Cerebral and retinal vascular complications of inflammatory bowel disease.

Recurrent retinal branch artery occlusions, carotid thromboembolism, cerebral venous thrombosis, transient brainstem ischemia, and massive brainstem and cerebral infarction complicated the course of inflammatory bowel disease in 5 patients. Three patients had ulcerative colitis and 2 had regional enteritis. The usual risk factors for stroke were absent. Neuropathological examination in 1 patient showed in situ thrombosis of small cerebral and brainstem arteries and veins. Coagulation studies showed thrombocytosis, short partial thromboplastin times, and elevation of fibrinogen and Factor VIII levels. Platelet counts and coagulation factors returned toward normal after control of intestinal inflammation in each of the 4 surviving patients. Inflammatory bowel disease can be accompanied by a hypercoagulable state that predisposes to stroke.     

Cerebral amyloid angiopathy: the vascular pathology and complications

Twenty-five cases with cerebral amyloid angiopathy (CAA) were studied. Senile plaques (SP) were present in all cases. In only eight cases which also displayed either SP (two cases), or both SP and Alzheimer's neurofibrillary tangles (NFT) (six cases), was there a history of dementia. In five cases, SP and NFT were observed without a history of dementia. Seven cases had significant cerebral hemorrhage, single or multiple, which could be related to CAA. Ten cases had cerebral infarcts, but only in seven of these cases could the infarcts be related to CAA. In five cases, with moderate to severe CAA and no history of dementia other distinctive vascular changes were also noted in the brain. These CAA-associated vasculopathies (CAA-AV) consisted of: clusters of multiple arteriolar lumina, the so-called "glomerular" formations, with various degrees of amyloid infiltration; aneurysmal vessels with amyloid infiltration; obliterative intimal changes; "double barreling", chronic inflammatory perivascular or transmural infiltrates; hyaline (nonamyloid) arteriolar degeneration, with or without aneurysmal dilatation; and fibrinoid necrotizing vascular change. In all five cases with CAA-AV, there were cerebral infarcts or hemorrhages which were considered to be direct complications of amyloid angiopathy, or of the vasculopathies developing secondary to the amyloid infiltration of vessel walls. It is possible that the associated vasculopathies represented secondary vascular changes that followed amyloid deposition in the blood vessel walls.     

Natural history of lacunar syndromes. Contribution of the Dijon registry of cerebrovascular complications

In a consecutive series of 984 first-ever strokes (from 1985 to 1989) in a population based study, 165 (16.7%) had lacunar infarction confirmed by CT-scan or M.R.I. The annual incidence was 35.6/100,000 in women, and 47.8/100,000 in men. Survival rates were 90% at 1 month, and 78% at 2 years. The rate of recurrent strokes was 11% at 2 years. The natural history of lacunar infarction could be drawn in this study which was population-based; 29% of lacunar infarctions are indeed not managed in hospitals. Lacunar infarctions should be identified as such in therapeutic trials since their course is clearly different from other types of strokes.     

Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes

Ten histologic sections were sampled from similar cortical regions in each of 84 autopsy brains removed from patients aged 60 to 97 years. The sections were stained by the Congo-red method and examined under polarized light for the presence of cortical (parenchymal) cerebral amyloid angiopathy (CAA). Some degree of CAA was found in 36% of all brains examined, with a higher proportion of patients affected in each successive decade of life. Angiopathy was seen most frequently and was of greater severity in the parietal and occipital gray matter. Overall, it was often a patchy and asymmetric lesion. There was sparing of subcortical white matter and the hippocampi. CAA was most severe in cases of Alzheimer's disease, but occurred in the absence of this condition.     

Cerebral amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage

The clinical and pathologic findings in eleven patients with fatal cerebral hemorrhages related to cerebral amyloid angiopathy (CAA) are described. The hemorrhages were bihemispheric, though not necessarily of simultaneous onset in four patients, and favoured the fronto-parietal cortex and white matter in ten patients. Dissection into the subarachnoid space was common. Cerebrovascular lesions or cardiomegaly related to hypertension coexisted with those of CAA in three cases. Seven patients were not demented prior to the ictus. Ten of eleven brains contained abundant senile plaques and/or neurofibrillary tangles, whether or not the patient had been clinically demented. In the elderly, CAA is an important etiologic consideration for cerebral hemorrhage, especially if the hemorrhage occurs in a peripheral location in the brain and is superimposed on a history of dementia.     

Incidence of vascular hemiballism in the population of Belgrade.

Hemiballism is a relatively rare hyperkinetic disorder with unknown incidence. Stroke is the most common cause of hemiballism (vascular hemiballism), responsible for the disorder in 50% to 100% of cases. We studied the incidence of vascular hemiballism in the population of Belgrade (Serbia) 40 years of age or older during the period 1 January 1991 to 31 December 2002. During that time period, 37 patients with hemiballism due to stroke were diagnosed. The annual incidence rates varied from 0.14 to 0.87/100,000 (average 0.45/100,000) of general population.     

Angiogenesis in gestational vascular complications

Vascular endothelial growth factor (VEGF) is a key player in vasculogenesis and angiogenesis in the embryo, and essential in neovascularization in adults. Natural VEGF inhibitors such as soluble VEGF receptors, among them the soluble VEGF-trapping receptor Flt1 (sFlt1), participate in VEGF regulation. Decreased levels of VEGF and increased levels of sFlt1 have been implicated in the pathophysiology of preeclampsia. We discovered a soluble receptor, sFlt1-14, qualitatively different from sFlt1 and a potent VEGF inhibitor. It is generated in a cell type specific fashion, primarily in nonendothelial cells, most notably in vascular smooth muscle cells. We showed that increased production of soluble VEGF receptors in pregnancy is owing to expression of sFlt1-14, from the end of the first trimester to term. This expression is markedly elevated in preeclampsia, and is expressed chiefly by syncitial knots. In subsequent studies we found that sFlt1 is a strong heparin binder: this capability enables it to stay attached to blood vessels and to the placenta. Ex vivo, sFlt1 can be heparin displaced to medium from aortic segments and placental villi. In vivo, pregnant women treated with the low molecular weight heparin (LMWH) have elevated sFlt1 levels in their circulations. Interestingly, LMWH raised VEGF levels over and above the increase in sFlt1 levels in these patients. Heparanaseoverexpressing non-pregnant as well as pregnant transgenic mice present elevated levels of sFlt1 in their circulations. Ex vivo prevention of heparanase maturation through cathepsin L inhibition, or targeting heparanase directly with a neutralizing antibody, both resulted in a marked reduction in sFlt1 secretion to medium of normal and preeclamptic placental expiants. These findings uncover a new level of regulation that controls sFlt1 bio-distribution, and directs it to function in the vicinity of its producing cell. Heparanase or LMWH has the ability to liberate sFlt1 from its retention, so this process may be a potential target for preeclampsia treatment.     

Cerebral haemorrhage in a French prospective population study.

The incidence of cerebral haemorrhage was studied from a population-based stroke registry. The incidence was 12.3 per 100,000 per year in women and 13.9 per 100,000 per year in men, with a peak in the eighth decade and a male preponderance. Haemorrhages were deep seated and mostly due to hypertension. Recognised clinical characteristics of haemorrhage are acute onset, convulsion, vomiting, and disturbed consciousness. This study showed that cerebral haemorrhage may present with pure motor deficit or transient deficit preceding the stroke. The mortality was 51% in the first month, and 61% by two years.     

Cerebral complications of coronary by-pass surgery. A prospective study

ABSTRACT— A prospective study was undertaken of cerebral complications in 91 patients undergoing coronary by-pass surgery. Patients showing clinically relevant neurological complications had longer pump-times but did not differ in pre-operative variables. Worsening of neurological state correlated with duration of pump-time but not with pre-operative variables. Duration of pump-time appears to be the main predictor of neurological complications after coronary by-pass surgery.     

脑血管病患者的脑血流自身调节潜力分析

目的 应用TCD和倾斜试验评价脑血管病患者的脑血流自身调节.方法 脑血管狭窄患者32例(A组),无血管狭窄的脑梗死患者28例(B组),健康对照26名.通过呼吸试验计算呼吸抑制指数(BHI)及血管运动反应性(VMR)评价脑小血管CO2反应性;头高位70°倾斜试验改变体位,记录卧立位脑血流速度(CBFV)及血压、心率,评价脑小血管的血压-自动调节.结果 与对照组比较,A组、B组VMR(分别为0.18±0.02和0.26±0.04,对照组为0.43±0.06)、BHI(分别为0.76±0.15和1.05±0.15,对照组为1.52±0.19)显著降低(P＜0.05).A组患侧与对侧VMR(分别为0.10±0.01、0.22±0.02)及BHI(分别为0.51±0.14、0.94±0.16),差异有统计学意义(P＜0.05).A组患侧BHI值小于0.69(P＜0.05).Logistic回归分析显示BHI下降与脑梗死相关(B=2.234,P=0.016).直立位时血压、心率增加,CBFV下降.3例直立性低血压患者直立位血压和CBFV均显著下降,二者之间相关(r=0.430,P=0.004).结论 脑梗死及脑血管狭窄患者脑小血管CO2反应性受损.自身调节能力受损,卒中风险可能增加.直立位时,机体通过提高周围血压和心率,参与颅内自动调节.     

Involvement of microparticles in diabetic vascular complications

Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear. We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels of MPs originated from platelet and endothelial cells and negatively-charged phospholipid-bearing MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (<0.7) but high in patients with coronary artery disease and foot ulcers (>1.8, p≥0.002). MPs of all T2DM patients induced a more than two-fold increase in endothelial cell TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were longest and most stable in endothelial cells that were incubated with MPs of healthy controls, whereas no tube formation occurred in MPs of diabetic patients with coronary artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced branched tube networks that were unstable and collapsed over time. This study demonstrates that MP characteristics are related to the specific type of vascular complications and may serve as a bio-marker for the pro- coagulant state and vascular pathology in patients with T2DM.     

Cerebral blood flow regulation: vascular resistance adjustments in the circle of Willis.

Continuous measurements of systemic blood pressure (BP), cerebral perfusion pressure and CBF were accomplished in the cat during transient hypertension, hypercapnia and bilateral carotid artery occlusion. From these measurements resistance values in the circle of Willis and in the cerebral arteries distal to the circle were calculated. The results indicate that the arteries of the circle of Willis and the arteries distal to the circle of Willis dilate and contract independently.     

Cerebral perfusion and vascular reserve in fibromuscular dysplasia of the internal carotid artery.

We report of a case of abnormal cerebral perfusion but normal vascular reserve by single-photon emission computed tomographic imaging in a 65-year-old woman with fibromuscular dysplasia of the internal carotid artery (ICA). The patient had an aneurysm in her left ICA at the level of second cervical vertebra without evidence of stenosis and was excised with primary anastomosis 3 years ago when she presented with months of dizziness. But follow-up angiography showed high-grade long segmental stenosis in her left ICA, characteristic of fibromuscular dysplasia. Because she was asymptomatic with normal vascular reserve, she was treated medically. This report suggests the usefulness of functional imaging in fibromuscular dysplasia. The potential improvement of cerebral perfusion in this rare disease with acetazolamide or dipyridamole is worthy of further clinical investigation.