Editorial: Advancing Precision Medicine in Acute Stroke Care - Personalized Treatment Strategies and Outcomes

Mohamed F Doheim¹Nirav Bhatt¹Alhamza R. Al-Bayati¹Jean-Claude Baron²Joao Brainer Clares Andrade^3*

• ¹UPMC, Pittsburgh, United States
• ²Groupe Hospitalier Universitaire Paris Sainte-Anne Form@tion, Paris, France
• ³Federal University of São Paulo, São Paulo, Brazil

Precision medicine in acute stroke care has matured from a visionary concept to an operational framework. The articles in this Research Topic, spanning molecular biomarkers, imaging phenotypes, therapeutic optimization, neuro-recovery science, and health-system engineering, converge on a single imperative of individualizing decisions at the speed and scale required by cerebrovascular emergencies. Below, we synthesize the cross-cutting insights, highlighting how this body of work collectively reframes the concept of "time is brain" as "the right treatment for this brain now." Routine and low-cost lab tests can carry disproportionate prognostic value and a huge return in investment presenting an opportunity for risk stratification and decoding prognosis. For instance, in a large ischemic stroke cohort including 11,405 patients reported by Wang et al, baseline alkaline phosphatase (ALP) was associated with 3-month and 1-year mortality, poor function outcomes, and increased disability. Marked variability was noted among subtypes representing different etiologies. The results may suggest potential links between mineral metabolism, vascular calcification, and neurorepair while arguing for validation of ALP as a triage signal for follow-up intensity. Likewise, a retrospective study including 200 patients with aneurysmal subarachnoid hemorrhage (aSAH) reported by Min et al and showed that, on postoperative day 7, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII) were significantly higher in patients with poor versus good outcomes. In multivariate analysis, cerebrospinal fluid (CSF) red blood cell (RBC) count on day 1 (≥177 × 10⁹/L; OR 7.227, 95% CI: 1.160-45.050, P = 0.034), surgical duration (≥169 min), Fisher grade (III-IV), hypertension, and infections were associated with poor outcome. On day 7, CSF RBC count (≥54 × 10⁹/L; OR 39.787, 95% CI: 6.799-232.836, P < 0.001) and NLR (≥8.16; OR 6.362, 95% CI: 1.424-28.428, P = 0.015) remained independent predictors. NLR (r = 0.297, P = 0.007) and SIRI (r = 0.325, P = 0.003) correlated with CSF RBC count. Overall, elevated NLR and CSF RBC count were strongly associated with poor prognosis in aSAH. These findings may suggest neuroinflammation as both a marker and modifiable pathway.Building on the same story, renal indices do not reflect a mere comorbid noise. Rocha et al showed, in a cohort of 230 patients with acute large vessel occlusion (LVO) stroke, that nearly one-third exhibited a fast progressor phenotype, characterized by higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and substantially worse clinical outcomes. Elevated creatinine (≥1.2 mg/dL) independently predicted fast progression, poor 90-day functional recovery, and mortality, while reduced eGFR (<60 mL/min/1.73m²) was associated with fast progression but not longer-term outcomes. These findings may suggest that simple, routinely available creatinine-based biomarkers of renal dysfunction may serve as early indicators of aggressive infarct dynamics, helping clinicians identify high-risk patients during emergency evaluation and prioritize them for expedited endovascular therapy.Two contributions extend this biological lens even further. A systematic review performed by Al-Jehani et al positions microRNAs as plausible tools for stratifying risk and forecasting outcomes in ischemic stroke, spanning signatures of endothelial dysfunction, inflammation, and thrombus biology. In contrast, a study including 317 patients of wholeblood viscosity (WBV) after thrombectomy reported by Thapa et al found no association with discharge disability, though this finding may be influenced by limitations in the formula used to estimate shear rates. While this report suggested WBV alone does not directly impact prognosis, other determinants of blood viscosity may still meaningfully influence outcomes after thrombectomy and warrant further investigation. Several studies clarify which images matter when the stakes are highest. In a study by Yeo et al, including 325 consecutive patients with anterior circulation LVO, multiphase CTA collateral grade strongly discriminated 3-month outcomes among EVT candidates, reinforcing collateral-aware selection and expectation-setting beyond "time alone". Li et al, on the other hand, showed that high-resolution vessel-wall MRI features (intraplaque hemorrhage and normalized wall index) combined with clinical scores effectively predict recurrence risk in high-risk non-disabling ischemic cerebrovascular events patients, and the resulting nomogram offers a practical tool for identifying high-risk individuals.Beyond occlusion-centric selection, covert substrate matters. Abdulsalam et al reported that silent brain infarcts and leukoaraiosis co-occurred in middle-aged adults and were associated with each other in a cohort comprising 50 patients, arguing that small-vessel disease burden should inform cognitive surveillance and counseling after apparently "minor" strokes.Two articles deepen physiologic precision. A prospective, serial-MRI study by Carbó et al quantified impaired microvascular reperfusion (IMR) in one-quarter of "successfully reperfused" patients; larger IMR volumes correlated with worse early neurologic status, highlighting evidence that tissue-level heterogeneity persists despite angiographic success and that IMR is a plausible target and imaging surrogate for adjuvant therapies. A radiomics approach reported by Yang and colleagues that fused DSC-PWI "criticalmoment" features with conventional parameter maps achieved superior outcome prediction (AUC ~0.92), illustrating the value of richer spatiotemporal signatures. This approach has the potential to improve AIS prognosis assessment and aid clinicians in selecting optimal treatments Imaging also refines our identification of etiology. A meta-analysis by Xu et al showed cardiac CT angiography (CCTA) detects intracardiac thrombus in ~8% of AIS within one month including many without documented AF, supporting early CCTA where TEE is delayed or poorly tolerated to accelerate secondary prevention. Therapeutic precision spans drugs, devices, and dosing. A network meta-analysis by Sun et al across randomized trials suggested reteplase may increase the odds of excellent 90day outcome versus alteplase, and tenecteplase 0.25 mg/kg ranked best for good outcomes with broadly similar safety-encouraging phenotype-and dose-specific trials. In MRIselected mild stroke (NIHSS ≤ 5) reported by Li et al, dual antiplatelet pretreatment + lowdose rtPA (0.6 mg/kg) yielded higher early neurologic improvement and better 90-day function than rtPA or DAPT alone, without excess hemorrhagehypothesis-generating evidence that biology-and imaging-guided dose tailoring may benefit mild phenotypes.Adjunctive strategies are moving from theory to plausible practice. In a propensitymatched cohort by ElBassiouny et al, early cerebrolysin after thrombectomy for cardioembolic LVO was associated with higher independence and less hemorrhagic transformation-signals now demanding randomized confirmation, ideally with IMR-type tissue metrics as mechanistic endpoints. For intracerebral hemorrhage, minimally invasive evacuation using a YL-1 hematoma crushing needle accelerated resolution and improved short-term function versus conservative care in a retrospective series reported by Chen et al-supportive of MIS pathways where craniotomy risk or delay is prohibitive, pending controlled trials.Posterior circulation epidemiology reminds us that case-mix dominates. In the U.S.National Inpatient Sample analysis conducted by Saha et al, focusing on vertebrobasilar occlusion (VBAO), showed that younger patients (18-64 years) tended to receive EVT more frequently than older patients, with no significant differences observed between sexes, likely reflecting selection and severity. Cancer-related stroke exemplifies uncertainty where precision is needed most. Kielkopf et al showed that, in active cancer AIS, anticoagulation vs antiplatelet therapy at discharge yielded similar adjusted risks for 1-year mortality and recurrent stroke, highlighting the need for randomized, biologyanchored selection. Operational precision is where biomarkers and images become minutes saved. A Hybrid Emergency Room System (HERS) reported by Kashiura et al shaved ~30-40 min off doorto-puncture and door-to-recanalization for EVT-an implementation signal that invites multicenter, phenotype-enriched evaluations where time sensitivity is greatest. Populationlevel lenses ensure translation is equitable and context-aware. In Jordan, the 1-year stroke incidence in AF was 3.4%, with diabetes and prior stroke conferring ≈2.6-fold higher odds as reported by Al-Shatanawi et al. This can tailor anticoagulation strategies to local comorbidity profiles. In China, as reported by Tang et al, ischemic stroke burden attributable to high fasting plasma glucose increased in absolute terms with projections suggesting future decline under current trends, reinforcing glycemic control as a population lever for precision prevention. Precision extends to neurorecovery. A systematic review of sensorimotor network (SMN) alterations across fMRI studies by Sahrizan et al documented early disruptions with progressive reintegration through compensatory reorganization; lesion topology modulated trajectories, advocating network-aware rehabilitation that adapts to time since stroke and structural substrate. Collectively, these studies outline a layered, workflow-embedded model (Figure 1): 1) Baseline biology, such as ALP, creatinine/eGFR, microRNAs, and inflammatory signals, flags trajectories (fast progression, poor repair) and informs hemodynamic goals, nephro-pharmacologic caution, and surveillance intensity.2) Imaging phenotypes, such as collaterals, vessel-wall features, IMR, radiomics, and covert SVD, personalize EVT candidacy, adjuvant choices, and cognitive follow-up.3) Etiologic precision, such as early CCTA to expose thrombus even without known AF, accelerates anticoagulation in selected patients. 4) Therapeutic tailoring-dose-and phenotype-aware thrombolysis, candidate neuroprotective adjuncts (e.g., cerebrolysin), and MIS for ICH, where feasible, should be tested with tissue-level surrogates (e.g., IMR) and patient-centered endpoints. 5) Operational precision, such as HERS-like infrastructures and collateral/fast-progressortriggered fast tracks, must prove they convert minutes into disability-free days, especially in posterior circulation and cancer-related phenotypes where equipoise persists. This Research Topic offers a coherent, actionable blueprint for precision stroke care: measure what matters, when it matters, for the patient in front of you. By combining accessible biomarkers (ALP, renal indices, microRNAs), richer imaging phenotypes (collaterals, vessel-wall features, IMR, radiomics, covert SVD), optimized reperfusion and adjunct strategies (dose-tuned thrombolysis, neuroprotection, MIS), and systems engineering (HERS, phenotype-triggered pathways), the field is poised to transform variability into value. The next phase hinges on rigorous external validation, workflowembedded trials, and equitable deployment so that personalization augments, rather than replaces, clinical judgment for every patient we serve.