 1.03-36.81).Conclusions: The association between the clot burden score and functional outcome varied for different collateral scores. The FLAIR vascular hyperintensity score might be a valuable prognostic factor, especially when contrast-based vascular imaging is not available.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy–mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy–mild cognitive impairment and non-cerebral amyloid angiopathy–mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy–mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy–mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy–mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

Intracerebral hemorrhage (ICH) accounts for 10% to 20% of all strokes worldwide and is associated with high morbidity and mortality. Neuroimaging is clinically important for the rapid diagnosis of ICH and underlying etiologies, but also for identification of ICH expansion, often as-sociated with an increased risk for poor outcome. In this context, rapid assessment of early hema-toma expansion risk is both an opportunity for therapeutic intervention and a potential hazard for hematoma evacuation surgery. In this review, we provide an overview of the current literature surrounding the use of multimodal neuroimaging of ICH for etiological diagnosis, prediction of early hematoma expansion, and prognostication of neurological outcome. Specifically, we discuss standard imaging using computed tomography, the value of different vascular imaging modalities to identify underlying causes and present recent advances in magnetic resonance imaging and computed tomography perfusion.

ObjectiveTo investigate the prevalence, predictors, and prognostic effect of hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) with unclear symptom onset (USO).MethodsWe performed a retrospective analysis of patients with primary spontaneous ICH admitted at 5 academic medical centers in the United States and Italy. HE (volume increase >6 mL or >33% from baseline to follow-up noncontrast CT [NCCT]) and mortality at 30 days were the outcomes of interest. Baseline NCCT was also analyzed for presence of hypodensities (any hypodense region within the hematoma margins). Predictors of HE and mortality were explored with multivariable logistic regression.ResultsWe enrolled 2,165 participants, 1,022 in the development cohort and 1,143 in the replication cohort, of whom 352 (34.4%) and 407 (35.6%) had ICH with USO, respectively. When compared with participants having a clear symptom onset, patients with USO had a similar frequency of HE (25.0% vs 21.9%, p = 0.269 and 29.9% vs 31.5%, p = 0.423). Among patients with USO, HE was independently associated with mortality after adjustment for confounders (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.43–4.89, p = 0.002). This finding was similar in the replication cohort (OR 3.46, 95% CI 1.86–6.44, p < 0.001). The presence of NCCT hypodensities in patients with USO was an independent predictor of HE in the development (OR 2.59, 95% CI 1.27–5.28, p = 0.009) and replication (OR 2.43, 95% CI 1.42–4.17, p = 0.001) population.ConclusionHE is common in patients with USO and independently associated with worse outcome. These findings suggest that patients with USO may be enrolled in clinical trials of medical treatments targeting HE.

ObjectiveIndividualized patient selection for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large ischemic core (LIC) at baseline is an unmet need. We tested the hypothesis that assessing the functional relevance of both infarcted and hypoperfused brain tissue would improve the selection framework of patients with LIC for MT.MethodsWe performed a multicenter, retrospective study of adults with LIC (ischemic core volume >70 mL on MRI diffusion-weighted imaging) with MRI perfusion treated with MT or best medical management (BMM). Primary outcome was 3-month modified Rankin Scale (mRS), favorable if 0–3. Global and regional eloquence-based core perfusion mismatch ratios were derived. The predictive accuracy for clinical outcome of eloquent regions involvement was compared in multivariable and bootstrap random forest models.ResultsA total of 138 patients with baseline LIC were included (MT n = 96 or BMM n = 42; mean age ± SD, 72.4 ± 14.4 years; 34.1% female; mRS 0–3: 45.1%). Mean core and critically hypoperfused volume were 100.4 mL ± 36.3 mL and 157.6 ± 56.2 mL, respectively, and did not differ between groups. Models considering the functional relevance of the infarct location showed a better accuracy for the prediction of mRS 0–3 with a c statistic of 0.76 and 0.83 for logistic regression model and bootstrap random forest testing sets, respectively. In these models, the interaction between treatment effect of MT and the mismatch was significant (p = 0.04). In comparison, in the logistic regression model disregarding functional eloquence, the c statistic was 0.67 and the interaction between MT and the mismatch was insignificant.ConclusionsConsidering functional eloquence of hypoperfused tissue in patients with a large infarct core at baseline allows for a more precise estimation of treatment expected benefit.Classification of EvidenceThis study provides Class II evidence that, in patients with AIS and LIC, considering the functional eloquence of the infarct location improves prediction of disability status at 3 months.

BackgroundIn acute ischemic stroke due to anterior large vessel occlusion (AIS-LVO), accessing the target occluded vessel for mechanical thrombectomy (MT) is sometimes impossible through the femoral approach. We aimed to evaluate the safety and efficacy of direct carotid artery puncture (DCP) for MT in patients with failed alternative vascular access.MethodsWe retrospectively analyzed data from 45 stroke centers in France, Switzerland and Germany through two research networks from January 2015 to July 2019. We collected physician-centered data on DCP practices and baseline characteristics, procedural variables and clinical outcome after DCP. Uni- and multivariable models were conducted to assess risk factors for complications.ResultsFrom January 2015 to July 2019, 28 149 MT were performed, of which 108 (0.39%) resulted in DCP due to unsuccessful vascular access. After DCP, 77 patients (71.3%) had successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b) and 28 (25.9%) were independent (modified Rankin Scale (mRS) score 0–2) at 3 months. 20 complications (18.5%) attributed to DCP occurred, all of them during or within 1 hour of the procedure. Complications led to extension of the intubation time in the intensive care unit in 7 patients (6.4%) and resulted in death in 3 (2.8%). The absence of use of a hemostatic closure device was associated with a higher complication risk (OR 3.04, 95% CI 1.03 to 8.97; p=0043).ConclusionIn this large multicentric study, DCP was scantly performed for vascular access to perform MT (0.39%) in patients with AIS-LVO and had a high rate of complications (18.5%). Our results provide arguments for not closing the cervical access by manual compression after MT.

ObjectiveTo describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.MethodsIn this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.ResultsThe cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20–92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome (p= 0.006) and more frequently had corticospinal tract signs (p= 0.02). Patients with encephalitis were younger (p= 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p= 0.009).ConclusionsPatients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.ClinicalTrials.gov identifierNCT04368390.

International audience; Intracranial vasculopathies are routinely investigated by lumen-based modalities such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), and digital subtraction angiography (DSA). These techniques are useful to analyze the vessel lumen, allowing to detect vessel stenosis or occlusion. However, the primum movins of the disease, i.e., an abnormal thickening of the vessel wall, remains within the arterial wall. The vasculopathy can moreover be present without always narrowing the lumen or modifying its regularity. Hence, there is a need to detect directly and analyze vessel wall abnormalities. Development of 3D high-resolution black blood sequences for intracranial vessel wall MR imaging (VW-MRI) enabled routine clinical applications not only vasculitis, but also of intracranial atherosclerotic disease (ICAD), intracranial dissections, reversible intracranial dissections, reversible cerebral vasoconstriction syndrome (RCVS), Moyamoya disease, and intracranial aneurysms. This high-resolution intracranial VW- MRI approach is increasingly used on a clinical basis at many centers to solve diagnostic problems, especially in patients with ischemic stroke or intracranial hemorrhage. An expert consensus Guideline from the American Society of Neuroradiology provides recommendations for clinical implementation of intracranial vessel wall MRI. There are several technical aspects needed to be considered when implementing VW-MRI in intracranial vessels, including flow suppression, both in blood and cerebrospinal fluid (CSF), spatial resolution and signal-to-noise ratio (SNR). In this article, we review the technical aspects of VW-MRI, and recommend applications for vascular diseases including non-occlusive intracranial vasculopathies, Moyamoya disease, and identifying culprit plaques. We also give a focus on the utility of VW-MRI for determining stroke etiology in adults and in children and young adults.

Background and Purpose: Although the efficacy of endovascular treatment (EVT) in patients with anterior circulation ischemic stroke (AIS) is well documented, early neurological deterioration after EVT remains a serious issue associated with poor outcome. Besides obvious causes, such as lack of reperfusion, procedural complications, or parenchymal hemorrhage, early neurological deterioration may remain unexplained (UnEND). Our aim was to investigate predictors of UnEND after EVT in patients with AIS. Methods: Patients who underwent EVT for AIS, with an initial National Institutes of Health Stroke Scale score >5, Alberta Stroke Program Early CT Score ≥6, and included in a multicenter prospective observational registry were analyzed. Predictors of UnEND, defined as ≥4-point increase in the National Institutes of Health Stroke Scale score between baseline and day 1 after EVT, were determined via center-adjusted analyses. Results: Among the 1925 included in the analysis, 128 UnEND (6.6%) were recorded. In multivariate analysis, predictors of UnEND were diabetes mellitus (odds ratio [OR], 2.17 [95% CI, 1.32–3.56]), prestroke modified Rankin Scale score ≥2 (OR, 2.22 [95% CI, 1.09–4.55]), general anesthesia (OR, 2.55 [95% CI, 1.51–4.30]), admission systolic blood pressure (OR, 1.10 [95% CI, 1.01–1.20]), age (OR, 1.38 [95% CI, 1.14–1.67]), number of passes (OR, 1.16 [95% CI, 1.04–1.28]), direct admission or not to a comprehensive stroke center (OR, 0.49 [95% CI, 0.30–0.81]), and initial National Institutes of Health Stroke Scale score (OR, 0.65 [95% CI, 0.52–0.81]). Conclusions: Severely impaired AIS patients with nonmodifiable factors are more likely to develop UnEND. Some modifiable predictors of UnEND such as the number of EVT passes could be the object of improvement in AIS management.

OBJECTIVEHydrocephalus is a strong determinant of poor neurological outcome after intracerebral hemorrhage (ICH). In children, ruptured brain arteriovenous malformations (bAVMs) are the dominant cause of ICH. In a large prospective cohort of pediatric patients with ruptured bAVMs, the authors analyzed the rates and predictive factors of hydrocephalus requiring acute external ventricular drainage (EVD) or ventriculoperitoneal shunt (VPS).METHODSThe authors performed a single-center retrospective analysis of the data from a prospectively maintained database of children admitted for a ruptured bAVM since 2002. Admission clinical and imaging predictors of EVD and VPS placement were analyzed using univariate and multivariate statistical models.RESULTSAmong 114 patients (mean age 9.8 years) with 125 distinct ICHs due to ruptured bAVM, EVD and VPS were placed for 55/125 (44%) hemorrhagic events and 5/114 patients (4.4%), respectively. A multivariate nominal logistic regression model identified low initial Glasgow Coma Scale (iGCS) score, hydrocephalus on initial CT scan, the presence of intraventicular hemorrhage (IVH), and higher modified Graeb Scale (mGS) score as strongly associated with subsequent need for EVD (all p < 0.001). All children who needed a VPS had initial hydrocephalus requiring EVD and tended to have higher mGS scores.CONCLUSIONSIn a large cohort of pediatric patients with ruptured bAVM, almost half of the patients required EVD and 4.4% required permanent VPS. Use of a low iGCS score and a semiquantitative mGS score as indicators of the IVH burden may be helpful for decision making in the emergency setting and thus improve treatment.

International audience; No abstract available

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 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.

Background: Tenecteplase (TNK) is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase. The recent Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial demonstrated that increased reperfusion with TNK compared to alteplase prior to endovascular thrombectomy (EVT) in large vessel occlusion ischaemic strokes. However, only 6 patients with basilar artery occlusion (BAO) were included. We aimed to investigate the efficacy of TNK versus alteplase before EVT in patients with basilar artery occlusion (BAO). Methods: Clinical and procedural data of consecutive BAO diagnosed on CT Angiography or MR Angiography from the multisite international Basilar Artery Treatment and MANagement (BATMAN) collaboration were retrospectively analysed. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or absence of retrievable thrombus at the time of the initial angiographic assessment. Results: We included 119 BAO patients treated with intravenous thrombolysis prior to EVT; mean age 68 (SD 14), median NIHSS 16 (IQR 7-32). Eleven patients were treated with TNK (0.25mg/kg or 0.4mg/kg) and 108 with alteplase (0.9mg/kg). Overall, 113 patients had catheter angiography or early repeat imaging after thrombolysis. Reperfusion of greater than 50% of the ischemic territory or absence of retrievable thrombus occurred in 4/11 (36%) of patients treated with TNK vs 8/102 (8%) treated with alteplase (p=0.02). Onset-to-needle time did not differ between the two groups (p=0.4). Needle-to-groin-puncture time was 61 (IQR 33-100) mins in patients reperfused with TNK vs 111 (IQR 86-198) mins in patients reperfused with alteplase (p=0.048). Overall, the rate of symptomatic haemorrhage was 3/119 (2.5%). No differences were found in the rate of symptomatic intracranial haemorrhage (p=0.3) between the two thrombolytic agents. Conclusions: Despite shorter needle-to-groin-puncture times, tenecteplase was associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare tenecteplase with alteplase in BAO patients before endovascular thrombectomy are warranted.

Background and Purpose— We aimed to explore the association between presence of cerebral cortical microinfarcts (CMIs) on magnetic resonance imaging and other small-vessel disease neuroimaging biomarkers in cerebral amyloid angiopathy (CAA) and to analyze the role of CMIs on individual cognitive domains and dementia conversion. Methods— Participants were recruited from an ongoing longitudinal research cohort of eligible CAA patients between March 2006 and October 2016. A total of 102 cases were included in the analysis that assessed the relationship of cortical CMIs to CAA neuroimaging markers. Ninety-five subjects had neuropsychological tests conducted within 1 month of magnetic resonance imaging scanning. Seventy-five nondemented CAA patients had cognitive evaluation data available during follow-up. Results— Among 102 patients enrolled, 40 patients had CMIs (39%) on magnetic resonance imaging. CMIs were uniformly distributed throughout the cortex without regional predilection ( P =0.971). The presence of CMIs was associated with lower total brain volume (odds ratio, 0.85; 95% CI, 0.74–0.98; P =0.025) and presence of cortical superficial siderosis (odds ratio, 2.66; 95% CI, 1.10–6.39; P =0.029). In 95 subjects with neuropsychological tests, presence of CMIs was associated with impaired executive function (β, −0.23; 95% CI, −0.44 to −0.02; P =0.036) and processing speed (β, −0.24; 95% CI, −0.45 to −0.04; P =0.020). Patients with CMIs had a higher cumulative dementia incidence compared with patients without CMIs ( P =0.043), whereas only baseline total brain volume (hazard ratio, 0.76; 95% CI, 0.62–0.92; P =0.006) independently predicted dementia conversion. Conclusions— Magnetic resonance imaging–detected CMIs in CAA correlated with greater overall disease burden. The presence of CMIs was associated with worse cognitive performance, whereas only total brain atrophy independently predicted dementia conversion.