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  • 1
    In: JAMA Neurology, American Medical Association (AMA), Vol. 80, No. 3 ( 2023-03-01), p. 233-
    Abstract: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC). Objective To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion. Design, Setting, and Participants This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021. Exposures Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation. Main Outcomes and Measures The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses. Results Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion. Conclusions and Relevance In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 2
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 93, No. 6 ( 2022-06), p. 588-598
    Abstract: To investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF). Methods We analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke. Results Among 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy. Conclusions Stroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed. Trial registration number ISRCTN48292829 .
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1480429-3
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  • 3
    In: Journal of Stroke, Korean Stroke Society, Vol. 24, No. 2 ( 2022-05-31), p. 266-277
    Abstract: Background and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce.Methods We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR] , 1.33; 95% confidence interval [CI] , 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031).Conclusions Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.
    Type of Medium: Online Resource
    ISSN: 2287-6391 , 2287-6405
    Language: English
    Publisher: Korean Stroke Society
    Publication Date: 2022
    detail.hit.zdb_id: 2814366-8
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  • 4
    In: Annals of Neurology, Wiley, Vol. 89, No. 1 ( 2021-01), p. 42-53
    Abstract: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes. Methods This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months. Results Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2–11]) compared with VKA (6, [2–14] ) and controls (7, [3–15], p   〈  0.001; quantile regression: β −2.1, 95% confidence interval [CI] −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%] ; adjusted odds ratio [aOR] 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 [15%] ; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51). Interpretation Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2037912-2
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 7 ( 2023-07), p. 1708-1717
    Abstract: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64–82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3–10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85–1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35–2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07–2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0–2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 3, No. S2 ( 2023-11)
    Abstract: The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06] , p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 3144224-9
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  • 7
    In: Journal of Neuroimaging, Wiley, Vol. 33, No. 3 ( 2023-05), p. 422-433
    Abstract: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. Methods We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non‐interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p   〈  .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances ( p  = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups ( p   〉  .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p  = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p   〈  .01). Conclusions Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2035400-9
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Background: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to medical management may differ between clinician specialties. Methods: We conducted an international survey (1/1/22-3/31/22) regarding management strategies in acute BAO prior to the announcement of 2 trials indicating superiority of EVT, and compared responses between interventionalists (INT) and non-interventionalists (nINT). Selection practices for routine EVT based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results: Among the 1245 respondents (nINT=702), INT more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p 〈 0.01). A similar proportion of INT and nINT responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific circumstances (p=0.45). Among respondents who would recommend EVT, there was no difference in the maximum pre-stroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p 〉 0.05), although nINT more commonly preferred perfusion imaging (24.2% vs. 19.7%, p=0.04). Among respondents who indicated they would randomize to medical management, INT were more likely to randomize when the NIHSS was ≥10 (15.9% vs. 6.9%, p 〈 0.01). Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a patient to medical treatment. There were small differences in preference of advanced neuroimaging, although these preferences were unsupported by clinical trial data.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 9
    In: Annals of Neurology, Wiley, Vol. 92, No. 2 ( 2022-08), p. 184-194
    Abstract: To examine rates of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), door‐to‐needle (DTN) time, door‐to‐puncture (DTP) time, and functional outcome between patients with admission magnetic resonance imaging (MRI) versus computed tomography (CT). Methods An observational cohort study of consecutive patients using a target trial design within the nationwide Swiss‐Stroke‐Registry from January 2014 to August 2020 was carried out. Exclusion criteria included MRI contraindications, transferred patients, and unstable or frail patients. Multilevel mixed‐effects logistic regression with multiple imputation was used to calculate adjusted odds ratios with 95% confidence intervals for IVT, MT, DTN, DTP, and good functional outcome (mRS 0–2) at 90 days. Results Of the 11,049 patients included (mean [SD] age, 71 [15] years; 4,811 [44%] women; 69% ischemic stroke, 16% transient ischemic attack, 8% stroke mimics, 6% intracranial hemorrhage), 3,741 (34%) received MRI and 7,308 (66%) CT. Patients undergoing MRI had lower National Institutes of Health Stroke Scale (median [interquartile range] 2 [0–6] vs 4 [1–11] ), and presented later after symptom onset (150 vs 123 min, p   〈  0.001). Admission MRI was associated with: lower adjusted odds of IVT (aOR 0.83, 0.73–0.96), but not with MT (aOR 1.11, 0.93–1.34); longer adjusted DTN (+22 min [13–30]), but not with longer DTP times; and higher adjusted odds of favorable outcome (aOR 1.54, 1.30–1.81). Interpretation We found an association of MRI with lower rates of IVT and a significant delay in DTN, but not in DTP and rates of MT. Given the delays in workflow metrics, prospective trials are required to show that tissue‐based benefits of baseline MRI compensate for the temporal benefits of CT. ANN NEUROL 2022;92:184–194
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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  • 10
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 102, No. 1 ( 2024-01-9)
    Abstract: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. Methods We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013–2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. Results The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62–80] years, baseline NIH Stroke Scale 6 [2–12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145–185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. Discussion CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
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