Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe two members of a German family with cerebral autosomal dominant arteriopathy (CADASIL), which is characterized by recurrent subcortical ischemic strokes, mild dementia and leukoencephalopathy. The clinical features of the disease are suggestive of Binswanger's subcortical arteriosclerotic encephalopathy. However, it differs by the lack of hypertension and familial aggregation with autosomal dominant inheritance. Magnetic resonance imaging (MRI) of the brain shows subcortical ischemic infarcts affecting the periventricular white matter, the basal ganglia and the brain stem. On T2-weighted imaging, areas of hyperintensity were found in the white matter of both cerebral hemispheres with preponderance of frontal and anterotemporal regions. We assume that the underlying disease in this family is CADASIL with subcortical infarcts and leukoencephalopathy. The recently assigned disease locus on chromosome 19 was confirmed in this family. A treatment trial with acetylsalicylate was started in the affected members of the family.
 ...
PMID:[Hereditary CADASIL cerebral arteriopathy. Report of a family]. 858 78

A possible relation between cerebral white-matter injury and dementia was intuitively attributed by Alzheimer to changes affecting the small penetrating vessels that supply the cerebral white matter. Several observations support the view that white-matter changes detectable by neuroimaging may contribute to cognitive deficits in the elderly. But many questions concerning this matter remain partially answered. In this communication we review: (1) Selected anatomic features of the blood vessels supplying the white matter; (2) possible pathogenetic mechanisms responsible for the white-matter changes; (3) observations on humans and animals suggesting a causal relationship between ischemia/hypoxemia and white-matter injury; (4) epidemiologic studies linking white-matter abnormalities with cognitive disorders. We conclude that abnormalities in the small vessels caused by aging and arterial hypertension, or other processes (cerebral amyloid angiopathy, CADASIL) together with systemic circulatory disturbances, such as abrupt variations in blood pressure values or cardiac diseases, may be the substrate of selective white-matter injury. The damage is structurally characterized by incomplete infarction or selective cellular injury.
 ...
PMID:Cognitive impairment and cellular/vascular changes in the cerebral white matter. 932 83

The emergence of sensitive techniques for brain imaging has drawn attention to the occurrence of diffuse or multifocal changes affecting the cerebral white matter. The white matter changes are usually termed periventricular leukoencephalopathy, or leukoaraiosis. Microscopic studies of affected areas in the deep white matter have shown mostly demyelination, reactive gliosis, and arteriolosclerosis, proportional to the degree of radiologic changes. Yet, many other disease conditions need to be ruled out. Risk factors for ischemic leukoaraiosis include arterial hypertension, a history of stroke, and age. In the hereditary disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), severe white matter changes occur in the absence of hypertension. In "ordinary" cases of leukoaraiosis, genetic factors might similarly determine the effect of risk factors on the aging brain and might explain, for example, why not all patients with severe hypertension develop leukoaraiosis. Not surprisingly, diffuse demyelination affects cognitive function. Although reduced speed of mental processes is the most characteristic sign, attention, concentration, and verbal and visual memory are also affected. Most importantly, less severe forms of cognitive impairment represent a silent and perhaps largely preventable epidemic among aged or even middle-aged subjects. They live independently, but mentally they perform on a level well below their previous capacities. Although being "a bit odd" does not lead to hospital admissions, it seriously affects quality of life of a large part of the community. Moderate grades of leukoaraiosis constitute a major public health problem and deserve the attention of the scientific community.
 ...
PMID:Leukoaraiosis and vascular dementia. 974 23

Although epidemiological studies are limited by diagnostic uncertainties, they suggest that stroke increases the risk of dementia. The mortality rate is higher in vascular dementia (VaD) than in Alzheimer's disease (AD). Community-based studies have provided several consistent findings: (i) age dependence with prevalence rates doubling every 5 years, (ii) a higher frequency in men and (iii) nation-to-nation differences. The prevalence of VaD ranges from 2.2% in 70- to 79-year-old women, to 16.3% in men >80 years. One sixth of acute stroke patients have preexisting dementia. The incidence of VaD has been studied much less extensively than that of AD, and substantial variations in the incidence rates have been observed: annual incidence rates (per 100,000) range from 20 to 40 between 60 and 69 years of age and from 200 to 700 over 80. The incidence rate of VaD declined over the last 2 decades, probably as a consequence of effective stroke prevention. It is generally assumed that risk factors for VaD are those of stroke, with arterial hypertension as leading factor, followed by atherosclerotic disease, low education level, alcohol abuse and heart disease. Stroke characteristics, such as lacunar infarction and left-sided hemispheric lesions, are major determinants of VaD. The cerebrovascular lesions are likely to be the only cause of dementia in strategic infarcts, in lacunar state, in hereditary cystatin C amyloid angiopathy and in CADASIL. However, white matter changes, and associated Alzheimer pathology, which are both frequent in this age category, may also contribute to the cognitive decline.
 ...
PMID:Epidemiology of vascular dementia. 1042 61

This decade witnessed a resurgence of interest in vascular dementia (VaD) as an increasingly important cause of senile dementia. Although definitions of dementia in general, and of VaD in particular, are still controversial recent diagnostic criteria for VaD acknowledge that pathogenetic mechanisms different from multi-infarct dementia are important in dementia causation. These include subcortical strokes, mainly lacunes, global hypoxic-ischemic events during acute stroke, and ischemic periventricular white matter lesions of the Binswanger type. These lesions tend to be manifested primarily by alterations of frontal executive function control. The importance of these ischemic vascular lesions in the clinical expression of Alzheimer's disease (AD) in very old subjects has also been recognized. Clinically, VaD may present in two forms: Acute VaD includes large-vessel infarction, and lacunar dementia due to small-vessel disease, including thalamic and caudate strokes. Subacute VaD includes Binswanger's disease (BD), cerebral angiopathy with leukoencephalopathy and CADASIL. The discovery of CADASIL, a genetic form of VaD mapped to chromosome 19 as a mutation of the Notch 3 gene, opened research avenues into the pathogenesis of BD. Finally, epidemiological evidence suggests that it may be possible to prevent VaD--and perhaps degenerative senile dementia--by controlling hypertension and other vascular risk factors. These findings offer hope for prevention of this growing public health problem.
 ...
PMID:Vascular dementia today. 1063 40

The most common form of familial vascular dementia is considered to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is now also increasingly manifest in the United Kingdom. CADASIL has been previously dubbed as a familial form of Binswanger disease. However, unlike in Binswanger disease CADASIL does not involve hypertension or other risk factors associated with cardiovascular disease. CADASIL appears to be essentially a disorder of the arteries that is linked to single missense mutations in the NOTCH 3 gene locus on chromosome 19. The pathogenesis of the disorder or the genetic mechanism leading to brain infarcts and dementia is not known. The elucidation of the microvascular pathology evident in CADASIL may be an interesting way to delineate effects of defective genes on brain cells from systemic vascular influences.
 ...
PMID:Hereditary vascular dementia linked to notch 3 mutations. CADASIL in British families. 1081 18

Clinical data and MRI findings are presented on 18 subjects from two families with neuropathologically confirmed CADASIL. DNA analysis revealed mutations in exon 4 of Notch 3 gene in both families. All family members with mutations in Notch 3 gene had extensive abnormalities on MRI, principally lesions in the white matter of the frontal lobes and in the external capsules. Of several family members in whom a diagnosis of CADASIL was suspected on the basis of minor symptoms, one had MRI changes consistent with CADASIL; none of these cases carried a mutation in the Notch 3 gene. MRI and clinical features that may alert the radiologist to the diagnosis of CADASIL are reviewed. However, a wide differential diagnosis exists for the MRI appearances of CADASIL, including multiple sclerosis and small-vessel disease secondary to hypertension. The definitive diagnosis cannot be made on MRI alone and requires additional evidence, where available, from a positive family history and by screening DNA for mutations of Notch 3 gene.
 ...
PMID:Diagnosing CADASIL using MRI: evidence from families with known mutations of Notch 3 gene. 1087 67

Atypical phenotypes of CADASIL and corresponding anatomical data in two cases are described in 6 members of 2 new French families. In the first family, 4 cases in the same kindred were probably affected, two of them with a predominant psychiatric presentation, two others with dementia and a pseudo-bulbar syndrome of progressive evolution. No history of migraine or ischemic event were documented in any. In the propositus, the diagnosis was documented by skin biopsy, Notch 3 gene mutation and autopsy after the patient had died when 67 years old, 8 years after onset. Brain examination showed a widespread leukoencephalopathy with subcortical infarcts. Characteristic granular lesions of the small arteries of the brain and other organs were observed. In the second family, two cases are reported. One patient died when 63 years old after a subacute evolution mimicking intracranial hypertension. The anatomical diagnosis was retrospectively proven typical of CADASIL with Notch 3 immunostaining of arterial smooth muscle cells. The other case had a progressive evolution over 20 years of limb paresthesia with a mild spasticity diagnosed as a progressive form of multiple sclerosis. It was followed by a pseudo-bulbar syndrome and a mild subcortical dementia without acute ischemic attack. The diagnosis was confirmed by skin biopsy and mutation of the Notch 3 gene. This report illustrates
 ...
PMID:[Atypical CADASIL phenotypes and pathological findings in two new French families]. 1145 85

To clarify the characteristics of CADASIL in Japan, we performed clinical and genetic investigations for six patients from 5 Japanese families diagnosed as CADASIL. We identified that the onset of focal neurologic deficits ranged from 38 to 63 years old (mean 49 +/- 9.4 yrs) and the occurrence rates of main neurologic symptoms and signs were 1/6 for migraine, 3/6 for recurrent stroke episodes, 6/6 for dementia, and 4/6 for pseudobulbar palsy. The marked narrowing of retinal arteries were observed in 3/6. The notch 3 mutations were all found in exon 4. Although other several families shared similar phenotype of CADASIL, there were no deposition of granular osmiophilic materials within the basal lamina of smooth muscle cells in the arterioles of biopsied muscle and no mutations in the cording regions of notch 3 gene. We investigated prospectively the incidence of CADASIL and CADASIL-like disease in Kumamoto district from 1999 to 2000. One thousand and thirty four patients with stroke were hospitalized in 6 hospitals which have stroke care unit. Among them, 7 patients fulfilled the criteria that were less than 60 years old, lacunar strokes and/or TIA, presence of a family history, and no risk factors such as hypertension, diabetes mellitus, and hyperlipidemia. One of seven patients was diagnosed as CADASIL by DNA analysis. It was suspected the incidences of CADASIL and CADASIL-like disease were not so rare in Japan.
 ...
PMID:[CADASIL: clinical analysis of CADASIL and CADASIL-like disorders in Japan]. 1146 69

Cerebral amyloid angiopathy (CAA) is one of the two most common cerebral arteriopathies seen in the brains of elderly patients. The other is arteriosclerosis (AS), historically considered a consequence of chronic hypertension and also described as lipohyalinosis (LH), a clinicopathologic association that is increasingly questioned. These and other less frequently encountered degeneralions of the cerebral microvasculature (CADASIL, Binswanger subcortical leukoencephalopathy) share the common feature of degeneration of the medial smooth muscle layer within arteriolar walls. This can be dramatic in CAA, in the course of which complete replacement of medial smooth muscle by fibrillar amyloid may occur. It is a less prominent feature of CADASIL and BSLE: in the latter condition, medial smooth muscle hyperplasia, possibly a response to some kind of injury, is a more dramatic finding. In some of these "angiomyopathies", fibrinoid necrosis of the arterial wall and microaneurvsm formation may lead to stroke, manifest as cerebral hemorrhage. With CADASIL and BSLE, ischemic brain injury is more common. In the case of CAA, upregulation of the Abeta-amyloid precursor protein occurs when arteriolar smooth muscle cells in culture are exposed to prolonged hypoxia, especially with reoxygenation. Injury to arteriolar smooth muscle cells may be one mechanism by which angiomyopathies progress and become symptomatic.
 ...
PMID:Non-CAA angiopathies and their possible interactions with cerebral amyloid angiopathy. 1167 85


1 2 3 Next >>