Background: Blood–brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischemia injury, and its clinical relevance at different timepoints post stroke. Aims: The main objective of this study is to assess BBBp evolution through stroke phases and its implications on patient outcomes. Methods: We screened PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials up to 31 December 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random-effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed a subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation, and imaging method. Results: We identified 3761 studies, of which 22 (1592 patients and 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, 8 for the acute, 5 for the subacute, and 2 for the chronic phase. All phases were associated with increased BBBp: 0.74 (0.48–0.99), 1.68 (0.94–2.42), 1.98 (0.96–3.00), and 1.00 (0.45–1.55), respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase and with improved functional outcomes in the late subacute phase. Conclusion: BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.
Stroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through different hemodynamic phases, namely the hyperacute, acute, subacute, and chronic phases. Stroke treatment is highly reliant on recanalization therapies, which are limited to only a subset of patients due to their narrow therapeutic window; hence, there is a huge need for new stroke treatments. Nonetheless, the vast majority of promising treatments are not effective in the clinical setting due to their inability to cross the blood-brain barrier and reach the brain. In this context, nanotechnology-based approaches such as nanoparticle drug delivery emerge as the most promising option. In this review, we will discuss the current status of nanotechnology in the setting of stroke, focusing on the diverse available nanoparticle approaches targeted to the different pathological and physiological repair mechanisms involved in each of the stroke phases.
21 December 2023 in American Journal of Neuroradiology
BACKGROUND: The optimal imaging method for detecting distal medium vessel occlusions (DMVOs) remains undefined. PURPOSE: The objective of this study is to compare the diagnostic performance of CTA with CTP in detecting DMVOs. DATA SOURCES: We searched PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials up to March 31, 2023 (PROSPERO: CRD42022344006). STUDY SELECTION: A total of 12 studies reporting accuracy values of CTA and/or CTP were included, comprising 2607 patients with 479 cases (18.3%) of DMVOs. DATA ANALYSIS: Pooled sensitivity and specificity of both imaging methods were compared using a random-effects model. Subgroup analyses were performed based on the technique used in CTA (multi or single-phase) and the subtype of DMVOs (M2-only vs. M2 and other DMVOs). We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria. DATA SYNTHESIS: CTA demonstrated significantly lower sensitivity compared to CTP in detecting DMVOs [0.74, 95%CI (0.63–0.82) vs. 0.89, 95% CI (0.82–0.93), P < 0.01]. When subgrouped into single-phase and multi-phase CTA, multi-phase CTA exhibited higher sensitivity for DMVO detection than single-phase CTA [0.91, 95%CI (0.85–0.94) vs. 0.64, 95%CI (0.56–0.71), P < .01], while reaching similar levels to CTP. The sensitivity of single-phase CTA substantially decreased when extending from M2 to other non-M2 DMVOs [0.74, 95%CI (0.63–0.83) vs. 0.61, 0.95%CI (0.53–0.68), P = .02]. LIMITATIONS: We identified an overall high risk of bias and low quality of evidence, attributable to the design and reference standards of most studies. CONCLUSIONS: Our findings highlight a significantly lower sensitivity of single-phase CTA compared to multi-phase CTA and CTP in diagnosing DMVOs.
25 November 2022 in International Journal of Stroke
Background: Twitter is a social media platform popularly used by health practitioners, a trend that has been followed by medical journals. The impact of Twitter in bibliometrics of stroke-related literature is yet to be determined. Aims: We aimed to qualitatively assess the usage of Twitter by stroke journals and study the relationship between Twitter activity and citation rates of stroke articles. Methods: We used Journal Citation Reports to identify stroke journals. We collected the 2021 Impact Factor (IF) and the top 50 articles contributing to each journal IF. Relevant metrics were collected through Twitonomy, Altmetric, and Web of Science. The association between Twitter activity and citation rates was tested by a negative binomial regression model adjusted to journal’s IF. A bivariate correlation and a log-linear regression model adjusted to journal’s IF tested the relationship between number of tweets, tweeters, and the number of citations. Results: We collected 450 articles across nine stroke-dedicated journals, five of which had a Twitter account. Only 95 (21%) articles had no Twitter mentions. The median number of citations in articles with versus without Twitter activity was 19 (10–39) versus 11(7–17) ( P < 0.001). Twitter activity was associated with higher citation rates controlling for the IF (odds ratio (OR): 2.7, 95% confidence interval (CI) 2.12–3.38, P < 0.001). We found number of tweets to be predicted by the number of citations controlling for the IF (B = 0.33, 95% CI 0.29–0.40, β = 0.54, P < 0.001). Conclusions: Tweeted stroke articles tend to have higher citation rates which can be predicted by the number of tweets.
BACKGROUND: The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment for acute ischemic stroke in patients with tandem occlusion secondary to cervical carotid artery dissection. METHODS: This was a secondary analysis of patients treated with endovascular treatment for acute ischemic stroke due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection). We compared patients with and without emergent stenting. The primary efficacy and safety outcomes were 90-day functional independence (modified Rankin Scale score, 0–2) and symptomatic intracranial hemorrhage within 24 hours after endovascular treatment. Procedural outcome was successful intracranial recanalization (modified Thrombolysis in Cerebral Infarction score of 2b/3). We used mixed-effects logistic regression adjusting for site, age, and National Institutes of Health Stroke Scale. In additional analyses, we used inverse probability of treatment weighting and adjusted for Alberta Stroke Program Early CT Score. RESULTS: Of the 4023 patients enrolled in STOP-CAD, 328 presented with anterior circulation acute ischemic stroke due to tandem occlusion and underwent endovascular treatment. The median age was 51 (interquartile range, 44–58) years, and 96 patients (29.3%) were female. One hundred fifty patients (45.7%) underwent emergent stenting. There was no significant association between stenting and 90-day functional independence (62.0% versus 59.7%; adjusted odds ratio, 1.23 [95% CI, 0.82–1.86]; P =0.315) or symptomatic intracranial hemorrhage (7.3% versus 7.9%; adjusted odds ratio, 0.95 [95% CI, 0.41–2.2]; P =0.913). Emergent carotid stenting was associated with successful intracranial recanalization (81.8% versus 76.6%; adjusted odds ratio, 2.62 [95% CI, 1.52–4.5]; P <0.001). Results did not meaningfully change in additional analyses. CONCLUSIONS: In patients presenting with an acute anterior circulation tandem occlusion secondary to cervical carotid artery dissection, emergent stenting was associated with a higher likelihood of successful intracranial recanalization but not improved functional outcomes or increased symptomatic intracranial hemorrhage. It remains unclear whether emergent stenting led to successful intracranial recanalization or patients with successful intracranial recanalization were more likely to be stented. Randomized trials are warranted.
BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.