1/8. Cerebral blood flow and glucose metabolism in multi-infarct-dementia related to primary antiphospholipid antibody syndrome.The primary antiphospholipid antibody syndrome (PAPS) has been described in patients with a history of fetal loss, thrombocytopenia and arterial or venous thrombosis. In PAPS, a prothrombotic state is mediated by antiphospholipid antibodies (aPLs) leading to disseminated thromboembolic vascular occlusion. Today, the presence of aPLs in the serum is considered as a distinct risk factor for recurrent stroke in young adults. Some PAPS patients develop a multi-infarct-syndrome with a stepwise decline of higher cortical functions. We report on a 55-year-old man suffering from progressive dementia and PAPS, in whom cerebral glucose metabolism and blood flow were examined by positron emission tomography (PET). Cerebral atrophy and moderate signs of leukaraiosis were detected in magnetic resonance imaging (MRI), whereas the PET scans showed a considerable diffuse impairment of cortical glucose metabolism combined with a reduced cerebral perfusion in the arterial border zones. These findings indicate that PAPS-associated vascular dementia is accompanied by a cortical neuronal loss, presumably caused by a small-vessel disease with immune-mediated intravascular thrombosis. This case shows that pathological findings in PAPS are congruent to cerebral changes of metabolism and blood flow in systemic lupus erythematosus (SLE).- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
2/8. Retinal findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil).We describe a 45-year-old man with biopsy proven cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). This patient demonstrated unique retinal findings, including arteriole narrowing and sheathing, irregular choroidal filling on fluorescein angiography, and patchy visual field loss. cadasil is a hereditary, nonamyloid, nonathersclerotic microangiopathy. This disorder has been mapped to chromosome 19 with mutations in the Notch 3 gene. Deposits of granular osmiophilic material in the basal lamina of the smooth muscle cells of small vessels are considered pathognomonic for cadasil and are typically seen only on electron microscopy. Although cadasil is a systemic vascular disease affecting the entire arteriole tree, we are unaware of other reports describing the retinal findings observed in our patient.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
3/8. cadasil (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): a neurovascular disease diagnosed by ultrastructural examination of the skin.BACKGROUND: cadasil (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a recently recognized neurovascular disease due to mutations of the Notch3 gene, manifesting with strokes or stroke-like episodes, major psychiatric symptoms and dementia. The diagnosis can be confirmed either by molecular analysis or by ultrastructural examination of the brain or more simply the skin. methods: The skin of a patient with a suspected diagnosis of cadasil was studied by electron microscopy. RESULTS: Characteristic granular osmiophilic material within the basement membrane surrounding pericytes and smooth muscle cells of small and medium-sized vessels of the skin were found, confirming the diagnosis of cadasil. CONCLUSIONS: cadasil is an additional example of a neurologic disease that can be diagnosed thanks to electron microscopic examination of the skin. Dermatopathologists should be aware of these ultrastructural findings, all the more so since the disease could be more common than originally thought.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
4/8. A novel mutation (C67Y)in the NOTCH3 gene in a Korean cadasil patient.We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of cadasil. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that cadasil may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
5/8. Histopathological abnormalities in ocular blood vessels of cadasil patients.PURPOSE: To assess histopathological findings in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). DESIGN: case reports and histopathological evaluation of enucleated eyes. methods: Four eyes from two cadasil patients were enucleated at autopsy and prepared for histopathological analysis using light and electron microscopy. RESULTS: Thickening of arterial walls with fibrosis, eosinophilic periodic acid Schiff-positive basement membrane material and loss of vascular smooth muscle cells (VSMC) in the central retinal artery and its branches, the leptomeninges, the ocular adnexa, and the optic disk were observed. On electron microscopy, numerous deposits of granular, osmiophilic material in arterial walls as well as VSMC and pericyte degeneration were noted. In contrast to retinal vessels, the choroid was not affected. CONCLUSION: Our findings suggest a differential involvement of small blood vessels in cadasil, depending on the angioarchitecture and support autopsy data of nervous tissue describing that loss of VSMCs is most pronounced in tissues depending on blood-tissue barriers.- - - - - - - - - - ranking = 6keywords = vessel (Clic here for more details about this article) |
6/8. Diffuse white matter involvement seen in patients in longstanding bedridden state from cerebrovascular dementia.We report here two autopsied cases of patients who had been in a longstanding bedridden state from cerebrovascular dementia. They showed a clinical history of persistent hypertension, a history of acute strokes, a lengthy clinical course with long plateau periods and a gradual accumulation of focal neurological symptoms and signs, including dementia and prominent motor disturbances and pseudobulbar palsy. They had been in a bedridden state for the last several years and had to be fed. The pathology seemed to predominently affect the perforating vessels to the subcortical gray and white matter. Demyelination, loss of axons, patchy gliosis and infiltration by macrophages were noted in the involved regions. The long penetrating vessels of the white matter showed advanced arteriosclerotic changes. There was a relative sparing of the cortex. The low attenuation of the white matter with moderate to severe atrophy, and an infarction might well be significant features on a CT-scan of these conditions. One of the possible mechanisms on the pathogenesis of chronic vascular disease includes diffuse ischemia related to hypertensive vasculopathy.- - - - - - - - - - ranking = 2keywords = vessel (Clic here for more details about this article) |
7/8. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: study of two American families with predominant dementia.Few European families have been reported with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). We describe four patients from two independent American families. All four cases underwent comprehensive clinical, neuropsychological and pathological examination. Pathological data were correlated with clinical features. dementia was a prominent and constant feature in all subjects. The families differed in phenotypical presentation and we analyzed possible pathological substrates that may account for the differences. autopsy showed multiple ischemic infarcts in the white matter, abnormal vasculature with thickening and degeneration of the vessel wall. The clinical course in the first family was characterized by early dementia without stroke-like episodes; however, autopsy demonstrated strokes in the basal ganglia and thalamus. The members of the second family developed dementia later and had history of several clinically evident strokes. Pathological examination showed only widespread degeneration of the white matter. Our study of two American families with cadasil suggests that involvement of the basal ganglia and thalamus is important for early development of dementia and clinically can present as a gradual dementia, resembling a neurodegenerative process. Selective damage of the white matter and central gray matter provides further insight to the pathogenesis of vascular dementia.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
8/8. Phenotypic variability of cadasil and novel morphologic findings.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is a non-arterio-atherosclerotic, non-amyloidotic arteriopathy affecting preferentially the small arteries and arterioles of the brain. The morphologic hallmark is the presence of a characteristic granular alteration of the arterial media that ultrastructurally corresponds to the accumulation of electron-dense material surrounding the smooth muscle cells. Although the presence of this granular osmiophilic material (GOM) was originally described as limited to brain vessels, identical electron microscopic findings have been demonstrated in the media of peripheral tissue arteries, allowing for a pathologic diagnosis of the disease by a simple skin, muscle or nerve biopsy. We report some atypical features identified in our cadasil patients that broaden the phenotypic expression of this disease. Firstly, we identified a cortical infarct in an otherwise typical cadasil patient. Secondly, we observed GOM in skin arteries of a 30-year-old man with hemiplegic migraine, the son of a woman who had died with cadasil. This confirms that it may be possible to diagnose the disease at a preclinical stage by the ultrastructural evaluation of peripheral tissue biopsy material, particularly for individuals for whom there is a supporting family history. Thirdly, ultrastructural examination of the skin, and subcutaneous and striated muscle of an unrelated and apparently sporadic patient with neuropathologic and neuroradiologic evidence of cadasil in meningeal and cerebral vessels failed to reveal diagnostic lesions in peripheral arteries. Thus, the possibility of a false-negative pathologic diagnosis in patients with a clinicoradiologic diagnosis of cadasil, if one relies solely on a peripheral tissue biopsy, does exist. Additionally, we have identified heat shock proteins (Hsp70 and alphaB crystallin) and ubiquitin in the vascular myocytes of affected arteries.- - - - - - - - - - ranking = 2keywords = vessel (Clic here for more details about this article) |