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  • 1
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    Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data
    Elsevier BV ; 2020
    In:  The Lancet Vol. 396, No. 10262 ( 2020-11), p. 1574-1584
    Details
    In: The Lancet, Elsevier BV, Vol. 396, No. 10262 ( 2020-11), p. 1574-1584
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(20)32163-2
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
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    Abstract TMP12: Large Vessel Vasculopathy is Associated With Oxygen Metabolic Stress in Children and Young Adults With Sickle Cell Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: Large-vessel vasculopathy (LVV), such as moyamoya syndrome, increases stroke risk with sickle cell disease (SCD). We hypothesized that tissue-based cerebral blood flow (CBF) and oxygen extraction fraction (OEF), as indicators of hemodynamic and metabolic stress, would differ in hemispheres with vs. without LVV. Methods: Patients underwent serial brain MRI and time-of-flight MRA to quantify voxel-wise CBF, OEF, and infarcts. LVV was defined as 75-99% stenosis of a major anterior circulation artery. Hemispheres with large vessel occlusion or revascularization surgery were excluded. Infarcted voxels were removed. Mean hemispheric (hemi-) CBF, OEF of the anterior circulation were extracted based on a vascular territory template. Hemi- OEF was normalized to whole brain OEF (nOEF). Hemi- cerebral metabolic rate of oxygen utilization (CMRO 2 ) was calculated from arterial oxygen content, hemi- CBF, and hemi- OEF. Mann-Whitney U was used to compare hemispheres with vs. without LVV. Effects of age, hemoglobin, and repeated MRIs were adjusted for in linear mixed model. Results: Of 158 patients, 221 MRI and MRAs were performed. At baseline, LVV occurred in 5% of hemispheres. Median infarct volume was larger in hemispheres with vs. without LVV (6.5 vs. 0.04 mL, p 〈 0.001). In baseline univariate analysis, hemispheres with LVV had lower CBF (25.8 vs 31.3 mL/100g/min, p =0.04), non-significantly higher nOEF (0.99 vs. 0.96, p =0.067), and lower CMRO 2 (8.1 vs. 12.4 mL/100g/min, p =0.002) vs. without LVV. In mixed model, with all MRIs included, LVV was independently associated with nOEF (β = 0.03, p =0.04) and showed a trend for association with CBF (β = -5.4, p =0.09) and CMRO 2 (β = -35.2, p =0.08). Discussion: In SCD, hemispheric OEF was increased as a compensatory response to flow-limiting stenosis, yet may be inadequate to prevent infarction as CMRO 2 decreased. Hemispheric OEF, as an indicator of increased stroke risk, may guide medical management and surgical intervention.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.TMP12
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
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  • 3
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    Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia
    American Society of Hematology ; 2019
    In:  Blood Vol. 133, No. 22 ( 2019-05-30), p. 2436-2444
    Details
    In: Blood, American Society of Hematology, Vol. 133, No. 22 ( 2019-05-30), p. 2436-2444
    Abstract: Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P & lt; .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%] ), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-09-876318
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 4
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    Correlation Between Cerebral Blood Flow Velocities Measured By Magnetic Resonance and Transcranial Doppler Ultrasound in Children with Sickle Cell Anemia
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 2496-2496
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2496-2496
    Abstract: Background Transcranial Doppler (TCD) ultrasonography is the standard stroke screening test for children with sickle cell anemia (SCA). However, approximately 10% of children have inadequate ultrasonographic windows for a successful TCD study, and some clinical sites may lack the equipment or personnel to perform TCDs in children. Magnetic resonance imaging (MRI) techniques can also measure blood flow velocities and could substitute for TCD in these clinical scenarios. We tested the hypothesis that MRI-derived middle cerebral artery (MCA) blood flow velocities would correlate with TCD-derived MCA blood flow velocities in children with SCA. Methods Children age 6 years and up with SCA at their baseline state of health underwent TCD and MRI as part of a prospective clinical study. Imaging TCD of the bilateral MCAs to determine time-average mean of maximum blood flow velocities (TCD-CBFV) were performed using clinical ultrasound equipment. MRIs were performed at 3T without sedation. MRI cerebral time-averaged mean blood flow velocities (MR-CBFV) were measured in the MCAs using phase contrast sequences without cardiac cycle gating to shorten acquisition time and reduce ghosting artifacts. TCD- and MR-CBFV of each hemisphere were compared. Silent cerebral infarctions (SCIs) were categorized as present or absent in each hemisphere. Non-parametric tests were used with a level of significance of 〈 0.05. Statistics were performed in SPSS version 21. Results Twenty hemispheres from 15 children had both TCD-CBFV and MR-CBFV measurements. Median age was 9 years (IQR 6.25-10). In these children, two hemispheres had unobtainable TCDs due to skull thickness, and eight hemispheres had MR-CBFV excluded due to patient motion or poor positioning. The median TCD-CBFV was 116 cm/sec (IQR 90.25-124) and none of the included hemispheres had arterial stenosis or TCD-CBFV in the conditional or abnormal range. Eight included hemispheres were from children receiving chronic blood transfusion therapy for primary or secondary stroke prevention. There was a linear relationship between TCD-CBFV and MR-CBFV (Spearman correlation, ρ=0.781, p 〈 0.001, Figure) although MR-CBFV values were lower than TCD-CBFV values (median difference 32.6%, IQR 26.7-42.8). When evaluating only the children not receiving chronic transfusion therapy, MR-CBFV was significantly higher in 8 hemispheres without SCIs (median 80 cm/sec, IQR 77.8-87.8) than in 4 hemispheres with SCIs (median 60 cm/sec, IQR 44.6-72.3, p=0.004). In a multivariate model adjusting for age, MR-CBFV continued to be associated with presence of SCIs (p=0.036). There was no significant difference in TCD-CBFV when analyzed by SCI status (p=0.2), consistent with published studies of TCD-CBFV and SCIs. Conclusions In this small cohort of children with SCA, MR-CBFV correlated significantly with TCD-CBFV, but MR-CBFV values were approximately 30% lower than TCD-CBFV. This may be due to the method of acquiring MR-CBFV via non-gated methodology, which is known to produce lower blood flow velocity estimates. Further work is needed to determine a threshold for high-risk MR-CBFV values before this modality could be used as a substitute for TCD screening. Lower MR-CBFV was associated with SCIs, suggesting a potential role for MR-CBFV in predicting SCI risk. The relationship between MR-CBFV and SCIs should be explored further. Disclosures Hulbert: Pfizer, Inc.: Other: spouse employment. Fields:NeuroPhage Pharmaceuticals: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.2496.2496
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
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  • 5
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    Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 7 ( 2022-07-29), p. 2394-2406
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 7 ( 2022-07-29), p. 2394-2406
    Abstract: During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac080
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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    SSG: 12
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  • 6
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    Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results
    Wiley ; 2018
    In:  Annals of Neurology Vol. 83, No. 5 ( 2018-05), p. 980-993
    Details
    In: Annals of Neurology, Wiley, Vol. 83, No. 5 ( 2018-05), p. 980-993
    Abstract: 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
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v83.5
    DOI: 10.1002/ana.25235
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2037912-2
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  • 7
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    Cerebral oxygen metabolic stress is increased in children with sickle cell anemia compared to anemic controls
    Wiley ; 2022
    In:  American Journal of Hematology Vol. 97, No. 6 ( 2022-06), p. 682-690
    Details
    In: American Journal of Hematology, Wiley, Vol. 97, No. 6 ( 2022-06), p. 682-690
    Abstract: Patients with sickle cell anemia (SCA) experience cerebral metabolic stress with an increase in oxygen extraction fraction (OEF) to compensate for reduced oxygen carrying capacity due to anemia. It remains unclear if anemia alone drives this metabolic stress. Using MRI, we collected voxel‐wise OEF measurements to test our hypothesis that OEF would be elevated in anemic controls without SCA (AC) compared to healthy controls (HC), but OEF would be even higher in SCA compared to AC. Brain MRIs ( N  = 159) were obtained in 120 participants (34 HC, 27 AC, 59 SCA). While hemoglobin was lower in AC versus HC ( p   〈  0.001), hemoglobin was not different between AC and SCA cohorts ( p  = 0.459). Whole brain OEF was higher in AC compared to HC ( p   〈  0.001), but lower compared to SCA ( p  = 0.001). Whole brain OEF remained significantly higher in SCA compared to HC ( p  = 0.001) while there was no longer a difference between AC versus HC ( p  = 0.935) in a multivariate model controlling for age and hemoglobin. OEF peaked within the border zone regions of the brain in both SCA and AC cohorts, but the volume of white matter with regionally elevated OEF in AC was smaller (1.8%) than SCA (58.0%). While infarcts colocalized within regions of elevated OEF, more SCA participants had infarcts than AC ( p   〈  0.001). We conclude that children with SCA experience elevated OEF compared to AC and HC after controlling for the impact of anemia, suggesting that there are other pathophysiologic factors besides anemia contributing to cerebral metabolic stress in children with SCA.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    URL: Article
    DOI: 10.1002/ajh.v97.6
    DOI: 10.1002/ajh.26485
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1492749-4
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  • 8
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    Abstract 171: Cerebral Blood Flow and Oxygen Extraction Fraction are Age-dependent in Children and Young Adults with and without Sickle Cell Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. suppl_1 ( 2017-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. suppl_1 ( 2017-02)
    Abstract: Introduction: Children with sickle cell disease (SCD) are a high risk population for pediatric stroke. Young children with SCD have a higher stroke incidence than older children. Cerebral oxygen metabolism, the product of CBF, OEF and arterial oxygen content (CaO 2 , [oxygen saturation (SpO 2 ) x hemoglobin (Hb) x 1.36]) is age-dependent in healthy children, peaking at 5-9 years of age. CBF is age-dependent, but OEF variation across childhood is not well-studied. In non-SCD adults, elevated OEF confers higher stroke risk. Children with SCD have higher CBF and OEF than healthy controls, but also have lower CaO 2 . It is unknown if age independently influences CBF and OEF. We hypothesized that age, sex and CaO 2 influence components of cerebral oxygen metabolism, as measured by MRI. Methods: Subjects with SCD and sibling/relative controls without SCD underwent brain MRI with measurement of CBF and OEF by pseudocontinuous arterial spin labeling and asymmetric spin echo sequences, respectively. Blood samples were obtained for Hb and hematocrit values. A fast inversion recovery sequence measured T1 values in the superior sagittal sinus. A multiple regression model determined significant factors influencing CBF and OEF (age, sex, CaO 2 ). Results: We scanned 25 subjects without SCD (ages 6-27) and 56 subjects with SCD (ages 5-28). In multiple regression analysis, age (p=0.0009) and CaO 2 (p 〈 0.0001) were significantly predictive of CBF, controlling for sex. Age (p=0.027) and CaO 2 (p 〈 0.0001), were also significantly predictive of OEF, controlling for sex. Conclusion: Age is an independent predictor of CBF and OEF. Younger children have higher CBF and OEF, even after controlling for the lower CaO 2 associated with SCD. This may explain the increased stroke incidence in young children with SCD.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.48.suppl_1.171
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 9
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    Abstract T P370: Blood Transfusions in Pediatric Sickle Cell Disease Normalize Cerebral Blood Flow While Maintaining Constant Cerebral Oxygen Metabolism
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. suppl_1 ( 2015-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. suppl_1 ( 2015-02)
    Abstract: Background: Chronic blood transfusions (Tx) reduces stroke risk in pediatric sickle cell disease (SCD). Cerebral blood flow (CBF) is elevated in SCD, likely representing a compensatory mechanism to maintain cerebral oxygen metabolism (CMRO2) in the setting of reduced arterial oxygen content (CaO2) from chronic anemia. When exhausted compensatory mechanisms are unable to meet oxygen demands, stroke ensues. We measured MR-derived CBF and oxygen extraction fraction (OEF) pre- and post-Tx, hypothesizing that Tx ‘resets’ the CBF baseline by increasing CaO2 via increased hemoglobin (Hb), while maintaining cerebral oxygen delivery and metabolism. Methods: SCD children on chronic Tx were enrolled in a prospective, observational MRI study. MR-CBF and MR-OEF were acquired before and 2 hours after exchange Tx. MR-CBF and MR-OEF were measured using pseudocontinuous arterial spin labelling and a novel asymmetric spin echo sequence, respectively. CaO2 =1.35 x [Hb] x SaO2. CMRO2 = CaO2 x CBF x OEF. Results: Two SCD children underwent MRI pre- and post-Tx (six more are anticipated prior to ISC). For subject #1 (18 yo F with overt stroke), mean global CBF was 128 and 98 ml/min/100g pre- and post-Tx, respectively, indicating a 24% CBF reduction. For subject #2 (6 yo F with elevated transcranial Doppler velocities), mean global CBF was 189 and 129 ml/min/100g pre- and post-Tx, respectively, a 32% CBF reduction (Fig). Both Hb and CaO2 were increased after Tx, resulting in unchanged oxygen delivery (CaO2 x CBF) post-Tx. Moreover, OEF and CMRO2 were not significantly different pre- and post-Tx, consistent with our hypothesis that CBF increases to maintain oxygen delivery. Conclusions: Elevated CBF is likely a compensatory mechanism to maintain constant oxygen delivery in SCD children who have chronically low CaO2. In our subjects, Tx improved CaO2, allowing CBF to normalize. This reduced hemodynamic stress likely contributes to the lower stroke risk in chronically transfused SCD children.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.46.suppl_1.tp370
    RVK:
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 10
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    Abstract 36: Acute Stroke Evolution is in the Eye of the Beholder: Effects of Interrater Variability on Patient Selection and Outcomes in the Mr Witness (nct01282242) Multicenter Thrombolysis Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. suppl_1 ( 2017-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. suppl_1 ( 2017-02)
    Abstract: 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 〈 4.5 hr duration, but visual inspection alone may be unreliable and insensitive. Signal intensity ratios (SIR) of manual outlines (lesion/contralateral side) increase sensitivity but can lead to variability in patient selection. We investigated the influence of interrater variability on clinical and safety outcomes. 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 〈 1.15. Good outcome was defined as 90 Day modified Rankin Scale (mRS) 〈 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 〈 .001) and kappa was 67% (P 〈 .0001). Among the 80 subjects enrolled using SIR 〈 1.15 by site reading, 15 (18.8%) subjects would have been excluded based on Core readings. These 15 subjects were younger with worse NIHSS and 90-day mRS (Table). Subset analyses of subjects with pre-stroke mRS 〈 2 showed no statistical difference (P=0.19) between subjects deemed eligible and not eligible by core readers. No difference in hemorrhagic transformation (HT) or good outcome rates was found. Using SIR 〈 1.25 would have only excluded 3 subjects by Core readings, all of whom had HT, and poor 90 day outcomes. 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.48.suppl_1.36
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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