Cerebral small vessel disease (CSVD) is a major cause of stroke and dementia, with its treatment paradigm shifting from conventional risk factor management to targeted pathophysiological interventions. This article reviews the current landscape and key challenges in CSVD treatment research, focusing on patient selection, optimization of study endpoints, and development of targeted therapeutic strategies. Additionally, it explores the FINESSE framework, which aims to refine CSVD clinical trial design and accelerate advancements in treatment.

Hemorrhagic transformation (HT) is one of the severe complications of ischemic stroke, which may occur either during the natural course or as a consequence of treatments such as thrombolysis and thrombectomy. HT is associated with poor prognosis after ischemic stroke and influences clinical treatment decisions. Disruption of blood-brain barrier (BBB) has been demonstrated as the main mechanism underlying HT. Inflammatory responses contribute to this process by activating endothelial cells, recruiting immune cells such as neutrophils and macrophages, and releasing inflammatory mediators including proteases and reactive oxygen species, which further exacerbate vascular injury and BBB permeability, thereby promoting HT. Blood inflammatory markers may reflect these pathological processes and offer valuable biological information for early identification and risk stratification of HT. Classical inflammatory markers, such as matrix metalloproteinase-9 (MMP-9) and ferritin, have been demonstrated predictive value for HT. Recently increasing attention has been paid to investigate the mechanism and predictive potential of novel markers, such as neutrophil gelatinase-associated lipocalin (NGAL), high-mobility group box 1 (HMGB1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, for predicting HT. This review focuses on the novel blood inflammatory markers and systematically describes their correlation with HT, with the aim of providing a scientific basis for the mechanism investigation, accurate prediction and individualized therapeutic strategies of HT.

Lobar hemorrhage is an important subtype of cerebral hemorrhage, which is associated with cerebral amyloidosis angiopathy (CAA) and has a high incidence rate, recurrence rate and disability rate. It is of great significance to predict its clinical prognosis using plain CT. Previous studies have found that the volume and morphology (irregular morphology of edges, island sign, spot sign, finger- like projection) of cerebral hemorrhage on CT images, combined with subarachnoid hemorrhage (SAH), CT cerebral small vessel disease (CSVD) score, and CT radiomics, have certain predictive value for early hematoma expansion, neurological deterioration, and long - term poor functional prognosis, and recurrence in lobar hemorrhage. We review the predictive value of the above imaging features for the prognosis in lobar hemorrhage, providing a theoretical basis for precise prognostic stratification and individualized intervention.

Objective: To explore the impact of acute-phase volume load on clinical outcome in patients with branch atheromatous disease (BAD)-related stroke. Methods: A total of 345 patients with BAD-related stroke were enrolled from June 2021 to June 2023 in the multicenter prospective cohort study (BAD-study) involving 20 comprehensive stroke centers across China. Neurological functional outcome at 90 d was assessed by modified Rankin Scale (mRS). Univariate and multivariate Logistic regression analyses were performed to identify factors influencing 90 d excellent outcome. Results: Multivariate Logistic regression analysis showed that a daily average intake of < 2000 ml (OR = 0.345, 95%CI: 0.133-0.897; P = 0.029), a daily average net intake of > 500 ml (OR = 0.457, 95%CI: 0.222-0.940; P = 0.033), advanced age (OR = 0.961, 95%CI: 0.929-0.994; P = 0.021), diabetes mellitus (OR = 0.494, 95%CI: 0.245-0.995; P = 0.048), previous statin use (OR = 0.159, 95%CI: 0.037-0.684; P = 0.014), higher baseline National Institutes of Health Stroke Scale (NIHSS) score (OR = 0.688, 95%CI: 0.613-0.772; P = 0.000), anticoagulant therapy (OR = 0.416, 95%CI: 0.203-0.850; P = 0.016) and early neurological deterioration (OR = 0.142, 95%CI: 0.059-0.343; P = 0.000) were risk factors for failture to achieve excellent outcome. Conclusions: For BAD-related stroke patients, a daily average intake of 2000-2500 ml and a daily average net intake of 0-500 ml in the acute-phase may have a better prognosis, suggesting that acute-phase volume management should balance the dual goals of avoiding hypovolemia and preventing volume overload, with individualized fluid rehydration strategies.

Objective: To analyze the distribution characteristics of imaging biomarkers in cerebral small vessel disease (CSVD) in high - altitude plateau, investigate interrelationships among imaging features, and identify influencing risk factors for high CSVD burden. Methods: A total of 131 CSVD patients diagnosed and treated at People's Hospital of Xizang Autonomous Region between January 2021 and December 2022 were enrolled. Clinical data were collected, and brain MRI was performed to assess white matter hyperintensity (WMH), lacunar infarcts (LACI), cerebral microbleeds (CMBs), and enlarged perivascular space (EPVS), with subsequent calculation of the total CSVD burden score. The distribution patterns of CSVD imaging markers were analyzed. Spearman rank correlation analysis was used to investigate the association among imaging biomakers, including WMH, LACI, CMBs and EPVS. Univariate and multivariate Logistic regression analyses were applied to examine risk factors for high CSVD burden. Results: Total 131 patients with CSVD were divided into high CSVD burden group (1-4 points, n = 85) and low CSVD burden group (0 point, n = 46) according to total CSVD burden score. Compared to the low CSVD burden group, the high CSVD burden group exhibited significantly older age (t = - 5.410, P = 0.000) and a higher prevalence of hypertension (χ² = 14.853, P = 0.000). Among patients with CSVD in high-altitude plateau, the prevalence of WMH was 95.42% (125/131); LACI accounted for 34.35% (45/131), and were commonly located in the basal ganglia region; CMBs were predominantly of the mixed type (40.54%, 15/37); the prevalence of EPVS was 54.96% (72/131). Spearman rank correlation analysis revealed that CMBs were positively correlated with WMH (r_s = 0.255, P = 0.003) and LACI (r_s = 0.289, P = 0.001). Logistic regression analysis revealed that older age (OR = 1.056, 95%CI: 1.026- 1.088; P = 0.000) and hypertension (OR = 2.482, 95%CI: 1.071 -5.753; P = 0.034) were risk factors for high CSVD burden. Conclusions: Prevention and management strategies for CSVD in these populations should prioritize elderly individuals and hypertensive patients. While high-altitude environment may exacerbate cerebrovascular pathology, their specific mechanistic roles require further investigation.

Objective: A preliminary study on the correlation between serum non - high - density lipoprotein cholesterol (non - HDL - C) and the severity of total burden of cerebral small vessel disease (CSVD), and influencing factors of the severity of CSVD total burden were screened. Methods: A total of 166 patients diagnosed with arteriosclerotic CSVD (aCSVD) admitted to Cangzhou Central Hospital from December 2024 to February 2025 were retrospectively enrolled. We evaluated white matter hyperintensity (WMH), lacunar infarct (LACI), cerebral microbleeds (CMBs) and enlarged perivascular space (EPVS) based on the cranial MRI to calculate the CSVD total burden score. Spearman rank correlation analysis was performed to analyse the relationship between non - HDL - C and CSVD total burden. Univariate and multivariate Logistic regression analyses were further used to identify influencing factors for the severity of CSVD total burden. Results: According to the CSVD total burden score, the patients were divided into the mild total burden (0-1 point) group (n = 79) and the moderate and severe total burden (2-4 points) group (n = 87). There was a positive correlation between non - HDL - C level and CSVD total burden score (r_s = 0.184, P = 0.018). Logistic regression analysis revealed that older age (OR = 1.046, 95%CI: 1.001-1.094; P = 0.045), increased homocysteine (OR = 1.057, 95%CI: 1.003-1.115; P = 0.040) and increased non-HDL-C (OR = 1.376, 95%CI: 1.026-1.848; P = 0.033) were risk factors for the moderate and severe CSVD total burden. Conclusions: Increased non - HDL - C is a risk factor for the moderate and severe CSVD total burden, or it may potentially serve as an target of intervention for aCSVD.

Objective: To investigate the predictive value of a modified Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score, in which the triglyceride glucose (TyG) index replaces the glucose parameter of ASTRAL score, for poor prognosis in ischemic stroke patients. Methods: This study was based on the ischemic stroke database of The First Affiliated Hospital of Zhengzhou University. A total of 3393 ischemic stroke patients from January 2019 to December 2021 were enrolled. Baseline information was collected, and the TyG index and ASTRAL score were calculated. Replace the glucose parameter of ASTRAL score with the TyG index to construct ASTRAL-TyG model. Modified Rankin Scale (mRS) score was used to evaluate the functional outcome. Univariate and multivariate Logistic regression analyses were performed to screen for influencing factors of poor prognosis. Receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the predictive value of the ASTRAL - TyG model. Results: Based on the mRS score, patients were stratified into a good prognosis group (mRS ≤ 2, n = 2961) and a poor prognosis group (mRS > 2, n = 432). Logistic regression analysis showed that both increased ASTRAL score witnin 24 h of admission (OR = 1.156, 95%CI: 1.133-1.179; P = 0.000) and increased TyG index (OR = 1.731, 95%CI: 1.489-2.013; P = 0.000) were risk factors for poor prognosis (Model 1, TyG index was included as a continuous variable). Increased ASTRAL score within 24 h of admission (OR = 1.156, 95%CI: 1.133-1.179; P = 0.000), TyG index of 8.69-9.08 (OR = 1.445, 95%CI: 1.025-2.039; P = 0.036), and TyG index ≥ 9.55 (OR = 2.103, 95%CI: 1.532-2.888; P = 0.000) were risk factors for poor prognosis (Model 2, TyG index was included as a categorical variable). The ROC curve demonstrated that the AUC for predicting one year poor prognosis was 0.754 (95%CI: 0.728-0.779, P = 0.000) for the ASTRAL score and 0.768 (95%CI: 0.743-0.794, P = 0.000) for the ASTRAL-TyG model. The sensitivity was 65.05% and 65.97%, while the specificity was 74.23% and 78.01%, respectively. The predictive value of the ASTRAL - TyG model was significantly higher than that of the ASTRAL score (Z = 2.084, P = 0.037). Conclusions: The ASTRAL score modified by the TyG index (ASTRAL - TyG model) improved the predictive value for poor prognosis in ischemic stroke patients.

Objective: To compare the efficiency and safety between balloon dilation and stent implantation in young ischemic stroke patients with symptomatic intracranial artery stenosis (ICAS). Methods: Total 37 young ischemic stroke patients who received endovascular treatment in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from February 2019 to February 2023 were enrolled. According to the Mori classification and the location of the lesions, balloon dilation was performed in 12 cases and stent implantation was performed in 25 cases. The primary outcomes were vascular restenosis rate, stroke recurrence rate and mortality events during the follow? up period (3-12 months after operation), and the secondary outcomes were the surgical success rate and the peri?operative complications rate. Results: For the primary outcomes, after an average follow?up of (5.21 ± 2.19) months, among the 36 patients who completed the follow? up, 6 cases (16.67%) had vascular restenosis, with 2 cases (2/12) in balloon dilation group and 4 cases (16.67%) in stent implantation group. There was no statistically significant difference between the 2 groups (Fisher's exact probability: P = 1.000). No stroke recurrence or mortality events occurred. For the secondary outcomes, the surgical success rate reached 100% (37/37). Three cases (8.11%) experienced peri?operative complications, with one case (1/12) in balloon dilation group and 2 cases (8%) in stent implantation group. There was no statistically significant difference between the 2 groups (Fisher's exact probability: P = 1.000). No thrombosis occurred within the stent or the diseased blood vessels. Conclusions: For young ischemic stroke patients with ICAS, the efficacy and safety of balloon dilation and stent implantation are comparable. Further exploration through multicenter, large?sample clinical trials are needed.

Objective: To investigate the clinical characteristics and current treatment status of spontaneous intracerebral hemorrhage (ICH) patients in Xizang Autonomous Region and to screen for factors influencing short - term poor neurological prognosis. Methods: A total of 200 spontaneous ICH patients admitted to People's Hospital of Xizang Autonomous Region between April 2020 and November 2022 were included. The modified Rankin Scale (mRS) was used to assess short - term neurological prognosis at discharge. Univariate and multivariate Logistic regression analyses were performed to identify influencing factors associated with short-term poor neurological prognosis. Results: The study included 200 patients with ICH. Their average age of onset was (65.42 ± 7.78) years, with a high prevalence of hypertension (97.50%, 195/200) and basal ganglia hemorrhage (59%, 118/200). The age at onset was older and the mortality rate (2%, 4/200) was lower than previously reported. Based on mRS score at discharge, patients were divided into a good prognosis group (0-2 points, n = 72) and a poor prognosis group (3-6 points, n = 128). Logistic regression analysis in the 148 patients without intraventricular extension showed that basal ganglia hemorrhage (OR = 7.098, 95%CI: 3.043-16.557; P = 0.000) and hemorrhage volume (per 10 ml increase; OR = 1.485, 95%CI: 1.240-1.777, P = 0.000) were risk factors for short - term poor neurological prognosis. Conclusions: Spontaneous ICH in Xizang region exhibits unique epidemiological characteristics, with a notably high prevalence of hypertension and basal ganglia hemorrhage, and a delay in the age at onset and a reduction in the mortality rate compared to previous reports. Hemorrhage volume and basal ganglia involvement are critical determinants of short - term poor neurological prognosis. Strengthening hypertension management, optimizing acute-phase treatment, and enhancing medical resource allocation are essential to improving prognosis.

Objective: To investigate the correlation between vestibular symptoms and balance/walking function in patients with acute brain stem infarction. Methods: Fifty-one patients with acute brain stem infarction with a Functional Ambulation Category Scale (FAC) grade > 3 admitted to Tianjin Huanhu Hospital between November 2023 and December 2024 were included. The subjective visual vertical skew angle was measured using the Bucket Test. The degree of dizziness/vertigo was evaluated by the Visual Analogue Scales (VAS). The vestibulo-ocular reflex function was assessed by dynamic visual acuity (DVA). The Activities-Specific Balance Confidence Scale (ABC) was used to evaluate the balance confidence during performing various tasks, and the Dynamic Gait Index (DGI) was applied to assess the objective dynamic balance function. Results: Spearman rank correlation analysis showed that the ABC score was negatively correlated with the subjective visual vertical skew angle (r_s = -0.414, P = 0.003) and dizziness/vertigo VAS score (r_s = -0.463, P = 0.000), and the DGI index was negatively correlated with subjective visual vertical skew angle (r_s = -0.347, P = 0.012), dizziness/vertigo VAS score (r_s = -0.472, P = 0.000) and the number of rows lost in the yaw plane of DVA (r_s = -0.326, P = 0.019). Multifactor linear stepwise regression analysis showed that the strength of the effect of dizziness/vertigo VAS score (standardized partial regression coefficient = -0.593, P = 0.000) on ABC score was approximately 2.21 times greater than that of the subjective visual vertical skew angle (standardized partial regression coefficient = -0.268, P = 0.015); the effect of dizziness/vertigo VAS score (standardized partial regression coefficient = -0.666, P = 0.000) was 2.53 times stronger on the DGI index than the number of rows lost in the yaw plane of DVA (standardized partial regression coefficient = -0.263, P = 0.010). Further Spearman rank correlation analysis showed a positive correlation between dizziness/vertigo VAS score and the proportion of the stance phase time of gait parameter (r_s = 0.289, P = 0.039). Conclusions: Dynamic balance function in patients with acute brain stem infarction is mainly affected by the dizziness/vertigo severity. Furthermore, the degree of dizziness/vertigo shows a positive correlation with the proportion of stance phase duration during walking, which warrants heightened attention from both clinicians and rehabilitation therapists.

Objective: To analyze the protective effect and mechanism of nuclear factor-erythroid 2-related factor 2 (Nrf2) signal pathway agonist tertiary butylhydroquinone (tBHQ) on astrocytes under oxygen glucose deprivation (OGD). Methods: Astrocytes were divided into 3 groups: the control group, the OGD group, and the tBHQ group. The cell proliferation activity after OGD and tBHQ intervention was assessed using the CCK -8 assay. Oxidative stress levels were evaluated by measuring superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The relative expression levels of pyroptosis-related genes (Caspase-1, NLRP3, IL-1β, IL 18) and antioxidant-related genes (HO-1, NQO1) were detected using real time fluorescent quantitative polymerase chain reaction (PCR). Results: Significant differences were observed among different treatment groups in cell proliferation activity (F = 8.676, P = 0.003), SOD activity (F = 5.818, P = 0.013), MDA content (F = 9.049, P = 0.004), relative expression of pyroptosis-related genes Caspase-1 (F = 17.926, P = 0.003), NLRP3 (F = 10.164, P = 0.012), IL-1β (F = 13.472, P = 0.006), IL-18 (F = 8.292, P = 0.019), and antioxidant -related genes HO-1 (F = 30.468, P = 0.001), NQO1 (F = 29.621, P = 0.001). Compared with the control group, the OGD group exhibited reduced cell proliferation activity (t = 4.114, P = 0.001) and SOD activity (t = 2.149, P = 0.029), increased MDA content (t = -2.852, P = 0.015), upregulated expression of pyroptosis-related genes Caspase-1 (t = -3.759, P = 0.009), NLRP3 (t = -4.119, P = 0.006), IL-1β (t = -4.747, P = 0.003) and IL 18 (t = -3.122, P = 0.021), and downregulated expression of antioxidant-related genes HO-1 (t = 3.816, P = 0.009) and NQO1 (t = 5.303, P = 0.002). Following tBHQ intervention, cell proliferation activity increased (t = 2.621, P = 0.019), SOD activity increased (t = 3.292, P = 0.005), MDA content decreased (t = -4.160, P = 0.001), expression of Caspase-1 (t = -5.916, P = 0.001), NLRP3 (t = -3.647, P = 0.011), IL-1β (t = -4.193, P = 0.006) and IL-18 (t = -3.825, P = 0.009) decreased, and expression of HO-1 (t = 7.805, P = 0.000) and NQO1 (t = 7.483, P = 0.000) increased. Conclusions: OGD can suppress the expression of antioxidant-related genes HO-1 and NQO1, promote astrocytes pyroptosis and oxidative stress, and inhibit cell proliferation activity. Nrf2 signal pathway agonist tBHQ can enhance the expression of HO-1 and NQO1, reduce oxidative stress in OGD-exposed astrocytes, reverse pyroptosis, and exert protective effects on the cells.

Objective: To investigate the short -term efficacy, long -term outcome and safety of recanalization treatment in patients with acute ischemic stroke presenting with large infarct core caused by intracranial atherosclerotic stenosis (ICAS) versus cardiac embolism (CE). Methods: A total of 96 acute ischemic stroke patients with large infarct core who underwent recanalization treatment at The People's Hospital of Anyang City from January 2022 to January 2023 were enrolled. Based on etiology, patients were divided into ICAS group (n = 52) and CE group (n = 44). Short-term efficacy was assessed using the National Institutes of Health Stroke Scale (NIHSS) at 14 d postoperatively, while long -term outcome was evaluated using the modified Rankin Scale (mRS) at 90 d postoperatively. Safety outcome included rate of symptomatic intracranial hemorrhage (sICH), intracranial hemorrhage, cerebral herniation within 24 h postoperatively, and fatality rate at 90 d postoperatively. Results: A statistically significant difference in NIHSS score was observed between the ICAS group and the CE group (F = 5.821, P = 0.023), with the CE group having higher NIHSS score than the ICAS group at admission (t = -2.324, P = 0.022). Both groups showed significant differences in NIHSS score between admission and 14 d postoperatively (F = 589.322, P = 0.000), with the CE group demonstrating lower NIHSS score at 14 d postoperatively compared to admission (t = 4.173, P = 0.001). The ICAS group exhibited a higher rate of favorable outcome at 90 d postoperatively [44.23% (23/52) vs. 25% (11/44); χ² = 3.853, P = 0.050]. No significant differences were observed between the 2 groups in sICH, intracranial hemorrhage, cerebral herniation rate, or 90 d fatality rate (P > 0.05, for all). Conclusions: Recanalization treatment for acute ischemic stroke patients with large infarct core caused by CE demonstrates more pronounced short-term efficacy, while ICAS presenting with better long-term outcome, and there is no significant difference in safety between the 2 groups.

Cryptogenic stroke (CS) is a type of ischemic stroke with an unknown cause, and it is closely associated with right-to-left shunt (RLS). Patent foramen ovale (PFO) and pulmonary arteriovenous fistula (PAVF) are two common types of RLS. While there has been extensive research on PFO, there has been relatively less attention paid to PAVF. Writer provides a review of the clinical features, advances in ultrasonography and imaging diagnostic techniques, as well as treatment methods and prognosis analysis of PAVF, with the aim of providing reference for clinical practice.