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  • 1
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    Online Resource
    Primary Angiitis of the CNS : A Systematic Review and Meta-analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 8, No. 6 ( 2021-11), p. e1093-
    Details
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 6 ( 2021-11), p. e1093-
    Abstract: To facilitate and improve the diagnostic and therapeutic process by systematically reviewing studies on patients with primary angiitis of the CNS (PACNS). Methods We searched PubMed, looking at the period between 1988 and February 2020. Studies with adult patients with PACNS were included. We extracted and pooled proportions using fixed-effects models. Main outcomes were proportions of patients with certain clinical, imaging, and laboratory characteristics and neurologic outcomes. Results We identified 46 cohort studies including a total of 911 patients (41% biopsy confirmed, 43% angiogram confirmed, and 16% without clear assignment to the diagnostic procedure). The most frequent onset symptoms were focal neurologic signs (63%), headache (51%), and cognitive impairment (41%). Biopsy- compared with angiogram-confirmed cases had higher occurrences of cognitive impairment (55% vs 39%) and seizures (36% vs 16%), whereas focal neurologic signs occurred less often (56% vs 95%). CSF abnormalities were present in 75% vs 65% and MRI abnormalities in 97% vs 98% of patients. Digital subtraction angiography was positive in 33% of biopsy confirmed, and biopsy was positive in 8% of angiogram-confirmed cases. In 2 large cohorts, mortality was 23% and 8%, and the relapse rate was 30% and 34%, during a median follow-up of 19 and 57 months, respectively. There are no randomized trials on the treatment of PACNS. The initial treatment usually includes glucocorticoids and cyclophosphamide. Discussion PACNS is associated with disabling symptoms, frequent relapses, and significant mortality. Differences in symptoms and neuroimaging results and low overlap between biopsy and angiogram suggest that biopsy- and angiogram-confirmed cases represent different histopathologic types of PACNS. The optimal treatment is unknown.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    URL: Article
    DOI: 10.1212/NXI.0000000000001093
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2767740-0
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  • 2
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    CT Hypoperfusion-Hypodensity Mismatch to Identify Patients With Acute Ischemic Stroke Within 4.5 Hours of Symptom Onset
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 97, No. 21 ( 2021-11-23), p. e2088-e2095
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 21 ( 2021-11-23), p. e2088-e2095
    Abstract: To test the hypothesis that CT hypoperfusion-hypodensity mismatch identifies patients with ischemic stroke within 4.5 hours of symptom onset. Methods We therefore performed the Retrospective Multicenter Hypoperfusion-Hypodensity Mismatch for The identification of Patients With Stroke Within 4.5 Hours study of patients with acute ischemic stroke and known time of symptom onset. The predictive values of hypoperfusion-hypodensity mismatch for the identification of patients with symptom onset within 4.5 hours were the main outcome measure. Results Of 666 patients, 548 (82.3%) had multimodal CT within 4.5 hours and 118 (17.7%) beyond 4.5 hours. Hypoperfusion-hypodensity mismatch was visible in 516 (94.2%) patients with symptom onset within and in 30 (25.4%) patients beyond 4.5 hours. CT hypoperfusion-hypodensity mismatch identified patients within 4.5 hours of stroke onset with 94.2% (95% confidence interval [CI] 91.9%–95.8%) sensitivity, 74.6% (95% CI 66.0%–81.6%) specificity, 94.5% (95% CI 92.3%–96.1%) positive predictive value, and 73.3% (95% CI 64.8%–80.4%) negative predictive value. Interobserver agreement for hypoperfusion-hypodensity mismatch was substantial (κ = 0.61, 95% CI 0.53–0.69). Discussion Patients with acute ischemic stroke with absence of a hypodensity on native CT (NCCT) within the hypoperfused core lesion on perfusion CT (hypoperfusion-hypodensity mismatch) are likely to be within the time window of thrombolysis. Applying this method may guide the decision to use thrombolysis in patients with unknown time of stroke onset. Trial Registration Information ClinicalTrials.gov Identifier: NCT04277728. Classification of Evidence This study provides Class III evidence that CT hypoperfusion-hypodensity mismatch identifies patients with stroke within 4.5 hours of onset.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000012891
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 3
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    Data_Sheet_3.PDF
    Frontiers Media SA ; 2024
    In:  Frontiers in Neurology Vol. 15 ( 2024-4-9)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 15 ( 2024-4-9)
    Abstract: The “translational roadblock” between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution. Methods To verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later. Results Our preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%. Conclusion Our study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2024.1383494
    DOI: 10.3389/fneur.2024.1383494.s001
    DOI: 10.3389/fneur.2024.1383494.s002
    DOI: 10.3389/fneur.2024.1383494.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2564214-5
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  • 4
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    Why Most Acute Stroke Studies Are Positive in Animals but Not in Patients: A Systematic Comparison of Preclinical, Early Phase, and Phase 3 Clinical Trials of Neuroprotective Agents
    Wiley ; 2020
    In:  Annals of Neurology Vol. 87, No. 1 ( 2020-01), p. 40-51
    Details
    In: Annals of Neurology, Wiley, Vol. 87, No. 1 ( 2020-01), p. 40-51
    Abstract: To analyze why numerous acute stroke treatments were successful in the laboratory but failed in large clinical trials. Methods We searched all phase 3 trials of medical treatments for acute ischemic stroke and corresponding early clinical and experimental studies. We compared the overall efficacy and assessed the impact of publication bias and study design on the efficacy. Furthermore, we estimated power and true report probability of experimental studies. Results We identified 50 phase 3 trials with 46,008 subjects, 75 early clinical trials with 12,391 subjects, and 209 experimental studies with 〉 7,141 subjects. Three (6%) phase 3, 24 (32%) early clinical, and 143 (69.08%) experimental studies were positive. The mean treatment effect was 0.76 (95% confidence interval [CI] = 0.70–0.83) in experimental studies, 0.87 (95% CI = 0.71–1.06) in early clinical trials, and 1.00 (95% CI = 0.95–1.06) in phase 3 trials. Funnel plot asymmetry and trim‐and‐fill revealed a clear publication bias in experimental studies and early clinical trials. Study design and adherence to quality criteria had a considerable impact on estimated effect sizes. The mean power of experimental studies was 17%. Assuming a bias of 30% and pre‐study odds of 0.5 to 0.7, this leads to a true report probability of 〈 50%. Interpretation Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the stepwise efficacy decline of stroke treatments from experimental studies to phase 3 clinical trials. Even under conservative estimates, less than half of published positive experimental stroke studies are truly positive. ANN NEUROL 2020;87:40–51
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v87.1
    DOI: 10.1002/ana.25643
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2037912-2
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  • 5
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    Simplified Assessment of Lesion Water Uptake for Identification of Patients within 4.5 Hours of Stroke Onset: An Analysis of the MissPerfeCT Study
    Korean Stroke Society ; 2022
    In:  Journal of Stroke Vol. 24, No. 3 ( 2022-09-30), p. 390-395
    Details
    In: Journal of Stroke, Korean Stroke Society, Vol. 24, No. 3 ( 2022-09-30), p. 390-395
    Abstract: Background and Purpose Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether a simple method of computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours. Methods This retrospective analysis of the MissPerfeCT study (August 2009 to November 2017) includes consecutive patients with known onset of symptoms from seven tertiary stroke centers. We developed a simplified algorithm based on region of interest (ROI) measurements to quantify water uptake of the ischemic lesion and thereby quantify time of symptom onset within and beyond 4.5 hours. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in non-contrast CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. Results Of 263 patients, 204 (77.6%) had CT within 4.5 hours. Water uptake was significantly lower in patients with stroke onset within (6.7%; 95% confidence interval [CI] , 6.0% to 7.4%) compared to beyond 4.5 hours (12.7%; 95% CI, 10.7% to 14.7%). The area under the curve for distinguishing these patient groups according to percentage water uptake was 0.744 with an optimal cut-off value of 9.5%. According to this cut-off the positive predictive value was 88.8%, sensitivity was 73.5%, specificity 67.8%, negative predictive value was 42.6%. Conclusions Ischemic stroke patients with unknown time of symptom onset can be identified as being within a timeframe of 4.5 hours using a ROI-based method to assess water uptake on admission non-contrast head CT.
    Type of Medium: Online Resource
    ISSN: 2287-6391 , 2287-6405
    URL: Article
    DOI: 10.5853/jos.2022.00220
    Language: English
    Publisher: Korean Stroke Society
    Publication Date: 2022
    detail.hit.zdb_id: 2814366-8
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  • 6
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    Stroke in Patients with Bacterial Meningitis: A Cohort Study and Meta‐Analysis
    Wiley ; 2023
    In:  Annals of Neurology Vol. 93, No. 6 ( 2023-06), p. 1094-1105
    Details
    In: Annals of Neurology, Wiley, Vol. 93, No. 6 ( 2023-06), p. 1094-1105
    Abstract: The purpose of this study was to characterize patients with ischemic stroke due to bacterial meningitis. Methods In a single‐center retrospective study, we analyzed 102 patients with bacterial meningitis of which 19 had an ischemic stroke. Clinical characteristics, cerebrospinal fluid (CSF) analyses, and spatiotemporal distribution of infarcts were assessed. In addition, we searched PubMed from database inception to August 2021 for observational studies on ischemic stroke in patients with bacterial meningitis, and performed a meta‐analysis to investigate the frequency and timing of stroke as well as its effect on mortality. Results In our cohort, 15 (78.9%) patients with stroke had an modified Rankin scale (mRS)  3 at discharge compared to 33 (39.8%) in patients without stroke ( p   〈  0.01). Of 1,692 patients with bacterial meningitis from 15 cohort studies included in our meta‐analysis, cerebral infarcts were found in 332 (16%, 95% confidence interval [CI] = 0.13–0.20) patients. The occurrence of stroke was strongly associated with a higher mortality (odds ratio [OR]  = 2.38, 95% CI = 1.70–3.34, p   〈  0.0001). There was no association of any specific causative pathogen with the occurrence of stroke. Infarcts were mainly distributed in territories of arteries located in the vicinity to the infection focus and peaked at 3 to –7 days and at 2 weeks after onset of meningitis. In patients with ischemic stroke, vasculopathy was found in 63.2% and additional intracerebral hemorrhage in 15.8%. Interpretation This study found that ischemic stroke due to bacterial meningitis is caused by cerebral vasculopathy located in the vicinity of the infection focus, and that the time course of infarctions might enable a therapeutic intervention. ANN NEUROL 2023;93:1094–1105
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v93.6
    DOI: 10.1002/ana.26618
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2037912-2
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  • 7
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    Online Resource
    Immune Cell Infiltration into the Brain After Ischemic Stroke in Humans Compared to Mice and Rats: a Systematic Review and Meta-Analysis
    Springer Science and Business Media LLC ; 2021
    In:  Translational Stroke Research Vol. 12, No. 6 ( 2021-12), p. 976-990
    Details
    In: Translational Stroke Research, Springer Science and Business Media LLC, Vol. 12, No. 6 ( 2021-12), p. 976-990
    Abstract: Although several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet demonstrated a clear benefit of immune modulation in patients. Potential reasons include systematic differences of post-ischemic neuroinflammation between humans and rodents. We here performed a systematic review and meta-analysis to summarize and compare the spatial and temporal distribution of immune cell infiltration in human and rodent stroke. Data on spatiotemporal distribution of immune cells (T cells, macrophages, and neutrophils) and infarct volume were extracted. Data from all rodent studies were pooled by means of a random-effect meta-analysis. Overall, 20 human and 188 rodent stroke studies were included in our analyses. In both patients and rodents, the infiltration of macrophages and neutrophils preceded the lymphocytic influx. Macrophages and neutrophils were the predominant immune cells within 72 h after infarction. Although highly heterogeneously across studies, the temporal profile of the poststroke immune response was comparable between patients and rodents. In rodent stroke, the extent of the immune cell infiltration depended on the duration and location of vessel occlusion and on the species. The density of infiltrating immune cells correlated with the infarct volume. In summary, we provide the first systematic analysis and comparison of human and rodent post-ischemic neuroinflammation. Our data suggest that the inflammatory response in rodent stroke models is comparable to that in patients with stroke. However, the overall heterogeneity of the post-ischemic immune response might contribute to the translational failure in stroke research.
    Type of Medium: Online Resource
    ISSN: 1868-4483 , 1868-601X
    URL: Article
    DOI: 10.1007/s12975-021-00887-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2541897-X
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  • 8
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    Online Resource
    Prediction of Malignant Middle Cerebral Artery Infarction Using Computed Tomography-Based Intracranial Volume Reserve Measurements
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Stroke Vol. 42, No. 12 ( 2011-12), p. 3403-3409
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 12 ( 2011-12), p. 3403-3409
    Abstract: Early decompressive surgery in patients with malignant middle cerebral artery (MCA) infarction improves outcome. Elevation of intracranial pressure depends on both the space occupying brain edema and the intracranial volume reserve (cerebrospinal fluid [CSF] ). However, CSF volume was not investigated as a predictor of malignant infarction so far. We hypothesize that assessment of CSF volume in addition to admission infarct size improves early prediction of malignant MCA infarction. Methods— Stroke patients with carotid-T or MCA main stem occlusion and ischemic lesion (reduced cerebral blood volume [CBV]) on perfusion CT were considered for the analysis. The end point malignant MCA infarction was defined by clinical signs of herniation. Volumes of CSF and CBV lesion were determined on admission. Receiver-operator characteristics analysis was used to calculate predictive values for radiological and clinical measurements. Results— Of 52 patients included, 26 (50%) developed malignant MCA infarction. Age, a decreased level of consciousness on admission, CBV lesion volume, CSF volume, and the ratio of CBV lesion volume to CSF volume were significantly different between malignant and nonmalignant groups. The best predictor of a malignant course was the ratio of CBV lesion volume to CSF volume with a cut-off value of 0.92 (96.2% sensitivity, 96.2% specificity, 96.2% positive predictive value, and 96.2% negative predictive value). Conclusions— Based on admission native CT and perfusion CT measurements, the ratio of ischemic lesion volume to CSF volume predicts the development of malignant MCA infarction with higher accuracy than other known predictors, including ischemic lesion volume or clinical characteristics.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.111.619734
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Online Resource
    Feasibility Platform for Stroke Studies : An Online Tool to Improve Eligibility Criteria for Clinical Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. 1 ( 2015-01), p. 137-142
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 1 ( 2015-01), p. 137-142
    Abstract: Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. Methods— We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. Results— Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de , displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. Conclusions— FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.114.007124
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467823-8
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  • 10
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    Online Resource
    Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke : A Prospective Observational Study
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. 6 ( 2016-06), p. 1584-1592
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 6 ( 2016-06), p. 1584-1592
    Abstract: In patients with ischemic stroke, randomized trials showed a better functional outcome after endovascular therapy with new-generation thrombectomy devices compared with medical treatment, including intravenous thrombolysis. However, effects on mortality and the generalizability of results to routine clinical practice are uncertain. Methods— In a prospective observational register-based study patients with ischemic stroke treated either with thrombectomy, intravenous thrombolysis, or their combination were included. Primary outcome was the modified Rankin scale score (0 [no symptoms] to 6 [death] ) at 3 months. Ordinal logistic regression was used to estimate the common odds ratio as treatment effects (shift analysis). Propensity score matching was applied to compare patients treated either with intravenous thrombolysis alone or with intravenous thrombolysis plus thrombectomy. Results— Among 2650 recruited patients, 1543 received intravenous thrombolysis, 504 underwent thrombectomy, and 603 received intravenous thrombolysis in combination with thrombectomy. Later time-to-treatment was associated with worse outcomes among patients treated with thrombectomy plus thrombolysis. In 241 pairs of propensity score–matched patients with a proximal intracranial occlusion, thrombectomy plus thrombolysis was associated with improved functional outcome (common odds ratio, 1.84; 95% confidence interval, 1.32–2.57), and reduced mortality (15% versus 33%; P 〈 0.0001) compared with intravenous thrombolysis alone. Results were similar in various sensitivity analyses accounting for missing outcome data and different analytic methods. Conclusions— Results from this large prospective registry show that also in routine clinical care thrombectomy plus thrombolysis compared with thrombolysis alone improved functional outcome and reduced mortality in patients with ischemic stroke. Earlier treatment was associated with better outcomes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.116.012619
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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