Borja Enrique Sanz-Cuesta

Background: Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to internal carotid artery (ICA) or middle cerebral artery (MCA) M1 occlusion with a small ischemic core. However, the effect of EVT on acute stroke with a large ischemic core remains unclear. This study aimed to evaluate the association of EVT plus medical care versus medical care alone with outcomes in patients with acute stroke and a large ischemic core due to ICA or MCA M1 occlusion. Methods and findings: PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 2000 to September 25, 2024. There were no language restrictions. Randomized controlled trials (RCTs) of patients with acute stroke and a large ischemic core that compared EVT plus medical care versus medical care alone were evaluated. We computed the random-effects estimate based on the inverse variance method. Risk ratio (RR) with 95% confidence interval (CI) was used to measure outcomes of EVT plus medical care versus medical care alone. The primary outcome was functional independence, defined as modified Rankin Scale (mRS) of 0–2 at 90 days post-stroke; and the lead secondary outcome was reduced disability, defined as ordinal shift of mRS. Safety outcomes were requiring constant care or death (mRS 5–6), death, and early symptomatic intracranial hemorrhage (sICH). Grading of Recommendations Assessment, Development and Evaluations (GRADE) was used to evaluate summaries of evidence for the outcomes. We included six RCTs comprising 1870 patients (826 females [44.2%]) with acute stroke and a larger moderate or large ischemic core due to ICA or MCA M1 occlusion. All patients were nondisabled before stroke. Pooled results showed that at 90 days post-stroke, EVT plus medical care, compared with medical care alone, was associated with greater functional independence (RR 2.53, 95% CI [1.95, 3.29]; p < 0.001; number needed to treat [NNT], 9, 95% CI [6,15]) and reduced disability (common odds ratio 1.63, 95% CI [1.38, 1.93]; p < 0.001; NNT, 4 [minimum possible NNT, 2; maximum possible NNT, 6]). EVT plus medical care, compared with medical care alone, was associated with a lower risk of requiring constant care or death (RR 0.74, 95% CI [0.66, 0.84]; p < 0.001; NNT, 7, 95% CI [6,11]). EVT plus medical care, compared with medical care alone, was associated with a nonsignificantly higher proportion of patients with early symptomatic intracranial hemorrhage (RR 1.65, 95% CI [1.00, 2.70]; p = 0.05). The rates of death were not significantly different between the EVT plus medical care and medical care alone groups (RR 0.86, 95% CI [0.72, 1.02]; p = 0.08). Main limitations include variability in imaging definitions of large core and inclusion of both larger moderate and large cores in the analysis. Conclusions: Among patients with acute stroke and a larger moderate or large ischemic core due to ICA or MCA M1 occlusion who were nondisabled before stroke, EVT plus medical care, compared with medical care alone, may be associated with improved functional independence, reduced disability, and reduced rates of severe disability or death at 90 days post-stroke. PROSPERO registration number: CRD42024514605

Background: Endovascular thrombectomy (EVT) is standard treatment for an acute ischemic stroke due to large-vessel occlusions (AIS-LVO) with a small ischemic core, but the effect of EVT on AIS-LVO with a large ischemic core remains unclear. The objective was to assess the benefit and safety of EVT for AIS-LVO with large ischemic cores. Methods and Finding: PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1 2000 to September 25 2025. Randomized clinical trials (RCTs) of patients with AIS-LVO and large ischemic cores that compared EVT plus medical care vs. medical care alone were evaluated. Risk ratio (RR) with 95% CI was used to measure outcomes of EVT vs. medical care alone. Primary outcome was functional independence, defined as modified Rankin Scale (mRS) of 0 to 2 at 90 days; and lead secondary outcome was reduced disability, defined as ordinal shift of mRS. Safety outcomes were requiring constant care or death (mRS 5 to 6), death, and early symptomatic intracranial hemorrhage (sICH). We included 6 RCTs comprising 1870 patients (women 826 [44.2%]) with AIS-LVO. Pooled results showed that at 90 days, EVT vs. medical care alone was associated with greater functional independence (RR 2.53, 95% CI, 1.95-3.29; number needed to treat [NNT], 9) and reduced disability (common odds ratio 1.63, 95% CI 1.38-1.93; NNT, 4). EVT vs. medical care alone was associated with a lower risk of requring constant care or death (RR 0.74, 95% CI 0.66 to 0.84; NNT, 7). The rates of death and early sICH were not significantly different between the EVT and medical care alone groups. Conclusions: EVT combined with medical care compared with medical care alone may be associated with improved functional outcomes and reduced severe disability or death at 90 days for acute stroke with large ischemic cores. PROSPERO registration number: CRD42024514605

Background and Purpose: Statins were shown to increase hemorrhagic stroke (HS) in patients with a first cerebrovascular event in 2006 (SPARCL), likely due to off-target antithrombotic effects, but continued to sometimes be used in patients with elevated HS risk due to absence of alternative medications. Recently, the PCSK9Is (proprotein convertase subtilisin kexin 9 inhibitors) have become available as a potent lipid-lowering class with potentially less hemorrhagic propensity. Methods: We performed a systematic comparative meta-analysis assessing HS rates across all completed statin and PCSK9I randomized clinical trials with treatment >3 months, following PRISMA guidelines. In addition to HS rates across all trials, causal relation was probed by evaluating for dose-response relationships by medication (low versus high medication dose/potency) and by presence and type of preceding brain vascular events at inception (none versus ischemic stroke/transient ischemic attack versus HS). Results: The systematic review identified 36 statin randomized clinical trials (204 918 patients) and 5 PCSK9I randomized clinical trials (76 140 patients). Across all patient types and all medication doses/potencies, statins were associated with increased HS: relative risk 1.15, P =0.04; PCSK9Is were not ( P =0.77). In the medication dose/potency analysis, higher dose/potency statins (7 trials, 62 204 patients) were associated with magnified HS risk: relative risk, 1.53; P =0.002; higher dose/potency PCSK9Is (1 trial, 27 564 patients) were not ( P =0.99). In the type of index brain vascular injury analysis for statins (5 trials, 9772 patients), prior ischemic stroke/transient ischemic attack was associated with a magnified risk of HS: relative risk, 1.43; P =0.04; and index intracerebral hemorrhage was associated with an extremely high effect estimate of risk of recurrent HS: hazard ratio, 4.06. For PCSK9Is, prior ischemic stroke/transient ischemic attack (1 trial, 5337 patients) was not associated with increased HS risk ( P =0.97). Conclusions: Statins increase the risk of HS in a medication dose- and type of index brain vascular injury-dependent manner; PCSK9Is do not increase HS risk. PCSK9Is may be a preferred lipid-lowering medication class in patients with elevated HS risk, including patients with prior HS.

Background and purpose: The aim of the study was to analyze the effect of conventional glucose management, which aimed to maintain glucose levels P = 0.029).Conclusions: Lack of response to conventional treatment for glucose management in acute IS is frequent and associated with poor outcomes.

Objective: To quantitatively evaluate blood–brain barrier changes in ischemic stroke patients using dynamic contrast-enhanced (DCE) MRI. Methods: We examined 54 stroke patients (clinicaltrials.govNCT00715533, NCT02077582) in a 3T MRI scanner within 48 hours after symptom onset. Twenty-eight patients had a follow-up examination on day 5–7. DCE T1 mapping and Patlak analysis were employed to assess BBB permeability changes. Results: Median stroke K^trans values (0.7 × 10⁻³ min⁻¹ [interquartile range (IQR) 0.4–1.8] × 10⁻³ min⁻¹) were more than 3-fold higher compared to median mirror K^trans values (0.2 × 10⁻³ min⁻¹, IQR 0.1–0.7 × 10⁻³ min⁻¹, p < 0.001) and further increased at follow-up (n = 28, 2.3 × 10⁻³ min⁻¹, IQR 0.8–4.6 × 10⁻³ min⁻¹, p < 0.001). By contrast, mirror K^trans values decreased over time with a clear interaction of timepoint and stroke/mirror side (p < 0.001). Median stroke K^trans values were 2.5 times lower than in hemorrhagic transformed regions (0.7 vs 1.8 × 10⁻³ min⁻¹; p = 0.055). There was no association between stroke K^trans values and the delay from symptom onset to baseline examination, age, and presence of hyperintense acute reperfusion marker. Conclusion: BBB in acute stroke patients can be successfully assessed quantitatively. The decrease of BBB permeability in unaffected regions at follow-up may be an indicator of global BBB leakage even in vessel territories remote from the index infarct.

Objective: To perform a literature review of the epidemiology, clinical presentation, diagnostic evaluation, and clinical course of occipital condyle syndrome, including a new case report. Background: Occipital condyle syndrome (OCS) is a rare clinical syndrome, consisting of unilateral occipital headache accompanied by ipsilateral hypoglossal palsy. This headache typically radiates to the temporal region, and is triggered by contralateral head rotation. It is usually associated with skull base metastasis, often unrevealed in basic neuroimaging studies. OCS might be the first manifestation of malignancy, and its unfamiliarity can lead to a delay in the diagnosis. Methods: We performed a systematic literature review using PubMed and Embase for OCS, along with a new case report. Results: A total of 35 cases (mean age 59 years, range 25‐77), 24 (70%) men, presented typical unilateral headache followed by ipsilateral hypoglossal palsy from 0 to 150 days after headache presentation. In 16 patients (46%), initial neuroimaging studies were normal. OCS was due to skull base metastasis in 32 cases (91%). In 18 patients (51%), OCS was the first symptom of disease. Conclusions: OCS represents a warning sign and requires an exhaustive search for underlying neoplasm. An appropriate clinical evaluation can lead to an earlier diagnosis in patients with consistent headache.

Background and purpose The present study was conducted with the objective of evaluating the safety of primary mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke and comorbidities that preclude treatment with IV thrombolysis (IVT), compared with patients who received standard IVT treatment followed by MT. Secondary objectives were to analyse the recanalization rate and outcomes. Methods A prospective observational multicenter study (FUN-TPA) that recruited patients treated within 4.5 hours of symptom onset was performed. Treatments were IVT followed by MT if occlusion persisted, or primary MT when IVT was contraindicated. Outcome measures were procedural complications, symptomatic intracranial hemorrhage (SICH), recanalization rate, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, modified Rankin Scale (mRS) score and mortality at 90 days. Results Of 131 patients, 21 (16%) had medical contraindications for IVT and were treated primarily with MT whereas 110 (84%) underwent IVT, followed by MT in 53 cases (40%). The recanalization rate and procedural complications were similar in the two groups. There were no SICHs after primary MT vs 3 (6%) after IVT+MT. Nine patients (43%) in the primary MT group achieved independence (mRS 0–2) compared with 36 (68%) in the IVT+MT group (p=0.046). Mortality rates in the two groups were 14% (n=3) vs 4% (n=2) (p=0.13). Adjusted ORs for independence in patients receiving standard IVT+MT vs MT in patients with medical contraindications for IVT were 2.8 (95% CI 0.99 to 7.98) and 0.24 (95% CI 0.04 to 1.52) for mortality. Conclusions MT is safe in patients with potential comorbidity-derived risks that preclude IVT. MT should be offered, aiming for prompt recanalization, to patients with LVO stroke unsuitable for IVT. Trial registration number NCT02164357; Results.

Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010–2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5–1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR 2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006–4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173–3.789) as well as INR 1.5–1.9 (OR 3.676, 95 % CI 1.510–8.946) were associated with favorable outcomes (mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT.