Blood urea nitrogen to albumin ratio is associated with cerebral small vessel diseases.

Blood urea nitrogen (BUN) to albumin ratio (BAR) is a comprehensive parameter that reflects renal, inflammatory, nutritional, and endothelial functions. BAR has been shown to be associated with various cancers, pneumonia, sepsis, and pulmonary and cardiovascular diseases; however, few studies have been conducted on its association with cerebrovascular diseases. In this study, we evaluated the association between BAR and cerebral small vessel disease (cSVD) in health check-up participants. We assessed consecutive health check-up participants between January 2006 and December 2013. For the cSVD subtype, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of lacune and cerebral microbleeds (CMBs). The BAR was calculated by dividing BUN by albumin as follows: BAR = BUN (mg/dl)/albumin (g/dl). A total of 3012 participants were evaluated. In multivariable linear regression analysis, BAR showed a statistically significant association with WMH volume after adjusting for confounders [ß = 0.076, 95% confidence interval (CI): 0.027-0.125]. In multivariable logistic regression analyses, BAR was significantly associated with lacunes [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.00-1.44] and CMBs (aOR = 1.28, 95% CI: 1.06-1.55). BAR was associated with all types of cSVD in the health check-up participants.

White matter hyperintensities combined with serum NLRP3 in diagnosis of cognitive impairment in patients with cerebral small vessel disease.

Background: White matter hyperintensities (WMH) are widely used for the diagnosis of cerebral small vessel disease (CSVD). However, whether NLRP3 is correlated with cognitive impairment after CSVD is still not clear.Objective: This study aimed to investigate the diagnostic value of WMHs combined with NLRP3 for cognitive impairment after CSVD.Methods: This prospective observational study enrolled a total of 188 CSVD patients from September 2019 to May 2022. All patients received brain MRI assessment and WMH Fazekas score, as well as WMH volume, was recorded. Serum NLRP3 level was measured by ELISA. Patients' cognitive function was measured by MoCA after 6 months of diagnosis of CSVD. The serum levels of C reactive protein (CRP), interleukin (IL)-6, total cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL) and low-density leptin cholesterol (LDL) were recordedResults: CSVD patients with cognitive impairment had significantly higher Fazekas scores, WMH volumes, serum NLRP3 and IL-6 levels compared to patients without cognitive impairment. A positive correlation was found among Fazekas scores, WMH volumes and NLRP3 levels. The combination of WMH volume and NLRP3 could achieve a better specificity for the diagnosis of cognitive impairment. Coronary syndrome history, WMH volume and NLRP3 were found as independent risk factors for cognitive impairment after CSVD.Conclusion: Fazekas scores, WMH volume and serum NLRP3 levels are associated with cognitive impairment after CSVD and have the potential to be used as diagnostic biomarkers.

[When to look for rare causes of cerebral small vessel disease?] / Quand rechercher des causes rares de maladie des petits vaisseaux cérébraux ?

The majority of small vessel diseases is related to vascular risk factors or sporadic amyloid angiopathy, but a minority is caused by genetic, immune, or infectious diseases. In this article, we propose a pragmatic approach for the diagnosis and treatment of rare causes of cerebral small vessel disease.

La majorité des maladies des petits vaisseaux est liée à des facteurs de risque vasculaire ou à l'angiopathie amyloïde sporadique, mais une minorité est causée par des maladies génétiques, immunologiques ou infectieuses. Dans cet article, nous proposons une approche diagnostique et une prise en charge pragmatiques des maladies rares des petits vaisseaux cérébraux.

[Cerebral small vessel disease]. / Microangiopathie cérébrale.

Cerebral microangiopathy is the second leading cause of dementia after Alzheimer's disease and is a co-factor in the majority of dementias. Its clinical manifestations are multiple and include in addition to cognitive and neuropsychiatric manifestations, also problems of gait, urinary continence, and lacunar-ischaemic and haemorrhagic strokes. Patients with similar radiologic images can present very variable clinical pictures, partially resulting from damage to the neurovascular unit, not visible on conventional MRI, and affecting different neural networks. Management and prevention are possible and effective with well-known, readily available and affordable treatments, through aggressive management of cerebrovascular risk factors.

La microangiopathie cérébrale est la deuxième cause de démence après la maladie d'Alzheimer et est un cofacteur dans la majorité des démences. Ses manifestations cliniques sont multiples et incluent, en plus des troubles cognitifs, des troubles de la marche, de la continence urinaire, neuropsychiatriques, et des AVC lacunaires-ischémiques et hémorragiques. Des patients avec des images radiologiques similaires peuvent présenter des tableaux cliniques très variables, en partie découlant d'atteintes de l'unité neurovasculaire, non visibles en IRM conventionnelle, et altérant des réseaux neuronaux différents. Une prise en charge et une prévention sont possibles et efficaces avec des traitements bien connus, disponibles à un prix abordable, par un traitement agressif des facteurs de risque cérébrovasculaire.

[Neuroimaging of cerebral small vessel disease in mild cognitive impairment in older adults.]

Cerebral small vessel disease (CSVD) - is a clinical and radiological phenomenon characteristic of older adults. Currently, the extent of white matter lesions (WML) in patients with moderate cognitive disorders remains uncertain. Also, the relationship of cognitive impairment with the volume of WML has not been sufficiently studied. The aim of the study was to analyze the WML volumes in patients with subcortical vascular mild cognitive impairment (svMCI) and in the control group according to magnetic resonance imaging (MRI). The study included 50 people: 25 patients with svMCI (average age 75,88±4,04 years) and 25 conditionally healthy volunteers (average age 69,96±3,07 years). Significant differences in the volume of WML between the study groups were obtained. The fraction of hypointense WML was 0,74±0,41 in patients with svMCI and 0,15±0,07 in the control group. In the correlation analysis in the svMCI group, only the function of mental control showed a negative relationship with the fraction of WML. The data obtained suggest that the assessment of the volume of WML is important in patients with svMCI, but does not fully explain the decline in cognitive functions.

Electrical Activity During Slow-Wave Sleep and the Relationship With Enlarged Perivascular Spaces in Arteriosclerotic Cerebral Small Vessel Disease.

PURPOSE: We sought to analyze EEG spectral power during slow-wave sleep among patients with arteriosclerotic cerebral small vessel disease (CSVD) compared with community-dwelling individuals. We also sought to determine the relationship between EEG activity and the severity of enlarged perivascular spaces (EPVSs). METHODS: Consecutive subjects with arteriosclerotic CSVD ( n = 36) and community-dwelling individuals ( n = 26) between 50 and 80 years of age were included. Nocturnal polysomnography was performed, and EEG spectral analysis was conducted during slow-wave sleep using the F4/M1 and C4/M1 channel. Regionalized EPVSs in the basal ganglia and centrum semiovale were assessed on a validated 4-point visual rating scale (0 = none, 1 = 1-10, 2 = 11-20, 3 = 21-40, and 4 = >40) using MRI. RESULTS: CSVD group showed lower delta:beta ratios in the frontal ( P = 0.017) and central ( P = 0.038) regions after adjusting for age, sex, mini-mental state examination score, and arousal index. The significance still remained in the frontal region when including age, sex, mini-mental state examination, and apnea-hypopnea index as covariates ( P = 0.037). Among patients with arteriosclerotic CSVD, decreased delta power ( P = 0.031) and theta power ( P = 0.034) in the frontal region were associated with a higher degree of EPVSs in the centrum semiovale rather than in the basal ganglia. Delta power in the central region showed an extremely weak association with EPVSs in the centrum semiovale ( P = 0.047). CONCLUSIONS: Among patients with arteriosclerotic CSVD, the intrusion of high-frequency EEG activity into slow-wave sleep was identified, and slow-wave activity during slow-wave sleep might be negatively associated with the severity of EPVSs in the centrum semiovale. Further studies are required to corroborate the conclusions.

Neuropsychological Profile of Early Cognitive Impairment in Cerebral Small Vessel Disease.

INTRODUCTION: The neuropsychological feature of vascular mild cognitive impairment is a deficit of the frontal-subcortical circuit; however, the features in the early stage are not consistent. In the present study, we aimed to investigate the neuropsychological features of the very early stage of cognitive impairment with cerebral small vessel disease (CSVD) and to elucidate the cognitive differences among CSVD subtypes. METHODS: A comprehensive neuropsychological test battery was applied to nondemented subjects scoring below the cutoff point 26 of the Japanese version of the Montreal Cognitive Assessment. After factor analysis was conducted to identify covert cognitive factors in the battery, correlation analyses were performed between the factors and CSVD subtypes: white matter hyperintensity (WMH), lacunar infarcts (LIs), cerebral microbleeds (CMBs), perivascular spaces, and cortical atrophy. RESULTS: Among the 465 recruited patients, 139 underwent a full neuropsychological test battery. Through factor analysis, the following three factors were extracted: executive function, memory, and attention. Of the CSVD features, total WMH was correlated with executive function and memory, whereas deep WMH was correlated with memory alone. Of the CSVD subtypes, LIs and CMBs were correlated only with executive function. Frontal and posterior atrophy were correlated with memory and attention, whereas medial temporal atrophy was correlated with memory alone. CONCLUSIONS: Executive dysfunction accompanied by subtle impairment of memory and processing speed was the main feature of neuropsychological profiles in the subjects with CSVD, even in the very early stage. Furthermore, each CSVD feature and focal cerebral atrophy are associated with cognitive impairment.

Diagnostic Value of Hcy Combined with Blood Pressure Variability Index in the Severity of Hypertension Complicated with CSVD and Its Correlation with Cognitive Function and CysC Expression.

This paper explores the diagnostic value of Hcy combined with the blood pressure variability index in the severity of hypertension complicated with CSVD and its correlation with cognitive function and CysC expression. 200 patients with ischemic small cerebral vessels are selected as the research object. According to the MRI findings, they are divided into 48 cases of white matter lesions (WML), 44 cases of lacunar infarction (LI), 44 cases of enlarged perivascular spaces (EPVs), and 46 cases in the mixed group (referring to two or more types of ischemic cerebrovascular disease on imaging). Different cognitive domains of different types of ischemic cerebrovascular diseases are analyzed. The risk factors of cognitive decline in patients with ischemic cerebrovascular disease are analyzed by univariate analysis and multivariate logistic regression analysis. There is an ancestral correlation between serum Hcy and CSVD, which is an independent risk factor for CSVD.

[The cerebral microangiopathy]. / Tserebral'naya mikroangiopatiya.

The review article highlights the main points of the development of cerebral microangiopathy - «small vessel diseases¼. Cerebral microangiopathy or small vessel disease. Cerebral microangiopathy is one of the leading causes of the development of acute and/or chronic cerebral circulatory disorders and cognitive disorders up to severe dementia. The article analyzes the relationship of pathoanatomic, neuroimaging and clinical manifestations of the course of cerebral microangiopathy.

Intelligent Algorithm-Based Quantitative Electroencephalography in Evaluating Cerebral Small Vessel Disease Complicated by Cognitive Impairment.

To analyze the application value of artificial intelligence model based on Visual Geometry Group- (VGG-) 16 combined with quantitative electroencephalography (QEEG) in cerebral small vessel disease (CSVD) with cognitive impairment, 72 patients with CSVD complicated by cognitive impairment were selected as the research subjects. As per Diagnostic and Statistical Manual (5th Edition), they were divided into the vascular dementia (VD) group of 34 cases and vascular cognitive impairment with no dementia (VCIND) group of 38 cases. The two groups were analyzed for the clinical information, neuropsychological test results, and monitoring results of QEEG based on intelligent algorithms for more than 2 hours. The accuracy rate of VGG was 84.27% and Kappa value was 0.7, while that of modified VGG (nVGG) was 88.76% and Kappa value was 0.78. The improved VGG algorithm obviously had higher accuracy. The test results found that the QEEG identified 8 normal, 19 mild, 10 moderate, and 0 severe cases in the VCIND group, while in the VD group, the corresponding numbers were 4, 13, 11, and 7; in the VCIND group, 7 cases had the normal QEEG, 11 cases had background changes, 9 cases had abnormal waves, and 11 cases had in both background changes and abnormal waves, and in the VD group, the corresponding numbers were 5, 2, 5, and 22, respectively; in the VCIND group, QEEG of 18 patients had no abnormal waves, QEEG of 11 patients had a few abnormal waves, and QEEG of 9 patients had many abnormal waves, and QEEG of 0 people had a large number of abnormal waves, and in the VD group, the corresponding numbers were 7, 6, 12, and 9. The above data were statistically different between the two groups (P < 0.05). Hence, QEEG based on intelligent algorithms can make a good assessment of CSVD with cognitive impairment, which had good clinical application value.

[Current state of cerebral microangiopathy in hypertension]. / Sovremennoe sostoyanie problemy tserebral'noi mikroangiopatii pri arterial'noi gipertenzii.

Hypertension is the main cause and the most important risk factor for both acute cerebrovascular accident and chronic progressive cerebrovascular insufficiency that is accompanied by severe neurological and mental disorders even to the extent of developing dementia. They are based on hypertension-induced pathology of the intracerebral arteries and cerebral microvasculature - cerebral microangiopathy that leads to small deep (lacunar) infarcts (SDIs) and diffuse cerebral white matter diseases. This review highlights the morphology, pathogenesis, clinical and neuroimaging diagnosis of hypertensive SDIs, and their differential diagnosis with atherosclerotic SDIs in the historical aspect. It is emphasized that the lacunar state of the brain in hypertension is a predictor of massive cerebral hemorrhages. Special attention is paid to current studies of the morphology and pathogenesis of diffuse changes in white matter and to the role of blood-brain barrier impermeability in the development of progressive leukoencephalopathy.

Clinicoradiographic and genetic features of cerebral small vessel disease indicate variability in mode of inheritance for monoallelic HTRA1 variants.

BACKGROUND: Biallelic pathogenic variants in HTRA1 cause CARASIL. More recently, monoallelic variants have been associated with the autosomal dominant disorder CADASIL2 but not all carriers develop disease manifestations. We describe the clinicoradiologic and mutation spectrum of four new CADASIL2 individuals. METHODS: Medical records at Mayo Clinic between 2013 and 2020 were retrospectively reviewed to identify patients with cerebral small vessel disease related to monoallelic HTRA1 variants. RESULTS: Four patients met the study inclusion criteria for cerebral small vessel disease related to HTRA1 monoallelic variants. The mean age at onset of first clinical stroke was 51.25 years (range 41-64 years). The mean disease duration was 6.5 years (range 4-12). All individuals had recurrent strokes within the duration of follow-up with a mean number of strokes per patient being 5.5 (range 2-12). Three individuals had leukoencephalopathy with brain stem involvement. Microhemorrhages were seen on brain MRI in three patients. HTRA1 monoallelic variants identified in our cohort were missense variants in three patients and a novel frameshift variation in one patient. Interestingly, two of these missense variants were previously reported in an autosomal recessive pattern of inheritance and here are associated with a dominant effect. CONCLUSIONS: Clinicoradiologic characteristics of heterozygous HTRA1-related CSVD may overlap with sporadic CSVD. Heterozygous HTRA1 variants can contribute to dominant or recessive disease mechanisms.

Hereditary Cerebral Small Vessel Diseases and Stroke: A Guide for Diagnosis and Management.

Cerebral small vessel diseases represent a frequent cause of stroke and cognitive or motor disability in adults. A small proportion of cerebral small vessel diseases is attributable to monogenic conditions. Since the characterization in the late 1990s of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, several other monogenic conditions leading to adult-onset ischemic or hemorrhagic stroke have been described. In this practical guide, we summarize the key features that should elicit the differential diagnosis of a hereditary cerebral small vessel diseases in adult stroke patients, describe the main clinical and imaging characteristics of the major hereditary cerebral small vessel diseases that can manifest as stroke, and provide general recommendations for the clinical management of affected patients and their relatives.

Two Unique Mutations in HTRA1-Related Cerebral Small Vessel Disease in North America and Africa and Literature Review.

OBJECTIVE: To describe and compare two cases of North American and African patients who were diagnosed with HTRA1-related cerebral small vessel disease (CSVD) with homozygous and heterozygous mutations, respectively, in the linker domain of the HTRA1 gene. MATERIALS AND METHODS: Case reports and literature review. RESULTS: A 49-year-old man from Mexico presented with recurrent lacunar strokes and memory loss. A 46-year-old woman from Eritrea presented with progressive memory loss. Neither patient had alopecia. MRI of the brain and spine in both patients showed leukoencephalopathy, microbleeds and spondylosis. Microbleeds along the subpial surfaces of the brainstem were only seen in the Mexican man. Genetic sequencing of HTRA1 gene revealed a novel homozygous mutation of p.A173S in the Mexican man supporting cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). A heterozygous mutation of p.V175M was detected in the African woman, which has not been reported in patients of African ethnicity. In reviewing literature, CARASIL patients with mutation in the linker domain are older at neurological symptom onset and more frequently presented with stroke compared to patients with non-linker domain mutations. In patients of HTRA1-CSVD from heterozygous mutations, male is more common. CONCLUSIONS: HTRA1-related CSVD may be seen in patients of non-Asian ethnicity without alopecia. These case reports extend the clinical and radiographic spectrum of HTRA1-related CSVD.

Diabetes Mellitus and Cognition: Pathway Analysis in the MEMENTO Cohort.

OBJECTIVE: To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. METHODS: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report. We used structural equation modeling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aß42/Aß40 ratio, and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (5 neuropsychological tests), adjusting for potential confounders. RESULTS: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089, -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. CONCLUSION: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.

Cerebral Microvascular Erdheim-Chester Disease: A Perivascular Hematopoietic Vasculopathy.

Erdheim-Chester disease (ECD) is a rare and elusive hematopoietic malignancy that may involve the nervous system in various ways. Cerebrovascular ECD involves the perivascular infiltration and compromise of any cervicocranial vessel by transformed proliferating histiocytes. Presented is the novel case of a patient with pathologically proven perivascular microangiopathy, manifesting in multifaceted fashion with ischemia, hemorrhage, mass lesions, and edema.

Recurrent Ischemic Stroke - A Systematic Review and Meta-Analysis.

OBJECTIVES: Recurrent stroke remains a challenge though secondary prevention is initiated immediately post-stroke. Stroke subtype may determine the risk of recurrent stroke and require specific preventive measures. We aimed to identify subtype-specific stroke recurrence and associated risk factors over time. METHODS AND MATERIALS: A systematic review was performed using PubMed and Embase for studies including adults >18 years, first-ever ischemic stroke in population-based observational studies or registries, documented TOAST-criteria and minimum 1-year follow-up. Meta-analysis on stroke recurrence rate was performed. Final search: November 2019. RESULTS: The search retrieved 26 studies (between 1997 and 2019). Stroke recurrence rate ranged from 5.7% to 51.3%. Recurrent stroke was most frequent in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke with recurrent stroke similar to index stroke subtype. We identified a lower recurrence rate for small vessel occlusion (SVO) stroke with recurrence frequently of another stroke subtype. Based on a meta-analysis the summary proportion recurrence rate of recurrent stroke in studies using TOAST-criteria = 0.12 and = 0.14 in studies using TOAST-like criteria. Hypertension, diabetes mellitus, atrial fibrillation previous transient ischemic attack, and high stroke severity were independent risk factors for recurrence. CONCLUSION: Stroke recurrence rates seem unchanged over time despite the use of secondary prevention. The highest recurrence rate is in LAA and CE stroke eliciting same subtype recurrent stroke. A lower recurrence rate is seen with SVO stroke with a more diverse recurrence pattern. Extensive workup is important in all stroke subtypes - including SVO stroke. Future research needs to identify better preventive treatment and improve compliance to risk factor prevention to reduce stroke recurrence.

Advances in Understanding the Pathogenesis of Lacunar Stroke: From Pathology and Pathophysiology to Neuroimaging.

Lacunar stroke (LS) accounts for about one-quarter of all acute ischemic strokes, represents an important marker of cerebral small vessel disease (CSVD), and has prognostic significance in terms of recurrent vascular events and vascular cognitive impairment. Our understanding of the etiology and pathogenesis of LS is largely based on the meticulous postmortem work of C. Miller Fisher in the late 1960s, with scarce subsequent pathological analysis of the "lacunar hypothesis" and no reliable approaches for direct in vivo imaging of the small intracranial vessels. The recent development of high-resolution MRI, which allows both large-vessel wall and perforating arteries to be imaged in one setting, provides the opportunity to advance understandings of the clinical mechanisms, imaging characteristics, and pathogenesis of LS. Given accumulating evidence of endothelial dysfunction and blood-brain-barrier disruption as early features of CSVD-related LS, advanced imaging may allow various underlying pathogenetic mechanisms to be defined and for better targeting of therapeutic approaches in LS. In this review, progress in understanding the pathogenesis of LS is outlined, covering pathology, pathophysiology, and imaging characteristics, with a focus toward future directions in the complex entity of LS.