National Institute of Neurological Disorders and Stroke

Background: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke, often resulting from reperfusion therapy. Early prediction of HT can enable stroke neurologists to undertake measures to avoid clinical deterioration and make optimal treatment strategies. Moreover, the trend of extending the time window for reperfusion therapy (both for intravenous thrombolysis and endovascular treatment) further requires more precise detection of HT tendency. Summary: In this review, we summarized and discussed the neuroimaging markers of HT prediction of acute ischemic stroke patients, mainly focusing on neuroimaging markers of ischemic degree and neuroimaging markers of blood-brain barrier permeability. This review is aimed to provide a concise introduction of HT prediction and to elicit possibilities of future research combining advanced technology to improve the accessibility and accuracy of HT prediction under emergent clinical settings. Key Messages: Substantial studies have utilized neuroimaging, blood biomarkers, and clinical variables to predict HT occurrence. Although huge progress has been made, more individualized and precise HT prediction using simple and robust imaging predictors combining stroke onset time should be the future goal of development.

Neuroimaging Prediction of Hemorrhagic Transformation for Acute Ischemic Stroke

Background and aimWe determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke.MethodsThe THAWS was a mult...

Cerebral microbleeds development after stroke thrombolysis: A secondary analysis of the THAWS randomized clinical trial:

Stroke constitutes a major cause of functional disability and mortality, with increasing prevalence. Thus, the timely and accurate prognosis of stroke outcomes based on clinical or radiological markers is vital for both physicians and stroke survivors. Among radiological markers, cerebral microbleeds (CMBs) constitute markers of blood leakage from pathologically fragile small vessels. In the present review, we evaluated whether CMBs affect ischemic and hemorrhagic stroke outcomes and explored the fundamental question of whether CMBs may shift the risk–benefit balance away from reperfusion therapy or antithrombotic use in acute ischemic stroke patients. A literature review of two databases (MEDLINE and Scopus) was conducted to identify all the relevant studies published between 1 January 2012 and 9 November 2022. Only full-text articles published in the English language were included. Forty-one articles were traced and included in the present review. Our findings highlight the utility of CMB assessments, not only in the prognostication of hemorrhagic complications of reperfusion therapy, but also in forecasting hemorrhagic and ischemic stroke patients’ functional outcomes, thus indicating that a biomarker-based approach may aid in the provision of counseling for patients and families, improve the selection of more appropriate medical therapies, and contribute to a more accurate choice of patients for reperfusion therapy.

https://www.mdpi.com/2035-8377/15/1/14/pdf?version=1675241812

Exploring the Impact of Cerebral Microbleeds on Stroke Management

Background and purpose As a part of the natural course of ischemic stroke, hemorrhagic transformation (HT) is a serious complication after reperfusion treatment, which may affect the prognosis of patients with ischemic stroke. White matter lesions (WMLs) refer to focal lesions on neuroimaging and have been suggested to indicate a high risk of HT. This systematic review and meta-analysis aimed to summarize current evidence on the relation between WML and HT. Methods This systematic review was prepared with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for publications on WML and HT in patients with ischemic stroke. Odds ratios (ORs) and 95% confidence intervals (CIs) from eligible studies were combined to quantify the association between the severity of WML and the risk of HT. In addition, the descriptive analysis was adopted to evaluate the influence of different WML distributions on predicting HT. Results A total of 2,303 articles were identified after removing duplicates through database searching, and 41 studies were included in our final analysis. The meta-analysis showed that the presence of WML was associated with HT (OR = 1.62, 95%CI 1.08–2.43, p = 0.019) and symptomatic intracerebral hemorrhage (sICH) (OR = 1.64, 95%CI 1.17–2.30, p = 0.004), and moderate-to-severe WML indicated a high risk of HT (OR = 2.03, 95%CI 1.33–3.12, p = 0.001) and sICH (OR = 1.92, 95%CI 1.31–2.81, p < 0.001). The dose–response meta-analysis revealed risk effects of increasing the severity of WML on both HT and ICH. In addition, both periventricular WML (PWML) (five of seven articles) and deep WML (DWML) (five of six articles) were shown to be associated with HT. Conclusions White matter lesions are associated with overall HT and sICH in patients with ischemic stroke, and more severe WMLs indicate a high risk of HT and sICH. In addition, both PWML and DWMLs could be risk factors for HT. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42022313467.

https://www.frontiersin.org/articles/10.3389/fnagi.2022.1053149/pdf

The association between the severity and distribution of white matter lesions and hemorrhagic transformation after ischemic stroke: A systematic review and meta-analysis

Objective To test the hypothesis that remote intracerebral hemorrhages (r-ICHs) after IV thrombolysis occur in preexisting brain lesions. Method We prospectively collected baseline data from consecutive patients treated with IV thrombolysis for cerebral ischemia and reviewed their baseline MRI scans to identify preexisting lesions in those who developed r-ICH. We evaluated outcomes with the modified Rankin Scale (mRS) and defined good outcomes as scores of 0 to 2 or similar to the preexisting mRS score. Results Of 944 patients, 24 (2.5%) had r-ICH: lobar in 14, deep in 7, and both in 3. Sixteen of them (1.7% of all patients, 66.7% of those with r-ICH) were asymptomatic. Of the 41 r-ICHs found in these patients, 17 (41%) occurred within a lesion present before thrombolysis: 6 cerebral microbleeds (CMBs), 6 old and 1 recent infarct, and 4 areas of white matter hyperintensity. Patients with r-ICH were more likely to have strictly lobar CMBs (p = 0.049). They were 10 years older (p = 0.007), had a 16–mm Hg higher systolic blood pressure (p = 0.035) at baseline, and had more CMBs (p = 0.007). r-ICHs were better predicted by clinical (age, baseline systolic blood pressure) than imaging (purely lobar CMBs and having >5 CMBs) variables. r-ICHs tended to be associated with worse outcomes. Conclusion We identified preexisting brain lesions in nearly half of the patients with r-ICH. All were of vascular origin, supporting the hypothesis that r-ICHs occur in preexisting brain lesions. Higher-field machines could help identifying preexisting lesions in those who developed r-ICH in an apparently normal area.

Remote brain hemorrhage after IV thrombolysis: Role of preexisting lesions.

Background and objective Predictors of symptomatic haemorrhagic transformation (s-HT) of cerebral ischaemia after intravenous recombinant tissue-plasminogen activator (rt-PA) were identified in studies using CT scans. We evaluated whether MRI can identify other predictors. Method We analysed predictors of s-HT in a cohort of consecutive patients who received intravenous rt-PA for cerebral ischaemia after MRI at baseline. We used receiver operating characteristic curves considering an area under the curve (AUC) of 0.70 or higher as indicating acceptable discrimination. Results Of 944 patients, 49 patients (5.2%) developed s-HT. Clinical factors independently associated with s-HT were age (adjusted OR (adjOR) 1.03 for 1 year increase; 95% CI 1.01 to 1.05), excessive alcohol consumption (adjOR 3.13; 95% CI 1.32 to 7.42), recent transient ischaemic attack (adjOR 2.88; 95% CI 1.04 to 7.95) and baseline national institutes of health stroke scale score (adjOR 1.06 for 1 point increase; 95% CI 1.02 to 1.10). MRI predictors were vascular hyperintensities (adjOR 3.89; 95% CI 1.50 to 10.08), old infarcts (adjOR 2.01; 95% CI 1.11 to 3.66) and volume of diffusion-weighted imaging (DWI) abnormality (adjOR 1.02 for 1 cm3 increase; 95% CI 1.01 to 1.03). The only variable with an acceptable discrimination was volume of DWI abnormality (AUC 0.72; 95% CI 0.64 to 0.79), a value of 4 cm3 predicting s-HT with a 78% sensitivity and 58% specificity. Variables that can be assessed only with MRI did not predict s-HT. Conclusion Although the volume of DWI abnormality predicts s-HT, other imaging characteristics that can only be assessed with MRI were not significantly associated with s-HT. Trial
registration number NCT01614080

https://jnnp.bmj.com/content/jnnp/early/2020/02/03/jnnp-2019-321904.full.pdf

Use of MRI to predict symptomatic haemorrhagic transformation after thrombolysis for cerebral ischaemia.

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Remote brain hemorrhage after IV thrombolysis: Role of preexisting lesions.

Use of MRI to predict symptomatic haemorrhagic transformation after thrombolysis for cerebral ischaemia.