Recent Infarction Research Articles

Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct.

After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI. We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression. Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment. 'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.

Association Between Systemic Inflammatory Response Index and Cerebral Small Vessel Disease.

This study aimed to explore the relationship between the Systemic Inflammatory Response Index (SIRI) and Cerebral Small Vessel Disease (CSVD), focusing on its key imaging markers. We enrolled 344 patients admitted to the neurology department between January 2022 and September 2024, comprising 223 patients diagnosed with CSVD and 121 without CSVD. Baseline characteristics were compared between groups, and multivariate logistic regression was performed to assess the impact of SIRI on CSVD risk. Further, univariate and multivariate logistic regression analyses were conducted to examine the relationship between SIRI and CSVD imaging markers, including White Matter Hyperintensity (WMH), lacunes, Perivascular Space (PVS), and Recent Small Subcortical Infarct (RSSI). Significant differences were observed between the CSVD and non-CSVD groups in terms of age, sex, history of hypertension, diabetes, white blood cell count, neutrophil count, lymphocyte count, homocysteine levels, and SIRI values. Multivariate analysis confirmed that elevated SIRI is independently associated with an increased risk of CSVD. Additionally, higher SIRI values were linked with more severe CSVD imaging features, including moderate-to-severe WMH, the presence of lacunes, and RSSI. These findings demonstrate that elevated SIRI is independently associated with both the occurrence of CSVD and the severity of key imaging markers such as WMH, lacunes, and RSSI. This suggests that SIRI could serve as a useful inflammatory marker for assessing CSVD risk and progression.

Pathogenic spectrum of infective endocarditis and analysis of prognostic risk factors following surgical treatment in a tertiary hospital in China

BackgroundThis study aimed to summarize the pathogenic spectrum of infective endocarditis (IE) and analyze the risk factors for poor prognosis in surgical patients in a tertiary hospital in China.MethodsWe retrospectively included patients diagnosed with IE between January 2013 and January 2022. The pathogenic spectrum was summarized; the risk factors for early postoperative mortality and embolic events were analyzed using multivariate logistic regression.ResultsAmong 630 patients who underwent blood cultures, the positivity rate was 56.83%. The most prevalent pathogens were viridans streptococci, Staphylococcus aureus, enterococci, and coagulase-negative staphylococci (CoNS). The prevalence of viridans streptococci significantly increased in the surgically treated group, compared to the medically treated group (50.80% vs. 27.78%, P < 0.001), while that of CoNS decreased (5.60% vs. 12.04%, P = 0.034). There has been a declining trend in the blood culture positivity in recent years compared to earlier years (2018–2022 vs. 2013–2017 = 60.95% vs. 47.30%, P = 0.037), with an increasing trend in viridans streptococci and a decreasing trend in CoNS. Multivariate logistic regression analysis identified male gender, coronary artery disease, platelet count < 100 × 109/L, albumin < 35 g/L, elevated creatinine, and prosthetic valve as independent risk factors for early postoperative mortality. Risk factors for embolic events included recent cerebral infarction within 3 months, history of peripheral vasculopathy, and hemoglobin (Hb) < 90 g/L.ConclusionsViridans streptococci predominates as the most common IE pathogen, with its incidence rising recently, especially among surgical patients. Blood culture positivity is decreasing. Understanding risk factors for early postoperative mortality and embolic events is crucial for optimizing patient management and prognosis.Clinical trial numberNot applicable.

Factors associated with the distribution of brain metastases in lung cancer: a retrospective study.

The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.

Cervical cancer with patent foramen ovale metastasis to the left ventricle: a case report

BackgroundMetastasis of malignant tumors to the cardiac endocardium is rare and mainly involves the right side of the heart. It is extremely rare to involve the left cardiac endocardium, especially when there is neither pulmonary metastasis nor primary lung cancer, which we call “isolated” left cardiac endocardium metastasis in this paper. Few such cases previously reported in the literature were not screened for patent foramen ovale (PFO).Case presentationThis article reports a case of a young woman with a history of surgery for cervical cancer, who was transferred to our hospital with a suspected diagnosis of PFO after recent recurrent multiple cerebral infarctions. On admission, transthoracic echocardiography revealed multiple stringy vegetations in the left ventricle, which were subsequently removed surgically, with intraoperative confirmation of a patent foramen ovale and closure of it simultaneously. According to her medical history and pathological results, she was diagnosed with left ventricular metastasis of cervical cancer, a rare case of isolated left heart endocardium metastasis without previous pulmonary metastasis, presumably through the patent foramen ovale.ConclusionPFO may play an important role in the process of isolated left heart endocardium metastasis in patients with distant malignancies and paradoxical embolism. Screening for PFO in high-risk patients may have significant clinical significance.

Prevalence and Clinical Implications of Hemosiderin Deposits in Recent Small Subcortical Infarcts.

A quarter of ischemic strokes are of lacunar clinical subtype and have an underlying recent small subcortical infarct (RSSI), but their long-term outcomes remain poorly characterized. Hemosiderin deposits (HDs) have been noted in RSSIs at chronic stages and might mimic primary hemorrhage. We characterized HDs' morphology, frequency, and clinical relevance. Participants with RSSIs were identified from a prospective longitudinal study and evaluated on 3T MRI including susceptibility-weighted imaging (SWI) from stroke diagnosis to 12 months. We categorized HDs in RSSIs on SWI at all available time points into 4 types (spots, smudge, rim, cluster) and assessed their associations with demographic factors, stroke-related factors, and image markers with adjusted logistic regression. HDs were observed in 43 (55.0%) of 108 participants within 3 months and 83 (76.9%) of 108 within 12 months after stroke onset. The mean time to first detection of HDs was 87 (interquartile range 53-164) days. A "rim" pattern (similar to late appearance of primary hemorrhage) occurred in at least 26.5% of RSSIs at all follow-up time points, mainly those located in the lentiform/internal capsule (50.0%) or thalamus (36.4%). Infarct volume (odds ratio [OR] 1.003, 95% CI 1.001-1.006; p = 0.004) and the total small vessel disease (SVD) score at baseline (OR 2.50, 95% CI 1.28-4.86, p = 0.007) independently predicted HDs at 12 months. HDs were positively associated with more lacunes (OR 1.60, 95% CI 1.13-2.26, p < 0.01), but not the Fazekas score, number of microbleeds, basal ganglia mineral deposit score, or clinical outcomes. HDs occur commonly in RSSIs and may be associated with infarct volume and SVD score. Hemosiderin "rim" is common in RSSIs, urging caution to avoid mistaking ischemic RSSI for primary hemorrhage in subacute and chronic stages.

Deep medullary veins integrity and relationships with small vessel disease and interstitial diffusivity measures in patients with a recent small subcortical infarct.

The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary veins integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct. We gathered demographic, clinical, and 3 Tesla-MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluate the venular integrity using two visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary-small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score. In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter and DTI-along the perivascular spaces, were associated with one or both venular scores. In multivariate analysis (OR, 95% CI), free water (1.33, 1.03-1.73), mean diffusivity (4.56, 1.32-15.81), fractional anisotropy (0.77, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (2.39, 1.06-5.39;0.78, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (0.48, 0.25-0.94), fractional anisotropy with and without free water correction (0.82,0.86-0.99; 0.83, 0.7-0.99, respectively) remained significant for vein count. In patients with a recent small subcortical infarct, disruption of the deep medullary veins, increased extracellular water, and white matter injury appear to be associated. SVD=small vessel disease; DMV=deep medullary veins; WMH=white matter hyperintensities; PVS=perivascular spaces; DTI-ALPS=diffusion tensor image analysis along the perivascular spaces; FW=free water; MD=mean diffusivity; FA= fractional anisotropy; BG=basal ganglia.

Clinical Relevance of Different Loads of Perivascular Spaces According to Their Localization in Patients with a Recent Small Subcortical Infarct.

Background and Purpose: Perivascular spaces (PVS) are usually enlarged in small vessel disease (SVD). However, the significance of PVS patterns in different locations is uncertain. Hence, we analyzed the distribution of PVS in patients with a recent small subcortical infarct (RSSI) and their correlation with clinical and imaging factors. Materials and Methods: In a cohort of 71 patients with an RSSI with complete clinical data, including the Pittsburgh Sleep Quality Index (PSQI), we segmented PVS in white matter (WM-PVS), basal ganglia (BG-PVS), and brainstems (BS-PVS) on 3T-MRI T2-weighted sequences, obtaining fractional volumes (%), and calculated the WM/BG-PVS ratio. We analyzed the Pearson's correlation coefficients between PVS regional loads. We used normalized PVS measures to assess the associations with clinical and MRI-SVD features (white matter hyperintensities (WMHs), number of lacunes, and microbleeds) in univariable and multivariable linear regressions adjusted for age, sex, and hypertension. Results: In our cohort (mean age 70 years; 27% female), the Pearson's correlation coefficients between WM-PVS/BG-PVS, WM-PVS/BS-PVS, and BG-PVS/BS-PVS were 0.67, 0.61, and 0.59 (all p < 0.001). In the adjusted models, BG-PVS were associated with lacunes (p = 0.034), WMHs (p = 0.006), and microbleeds (p = 0.017); WM-PVS with lacunes (p = 0.003); while BS-PVS showed no associations. The WM/BG-PVS ratio was associated with lacunes (p = 0.018) and the PSQI (p = 0.046). Conclusions: PVS burdens in different regions are highly correlated in patients with RSSI but with different SVD patterns. Sleep quality impairment might affect waste removal mechanisms differently in the WM and BG regions.

Predictors and Outcomes of Periprocedural Intracranial Hemorrhage after Stenting for Symptomatic Intracranial Atherosclerotic Stenosis.

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis. We retrospectively analyzed patients with symptomatic intracranial atherosclerotic stenosis stent placement in a prospective cohort at a high-volume stroke center. Clinical, radiologic, and periprocedural characteristics and long-term outcomes were reviewed. Periprocedural intracranial hemorrhage was classified as procedure-related hemorrhage (PRH) and non-procedure-related hemorrhage (NPRH). The long-term outcomes were compared between patients with PRH and NPRH, and the predictors of NPRH were explored. Among 1849 patients, 24 (1.3%) had periprocedural intracranial hemorrhage, including PRH (4) and NPRH (20). The postprocedural 30-day mRS was 0-2 in 9 (37.5%) cases, 3-5 in 5 (20.8%) cases, and 6 in 10 (41.7%) cases. For the 14 survivors, the long-term (median of 78 months) mRS were 0-2 in 10 (76.9%) cases and 3-5 in 3 (23.1%) cases. The proportion of poor long-term outcomes (mRS ≥3) in patients with NPRH was significantly higher than those with PRH (68.4% versus 0%, P = .024). Anterior circulation (P = .002), high preprocedural stenosis rate (P < .001), and cerebral infarction within 30 days (P = .006) were independent predictors of NPRH after stent placement. Patients with NPRH had worse outcomes than those with PRH after stent placement for symptomatic ICAS. Anterior circulation, severe preprocedural stenosis, and recent infarction are independent predictors of NPRH.

12391 When Pressure Drops, Consequences Rise: A Case Of Pituitary Apoplexy And Watershed Infarcts

Abstract Disclosure: D. Moreno Watashi: None. H.R. Alkaissi: None. M.B. Sharma: None. Introduction: Pituitary apoplexy (PA) results from sudden hemorrhaging and infarction of the pituitary gland, typically within a pituitary adenoma. The primary symptom is a sudden, severe headache, often followed by acute endocrine dysfunction, ophthalmoplegia and visual or neurological disturbances. Case Description: A 68-year-old male with a past medical history of hypertension presented to the emergency department with acute chest and upper back pain, beginning one day prior. No history of smoking, alcohol intake or drug use. Blood pressure (BP) on arrival was 180/95 mmHg. Initial labs revealed mild electrolyte abnormalities. Troponins were normal, but ECG showed diffuse T wave inversion and ST depression. CT angiography revealed a type B aortic dissection. He was managed in the critical care unit with continuous esmolol intravenous (IV) infusion and planned for endovascular repair. During his stay, he became disoriented and hypotensive. MRI from the brain incidentally discovered a pituitary macroadenoma measuring 2.9x2.2x3cm and recent infarcts, with a distribution concerning for hypoperfusion. Fundoscopy concerning for optic chiasm compression. Labs indicated secondary hypothyroidism and hypogonadism (TSH 0.3 uUI/ml, free T4 0.88 ng/dL, total testosterone 56.3 ng/dL). Neurosurgical intervention was deferred until after aortic repair. Endovascular aortic repair was performed with episodes of hypotension. Post-procedure, the patient developed fever (39.5°C) and worsening mental status. Head CT revealed an increased suprasellar extension of the pituitary macroadenoma and vasogenic edema, consistent with hemorrhage of the lesion. He was started on stress doses of hydrocortisone, levothyroxine 125mcg and managed conservatively due to a high surgical risk. Discussion: PA's extrinsic risk factors include angiographic procedures, endocrinological dynamic tests, anticoagulation therapy, exogenous estrogen administration, orthopedic and cardiac surgeries (due to BP fluctuations). The intrinsic risk factors are non-functioning adenomas, macroadenomas and suprasellar extension. Treatment is focused on immediate correction of endocrine derangements and relieving local compression. Stress dosage of corticosteroids should be administered IV as soon as the diagnosis is confirmed to prevent life-threatening corticotropic deficiency. Neurosurgical decompression via a transsphenoidal approach is the definitive therapy to relieve local compression with severe visual loss, obtundation or rapidly progressive course. The potential outcomes are based on the extent of hemorrhage, necrosis, and edema. PA should be treated as a medical emergency in the setting of hemodynamic changes from acute corticotropic deficiency and irreversible neurological damage from acute intracranial compression. The risk factors for PA should be known to assist in early diagnosis. Presentation: 6/1/2024

Thrombectomy for Stroke With Large Infarct on Noncontrast CT

Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset. To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset. Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023. The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone. The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage. The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages. Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study. ClinicalTrials.gov Identifier: NCT03805308.

Serum fibrinogen/albumin ratio and early neurological deterioration in patients with recent small subcortical infarction

Background Serum fibrinogen/albumin ratio (FAR) is a new inflammatory marker related to a variety of diseases, and it has been shown to be associated with stroke. This study is to investigate the relationship between serum FAR and early neurological deterioration (END) in patients with recent small subcortical infarction (RSSI). Patients and methods Consecutive RSSI patients admitted to the First Affiliated Hospital of Zhengzhou University from June 2015 to June 2022 were enrolled. The National Institute of Health Stroke Scale (NIHSS) was utilized to evaluate the severity of the patients at admission and within seven days post-admission. END was defined as an increase of ≥2 points in NIHSS score from admission or ≥1 point in the motor item of the score within seven days post-admission. Multivariate logistic regression analysis was employed to identify risk factors for END. The correlation between FAR and END was investigated using restricted cubic spline (RCS) analysis. Subgroup analysis was used to assess stability across different populations. Results A total of 766 RSSI patients were included in the analysis, with 538 males (70.24%). END occurred in 115 (15.01%) patients. Multivariate logistic regression analysis revealed that FAR (OR = 1.016, 95%CI: 1.005–1.028), PAD (OR = 1.805, 95%CI: 1.161–2.807) and age (OR = 1.028, 95%CI: 1.009–1.048) were associated with END in RSSI patients. RCS analysis indicated a linear correlation between FAR and END (p for nonlinear = .128). Subgroup analysis indicated association between FAR and END in male (OR = 1.02, 95%CI: 1.00–1.03), patients aged ≤65 years (OR = 1.02, 95%CI: 1.00–1.03) and patients without smoking history (OR = 1.02, 95%CI: 1.00–1.03). Conclusions Elevated FAR levels were associated with the occurrence of END within seven days after admission in RSSI patients, especially in men, age ≤65 years, or patients without smoking history.

GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Causal relationship of inflammatory cytokines and serum metabolites in cerebral small vessel disease: a two-step Mendelian randomization study.

The aim was to investigate the causal relationships of inflammatory cytokines and serum metabolites in cerebral small vessel disease (CSVD). Bidirectional Mendelian randomization was first conducted to screen inflammatory cytokines and serum metabolites that were associated with imaging features of CSVD, including white matter hyperintensities, recent small subcortical infarcts, cortical cerebral microinfarcts, cerebral microbleeds, lacunes and enlarged perivascular spaces. Sensitivity analyses were performed to evaluate the robustness and pleiotropy of these results. Subsequently, inflammatory cytokines and serum metabolites that were associated with CSVD were subjected to functional enrichment. Finally, mediation analysis was employed to investigate whether inflammatory cytokines or serum metabolites acted as an intermediary for the other in their causal relationship with CSVD. Of the inflammatory cytokines, five were risk factors (e.g., tumour-necrosis-factor-related apoptosis-inducing ligand) and five (e.g., fibroblast growth factor 19) were protective factors for CSVD. Eleven serum metabolites that increased CSVD risk and 13 metabolites that decreased CSVD risk were also identified. The majority of these markers of CSVD susceptibility were lipid metabolites. Natural killer cell receptor sub-type 2B4 was determined to act as a mediating factor of an unidentified metabolite for the enlargement of perivascular spaces. Several inflammatory cytokines and serum metabolites had causal relationships with imaging features of CSVD. A natural killer cell receptor mediated in part the promotional effect of a metabolite on perivascular space enlargement.

Retinal sub-layer thicknesses, presence of lacunes, and their interaction with cognitive performance in recent single subcortical infarction.

Retinal sub-layer thicknesses, presence of lacunes, and their interaction with cognitive performance in recent single subcortical infarction.

Application of artificial intelligence-based magnetic resonance imaging in diagnosis of cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is an important cause of stroke, cognitive impairment, and other diseases, and its early quantitative evaluation can significantly improve patient prognosis. Magnetic resonance imaging (MRI) is an important method to evaluate the occurrence, development, and severity of CSVD. However, the diagnostic process lacks quantitative evaluation criteria and is limited by experience, which may easily lead to missed diagnoses and misdiagnoses. With the development of artificial intelligence technology based on deep learning, the extraction of high-dimensional features in imaging can assist doctors in clinical decision-making, and it has been widely used in brain function and mental disorders, and cardiovascular and cerebrovascular diseases. This paper summarizes the global research results in recent years and briefly describes the application of deep learning in evaluating CSVD signs in MRI imaging, including recent small subcortical infarcts, lacunes of presumed vascular origin, vascular white matter hyperintensity, enlarged perivascular spaces, cerebral microbleeds, brain atrophy, cortical superficial siderosis, and cortical cerebral microinfarct.

Association between blood-brain barrier permeability and changes in pulse wave velocity following a recent small subcortical infarct.

Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r [95% CI], WB 0.651 [0.363-0.839]; GM 0.657 [0.373-0.845], WM 0.530[0.197-0.777]) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b[95% CI], WB 0.725[0.384-1.127], GM 0.629 [0.316-1.369], WM 0.865 [0.455-0.892]) or Δ24-h DBP (b[95% CI], WM 0.707 [0.370-1.103], GM 0.643 [0.352-1.371], WM 0.772 [0.367-0.834]). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

Recurrent cerebrovascular events after recent small subcortical infarction

BackgroundRecent 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.Patients and methodsThis 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.ResultsWe analysed 332 consecutive patients (mean age 68 years, 36% women; median follow-up time 12 years). 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).ConclusionPatients 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.

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.