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Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network connections. Brain networks were reconstructed from diffusion-weighted MRI scans in 72 individuals (75 ± 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non-central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non-central network connections (r = 0.41 vs. r = 0.27; P 50%–10% connections). Higher SVD burden was associated with lower FA in central as well as non-central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): −0.15 (−0.35 to −0.02)]. The mediation effect was not observed for FA alterations in non-central network connections [−0.03 (−0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. Hum Brain Mapp 37:2446–2454, 2016.

Background and Purpose— We aimed to identify prognostic and associated factors of incident cerebral microbleeds (CMBs) in intracerebral hemorrhage (ICH) survivors. Methods— Observational prospective cohort of 168 ICH survivors who underwent 1.5T magnetic resonance imaging at ICH onset and during follow-up (median scan interval, 3.4; interquartile range, 1.4–4.7) years. We used logistic regression adjusted for age, sex, and scan interval. Analyses were stratified according to the index ICH location (58 lobar ICH, 103 nonlobar ICH, excluding patients with multiple or unclassifiable ICH). Results— Eighty-nine (53%) patients had CMBs at ICH onset, and 80 (48%) exhibited incident CMBs during follow-up. Predictors of incident CMBs at ICH onset were ≥1 CMBs (adjusted odds ratio [aOR], 2.27; 95% confidence interval [CI], 1.18–4.35), old radiological macrohemorrhage (aOR, 6.78; 95% CI, 2.76–16.68), and CMBs in mixed location (aOR, 3.73; 95% CI, 1.67–8.31). When stratifying by ICH location, incident CMBs were associated in nonlobar ICH with incident lacunes (aOR, 2.86; 95% CI, 1.04–7.85) and with the use of antiplatelet agents (aOR, 2.89; 95% CI, 1.14–7.32). In lobar ICH, incident CMBs were associated with incident radiological macrohemorrhage (aOR, 9.76; 95% CI, 1.07–88.77). Conclusions— Prognostic and associated factors of incident CMBs differed according to the index ICH location. Whereas in lobar ICH, incident CMBs were associated with hemorrhagic biomarkers, in nonlobar ICH, ischemic burden also increased. CMBs may be interesting biomarkers to monitor in randomized trials on restarting antithrombotic drugs after ICH.

Identifying extra spinal causes of a lumbar radiculopathy or polyneuropathy can be a tricky diagnosis challenge, especially in children. Among them, traumatic or iatrogenic pseudoaneurysms of iliac arteries have been seldom reported, in adults' series. The authors report an unusual case of progressive paralyzing left sciatica and lumbar plexopathy in a 12 years old boy, 12 months after a pelvic osteotomy for bilateral hip luxation secondary to osteochondritis dissecans. Spine MRI and pelvic CT angiography revealed a giant internal iliac artery pseudoaneurysm, enclosed in a chronic hematoma. The patient was successfully treated with endovascular coil embolization, and subsequent surgical hematoma evacuation. However, three months after treatment, neurological recovery was incomplete. This case highlights the importance of a rapid and extensive diagnosis work up of all causes of lower limb radiculopathies in children, including pelvic arteries lesions especially after pelvic surgery to avoid therapeutic delays that may jeopardize the chances of neurological recovery.

Objectifs Le fait que les caracteristiques angio-architecturales des malformations arterio-veineuses cerebrales (MAVc) rompues puissent variees au cours de la vie est inconnu [1] , [2] . Notre objectif etait d’identifier les caracteristiques associees a une rupture precoce des MAVc. Materiel et methodes Les patients ayant une MAVc rompue referee dans deux centres academiques distincts entre 2000 et 2018 ont ete inclus retrospectivement. L’imagerie a ete retrospectivement evaluee a la recherche de caracteristiques angio-architecturales incluant, la taille du nidus, la localisation, le grade de Spetzler–Martin, le drainage veineux et la presence d’anevrysme intra ou pre-nidaux. Les variations de l’angio-architecture au travers des groupes d’âge ont ete analysees en utilisant des modeles uni- et multivaries puis les cohortes ont ete groupees et analysees en utilisant des modeles Kaplan–Meier et Cox afin de determiner les facteurs associes avec une rupture precoce. Resultats Sur les 320 patients inclus, 122 enfants (moyenne d’âge ± SD : 9.8 ± 3.8 ans) et 198 adultes (43.3 ± 15.7 ans) ont ete analyse. Les MAVc pediatriques etaient plus frequemment profondes (56.3 % vs 21.2 %, p Tableau 1 ) ( Fig. 1 ). Conclusion L’angio-architecture des MAVc rompues varie significativement au cours de la vie et la presence de certaines caracteristiques pourraient orienter vers une prise en charge therapeutique chez les patients avec une MAVc rompue.

Objectif La thrombectomie mecanique (TM) est recemment devenue, en association avec la thrombolyse intraveineuse, le traitement de reference des accidents ischemiques cerebraux (AIC) a la phase aigue avec occlusion d’une artere de gros calibre. Malgre un taux de reperfusion eleve, le taux d’echec de la TM peut s’elever jusqu’a 15 % des cas. Parmi les facteurs source d’echec de TM, la nature du caillot semble avoir une part importante. Les emboles calciques (EC), survenant le plus souvent au decours d’interventions cardiovasculaires, font partie de ces caillots refractaires. L’objectif de l’etude Mechanical Thrombectomy in Acute Ischemic Stroke Related to Calcic Emboli (MASC) est de constituer un registre national permettant d’analyser l’incidence des EC traites par TM, ainsi que l’efficacite, en terme de reperfusion et d’evolution neurologique favorable, de la TM dans cette indication. Materiel et methode L’etude MASC est un registre retrospectif multicentrique, qui vise a colliger l’ensemble des patients adultes (≥ 18 ans) ayant beneficie en France d’une TM pour un AIC lie a l’occlusion d’une artere intracrânienne de gros calibre, en rapport avec un EC de janvier 2015 a septembre 2019. Les donnees demographiques, score NIHSS pre-TM, contexte de l’AIC vont etre colligees via un questionnaire standardise envoye aux 37 centres de neuroradiologie interventionnelle (NRI) francais. Le taux de reperfusion, defini comme un score modified Thrombolysis In Cerebral Infarction (mTICI) ≥ 2B, le taux de complication (hematomes intracrâniens, emboles dans un autre territoire) ainsi que l’evolution neurologique (definie comme favorable pour un score de Rankin modifie [mRS] ≤ 2) seront egalement systematiquement collectes. Enfin, les strategies utilisees pour ces TM (stent retriever, aspiration, technique combinee ± utilisation d’un catheter a ballon) seront systematiquement recueillies. Resultats Le recueil des donnees est actuellement en cours. Les questionnaires ont ete envoyes aux differents centres de NRI. Conclusion Les emboles calciques sont une entite rare responsable d’AIC avec occlusion d’une artere intracrânienne de gros calibre. Le registre MASC permettra de connaitre la prevalence de ces AIC sur EC, le taux de reperfusion de la TM dans cette indication, la(les) meilleure(s) strategie(s) de reperfusion ainsi que l’evolution clinique de ces patients.

Objectifs Comparer la securite et l’efficacite de la TM chez les patients presentant une occlusion en tandem du tronc basilaire (OTB-t) avec celles des occlusions « non-en tandem » du tronc basilaire (OTB-nt). Materiels et methodes Analyse retrospective d’une base de donnees prospective de 2 centres universitaires (hopitaux universitaires Pitie-Salpetriere et Sainte-Anne, Paris, France). Dix-huit patients avec OTB-t traites par TM ont ete apparies avec 36 patients traites par TM pour OTB-nt sur les facteurs suivants : National Institute of Health Stroke Scale (NIHSS) a l’admission, âge et sexe. Resultats L’âge moyen etait de 60,9 ± 11,7 ans vs 63,6 ± 13,8 ans, (p = 0,96) et le NIHSS median a l’admission etait de 21 (IQR : 10–39) contre 21 (IQR : 9–39 ; p = 0,97) dans les groupes OTB-t et OTB-nt, respectivement. Dans les deux groupes, 77,8 % des patients etaient des hommes ; 55,6 % et 52,8 % des groupes OTB-t et OTB-nt (p = 1,00), respectivement, ont recu une thrombolyse intraveineuse. Une bonne reperfusion, definie comme un score modified Thrombolysis In Cerebral Infarction (mTICI) ≥ 2b a ete obtenue dans 66,7 % et 80,6 % chez les patients avec OTB-t et OTB-nt (p = 0,32 ; OR : IC95 % : 0,48, 0,13–1,74),respectivement. Une evolution neurologique favorable, definie par un score modified Rankin Scale (mRS) (0–2) a 3 mois, a ete observee chez 22,2 % des patients avec OTB-t contre 30,8 % des patients du groupe OTB-nt (p = 0,75 ; OR : IC95 % : 0,65, 0,17–2,43). La mortalite a 3 mois etait de 44,4 % vs 25 % dans les groupes OTB-t et OTB-nt, respectivement, (p = 0,22 ; OR : IC95 % : 2,4, 0,73–7,95). Conclusion Les OTB-t sont des bons candidats a la thrombectomie mecanique, avec une securite et une efficacite du geste similaire a celles des occlusions simples du tronc basilaire ( Fig. 1 ).

Aims and scope Procedural time, quality of reperfusion and number of passes are known prognosis factors for patients with acute ischemic stroke due to large vessel occlusion strokes treated by mechanical thrombectomy (MT) [1] , [2] , [3] . These procedural efficiency metrics are known to vary with various factors, amongst which operator's previous endo-vascular experience as well as center annual procedural volume [4] . We aimed to evaluate amongst trained interventional neuroradiologist (INR), whether increasing experience was associated with an improvement in MT procedural performance metrics. Material and method This retrospective cohort study pooled MT procedural data across 3 high volume academic comprehensive stroke centers. Main study endpoints were duration of procedure, final angiographic recanalisation according to mTICI classification, number of passes, rate of first-pass complete recanalisation and rate of arterial perforation. Operator experience was defined for each operator as a continuous variable, cumulating the number of mechanical thrombectomy procedures performed since January 2015 or, if ulterior, since the operator started performing mechanical thrombectomies. Experience > 2 years as a senior INR before 2015 was rated as a nominal variable. Results A total of 1872 patients were included, treated by 14 operators (Mean 133 MT/operator, min 57 max 218). After adjustment for age, IV thrombolysis, on vs. off hours and occlusion location, increasing operator experience was significantly associated with shortened procedure duration. (Beta −3,50; 95% CI [−5.03 to −1.98]; P Fig. 1 ). Previous experience > 2 years in INR was also associated with shorter procedural duration. No significant association was found between increasing operator experience and successful reperfusion (mTICI 2b-3), number of passes or first pass recanalisation rates. Conclusion In trained interventional neuroradiologists, increasing experience in mechanical thrombectomy is associated with significantly shorter procedural duration. Whether these delays reductions translate to better clinical outcomes should be investigated in larger scale registries. These results may inform future training guidelines to set minimal experience standards before seniorisation.

Objective L’hydrocephalie est un facteur pronostic independant et modifiable de mauvais devenir neurologique apres une hemorragie intracerebrale (HIC). Chez l’enfant, les malformations arterio-veneuses cerebrales (MAVc) sont la cause plus frequente d’HIC. Dans une large cohorte prospective d’enfants avec des MAVc rompues, nous avons analyse les facteurs predictifs d’hydrocephalie necessitante une derivation ventriculaire externe (DVE) dans la phase aigue ou une derivation ventriculo-peritoneale (DVP). Methodes Il s’agit d’une analyse retrospective des donnees d’une base de donnees maintenue d’une facon prospective d’enfants (âge moins 18 ans) adresses a l’hopital Necker apres une rupture de MAVc entre 2002 et 2019. Les facteurs predictifs radiologiques et cliniques pour la necessite d’une DVE ou une DVP ont ete analyses en utilisant des modeles statistiques uni- et multivaries. Resultats Parmi 114 patients (âge moyenne 9,8 ans ± 3,9 ans DS), avec 125 episodes d’HIC apres rupture de MAVc, 55 (44 %) patients ont necessite une DVE et 5 (4,4 %) une DVP. Le modele de regression nominale multiple a identifie : un Glascow Coma Scale initial (GCSi) bas, une hydrocephalie sur le scanner cerebrale initial, la presence d’une hemorragie intraventriculaire (HIV) et un modified Graeb score (mGS) eleve comme facteurs associes a la necessite d’une DVE (tous p Conclusion Dans une grande cohorte pediatrique des MAVc rompues, presque la moitie des patients ont necessite une DVE et 4,4 % une DVP. Un GCSi bas et l’imagerie initiale par la mesure semi-quantitative de l’HIV par le mGS peuvent guider les decisions de prise en charge invasive dans ces situations.

Background and Purpose— Optimal management of the extracranial occlusive component remains controversial in patients with acute ischemic stroke by tandem occlusion treated with mechanical thrombectomy. We investigated the association between extracranial internal carotid artery (ICA) patency at day 1 and the clinical outcome after mechanical thrombectomy. Methods— Consecutive patients with acute ischemic stroke with tandem occlusion were identified from a hospital-based prospective registry from 2011 to 2017. Baseline characteristics, angiographic outcomes, and day 1 ICA patency assessed by MR angiography were analyzed with regard to their associations with 3-month modified Rankin Scale scores. Favorable outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. Results— Of 594 patients with acute ischemic stroke treated with mechanical thrombectomy during the study period, 83 met inclusion criteria. Successful recanalization (modified Thrombolysis in Cerebral Infarction, 2b/3) was achieved in 61.5%. Extracranial ICA was patent in 37 of 83 patients (44.6%) at day 1, more frequently in those with prior intravenous thrombolysis ( P =0.035) or with cervical revascularization procedure (balloon angioplasty or stenting, P =0.034). Favorable 3-month functional outcome was more frequent in patients with patent extracranial ICA at day 1 (adjusted odds ratio, 4.72; 95% CI, 1.76–13.34; P =0.003) independent of intracranial recanalization success. Conclusions— Day 1 stable extracranial ICA patency is associated with better clinical outcome in patients with acute ischemic stroke with tandem occlusions. Randomized studies are needed.

BackgroundAs interfacility transfer of patients with stroke becomes increasingly common, understanding fluctuations in deficits during transfer may help predict resource needs. We sought to characterize changes in NIH Stroke Scale (NIHSS) scores during transfer and identify factors associated with early rapid improvement (ERI).MethodsWe used prospectively collected data from our Comprehensive Stroke Center's (CSCs) stroke and telestroke network databases. We calculated changes in NIHSS scores for all patients transferred to our CSC after an initial telestroke evaluation from January 2010 to December 2015. Logistic regression identified factors associated with ERI, controlling for patient characteristics available on arrival.ResultsAmong the 505 patients included, the median initial NIHSS score was 11 (interquartile range [IQR] 5–18), and on CSC arrival, it was 9 (IQR 3–17), with a median change of 0 (−3 to −0). Of note, 74.5% of scores changed by fewer than 4 points (7% increased ≥4 points, and 19% decreased ≥4). In 85% of cases, the NIHSS score change did not cross a threshold to alter eligibility for thrombectomy. In multivariable modeling, ERI was associated with ability to ambulate before the index stroke (odds ratio [OR] 5.79, p = 0.02) and higher initial NIHSS (OR 1.06 per point, p = 0.001).ConclusionsThese findings may be valuable for resource planning and for inclusion in thrombectomy alert activation processes at the receiving hospital.

Background and Purpose— Noncontrast computed tomographic (CT) hypodensities represent an alternative to the CT angiography spot sign (SS) to predict intracerebral hemorrhage (ICH) expansion. However, previous studies suggested that these markers predicted hematoma expansion independently from each other. We investigated whether the integration of SS and hypodensity (HD) improved the stratification of ICH expansion risk. Methods— A single-center cohort of consecutive patients with ICH was retrospectively analyzed. Patients with available CT angiography, baseline, and follow-up noncontrast CT images available were included. Trained readers reviewed all the images for SS and HD presence, and the study population was classified into 4 groups: SS and HD negative (SS−HD−), SS positive only (SS+HD−), HD positive only (SS−HD+), and SS and HD positive (SS+HD+). ICH expansion was defined as hematoma growth >33% or >6 mL. The association between SS and HD presence and ICH expansion was investigated with multivariable logistic regression. Results— A total of 745 subjects qualified for the analysis (median age, 73 years; 54.1% men). The rates of ICH expansion were 9.3% in SS−HD−, 25.8% in SS+HD−, 27.4% in SS−HD+, and 55.6% in SS+HD+ patients ( P P =0.002 and odds ratio, 3.02, P P Conclusions— Integration of SS and HD improves the stratification of hematoma growth risk and may help the selection of patients with ICH for antiexpansion treatment in clinical trials.

Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffusion tensor imaging within 12 h and at day 3–5 post stroke. Early neurological outcomes were measured as the change in NIH Stroke Scale score from admission to day 3–5 post stroke. Target mismatch profile, percent mismatch lost, infarct growth, and rates of good perfusion were measured to assess ischemic tissue outcomes. NAWM mean diffusivity was significantly lower in the group with early neurological improvement (ENI, 0.79 vs. 0.82 × 10−3, mm2/s; P = 0.02). In multivariable logistic regression, NAWM mean diffusivity was an independent radiographic predictor of ENI (β = − 17.6, P = 0.037). Median infarct growth was 118% (IQR 26.8–221.9%) despite good reperfusion being observed in 65.6% of the cohort. NAWM and WMH diffusivity metrics were not associated with target mismatch profile, percent mismatch lost, or infarct growth. Our results suggest that, in AIS patients, white matter structural integrity is associated with poor early neurological outcomes independent of ischemic tissue outcomes.

BackgroundSusceptibility vessel sign (SVS) can be a useful MRI biomarker of an occlusion but its relationship with clinical outcomes of acute ischemic stroke (AIS) is yet to be fully elucidated.ObjectiveTo investigate SVS in relation to the clinical outcomes after mechanical thrombectomy using a stent retriever (SR) as first-line approach in patients with AIS.Material and methodsWe included patients with a first-line SR approach for anterior AIS from the the Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) and THRombectomie des Artères CErebrales (THRACE) trials when both baseline imaging of SVS and 90-day modified Rankin Scale (mRS) scores were available. Patients were assigned to two groups based on the presence of an SVS (independent core laboratory), and the overall distributions of the mRS score at 90 days (shift analysis) and clinical independence (mRS score ≤2) were compared.Results217 patients were included and SVS was diagnosed in 76.0% of cases (n=165, 95% CI 70.4% to 81.7%). After adjustment for potential confounders, SVS+ was significantly associated with 90-day mRS improvement (adjusted common OR=2.75; 95% CI 1.44 to 5.26) and favorable outcome (adjusted common OR=2.76; 95% CI 1.18 to 6.45).ConclusionBased on results for patients of the ASTER and THRACE trials receiving first-line SR treatment, SVS was associated with lower disability at 3 months. Large prospective studies using MRI-based thrombus evaluation are warranted.

BACKGROUND Whether delayed cerebral infarction (DCIn) after aneurysmal subarachnoid hemorrhage (aSAH) is driven by large artery vasospasm is still controversial. OBJECTIVE To study the association between DCIn and vasospasm by using quantitative assessment of vasospasm up to distal arteries with time and territorial-based correlation. METHODS Clinical and imaging data of 392 patients with aSAH treated at our center between 2012 and 2017 were reviewed. DCIn was defined as any cerebral infarction occurring within 3 to 21 d after ictus and not related to other specific cause. In patients with DCIn, vasospasm was assessed within 24 h around DCIn for each cerebral artery up to the end of the 2nd segments. DCIn and vasospasm analyses were blinded. RESULTS DCIn was found in 11% of patients (inter-rater k = 0.90, computed tomography (CT)-scan = 100%, follow-up MRI = 91%). Vasospasm was quantified in 258 artery territories including 66 with and 192 without DCIn (DSA = 93%, computed tomography angiography = 7%). Vasospasm was more severe in DCIn than in non-DCIn territories (60% [55-69] vs 20% [0-50], P

Purpose To identify wall enhancement patterns on vessel wall MRI that discriminate between stable and unstable unruptured intracranial aneurysm (UIA). Materials and Methods Patients were included from November 2012 through January 2016. Vessel wall MR images were acquired at 3 T in patients with stable (incidental and nonchanging over 6 months) or unstable (symptomatic or changing over 6 months) UIA. Each aneurysm was evaluated by using a four-grade classification of enhancement: 0, none; 1, focal; 2, thin circumferential; and 3, thick (1 mm) circumferential. Inter- and intrareader agreement for the presence and the grade of enhancement were assessed by using κ statistics and 95% confidence interval (CI). The sensitivity, specificity, and negative and positive predictive values of each enhancement grade for differentiating stable from unstable aneurysms was compared. Results The study included 263 patients with 333 aneurysms. Inter- and intrareader agreement was excellent for both the presence of enhancement (κ values, 0.82 [95% CI: 0.67, 0.99] and 0.87 [95% CI: 0.7, 1.0], respectively) and enhancement grade (κ = 0.92 [95% CI: 0.87, 0.95]). In unruptured aneurysms (n = 307), grade 3 enhancement exhibited the highest specificity (84.4%; 233 of 276; 95% CI: 80.1%, 88.7%; P = .02) and negative predictive value (94.3%; 233 of 247) for differentiating between stable and unstable lesions. There was a significant association between grade 3 enhancement and aneurysm instability (P.0001). Conclusion In patients with intracranial aneurysm, a thick (1 mm) circumferential pattern of wall enhancement demonstrated the highest specificity for differentiating between stable and unstable aneurysms. © RSNA, 2018.

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

Objective Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). Methods Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). Results Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. Interpretation Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993.

Background: Alterations to microstructural integrity in white matter hyperintensities (WMH) in patients with severe leukoaraiosis are poorly understood. Neurite density and orientation dispersion imaging (NODDI) produce better estimates of myelin density than diffusion tensor MRI (DTI) and therefore may provide additional in vivo insight into WMH pathophysiology. Methods: NODDI was acquired in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Median values were measured in in the hemisphere contralateral to the incident stroke in regions of WMH and in normal appearing white matter (NAWM) and compared (paired Wilcoxon-exact test). Linear regression was performed to evaluate univariate predictors of log-transformed WMH volumes (log WMHv). Results: Patient characteristics were: mean±SD age 69±10 y, time-to-MRI 2.8±1.2 days, median [IQ] normalized WMHv 4.7 [2.3-9.3] and 61% men. MD, AD and RD were greater, while FA, MK, AK, RK, OD and ND were lower in WMH compared to NAWM (P Discussion: Diffusivity, kurtosis and ND and OD in acute stroke patients with moderate to severe leuokoaraiosis differed significantly between NAWM and WMH in the contralateral hemisphere. Reduced neurite density is suggestive of microstructural injury. Reduced OD is typically associated with greater organization, but might also reflect restricted extracellular space diffusivity. The association of MD, AD, AK and OD in NAWM with WMH burden suggests there is ongoing risk for developing future WMH.

Introduction: Interfacility transfer of patients with suspected large vessel occlusion for endovascular intervention is increasingly common. Eligibility depends on stroke severity (NIHSS), yet changes in NIHSS during transfer have not been well-described. Objective: to characterize changes in NIHSS during transfer, and identify factors associated with early rapid improvement. Methods: Using prospectively collected data from our institution’s Get with the Guidelines-Stroke registry and telestroke network portal, we identified all stroke patients transferred to our hospital from 01/01/10-01/01/16. We calculated change in NIHSS (arrival score minus telestroke score at transferring outside hospital, OSH). Logistic regression identified factors associated with early rapid improvement, controlling for patient characteristics available on arrival, including tPA use. Results: Among the 505 patients included, median NIHSS at OSH was 11 (IQR 5-18) and on arrival was 9 (IQR 3-17); median change of 0 (IQR -3-0). Scores increased by ≥4 points among 7%, and decreased by ≥4 among 19%. In bivariate analysis, early rapid improvement was more likely in patients who were ambulatory at baseline, had higher NIHSS at OSH, and were treated with tPA, and less likely among patients with history of hypertension (Table). In multivariable modeling, early rapid improvement was associated with history of coronary artery disease (CAD) and higher NIHSS at OSH (Table). Patients with early rapid improvement were more likely to be discharged home in bivariate (OR 1.58, 95%CI 1.01-2.50) and multivariable analyses (OR 4.07, 95%CI 1.58-10.49). Conclusion: In this cohort of transferred patients, NIHSS scores were frequently unchanged or decreased during transfer. History of CAD and higher baseline NIHSS were associated with early rapid improvement during transfer. If confirmed in a larger sample, these results may be useful for triage and intervention planning for transferred patients.

Background: Advanced diffusion imaging approaches that model intracellular and extracellular diffusion components such as neurite orientation dispersion and density imaging (NODDI) may provide additional insight into evolution of acute ischemic stroke (AIS) injury over standard diffusion tensor imaging approaches (DTI). Methods: NODDI was acquired at discharge in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Follow-up (FU) infarct volumes were drawn on discharge FLAIR. MD, AD, RD, FA, MK, AK, RK, OD and ND values were compared (1-way ANOVA) in infarct core (abnormal acute DWI), Growth (normal acute DWI, abnormal FU) and normal contralateral gray matter (nGM) and white matter (nWM). Results: Patient characteristics were: mean±SD age 69±10 y, median [IQR] initial NIH SS score 6 [3-11], time-to-acute MRI 7.3±5.3 h, time-to-FU MRI 2.8±1.2 days, acute DWI lesion 3.1 [0.5-18.8] cm 3 , FU lesion 8.1 [1.2-45.4] cm 3 and 61% men. Figure A shows examples of maps from a single subject. Core and growth values differed significantly (P Discussion: Increased OD is expected with tissue infarction due to loss of structural integrity. In contrast, increased ND in the subacute time-frame is paradoxical. One possible mechanism could be that hyperacute ischemia-induced cellular swelling increases tortuosity of water diffusion paths, imposing direction-dependent restrictions upon diffusion, increasing intracellular and extracellular diffusion.

Background: Previous pathologic reports have suggested that the underlying vasculopathy in cerebellar intracerebral hemorrhage (ICH) patients may be related to the location of the bleed whithin the cerebellum. We sought to determine whether the location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small vessel disease pathology (hypertensive vasculopathy or cerebral amyloid angiopathy, CAA). Methods: Consecutive cerebellar-ICH patients were recruited from January 1998 to January 2016. Based on data from pathologic reports, patients were divided according to the location of the primary cerebellar hematoma (superficial, Figure, panel A-B, blu circles in panel E vs deep, Figure, panel C-D, orange circles in panel E ). Location of cerebral microbleeds (CMB; strictly-lobar, strictly-deep and mixed-CMB) was evaluated on MRI. Results: One-hundred and eight patients (84%) had a deep cerebellar hematoma and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in superficial cerebellar-ICH patients (89% vs 65%, respectively; p Conclusions: Our study showed that superficial cerebellar-ICH is related to the presence of strictly lobar-CMB, a pathologically proven marker of CAA. Cerebellar hematoma location may thus help to identify those patients likely to have CAA pathology.

Background and Purpose— For suspected large vessel occlusion patients efficient transfer to centers that provide endovascular therapy (ET) is critical to maximizing treatment opportunity. Our objective was to examine associations between transfer time, modes of transfer, ET, and outcomes within a hub-and-spoke telestroke network. Methods— Patients with ischemic stroke were included if transferred to a single hub hospital between January 2011 and October 2015 with National Institutes of Health Stroke Scale>6, onset Results— Of 234 patients that met inclusion criteria, 51% were transferred by ambulance and 49% by helicopter; 27% underwent ET (36% achieved modified Rankin Scale score of 0–2 at 90 days). Median actual transfer time was 132 minutes (interquartile range, 103–165), compared with median ideal transfer time at 102 minutes (interquartile range, 96–123). Longer transfer time was associated with decreased likelihood of undergoing ET (odds ratio, 0.990; P =0.003). Nocturnal transfer (18:00 to 06:00 hours) was associated with significantly longer delay (β=20.5; P Conclusions— Within a large telestroke network, there was an association between longer transfer time and decreased likelihood of undergoing ET. Nocturnal transfers were associated with a substantial delay relative to daytime transfers. In contrast, delivery of tPA was not associated with delays, underscoring the impact of effective protocols at spoke hospitals. More efficient transfer may enable higher ET treatment rates. Metrics and protocols for transfer, especially at night, may improve transfer times.

ObjectiveTo determine the prevalence of cortical superficial siderosis (cSS), its clinical and neuroimaging associated markers, and its influence on the risk of recurrent intracerebral hemorrhage (ICH) in a prospective observational ICH cohort.MethodsWe investigated clinical and radiologic markers associated with cSS using multivariable analysis. In survival analyses, we used Cox models to identify predictors of recurrent ICH after adjusting for potential confounders.ResultsOf the 258 patients included in the study, 49 (19%; 95% confidence interval [CI] 14%–24%) had cSS at baseline. Clinical factors independently associated with the presence of cSS were increasing age (odds ratio [OR] 1.03 per 1-year increase, 95% CI 1.001–1.06, p = 0.044), preexisting dementia (OR 2.62, 95% CI 1.05–6.51, p = 0.039), and history of ICH (OR 4.02, 95% CI 1.24–12.95, p = 0.02). Among radiologic biomarkers, factors independently associated with the presence of cSS were ICH lobar location (OR 24.841, 95% CI 3.2–14.47, p < 0.001), severe white matter hyperintensities score (OR 5.51, 95% CI 1.17–5.78, p = 0.019), and absence of lacune (OR 4.46, 95% CI 1.06–5.22, p = 0.035). During a median follow-up of 6.4 (interquartile range 2.9–8.4) years, recurrent ICH occurred in 19 patients. Only disseminated cSS (hazard ratio 4.69, 95% CI 1.49–14.71, p = 0.008), not the presence or absence of cSS or focal cSS on baseline MRI, was associated with recurrent symptomatic ICH.ConclusionIn a prospective observational cohort of spontaneous ICH, clinical and radiologic markers associated with cSS suggest the implication of underlying cerebral amyloid angiopathy. Disseminated cSS may become a key prognostic neuroimaging marker of recurrent ICH that could be monitored in future clinical trials dedicated to patients with ICH.

Background and Purpose— Spontaneous cerebellar intracerebral hemorrhage (ICH) has been reported to be mainly associated with vascular changes secondary to hypertension. However, a subgroup of cerebellar ICH seems related to vascular amyloid deposition (cerebral amyloid angiopathy). We sought to determine whether location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small-vessel disease pathology (cerebral amyloid angiopathy or hypertensive vasculopathy). Methods— Consecutive patients with cerebellar ICH from a single tertiary care medical center were recruited. Based on data from pathological reports, patients were divided according to the location of the primary cerebellar hematoma (deep versus superficial). Location of cerebral microbleeds (CMBs; strictly lobar, strictly deep, and mixed CMB) was evaluated on magnetic resonance imaging. Results— One-hundred and eight patients (84%) had a deep cerebellar hematoma, and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in patients with superficial cerebellar ICH (89% versus 65%, respectively; P P =0.004). Conclusions— Our study showed that superficial cerebellar ICH is related to the presence of strictly lobar CMB—a pathologically proven marker of cerebral amyloid angiopathy. Cerebellar hematoma location may thus help to identify those patients likely to have cerebral amyloid angiopathy pathology.

Moya-Moya disease is a rare arterial occlusive disease affecting the internal carotid artery and its branches. It is found in both pediatric and adult populations, and it may lead to severe clinical presentations such as stroke and intracranial hemorrhage. Several surgical procedures have been developed to improve its clinical outcome. Imaging techniques have a key role in management of Moya-Moya disease, as they are necessary for diagnosis, choice of treatment and follow-up. Although catheter angiography remains the diagnostic gold standard, and nuclear-medicine techniques best perform hemodynamic studies, less invasive imaging techniques have become efficient in serving these purposes. Conventional MRI and MR angiography, as well as MR functional and metabolic studies, are now widely used in each stage of disease management, from diagnosis to follow-up. CT scan and Doppler sonography may also help assess severity of disease and effects of treatment. The aim of this review is to clarify the utility, efficiency and latest developments of each imaging modality in management of Moya-Moya disease.

Resume Les anevrismes intracrâniens doivent etre recherches en cas d’hemorragie sous-arachnoidienne et dans cette situation, l’angioscanner est la technique privilegiee. Dans le cadre de formes familiales ou de maladies du tissu elastique, un depistage peut etre organise et l’angiographie par resonance magnetique est alors l’examen de premiere intention. Ces methodes non invasives ont aujourd’hui supplante l’angiographie conventionnelle qui est reservee a la phase pretherapeutique. Une bonne connaissance technique de ces methodes d’imagerie, des artefacts et des images pieges permettent une detection fiable des anevrismes intracrâniens et la realisation d’un compte rendu precis a transmettre aux cliniciens.

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

Purpose To propose and validate a modified pediatric intracerebral hemorrhage (PICH) (mPICH) score and to compare its association with functional outcome to that of the original PICH score. Materials and Methods Data from prospectively included patients were retrospectively analyzed. Consecutive patients with nontraumatic PICH who had undergone clinical follow-up were included. The study population was divided into a development cohort (2008-2012, n = 100) and a validation cohort (2013-2016, n = 43). An mPICH score was developed after variables associated with poor outcome were identified at multivariate analysis (King's Outcome Scale for Childhood Head Injury score5a) in the development cohort. The accuracy of the score for prediction of poor outcome was evaluated (sensitivity, specificity). Discrimination and calibration of associations between the mPICH score and poor outcome cohorts were assessed (C statistics, Hosmer-Lemeshow test). Results The mPICH score assessed as follows: brain herniation, four points; altered mental status, three points; hydrocephalus, two points; infratentorial PICH, two points; intraventricular hemorrhage, one point; PICH volume greater than 2% of total brain volume, one point. An mPICH score greater than 5 was associated with severe disability or worse, with sensitivity of 97% (95% confidence interval [CI]: 83%, 100%) and specificity of 61% (95% CI: 49%, 73%). The C statistic was 0.81 (95% CI: 0.73, 0.89). In the validation cohort, sensitivity and specificity were 95.2% (95% CI: 76%, 99%) and 77% (95% CI: 55%, 92%), respectively. There was no significant difference between the observed and predicted risks of poor outcome (P = .46). Conclusion An mPICH score was developed as a simple clinical and imaging grading scale for acute prognosis in patients with PICH.

We thank Gross et al for their thoughtful comments and think we share many of the concerns raised in their letter. The authors present their view that a policy requiring pretransfer vascular imaging would promote a decline rather than improvement in the efficient triage of and timely access to endovascular thrombectomy (EVT) for stroke patients with suspected large vessel occlusion. It is abundantly clear that timely and efficient access to EVT is a high priority for all eligible patients. However, in resource-constrained healthcare environments, it is critical to consider all performance characteristics of a screening test when triaging patients for a time-critical treatment of proven efficacy when the consequences of not treating eligible patients is so profound. Selecting potentially EVT-eligible subjects by using National Institutes of Health Stroke Scale (NIHSS) threshold and noncontrast computed tomography (CT) alone will increase sensitivity and frequency of transfers, and likely shorten the time to EVT for treated patients, but may also amplify the cost, inconvenience, and potential harm to the many subjects who will turn out not to be EVT-eligible on arrival. It will also reduce emergency medical …

Background Cerebral amyloid angiopathy (CAA) is associated with hemorrhagic and nonhemorrhagic markers small vessel disease (SVD). A composite score to quantify the total burden of SVD on MRI specifically for CAA patients was recently developed. Brain network alterations related to individual MRI markers of SVD in CAA were demonstrated. Objectives Considering diffusion based network measures sensitive to detect different relevant SVD-related brain injury, we investigated if increased overall SVD injury on MRI corresponds to worse global brain connectivity in CAA. Methods Seventy-three patients (79.5% male, mean age 70.58 ± 8.22 years) with a diagnosis CAA were considered. SVD markers in total MRI SVD score included: lobar cerebral microbleeds, cortical superficial siderosis (cSS), white matter hyperintensities (WMH) and centrum semiovale-enlarged perivascular spaces. Diffusion imaging based network reconstruction was made. The associations between total MRI SVD score and global network efficiency (GNE) were analyzed. Results A modest significant inverse correlation between total MRI SVD score and GNE existed (p = 0.013; R2 = 0.07). GNE was related with the presence of cSS and moderate-severe WMHs. Conclusions An increased burden of SVD neuroimaging markers corresponds to more reductions in global brain connectivity, implying a possible cumulative effect of overall SVD markers on disrupted physiology. GNE was related with some components of the score, specifically cSS and moderate-severe WMHs.

Objective:To validate various noncontrast CT (NCCT) predictors of hematoma expansion in a large international cohort of ICH patients and investigate whether intensive blood pressure (BP) treatment reduces ICH growth and improves outcome in patients with these markers.Methods:We analyzed patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized controlled trial. Participants were assigned to intensive (systolic BP 33% and unfavorable outcome was defined as modified Rankin Scale score >3 at 90 days. Logistic regression was used to identify predictors of ICH expansion and explore the association between NCCT signs and clinical benefit from intensive BP treatment.Results:A total of 989 patients were included (mean age 62 years, 61.9% male), of whom 186/869 experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable outcome. NCCT markers independently predicted ICH expansion (all p < 0.01) with overall accuracy ranging from 61% to 78% and good interrater reliability (k > 0.6 for all markers). There was no evidence of an interaction between NCCT markers and benefit from intensive BP reduction (all p for interaction >0.10).Conclusions:NCCT signs reliably identify ICH patients at high risk of hematoma growth. However, we found no evidence that patients with these markers specifically benefit from intensive BP reduction.Clinicaltrials.gov identifier:NCT01176565.

Background and Purpose— Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. Methods— We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. Results— Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P =0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P =0.04), and lower rate of tobacco use (21.1% versus 35.9%; P =0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score P =0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. Conclusions— Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism.

We thank Dr Stanley et al for pointing out a potentially important aspect of the ischemic insult in primary and secondary cerebral vasculitis as assessed by signal changes in diffusion-weighted imaging. The authors report that, in their experience, both diffusion-weighted imaging positivity and decreased diffusion coefficient on apparent diffusion coefficient maps can be sustained long after 3 weeks in those pathological conditions. This is of importance, given the fact that acute ischemic lesions, detected by magnetic resonance imaging diffusion-weighted imaging sequences, are known as the most prevalent feature of primary angiitis of the central nervous system at …

ObjectiveTo assess the predominant type of cerebral small vessel disease (SVD) and recurrence risk in patients who present with a combination of lobar and deep intracerebral hemorrhage (ICH)/microbleed locations (mixed ICH).MethodsOf 391 consecutive patients with primary ICH enrolled in a prospective registry, 75 (19%) had mixed ICH. Their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to those of 191 patients with probable cerebral amyloid angiopathy (CAA-ICH) and 125 with hypertensive strictly deep microbleeds and ICH (HTN-ICH). ICH recurrence and case fatality were also analyzed.ResultsPatients with mixed ICH showed a higher burden of vascular risk factors reflected by a higher rate of left ventricular hypertrophy, higher creatinine values, and more lacunes and severe basal ganglia (BG) enlarged perivascular spaces (EPVS) than patients with CAA-ICH (all p < 0.05). In multivariable models mixed ICH diagnosis was associated with higher creatinine levels (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2–5.0, p = 0.010), more lacunes (OR 3.4, 95% CI 1.7–6.8), and more severe BG EPVS (OR 5.8, 95% CI 1.7–19.7) than patients with CAA-ICH. Conversely, when patients with mixed ICH were compared to patients with HTN-ICH, they were independently associated with older age (OR 1.03, 95% CI 1.02–1.1), more lacunes (OR 2.4, 95% CI 1.1–5.3), and higher microbleed count (OR 1.6, 95% CI 1.3–2.0). Among 90-day survivors, adjusted case fatality rates were similar for all 3 categories. Annual risk of ICH recurrence was 5.1% for mixed ICH, higher than for HTN-ICH but lower than for CAA-ICH (1.6% and 10.4%, respectively).ConclusionsMixed ICH, commonly seen on MRI obtained during etiologic workup, appears to be driven mostly by vascular risk factors similar to HTN-ICH but demonstrates more severe parenchymal damage and higher ICH recurrence risk.

Objective:In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci.Methods:Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0–4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH.Results:The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9–5.1 years), the annual ICH recurrence rates per cSS scores (0–4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77–5.75; p < 0.0001).Conclusions:The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.

Background: MR WITNESS was a safety trial giving tPA to acute ischemic stroke (AIS) patients with unwitnessed onset with MRI findings of early stroke. A DWI-positive, FLAIR negative pattern has been shown to identify strokes Methods: Core readers blinded to enrollment status and clinical presentation reviewed MRI of screened patients. The MR WITNESS algorithm enrolled subjects with no visible FLAIR or a pre-specified SIR < 2. SIR consistency was measured with intraclass coefficient (ICC) and reader agreement assessed with Fleiss’ Kappa. Statistical analysis included 2-sided Fisher’s Exact test or Wilcoxon Exact test as appropriate. Results: 201 subjects were screened. 153 baseline MRIs with DWI lesions were reviewed. ICC was 71% (P Discussion: Although SIR reads between Core and sites showed good agreement, there was still variability in the absolute values. This demonstrates the potential limitation of subjective lesion volume delineation. Automated approaches should be investigated.

Background: Women are known to have worse post-stroke outcomes; however, the underlying mechanisms remain unclear. We evaluated sex-specific clinical and neuroimaging characteristics linked to cerebrovascular brain health in association with functional recovery after acute ischemic stroke (AIS). Methods: We reviewed 316 AIS patients with acute MRI ( Results: Women comprised 41.1% of this AIS cohort, and as compared to men, they were older (68 vs. 62.8 years, p = 0.002), had higher prevalence of atrial fibrillation (21.5% vs. 12.4%, p = 0.04), and less tobacco use (21.1% vs. 36.3%, p = 0.03). There was no statistically significant difference between men and women in admission stroke severity, TOAST stroke subtype distribution, DWIv or WMHv. However, women were significantly less likely to have a favorable outcome (mRS Conclusion: Despite no differences in admission NIHSS, acute infarct size, WMH burden or stroke subtype, women with AIS had significantly worse post-stroke outcomes in our cohort. Our findings suggest that microstructural integrity, as assessed by NAWM diffusivity anisotropy measurements, may represent a neuroimaging correlate of worse outcomes in women. The correlation between markers of white matter microstructural integrity and long-term mRS provides insight into the underlying mechanisms of disease that may influence functional recovery after stroke.

Introduction: Although early hemorrhagic transformation (HT) in acute ischemic stroke has been studied, less is known about patients who develop hemorrhage after the acute phase. We hypothesized that patients with late hemorrhage (LH) would have more severe strokes than those without, and tested this hypothesis in a cohort of thrombolysed patients from the MR WITNESS trial. Methods: Subjects were recruited from 10 sites between Jan 2011-Oct 2015. MR WITNESS enrolled subjects if they were last seen between 4.5 and 24 hours prior to evaluation, but otherwise qualified for IV tPA in the 3-4.5 hr window per AHA guidelines, and if their brain MRI findings indicated very early infarction: either no FLAIR hyperintensity or subtle hyperintensity, ie signal increase Results: Among the 80 patients included in the MR WITNESS cohort, 53 met our inclusion criteria and were analysed. When compared to those with no HT, patients with LH had larger baseline infarct volumes and perfusion defects, as well as more frequent proximal vessel occlusion at baseline (all p Conclusion: Patients with LH demonstrate a more severe imaging profile at baseline and a worse functional outcome at 90 days when compared to patients without hemorrhage. Understanding the underlying pathophysiology of LH may shed light on to the mechanisms of acute and subacute brain injury.

Background: The predominant type of cerebral small vessel disease (SVD) and clinical outcomes of patients who present with a combination of lobar and deep intracerebral hemorrhage (ICH)/microbleed (MB) locations (Mixed-ICH, see figure) is unknown. Methods: Out of 391 consecutive ICH, 75 (19%) had Mixed-ICH, and their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to 191 probable Cerebral Amyloid Angiopathy (CAA-ICH) and 125 strictly deep-MB and ICH (Deep-ICH) patients. ICH-recurrence on follow up was also analyzed. Results: Mixed-ICH patients had a higher prevalence of hypertension, diabetes, left ventricular hypertrophy rates, higher creatinine values, as well as more prevalent lacunes and basal ganglia (BG) enlarged perivascular spaces (EPVS) than CAA-ICH (all p Conclusions: Mixed-ICH, commonly seen when MRI obtained during etiologic workup, appears to be mostly driven by vascular risk factors similar to Strictly Deep-ICH, but demonstrates more severe parenchymal damage and higher ICH-recurrence risk.

Introduction: When transferred from a referring hospital (RH) to a thrombectomy capable stroke center (TCSC), patients with initially favorable imaging profile (ASPECT score ≥6) often demonstrate infarct progression significant enough to make them ineligible at arrival. We sought to determine the clinical and imaging factors associated with this phenomenon in transferred ischemic stroke patients. Methods: We identified adult stroke patients transferred from one of 30 RH between 2010 and 2016 for which (1) a RH computed tomography (CT) and (2) a CT Angiography (CTA) at arrival were available for review. ASPECT scores were evaluated by 2 raters. The adequacy of leptomeningeal collateral flow was rated as none/poor, decreased, adequate or augmented per the Maas et al (Stroke 2009), modified scale. ASPECTS decay was defined as an ASPECT initial score ≥6 worsening between RH and TCSC CTs to a score Results: A total of 330 patients were included in the analysis (mean age 70.2 ± 14.2, 43.3% females). Univariable subgroup analyses showed that patients with ASPECTs decay were more likely to be females (55% vs 40%, p=0.02), not on anticoagulants (4% vs 15%, p=0.01), and with higher initial NIHSS (Median [IQR] 19 [15.3-22] vs 11 [6-17], p Conclusion: In ischemic stroke patients transferred for thrombectomy, poor collateral flow, stroke severity and proximal vascular occlusion, but not time interval, are the main determinants of ASPECTs decay.

Introduction: Guideline-based eligibility criteria for endovascular thrombectomy (EVT) are commonly used as criteria to select patients for transfer from referring hospitals (RH) to thrombectomy capable stroke centers (TCSC), resulting in a large amount of futile transfers. We sought to determine the baseline clinical and imaging factors associated with greater likelihood of receiving EVT after transfer, and explored the impact of simulated vascular imaging availability at RH on reducing the number of futile transfers for EVT. Methods: We identified stroke patients transferred from 30 RH between 2010 and 2016 for which (1) the RH computed tomography (CT) and (2) either CT/CT angiography or MRI at arrival were available for review. Initial ASPECT scores and baseline imaging characteristics were evaluated by 2 raters. The main outcome variable was pre-defined as receiving EVT at the TCSC after transfer. To analyze different options for improving triaging criteria for EVT at the RH, we generated various data-based situations accounting for the presumed vascular occlusion status based first on data available only at the RH and then by imputing vascular imaging information gathered at the TCSC presuming it could have been captured at the RH. The predictive ability of each situation, using varying NIHSS thresholds, was evaluated to find an optimal sensitivity (Se) - specificity (Sp) threshold. Results: A total of 508 patients were included in the analysis (mean age 69.7 ± 14.8, 41.9% females). Application of current guidelines for EVT eligibility (NIHSS >6, ASPECTs≥6, Time Conclusion: Implementation of vascular imaging at RH would result in significantly fewer futile transfers for EVT. The optimal trade-off between time, cost and imaging will impact the number needed to transfer and will depend on local resources and capabilities.

Objective: To investigate whether magnetic resonance imaging (MRI) markers of cerebral small vessel disease predict overall mortality in cerebral amyloid angiopathy (CAA) patients. Methods: Subjects were consecutive survivors (age≥55) of spontaneous symptomatic CAA-related-lobar ICH and CAA presenting without lobar ICH, diagnosed according to the Boston criteria drawn from an ongoing longitudinal cohort study and Memory Disorder Unit. All subjects had brain MRI at presentation. Baseline clinical, imaging, laboratory data and mortality information were collected. Neuroimaging markers including focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), cortical subarachnoid hemorrhage (cSAH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) were evaluated. Overall mortality risk was assessed using Cox proportional hazards models adjusting for potential confounders. Results: A total of 335 patients with probable CAA were enrolled, 196 presenting with lobar ICH and 139 without lobar ICH. During a median follow-up time of 3.44 years (interquartile range 1.61- 5.52 years), 181 of 335 patients (54.0%) died, 37.3% were patients with lobar ICH and 16.7% were those without. In univariable analysis, disseminated cSS, moderate to severe WMH, higher age and CAA related-lobar ICH group were predictors of overall mortality (p75 years) with disseminated cSS (HR 1.86; 95% CI 1.08-3.23, p = 0.026). Conclusion: Disseminated cSS is an independent neuroimaging biomarker of increased risk of overall mortality in probable CAA, particular in those patients with lobar ICH and older age. These findings may serve identify important markers of CAA severity.

Background: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. CAA-related ICH survivors are at substantial risk for recurrent ICH, accounting for the significant morbidity of the disease. Identifying predictors of recurrence is therefore crucial. Recent data have implicated cortical superficial siderosis (cSS) as a key hemorrhagic MRI signature of CAA, and a possible marker of increased risk for CAA-ICH recurrence. However, data remain limited. We obtained precise estimates on cSS as an independent predictor of ICH recurrence risk in CAA cohorts from a systematic review of published studies pooled with data from our centre. Methods: We included cohort studies of consecutive CAA-related ICH patients based on the original Boston criteria, with available blood-sensitive MRI sequences at baseline for cSS assessment, and adequate follow-up for recurrent symptomatic ICH. The strength of the association between cSS and recurrent ICH was quantified using random effects models. Covariate-adjusted hazard rations (adj-HR) as provided from pre-specified Cox proportional hazard models were used for a two-stage meta-analysis. Results: Three cohorts including 443 CAA-ICH patients were eligible for analysis. The pooled prevalence of cSS presence and disseminated cSS (>3 affected sulci) was 32% (95%CI: 32%-41%) and 21% (95%CI: 18%-25%) respectively. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH, a pooled risk ratio of 6.9% per year (I 2 : 63%, p=0.07). In adjusted pooled analysis, any cSS and disseminated cSS were both independently associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95%CI: 1.5-3.8; p2 : 0% and adj-HR: 4.1; 95%CI: 2.6-6.6; p2 : 47%), after adjusting for multiple strictly lobar microbleeds presence and increasing age. Conclusions: Our findings in a large population of CAA patients with ICH and a large number of recurrence events, indicate that cSS, particularly if disseminated, is the single most important prognostic risk factor on MRI for future recurrent lobar ICH. The provided estimates may help stratify future bleeding risk in CAA, with clinical implications for prognosis and treatment.

Objective: Cerebral amyloid angiopathy (CAA) is increasing recognized as a cause of cognitive impairment and dementia in older individuals. This study aimed to investigate predictors of dementia, including imaging markers, in CAA patients from a stroke unit. Methods: A total of 71 non-demented patients from a stroke unit were included according to modified Boston Criteria for probable CAA with available cognitive follow up. These CAA patients included both patients with and patients without previous intracerebral hemorrhage (ICH). At baseline, neuroimaging markers, including lobar microbleeds (CMBs), white matter hyperintensities (WMH), cortical superficial siderosis (cSS) and MRI-visible centrum semiovale perivascular spaces (CSO-PVS) were assessed. The small vessel disease (SVD) score for CAA was calculated by the scores of CMBs, WMH, cSS and CSO-PVS. The association between these neuroimaging markers and dementia conversion was analyzed. Results: The median follow up time is 1.91 years (quartiles 1.14-4.23 years). Fourteen (19.72%) CAA patients developed dementia during follow up period. Thirty-seven CAA patients (52.11%) had previous symptomatic ICH. Age, lobar CMBs≥20 and SVD score were selected from the univariate Cox-regression analysis with p value less than 0.1 (Table1). In a backward stepwise multivariabte analysis including age, previous ICH history and either SVD score or number of CMBs, age and SVD score independently predicted dementia conversion (Table 1). The individual neuroimaging markers for SVD related brain damage (CSO-PVS, cSS, lobar MBs and WMH) did not predict dementia conversion for probable CAA patients. Conclusion: Our results demonstrate that cognitive deterioration of CAA patients appears attributed to cumulative CAA related vasculopathic changes.

Objective: We performed a meta-analysis of randomized controlled trials (RCTs) to assess whether intensive blood pressure (BP) lowering in acute intracerebral haemorrhage (ICH) patients is safe and effective in improving clinical outcomes. Methods: We searched PubMed, EMBASE and the Cochrane databases for relevant RCTs and calculated pooled odds ratios (OR) for 3-month mortality (safety outcome) and 3-month death or dependency (efficacy outcome), in acute ICH patients randomized to either intensive BP-lowering vs. standard BP lowering treatment protocols. We also investigated the association between treatment arm and significant ICH expansion at 24h. Random effects models with DerSimonian-Laird weights were used. Results: Five eligible studies including 4360 acute ICH patients were pooled in meta-analysis. The risk of 3-month mortality was similar between patients randomized to intensive BP-lowering treatment vs. standard BP-lowering treatment (OR: 0.99; 95%CI: 0.82-1.20, p=0.909). Intensive BP-lowering treatment showed a (non-significant) trend for an association with lower 3-month death or dependency risk compared to standard treatment (OR: 0.91; 95%CI: 0.80-1.02), p=0.106). Intensive BP-reduction was associated with a trend for lower risk of significant ICH expansion compared to standard treatment (OR: 0.82; 95%CI: 0.68-1.00, p=0.056), especially in larger RCTs. Conclusion: For acute ICH patients similar to those included in RCTs and without contraindication to acute BP treatment, intensive acute BP-lowering is safe (Class I; Level of Evidence A), but does not seem to provide an incremental clinical benefit in terms of functional outcomes (Class I; Level of Evidence B). The effect of intensive BP-lowering on significant hematoma expansion at 24 hours warrants further investigation.

Introduction: Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease (SVD). Patients without ICH typically present with transient focal neurological episodes (TFNEs) or cognitive symptoms. We sought to determine if SVD lesion burden differed between CAA patients first presenting with TFNEs versus cognitive symptoms. Methods: A total of 647 patients presenting either to a stroke department (n=205) or an outpatient memory clinic (n=442), were screened for eligibility. Patients meeting modified Boston criteria for probable CAA were included and markers of SVD were quantified including cerebral microbleeds (CMBs), perivascular spaces, cortical superficial siderosis (cSS), and white matter hyperintensities (WMH). Patients were classified according to presentation symptoms (TFNEs vs cognitive). Total CAA-SVD burden was assessed using a validated summary score. Individual neuroimaging markers and total SVD burden were compared between groups using univariable and multivariable models. Results: There were 261 probable CAA patients included. After adjustment for confounders, patients first seen for TFNEs (n=97) demonstrated a higher prevalence of cSS (p Conclusion: We present a large cohort of probable CAA patients without ICH and show that those first evaluated for TFNEs bear a higher burden of structural MRI SVD related damage compared to those first seen for cognitive symptoms. This study sheds light on CAA disease phenotypes, adds to the understanding of CAA clinical expression, and sets the basis for future works investigating CAA prognosis amongst phenotypes.

Background/Aims: To evaluate whether the burden of lacunes located at deep and lobar brain regions, would differ between intracerebral hemorrhage patients (ICH) with cerebral amyloid angiopathy (CAA) vs patients with strictly deep cerebral microbleeds (CMB) and ICH (Deep HTN-ICH). Methods: We defined lobar and deep lacunes similar to the topographic distribution used for ICH and microbleeds. We then compared their distribution between CAA and Deep HTN-ICH patients. The independent associations of lacune location (lobar vs deep) with diagnosis of CAA-ICH and Deep HTN-ICH were evaluated using multivariable models. The relationship between lobar and deep lacunes and WMH volume was evaluated using partial correlation analyses adjusting for age and by means of a validated visual scale. Results: In our cohort of 316 ICH patients, lobar lacunes were more commonly present in CAA (20.4% vs 5.7% in Deep HTN-ICH, pr=0.52, p Conclusions: Lobar lacunes are associated with CAA whereas deep lacunes are more frequent in patients with Strictly deep CMBs and ICH, they can thus be clinically useful in the appropriate context. Lobar lacunes seem to have a close relationship with WMH suggesting a possible common origin.

A 68-year-old woman presented with visual field defect, caused by right optic nerve compression by a giant carotid-ophthalmic aneurysm. Steroids were initiated at 1 mg/kg/d with a 3-month dose decrease and resolution of symptoms. Any other intervention was refused. Vessel wall MRIs (figure) showed a decrease in intensity and thickness of initial circumferential aneurysm wall enhancement (CAWE) at 6 weeks, sustained at 1 year. CAWE is hypothesized to be related to inflammation,1 a marker of aneurysm instability.2 This observation suggested an anti-inflammatory effect of steroids on aneurysm wall enhancement that may have contributed to the resolution of the optic nerve palsy.