Neuroimaging standards for research into small vessel disease-advances since 2013.
The Lancet. Neurology
Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2.
10.1016/S1474-4422(23)00131-X
Prevalence and characterization of cerebral small vessel disease in young adults with intracerebral hemorrhage.
International journal of stroke : official journal of the International Stroke Society
BACKGROUND AND AIMS:Cerebral small vessel disease (CSVD) is the main cause of intracerebral hemorrhage (ICH) in older individuals but has not been systematically studied in younger people. We aimed to evaluate the prevalence and characteristics of CSVD in young adults with symptomatic ICH. METHODS:We conducted a cohort study of consecutive adults aged 18-50 years with non-traumatic ICH. All patients were evaluated with brain and vascular imaging. Using validated imaging markers (cerebral microbleeds (CMBs), white matter hyperintensities and/or lacunes), patients were categorized as having CSVD-related ICH or non-CSVD-related ICH. Factors associated with CSVD were evaluated using multivariable analyses. CSVD subtypes were characterized using pre-specified criteria. RESULTS:Of 146 young adults with ICH (mean age = 37.7), CSVD was present in 41 patients (28.1%; 95% confidence interval (CI) = 21.0-36.1). In multivariable analysis, older age, male sex, and hypertension were independently associated with the presence of CSVD. Deep perforator arteriopathy (48.8%) and mixed CSVD (31.7%) were the most common CSVD subtypes. CONCLUSION:Our results suggest that CSVD is a frequent cause of ICH in young adults and provide new insights into the characterization of the disease. These findings may have important implications since the treatment and management differ from other causes of ICH.
10.1177/17474930221093526
Cerebral small vessel disease was associated with the prognosis in ischemic stroke with atrial fibrillation.
CNS neuroscience & therapeutics
BACKGROUND:The purpose of this study was to explore the relationship between atrial fibrillation (AF), cerebral small vessel disease (CSVD), and ischemic stroke. METHODS:Data were extracted from China's Third National Stroke Registry (CNSR-III), which registered 15,166 patients in China. A total of 12,180 ischemic stroke patients were included excluding those diagnosed with TIA or without MRI. Logistic regression was to explore the relationship between AF, CSVD, and poor functional outcomes at 12-month follow-up. Cox regression is to explore AF, CSVD, and stroke recurrence as well as all-cause mortality at 12-month follow-up. RESULTS:The average age was 62.40 ± 11.22 years old, and 8362 (68.65%) were men at baseline. Patients with AF had an increased risk of stroke recurrence and all-cause mortality at 12-month follow-up. Those with AF and CSVD imaging such as lacunes, white matter hyperintensity (WMH), and the presence of cerebral microbleeds (CMBs) had an increased risk of poor prognosis. And those with both AF and CSVD burden had an increased risk of worse prognosis at 12-month follow-up. CONCLUSION:Among Chinese patients with acute ischemic stroke, those with AF were associated with a higher risk of 12-month mortality and stroke recurrence. When AF was combined with some CSVD imaging features such as lacunes, WMH, presence of CMBs or burdens, the 12-month poor prognosis worsened.
10.1111/cns.70052
Prevalence and Risk Factors of Cerebral Small Vessel Disease from a Population-Based Cohort in China.
Neuroepidemiology
INTRODUCTION:Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited. METHODS:Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression. RESULTS:A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score. CONCLUSIONS:In this Chinese cohort with community-based adults aged 50-75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community.
10.1159/000533678
The Spectrum of Cerebral Small Vessel Disease: Emerging Pathophysiologic Constructs and Management Strategies.
Neurologic clinics
Cerebral small vessel disease (CSVD) is a spectrum of disorders that affect small arterioles, venules, cortical and leptomeningeal vessels, perivascular spaces, and the integrity of neurovascular unit, blood brain barrier, and surrounding glia and neurons. CSVD is an important cause of lacunar ischemic stroke and sporadic hemorrhagic stroke, as well as dementia-which will constitute some of the most substantive population and public health challenges over the next century. This article provides an overview of updated pathophysiologic frameworks of CSVD; discusses common and underappreciated clinical and neuroimaging manifestations of CSVD; and reviews emerging genetic risk factors linked to sporadic CSVD.
10.1016/j.ncl.2024.03.003
Diagnosis and Management of Cerebral Small Vessel Disease.
Continuum (Minneapolis, Minn.)
OBJECTIVE:Cerebral small vessel disease (CSVD) is a common neurologic condition that contributes to considerable mortality and disability because of its impact on ischemic and hemorrhagic stroke risk and dementia. While attributes of the disease have been recognized for over two centuries, gaps in knowledge remain related to its prevention and management. The purpose of this review is to provide an overview of the current state of knowledge for CSVD. LATEST DEVELOPMENTS:CSVD can be recognized by well-defined radiographic criteria, but the pathogenic mechanism behind the disease is unclear. Hypertension control remains the best-known strategy for stroke prevention in patients with CSVD, and recent guidelines provide a long-term blood pressure target of less than 130/80 mm Hg for patients with ischemic and hemorrhagic stroke, including those with stroke related to CSVD. Cerebral amyloid angiopathy is the second leading cause of intracerebral hemorrhage and may be increasingly recognized because of newer, more sensitive imaging modalities. Transient focal neurologic episodes is a relatively new term used to describe "amyloid spells." Guidance on distinguishing these events from seizures and transient ischemic attacks has been published. ESSENTIAL POINTS:CSVD is prevalent and will likely be encountered by all neurologists in clinical practice. It is important for neurologists to be able to recognize CSVD, both radiographically and clinically, and to counsel patients on the prevention of disease progression. Blood pressure control is especially relevant, and strategies are needed to improve blood pressure control for primary and secondary stroke prevention in patients with CSVD.
10.1212/CON.0000000000001232
Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.
The Journal of clinical investigation
Cerebral small vessel disease (cSVD) encompasses a heterogeneous group of age-related small vessel pathologies that affect multiple regions. Disease manifestations range from lesions incidentally detected on neuroimaging (white matter hyperintensities, small deep infarcts, microbleeds, or enlarged perivascular spaces) to severe disability and cognitive impairment. cSVD accounts for approximately 25% of ischemic strokes and the vast majority of spontaneous intracerebral hemorrhage and is also the most important vascular contributor to dementia. Despite its high prevalence and potentially long therapeutic window, there are still no mechanism-based treatments. Here, we provide an overview of the recent advances in this field. We summarize recent data highlighting the remarkable continuum between monogenic and multifactorial cSVDs involving NOTCH3, HTRA1, and COL4A1/A2 genes. Taking a vessel-centric view, we discuss possible cause-and-effect relationships between risk factors, structural and functional vessel changes, and disease manifestations, underscoring some major knowledge gaps. Although endothelial dysfunction is rightly considered a central feature of cSVD, the contributions of smooth muscle cells, pericytes, and other perivascular cells warrant continued investigation.
10.1172/JCI172841
Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management.
Current opinion in neurology
PURPOSE OF REVIEW:We present recent developments in the field of small vessel disease (SVD)-related vascular cognitive impairment, including pathological mechanisms, updated diagnostic criteria, cognitive profile, neuroimaging markers and risk factors. We further address available management and therapeutic strategies. RECENT FINDINGS:Vascular and neurodegenerative pathologies often co-occur and share similar risk factors. The updated consensus criteria aim to standardize vascular cognitive impairment (VCI) diagnosis, relying strongly on cognitive profile and MRI findings. Aggressive blood pressure control and multidomain lifestyle interventions are associated with decreased risk of cognitive impairment, but disease-modifying treatments are still lacking. Recent research has led to a better understanding of mechanisms leading to SVD-related cognitive decline, such as blood-brain barrier dysfunction, reduced cerebrovascular reactivity and impaired perivascular clearance. SUMMARY:SVD is the leading cause of VCI and is associated with substantial morbidity. Tackling cardiovascular risk factors is currently the most effective approach to prevent cognitive decline in the elderly. Advanced imaging techniques provide tools for early diagnosis and may play an important role as surrogate markers for cognitive endpoints in clinical trials. Designing and testing disease-modifying interventions for VCI remains a key priority in healthcare.
10.1097/WCO.0000000000000913
Cerebral small vessel disease: Recent advances and future directions.
International journal of stroke : official journal of the International Stroke Society
Cerebral small vessel disease (SVD) causes lacunar stroke and intracerebral hemorrhage, and is the most common pathology underlying vascular cognitive impairment. Increasingly, the importance of other clinical features of SVD is being recognized including motor impairment, (vascular) parkinsonism, impaired balance, falls, and behavioral symptoms, such as depression, apathy, and personality change. Epidemiological data show a high prevalence of the characteristic magnetic resonance imaging (MRI) features of white matter hyperintensities and lacunar infarcts in community studies, and recent data suggest that it is also a major health burden in low- and middle-income countries. In this review, we cover advances in diagnosis, imaging, clinical presentations, pathogenesis, and treatment.The two most common pathologies underlying SVD are arteriolosclerosis caused by aging, hypertension, and other conventional vascular risk factors, and cerebral amyloid angiopathy (CAA) caused by vascular deposition of β-amyloid. We discuss the revised Boston criteria of CAA based on MRI features, which have been recently validated. Imaging is providing important insights into pathogenesis, including improved detection of tissue damage using diffusion tensor imaging (DTI) leading to its use to monitor progression and surrogate endpoints in clinical trials. Advanced MRI techniques can demonstrate functional or dynamic abnormalities of the blood vessels, while the high spatial resolution provided by ultrahigh field MRI at 7 T allows imaging of individual perforating arteries for the first time, and the measurement of flow velocity and pulsatility within these arteries. DTI and structural network analysis have highlighted the importance of network disruption in mediating the effect of different SVD pathologies in causing a number of symptoms, including cognitive impairment, apathy, and gait disturbance.Despite the public health importance of SVD, there are few proven treatments. We review the evidence for primary prevention, and recent data showing how intensive blood pressure lowering reduces white matter hyperintensities (WMH) progression and delays the onset of cognitive impairment. There are few treatments for secondary prevention, but a number of trials are currently evaluating novel treatment approaches. Recent advances have implicated molecular processes related to endothelial dysfunction, nitric oxide synthesis, blood-brain barrier integrity, maintenance and repair of the extracellular matrix, and inflammation. Novel treatment approaches are being developed to a number of these targets. Finally, we highlight the importance of large International collaborative initiatives in SVD to address important research questions and cover a number which have recently been established.
10.1177/17474930221144911
Cerebral small vessel disease: A review.
Chojdak-Łukasiewicz Justyna,Dziadkowiak Edyta,Zimny Anna,Paradowski Bogusław
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
Cerebral small vessel disease (CSVD) is the most common, chronic and progressive vascular disease. The changes affect arterioles, capillaries and small veins supplying the white matter and deep structures of the brain. It is the most common incidental finding on brain scans, especially in people over 80 years of age. Magnetic resonance imaging (MRI) plays a key role in the diagnosis of CSVD. The nomenclature and radiological phenotypes of CSVD were published in 2013 based on the unified position of the so-called Centres of Excellence in Neurodegeneration. The disease is characterized by a diverse clinical and radiological picture. It is primarily responsible for stroke incidents, gait disturbances, depression, cognitive impairment, and dementia in the elderly. The CSVD contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Common causes of CSVD include arteriosclerosis, cerebral amyloid angiopathy (CAA), genetic small vessel angiopathy, inflammation and immune-mediated small vessel diseases, and venous collagenosis. There is no causal treatment and management is mainly based on combating known risk factors for cardiovascular disease (CVD).
10.17219/acem/131216