Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence.

OBJECTIVE: Black and Hispanic survivors of intracerebral hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic cerebral small vessel disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk. METHODS: We analyzed data from the Massachusetts General Hospital ICH study (n = 593) and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n = 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk. RESULTS: We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD (p = 0.011) and HTNA burden (p = 0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed-etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all p < 0.05). CONCLUSIONS: We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial/ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity and investigating social determinants of health.

[Clinico-radiological spectrum of cerebral small vessel diseases]. / Spectre clinico-radiologique des maladies des petits vaisseaux cérébraux.

Cerebral small vessel diseases are frequent and can be seen through all ages. Although the most frequent forms related to age and hypertension or to cerebral amyloid angiopathy are mainly observed in subjects over 50 years of age, rarer forms may affect young people, sometimes even children. Some familial or inflammatory forms can be particularly misleading with some presentations very difficult to relate to a microvascular origin. Cerebral small vessel diseases thus raise both daily therapeutic issues and much rarer diagnostic questions, sometimes extremely complex. Our aim was to review the main clinical initial presentations and the clinico-radiological spectrum of associated underlying conditions.

Cerebral Small Vessel Disease.

PURPOSE OF REVIEW: This article reviews the clinical significance and neuroimaging characteristics of cerebral small vessel disease and the impact on neurologic disease and current and potential therapeutic approaches. RECENT FINDINGS: Cerebral small vessel disease is increasingly prevalent and highly heterogeneous in neuroimaging and clinical presentation. Small subcortical infarcts, lacunes, cerebral microbleeds, cortical microinfarcts, and white matter hyperintensity of presumed vascular origin represent the major neuroimaging markers of small vessel disease. Increasing small vessel disease burden is associated with risk of incident stroke and dementia, as well as other neuropsychiatric symptoms. Current research strategies are targeting elucidation of the mechanisms of small vessel disease pathogenesis and pursuing clinical trials of therapeutic agents to reduce the clinical manifestations of cerebral small vessel disease. SUMMARY: Cerebral small vessel disease is common in aging adults and represents a major risk factor for multiple acute and chronic neurologic diseases. Increased awareness of cerebral small vessel disease as a modifiable risk factor holds potential for reducing neurologic disease morbidity and mortality across diverse populations in the United States and worldwide.

Comparison Study of ASCO and TOAST Classification System in Chinese Minor Stroke Patients.

BACKGROUND: Precise subtype classification based on underlying pathophysiology is important to prevent recurrent attack in minor stroke patients. A newly developed Atherosclerosis, Small vessel disease, Cardiac source, Others (ASCO) phenotypic classification system aims to characterize patients using different grades of evidence for stroke subtypes. However, this system has not been specifically applied to minor stroke population. In our study, the impact of using the newer ASCO criteria on minor stroke etiologies was investigated, and compared with that of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. METHODS: Consecutive patients with minor ischemic stroke (NIHSS ≤3) were assessed and subtyped by the ASCO and TOAST systems. Stroke etiologies were presented and compared. The McNemar test and k statistic were used to analyze the difference and concordance between the 2 algorithms, respectively. RESULTS: A total of 604 first-ever minor stroke patients were analyzed in the present study. Using TOAST classification, large artery atherosclerosis was the most frequent subtype (281, 46.5%), followed by small artery occlusion category (165, 27.3%). When ASCO was applied, 37 different profiles of stroke etiologies were identified. Using grade 1 of evidence, atherosclerosis (A1) was the most frequent subtype (308, 51.0%), followed by small vessel disease (S1, 178, 29.5%). Under consideration of grades 1 and 2, 239 (39.6%) patients were classified into more than 1 category. The ASCO system revealed determined etiologies in 104 of the 137 patients classified to cause undetermined subtype by TOAST classification. Good to very good accordance was observed between ASCO grade 1 and TOAST schemes across etiologic subtypes (κ = 0.719-0.832) except cause undetermined category (κ = 0.470). CONCLUSION: Application of ASCO decreased the proportion of patients assigned to cause undermined category compared to TOAST system. Comprehensive characteristics of ASCO system might be helpful in the personalized therapy or secondary prevention for individual patients in the future.

Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) is composed of several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain, and refers to several pathological processes and etiologies. Neuroimaging features of CSVD include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The main clinical manifestations of CSVD include stroke, cognitive decline, dementia, psychiatric disorders, abnormal gait, and urinary incontinence. Currently, there are no specific preventive or therapeutic measures to improve this condition. In this review, we will discuss the pathophysiology, clinical aspects, neuroimaging, progress of research to treat and prevent CSVD and current treatment of this disease.

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.

Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

ASCO classification in clinical practice.

ASCO (Atherosclerosis, Small vessel disease, Cardiac source, Other cause) is a new of classification of ischemic cerebrovascular diseases. This classification categorizes the data of the patients according to all underlying diseases and allows the clinician to grade the severity of cause (Each of the four phenotypes can be graded 1, 2, or 3). It is suggested to use ASCO classification in large epidemiologic studies but this classification may be used in daily practice. In this study we aimed to analyze the clinical features of patients with ischemic stroke and to investigate results of ASCO classification of these patients and data of 35 patients with ischemic stroke is analyzed. Use of ASCO classification is discussed with the special example cases. Patients' etiology of stroke was classified according to ASCO as known, unknown, completely unknown and unclassifiable group. Percentile of the patients classified as "known" was 71.4% (n = 25), "unknown" was 17.1% (n = 6), "completely unknown" was 5.7% (n = 2) and "unclassifiable group" was 5.7% (n = 2). We think that the ASCO classification which is thought to be more useful in large epidemiologic studies may be used in clinical follow-up period of the stroke patients. Further studies, from different neurology centers and stroke units, are needed to expand our experiences about use of ASCO classification in clinical practice.

Two different clinical entities of small vessel occlusion in TOAST classification.

BACKGROUND: Small deep infarcts might be classified into 2 types: lacunar and branchatheromatous infarcts. However, since their initial description, small deep infarcts were still regarded as the same category of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, small vessel occlusion (SVO). We hypothesized that the 2 types of small deep infarcts would be distinct clinical entities. This study was conducted to investigate the clinical characteristics in the 2 groups of patients according to lesion pattern and combined atherosclerotic diseases. METHODS: We included patients with small deep infarcts in the subcortical area. The patients were divided into 2 groups: (1) island lesions and (2) linear lesions on coronal diffusion weighted imaging. The status of the relevant artery was categorized as no stenosis, non-significant (<50% of luminal narrowing) and significant (≥ 50% of luminal narrowing). We compared the clinical and imaging characteristics of two lesion types according to various arterial status. RESULTS: This study analyzed a total of 248 patients. Independent factors for island lesions on coronal DWI were male, severe leukoaraiosis, microbleeds, abnormal glycated hemoglobin (HbA1C), and abnormal estimated glomerular filtration ratio (eGFR) adjusted by age, sex, and initial National Institutes of Health Stroke Scale. In addition, in patients without significant relevant arterial stenosis, island lesion patterns were more frequently associated with severe periventricular white matter hyperintensity, diabetes mellitus, abnormal eGFR and abnormal HbA1C than linear lesion patterns. CONCLUSION: This study demonstrated that SVO of TOAST classifications had different imaging and clinical characteristics according to the lesion patterns of coronal imaging. It suggests that two types of SVO should be regarded as the different categories of stroke classification.

Hereditary cerebral small vessel diseases: a review.

Cerebral microangiopathies are responsible of a great number of strokes. In the recent years advances in molecular genetics identified several monogenic conditions involving cerebral small vessels and predisposing to ischemic and/or hemorrhagic stroke and diffuse white matter disease leading to vascular dementia. Clinical features and diagnostic clues of these conditions, [cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), COL4A1-related cerebral small vessel diseases, autosomal dominant retinal vasculopathy with cerebral leukodystrophy (AD-RVLC), and Fabry's disease] are here reviewed. Albeit with variable phenotypes and with different defective genes, all these disorders produce arteriopathy and microvascular disintegration with changes in brain functions. Specific diagnostic tools are recommended, genetic analysis being the gold standard for the diagnosis.

Risk factors for and incidence of subtypes of ischemic stroke.

The TOAST classification divides patients with ischemic stroke into five subgroups according to the presumed etiological mechanism. The aims of the present study were to evaluate the distribution of the different etiological stroke subtypes in a hospital-based sample of stroke patients, and to investigate the association between important risk factors and stroke subtypes. A total of 210 patients with a first-ever ischemic stroke admitted to the stroke unit of Asker and Bærum Hospital in Norway between February 2007 and July 2008 were enrolled in the study. Information on vascular risk factors was collected at admittance, examination of neurological deficits was carried out during their stay, and classification was made according to the TOAST criteria. According to the TOAST classification, 24 (11.4%) of the patients suffered from large vessel disease, 66 (31.4%) from cardioembolic disease, 66 (31.4%) from small vessel disease and 54 (25.7%) from a stroke of undetermined etiology. The presence of hyperlipidemia and atrial fibrillation varied significantly between the different subtypes. In multivariate analyses, hyperlipidemia [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.32-4.60] and current smoking (OR 2.06, 95% CI 1.04-4.08) were the only variables that were related to small vessel disease. Small vessel disease was observed more frequently and large vessel disease less frequently than previously reported. Small vessel disease was significantly associated with hyperlipidemia and current smoking. Our study supports the view that the etiology of lacunar strokes is multifactorial.

Stroke subtype classification: a comparative study of ASCO and modified TOAST.

BACKGROUND AND PURPOSE: The ASCO stroke classification may be an improvement over the modified TOAST for etiological diagnoses. We aimed to compare the differences in stroke subtype classification between these two classification system. METHODS: Selected for this study were 425 first-time acute ischemic stroke patients. For each, the cause of ischemic stroke was classified according to both the ASCO and modified TOAST criteria. The κ statistic and McNemar test were used to compare the similarities and differences, respectively, between the two approaches. RESULTS: More patients were classified as having an atherosclerotic etiology under the ASCO 1 category than the modified TOAST system (60.2% vs. 57.9%; P=0.132). There was no significant difference between the proportion of patients with undetermined etiology as defined by the ASCO 1 and the modified TOAST (15.5% vs. 16.2%; P=0.795). Both the modified TOAST and ASCO-1 correctly identified all patients with etiology "other cause". Agreement between the two classification systems was high in every subtype category except 'undetermined' (κ>0.81 for atherosclerosis, κ=0.61 to κ=0.8 for cardiac disease, and κ=0.480 for undetermined). When ASCO-1 to ASCO 3 were applied, atherosclerosis was identified as the cause in 76.0% of patients, small artery disease in 46.4%, and cardiac disease in 11.3%. CONCLUSION: There is a moderately high agreement between the ASCO and modified TOAST classification schemes in all subtypes except that of "undetermined" etiology. Application of ASCO-1 did not reduce the proportion of patients 'undetermined' etiology compared to modified TOAST.