Autopsy study of cerebrovascular disease in Japanese men who lived in Hiroshima, Japan, and Honolulu, Hawaii

Evidence of cerebrovascular disease at autopsy was compared in 2 groups of men: 186 long-time residents of Hiroshima, Japan, and 253 men of Japanese ancestry long resident in Honolulu, Hawaii. They were 45 to 71 years-of-age at death. Atherosclerosis of the circle of Willis and its major branches, sclerosis of the intraparenchymal arteries and the frequency of cerebral hemorrhage and cerebral infarct were compared in the 2 populations. The Honolulu subjects had significantly more atherosclerosis of the circle of Willis, but less intraparenchymal artery sclerosis and less cerebral infarction. Cerebral hemorrhage was equally frequent in the 2 cities. It was concluded that cerebral infarction is more frequent in Japanese men in Hiroshima than Honolulu, and that men of Japanese ancestry in Honolulu are spared an appreciable risk of cerebral infarction through decreased frequency of intraparenchymal arterial sclerosis despite higher levels of atherosclerosis of large intracranial arteries.     

Concentrations of putative neurovascular transmitters in major cerebral arteries and small pial vessels of various species

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were dramatically reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various species; the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.     

Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles

The role of intracranial atherosclerosis in Alzheimer's disease (AD) has been a subject of debate since the first decade of the last century. The initial "vascular hypothesis" of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods, however, and the investigators did not appear to consider the possibility that intracranial atherosclerosis might have a probabilistic, rather than an absolute, effect on AD risk. Recent studies by three independent groups have found a significant statistical association between postmortem measures of circle of Willis atherosclerosis and AD. The present study was undertaken to further address the validity of this association in a large autopsy series, including cases diagnosed neuropathologically with vascular dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of circle of Willis atherosclerosis was performed in 397 subjects classified by neuropathological diagnosis, including 92 non-demented elderly controls, 215 with AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis was more severe in subjects with AD and VaD than in control subjects, while it was equivalent between control subjects and subjects with non-AD dementias. Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses of both AD and VaD and also increased the ORs for both increased neuritic plaque density and higher Braak neurofibrillary tangle stage. The significance of these associations was retained after consideration of the effects of age, gender and the apolipoprotein E-epsilon4 allele. The results suggest that the statistical association between intracranial atherosclerosis and AD is not an artifact of diagnostic misclassification or of unequal distribution of the apolipoprotein E-epsilon4 allele.     

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.     

Intracranial hemorrhage in autopsy cases with occlusion of the circle of Willis (author's transl)

Seventeen autopsy cases with occlusion of the circle of Willis were examined clinicopathologically. These patients ranged in age from 8 years to 64 years and consisted of 6 males and 11 females. The following results were obtained. 1. Fresh and massive intracerebral hemorrhage was confirmed in 13 of 17 patients and cerebral infarct in 4 of 17 patients. 2. Among these 13 patients, massive hemorrhage was found in basal ganglia, thalamus and hypothalamus of 9 patients, and in thalamus, cerebral peduncle and midbrain of 4 patients. 3. Rupture of the dilated muscular-type arteries was noted in the thalamus and basal ganglia in 2 of 13 patients. Ruptured arteries with organization of the lumen were found in the old hemorrhagic foci in one of them. 4. Overgrown and dilated arteries, branching off from the circle of Willis, were confirmed in 11 patients. These arteries consisted of "perforating" arteries well developed as collateral circulation. 5. No ruture in these arteries of the subarachnoidal spaces was found in 11 patients. In one of them, a small saccular aneurysm was found. These findings strongly suggest that in patients with occlusion of the circle of Willis intracerebral rupture of overgrown "perforating" arteries as collateral circulation may be the main cause of intracranial hemorrhage and intracerebral hemorrhage due to rupture of the arteries may be repeated.     

Ventral porencephaly: A cerebral defect associated with multiple congenital anomalies

Summary An infant with multiple congenital anomalies was found at autopsy to have a porencencephalic defect on the ventral surface of the left frontal lobe. The intracranial defect was seen in association with an anomalous configuration of the circle of Willis. The zone of tissue destruction corresponded to the vascular territory of the anterior choroidal and lenticulo-striate branches of the proximal middle cerebral arteries, which were absent on the left. The developmental anomaly of the circle of Willis may have predisposed to tissue destruction by compromising cerebral perfusion at midgestation, a stage of rapid brain growth.Supported in part by USPS grants. M 16674, MH 25515 and MH 01215     

Evidence for the presence of cholinergic nerves in cerebral arteries: an immunohistochemical demonstration of choline acetyltransferase

The presence of cholinergic nerves in cerebral arteries of several species was investigated by an immunohistochemical method using antibodies against choline acetyltransferase (ChAT). In cats, pigs, rats, and dogs, ChAT immunoreactivities were found to be associated with large bundles and single fibers in the circle of Willis and anterior cerebral, middle cerebral, and basilar arteries. In the rabbit, the ChAT-immunoreactive (ChAT-I) nerves were also observed in the circle of Willis and anterior and middle cerebral arteries, but only few or none were found in the basilar and vertebral arteries. The ChAT-I nerves were found only in the adventitial layer of vessels examined. Superior cervical ganglionectomy did not appreciably affect the distribution of ChAT-I nerves. These results indicate the presence of cholinergic nerves in cerebral arteries. The distribution pattern of ChAT-I nerves was different from that of vasoactive intestinal polypeptide (VIP)-like-immunoreactive nerves and acetylcholinesterase-positive nerves. The possible coexistence of ChAT and VIP-like substance in the same neuron is discussed.     

Interaction of cardiovascular disease and neurodegeneration: transcranial Doppler ultrasonography and Alzheimer's disease

OBJECTIVE: Recent post-mortem studies have reported that the severity of atheromatous deposits in the circle of Willis is significantly greater, relative to non-demented (ND) elderly persons, in subjects with neuropathologically diagnosed Alzheimer's disease (AD). Additionally, the severity of intracranial atherosclerosis correlates significantly with the densities of neuritic plaques and neurofibrillary tangles. In this study, we examine the arteries of the circle of Willis by transcranial Doppler (TCD) ultrasonography. METHODS: TCD was used to measure, in 25 AD patients and 30 ND elderly subjects, mean flow velocities and pulsatility indices in 16 different segments of the circle of Willis. The data were compared with and without adjustment for age, gender and systolic blood pressure. RESULTS: The AD patients had systematically higher pulsatility indices (p<0.005) than the ND group. Incremental increases of pulsatility indices in these segments had odds ratios ranging from 1.8 to 48 for the presence of AD when adjusted for age, gender and systolic blood pressure. The left internal carotid artery siphon and the left posterior cerebral artery were the two vessels that were strongly associated with AD diagnosis. Mean flow velocities were generally lower in patients with AD but the differences did not reach the significance level. DISCUSSION: The pulsatility indices of the arteries of AD patients were generally greater than those of similarly-aged ND subjects. This difference is most likely due to increased arterial wall rigidity imposed by atherosclerotic changes. Atherosclerotic disease of intracranial arteries may be a risk factor for AD.     

大动脉粥样硬化型与小动脉闭塞型青年缺血性卒中高危因素相关分析

目的探讨青年缺血性卒中两种不同病因分类亚型的高危因素的差别。方法收集北京大学第一医院神经内科(2006-2011年,18～45岁)缺血性卒中病人。入选66例,分为大动脉粥样硬化组(46例)及小动脉闭塞组(20例)。以性别、年龄、既往病史(包括高血压、糖尿病、长期大量吸烟、饮酒史)以及周围血检测(甘油三脂、低密度脂蛋白、高密度脂蛋白、同型半胱氨酸)研究变量。结果单变量分析发现大动脉粥样硬化组低密度脂蛋白升高率及甘油三酯升高率与小动脉闭塞组比较有显著性差异(P<0.05)。小动脉闭塞组血压升高率与大动脉粥样硬化组比较有显著性差异(P<0.05),其他高危因素比较差异无显著性意义(P>0.05)。logistic回归分析发现甘油三酯升高率(wald=4.372,95%CI 0.089-0.925,p=0.037)与大动脉粥样硬化性青年缺血性卒中有关。高血压(wald=4.764,95%CI 1.196-21.986,p=0.029)与小动脉闭塞性青年缺血性卒中有关。结论两种不同病因的青年缺血性卒中主要致病高危因素不同,大动脉粥样硬化型需要更好的调控血脂,尤其是甘油三酯,而小动脉闭塞型需要更好的控制血压。     

The arterial patterns associated with internal carotid disease and cerebral infarcts

In 20 necropsies with 15 stenosed and 17 thrombotic occluded internal carotid arteries there were 46 cerebral infarcts larger than 1 cm diameter. Using portmortem arteriographic and pathological techniques the patterns of the neck and brain artery systems were correlated with the situation and extent of the brain infarcts. Massive infarcts involving two major cerebral artery territories were associated with distal internal carotid artery occlusion and grossly ineffective cervical and circle of Willis anastomoses. Isolated middle cerebral artery territory infarcts were associated with internal carotid occlusion or stenosis and impairment of the circle of Willis anastomoses, perhaps with middle cerebral artery stenosis. The pattern of adequate size arteries determined if these infarcts were total, deep central, anterior, medium or posterior partial territory infarcts. Boundary zone infarcts were associated with internal carotid artery disease and limitation of anterior or posterior circle of Willis anastomoses. These limitations determined which boundary zones were affected. Isolated anterior cerebral artery territory infarcts were associated with bilateral internal carotid disease and an anterior cerebral artery stenosis or small caliber anterior communicating artery. Isolated posterior cerebral artery territory infarcts were associated with internal carotid disease and a direct impairment of the ipsilateral posterior cerebral artery capability.     

Serum autoantibodies to actin are associated with carotid artery wall adventitial thickness assessed using B-mode ultrasound

Atherosclerosis, as a chronic inflammatory condition, can be mediated by immunological reactions. Therefore, it is possibly related to a specific antigen. Because autoimmunological reactions occur during atherogenesis, it is possible that alpha-actin expression induces a specific autoimmune reaction. We determined whether the intima-media (IMT) and adventitial thickness (AT) of carotid arteries, assessed by an ultrasound method, correlate with the level of anti-actin autoantibodies (AAA) in human serum. The study involved a group of 128 patients (66 women and 62 men). The mean age was 65.0 (+/- 7.9) years. Fifty-four patients had suffered an ischaemic stroke, whereas the remaining (as controls) had no history of cerebrovascular disease. High-resolution ultrasonography was used to evaluate the IMT and AT of their common carotid arteries. The mean carotid IMT was 0.95 (+/- 0.36) mm and the mean AT was 0.94 (+/- 0.20) mm. There was a significant correlation between carotid AT and the AAA serum level (r = 0.20; p = 0.024). However, there was no association between the mean IMT and AAA serum levels in the carotid arteries (r = 0.08; p = 0.328). In this preliminary (in vivo) study, we found that the level of AAA correlated positively with ultrasonographically assessed AT during carotid atherosclerosis.     

Evaluation of cross-circulation through circle of Willis using an ultrasonic Doppler technique. Part I. Comparison between blood flow velocity by ultrasonic Doppler flowmetry and angiogram

In 24 patients with cerebrovascular disease and 6 without organic brain lesions, the increased velocity of blood flow in both the internal carotid and vertebral arteries during a contralateral carotid compression was compared with the angiographic appearance of the circle of Willis. The flow velocity was measured using ultrasonic Doppler flowmetry. It was not possible to investigate fully the relationship between the increase of velocity of blood flow in the internal carotid artery and the anatomical variations of the circle of Willis, specifically the anterior cerebral and communicating arteries. The velocity of flow in the patients with an aplastic proximal portion of the anterior cerebral artery showed no increase. There were no differences in the increase of velocity of flow in the vertebral artery in patients with hypoplastic, normal and fetal posterior communicating arteries. It is considered that although anatomical variations of the circle vessels influence the cross-circulation via the circle of Willis, peripheral vascular factors distal to the circle also play an important role in the quantity of cross-circulation through the circle.     

Visualization of the Cerebral Circulation Using Three–dimensional Transcranial Power Doppler Ultrasound Imaging

The purpose of this study was to evaluate the anatomy of the cerebral circulation, particularly the circle of Willis, using three–dimensional ultrasound (3DUS) imaging. Image data were obtained through the right transtemporal window from 8 young, healthy volunteers by acquiring gray–scale and color Doppler spectral (CDI) and energy (CDE) images using two–dimensional ultrasound equipment with a 2–MHz probe. Images and transducer position coordinates were fed into a graphics workstation, reprojected, analyzed to extract the blood flow signal, volume rendered, and displayed interactively. The architecture of the cerebral circulation was evaluated from multiple orientations using stereo viewing glasses and rotation to enhance the understanding of vessel position. The primary vessels of the cerebral circulation including the circle of Willis and bilateral views of the branching arteries (middle, anterior, and posterior cerebral arteries and internal carotid artery) could be imaged readily with 3DUS through one transtemporal window. Acquisition time was typically less than 30 seconds. Volume–rendering methods greatly assisted in showing the overall spatial relationships and continuity of cranial vessels. Secondary branches of the cerebral arteries were seen in 2 patients. Color data from two–dimensional ultrasound imaging that otherwise might be identified as artifact was found to represent continuous small vessels on three–dimensional viewing. 3DUS facilitates imaging of cranial vascular anatomy by clarifying overall spatial relationships and enhancing comprehension, compared to two–dimensional ultrasound methods. The method is rapid and the circle of Willis can be visualized from one side of the head.     

Vascular dysplasia in Down syndrome: a possible relationship to moyamoya disease.

The brain of a child with Down syndrome (DS) and vascular abnormalities is described. Neuropathological examination showed a large cerebral infarction. In the circle of Willis there was hypoplasia of the left middle and posterior communicating cerebral arteries, and microscopically there was thickening of intima and focal disruption of internal elastica in some areas of the circle of Willis. Several reports suggest that the incidence of moyamoya disease is higher in children with DS than in other children. The high incidence of congenital heart disease in DS suggests an abnormality of vascular development that may manifest intracranially as a structural vascular defect, creating a vulnerability to unknown factors important in the pathogenesis of the moyamoya abnormality.     

Collateral variations in circle of willis in atherosclerotic population assessed by means of transcranial color-coded duplex ultrasonography

BACKGROUND AND PURPOSE: Transcranial color-coded duplex ultrasonography combined with common carotid artery (CCA) compression can be used to assess the collateral function of the circle of Willis. The aim of this study was to assess the unknown fraction of hemodynamic functional anterior and posterior communicating arteries (AcoA and PcoA, respectively) in an atherosclerotic population with no cerebrovascular symptoms. METHODS: In 76 patients with a mean age of 61 (35 to 89) years, the blood flow velocity changes in the precommunicating parts (A1 and P1, respectively) of the anterior and posterior cerebral arteries were measured during CCA compression. The AcoA was defined as functional if blood flow was reversed in the ipsilateral A1 and enhanced in the contralateral A1 during CCA compression. The PcoA was defined as functional if the flow velocity in the P1 was enhanced >20% during ipsilateral CCA compression. RESULTS: It was possible to assess cross flow through the anterior part of the circle of Willis in 95% of the subjects. Failure of this collateral pathway was caused by a hypofunctional AcoA in 4% and a hypofunctional A1 in 1% of the subjects. Anomalies in the posterior part of the circle of Willis hampering collateral flow from the basilar to the internal carotid artery were found in 45% of the hemispheres. Thirty-eight percent of PcoAs were hypofunctional, and 7% of the posterior cerebral arteries had a persistent fetal anatomy. CONCLUSIONS: We found that in subjects with no cerebrovascular symptoms, the anterior collateral pathway of the circle of Willis was nearly always functional. In contrast, the posterior collateral pathway was nonfunctional in almost half of the total number of hemispheres. Comparing these basic data with data from patients with cerebral ischemic disease might further help to elucidate the importance of the collateral capacity of the circle of Willis.     

Collateral configuration of the circle of Willis: transcranial color-coded duplex ultrasonography and comparison with postmortem anatomy

BACKGROUND AND PURPOSE: The anterior communicating artery (AcoA) and posterior communicating arteries (PcoA) of the circle of Willis provide the main route for collateral blood flow in cases of carotid artery obstruction. Transcranial color-coded duplex ultrasonography (TCCD) allows real-time measurement of the collateral function of the AcoA and PcoA. The primary objective of this study was to determine the collateral artery threshold diameters for supplying collateral flow. METHODS: In 12 acute stroke patients with a median age of 75 years (51 to 91 years), the collateral integrity of the circle of Willis as assessed by TCCD and carotid compression tests was compared with their postmortem anatomy. The lengths and diameters of the collateral arteries were measured. RESULTS: TCCD demonstrated absent anterior collateral flow in 3 patients. In 1 of these patients, absence of anterior cross-flow was due to an occluded anterior cerebral artery, which was revealed at autopsy. Absent posterior collateral flow was found in 14 hemispheres. In 2 of these hemispheres, autopsy revealed a fetal configuration of the posterior cerebral artery hampering posterior collateral flow. The median (range) diameters as found at autopsy of the functional (n=19) and nonfunctional (n=16) collateral arteries of the circle of Willis were 1.1 (0.4 to 2.0) and 0.5 (0.3 to 0.7) mm, respectively (P=0.003). PcoA diameters were found to correlate negatively (rho=-0. 50, P=0.01) to the diameters of their accessory P1 segments. CONCLUSIONS: The threshold diameter allowing for cross-flow through the primary collateral arteries of the circle of Willis is between 0. 4 and 0.6 mm.     

Cerebral aneurysms and variations in the circle of Willis

In order to obtain information about the relationship between variations in the circle of Willis and aneurysms, 44 complete circles of Willis with aneurysm were studied macroscopically. The incidence of variations was significantly higher in the aneurysm series than in the control circles without aneurysm. There was a definite correlation between asymmetric proximal segments of the anterior cerebral artery and aneurysms of the anterior communicating artery, and a tendency to correlation was found in the case of asymmetric posterior communicating arteries and aneurysms on the internal carotid artery-posterior communicating artery junction. In the light of these findings it seems likely that through hemodynamic changes variation in the circle of Willis plays some role in the development of cerebral aneurysms.     

Subcortical arteriosclerotic encephalopathy (Binswanger''s type) and cortical infarcts in a young normotensive patient.

A 49-year-old normotensive man died after a series of strokes, slowly evolving dementia and personality change occurring over a period of 23 years. CT scan showed large infarcts involving the cortex and white matter of the temporo-occipital areas, small subcortical infarcts and low attenuation in the white matter of the frontal and parietal lobes. Neuropathological examination revealed large cortical and small subcortical infarcts corresponding to the radiological findings as well as degeneration/demyelination of central white matter corresponding to the areas of low attenuation seen on CT. The basic underlying pathological process was hyaline arteriosclerosis and atheroma which diffusely affected the small intracerebral arteries and to a lesser extent the arteries of the circle of Willis. Though usual because of the absence of hypertension, the very early age at onset of the syndrome and the presence of large cortical infarcts this case illustrates the clinical, radiological and neuropathological features of subcortical arteriosclerotic encephalopathy (Binswanger's type).     

Serum alpha-1 antitrypsin in acute ischemic stroke: A prospective pilot study

BackgroundAlpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels.MethodsWe performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables.ResultsAmong eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038)ConclusionsMeasurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.     

Some cholecystokinin-8 immunoreactive fibers in large pial arteries originate from trigeminal ganglion

Cholecystokinin-8 immunoreactive (CCK8I) nerve fibers were demonstrated in whole mount preparations and cross-sections of pial blood vessels in the cat, guinea pig and rat using a specific antiserum and the avidin-biotin-peroxidase complex method. Positive fibers were present in nearly all pial arteries examined, and were located in the adventitial layer and at the junction of the adventitia and media. In general, CCK8I fibers were less abundant than substance P immunoreactive (SPI) fibers visualized in the same vessels. A marked depletion of CCK8I was noted in large cerebral arteries following treatment of adult guinea pigs with capsaicin, a drug shown previously to deplete CCK8 in some primary sensory neurons. The density of CCK8I-containing fibers was also decreased in the ipsilateral vessels of the cat circle of Willis following unilateral trigeminal ganglionectomies. These results indicate that CCK8I is contained in afferent fibers within large pial arteries of Willis' circle which project from neurons in the ipsilateral trigeminal ganglion. Whether CCK8 coexists with SP in these fibers remains to be determined.