Plasma metabolomic analysis of proximal occluded artery in acute large vessel occlusion stroke with futile recanalization

Q: What are the key findings of this study?

A combined four-metabolite panel from proximal occluded artery plasma predicted 90-day futile recanalization after stroke thrombectomy with an AUC of 0.965 (95% CI 0.918-1.000).

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Acute ischemic stroke due to anterior circulation large vessel occlusion treated with endovascular treatment (n=40). Intervention: Four-metabolite plasma panel (dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid) from proximal occluded artery vs. Effective recanalization (90-day mRS ≤ 2) / clinical prediction model. Primary outcome: Prediction of futile recanalization (90-day mRS > 2) using the combined four-metabolite model (AUC 0.965, 95% CI 0.918-1.000, p=<0.05).

Q: What does this research mean for the field?

A panel of four proximal occluded artery plasma metabolites—dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid—predicts futile recanalization after endovascular thrombectomy in acute ischemic stroke with high accuracy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To characterize the plasma metabolomic profile of the proximal occluded artery in futile recanalization following endovascular treatment for acute ischemic stroke due to anterior circulation large vessel occlusion.

Wensheng Zhang; Weifang Xing; Lei Ren; Yudi Li; Zhenqin Jiang; Jinzhao He; Li Ling

doi:10.1186/s12883-026-05461-9

October 27, 2026BMC NeurologyOpen Access

Plasma metabolomic analysis of proximal occluded artery in acute large vessel occlusion stroke with futile recanalization

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Key result

Four-metabolite panel predicts futile stroke recanalization with ~0.97 AUC.

AUC 0.965
95% CI 0.918-1.000
P<0.05
n=40

Why the study?

The plasma metabolomic profile of the proximal occluded artery in futile recanalization after endovascular treatment for acute ischemic stroke due to anterior circulation large vessel occlusion had not been systematically characterized.

Does a plasma metabolomic profile from the proximal occluded artery (specifically dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid) predict futile recanalization at 90 days in patients with anterior circulation large vessel occlusion acute ischemic stroke undergoing endovascular treatment?

Key Points

To characterize the plasma metabolomic profile of the proximal occluded artery in futile recanalization following endovascular treatment for acute ischemic stroke due to anterior circulation large vessel occlusion.
Prospectively evaluated 40 patients undergoing endovascular treatment (20 with futile recanalization [FR] and 20 with effective recanalization [ER]), collecting local arterial plasma before mechanical thrombectomy and recanalization.
Conducted untargeted metabolomics via LC-MS/MS, identifying candidate differential metabolites based on VIP > 1 and P < 0.05, followed by KEGG pathway enrichment and ROC curve analysis.
Identified 123 candidate differential metabolites; four key metabolites were selected: dehydroepiandrosterone (fold change 0.79, P = 0.013) and stearidonic acid (fold change 0.71, P = 0.010) were downregulated, whereas testosterone (fold change 2.07, P = 0.024) and progesterone (fold change 1.55, P = 0.003) were upregulated in FR.
KEGG analysis revealed significant enrichment in steroid hormone biosynthesis, cortisol synthesis and secretion, aldosterone synthesis and secretion, endocrine resistance, and alpha-linolenic acid metabolism.
A combined model of all four metabolites predicted futile recanalization with an AUC of 0.965 (95% CI: 0.918–1.000), achieving 80.0% sensitivity and 100.0% specificity at the optimal cut-off.

Study Design

Type

Observational (n=40)

Blinding

Single-blind

Multicenter

No

Structured PICO

Does a plasma metabolomic profile from the proximal occluded artery (specifically dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid) predict futile recanalization at 90 days in patients with anterior circulation large vessel occlusion acute ischemic stroke undergoing endovascular treatment?

P

Population

40 adult patients (mean age 66.6 years, 32.5% female) with anterior circulation large vessel occlusion acute ischemic stroke who achieved successful angiographic recanalization (eTICI 2b-3) after endovascular treatment, followed for 90 days.

E

Exposure

Untargeted plasma metabolomics analysis (using LC-MS/MS) of 5 mL arterial blood aspirated from the proximal aspect of the occluded artery during endovascular treatment (before mechanical thrombectomy and before recanalization), evaluating a four-metabolite predictive model (dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid).

C

Comparator

Comparison between futile recanalization (FR, 90-day mRS > 2, n=20) and effective recanalization (ER, 90-day mRS ≤ 2, n=20) groups; predictive performance of the four-metabolite model was also compared against a parsimonious clinical model (including age, sex, baseline NIHSS, and ASPECTS).

O

Outcome

Futile recanalization (FR), defined as modified Rankin Scale (mRS) score > 2 at 90 days post-EVT, assessed via standardized telephone interviews by trained neurology residents blinded to metabolomic results.hard clinical

Main Result

Effect estimate: AUC 0.965 (95% CI 0.918-1.000)

p-value: p=<0.05

This exploratory study provides the first characterization of proximal occluded artery plasma metabolomics in acute large vessel occlusion stroke, identifying steroid hormone dysregulation (downregulated DHEA and stearidonic acid; upregulated testosterone and progesterone) as a candidate biomarker signature for futile recanalization.

Limitations

Small sample size (n = 40) and lack of statistical significance after false discovery rate (FDR) correction, making findings exploratory
Single-center observational design limits generalizability and precludes causal inference
Blood was sampled from the proximal occluded artery on the arterial inflow side without paired systemic venous samples to confirm local specificity
Marked sex imbalance between groups (55.0% female in futile recanalization vs. 10.0% in effective recanalization), creating potential confounding for steroid hormone metabolites and unstable adjusted models
Bootstrap internal validation did not repeat the OPLS-DA-based metabolite selection process
Small sample size (n = 40; 20 FR events), resulting in all FDR-adjusted q-values > 0.05 and unstable adjusted logistic regression models
Arterial blood from the proximal occluded artery is on the arterial inflow side and does not directly drain the ischemic tissue
Other unmeasured confounders may exist, and findings are exploratory and hypothesis-generating
External validation is required before clinical application

Implication

May support futile recanalization risk stratification post-thrombectomy; leaves open prospective validation before clinical use.

Abstract

To characterize the plasma metabolomic profile of proximal occluded artery in futile recanalization (FR) after endovascular treatment (EVT) for acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). In this prospective study, plasma from the proximal occluded artery was collected from LVO-AIS patients during EVT, before mechanical thrombectomy and before recanalization. Untargeted metabolomics was performed using LC-MS/MS. Patients were divided into FR and non-FR groups based on 90-day modified Rankin Scale score. Differential metabolites were screened using VIP > 1 and P < 0.05, followed by KEGG pathway enrichment analysis. Among 40 patients (20 FR, 20 non-FR), 123 candidate differential metabolites were identified. Four key metabolites were selected: dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid. In FR patients, dehydroepiandrosterone and stearidonic acid were downregulated, while testosterone and progesterone were upregulated. Pathway enrichment showed involvement of steroid hormone biosynthesis, cortisol synthesis/secretion, and aldosterone synthesis/secretion, related to immune regulation, oxidative stress, and inflammation. All four metabolites were significantly associated with FR ( P < 0.05). Their combination predicted FR with an AUC of 0.965 (95% CI: 0.918–1.000), with a sensitivity of 80.0% and specificity of 100.0% at the optimal threshold. This first systematic description of proximal occluded artery plasma metabolomics in FR reveals steroid hormone metabolism disorder as a key feature, characterized by downregulation of dehydroepiandrosterone/stearidonic acid and upregulation of testosterone/progesterone. These four metabolites are candidate biomarkers for FR.

Discussion

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Cite This Study

Zhang et al. (2026) conducted an observational in Acute ischemic stroke due to anterior circulation large vessel occlusion treated with endovascular treatment (n=40). Four-metabolite plasma panel (dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid) from proximal occluded artery vs. Effective recanalization (90-day mRS ≤ 2) / clinical prediction model was evaluated on Prediction of futile recanalization (90-day mRS > 2) using the combined four-metabolite model (AUC 0.965, 95% CI 0.918-1.000, p=<0.05). A combined four-metabolite panel from proximal occluded artery plasma predicted 90-day futile recanalization after stroke thrombectomy with an AUC of 0.965 (95% CI 0.918-1.000).

synapsesocial.com/papers/6ae28f09cbadf70daf6c4413 https://doi.org/10.1186/s12883-026-05461-9

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Plasma metabolomic analysis of proximal occluded artery in acute large vessel occlusion stroke with futile recanalization

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Plasma metabolomic analysis of proximal occluded artery in acute large vessel occlusion stroke with futile recanalization

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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