Biomarkers of Impaired Distal Perfusion in ICAS

Hopefully your competent? doctor knows EXACTLY WHAT TO DO WITH THIS TO PREVENT YOUR NEXT STROKE!

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING?

My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size, location or any intervention needed, because my doctor knew nothing and did nothing.

Biomarkers of Impaired Distal Perfusion in ICAS

Johanna Seiden

, MD, MPH, @JohannaSeidenMDYaghi S, Khan F, Lewis S, Stipanovich A, Choi R, Baker R, Al Kasab S, Abu Qdais A, Yaddanapudi SS, Sultana S, et al. Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study. Stroke. 2025. 

The risk of recurrent ischemic stroke due to intracranial atherosclerosis (ICAS) among medically treated patients is higher than other etiologies.¹ There are a number of different submechanisms within ICAS — distal embolization, perforator disease, and hypoperfusion — and risk of subsequent ischemic stroke may not be the same for all causes. Prior studies suggest that impaired distal perfusion may be associated with increased risk of stroke recurrence,^2,3 but these studies did not acutely enroll patients after their index events. They beg the question: Are specific biomarkers of impaired distal perfusion — Anterior Circulation borderzone infarcts (ACBI) and hypoperfusion mismatch volume — associated with higher risk of recurrence within 90 days? The Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis (BIORISK ICAS) is a multicenter retrospective international study of 2050 patients with symptomatic ICAS (50-99% luminal stenosis of the intracranial vertebral, basilar, distal ICA or proximal MCA) who did not receive endovascular therapy as first line therapy. The study was conducted between 2019 and 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. The primary analysis examined acute ACBI, and secondary analysis performed on patients presenting within 72 hours of last known normal with perfusion imaging studied hypoperfusion mismatch volume at Tmax of 6 seconds. The primary analysis included 1891 patients. Mean age was 67 years, and 54.7% were men. ACBI was seen in 31.7% of patients, and 71.7% had 70-99% stenosis. 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory within 90 days. In univariate analysis, ACBI was associated with recurrent stroke at 90 days (38.5% [67/174] vs. 31% [532/1717], p=0.042). Hyperlipidemia, degree of stenosis 70-99% vs 50-69%, and nonsmokers had increased risk of recurrent stroke. Among patients who underwent perfusion imaging (509 patients), hypoperfusion mismatch was also associated with increased risk of recurrent stroke within 90 days (67.7% [42/62] vs. 53.5% [221/413], p=0.036). Hyperlipidemia and atrial fibrillation were also associated with increased risk of recurrent stroke. Patients with ACBI had increased risk of recurrent stroke within 90 days; this finding persisted even after adjustment for variables associated with recurrent ischemic stroke risk (aHR 1.40, 95% CI 1.02-1.93, p=0.038). In the interaction analyses, the association between ACBI and recurrent stroke was more pronounced in patients with 50-69% stenosis (aHR 3.10 95% CI 1.47-6.52) versus 70-99% stenosis (aHR 1.18 95% CI 0.83-1.68), P Interaction=0.026. In the perfusion imaging analysis, hypoperfusion mismatch >10 mL at Tmax 6 seconds was associated with recurrent stroke at 90 days even after adjustment (aHR 1.83, 95% CI 1.03-3.28, p=0.041). This multicenter international study of patients with symptomatic ICAS demonstrated that patients with impaired distal perfusion, measured either directly (through perfusion imaging) or indirectly (via evidence of ACBI), were at a higher risk of recurrent stroke at 90 days. Interestingly, this study found that the association between ACBI and recurrent ischemic stroke was more pronounced in patients with moderate stenosis versus severe stenosis. This finding could very well be due to chance, but the authors also hypothesize that the presence of borderzone infarcts in patients with severe stenosis may not be as helpful in risk stratification because they are inherently more common; however, in those with moderate stenosis, borderzone infarcts may portend a higher recurrence risk. Future studies will be important to further evaluate this finding. Limitations of this study include the retrospective and observational nature, while strengths include the large sample size and multicenter international population. Methods to risk stratify ICAS patients could help determine which patients might benefit from angioplasty, stenting, or other targeted interventions. Randomized trials testing maximal medical therapy against early reperfusion in these high-risk patients will be important moving forward.

References:Derdeyn CP, Chimowitz MI, Lynn MJ, Fiorella D, Turan TN, Janis LS,Montgomery J, Nizam A, Lane BF, Lutsep HL, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): The final results of a randomised trial. Lancet (London, England). 2014;383:333-341

Wabnitz AM, Derdeyn CP, Fiorella DJ, Lynn MJ, Cotsonis GA, Liebeskind DS, Waters MF, Lutsep H, López-Cancio E, Turan TN, et al. Hemodynamic markers in the anterior circulation as predictors of recurrent stroke in patients with intracranial stenosis. Stroke. 2018:Strokeaha11802084

Wang T, Yang Y, Wang H, Liu D, Wang J, Luo J, Yang R, Li T, Gong H, Sun X, et al. Ct perfusion for predicting ischemic stroke in patients with symptomatic carotid or middle cerebral artery occlusion: A post hoc analysis of the CMOSS study. Stroke. 2025;56:2579-2587

Improving “No‐Reflow” After Complete Reperfusion: The Role of Intravenous Thrombolysis in Vertebrobasilar Artery Occlusion Patients Undergoing Endovascular Treatment

Have you even identified the problem properly? 

I'd suggest this needing a solution: Capillaries that don't open due to pericytes

Improving “No‐Reflow” After Complete Reperfusion: The Role of Intravenous Thrombolysis in Vertebrobasilar Artery Occlusion Patients Undergoing Endovascular Treatment

Zhanglin Li, MD https://orcid.org/0009-0001-6813-8589, Yingjie Xu, MD https://orcid.org/0000-0002-4181-7450, Pan Zhang, MD https://orcid.org/0000-0001-6320-6987, Miaomiao Hu, MD https://orcid.org/0009-0006-1821-0534, Ruyue Wang, MD https://orcid.org/0009-0008-4184-744X, Zhixin Huang, PhD, Zuowei Duan, PhD, Xinfeng Liu, PhD https://orcid.org/0000-0002-8182-9632 xfliu2@ustc.edu.cn, and Wen Sun, PhD https://orcid.org/0000-0002-7268-2085 sunwen_medneuro@163.comAuthor Info & Affiliations

Journal of the American Heart Association

Volume 14, Number 16

https://doi.org/10.1161/JAHA.124.039278

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Abstract

Background

Previous studies have found that the use of intravenous thrombolysis (IVT) before endovascular treatment (EVT) could mitigate the “no‐reflow” phenomenon in large‐vessel occlusion of the anterior circulation. However, the effect of preoperative IVT on reducing the “no‐reflow” phenomenon in vertebrobasilar artery occlusion (VBAO) is still uncertain. This study aimed to compare the outcomes of IVT before EVT versus EVT alone in patients with VBAO with complete reperfusion (mTICI [Modified Thrombolysis in Cerebral Infarction] 3).

Methods

We performed a retrospective analysis of patients with acute VBAO at 65 stroke centers in China. Patients with complete reperfusion after EVT were included. These patients were divided into 2 groups on the basis of whether IVT was used before EVT, and propensity score matching was applied to balance the groups. The primary outcome was favorable functional outcome, defined as a modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were functional independence (modified Rankin Scale score of 0–2 at 90 days) and modified Rankin Scale shift at 90 days. Safety end points included symptomatic intracranial hemorrhage and death at 90 days.

Results

Of the 2422 patients with VBAO who received EVT, 1452 patients achieved complete reperfusion. Among these, 273 patients received IVT before EVT. After propensity score matching, 268 patients treated with IVT before EVT were compared with 519 patients without IVT. In the matched cohort, the group that received IVT before EVT showed a higher rate of favorable functional outcome (modified Rankin Scale score, 0–3) (adjusted odds ratio, 1.40 [95% CI, 1.03–1.91]; P=0.033) and a lower mortality rate at 90 days (adjusted odds ratio, 0.72 [95% CI, 0.52–0.99]; P=0.044) compared with the EVT alone group.

Conclusions

Our study indicates that IVT before EVT could improve favorable functional outcomes and reduce death in patients with VBAO who achieve complete reperfusion.

The No-Reflow Paradox: Unblocking the Vessel, Not the Damage?

 Well shit, you're describing Capillaries that don't open due to pericytes;

 known since September 2011. The whole stroke medical world IS COMPLETELY FUCKING INCOMPENT FOR NOT SOLVING THAT PROBLEM!

The No-Reflow Paradox: Unblocking the Vessel, Not the Damage?

• Shravan Sivakumar , MD , @sshravanMD

Rivet S, Churilov L, Yassi N, Kleinig TJ, Thijs V, Wu T, Dewey H, Desmond PM, Parsons MW, Donnan GA, et al. Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy. Stroke. 2025.

In real-world clinical practice, a substantial number of ischemic stroke patients fail to achieve functional independence, even after technically successful thrombectomy with excellent angiographic reperfusion scores (TICI 2C-3). This discordance has been described as futile recanalization and may be attributable to a phenomenon referred to as “no-reflow.” This has been conceptualized as the failure of downstream microvascular reperfusion at the tissue level despite successful macrovascular recanalization. Several mechanisms including microvascular obstruction by microthrombi, edema-related microvascular compression, and pericyte-induced capillary contraction may be at play.¹ Its clinical relevance is magnified in the context of recent trials expanding thrombectomy to patients with large core infarcts and perfusion mismatch — groups where optimizing tissue-level perfusion may be especially crucial. Prior research supports use of CTP imaging as a better predictor of outcomes following successful recanalization than CT angiogram alone and was even utilized as an indicator of therapeutic success in recent thrombolytic trials.

The authors Rivet et al. aimed to investigate the clinical impact of this no-reflow mechanism on functional outcomes by comparing patient characteristics between patients with “no-reflow” mechanism on perfusion imaging and varying degrees of angiographic recanalization (TICI scores). They conducted a post hoc analysis on the data from three clinical trials: EXTEND-IA (Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke) part 1 and 2 trials. Both qualitative and quantitative evidence of tissue perfusion evaluation for “no-reflow” were evaluated in a two-step process through application of commercially available fully automated software (RAPID; iSchemaView, Menlo Park, CA) on post-thrombectomy follow-up 24-hour perfusion imaging (CTP or MR Perfusion). The authors identified 2 distinct regions of interest (ROI) which were superimposed into perfusion maps and excluded signals associated with hemorrhagic transformation of infarct. No-reflow was defined when both qualitative and quantitative criteria were met — that is, visually demonstrable reduced intralesional rCBV or rCBF and >15% interside reduction in median rCBV or rCBF value² (Figure 1). It is worth noting that since the primary studies were not primarily designed to evaluate for this phenomenon, not all patients had both MRP and CTP.

Figure 1. Imaging analysis method.

They compared both clinical and radiological characteristics of patients with combinations of no-reflow or completeFlow with different levels of angiographic success (full-TICI 2c3, partial-2b, unsuccessful-0-2a). No significant difference in the rate of no-reflow detection according to imaging modality (CT perfusion 13.6% [n=9/66] versus MRP 25.0% [n=21/84]; P=0.10) was observed. No-reflow mechanism occurred more frequently in successful angiographic recanalization (TICI 3) (n=17/30, 56.7%). Among patient characteristics across varying degrees of technical success, it is worth noting a statistically significant difference among time of onset and proportion of patients receiving thrombolytic (alteplase or tenecteplase).

The primary outcome of functional independence (mRS score of 0–2) was achieved in 43.33% (n=13/30) of patients with eTICI 2c3–NoReflow, versus 67.50% (n=81/120) of patients with eTICI 2c3–CompleteFlow, 63.03% (n=150/238) of patients with eTICI 2b and 50.00% (n=34/68) of patients with unsuccessful thrombectomy. In unadjusted analysis, patients with no-reflow  were less likely to experience functional independence despite technical success, TICI 2c-3 compared to completeFlow (odds ratio [OR], 0.37 [95% CI, 0.16–0.83]; P=0.02) or those with eTICI 2b (OR, 0.45 [95% CI, 0.21–0.97]; P=0.04) but had similar rate to patients with unsuccessful thrombectomy (OR, 0.76 [95% CI, 0.32–1.82]; P=0.54). When adjusted for age, premorbid mRS, baseline NIHSS, and baseline core volume, multivariable analysis confirmed lower odds of functional independence with no-reflow and full/partial recanalization, and similar odds of functional independence with unsuccessful thrombectomy. Furthermore, exploratory analysis of functional infarct volumes (FIV) showed that despite similar volumes, patients with no-reflow had worse outcomes despite full recanalization compared to partial recanalization.

These findings suggest that “no-reflow” phenomenon negates benefit of macrovascular recanalization in achieving favorable clinical outcome. The authors further caution that no-reflow mechanism tends to occur more frequently with prolonged periods of ischemic injury, suggesting that this prevalence could be underestimated by this study given the inclusion of patients within the 4.5-hour time window. Their major strength includes use of prospectively collected data from clinical trials. As we push the boundaries of thrombectomy eligibility, tackling the no-reflow phenomenon may be the next frontier in improving patient-centered outcomes — representing a crucial step not only in restoring macrovascular blood flow but also in minimizing downstream ischemic injury, thereby broadening the therapeutic benefit for patients with acute ischemic stroke.

Effects of low-intensity pulsed focal ultrasound-mediated delivery of endothelial progenitor-derived exosomes in tMCAo stroke

 

Will your competent? doctor ensure human testing gets done? Or has the board of directors incompetence let your stroke medical 'professionals' DO NOTHING that will further stroke recovery?

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

Effects of low-intensity pulsed focal ultrasound-mediated delivery of endothelial progenitor-derived exosomes in tMCAo stroke

Ahmet Alptekin¹Mohammad B. Khan²Mahrima Parvin¹Hasanul Chowdhury¹Sawaiz Kashif¹Fowzia A. Selina¹Anika Bushra¹Justin Kelleher¹Santu Ghosh³Dylan Williams²Emily Blumling²Roxan Ara⁴Asamoah Bosomtwi⁴Joseph A. Frank⁵Krishnan M. Dhandapani⁶Ali S. Arbab^1*†

• ¹Tumor Angiogenesis Laboratory, GCC, Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, United States
• ²Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, United States
• ³Department of Biostatistics, Medical College of Georgia, Augusta University, Augusta, GA, United States
• ⁴Small Animal Imaging Core, GCC, Medical College of Georgia, Augusta University, Augusta, GA, United States
• ⁵Laboratory of Diagnostic Radiology Research, Clinical Center, National Institutes of Health, Bethesda, MD, United States
• ⁶Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, United States

Introduction: Exosomes from different sources have been used for therapeutic purposes to target stroke and other disorders. However, exosomes from endothelial progenitor cells (EPCs) have not been tested in any stroke model, and in vivo bio-distribution study is lacking. Targeted delivery of IV-administered exosomes has been a significant challenge. Delivery of exosomes to the brain is a daunting task, and a blood–brain barrier (BBB)-penetrable peptide is being considered. However, the next step in practical treatment will be delivering naïve (unmodified) exosomes to the stroke site without destroying host tissues or disrupting BBB, or the membranes of the delivery vehicles. Low-intensity-pulsed focused ultrasound (LIPFUS) is approved for clinical use in the musculoskeletal, transcranial brain, and physiotherapy clinics. The objectives of the proposed studies were to determine whether LIPFUS-mediated increased delivery of EPC-derived exosomes enhances stroke recovery and functional improvement in mice with transient middle cerebral artery occlusion (tMCAo) stroke.

Methods: To enhance exosome delivery to the stroke area, we utilized LIPFUS. We evaluated stroke volume using MRI at different time points and conducted behavioral studies parallel to MRI to determine recovery. Ultimately, we studied brain tissue using immunohistochemistry to assess the extent of stroke and tissue regeneration.

Results and Discussion: In vivo, imaging showed a higher accumulation of EPC exosomes following LIPFUS without any damage to the underlying brain tissues, increased leakage of albumin, or accumulation of CD45+ cells. Groups of mice (14–16 months old) were treated with Vehicle (PBS), LIPFUS only, EPC-exosomes only, and LIPFUS+EPC-exosomes. LIPFUS + EPC exosomes groups showed a significantly decreased stroke volume on day 7, decreased FluoroJade+ cells, and significantly higher numbers of neovascularization in and around the stroke areas compared to that of other groups.

Introduction

Stroke is a significant cause of adult mortality and remains a leading contributor to adult disability. The majority of strokes are often ischemic (87%) resulting from a significant vascular occlusion due to a thromboembolic (TE) clot; therefore, the desired amount of stroke-salvaging drugs cannot be delivered to the core of the stroke (1, 2). In addition, the blood–brain barrier (BBB) is largely impermeable to most therapeutics. To date, IV tissue plasminogen activator (tPA) and/or endovascular thrombectomy (ET) are the only two Food and Drug Administration (FDA)-approved therapies to treat ischemic stroke. However, the recanalization of major vessels with IV-tPA/ET does not ensure adequate microvascular perfusion and recovery of tissue damage due to the associated risk of the “no-reflow” phenomenon that is exacerbated under stroke-related comorbidities such as aging, diabetes, or hypertension(So you haven't even attempted to solve Capillaries that don't open due to pericytes?)

. Preclinical modeling using the transient middle cerebral artery occlusion (tMCAo) model, validated in both mice and rats, can replicate confirmed recanalization and is widely accepted in stroke research (3). Thrombectomy in patients, and tMCAo in animals, assures that the test drug or treatment reaches the brain after ischemia and reperfusion (4). Thus, effective therapy and a new way of delivering therapeutic agents that can be safe in a larger comorbid stroke population and remain usable in multiple settings with or without IV-tPA/ET even after the therapeutic window are greatly needed.

Stem cell (or progenitor cell) treatments have shown to be successful in various preclinical models for different disease treatments, including stroke. Our previous studies showed the effectiveness of endothelial progenitor cells (EPCs) and neural stem cells (NSCs) in stroke models, with both in vivo magnetic resonance imaging (MRI) and functional behavioral studies showing improvement in stroke recovery (5–9). We postulate that both types of cells exerted a paracrine effect through exosomes, which might carry materials from their parental cells (10–12). Exosomes can interact with cells by fusion with the plasma membrane and subsequent endocytosis and release of their cargo, consisting of proteins, soluble factors, lipids, DNAs, microRNAs (miRNAs), and RNAs (13–16). Leveraging exosomes to harness the therapeutic potential of stem and progenitor cells would overcome the challenge that cell-based treatments face in clinical settings.

Exosomes are 30–150 nm in size and contain certain tetraspanins, heat shock proteins, biogenesis-related proteins, membrane transport and fusion proteins, nucleic acids, and lipids (17–19). Due to their biocompatibility, low toxicity, immunogenicity, permeability (including through the BBB), stability in biological fluids, and ability to accumulate in the lesions with higher specificity (20–26), investigators have used exosomes in different disease conditions in the brain, such as stroke, traumatic brain injury, and tumors (22, 27–30). Investigators have used exosomes and miRNA-rich exosomes collected from mesenchymal stem cells (MSCs) to enhance stroke recovery and showed that miRNA promoted neural plasticity and functional recovery (31, 32). Our group recently reported NSC-derived exosomes’ effect on improving tissue and functional recovery in the murine TE stroke model (33). However, exosomes from EPCs, which play an important role in vascular regeneration, have not been tested in any stroke model, and an in vivo bio-distribution study is lacking. Our published studies showed a dramatic reduction in stroke injury when EPCs were administered 24 h following stroke (5). Based on these results, we anticipate that EPCs-derived exosomes will cease the progression of stroke lesions and improve post-stroke outcomes if delivered efficiently to the site of stroke injury.

Targeted delivery of IV-administered exosomes has been a great challenge. Modification of the exosome surface to carry different ligands or peptides has been tried to increase delivery to target tissues (34, 35); however, the overall results are not encouraging (36, 37). Delivery of exosomes to the brain is a daunting task, and a BBB-penetrable peptide is being considered (38, 39). However, a method that can deliver naïve (unmodified) exosomes to the site of stroke without destroying host tissues, disrupting BBB, or affecting the membranes of the delivery vehicles (such as exosomes) would be a significant breakthrough.

High-Intensity Pulsed Focused ultrasound (HIPFUS) is being investigated to enhance permeability and retention (EPR) of nanoparticles/gene/plasmid/vectors to the sites of interest (40–45) but has been shown to cause widespread damage to local tissues including the brain (46). The basic mechanism behind HIPFUS’s effect is primarily through mechanical forces (acoustic radiation and acoustic cavitation) that increase the permeability of the vasculature, resulting in leakage of circulating nanoparticles, plasmids, or vectors into targeted sites and EPR (47–49). Low-intensity-pulsed ultrasound is approved for clinical use in musculoskeletal, central nervous system, and physiotherapy clinics. We have previously demonstrated that low-intensity-pulsed focused ultrasound (LIPFUS) increases the delivery of intravenously administered exosomes to stroke areas without causing damage to the brain (50). The objectives of the proposed studies are to determine whether LIPFUS-mediated increased delivery of EPC exosomes enhances stroke recovery and functional improvement in mice with tMCAo stroke.

In this study, we utilized EPC-derived exosomes for stroke treatment. To enhance exosome delivery to the stroke area, we employed LIPFUS without an ultrasound contrast agent microbubble/nanobubble infusion, which might temporarily disrupt the BBB, as described in our previous study (50). We assessed stroke volume using MRI at different time points and conducted behavioral studies parallel to MRI to evaluate recovery. In the end, we examined the brain tissue using immunohistochemistry studies to evaluate the extent of stroke and tissue regeneration. We found that EPC-derived exosome treatment reduced stroke volume 1 week after the stroke onset.

Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy

 Just maybe you've rediscovered Capillaries that don't open due to pericytes September 2011. What the fuck is your solution to that problem? Describing a problem with NO solution is grounds for firing! My God, the amount of absolute stupidity in stroke is appalling!

Hypoperfusion is a term that describes "a reduced amount of blood flow".

Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy

Samantha Rivet, MDCM https://orcid.org/0000-0001-6099-237X, Leonid Churilov, PhD https://orcid.org/0000-0002-9807-6606, Nawaf Yassi, MBBS, PhD https://orcid.org/0000-0002-0685-0060, Timothy J. Kleinig, MBBS(Hons), PhD https://orcid.org/0000-0003-4430-3276, Vincent Thijs, MD, PhD https://orcid.org/0000-0002-6614-8417, Teddy Wu, MBChB, PhD https://orcid.org/0000-0003-1845-1769, Helen Dewey, MBBS, PhD https://orcid.org/0000-0001-9484-2070, … Show All … , and Felix Chun Ng, MBBS, PhD https://orcid.org/0000-0001-6973-8677 ng.f@unimelb.edu.auAuthor Info & Affiliations

Stroke

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https://doi.org/10.1161/STROKEAHA.124.049574

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Abstract

BACKGROUND:

Tissue-level hypoperfusion (no-reflow) persists in 30% of patients with seemingly successful upstream angiographic recanalization at thrombectomy. We investigated the clinical impact of the no-reflow phenomenon by comparing patients with no-reflow versus patients with varying degrees of angiographic recanalization.

METHODS:

In a post hoc pooled analysis of the EXTEND-IA (Endovascular Therapy for Ischemic Stroke With Perfusion-Imaging Selection) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke) part 1 and 2 trials, clinical and radiological outcomes were compared between patients with (1) full angiographic recanalization with no-reflow (expanded Treatment in Cerebral Ischemia [eTICI] 2c3–NoReflow), defined as >15% reduction in relative cerebral blood flow or Volume within the infarct relative to a contralateral homolog on 24-hour-follow-up perfusion computed tomography or magnetic resonance imaging despite eTICI grade 2c-3 angiographic recanalization, (2) full angiographic recanalization and tissue reperfusion (eTICI 2c3–CompleteFlow), (3) partial angiographic recanalization (eTICI 2b), and (4) unsuccessful thrombectomy (eTICI 0-2a). The primary outcome, functional independence at 90 days, was investigated using a mixed effect logistic regression model, both unadjusted and adjusted for a priori-selected covariates, namely age, premorbid modified Rankin Scale, baseline National Institutes of Health Stroke Scale, and baseline core volume.

RESULTS:

Among 537 patients from the overall pooled cohort, 456 patients were included in the analysis. The mean age of the included patients was 71 years old, and 54% were male. A favorable outcome (90-day modified Rankin Scale score of 0–2 or return to baseline modified Rankin Scale) was observed in 43.33% (n=13/30) of patients with eTICI 2c3–NoReflow, 67.50% (n=81/120) of eTICI 2c3–CompleteFlow, 63.03% (n=150/238) of eTICI 2b, and 50.00% (n=34/68) of unsuccessful thrombectomy. In multivariable analysis, patients with eTICI 2c3–NoReflow had lower odds of favorable outcome compared with those with eTICI 2c3–CompleteFlow (adjusted odds ratio, 0.31 [95% CI, 0.12–0.77]; P=0.01) and eTICI 2b (adjusted odds ratio, 0.40 [95% CI, 0.17–0.96]; P=0.04) but not unsuccessful thrombectomy (adjusted odds ratio, 1.02 [95% CI, 0.38–2.73]; P=0.97). Patients with eTICI 2c3–NoReflow had similar follow-up infarct volume to unsuccessful thrombectomy (β=−8.26 [95% CI, −27.38 to 10.86]; P=0.40) and eTICI 2b (β=9.38 [95% CI, −7.33 to 26.09]; P=0.27) but had larger infarcts compared with eTICI 2c3–CompleteFlow (β=18.85 [95% CI, 1.16–36.54]; P=0.04).

CONCLUSIONS:

When no-reflow occurred, clinical and radiological outcomes in patients with full angiographic recanalization were similar to patients with unsuccessful thrombectomy. Preventing or reversing no-reflow has the potential to augment the clinical benefit of reperfusion treatment in ischemic stroke.

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No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies

Hopefully your competent? doctor has a solution for this problem. 

No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies

Feiyue Sun, Jing Zhou, […], and Zhigang Mei meizhigang@hnucm.edu.cn+5View all authors and affiliations

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https://doi.org/10.1177/0271678X241237159

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Abstract

Endovascular reperfusion therapy is the primary strategy for acute ischemic stroke. No-reflow is a common phenomenon, which is defined as the failure of microcirculatory reperfusion despite clot removal by thrombolysis or mechanical embolization. It has been reported that up to 25% of ischemic strokes suffer from no-reflow, which strongly contributes to an increased risk of poor clinical outcomes. No-reflow is associated with functional and structural alterations of cerebrovascular microcirculation, and the injury to the microcirculation seriously hinders the neural functional recovery following macrovascular reperfusion. Accumulated evidence indicates that pathology of no-reflow is linked to adhesion, aggregation, and rolling of blood components along the endothelium, capillary stagnation with neutrophils, astrocytes end-feet, and endothelial cell edema, pericyte contraction, and vasoconstriction. Prevention or treatment strategies aim to alleviate or reverse these pathological changes, including targeted therapies such as cilostazol, adhesion molecule blocking antibodies, peroxisome proliferator-activated receptors (PPARs) activator, adenosine, pericyte regulators, as well as adjunctive therapies, such as extracorporeal counterpulsation, ischemic preconditioning, and alternative or complementary therapies. Herein, we provide an overview of pathomechanisms, predictive factors, diagnosis, and intervention strategies for no-reflow, and attempt to convey a new perspective on the clinical management of no-reflow post-ischemic stroke.

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