Recent Small Subcortical Infarcts Research Articles

Recurrent cerebrovascular events after recent small subcortical infarction.

Recent small subcortical infarcts (RSSI) are the neuroimaging hallmark feature of small vessel disease (SVD)-related acute lacunar stroke. Long-term data on recurrent cerebrovascular events including their aetiology after RSSI are scarce. This retrospective study included all consecutive ischaemic stroke patients with an MRI-confirmed RSSI (in the supply area of a small single brain artery) at University Hospital Graz between 2008 and 2013. We investigated associations between clinical and SVD features on MRI (STRIVE criteria) and recurrent cerebrovascular events, using multivariable Cox regression adjusted for age, sex, vascular risk factors and MRI parameters. We analysed 332 consecutive patients (mean age 68years, 36% women; median follow-up time 12years). A recurrent ischaemic cerebrovascular event occurred in 70 patients (21.1%; 54 ischaemic strokes, 22 transient ischaemic attacks) and was mainly attributed to SVD (68%). 26 patients (7.8%) developed intracranial haemorrhage. In multivariable analysis, diabetes (HR 2.43, 95% CI 1.44-3.88), severe white matter hyperintensities (HR 1.97, 95% CI 1.14-3.41), and cerebral microbleeds (HR 1.89, 95% CI 1.32-3.14) on baseline MRI were related to recurrent ischaemic stroke/TIA, while presence of cerebral microbleeds increased the risk for intracranial haemorrhage (HR 3.25, 95% CI 1.39-7.59). A widely used SVD summary score indicated high risks of recurrent ischaemic (HR 1.22, 95% CI 1.01-1.49) and haemorrhagic cerebrovascular events (HR 1.57, 95% CI 1.11-2.22). Patients with RSSI have a substantial risk for recurrent cerebrovascular events-particularly those with coexisting chronic SVD features. Recurrent events are mainly related to SVD again.

Correlation between Carotid Blood Flow Velocity and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients with Recent Small Subcortical Infarcts

Background: The common and internal carotid arteries are the upstream vessels of the small cerebral vessels. The relationship between hemodynamic changes in the significant cervical vessels and cerebral small vessel disease (CSVD) remains uncertain. This research sought to analyze the correlation between carotid blood flow velocity and the total magnetic resonance imaging (MRI) burden of CSVD in patients with recent small subcortical infarcts (RSSIs). Methods: Data were gathered from individuals diagnosed with RSSIs admitted to Changzhou Second People's Hospital between January 2022 and June 2023. Brain MRI was performed on every patient to determine the overall MRI burden of CSVD, along with carotid duplex ultrasound to evaluate carotid blood flow velocity and pulsatility index (PI) of the common carotid (CCA) and internal carotid (ICA) arteries. The association between carotid blood flow velocity and the total MRI load of CSVD was examined using univariate and multivariate analyses. Results: For our investigation, 272 individuals with RSSIs were screened. 82 individuals had a moderate to severe load of CSVD, while 190 participants showed a mild burden. Patients with moderate to severe burden of CSVD had lower end-diastolic velocity (EDV) and higher PI in CCA and ICA than those with mild load (P < 0.001). After adjusting for variables like age, hypertension, systolic blood pressure, and blood homocysteine levels, multivariate logistic regression analysis showed that EDV in CCA (OR, 0.894; P = 0.011), PI in CCA (OR, 5.869; P = 0.017), EDV in ICA (OR, 0.909; P = 0.008), and PI in ICA (OR, 5.324; P = 0.041) were independently related to moderate to severe CSVD burden. Spearman correlation analysis showed that EDV in CCA and ICA was negatively related to the total MRI load of CSVD in patients with RSSIs (P < 0.001). PI in CCA and ICA was positively associated with the whole MRI load of CSVD (P < 0.001). Conclusion: Low carotid blood flow velocity and high carotid pulsatility index are independently associated with moderate to severe burden of CSVD.

Analysis of the Relationship between Recent Small Subcortical Infarcts and Autonomic Nervous Dysfunction.

Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV). A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population. Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI. Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.

Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood-brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood-brain barrier function.

Modified Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease and Related Risk Factors in Patients With Thalassemia.

This study aimed to explore the burden of magnetic resonance imaging (MRI) of cerebral small vessel disease (CSVD) in patients with thalassemia and related risk factors. The clinical data and MRI of patients with thalassemia were retrospectively analyzed, and non-thalassemia controls with matched sex and age were selected. The modified MRI burden of CSVD included recent small subcortical infarct, presumed vasogenic white matter hyperintensity, presumed vasogenic lacunae, perivascular space (PVS), and brain atrophy. This study included 110 patients in each of the thalassemia and control groups. There was no significant difference in sex, age, and common cerebrovascular disease risk factors between the 2 groups. The patients with thalassemia had a higher red blood cell count and lower content of hemoglobin. The PVS and modified MRI burden scores in the thalassemia group were higher than in the control group. With the increase in age, patients with thalassemia have a more severe CSVD burden. Patients with thalassemia have a heavier modified MRI burden of CSVD than non-thalassemia patients, particularly PVS, and aging is an important risk factor for CSVD changes.

Enlarged Perivascular Space in the Basal Ganglia is Associated with Cerebral Venous Reflux in Patients with Recent Small Subcortical Infarction.

Research has linked enlarged perivascular spaces (EPVS) to cerebral venous reflux (CVR) in patients with hypertensive intracerebral hemorrhage, but it is unclear whether this association exists in recent small subcortical infarct (RSSI) patients. This study aimed to investigate the correlation between EPVS and CVR in patients with RSSI. This study included 297 patients, selected from patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University. CVR was assessed by time-of-flight magnetic resonance angiography (TOF-MRA). The relationship between EPVS and CVR was studied using multiple logistic regression analysis. This study included patients with an average age of 59.84±12.27 years, including 201 males (67.7%). CVR was observed in 40 (13.5%) patients. Compared to the group without CVR, the proportions of male patients and patients with a history of smoking and drinking were higher in the CVR group. The proportions of high-grade EPVS in the centrum semiovale region [23 cases (57.5%) vs. 108 cases (42.0%), p =0.067] and the basal ganglia region [30 cases (75.0%) vs. 133 cases (51.8%), p =0.006] were higher in the CVR group. After multiple logistic regression analysis, high-grade EPVS in the basal ganglia region was still associated with CVR (OR, 2.68; 95% CI, 1.22-5.87; p =0.014). In the population with RSSI, EPVS in basal ganglia is significantly associated with CVR, suggesting a close relationship between venous dysfunction and the formation of EPVS.

Inflammation-associated D-dimer predicts neurological outcome of recent small subcortical infarct: A prospective clinical and laboratory study

ObjectiveElevated level of D-Dimer often indicates a worse prognosis in cerebral infarction. However, there is limited research on this impact within recent small subcortical infarction (RSSI). We aim to explore the role of inflammation and the total magnetic resonance imaging (MRI) burden of cerebral small vessel disease (cSVD) in this process. Methods384 RSSI patients and 189 matched healthy controls were strictly registered in the current research. We evaluated short-term and long-term outcomes by measuring the percentage of the National Institutes of Health Stroke Scale (NIHSS) improvement and the modified Rankin Scale (mRS) at 3 months, respectively. We also assessed the chronic, sustained brain damage associated with cSVD using the total MRI burden and confirmed the relationship between prognosis and the total MRI burden of cSVD. Furthermore, we explored the associations between D-dimer and C-reactive protein (CRP) levels with NIHSS improvement and mRS at 3 months, as well as their relationships with both the total MRI burden of cSVD and its 4 imaging features. ResultsBoth NIHSS improvement and the mRS at 3 months were found to be correlated with the total MRI burden of cSVD. Higher D-dimer and CRP levels showed a linear correlation, indicating worse prognosis and a higher total MRI burden of cSVD. The four imaging features of the total MRI burden of cSVD did not exhibit entirely consistent patterns when exploring their correlations with prognosis and laboratory indicators. ConclusionInflammation-associated D-dimer predicts neurological outcomes in patients with recent small subcortical infarct, and reflects a more severe total MRI burden of cSVD.

Improved Visualization and Quantification of Net Water Uptake in Recent Small Subcortical Infarcts in the Thalamus Using Computed Tomography.

Diagnosing recent small subcortical infarcts (RSSIs) via early computed tomography (CT) remains challenging. This study aimed to assess CT attenuation values (Hounsfield Units (HU)) and net water uptake (NWU) in RSSI and explore a postprocessing algorithm's potential to enhance thalamic RSSI detection. We examined non-contrast CT (NCCT) data from patients with confirmed thalamic RSSI on diffusion-weighted magnetic resonance imaging (DW-MRI) between January 2010 and October 2017. Co-registered DW-MRI and NCCT images enabled HU and NWU quantification in the infarct area compared to unaffected contralateral tissue. Results were categorized based on symptom onset to NCCT timing. Postprocessing using window optimization and frequency-selective non-linear blending (FSNLB) was applied, with interpretations by three blinded Neuroradiologists. The study included 34 patients (median age 70 years [IQR 63-76], 14 women). RSSI exhibited significantly reduced mean CT attenuation compared to unaffected thalamus (29.6 HU (±3.1) vs. 33.3 HU (±2.6); p < 0.01). Mean NWU in the infarct area increased from 6.4% (±7.2) at 0-6 h to 16.6% (±8.7) at 24-36 h post-symptom onset. Postprocessed NCCT using these HU values improved sensitivity for RSSI detection from 32% in unprocessed CT to 41% in FSNLB-optimized CT, with specificities ranging from 86% to 95%. In conclusion, CT attenuation values and NWU are discernible in thalamic RSSI up to 36 h post-symptom onset. Postprocessing techniques, particularly window optimization and FSNLB, moderately enhance RSSI detection.

Symptomatic Non-stenotic Atherosclerotic Disease in Small Subcortical Infarcts: A North American Pilot Study.

Recent small subcortical infarcts (SSI) are a common radiographic predecessor to lacunar stroke. SSI is comprised of several pathophysiologic processes such as branch atherosclerotic disease (BAD) and lipohyalinosis, both of which have differing outcomes and natural history. Presently, there is not a proven method to determine whether a SSI is due to BAD or lipohyalinosis in non-stenotic vessels. However, high-resolution vessel wall imaging (HRVWI) has been reported in East Asian cohorts. We aimed to use HRVWI to identify individuals with BAD-related SSI in a North American cohort. We performed a cross-sectional study from the Rhode Island Hospital. All patients had a SSI as defined by consensus criteria. The presence of vessel wall enhancement of parent vessels were reviewed by two authors. Standard descriptive statistical techniques were used. Of 28 patients who underwent HRVWI, 7 met criteria for SSI. The median age was 68years and 3 were female. Parent vessel wall enhancement was present in 2 patients. In our North American cohort, HRVWI was able to dichotomize individuals based on parent vessel wall enhancement suggestive of a BAD-related SSI. Further studies are needed to expand our cohort size and confirm our findings.

Relationship of arterial stiffness and baseline vascular burden with new lacunes and microbleeds: A longitudinal cohort study.

Arterial stiffness may have a significant impact on the development of cerebral small vessel disease (cSVD). We obtained pulse wave velocity (24-h PWV) by means of ambulatory blood pressure monitoring (ABPM) in patients with a recent small subcortical infarct (RSSI). Patients with known cardiac or arterial embolic sources were excluded. Lacunes, microbleeds, white matter hyperintensities and enlarged perivascular spaces at baseline were assessed in a brain MRI and included in a cSVD score. A follow-up MRI was obtained 2 years later and assessed for the appearance of new lacunes or microbleeds. We constructed both unadjusted and adjusted models, and subsequently selected the optimal models based on the area under the curve (AUC) of the predicted probabilities. Ninety-two patients (mean age 67.04 years, 69.6% men) were evaluated and 25 had new lacunes or microbleeds during follow-up. There was a strong correlation between 24-h PWV and age (r = 0.942, p < 0.001). cSVD was associated with new lacunes or microbleeds when adjusted by age, 24-h PWV, NT-proBNP and hypercholesterolemia (OR 2.453, CI95% 1.381-4.358). The models exhibiting the highest discrimination, as indicated by their area under the curve (AUC) values, were as follows: 1 (AUC 0.854) - Age, cSVD score, 24-h PWV, Hypercholesterolemia; 2 (AUC 0.852) - cSVD score, 24-h PWV, Hypercholesterolemia; and 3 (AUC 0.843) - Age, cSVD score, Hypercholesterolemia. cSVD score is a stronger predictor for cSVD progression than age or hemodynamic parameters in patients with a RSSI.

Cerebral Small Vessel Disease and Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment: A Systematic Review and Meta‐Analysis

Background It remains unclear whether neuroimaging markers of cerebral small‐vessel disease (CSVD) affect the outcomes of patients with acute ischemic stroke receiving endovascular treatment (EVT). The aim of this systematic review and meta‐analysis was to evaluate the association between CSVD neuroimaging markers and outcomes in patients with acute ischemic stroke undergoing EVT. Methods We conducted a systematic search of PubMed and EMBASE databases up to July 2022 using keywords or Medical Subject Heading terms (“cerebral small‐vessel diseases,” “leukoaraiosis,” “microbleed,” “enlarged perivascular space,” “recent small subcortical infarct,” “atrophy,” “lacune,” and “thrombectomy”). The assessed clinical outcomes were a good functional outcome, 90‐day mortality, symptomatic intracranial hemorrhage, and early neurologic improvement after EVT. Results Overall, 30 studies on patients with acute ischemic stroke undergoing EVT were included. Patients with absent or mild white matter hyperintensities had higher good functional outcomes (odds ratio [OR], 2.94 [95% CI, 2.44–3.53]; P &lt;0.001) and lower mortality rate (OR, 0.42 [95% CI, 0.11–1.59]; P &lt;0.001), whereas the presence of cerebral microbleeds increased only the risk of 90‐day mortality (OR, 0.60 [95% CI, 0.44–0.83]; P =0.002). Moreover, patients with moderate/severe CSVD burden had worse functional outcomes than those with none/mild CSVD burden (OR, 2.94 [95% CI, 2.44–3.53]; P &lt;0.001), but neither mortality nor symptomatic intracranial hemorrhage was significantly different between the 2 groups. Conclusions The existence of CSVD affected the outcomes of patients with acute ischemic stroke receiving EVT. Future multicenter prospective cohort studies with little heterogeneity should be prioritized to confirm our results.

Correlation between enlarged perivascular space and brain white matter hyperintensities in patients with recent small subcortical infarct.

This study aimed to investigate the correlation between enlarged perivascular space (EPVS) and white matter hyperintensities (WMH) at different locations in patients with recent small subcortical infarct (RSSI). Data were collected from patients with RSSI who were hospitalized at Changzhou Second People's Hospital between October 2020 and December 2021. All patients underwent cranial magnetic resonance imaging, and the grades of EPVS and WMH were assessed, including basal ganglia EPVS (BG-EPVS), centrum semiovale EPVS (CSO-EPVS), deep WMH (DWMH), and periventricular WMH (PWMH). The volumes of EPVS and WMH at different locations were quantified using 3D Slicer software. Patients were grouped according to the severity of BG-EPVS and CSO-EPVS. Univariate and multivariate analyses were used to analyze the relationship between EPVS and WMH. A total of 215 patients with RSSI were included in the analysis. Patients with moderate-to-severe BG-EPVS had higher DWMH and PWMH severity than those with mild BG-EPVS, both in terms of volume and grade. There was no significant difference in WMH severity between patients with mild CSO-EPVS and those with moderate-to-severe CSO-EPVS. Multivariate analysis indicated that after adjustments were made for confounding factors, DWMH volume (β=0.311; 95% CI, 0.089-0.400; p=.002) and PWMH volume (β=0.296; 95% CI, 0.083-0.424; p=.004) were independently associated with BG-EPVS. Pearson correlation showed that PWMH volume (r=.589; p<.001) and DWMH volume (r=.596; p<.001) were positively related to BG-EPVS volume. DWMH and PWMH are closely related to BG-EPVS in patients with RSSI.

RELATIONSHIP OF ARTERIAL STIFFNESS AND BASELINE CEREBRAL SMALL VESSEL DISEASE SCORE, WITH THE OCCURRENCE OF NEW LESIONS AFTER 2 YEARS OF FOLLOW-UP, INDEPENDENTLY OF BP CONTROL

Objective: Hypertension is a prominent determinant of cerebral small vessel disease (cSVD). The aim of this study was to assess in subjects with a recent lacunar stroke, the factors associated with the occurrence of new lesions of cSVD after 2 years of follow-up. Design and method: Patients with a recent small subcortical infarct according to STRIVE criteria were consecutively included in this prospective study. Clinical BP was measured after 5 min of rest in a sitting position using a validated semiautomatic device (OMRON Digital Automatic Blood Pressure Monitor Model HEM-907XL, Kyoto, Japan). Three measurements of BP were averaged to determine values of clinical BP at baseline and at 3, 6, 12 and 24 months of follow-up. 24h-Ambulatory blood pressure monitoring (ABPM) was performed after hospital discharge within 30 days after stroke onset and after 2-years follow-up. The aortic pulse wave velocity (aPWV), the augmentation index (AIx) and 24h brachial and central BP (24h-ABPM) were measured by means of a Mobil-O-Graph PWV (IEM, Stolberg, Germany) device. The AIx was normalized for heart rate of 75 bpm (AIX75). Brain MRI was performed using a Phillips Achieva 1.5 T MRI at admission and at 2-years follow-up. Results: A total of 103 patients, aged 67.04 (10.9) years, 30.4% female, were included. Follow-up MRI was acquired in 92 patients. Backwards stepwise logistic regression analysis showed that 24h-PWV (OR 1.44 CI 95% 1.01-2,06 p = 0.044) and cSVD score (OR 2.3 CI 95% 1.41-3.77, p = 0.001) were associated with the presence of new lesions. Significance for 24h-PWV was lost after introducing age in de model, and only cSVD score remained significant (OR 2.33 CI95% 1.34-3.98, p = 0.002). The presence of new lesions was not significantly different between patients with or without BP control defined by BP &lt; 130/80 mm Hg during the 24h-ABPM. Conclusions: In subjects with a lacunar stroke, 24h-PWV and cSVD score were associated significantly with the presence of new lesions after 2 year of follow-up, independently of BP control

Plasma inflammatory biomarkers in cerebral small vessel disease: A review.

Cerebral small vessel disease (CSVD) is a group of pathological processes affecting small arteries, arterioles, capillaries, and small veins of the brain. It is one of the most common subtypes of cerebrovascular diseases, especially highly prevalent in elderly populations, and is associated with stroke occurrence and recurrence, cognitive impairment, gait disorders, psychological disturbance, and dysuria. Its diagnosis mainly depends on MRI, characterized by recent small subcortical infarcts, lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy. While the pathophysiological processes of CSVD are not fully understood at present, inflammation is noticed as playing an important role. Herein, we aimed to review the relationship between plasma inflammatory biomarkers and the MRI features of CSVD, to provide background for further research.

Diagnostic yield of diffusion-weighted brain MR imaging in patients with cognitive impairment: Large cohort study with 3,298 patients.

ObjectiveThere is a paucity of large cohort-based evidence regarding the need and added value of diffusion-weighted imaging (DWI) in patients attending outpatient clinic for cognitive impairment. We aimed to evaluate the diagnostic yield of DWI in patients attending outpatient clinic for cognitive impairment.Materials and methodsThis retrospective, observational, single-institution study included 3,298 consecutive patients (mean age ± SD, 71 years ± 10; 1,976 women) attending outpatient clinic for cognitive impairment with clinical dementia rating ≥ 0.5 who underwent brain MRI with DWI from January 2010 to February 2020. Diagnostic yield was defined as the proportion of patients in whom DWI supported the diagnosis that underlies cognitive impairment among all patients. Subgroup analyses were performed by age group and sex, and the Chi-square test was performed to compare the diagnostic yields between groups.ResultsThe overall diagnostic yield of DWI in patients with cognitive impairment was 3.2% (106/3,298; 95% CI, 2.6–3.9%). The diagnostic yield was 2.5% (83/3,298) for acute or subacute infarct, which included recent small subcortical infarct for which the diagnostic yield was 1.6% (54/3,298). The diagnostic yield was 0.33% (11/3,298) for Creutzfeldt-Jakob disease (CJD), 0.15% (5/3,298) for transient global amnesia (TGA), 0.12% (4/3,298) for encephalitis and 0.09% (3/3,298) for lymphoma. There was a trend towards a higher diagnostic yield in the older age group with age ≥ 70 years old (3.6% vs 2.6%, P = .12). There was an incremental increase in the diagnostic yield from the age group 60–69 years (2.6%; 20/773) to 90–99 years (8.0%; 2/25).ConclusionDespite its low overall diagnostic yield, DWI supported the diagnosis of acute or subacute infarct, CJD, TGA, encephalitis and lymphoma that underlie cognitive impairment, and there was a trend towards a higher diagnostic yield in the older age group.

Serum glial fibrillary acidic protein is sensitive to acute but not chronic tissue damage in cerebral small vessel disease

BackgroundSerum glial fibrillary acidic protein (sGFAP) has been proposed as a biomarker in various neurological diseases but has not yet been systematically investigated in patients with cerebral small vessel disease (CSVD). We explored whether sGFAP levels are increased in stroke patients with MRI-confirmed recent small subcortical infarcts (RSSI) and analyzed the subsequent course and determinants of sGFAP longitudinally.MethodsIn a prospectively-collected cohort of stroke patients with a single RSSI (n = 101, mean age: 61 years, 73% men), we analyzed brain MRI and sGFAP using a SIMOA assay at baseline and at 3- and 15-months post-stroke. Community-dwelling age- and sex-matched individuals (n = 51) served as controls.ResultsRSSI patients had higher baseline sGFAP levels compared to controls (median: 187.4 vs. 118.3 pg/ml, p < 0.001), with no influence of the time from stroke symptom onset to baseline blood sampling (median 5 days, range 1–13). At the 3- and 15-months follow-up, sGFAP returned to control levels. While baseline sGFAP correlated with larger infarct size (rs = 0.28, p = 0.01), neither baseline nor follow-up sGFAP levels were associated with chronic CSVD-related lesions (white matter hyperintensities, lacunes, microbleeds) after adjusting for age, sex and hypertension. Furthermore, sGFAP levels did not relate to the occurrence of new vascular brain lesions on follow-up MRI.ConclusionssGFAP is increased in patients with CSVD-related stroke and correlates with the size of the RSSI. However, sGFAP levels were not related to chronic neuroimaging features or progression of CSVD, suggesting that sGFAP is sensitive to acute but not chronic cerebrovascular tissue changes in this condition.

Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts

BackgroundAs currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes.MethodsIn a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS).ResultsIn a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21–6.84), multiple lacunes (aOR 3.5, CI 1.29–9.48) and higher total SVD burden (aOR 1.68, CI 1.11–2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up.ConclusionsPatients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation.

Advances in the Role of Endothelial Cells in Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) poses a serious socio-economic burden due to its high prevalence and severe impact on the quality of life of elderly patients. Pathological changes in CSVD mainly influence small cerebral arteries, microarteries, capillaries, and small veins, which are usually caused by multiple vascular risk factors. CSVD is often identified on brain magnetic resonance imaging (MRI) by recent small subcortical infarcts, white matter hyperintensities, lacune, cerebral microbleeds (CMBs), enlarged perivascular spaces (ePVSs), and brain atrophy. Endothelial cell (EC) dysfunction is earlier than clinical symptoms. Immune activation, inflammation, and oxidative stress may be potential mechanisms of EC injury. ECs of the blood–brain–barrier (BBB) are the most important part of the neurovascular unit (NVU) that ensures constant blood flow to the brain. Impaired cerebral vascular autoregulation and disrupted BBB cause cumulative brain damage. This review will focus on the role of EC injury in CSVD. Furthermore, several specific biomarkers will be discussed, which may be useful for us to assess the endothelial dysfunction and explore new therapeutic directions.

Increased level of FAM19A5 is associated with cerebral small vessel disease and leads to a better outcome.

ObjectiveFAM19A5 plays an essential role in the development and acute or chronic inflammation of the central nervous system. The present study aimed to explore the association between FAM19A5 and cerebral small vessel disease (cSVD).MethodsA total of 344 recent small subcortical infarct (RSSI) patients and 265 healthy controls were included in this study. The difference in the FAM19A5 level between the two groups was compared and the correlation between FAM19A5 and cerebral infarction volume was analyzed. Also, the association between FAM19A5 and the total magnetic resonance imaging (MRI) burden with its imaging characteristics was explored. Moreover, the correspondence of FAM19A5 with the outcome was assessed via Δ National Institutes of Health Stroke Scale score (NIHSS) and the percentage of NIHSS improvement.ResultsFAM19A5 was highly expressed in the RSSI group (P = 0.023), showing a positive correlation with cerebral infarction volume (P < 0.01). It was positively correlated with total MRI cSVD burden (P < 0.001) and reflected the severity of white matter hyperintensity (WMH) (P < 0.01) and enlarged perivascular space (EPVS) (P < 0.01), but did not show any association with cerebral microbleed (CMB) and lacune. Moreover, FAM19A5 suggested a larger Δ NIHSS (P = 0.021) and NIHSS improvement percentage (P = 0.007).ConclusionSerum FAM19A5 was increased in RSSI and positively correlated with the infarct volume. It also reflects the total MRI burden of cSVD, of which the imaging characteristics are positively correlated with WMH and EPVS. In addition, higher FAM19A5 levels reflect better outcomes in RSSI patients.

Hemorrhagic Focus Within the Recent Small Subcortical Infarcts on Long-Term Follow-Up Magnetic Resonance Imaging.

Hemorrhagic Focus Within the Recent Small Subcortical Infarcts on Long-Term Follow-Up Magnetic Resonance Imaging.