Yield of Screening for CADASIL Mutations in Lacunar Stroke and Leukoaraiosis

Dong, Yanbin; Hassan, Ahamad; Zhang, Zhongyi; Huber, Dionne; Dalageorgou, Chrysoula; Markus, Hugh S.

doi:10.1161/01.str.0000048162.16852.88

Cited by 83 publications

(50 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy has been shown to be caused by highly stereotyped mutations in the Notch3 gene, a large transmembrane receptor involved in cell fate decisions during embryogenesis and promotion of vascular smooth muscle cell survival but a rare condition in patients with cerebral SVD. 8 This heterogeneity of SVD applies not only to the underlying vessel lesions but also to brain lesions; there is, for example, both pathological and clinical evidence that small infarcts in the centrum ovale, probably lying in arterial border zone territories, are more commonly the consequence of cardiac and carotid disease than the classic deep-seated gray matter lesions. 9 The strong epidemiological association that exists among WML/LA, SBLI, and several cerebrovascular diseases suggests that ischemia may be a contributing factor.…”

Section: See P 900mentioning

confidence: 99%

C-Reactive Protein and Cerebral Small-Vessel Disease

Napoli

Papa

2005

Circulation

View full text Add to dashboard Cite

Stroke places a large burden on healthcare and social services resources in the older adult population. Because the incidence of stroke increases with advancing age, and the population is aging, the number of patients affected by stroke is increasing. See p 900The burden of stroke goes well beyond those cases that are clinically recognized. Imaging techniques of the brain have revealed a remarkably high prevalence of white matter lesions (WML) and silent brain lacunar infarcts (SBLI). In the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Health Study, SBLI Ն3 mm were found in 31% of all subjects. 1 Fewer than 15% of patients with such lesions had a clinical history of stroke. The prevalence of SBLI increased with advancing age; 22% of subjects 65 to 69 years old had SBLI, as compared with 43% in subjects Ն80 years old. WML involving in particular the centrum ovale are a subject of great interest. Partly this is because modern neuroimaging methods detect subcortical WM changes with increasing frequency in people Ͼ60 years old and also because these abnormalities may be associated with specific neurobehavioral deficits, including dementing syndromes. 2 The descriptive term leukoaraiosis (LA), frequently applied to these neuroimaging abnormalities of the WM, refers to bilateral and either patchy or diffuse areas of hypodensity on CT or hyperintensity on T2-weighted MRI. 3 In this issue of Circulation, van Dijk and colleagues 4 explore the relationship of C-reactive protein (CRP), a well-known systemic marker of inflammation, with the severity and progression of cerebral WML/LA on MRI scans. The investigators examined the prevalence and incidence of brain WML/LA and SBLI in the prospective cohort of 1033 older adult participants of the population-based Rotterdam Scan study. They confirmed a relationship between inflammation and the severity and progression of cerebral WML/LA and SBLI independent of other cardiovascular risk factors and severity of carotid atherosclerosis. The authors suggest that CRP and inflammatory processes could be involved in the pathogenesis of cerebral small-vessel disease (SVD), and in particular in the development of WML/LA. These data raise questions about the relationship between SVD and inflammation. That said, the evolving concept of using a highly sensitive assay for CRP as a marker of SVD risk is enticing, and the message suggested by results of this study is both provocative and in line with the increasing body of literature rapidly accumulating in the exciting field of cerebrovascular disease.The data of van Dijk et al on the positive correlation between CRP blood levels and SVD appear persuasive; CRP was largely independent of traditional factors and severity of systemic atherosclerosis as assessed by ultrasound carotid examination. The present Dutch cohort is the largest to report on WML/LA and SBLI prevalence as the primary end point. WML/LA severity correlated positively with CRP levels, with a progressive rise in WML/LA severity with CRP level in the top qua...

show abstract

Section: See P 900mentioning

confidence: 99%

C-Reactive Protein and Cerebral Small-Vessel Disease

Napoli

Papa

2005

Circulation

View full text Add to dashboard Cite

show abstract

“…It should be noted that a small percentage of CADASIL patients' mutations may not be detected via PCR analysis. This may relate to deletional mutations or mutations within the noncoding sequence of the gene that can be missed by PCR (2,11).…”

Section: Laboratory Findingsmentioning

confidence: 99%

Worsening Neurologic Deficits in a Pilot

Jewell

Tunell²,

Bouffard³

et al. 2006

Baylor University Medical Center Proceedings

View full text Add to dashboard Cite

“…CADASIL has a prevalence of at least 1 per 100,000 and accounts for about 2% of lacunar strokes under age 65. 36 Leukoariosis is a diffuse lesion of white matter resulting in hyperintensity on MRI scans often seen together with lacunae and thought to be due to a form of arteriolosclerosis or "microatheroma." 37 The extent of leukoariosis was found to be 71% heritable in World War II veteran twins.…”

Section: Heritability Of End-organ Damagementioning

confidence: 99%

Genetics of hypertension

Hopkins

Hunt

2003

Genetics in Medicine

View full text Add to dashboard Cite

Hypertension is the most prevalent cardiovascular disorder. In the 1999 to 2000 NHANES survey, the prevalence of hypertension progressively increased from 7.2% in those aged 18 to 39 to 30.1% in 40 to 59 year olds and 65.4% in those 60 and older. 1 Risk of both coronary atherosclerosis and stroke increase exponentially as blood pressure rises (see Fig. 1). 2 Although the relative risk for stroke increases more rapidly than coronary disease, at any pressure, the absolute risk for coronary disease is considerably greater than for stroke. An insight into this finding comes from autopsy studies that show that the carotid and intracerebral vascular beds are relatively protected from atherosclerosis as compared to the coronary circulation, particularly at lower blood pressures (see Fig. 2). 3,4 Probably the major means whereby hypertension accelerates atherosclerosis is through pressure-driven convection of LDL and other atherogenic particles into the arterial intima. 5-8 Indeed, without at least arterial pressures, atherosclerosis does not exist in the vascular tree 9 even in patients with homozygous familial hypercholesterolemia. 10,11 Increased turbulence (a rare occurrence in the human circulatory system) does not increase atherosclerosis. Rather, higher sheer stress is a strong stimulus for release of nitric oxide that locally decreases risk of atherosclerosis. Focal areas of low sheer stress are at inherently increased risk of atherosclerotic disease (such as the coronary arteries where flow stops during each systole). 12 Interestingly, in most studies, stroke risk has been affected little by serum total cholesterol, 13,14 although some recent studies identify clear associated risk. 15 At least some association with all standard cardiovascular risk factors should be expected, not only because thromboembolic stroke may be caused by carotid tree atherosclerosis, but because aortic plaques have been strongly implicated as an embolic source for ischemic stroke. 16 -18 Hypertension is not just a risk factor for atherosclerosis. High blood pressure can have direct adverse effects on arteries, arterioles, and the heart, resulting in potentially severe consequences beyond the more common manifestations of myocardial infarction and atherothrombotic stroke. Even modestly elevated blood pressure is a major risk factor for congestive heart failure. 19,20 Hypertension is a major contributor to left ventricular hypertrophy, a major risk factor for sudden death independent of other risk factors. 21,22 Hypertension can lead progressively to arterial and arteriolar hypertrophy, arteriosclerosis and arteriolosclerosis, and with very high pressures to fibrinoid change and fibrinoid necrosis in arterioles. These latter changes can result in lumen compromise of arterioles resulting in lacunar stroke, Charcot-Bouchard aneurysms, glomerulosclerosis and nephrosclerosis, and ultimately malignant hypertension in the kidney and retinal ischemia and blindness. Risk of intracerebral hemorrhage is increased 33-fold at stage 3 or higher pre...

show abstract

Yield of Screening for CADASIL Mutations in Lacunar Stroke and Leukoaraiosis

Cited by 83 publications

References 21 publications

C-Reactive Protein and Cerebral Small-Vessel Disease

C-Reactive Protein and Cerebral Small-Vessel Disease

Worsening Neurologic Deficits in a Pilot

Genetics of hypertension

Contact Info

Product

Resources

About