Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a type of small-artery stroke and vascular dementia-inducing pathology of the brain. In order to explain the molecular mechanisms behind the alterations to the blood vessels in CADASIL subjects, we scrutinized the expression of glycan and glycan-binding sites in the wall of vessels taken from five such subjects (vs. five control subjects matched for age and sex). Specimens were taken from the brain, heart, kidney, liver and lung. Although the main vessel lesions were observed in the tissues depending on the blood-brain barrier, alterations to systemic vessels were also observed despite the absence of any symptoms. The histochemical expression of a panel of 10 biotinylated neoglycoconjugates [Gal-beta(1-4)-D-Glc, Galbeta(1-3)GalNAc, alpha-D-GalNAc, beta-D-GalNAc, GalNAcalpha(1-3)-D-GalNAcalpha, GalNAcalpha(1-3)-D-GalNAcbeta, beta-D-Glc, alpha-D-Man, l-Fucose and D-Glcalpha(1-4)-D-Glc], eight plant lectins (PNA, MAA, SNA, DBA, WGA, ConA, GNA and UEA-1) and two antigalectin antibodies was monitored by means of semiquantitative and quantitative computer-assisted microscopy. The data show the altered histochemical binding of plant lectins, such as UEA-1 and ConA, in the vessel walls of CADASIL subjects. The present work, based upon staining by a panel of neoglycoconjugates, provides a biochemical characterization of the alteration of vessel walls in the brain compared to other organs including the heart, kidney, lung and liver in CADASIL as opposed to control subjects. These glycohistochemical results suggest a functional relevance of protein-carbohydrate interactions in this disease.
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PMID:Glycohistochemical characterization of vascular muscle cell destruction in CADASIL subjects by lectins, neoglycoconjugates and galectin-specific antibodies. 1288

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is a neurovascular disease caused by mutations of the notch3 gene, manifesting with strokes or stroke-like episodes, psychiatric symptoms, migraine and dementia. The diagnosis can be confirmed by screening exons of this gene. Involvement of the anterior temporal lobe and external capsule on MRI and presence of granular osmiophilic material on skin biopsy may help in diagnosis. We present two Norwegian families with eight members who have symptoms indicating CADASIL. The mutation R182C was demonstrated in exon 4 in seven; one refused gene testing. Two brothers without symptoms also tested positively for this gene mutation.
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PMID:[Hereditary cerebral arteriopathy]. 1461 73

Over a 5-year period, we investigated 77 consecutive patients (36 males, 41 females, mean age 40.9 years) referred to our hospital with the diagnosis of CNS vasculitis. Extensive workup including MRI, echocardiography, laboratory tests, angiography ( n=53), and biopsies at appropriate sites ( n=26) was performed based on individual history and symptoms. Prominent symptoms were stroke ( n=61), encephalopathy ( n=14), and headaches ( n=2). Vasculitis was finally diagnosed in 13 patients (17%) including isolated angiitis of the CNS ( n=3), giant cell arteritis ( n=4), and septic arteritis ( n=3). Thirty-two patients (42%) presented noninflammatory vasculopathies including moyamoya ( n=6), Sneddon's syndrome ( n=5), dissection ( n=4), CADASIL ( n=2), and collagen vascular disease ( n=9). Coagulopathy was found in 14 cases (18%) including antiphospholipid syndrome ( n=8) and APC resistance ( n=4). Other causes were cardiogenic embolism ( n=8), multiple sclerosis ( n=5), and migraine stroke ( n=3). Only a minority of patients referred for evaluation of suspected CNS vasculitis actually present with inflammatory vascular disease. Main differential diagnosis includes noninflammatory vasculopathies, coagulopathies, and cardiac disease. Since septic processes may be responsible for the symptoms, "blind" treatment with immunosuppressive agents should be strictly avoided.
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PMID:[Diagnosis and differential cerebral vasculitis diagnosis]. 1477 Feb 79

We report a 64-year-old Japanese woman with recurrent ischemic strokes and progressive dementia without any cardiovascular risk factors. Her first stroke was at 45 years old, and she has a family history of ischemic strokes compatible with an autosomal dominant trait. Marked leukoaraiosis and multiple lacunar infarcts were shown on brain MR images, and no atherosclerotic changes were observed in her extra- and intra-cranial arteries by cervical arterial echography and intracranial MR angiography. Excluded other inherited or metabolic diseases causing leukodystrophy by examination of her blood samples, her disease was diagnosed as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy). We demonstrated granular osmiophilic materials (GOM) on the wall of small arteries from a biopsied peripheral nerve tissue specimen and detected a mutation Arg169Cys of Notch 3 gene. Many CADASIL patients have been reported and over 28 kinds of mutations of the Notch 3 were identified in western countries, while few CADASIL patients have been reported in Japanese people. Among them, eleven CADASIL families have been reported and only five mutations (Arg133Cys, Cys174Phe, Arg213Lys, Arg90Cys and Arg141Cys) have been determined so far. The mutation of Notch 3 in our patient was determined as Arg169Cys, and this is the first report on a Japanese patient with CADASIL due to this mutation.
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PMID:[A case of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy) with Notch 3 (Arg169Cys) mutation and typical granular osmiophilic materials in peripheral small arteries]. 1528 9

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.
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PMID:Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia. 1553 26

Mutations in the NOTCH3 gene trigger adult-onset stroke and vascular dementia in patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). All CADASIL mutations described to date affect the epidermal growth factor-like (EGF-like) repeats located in the extracellular domain of the Notch3 receptor. These domains are also the target of sequential complex O-linked glycosylation mediated by protein O-fucosyltransferase 1 and Fringe. We investigated whether O-fucosylation or Fringe-mediated elongation of O-fucose on Notch3 is impaired by CADASIL mutations. Biochemical studies of a Notch3 fragment containing the first five EGF-like repeats of Notch3, including the mutational hot spot, showed that CADASIL mutations do not affect the addition of O-fucose but do impair carbohydrate chain elongation by Fringe. CADASIL changes also induced aberrant homodimerization of mutant Notch3 fragments and heterodimerization of mutant Notch3 with Lunatic Fringe itself. Together, these data suggest that Fringe plays a role in CADASIL pathophysiology.
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PMID:CADASIL mutations impair Notch3 glycosylation by Fringe. 1585 53

Assessing the risk of stroke in persons with migraine is complicated by the intricate relationship between these two conditions. Both migraine and stroke are common and co-morbidity may, in some cases, be coincidental. Given the overlap of clinical symptoms in stroke and migraine, each condition may also mimic the other. Numerous studies have, however, shown that migraine is an independent risk factor for stroke both during, and remote from, the migraine attack. Women of childbearing age and those with aura are at greatest risk of migraine-related stroke. Additional risk of stroke in migraineurs occurs in those using oral contraceptive pills and who smoke cigarettes. Elevated blood pressure, an important stroke risk factor, is less common in migraineurs. Acquired antiphospholipid antibodies, not clearly a cause of migraine per se, may raise the risk of infarction in migraineurs. Hereditary conditions, including CADASIL (cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactacidosis and stroke) and hereditary haemorrhagic telangiectasia, appear to predispose to both migraine and stroke. Purported mechanisms for migraine-associated stroke include involvement of the vasculature (including vasospasm, arterial dissection and small vessel arteriopathy), hypercoagulability (elevated von Willebrand Factor, platelet activation) and elevated risk of cardioembolism (patent foramen ovale, atrial septal aneurysm). Triptans and ergotamines, used to treat acute migraine attacks, appear to be safe in low-risk populations. These medications should be avoided in persons with haemiplegic migraine, basilar migraine, vascular risk factor and prior cerebral or cardiac ischaemia.
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PMID:The risk of stroke in patients with migraine and implications for migraine management. 1609 50

Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in the blood vessel wall have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function. Failure of the interactions between the 2 cell types, as seen in numerous genetic mouse models, results in severe and often lethal cardiovascular defects. Abnormal interactions between the 2 cell types are also implicated in a number of human pathological conditions, including tumor angiogenesis, diabetic microangiopathy, ectopic tissue calcification, and stroke and dementia syndrome CADASIL. In the present review, we summarize current knowledge concerning the identity, characteristics, diversity, ontogeny, and plasticity of pericytes. We focus on the advancement in recent years of the understanding of intercellular communication between endothelial and mural cells with a focus on transforming growth factor beta, angiopoietins, platelet-derived growth factor, spingosine-1-phosphate, and Notch ligands and their respective receptors. We finally highlight recent important data contributing to the understanding of the role of pericytes in tumor angiogenesis, diabetic retinopathy, and hereditary lymphedema.
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PMID:Endothelial/pericyte interactions. 1616 62

Monogenic disorders account for only a minority of strokes. Yet, they have been particularly helpful in exploring basic disease mechanisms. This article summarizes some recent data on monogenic stroke while focusing on two conditions: CADASIL, as a genetic variant of ischemic small vessel disease, and familial forms of cerebral amyloid angiopathy, which share many properties with sporadic disease.
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PMID:Monogenic causes of stroke. 1619 Dec 12

It is still a challenge to identify typical features of cognitive function in vascular dementia (VaD) in clinical as well as in preclinical stages. Selective empirical findings are described to illuminate degrees of cognitive decline. In predementia stages, speeded performance (motor and mental) and executive functions may be affected as demonstrated by CADASIL subjects and stroke survivors. In dementia stages, motor and mental speed as well as executive functions is commonly affected in addition to typical cognitive dysfunction in dementia (memory, verbal, and visuospatial). To summarize characteristics during preclinical and clinical stages, VaD appears to be associated with impairment in motor and mental speed as well as in executive function.
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PMID:Cognitive syndrome(s) in preclinical and clinical vascular dementia. 1619 Dec 29


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