Brain MRI in Monogenic Cerebral Small Vessel Diseases: A Practical Handbook

2021 ◽  
Vol 21 ◽  
Author(s):  
Leonardo Ulivi ◽  
Mirco Cosottini ◽  
Gianmichele Migaleddu ◽  
Giovanni Orlandi ◽  
Nicola Giannini ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Next Generation ◽  
Vessel Disease ◽  
Generation Sequencing ◽  
Cerebral Small Vessel Diseases

: Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described and new sequencing techniques such as Next generation sequencing are available. Brain imaging is a key exam in these diseases. First, since it is often the first exam performed, an MRI is key in selecting patients for genetic testing and for interpreting Next generation sequencing reports. In addition, neuroimaging can be helpful in describing the underlying pathological mechanisms involved in cerebral small vessel disease. With this review, we aim to provide Neurologists and Stroke physicians with an up-to date overview of the current neuroimaging knowledge on monogenic small vessel diseases.

NEXT GENERATION SEQUENCING IN FAMILIAL CEREBRAL SMALL VESSEL DISEASE - AN ONGOING STUDY

2015 ◽  
Vol 86 (11) ◽  
pp. e4.106-e4
Author(s):  
Rhea Tan ◽  
Hugh Markus
Keyword(s):  
Next Generation Sequencing ◽  
Diagnostic Tests ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Next Generation ◽  
Single Test ◽  
Vessel Disease ◽  
Phenotypic Information ◽  
Generation Sequencing

Cerebral small vessel disease (SVD) is the most common form of stroke and vascular dementia. CADASIL (notch3 mutations) is most frequent but other monogenic causes more recently identified include CARASIL (HTRA1 gene), RVCL (TREX1 gene) and COL4A1 and 2. Diagnostic tests for these are often inaccessible and expensive and there are families with clinical monogenic SVD in whom no known variants are detected.Next generation sequencing offers the potential to screen for these diseases, which present with similar phenotypes, more cost-effectively and rapidly in a single test. It could also identify novel genes underlying SVD. As part of the NHS GEL and NIHR BRIDGE projects, whole genome sequencing is being applied to SVD. Individuals with younger onset SVD and a family history, with negative notch3 screening, are being recruited from centres throughout England.Data (blood sample and phenotypic information) can be collected by phone and blood sent through the post, or participants seen at a research clinic in one of the seven recruitment sites. Testing is provided free of charge. Any SVD causative mutations are fed back to the patient via the referring clinician. We are interested in receiving potential recruits who can be referred to Rhea Tan [email protected].

scholarly journals Cerebral Small Vessel Disease

2020 ◽  
Vol 21 (24) ◽  
pp. 9729
Author(s):  
Jakub Litak ◽  
Marek Mazurek ◽  
Bartłomiej Kulesza ◽  
Paweł Szmygin ◽  
Joanna Litak ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Current Knowledge ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Vessels ◽  
Small Vessel ◽  
Epithelial Layer ◽  
Small Arteries ◽  
Vessel Disease ◽  
The Impact ◽  
Cerebral Small Vessel Diseases

Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger’s disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes. This paper presents the characteristics of CSVD and the impact of the current knowledge of this topic on the diagnosis and treatment of patients.

scholarly journals Pathomechanisms of HIV-Associated Cerebral Small Vessel Disease: A Comprehensive Clinical and Neuroimaging Protocol and Analysis Pipeline

2020 ◽  
Vol 11 ◽  
Author(s):  
Kyle D. Murray ◽  
Meera V. Singh ◽  
Yuchuan Zhuang ◽  
Md Nasir Uddin ◽  
Xing Qiu ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Neurovascular Unit ◽  
Flow Cytometric Analysis ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Imaging Biomarkers ◽  
Vessel Disease ◽  
Inflammatory Monocytes

Rationale: We provide an in-depth description of a comprehensive clinical, immunological, and neuroimaging study that includes a full image processing pipeline. This approach, although implemented in HIV infected individuals, can be used in the general population to assess cerebrovascular health.Aims: In this longitudinal study, we seek to determine the effects of neuroinflammation due to HIV-1 infection on the pathomechanisms of cerebral small vessel disease (CSVD). The study focuses on the interaction of activated platelets, pro-inflammatory monocytes and endothelial cells and their impact on the neurovascular unit. The effects on the neurovascular unit are evaluated by a novel combination of imaging biomarkers.Sample Size: We will enroll 110 HIV-infected individuals on stable combination anti-retroviral therapy for at least three months and an equal number of age-matched controls. We anticipate a drop-out rate of 20%.Methods and Design: Subjects are followed for three years and evaluated by flow cytometric analysis of whole blood (to measure platelet activation, platelet monocyte complexes, and markers of monocyte activation), neuropsychological testing, and brain MRI at the baseline, 18- and 36-month time points. MRI imaging follows the recommended clinical small vessel imaging standards and adds several advanced sequences to obtain quantitative assessments of brain tissues including white matter microstructure, tissue susceptibility, and blood perfusion.Discussion: The study provides further understanding of the underlying mechanisms of CSVD in chronic inflammatory disorders such as HIV infection. The longitudinal study design and comprehensive approach allows the investigation of quantitative changes in imaging metrics and their impact on cognitive performance.

scholarly journals Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽  
2017 ◽  
Vol 89 (20) ◽  
pp. 2108-2114 ◽  
Author(s):  
Thomas Gattringer ◽  
Daniela Pinter ◽  
Christian Enzinger ◽  
Thomas Seifert-Held ◽  
Markus Kneihsl ◽  
...  
Keyword(s):  
Single Molecule ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease

Objective:To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.Methods:In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.Results:Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up.Conclusions:Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

scholarly journals Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic

2021 ◽  
Vol 13 ◽  
Author(s):  
Yangyi Fan ◽  
Ming Shen ◽  
Yang Huo ◽  
Xuguang Gao ◽  
Chun Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cognitive Status ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Memory Clinic ◽  
Vessel Disease ◽  
Mri Features ◽  
The Impact

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P &lt; 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA &lt; 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA &lt; 26.Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.

scholarly journals Periodic Limb Movements Syndrome in Patients With Cerebral Small Vessel Disease: Protocol for a Prospective Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina Spektor ◽  
Ingo Fietze ◽  
Mikhail G. Poluektov
Keyword(s):  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Periodic Limb Movements ◽  
Apnea Hypopnea Index ◽  
Limb Movements ◽  
Vessel Disease

Background: Cerebrovascular diseases are the leading cause of cognitive decline and dementia. Therefore, the investigation of the potential ways to slow down the disease progression is an important research field. Periodic limb movements in sleep (PLMS) are known to be associated with transient changes in heart rate and blood pressure. These changes might influence the course of cerebral small vessel disease (cSVD). Nevertheless, the clinical significance of PLMS, particularly its influence on cardiovascular diseases course, is still controversial and underinvestigated.Methods/design: Patients from 60 to 75 years old diagnosed with cSVD will undergo nocturnal polysomnography. Subjects with apnea/hypopnea index under 5 will be enrolled. Sleep quality and daytime functioning will be assessed at baseline with self-reported questionnaires. Brain MRI and cognitive assessment will be performed at baseline and in the 2-year follow-up. Progression of cSVD markers and cognitive dysfunction will be compared between patients with PLMS index (PLMI) equal to or more than 15 movements per hour of sleep and controls (PLMI &lt;15/h).Discussion: The negative role of PLMS in cSVD progression and related cognitive decline is expected. We suppose that patients with PLMS tend to worsen in cognitive performance more rapidly than age-, gender-, and comorbidity-matched controls. We also expect them to have more rapid white matter hyperintensities and other cSVD marker progression. The limitations of the study protocol are the short follow-up period, the absence of a treatment group, and inability to make a conclusion about causality.

Abstract 40: Time Course of Cerebral Small Vessel Disease Lesions and Sensory Motor Changes in Spontaneously Hypertensive Stroke Prone Rats

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Eder Caceres ◽  
Cameron Rink ◽  
Jay L Zweier ◽  
Yousef Hannawi
Keyword(s):  
Time Course ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Male Rats ◽  
Small Vessel ◽  
Therapeutic Drug ◽  
Time Points ◽  
Vessel Disease ◽  
Average Group

Introduction: Animal models of human cerebral small vessel disease (CSVD) are important for the study of the disease underlying mechanisms and testing therapeutic interventions. Spontaneusly Hypertensive Rats - Stroke Prone (SHRSP) are used as an animal model of human CSVD. However, there is a lack of data regarding the time course of cognitive and motor impairment. Methods: Male age-matched SHRSP and Wistar Kyoto rats (WKY) were studied. Sensorimotor testing (open field test) and tail-cuff systolic blood pressure (SBP) measurements (Visitech Systems, Inc.) were performed weekly starting from 6 until 24 weeks of age. Brain MRI at 7 and 24 weeks was acquired using a 9.4T MRI system. Brain histology was completed at the same time points. Statistical analysis was performed using a linear mixed model with repeated measurements. P< 0.05 was considered significant. Results: 20 SHRSP and 20 WKY male rats were studied. 10 per group were euthanized following brain MRI at 7 weeks and the rest were followed until 24 weeks. SHRSP weighed on average 30 grams less than WKY throughout the study (P=0.0003). At 7 weeks SBP was not different (WKY 106.6±5.4 vs SHRSP 120.8±5.4, P=0.06). SHRSP started to develop hypertension at 9-12 weeks and maintained hypertension until 24 weeks (average group difference across time P<0.0001; SBP at 21 weeks WKY 134.8±5.4 vs SHRSP 168.9±5.4, P<0.0001). Sensorimotor testing showed higher total distance travelled (TDT) at 7 weeks in SHRSP that trended down with ageing. Both groups became similar at 21 weeks (TDT: at 7 weeks WKY 3.78±1.3 vs SHRSP 7.8±1.3, P =0.037; at 21 weeks: WKY 4±1.3 vs SHRSP 4.4±1.3, P=0.83; average group difference across time P=0.014). Brain MRI was normal at 7 weeks, but small white matter hyperintensities were seen at 24 weeks. Brain Histology showed normal histology on hematoxylin & eosin staining at 7 weeks in both groups, while at 24 weeks SHRSP showed CSVD histopathological changes including microbleed formation, homeostasis and vascular hyalinosis. Conclusions: SHRSP develops hypertension, sensorimotor deficits and CSVD pathology as they age suggesting their utility as human CSVD model. Intervention time points should be selected carefully in future therapeutic drug interventions.

Cerebral Small Vessel Disease in subclinical and clinical stages, role of inflammation for risk prediction and potential treatment targets, and management strategies

2016 ◽  
Vol 2 (11) ◽  
Author(s):  
C. Frances Fan ◽  
José R Romero
Keyword(s):  
Clinical Outcomes ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Management Strategies ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Potential Treatment ◽  
Treatment Targets ◽  
Vessel Disease

<p><span style="font-size: medium;">Stroke and dementia are the most common neurological disorders worldwide. Cerebrovascular disease, particularly cerebral small vessel disease (CSVD) is implicated in both, and the two main types of CSVD (hypertensive vasculopathy and cerebral amyloid angiopathy) account for the majority of cerebrovascular contributions to stroke and dementia. Current knowledge of CSVD may influence treatment decisions and preventive efforts. Although the causes of CSVD are not entirely elucidated, ongoing research of the pathophysiology of CSVD, such as the role of inflammation, is helping identify potential treatment targets, evaluate prediction models and develop preventive strategies. Given the detectability of CSVD in preclinical stages using brain MRI, a long window of opportunity is presented to implement existent preventive measures. This review considers CSVD including its subclinical manifestations detected using brain MRI, clinical manifestations, use of markers of CSVD as predictors of clinical outcomes such as dementia and stroke, and presents potential management strategies when seeing patients with cerebral small vessel disease to reduce its disease burden and clinical consequences.<span style="font-family: Calibri;"> C</span>linical trials have evaluated some aspects of CSVD treatment and are beginning to recognize CSVD as endpoint in subclinical stages. Future studies will clarify if this approach is able to delay onset of dementia and prevent stroke occurrence, meanwhile implementation of existent recommendations for the prevention and treatment of stroke and dementia may reduce disability and clinical outcomes related to CSVD. </span></p>

scholarly journals Cerebral small-vessel disease is associated with the severity of diabetic retinopathy in type 1 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002274
Author(s):  
Marika I Eriksson ◽  
Paula Summanen ◽  
Daniel Gordin ◽  
Carol Forsblom ◽  
Sara Shams ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Vessel Disease

IntroductionCerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain’s vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes.Research design and methodsFor this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33–45) years; 53% female; diabetes duration 21.6 (18.2–30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score).ResultsIn type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20–61) vs 20 (20–35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20–65) vs 20 (20–35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts.ConclusionsPresence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.

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