Lacunar Infarcts Research Articles

Perfusion Status in Lacunar Stroke: A Pathophysiological Issue

The pathophysiology of lacunar infarction is an evolving and debated field, where relevant information comes from histopathology, old anatomical studies and animal models. Only in the last years, have neuroimaging techniques allowed a sufficient resolution to directly or indirectly assess the dynamic evolution of small vessel occlusion and to formulate hypotheses about the tissue status and the mechanisms of damage. The core–penumbra concept was extensively explored in large vessel occlusions (LVOs) both from the experimental and clinical point of view. Then, the perfusion thresholds on one side and the neuroimaging techniques studying the perfusion of brain tissue were focused and optimized for LVOs. The presence of a perfusion deficit in the territory of a single small perforating artery was negated for years until the recent proposal of the existence of a perfusion defect in a subgroup of lacunar infarcts by using magnetic resonance imaging (MRI). This last finding opens pathophysiological hypotheses and triggers a neurovascular multidisciplinary reasoning about how to image this perfusion deficit in the acute phase in particular. The aim of this review is to summarize the pathophysiological issues and the application of the core–penumbra hypothesis to lacunar stroke.

Association of Baseline Metabolomic Profiles With Incident Stroke and Dementia and With Imaging Markers of Cerebral Small Vessel Disease.

Cerebral small vessel disease is a major cause of stroke and dementia. Metabolomics can help identify novel risk factors to better understand pathogenesis and predict disease progression and severity. We analyzed baseline metabolomic profiles from 118,021 UK Biobank participants. We examined cross-sectional associations of 325 metabolites with MRI markers of small vessel disease, evaluated longitudinal associations with incident stroke and dementia, and ascertained causal relationships using Mendelian randomization. In cross-sectional analyses, lower levels of apolipoproteins, free cholesterol, cholesteryl esters, fatty acids, lipoprotein particle concentrations, phospholipids, and triglycerides were associated with increased white matter microstructural damage on diffusion tensor MRI. In longitudinal analyses, lipoprotein subclasses of very large high-density lipoprotein cholesterol (HDL) were associated with an increased risk of stroke, and acetate and 3-hydroxybutyrate were associated with an increased risk of dementia. Mendelian randomization analyses identified strong evidence supporting causal relationships for many findings. A few metabolites had consistent associations across multiple analysis types. Increased total lipids in very large HDL and increased HDL particle size were associated with increased white matter damage (lower fractional anisotropy: OR: 1.44, 95% CI 1.07-1.95, and OR: 1.19, 95% CI 1.06-1.34, respectively; mean diffusivity: OR: 1.49, 95% CI 1.11-2.01, and OR: 1.24, 95% CI 1.11-1.40, respectively) and an increased risk of incident all stroke (HR: 4.04, 95% CI 2.13-7.64, and HR: 1.54, 95% CI 1.20-1.98, respectively) and ischemic stroke (HR: 3.12, 95% CI 1.53-6.38; HR: 1.37, 95% CI 1.04-1.81). Valine was associated with decreased mean diffusivity (OR: 0.51, 95% CI 0.30-0.88) and had a protective association with all-cause dementia (HR: 0.008, 95% CI 0.002-0.035). Increased levels of cholesterol in small HDL were associated with a decreased risk of incident all stroke (HR: 0.17, 95% CI 0.08-0.39) and ischemic stroke (HR: 0.19, 95% CI 0.08-0.46) and were supported by evidence of a causal association with MRI-confirmed lacunar stroke (OR: 0.96, 95% CI 0.93-0.99). In this large-scale metabolomics study, we found multiple metabolites associated with stroke, dementia, and MRI markers of small vessel disease. Further studies may help inform the development of personalized prediction models and provide insights into mechanistic pathways and future treatment approaches.

Automated detection of lacunar infarcts from MRI images

AbstractBackgroundWhen MRI images of patients with memory problems are assessed, the presence of lacunar infarcts is evaluated. Lacunar infarcts, fluid‐filled cavities of 3‐15 mm in diameter, are one possible result of cerebral small vessel disease and therefore relevant in dementia diagnostics. In this study, we propose an automated tool for detecting lacunar infarcts on MRI images.MethodWe adapted our previous approach [1] in three ways: 1) post‐processing steps were added to the convolutional neural network segmentation pipeline, e.g., to exclude enlarged perivascular spaces and segmentations located inside sulci or ventricles, 2) memory clinic data from the Amsterdam Dementia Cohort and PredictND cohort were included in addition to the LADIS cohort data, and 3) the ground truth was defined by three experienced neuroradiologists (A, B, C) instead of one rater. T1 and T2‐FLAIR images were available for all cases and T2 for a subset in visual rating. The dataset was composed of 393 subjects and each expert rated 1156 potential lacunar infarcts as “1 = no”, “2 = probably no”, “3 = probably yes” or “4 = yes”. A consensus (CO) was created by calculating the average and using a cutoff at 2.5. The agreement was measured between individual raters (A‐B, B‐C, A‐C), between automatic rating and individual raters (AU‐A, AU‐B, AU‐C), and between the automatic rating and the consensus rating (AU‐CO) using Kappa. Correlation coefficient for the number of lacunar infarcts per subject was defined. Cross‐validation was used in training the algorithm.ResultOut of 1156 candidate regions evaluated, 540 were considered as lacunar infarcts based on consensus. The individual raters agreed with each other in 74% of cases whether the shown lesion was lacunar infarct (kappa = 0.48). Correspondingly, automatic rating agreed with the individual raters in 74% of cases (kappa = 0.47). When automatic rating was compared with consensus, agreement/accuracy was 78% (kappa = 0.55). The correlation coefficient for the number of lacunar infarcts detected automatically from the whole image and visually (consensus) was 0.85 (Figure 1).ConclusionThis study suggests that the agreement in detecting lacunar infarcts automatically is comparable to inter‐rater variability between experienced neuroradiologists. [1] Jokinen et al. Stroke 2020 Nov 9; 50(1)

Physiological biomarkers of silent brain damage leading to cognitive impairment and Dementia – direct and accessible clinical evidence

AbstractBackgroundCognitive assessment is the best clinical tool to detect cognitive impairments, yet it is evident only at late stages of disease progression. In contrast, silent brain network changes occur at early stages of the disease and it is estimated that a large proportion of dementias may be prevented or at‐least delayed if detected during early pathophysiology stages. Neuroimaging studies have shown that silent brain network findings, including white matter hyperintensities, lacunar infarctions and temporal atrophy are evident before objective cognitive impairment is detected and even more in ‘at risk’ population with risk factors for dementia. We aimed to evaluate direct physiological biomarkers that provide accessible clinical evidence of silent brain network damage that precede clinical cognitive findings and provide early clinical biomarkers that can facilitate early interventions.MethodBrain network performance was evaluated in 168 subjects ‘at risk’ for developing dementia (Table 1). Direct electrophysiological imaging (“Delphi”) was used to measure magnetically induced brain network electrophysiological response. MRI scans included T1, T2, FLAIR, Diffusion Weighted Imaging (DWI) and (SWI). They were analysed according to Fazekas scale for white matter Hyperintensities (WMH), lacunar Infarctions and medial temporal lobe atrophy (MTA). Objective cognitive evaluations were performed by a neuropsychologist interview and a computerized cognitive battery (NeurotraxTM).ResultDirect electrophysiological imaging (“Delphi”) was able to distinguish between severities of different MRI detected silent brain network damage findings. Magnetically induced direct electrophysiological response wave form adherence (WFA) significantly decreased with increase in WMH (Fig.1A; p<0.0001) and increase in MTA levels (Fig.1B; p<0.0001). Furthermore, WFA significantly decreased in subjects with lacunar infarctions (Fig.1C; p<0.0001).ConclusionSilent brain network deficits preceding dementia and cognitive decline are widely under detected due to lack of accessible tools. Data presented in this study demonstrates “Delphi” technology’s ability to detect silent brain network damage findings and severity levels that are identified in MRI scans. “Delphi” is a clinically accessible, direct, and objective technology that can facilitate early detection, prevention, delayed progression and management of mild cognitive impairment and dementia.

Neuropathological correlates of neuropsychiatric symptoms in dementia

AbstractBackgroundNeuropsychiatric symptoms (NPS) are very common in Lewy body dementias (LBD), but their aetiology is poorly understood. In a post‐mortem study we aimed to characterise the contribution of neuropathological substrates to some of the most common NPS in dementia.MethodParticipants who passed away between 2004 and 2021 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies. Neuropathological data was collected for Lewy body neuropathology (LBD Braak score), neurofibrillary tangles (NFT Braak score), amyloid‐β burden (CERAD‐NP), TDP‐43, lacunar infarcts, cerebral amyloid angiopathy and hyaline atherosclerosis. Post‐mortem interviews were used to collect information regarding neuropsychiatric and cognitive status using the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR). A total of 948 cases were classified according to neuropathological assessment: (1) No pathology (NP) (n = 678); (2) Alzheimer’s Disease (AD) (n = 183); (3) LBD (n = 57); (4) AD+LBD (n = 30).ResultMultinomial logistic regression models comparing LBD, AD and AD+LBD to NP, adjusted for age, ethnicity, sex, and education level, showed significantly higher odds of hallucination and delusions across all groups compared to NP with the relative risk of hallucinations most elevated in AD+LBD cases (RRR = 19.3,[95%CI = 8.00‐46.3], p<0.001). All groups had increased risk of higher NPI scores relative to NP, but the greatest increase was for AD+LBD (RRR = 1.04, [95%CI = 1.02‐1.06], p<0.001). There were significantly greater risk of agitation and apathy in AD and AD+LBD groups relative to NP. (Table 1) Additionally, hallucinations were associated with higher Lewy body Braak scores (OR = 1.30, 95%CI = 1.13‐1.49, p<0.001). Higher NFT Braak scores were associated with depression (OR = 1.28, 95%CI = 1.09‐1.50, p<0.001), agitation (OR = 1.30, 95% CI = 1.07‐1.57, p = 0.009) and overall NPI score (IRR = 1.15, 95%CI = 1.05‐1.27, p = 0.004). Lacunar infarcts were associated with delusions (OR = 4.68, 95%CI = 1.12‐19.5, p = 0.03). More frequent neuritic plaques was inversely associated with apathy (OR = 0.70, 95%CI = 0.52‐0.93, p = 0.01). Cerebral amyloid angiopathy, hyaline atherosclerosis, and TDP‐43 did not associate with any of the neuropsychiatric symptoms in the multivariable logistic models. (Table 2)ConclusionLewy body pathology was the most significant contributor to the aetiology of hallucinations, while NFT were important contributors to depression and agitation in dementia. Supporting the dual importance of these pathologies, subjects with AD and LBD co‐pathology showed the greatest burden of NPS.

Retinopathies and cognitive dysfonction of patients with lacunar strokes

Retinopathies and cognitive dysfonction of patients with lacunar strokes

Post-traumatic ischaemic stroke in a teenager after head trauma: A case report

Lacunar strokes in the pediatric population are very uncommon, as well as trauma-induced strokes. It is extremely rare for a head trauma induced ischaemic stroke to occur in children and young adults.We describe a case of a 13-year-old boy who reported acute ischaemic lesions, and in particular a right basal ganglia ischaemic stroke after falling from a height of 10 m, presumably secondary to the stretching-induced occlusion of the recurrent artery of Heubner, with a favorable outcome.Ischaemic strokes can rarely be subsequent to head trauma in young adults, in relationship with the degree of maturity of the perforating vessels. Although very rare, it is important to avoid the lack of recognition of this condition, thus awareness is necessary.

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 < 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

Clinico-topographic evaluation of anterior versus posterior acute ischemic stroke and correlation with early mortality-based scale prediction

Posterior circulation ischaemic strokes (PCIs) are a clinical syndrome associated with ischemia related to stenosis, in situ thrombosis, or embolic occlusion of the posterior circulation and differ from anterior circulation ischaemic strokes (ACIs) in many aspects. In this study, ACIs and PCIs were evaluated in terms of clinico-radiological and demographic aspects, and the relevance of objective scales to early disability and mortality was investigated. The definition of ACIS or PCIS was classified according to the Oxfordshire Community Stroke Project (OCSP). There are mainly two groups divided into ACIs and PCIs. ACIs were included as total anterior circulation syndrome (TACS), partial anterior circulation syndrome (PACS) (right and left), and lacunar syndrome (LACS) (right and left), and PCIs were posterior circulation syndrome (POCS) (right and left). Arrival NIH Stroke Scale/Score (NIHSS) and Glasgow Coma Scale (GCS) scores were evaluated in clinical assessment and modified SOAR Score for Stroke (mSOAR) was for early mortality-based scale prediction. All data were compared, and mean, IQR (if applicable) values and ROC curve analysis were determined. A total of 100 AIS patients, 50 of whom were ACIs and 50 were PCIs, were included in the study and were evaluated within the first 24h. Hypertension was the most common disease for both groups. The second most common was hyperlipidemia (82%) in the ACIs and diabetes mellitus (40%) in the PCIs. The frequency of right hemisphere ischemia was higher in ACIs (63.6%) and PCIs (48%). The mean NIHSS and GCS score (also median IQR) was higher in the right ACIs and the highest NIHSS mean was in the right partial anterior circulation syndrome (PACS) (respectively median (IQR): 9.5 (13) and median (IQR):14.5 (3)). The mean NIHSS and GCS score of bilateral posterior circulation syndrome (POCS) were the highest in PCIs (median (IQR):3 (17), (IQR):15 (4) respectively). The mSOAR mean was the highest in the right PACS in ACIs (median (IQR):2.5 (2)) and in bilateral POCs among PCIs (median(IQR):2(2)). The association of PCIs with hyperlipidemia and the male gender was interpreted, and anterior infarcts were found to cause higher early clinical disability scores. The NIHSS scale was effective and reliable, especially in anterior acute strokes, but also emphasized the necessity of using the GCS assessment together in the first 24h in the assessment of PCIs. mSOAR scale is a helpful predictor in estimating early mortality not only in ACIs but also in PCIs, similar to GCS.

Amide proton transfer-weighted MRI features of acute ischemic stroke subtypes.

Stroke is a highly heterogeneous disorder with distinct subtypes, and the stroke subtype influences the outcome. Amide proton transfer-weighted (APTW) MRI has been demonstrated to be promising in stroke patients, but the image characteristics of stroke subtypes have not been sufficiently investigated. The purpose of this study was to investigate the APTW MRI features of different subtypes of acute ischemic stroke (AIS). Ninety-two AIS patients presenting within 96 h of symptom onset were enrolled and examined with a 3.0-T MRI system. Patients were grouped into four subtypes: lacunar circulation infarcts (LACI, n = 33); total anterior circulation infarcts (TACI, n = 9); partial anterior circulation infarcts (PACI, n = 28); and posterior circulation infarcts (POCI, n = 22). APTW values in the lesion (APTWlesion ) and the contralateral normal-appearing region (APTWcontral ) were measured. The change in APTW values between the acute ischemic lesion and the contralateral normal-appearing region (APTWles-con ) was calculated. A two-sample t-test, one-way ANOVA, and the Chi-square method were used. There were significant differences between APTWlesion and APTWcontral in the three categories of nonlacunar strokes (TACI, PACI, and POCI, all p < 0.01), but not for lacunar strokes (LACI, p = 0.080). TACI patients had the lowest APTWlesion and APTWles-con in all groups (p < 0.05). In the POCI group, patients with supratentorial infarcts showed significant differences between APTWlesion and APTWcontral (p = 0.001), while the differences were not significant for infratentorial infarcts (p = 0.135). Our results suggest that the APT effect was heterogeneous in different stroke subtypes, and that APTW MRI gave an excellent performence in depicting nonlacunar AIS in supratentorial locations.

Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease

Cerebral small vessel disease (cSVD) is a common cause of stroke (lacunar stroke), is the most common cause of vascular cognitive impairment, and impairs mobility and mood but has no specific treatment. To test the feasibility, drug tolerability, safety, and effects of 1-year isosorbide mononitrate (ISMN) and cilostazol treatment on vascular, functional, and cognitive outcomes in patients with lacunar stroke. The Lacunar Intervention Trial-2 (LACI-2) was an investigator-initiated, open-label, blinded end-point, randomized clinical trial with a 2 × 2 factorial design. The trial aimed to recruit 400 participants from 26 UK hospital stroke centers between February 5, 2018, and May 31, 2021, with 12-month follow-up. Included participants had clinical lacunar ischemic stroke, were independent, were aged older than 30 years, had compatible brain imaging findings, had capacity to consent, and had no contraindications to (or indications for) the study drugs. Data analysis was performed on August 12, 2022. All patients received guideline stroke prevention treatment and were randomized to ISMN (40-60 mg/d), cilostazol (200 mg/d), ISMN-cilostazol (40-60 and 200 mg/d, respectively), or no study drug. The primary outcome was recruitment feasibility, including retention at 12 months. Secondary outcomes were safety (death), efficacy (composite of vascular events, dependence, cognition, and death), drug adherence, tolerability, recurrent stroke, dependence, cognitive impairment, quality of life (QOL), and hemorrhage. Of the 400 participants planned for this trial, 363 (90.8%) were recruited. Their median age was 64 (IQR, 56.0-72.0) years; 251 (69.1%) were men. The median time between stroke and randomization was 79 (IQR, 27.0-244.0) days. A total of 358 patients (98.6%) were retained in the study at 12 months, with 257 of 272 (94.5%) taking 50% or more of the allocated drug. Compared with those participants not receiving that particular drug, neither ISMN (adjusted hazard ratio [aHR], 0.80 [95% CI, 0.59 to 1.09]; P = .16) nor cilostazol (aHR, 0.77 [95% CI, 0.57 to 1.05]; P = .10) alone reduced the composite outcome in 297 patients. Isosorbide mononitrate reduced recurrent stroke in 353 patients (adjusted odds ratio [aOR], 0.23 [95% CI, 0.07 to 0.74]; P = .01) and cognitive impairment in 308 patients (aOR, 0.55 [95% CI, 0.36 to 0.86]; P = .008). Cilostazol reduced dependence in 320 patients (aHR, 0.31 [95% CI, 0.14 to 0.72]; P = .006). Combination ISMN-cilostazol reduced the composite (aHR, 0.58 [95% CI, 0.36 to 0.92]; P = .02), dependence (aOR, 0.14 [95% CI, 0.03 to 0.59]; P = .008), and any cognitive impairment (aOR, 0.44 [95% CI, 0.23 to 0.85]; P = .02) and improved QOL (adjusted mean difference, 0.10 [95% CI, 0.03 to 0.17]; P = .005) in 153 patients. There were no safety concerns. These results show that the LACI-2 trial was feasible and ISMN and cilostazol were well tolerated and safe. These agents may reduce recurrent stroke, dependence, and cognitive impairment after lacunar stroke, and they could prevent other adverse outcomes in cSVD. Therefore, both agents should be tested in large phase 3 trials. ClinicalTrials.gov Identifier: NCT03451591.

A prospective reappraisal of motor outcome prediction in patients with acute stroke by using atlas-based diffusion tensor imaging biomarkers

ABSTRACT Background Diffusion tensor imaging (DTI) biomarkers can be used to quantify microstructural changes in the cerebral white matter (WM) following injury. Objectives This prospective single-center study aimed to evaluate whether atlas-based DTI-derived metrics obtained within 1 week after stroke can predict the motor outcome at 3 months. Methods Forty patients with small acute stroke (2–7 days after onset) involving the corticospinal tract were included. Each patient underwent magnetic resonance imaging (MRI) within 1 week and at 3 months after stroke, and the changes based on DTI-derived metrics were compared by performing WM tract atlas-based quantitative analysis. Results A total of 40 patients were included, with median age 63.5 years and a majority of males (72.5%). Patients were classified into good-prognosis group (mRS 0–2, n = 27) and poor-prognosis group (mRS 3–5, n = 13) by outcome. The median (25th-75th percentile) of MD (0.7 (0.6–0.7) vs. 0.7 (0.7–0.8); p = 0.049) and AD (0.6 (0.5, 0.7) vs. 0.7 (0.6, 0.8); p = 0.023) ratios within 1 week were significantly lower in the poor-prognosis group compared to the good-prognosis group. The ROC curve of the combined DTI-derived metrics model showed comparable Youden index (65.5% vs. 58.4%–65.4%) and higher specificity (96.3% vs. 69.2%–88.5%) compared to clinical indexes. The area under the ROC curve of the combined DTI-derived metrics model is comparable to those of the clinical indexes (all p > 0.1) and higher than those of the individual DTI-derived metrics parameters. Conclusions Atlas-based DTI-derived metrics at acute stage provide objective information for prognosis prediction of patients with ischemic or lacunar stroke.

Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis.

Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method. Our research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis. In the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027-1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105-1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust. Our study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS.

Reduced Left Atrial Rotational Flow Is Independently Associated With Embolic Brain Infarcts

BackgroundUp to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms. ObjectivesThis study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF. MethodsThe authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts. ResultsPatients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05). ConclusionsReduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.

The value of vestibular graviceptive pathway evaluation in the diagnosis of unilateral peripheral vestibular dysfunction.

Evaluation of vestibular graviceptive pathway (VGP) in patients with unilateral peripheral vestibular dysfunction (UPVD) has received increasing attention from researchers. The study aimed to investigate the value of VGP evaluation in the diagnosis of UPVD. Ninety-five UPVD patients were divided into attack and remission phase groups. VGP evaluation-related indicators, including subjective visual vertical (SVV), subjective visual horizontal (SVH), head tilt, ocular torsion (OT), and skew deviation (SD), were measured, and their correlations with cochleovestibular function test results were analyzed. The possible etiologies of contralesional VGP (c-VGP) were analyzed. Positive rates of SVV, SVH, OT, and SD were significantly higher, and the degrees of SVV, SVH, and OT were significantly greater in the attack phase group than the remission phase group. The sides with abnormal VGP evaluation results were correlated with the sides with hearing loss, abnormal caloric, and video head impulse test (vHIT) results. A total of 14 patients showed c-VGP, and possible etiologies included contralateral benign paroxysmal positional vertigo (n=4), bilateral hearing loss (n=8), bilateral vHIT gain reduction (n=1), autoimmune diseases (n=6), vascular risk factors (n=6), lacunar infarction (n=3), and endolymphatic hydrops (n=3). Alterations in SVV, SVH, OT, and SD were noted in UPVD patients in different phases, which are presumed to be related to dynamic vestibular compensation; correlations between VGP evaluation results and cochleovestibular function test results indicate that VGP evaluation may be helpful for the diagnosis of the side affected in UPVD; the presence of c-VGP may be related to bilateral labyrinth lesions or endolymphatic hydrops on the affected side; and the involvement of autoimmune mechanisms also deserves attention.

Leukocyte Telomere Length and Lacunar Stroke: A Mendelian Randomization Study

Leukocyte Telomere Length and Lacunar Stroke: A Mendelian Randomization Study

Acute Brain Infarction in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Korean Single-Center Study.

This study investigated the clinical and radiological features of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with acute brain infarction, using a cohort of Korean patients with AAV. This study included 263 patients with AAV. Acute brain infarction was defined as infarction that occurred within 7 days or less. The brain territories affected by acute brain infarction were investigated. Active AAV was arbitrarily defined as the highest tertile of Birmingham Vasculitis Activity Score (BVAS). The median age at diagnosis was 59.0 years, and 35.4% were male. Fourteen cases of acute brain infarction occurred in 12 patients (4.6%), which was calculated as 1332.2 per 100,000 patient-years and 10 times higher than the incidence rate in the Korean general population. Patients with AAV with acute brain infarction exhibited significantly older age, increased BVAS at diagnosis, and a more frequent history of prior brain infarction compared with those without. The brain territories affected in AAV patients were middle cerebral artery (50.0%), multiple territories (35.7%), and posterior cerebral artery (14.3%). Lacunar infarction and microhemorrhage were observed in 42.9% and 71.4% of cases, respectively. Prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction (hazard ratios, 7.037 and 1.089). Patients with AAV with prior brain infarction or BVAS for active AAV exhibited significantly lower cumulative acute brain infarction-free survival rates than those without. Acute brain infarction was observed in 4.6% of AAV patients, and both prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction.

Neuroimaging in Cerebral Small Vessel Disease

Objective: To determine the role of neuroimaging in cerebral small vessel disease’s diagnosis and treatment. Study Design: Cross-sectional study. Place and Duration of Study: Department of Neurology, Khairpur Medical College, Khairpur Mir’s from 1st January 2022 to 30th September 2022. Methodology: Seventy five patients were enrolled. The patients were divided in to 5 groups depending on a 5 year interval in their age. The cases of CSVD were included suffering from transient ischemic attack (TIA), lacunar syndromes, stoke with subacute symptoms as cognitive as well as motor disturbances. The age of the patients was &gt;45 years. Clinical examination was conducted through standard procedure and each patient underwent brain magnetic resonance index (MRI) imaging. The neuroimaging features including white matter hyperintensities (WMH), lacunar infarcts (LI), enlarged perivascular spaces (EPVS), microbleeds, lacunae, brain atrophy, and subcortical infarcts. Binswanger’s disease, as well as leukoaraiosis, lacunar strokes and cerebral microbleeds (CMBs) were also observed. The MRI used 3.0 MRI system, using 32-channel head coils.The regions scoring was done through Kippss or Dacies score, as well as through MTA-scale, Koedam score, and GCA-scale, ranging within 0-3 points Results: There are more cases of females suffering from CSVD than males, however only in year 70 there was an equal incidence within gender. There was a significance association of CSVD markers with age wherein the WMH has a significant increase in trend with the ascending of year interval. Fazekas scale was applied quantify amount of the white matter T2-hyperintense-lesions which are accredited to CSVD. It was observed that presence of SVD markers in various age stratification showed highest incidence of MTA scale, Koedam score, Kippss/Dacies score and 3 markers numbers The WMH, CMBs, LI and EPVS were observed highest in the age group of 61-65 years while BA was observed highest in 66-70 years of age Conclusion: Neuroimaging techniques prove beneficial in exact and timely diagnosis of cerebral small vessel disease. Increasing age has higher risk of CSVD presented through increase incidence in CSVD markers. Keywords: White matter, Cognitive, Recurrence, Mortality, Etiology

Evaluation of Endothelial Progenitor Cell Characteristics as Clinical Biomarkers for Elderly Patients with Ischaemic Stroke.

Ageing impairs endothelial function and predisposes the person to ischaemic stroke (IS). Endothelial progenitor cells (EPCs) repair endothelial damage and induce post-ischaemic neovascularisation. Given the prevalence of IS in older population, this study explored whether changes in EPC number and function may reliably predict the type or outcome of stroke in patients ≥ 65years of age. For this, blood samples were collected once from healthy volunteers (HVs, n = 40) and four times (admission and days 7, 30 and 90 post-stroke) from participants with lacunar (n = 38) or cortical (n = 43) stroke. EPCs were counted with flow cytometry and defined as non-haematopoietic cells (CD45-) expressing markers for stemness (CD34 +), immaturity (CD133 +) and endothelial maturity (KDR +). Clonogenesis, tubulogenesis, migration and proliferation assays were performed as measures of EPC functionality. Biochemical profile of plasma inflammatory and angiogenic agents were studied using specific ELISAs. Primary outcome was disability or dependence on day 90 post-stroke, assessed by the modified Rankin Scale (mRS). Compared to HVs, EPC numbers were higher in stroke patients at all time points studied, reaching significance at baseline and day 30. No differences in EPC counts and functionality were observed between lacunar and cortical stroke groups at any time. Plasma endostatin, PDGF-BB, TNF-α and VEGF levels were higher in stroke patients vs HVs. Patient outcome, evaluated by mRS on day 90 post-stroke, did not correlate with EPC count or functionality. Baseline EPC counts may serve as a diagnostic marker for stroke but fail to distinguish between different stroke subtypes and predict post-stroke outcome.

Depression in patients with cerebral microangiopathy

Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, – are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and postCOVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.