Chu, Heling; Huang, Chuyi; Ding, Hongyan; Dong, Jing; Gao, Zidan; Yang, Xiaobo; Tang, Yuping; Dong, Qiang
Cerebrovascular diseases are conditions caused by problems with brain vasculature, which have a high morbidity and mortality. Aquaporin-4 (AQP4) is the most abundant water channel in the brain and crucial for the formation and resolution of brain edema. Considering brain edema is an important pathophysiological change after stoke, AQP4 is destined to have close relation with cerebrovascular diseases. However, this relation is not limited to brain edema due to other biological effects elicited by AQP4. Till now, multiple studies have investigated roles of AQP4 in cerebrovascular diseases. This review focuses on expression of AQP4 and the effects of AQP4 on brain edema and neural cells injuries in cerebrovascular diseases including cerebral ischemia, intracerebral hemorrhage and subarachnoid hemorrhage. In the current review, we pay more attention to the studies of recent years directly from cerebrovascular diseases animal models or patients, especially those using AQP4 gene knockout mice. This review also elucidates the potential of AQP4as an excellent therapeutic target. PMID:27529222
Walcott, Brian P; Peterson, Randall T
Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish (Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens.
Colombo, Gianluca; Merico, Daniele; Boncoraglio, Giorgio; De Paoli, Flavio; Ellul, John; Frisoni, Giuseppe; Nagy, Zoltan; van der Lugt, Aad; Vassányi, István; Antoniotti, Marco
The NEUROWEB project supports cerebrovascular researchers' association studies, intended as the search for statistical correlations between a feature (e.g., a genotype) and a phenotype. In this project the phenotype refers to the patients' pathological state, and thus it is formulated on the basis of the clinical data collected during the diagnostic activity. In order to enhance the statistical robustness of the association inquiries, the project involves four European Union clinical institutions. Each institution provides its proprietary repository, storing patients' data. Although all sites comply with common diagnostic guidelines, they also adopt specific protocols, resulting in partially discrepant repository contents. Therefore, in order to effectively exploit NEUROWEB data for association studies, it is necessary to provide a framework for the phenotype formulation, grounded on the clinical repository content which explicitly addresses the inherent integration problem. To that end, we developed an ontological model for cerebrovascular phenotypes, the NEUROWEB Reference Ontology, composed of three layers. The top-layer (Top Phenotypes) is an expert-based cerebrovascular disease taxonomy. The middle-layer deconstructs the Top Phenotypes into more elementary phenotypes (Low Phenotypes) and general-use medical concepts such as anatomical parts and topological concepts. The bottom-layer (Core Data Set, or CDS) comprises the clinical indicators required for cerebrovascular disorder diagnosis. Low Phenotypes are connected to the bottom-layer (CDS) by specifying what combination of CDS values is required for their existence. Finally, CDS elements are mapped to the local repositories of clinical data. The NEUROWEB system exploits the Reference Ontology to query the different repositories and to retrieve patients characterized by a common phenotype.
Mehanna, Raja; Jankovic, Joseph
Movement disorders can occur as primary (idiopathic) or genetic disease, as a manifestation of an underlying neurodegenerative disorder, or secondary to a wide range of neurological or systemic diseases. Cerebrovascular diseases represent up to 22% of secondary movement disorders, and involuntary movements develop after 1-4% of strokes. Post-stroke movement disorders can manifest in parkinsonism or a wide range of hyperkinetic movement disorders including chorea, ballism, athetosis, dystonia, tremor, myoclonus, stereotypies, and akathisia. Some of these disorders occur immediately after acute stroke, whereas others can develop later, and yet others represent delayed-onset progressive movement disorders. These movement disorders have been encountered in patients with ischaemic and haemorrhagic strokes, subarachnoid haemorrhage, cerebrovascular malformations, and dural arteriovenous fistula affecting the basal ganglia, their connections, or both.
Rocha, M S; Brucki, S M; Ferraz, A C; Piccolo, A C
We report three cases of stroke secondary to neurocysticercosis. The first one is a 36 years old man with bilateral middle cerebral artery occlusions who had presented acute right hemiparesia and aphasia. MRI demonstrated several enhancing subarachnoid cysts surrounding the occluded vessels, a right parietal racemose cyst and a left temporal large infarction area. Angiographic study showed total occlusion of left middle cerebral artery and a subtotal occlusion of right middle cerebral artery. The second one is a 42 years old man with vasculitis of small cortical vessels who presented with headache, seizures and focal neurological deficit. CT scan demonstrated several calcifications and a left temporal infarction area. Cerebral angiographic study was normal. The third case was a woman, 53 years old, with a past history of six stroke events and an actual behavior disturbance and seizures. MRI demonstrated several cortical and subcortical infarction areas and cisternal cysts. Angiographic study showed diffuse arteritis of basilar and carotid arterial system. In all three cases CSF study showed linfomonocitic pleocytosis and positive ELISA for cysticercosis.
Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei
The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19-1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19-1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31-1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04-1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02-1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31-1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16-1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72-1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56-1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06-1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is associated with increased
Fan, Z; Li, F; Wang, Z; Huang, Z; Yi, Y; Zhang, Z; Yang, Z; Zhang, H; Ma, Y; Zen, X
The relationship between the mortality of cerebro-vascular diseases and farmer smokers in Shifang County was studied. The results indicated that the mortality of cerebro-vascular diseases in the male groups of cigarette-smokers older than 65 and cigar-smokers older than 55 was significantly higher than that of the nonsmokers (P < 0.05), the RR being 1.68-3.22. Also, the mortality in the female groups of cigarette-smokers older than 55 and cigar-smokers older than 65 was significantly higher than that of the non-smokers (P < 0.05), the RR being 1.99-3.19. The sex-specific mortalities of the other age groups revealed no significant differences in spite of some inequalities in smoking (P < 0.05). Age should be one of the risk factors for the death of cerebro-vascular diseases regardless of the sex. The mortality rose with the increasing accumulated amount of smoking. The relationship was not significant between the mortality of cerebro-vascular diseases and short-term smokers with small dose (P > 0.05). However, when the accumulated amount reached certain degree, i.e. the smoker consumed cigar more than 270 kg or consumed cigarette more than 10,000 packs, the relationship between the behavior of cigar-smoking and cigarette-smoking and the mortality became apparent, the RR being 2.53-3.91 (P < 0.01).
Fujino, Yoshihisa; Iso, Hiroyasu; Tamakoshi, Akiko
This study prospectively examined the association between perceived noise exposure at work and cerebrovascular diseases among Japanese male workers. A baseline survey was conducted between 1988 and 1990, which involved 110,792 inhabitants (age range: 40-79 yr) from 45 areas throughout Japan. Subsequent causes of death were identified from death certificates. The analysis was restricted to 14,568 men free of a cerebrovascular diseases (age range: 40-59 yr) who were in work at the time of the baseline survey. All subjects completed a self-administered questionnaire at the baseline. This included a question regarding perceived noise exposure at work. The Cox proportional-hazards model was used to estimate the risks of perceived noise exposure for death due to cerebrovascular diseases. The model included age, smoking, alcohol consumption, educational level, perceived mental stress, past medical history, body mass index, hours of walking, hours of exercise, shift work, and job type. During the 190,777 person-years of follow-up, a total of 1,064 deaths were recorded, 98 from cerebrovascular diseases, 27 deaths from subarachnoid haemorrhage, 35 deaths from intracerebral haemorrhage, and 25 deaths from cerebral infarction. Noise exposure did not increase the risk of cerebrovascular diseases, subarachnoid haemorrhage, or cerebral infarction. However, perceived noise exposure increased the risk of intracerebral haemorrhage diseases (hazard ratio (HR)=2.38, 95%CI: 1.20, 4.71, p=0.013). Furthermore, individuals with hypertension were highly susceptible to the effect of perceived noise exposure on the risk of intracerebral hemorrhage, but this association was not observed among the subjects without hypertension. Although the underlying mechanisms are not clear, hypertensive individuals with perceived noise exposure at work should be regarded as a high-risk group for intracerebral hemorrhage.
Jing, J.; Wang, Y. C.; Hong, W. X.; Zhang, W. P.
Cerebrovascular Disease (CVD) is also called stroke in Traditional Chinese Medicine (TCM). CVD is a kind of frequent diseases with high incidence, high death rate, high deformity rate and high relapse rate. The pathogenesis of CVD has relation to many factors. In modern medicine, we can make use of various instruments to check many biochemical parameters. However, at present, the early detection of CVD can mostly be done artificially by specialists. In TCM the salted expert can detect the state of a CVD patient by felling his (or her) pulse. It is significant to apply the modern information and engineering techniques to the early discovery of CVD. It is also a challenge to do this in fact. In this paper, the authors presented a detection method of CVD basing on analysis and pattern recognition of Manifestation of the Pulse of TCM using wavelet technology and Neural Networks. Pulse signals from normal health persons and CVD patients were studied comparatively. This research method is flexible to deal with other physiological signals.
Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked. PMID:25401133
Kraft, Peter; Drechsler, Christiane; Gunreben, Ignaz; Nieswandt, Bernhard; Stoll, Guido; Heuschmann, Peter Ulrich; Kleinschnitz, Christoph
Background and Purpose In animal models, von Willebrand factor (VWF) is involved in thrombus formation and propagation of ischemic stroke. However, the pathophysiological relevance of this molecule in humans, and its potential use as a biomarker for the risk and severity of ischemic stroke remains unclear. This study had two aims: to identify predictors of altered VWF levels and to examine whether VWF levels differ between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods A case–control study was undertaken between 2010 and 2013 at our University clinic. In total, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HV) were included. Blood was taken at days 0, 1, and 3 in patients with AIS or TIA, and once in CCD patients and HV. VWF serum levels were measured and correlated with demographic and clinical parameters by multivariate linear regression and ANOVA. Results Patients with CCD (158±46%) had significantly higher VWF levels than HV (113±36%, P<0.001), but lower levels than AIS/TIA patients (200±95%, P<0.001). Age, sex, and stroke severity influenced VWF levels (P<0.05). Conclusions VWF levels differed across disease subtypes and patient characteristics. Our study confirms increased VWF levels as a risk factor for cerebrovascular disease and, moreover, suggests that it may represent a potential biomarker for stroke severity, warranting further investigation. PMID:24937073
Cai, Zhiyou; Zhao, Bin; Deng, Yanqing; Shangguan, Shouqin; Zhou, Faming; Zhou, Wenqing; Li, Xiaoli; Li, Yanfeng; Chen, Guanghui
The Notch signaling pathway is a crucial regulator of numerous fundamental cellular processes. Increasing evidence suggests that Notch signaling is involved in inflammation and oxidative stress, and thus in the progress of cerebrovascular diseases. In addition, Notch signaling in cerebrovascular diseases is associated with apoptosis, angiogenesis and the function of blood-brain barrier. Despite the contradictory results obtained to date as to whether Notch signaling is harmful or beneficial, the regulation of Notch signaling may provide a novel strategy for the treatment of cerebrovascular diseases. PMID:27574001
Rokey, R.; Rolak, L.A.; Harati, Y.; Kutka, N.; Verani, M.S.
Coronary artery disease is the cause of death in most patients who have transient ischemic attacks or stroke. Evaluation for this condition is not routinely performed in such patients, and no prospective studies have been reported. We prospectively examined 50 consecutive patients with transient ischemic attacks or mild stroke to determine the prevalence and importance of coronary artery disease. All patients were examined by a cardiologist and underwent both exercise thallium-201 scintigraphy and exercise radionuclide ventriculography. Sixteen patients were suspected to have coronary artery disease on the basis of clinical evaluation. In 15 of these the was confirmed by the nuclear scans. The remaining 34 patients had no clinical evidence of heart disease, yet 14 had abnormal cardiac scans. Twenty of 22 patients with abnormal scans who underwent cardiac catheterization had significant coronary artery disease or a cardiomyopathy. The discovery of heart disease altered clinical management in 13 patients. Overall, 29 of 50 patients had significant coronary artery disease, compared with a 7% prevalence of the condition in other patients of similar age at the same institution.
Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu
Long-term studies demonstrating the effect of pioglitazone use on primary prevention of ischemic cerebrovascular disease in older people with type 2 diabetes mellitus are lacking. This study investigated the relationship between pioglitazone use and first attack of ischemic cerebrovascular disease in Taiwan.We conducted a case-control study using the database of the Taiwan National Health Insurance Program. There were 2359 type 2 diabetic subjects aged ≥65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to 2011 as the case group and 4592 sex- and age-matched, randomly selected type 2 diabetic subjects aged ≥65 years without ischemic cerebrovascular disease as the control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic cerebrovascular disease associated with pioglitazone use was measured by the multivariable unconditional logistic regression model.After adjustment for confounding factors, the multivariable logistic regression analysis disclosed that the adjusted ORs of first attack of ischemic cerebrovascular disease associated with cumulative duration of using pioglitazone were 3.34 for <1 year (95% CI 2.59-4.31), 2.53 for 1 to 2 years (95% CI 1.56-4.10), 2.20 for 2 to 3 years (95% CI 1.05-4.64), and 1.09 for ≥3 years (95% CI 0.55-2.15), respectively.Our findings suggest that pioglitazone use does not have a protective effect on primary prevention for ischemic cerebrovascular disease among older people with type 2 diabetes mellitus during the first 3 years of use. Whether using pioglitazone for >3 years would have primary prevention for ischemic cerebrovascular disease needs a long-term research to prove.
Jellinger, K A
Recent epidemiological and clinico-pathologic data suggest overlaps between Alzheimer disease (AD) and cerebrovascular lesions that may magnify the effect of mild AD pathology and promote progression of cognitive decline or even may precede neuronal damage and dementia. Vascular pathology in the aging brain and in AD includes: 1. cerebral amyloid angiopathy (CAA) with an incidence of 82-98% often associated with ApoE epsilon 2 and causing a) cerebral mass hemorrhages (around 70%, mainly in the frontal and parietal lobes), b) multiple or recurrent microhemorrhages (15%), and c) ischemic (micro-)infarcts or lacunes (around 20%). The frequency of these lesions increases with the severity of CAA and shows no correlation with that of senile amyloid plaques. CAA, significantly more frequent in patients with cerebral hemorrhages or infarcts than in aged controls, is an important risk factor for cerebrovascular lesions in AD. 2. Microvascular changes with decreased density and structural abnormalities causing regional metabolic and blood-brain barrier dysfunctions with ensuing neuronal damage. In large autopsy series of demented aged subjects, around 80% show Alzheimer type pathology, 20-40% with additional, often minor vascular lesions, 7-10% "pure" vascular dementia, and 3-5% "mixed" dementia (combination of AD and vascular encephalopathy). AD cases with additional minor cerebrovascular lesions have significantly more frequent histories of hypertension or infarcts than "pure" AD patients. Vascular lesions in AD include cortical microinfarcts, subcortical lacunes, white matter lesions / leukoencephalopathy, small hemorrhages and corticosubcortical infarcts, while in mixed type dementia multiple larger or hemispheral infarcts are more frequent. Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia
Lyon, J L; Bishop, C T; Nielsen, N S
Utah mortality rates for cerebrovascular disease (ICD numbers 430--438) are 13% below U.S. rates. About 70% of Utahns are members of the Church of Jesus Christ of Latter-day Saints, commonly called Mormons of LDS, which proscribes use of tobacco and alcohol. Other studies on this group have found significantly lower occurrence of many cancers and ischemic heart disease. We tested the hypothesis that Utah's lower cerebrovascular disease (CBVD) mortality was contributed by the LDS population. We classified by religion all CBVD deaths (2,521) (except subarachnoid hemorrhage and cerebral embolism) occurring in the state in 1968--1971. No significant difference was found between LDS and non-LDS, but both groups had mortality rates below U.S. expectation. Although recent studies have reported smoking to be a risk factor for CBVD, we found no consistent difference between the LDS and non-LDS, even in the younger age groups. The results do not support the hypothesis that tobacco is an important etiologic agent in CBVD mortality.
Lindenstrøm, E.; Boysen, G.; Nyboe, J.
OBJECTIVE--To estimate the influence of plasma total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease. DESIGN--The Copenhagen City Heart Study is a prospective observational survey with two cardiovascular examinations at five year intervals. Non-fasting plasma lipids were measured in participants once at each examination, along with other variables. The Cox regression model was used to establish the effect of the factors recorded on cerebrovascular events of mostly, but not exclusively, ischaemic origin. SUBJECTS--19,698 women and men at least 20 years old, randomly selected after age stratification from an area of central Copenhagen. MAIN OUTCOME MEASURES--Initial cases of stroke and transient ischaemic attack recorded from hospital records and death certificates from 1976 through 1988. RESULTS--660 non-haemorrhagic and 33 haemorrhagic events were recorded. Total cholesterol was positively associated with risk of non-haemorrhagic events, but only for levels > 8 mmol/l, corresponding to the upper 5% of the distribution in the study population. For lower plasma cholesterol values the relative risk remained nearly constant. Plasma triglyceride concentration was significantly, positively associated with risk of non-haemorrhagic events. The relative risk corresponding to an increase of 1 mmol/l was 1.12 (95% confidence interval 1.07 to 1.16). There was a negative, log linear association between high density lipoprotein cholesterol and risk of non-haemorrhagic events (0.53 (0.34 to 0.83)). There was no indication that the effects of plasma lipids were different in women and men. CONCLUSIONS--The pattern of the association between plasma cholesterol and risk of ischaemic cerebrovascular disease was not log linear, and the increased risk was confined to the upper 5% of the cholesterol distribution. Further studies should concentrate on the association between plasma cholesterol and verified haemorrhagic stroke. PMID
... 4 MB] More data Death rates for cerebrovascular diseases by sex, race, Hispanic origin, and age Health, United States, 2015, table 23 [ ... causes of death, by sex, race, and Hispanic origin Health, United States, 2015, table 18 [PDF - 9.8 ... Center for Chronic Disease Prevention and Health Promotion National Heart, Lung, and ...
van der Veen, Pieternella H; Muller, Majon; Vincken, Koen L; Witkamp, Theo D; Mali, Willem P T M; van der Graaf, Yolanda; Geerlings, Mirjam I
We estimated the progression of brain atrophy and cerebrovascular lesions on MRI in a prospective cohort of patients with various manifestations of arterial disease. Within the SMART-MR study, using brain MRI data from baseline and after on average 3.9 years of follow-up, intracranial volume (ICV), total brain, cortical gray matter, ventricular, white matter lesion volumes and visually rated infarcts were obtained from 663 patients (mean age 57 ± 9 years, 81% men). Global and cortical atrophy increased quadratically with age. Men showed more progression of global and cortical atrophy than women (mean difference in change (95% CI): -0.25 (-0.44; -0.06) and -0.94 (-1.35; -0.52)% ICV) and had an increased risk of new brain infarcts (OR = 2.7, 95% CI 1.2-6.1). Compared with coronary artery disease patients, cerebrovascular disease patients showed more progression of cortical and subcortical atrophy and an increased risk of new brain infarcts, and peripheral arterial disease patients showed more progression of cortical atrophy. These results were independent of cerebrovascular lesions and cardiovascular risk factors. In patients with manifest arterial disease, brain atrophy tended to accelerate with older age and men had more progression of brain atrophy and cerebrovascular lesions than women. Additionally, patients with cerebrovascular and peripheral arterial disease showed the most prominent progression of atrophy and lesions.
Nanhoe-Mahabier, Wandana; de Laat, Karlijn F; Visser, Jasper E; Zijlmans, Jan; de Leeuw, Frank-Erik; Bloem, Bastiaan R
Optimal management of chronic diseases not only requires tackling of the primary disease processes, but also necessitates timely recognition and treatment of comorbid conditions. In this article, we illustrate this two-pronged approach for two common age-related disorders: Parkinson disease (PD) and cerebrovascular disease (CVD). We first discuss the pathophysiological mechanisms that could provide a link between PD and CVD. Patients with PD have a series of risk factors that could promote development of CVD, but also have several protective factors. We then review the available clinical, radiological and neuropathological evidence to support an association between these two conditions. We conclude by discussing the potential implications for clinical practice, highlighting how comorbid CVD could alter the clinical presentation of PD and reviewing the possibilities for prevention and secondary prophylaxis. Additional research will be needed to fully evaluate the prevalence and clinical relevance of comorbid CVD in PD. Pending further evidence, we recommend that cerebral neuroimaging should be considered if patients with initially uncomplicated PD develop-either acutely or chronically-prominent and/or treatment-resistant gait impairment, postural instability, depression, cognitive decline, or urinary incontinence. Finding comorbid CVD in such patients could have prognostic implications, and could necessitate treatment to arrest further progression of CVD.
Love, Seth; Miners, J Scott
Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.
GHIZONI, Janaina Salomon; TAVEIRA, Luís Antônio de Assis; GARLET, Gustavo Pompermaier; GHIZONI, Marcos Flávio; PEREIRA, Jefferson Ricardo; DIONÍSIO, Thiago José; BROZOSKI, Daniel Thomas; SANTOS, Carlos Ferreira; SANT'ANA, Adriana Campos Passanezi
Objective: This study investigated the role of periodontal disease in the development of stroke or cerebral infarction in patients by evaluating the clinical periodontal conditions and the subgingival levels of periodontopathogens. Material and Methods: Twenty patients with ischemic (I-CVA) or hemorrhagic (H-CVA) cerebrovascular episodes (test group) and 60 systemically healthy patients (control group) were evaluated for: probing depth, clinical attachment level, bleeding on probing and plaque index. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were both identified and quantified in subgingival plaque samples by conventional and real-time PCR, respectively. Results: The test group showed a significant increase in each of the following parameters: pocket depth, clinical attachment loss, bleeding on probing, plaque index and number of missing teeth when compared to control values (p<0.05, unpaired t-test). Likewise, the test group had increased numbers of sites that were contaminated with P. gingivalis (60%x10%; p<0.001; chi-squared test) and displayed greater prevalence of periodontal disease, with an odds ratio of 48.06 (95% CI: 5.96-387.72; p<0.001). Notably, a positive correlation between probing depth and the levels of P. gingivalis in ischemic stroke was found (r=0.60; p=0.03; Spearman's rank correlation coefficient test). A. actinomycetemcomitans DNA was not detected in any of the groups by conventional or real-time PCR. Conclusions: Stroke patients had deeper pockets, more severe attachment loss, increased bleeding on probing, increased plaque indexes, and in their pockets harbored increased levels of P. gingivalis. These findings suggest that periodontal disease is a risk factor for the development of cerebral hemorrhage or infarction. Early treatment of periodontitis may counteract the development of cerebrovascular episodes. PMID:22437687
Stephens, W. P.; Ferguson, I. T.
Three cases are described in which extensive livedo reticularis was associated with premature cerebrovascular disease. The patients presented with transient cerebral ischaemic attacks and gradually developed permanent neurological damage with intellectual impairment. The value of detailed neuropsychological testing to identify bilateral cortical abnormalities is demonstrated. CAT scanning may reveal multifocal cerebral infarction. The nature of this condition is not understood. ImagesFig. 1 PMID:7100027
Kashcheev, V V; Chekin, S Yu; Maksioutov, M A; Tumanov, K A; Menyaylo, A N; Kochergina, E V; Kashcheeva, P V; Gorsky, A I; Shchukina, N V; Karpenko, S V; Ivanov, V K
The paper presents an analysis of the incidence of cerebrovascular diseases (CeVD) in the cohort of Russian workers involved in recovery tasks after the Chernobyl accident. The studied cohort consists of 53,772 recovery operation workers (liquidators) who arrived in the zone of the Chernobyl accident within the first year after this accident (26 April 1986-26 April 1987). The mean external whole body dose in the cohort was 0.161 Gy, while individual doses varied from 0.0001 Gy to 1.42 Gy. During the follow-up period 1986-2012, a total of 23,264 cases of CeVD were diagnosed as a result of annual health examinations. A Poisson regression model was applied for estimation of radiation risks and for an assessment of other risk factors of CeVD. The following factors were considered as risk factors for CeVD: the dose, duration of the liquidators' work in the Chernobyl zone, and the concomitant diseases (hypertension, ischemic heart disease, atherosclerosis, and diabetes). The baseline incidence of CeVD is statistically significantly (p < 0.001) associated with all studied concomitant diseases. The incidence of CeVD has revealed a statistically significant dose response with the lack of a latent period and with the average ERR/Gy = 0.45, 95% CI: (0.28, 0.62), p < 0.001. Radiation risks of CeVD statistically significantly (p = 0.03) varied with the duration of liquidators' stay in the Chernobyl zone; for those who stayed in the Chernobyl zone less than 6 wk, ERR/Gy = 0.64, 95% CI = (0.38; 0.93), p < 0.001. Among studied concomitant diseases, diabetes mellitus statistically significantly (p = 0.002) increases the radiation risk of CeVD: for liquidators with diagnosed diabetes, ERR/Gy = 1.29.
Iribarren, Carlos; Tolstykh, Irina V; Miller, Mary K; Sobel, Erica; Eisner, Mark D
Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.
Brea, Angel; Laclaustra, Martín; Martorell, Esperanza; Pedragosa, Angels
In Spain, cerebrovascular disease (CVD) is a very common cause of morbidity and hospitalization. They are the second leading cause of mortality in the general population, and the first in women. They also constitute a very high social spending, which is estimated to increase in coming years, due to the aging of our population. Data from the Hospital Morbidity Survey of the National Statistics Institute recorded, in 2011, 116,017 strokes and 14,933 transient ischemic attacks, corresponding, respectively, to an incidence of 252 and 32 events per 100,000 people. In 2002, the cost of hospitalization for each stroke was estimated at €3,047. The amount of total cost health care throughout the life of a stroke patient is calculated at €43,129. Internationally, the direct costs of stroke constitute 3% of national health spending, this being similar amount in different countries around us. Hypertension was the cardiovascular risk factor (CVRF) more prevalent in both ischemic and hemorrhagic strokes, followed by dyslipidemia and diabetes mellitus. Peripheral arterial disease and hypertension were more frequently associated with atherothrombotic events, atrial fibrillation with cardioembolic strokes, and obesity and high blood pressure to lacunar infarcts. In Spain, as showing several studies, we are far from optimal control of CVRF, especially in secondary prevention of stroke. According to the ICTUSCARE study, achieving recommended values was 17.6% in the case of hypertension, 29.8% in LDL-cholesterol, 74.9% of smoking, and 50.2% in diabetes mellitus. In this review, we analyze in detail the epidemiology, prevention and costs originated by CVD.
Last, Briana S; García Rubio, Maria-José; Zhu, Carolyn W; Cosentino, Stephanie; Manly, Jennifer J; DeCarli, Charles; Stern, Yaakov; Brickman, Adam M
Background/Study Context: Magnetic resonance imaging (MRI) markers of cerebrovascular disease and atrophy are common in older adults and are associated with cognitive and medical burden. However, the extent to which they are related to health care expenditures has not been examined. We studied whether increased Medicare expenditures were associated with brain markers of atrophy and cerebrovascular disease in older adults.
Rössner, S; Kjellin, K G; Mettinger, K L; Sidén, A; Söderström, C E
Serum lipoproteins were determined 8-12 weeks after the onset of ischemic cerebro-vascular disease (ICD) in 61 patients, 38 males and 23 females, before the age of 55. The results were compared with those of a matched control material. The diagnosis was based on clinical findings, CSF spectrophotometry, computer tomography, and angiography. Hyperlipoproteinemia was no common finding in these young and middle-aged patients with ICD. The normal mean total serum cholesterol concentration was the result of a slight increase in VLDL cholesterol and a concomitant HDL cholesterol reduction. In men, the HDL cholesterol concentration was lower than expected for any VLDL-TG concentration. The mean value of the HDL cholesterol concentration in the patients was 18% lower than in the control group. On agarose electrophoresis the lipoprotein variants "late prebeta", "sinking prebeta" and "rapid beta" lipoproteins could be demonstrated in the same frequency as in controls. There was no significant correlation between the degree of atherosclerosis, estimated by angiography, and any serum lipoprotein fraction. Several recent studies have stressed the importance of a low HDL concentration as an independent risk factor for atherosclerosis. The decreased HDL cholesterol levels found in the present material require further attention to the possible beneficial role of HDL in ICD.
Huttenlocher, P.R.; Moohr, J.W.; Johns, L.; Brown, F.D.
Cerebral blood flow (CBF) has been studied by the xenon-133 (/sup 133/Xe) inhalation method in 16 children with suspected sickle cell cerebrovascular disease. Abnormalities consisting of decreases in total, hemispheral, or regional CBF were found in 17 of 26 studies. Eleven studies performed immediately after stroke, transient ischemic attack, or depression of state of alertness showed abnormalities. In addition to confirming regional cerebrovascular insufficiency in children with stroke due to major cerebral artery occlusion, the method detected diffuse decrease in CBF in children with stupor, coma, and seizures who had normal angiographic findings. In contrast, six of seven studies obtained after exchange transfusion or during maintenance on hypertransfusion therapy showed normal findings. The difference between results in patients with acute neurologic disturbances and those receiving transfusion therapy was statistically significant (P less than .005). The data indicate that the /sup 133/Xe method reliably demonstrates cerebrovascular impairment in sickle cell disease. They also suggest that CBF changes in patients with sickle cell disease can be reversed by exchange transfusion and by hypertransfusion therapy. The /sup 133/Xe CBF method may be useful for following up children with sickle cell disease who are at high risk for recurrent stroke.
Skoog, I.; Hesse, C.; Aevarsson, O.; Landahl, S.; Wahlstrom, J.; Fredman, P.; Blennow, K.
OBJECTIVES—To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85year old people. METHODS—A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. RESULTS—At the age of 85, carriers of the apoE ε4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer's disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE ε4 allele was associated with mixed Alzheimer's disease-multi-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE ε4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE ε4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE ε4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The ε2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p<0.05). CONCLUSIONS—Neither the apoE ε4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia
Del Brutto, O H
Ischaemic cerebrovascular disease is a relatively common but under-recognised complication of neurocysticercosis. It is usually caused by inflammatory occlusion of the arteries at the base of the brain secondary to cysticercotic arachnoiditis. In most cases, the involved vessels are of small diameter and the neurological picture is limited to a lacunar syndrome secondary to a small cerebral infarct. However, large infarcts related to the occlusion of the middle cerebral artery or even the internal carotid artery have also been reported in this setting. CT and CSF examination usually support the cause-and-effect relationship between neurocysticercosis and the cerebral infarct by showing abnormalities compatible with cysticercotic arachnoiditis. An accurate diagnosis of this condition is important since early treatment with steroids is advised to ameliorate the subarachnoid inflammatory reaction which may cause recurrent cerebral infarcts. PMID:1583508
Leira, Yago; Blanco, Miguel; Blanco, Juan; Castillo, José
Periodontal disease and cerebrovascular disease are two of the most prevalent processes in elderly people. Various studies have shown an association between them, although some methodological differences exist and this difficult the data interpretation. The aim of this paper is to conduct a critical review of the studies published about this association. Eleven prospective studies and 11 retrospective studies are included in this review. We analyse the different methodological outcomes (study population, periodontal diagnosis, cerebrovascular disease definition, adjusted outcomes and odds ratio/relative risk). Furthermore, we review several pathogenic mechanisms implicated in the progression and the relationship between both processes.
Li, Ziru; Zhang, Xusheng
To explore the assessing technique which could objectively reflect the characteristics of Chinese medicine in the prevention of cardiovascular and cerebrovascular diseases, four balance features of infrared thermal images (ITI) corresponding to the up and down, left and right, proximal and distal balance of blood circulation of human body were studied. First, the ITI features of the middle-aged and elderly people with lipid abnormality history were compared with those of the healthy youth. It was found that the balance state of the youth was significantly better than that of the middle-aged and elderly, P<=0.01 for all the balance features. For the youth, the balance state of females was better than that of the males. But this sexual difference disappeared for the middle-aged and elderly group. Second, a double-blind randomized trial was carried out to study the influences of Shengyi capsule, a Chinese medicine health food with the function of helping to decrease serum lipid, on the balance features. The subjects were middle-aged and elderly people with lipid abnormality history. Shengyi capsule was taken by the trial group while Xuezhikang capsule (with lovastatin as the main effective component) by the control group for 108 days. The balance features of ITI showed that Shengyi was significantly better than Xuezhikang in improving the whole body balance of blood circulation (including the up and down, left and right, proximal and distal balance). The relative efficacy rate was 81.0% for the trial group and 33.3% for the control group, there was significant difference between the two groups (P=0.002). Shengyi could effectively decrease the low density lipoprotein cholesterol (LDL-C) but the effect of Xuezhikang in decreasing total cholesterol (TC) and LDL-C was better than Shengyi. Though the lipid-lowering effect of Shengyi was not as good as Xuezhikang, ITI reflected the obvious advantage of Shengyi in improving the whole body balance of blood circulation which
Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.
Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721
Maekawa, M; Awaya, S; Fukuda, S; Teramoto, A
The efficacy of encephalo-duro-arterio-synangiosis (EDAS) using superficial temporal artery was evaluated for the treatment of the occlusive/stenotic cerebrovascular disease. Nine patients with the occlusive/stenotic cerebrovascular disease underwent EDAS in our hospital. The mean follow-up period was 6.6 months. Postoperative angiography showed no collateral formation via EDAS in any of the nine patients. We analyzed the following points: 1) operative procedure, 2) follow up period after surgery, 3) preoperative cerebral blood flow, and 4) age of the patients. Results showed that EDAS as a treatment of occlusive/stenotic cerebrovascular disease was not effective. This study failed to reinforce the suggestion that indirect extracranial/intracranial bypass surgery is effective as the treatment of occlusive/stenotic cerebrovascular disease.
Chen, Shin-Yan; Cherng, Yih-Giun; Lee, Fei-Peng; Yeh, Chun-Chieh; Huang, Shih-Yu; Hu, Chaur-Jong; Liao, Chien-Chang; Chen, Ta-Liang
Abstract Little was known about the beneficial effects of uvulopalatopharyngoplasty (UPPP) on the outcomes after obstructive sleep apnea (OSA). The aim of this study is to investigate the effects of UPPP on reducing risk of cerebrovascular diseases in patients with OSA. Using Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 10,339 patients with new OSA between January 1, 2004, and December 31, 2009. The incident cerebrovascular disease was identified during the 1-year follow-up period in patients with and without receiving UPPP. The rate ratios (RRs) and 95% confidence intervals (CIs) of cerebrovascular disease associated with receiving UPPP in patients with OSA were calculated in multivariate Poisson regression. The 1-year incidences of cerebrovascular disease for OSA patients with and without UPPP were 1.06% and 5.14%, respectively. Patients with OSA receiving UPPP had lower risk of cerebrovascular disease compared with those without UPPP (RR, 0.45; 95% CI, 0.33–0.61). The decreased risk of cerebrovascular disease following UPPP was observed in both sexes and all age groups. In the stratified analysis of medical conditions, the RR of cerebrovascular disease associated with UPPP for patients with 0, 1, ≥ 2 medical conditions were 0.28 (95% CI 0.12–0.68), 0.39 (95% CI 0.21–0.73), and 0.63 (95% CI 0.43–0.93), respectively. Patients with OSA who received UPPP had lower risk of cerebrovascular disease within 1 year after surgery compared with patients not receiving UPPP. Clinical physicians could have more evidence to persuade patients to receive surgical intervention, especially those who have severe OSA symptoms or do not acquire adequate symptom relief under conservative treatments. PMID:26469923
Wang, Xingce; Bie, Rongfang; Wu, Zhongke; Zhou, Mingquan; Cao, Rongfei; Xie, Lizhi; Zhang, Dong
Background In recent years, cerebrovascular disease has been the leading cause of death and adult disability in the world. This study describes an efficient approach to detect cerebrovascular disease. Objective In order to improve cerebrovascular treatment, prevention, and care, an automatic cerebrovascular disease detection eHealth platform is designed and studied. Methods We designed an automatic eHealth platform for cerebrovascular disease detection with a four-level architecture: object control layer, data transmission layer, service supporting layer, and application service layer. The platform has eight main functions: cerebrovascular database management, preprocessing of cerebral image data, image viewing and adjustment model, image cropping compression and measurement, cerebrovascular segmentation, 3-dimensional cerebrovascular reconstruction, cerebrovascular rendering, cerebrovascular virtual endoscope, and automatic detection. Several key technologies were employed for the implementation of the platform. The anisotropic diffusion model was used to reduce the noise. Statistics segmentation with Gaussian-Markov random field model (G-MRF) and Stochastic Estimation Maximization (SEM) parameter estimation method were used to realize the cerebrovascular segmentation. Ball B-Spline curve was proposed to model the cerebral blood vessels. Compute unified device architecture (CUDA) based on ray-casting volume rendering presented by curvature enhancement and boundary enhancement were used to realize the volume rendering model. We implemented the platform with a network client and mobile phone client to fit different users. Results The implemented platform is running on a common personal computer. Experiments on 32 patients’ brain computed tomography data or brain magnetic resonance imaging data stored in the system verified the feasibility and validity of each model we proposed. The platform is partly used in the cranial nerve surgery of the First Hospital
Derriennic, F; Guilloud, M; Ducimetière, P
The relation between death rates from ischaemic heart and cerebro-vascular diseases among Frenchmen aged 45-64, and some dietary constituents was studied. Data concerned population groups defined by the geographic regions and the socioeconomic classes. A specific statistical model of variance analysis was considered. A positive association between the daily sugar intake and the death rates from ischaemic heart diseases were observed. On the other hand, several positive associations between the daily intake of protein, fat, carbohydrate and total calories (without alcohol) and death rates from cerebrovascular diseases were found. The quality of nutritional data, however, implies some prudence in interpreting these results.
Schindler, R J
Patients with vascular dementia (VaD) and Alzheimer's disease with cerebrovascular disease (AD + CVD) have dementia associated with underlying CVD. Although diagnosis of VaD is challenging, VaD is typically characterized by a stepwise progression of dementia that is closely associated with stroke and focal neurological findings, and a symptom profile that often includes executive dysfunction leading to decreased ability to perform instrumental activities of daily living (IADL). In contrast, AD + CVD patients typically present with progressive deterioration of cognition/memory that may also be influenced by concurrent cerebrovascular events. Early diagnosis and intervention are desirable to prevent further decline due to subsequent vascular events. Management of CVD can limit deterioration of cognitive symptoms in VaD patients, and treatment benefits with cholinesterase inhibitors may be realized as improvement above baseline levels in dementia symptoms. Results from a combined analysis of two 24-week, placebo-controlled clinical trials show that donepezil-treated VaD patients improve in cognition, global function, and performance of IADL. In contrast, AD + CVD patients may continue to decline despite management of CVD, and treatment benefits should be recognized as initial improvements followed by stabilization or slowed decline of dementia symptoms over time. In post-marketing studies, donepezil-treated AD and AD + CVD patients show similar benefits in cognition, global function, and quality of life. The results of these studies support the use of donepezil in treatment of patients with VaD or AD + CVD.
Brass, L.M.; Rattner, Z.
Every year, nearly half a million people in the United States have a stroke. Cerebrovascular disease is the third leading cause of death in the country, and it costs the economy approximately $25 billion annually. SPECT perfusion imaging is a sensitive indicator of stroke. Abnormal patterns of blood flow are recognized either as areas of hypoactivity (focal or diffused) or hyperactivity (hyperemia or luxury perfusion). Lesions are demonstrated earlier by SPECT than by CT or MRI, and the physiologic information from flow imaging is not available from such anatomic studies. Given the significance of stroke and the early sensitivity of SPECT, why do most neurologists not include SPECT in the evaluation of their patients? The authors feel that the answer is that most neurologists do not view SPECT flow imaging as providing additional information beyond the standard clinical and radiologic work-up. This article therefore concentrates on ways in which SPECT imaging can be useful in stroke, identifying the major concerns of clinicians, and demonstrating how some of these concerns can be addressed by SPECT. The goal is to expand the perspective of the nuclear-medicine physician and encourage investigations on urgent clinical problems in the diagnosis and management of patients with cerebrovascular diseases. Additional information may be obtained from several excellent reviews of SPECT imaging in stroke. 73 refs.
Desai, Amish J; Fuller, Cindy J; Jesurum, Jill T; Reisman, Mark
Patent foramen ovale (PFO) has been linked to ischemic strokes of undetermined cause (cryptogenic strokes). PFO-a remnant of fetal circulation when the foramen ovale does not seal after birth-can permit microemboli to escape the pulmonary filter into the intracranial circulation, causing stroke. Coexistent atrial septal aneurysm, pelvic deep vein thrombosis and inherited clotting factor deficiencies could potentiate stroke risk in patients with PFO. Transcatheter PFO closure, a minimally invasive procedure, is one technique used to prevent recurrent cerebrovascular events. A connection between PFO and migraine headache has been conceptualized from retrospective evidence of reduced migraine frequency and severity after PFO closure; however, prospective randomized trials are needed to verify the efficacy of PFO closure on migraine prevention. In this review we discuss embryologic origins, diagnostic techniques and treatment options for prevention of paradoxical embolism thought to be related to PFO, and the relation of PFO to cryptogenic stroke and migraine.
Zlokovic, Berislav V
Human apolipoprotein E (apoE) has 3 isoforms: apoE2, apoE3, and apoE4. APOE4 is a major genetic risk factor for Alzheimer disease and is associated with dementia in Down syndrome and poor neurological outcome after traumatic brain injury, cerebral hemorrhage, and other neuropathological disorders. While apoE4 can induce neuropathology by participating in various cellular and molecular pathways, herein I review data supporting the hypothesis that apoE4 has direct toxic effects on the cerebrovascular system that in turn can lead to secondary neuronal dysfunction and degeneration as well as accumulation of neurotoxins in brain such as β-amyloid (Aβ) in Alzheimer disease. I review Aβ-independent cerebrovascular effects of apoE, particularly activation of a proinflammatory cyclophilin A-mediated pathway in brain vascular pericytes by apoE4 that has recently been shown to lead to a loss of cerebrovascular integrity and blood-brain barrier breakdown causing neuronal injury. I also review Aβ-dependent cerebrovascular effects of apoE such as faulty Aβ clearance from brain to circulation by apoE4. Finally, I discuss isoform-specific interactions of apoE with low-density lipoprotein receptor-related protein 1 on brain vascular cells (ie, endothelial cells, pericytes), which play an important role in Aβ-independent and Aβ-dependent effects of apoE on cerebral vasculature.
Faerber, E.N.; Griska, L.A.B.; Swartz, J.D.; Capitanio, M.A.; Popky, G.L.
While conventional angiography has been used to demonstrate cerebrovascular occlusive disease in the past, digital subtraction angiography (DSA) is capable of showing progressive vascular involvement with ease, simplicity, and extremely low morbidity, making it particularly well suited for children and outpatients either alone or coordinated with computed tomography. The authors discuss the usefulness and advantages of DSA as demonstrated in 7 infants and children with hemiplegia, 4 of whom had sickle-cell disease.
Sipos, Kornel; Bodo, Michael; Szalay, Piroska; Szucs, Attila
In order to test the hypothesis that anxiety is a risk factor for cardiovascular disease, specifically stroke, we simultaneously measured anxiety and cerebral vascular alternation, using a computer-based system, "Cerberus." Sixty nine psychiatric patients (including an alcoholic subgroup) were selected as subjects for measurements conducted in Kecskemet, Hungary. The five-item short form of anxiety test (STAI) was administered twice during the same session. Between each test, brain pulse waves were recorded by rheoencephalogram (REG). A REG peak time above 180 milliseconds was considered a cerebrovascular alteration (modified after Jenkner). Data were sorted into two groups: low anxiety (N=10) and high anxiety (N=10). Significant differences were found between cardiovascular risk factors (p< 0.001), REG peak time (p<0.043), and heart rate (p< 0.045). Six subjects showed cerebrovascular alteration in the high anxiety group, and two in the low anxiety group. For the two anxiety groups, there were no significant differences in body mass index, cardiovascular sympathetic-parasympathetic balance, age and symptoms of transient ischemic attack. The correlation of REG and age was significantly different only for the alcoholic subgroup (Szalay et al, 2007). These data support the hypothesis that a correlation exists between cerebrovascular disorder and anxiety in the studied population.
Alzheimer's disease (AD) is a progressive chronic disorder and is characterized by β-amyloid plaques and angiopathy, tau pathology, neuronal cell death, and inflammatory responses. The reasons for this disease are not known. This review proposes the hypothesis that a chronic mild longlasting cerebrovascular dysfunction could initiate a cascade of events leading to AD. It is suggested that (vascular) risk factors (e.g. hypercholesterolemia, type 2 diabetes, hyperhomocysteinemia) causes either damage of the cerebrovascular system including silent strokes or causes dysregulation of beta-amyloid clearance at the blood-brain barrier resulting in increased brain beta-amyloid. A cascade of subsequent downstream events may lead to disturbed metabolic changes, and neuroinflammation and tau pathology. The role of NGF on the cell death of cholinergic neurons is discussed. Additional risk factors (e.g. acidosis, metals) contribute to plaque development. PMID:21112383
Chen, M Y; Ott, D J; Peele, V N; Gelfand, D W
Forty-six patients with cerebrovascular disease underwent videofluoroscopic examination of the oropharynx to assess location and severity of swallowing dysfunction with use of boluses of various consistencies. Low- and high-viscosity barium suspensions, a barium paste, and a paste-coated cookie were used; not all patients were given all materials. Thirty-nine patients had abnormalities of both oral and pharyngeal function. Two patients had oral dysfunction only, and five had pharyngeal abnormalities only. Mild swallowing difficulties occurred in 18 patients (39%), moderate dysfunction in 23 (50%), and severe dysfunction in five (11%). Thirty-one patients had pharyngeal stasis, which was symmetric in 25 patients (81%), right-sided in three, and left-sided in three. Asymmetric stasis did not correlate to the site of cerebrovascular disease. Twenty-four episodes of aspiration occurred, half of them with the low-viscosity barium suspension. Thus, video-fluoroscopy can be used to define the location and severity of oropharyngeal abnormalities, which is critical for feeding recommendations. The abnormalities present, however, were not useful in predicting the type of cerebrovascular disease.
Göthe, F; Enache, D; Wahlund, L O; Winblad, B; Crisby, M; Lökk, J; Aarsland, D
Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.
Gurdasani, Deepti; Sjouke, Barbara; Tsimikas, Sotirios; Hovingh, G. Kees; Luben, Robert N.; Wainwright, Nicholas W. J.; Pomilla, Cristina; Wareham, Nicholas J.; Khaw, Kay-Tee; Boekholdt, S. Matthijs; Sandhu, Manjinder S.
Objective While the association between circulating levels of lipoprotein(a) (Lp(a)) and risk of coronary artery disease (CAD) and stroke is well established, its role in risk of peripheral artery disease (PAD) remains unclear. Here, we examine the association between Lp(a) levels and PAD in a large prospective cohort. To contextualise these findings, we also examined the association between Lp(a) levels and risk of stroke and CAD and studied the role of LDL as an effect modifier of Lp(a) associated cardiovascular risk. Methods and Results Lp(a) levels were measured in apparently healthy participants in the EPIC-Norfolk cohort. Cox regression was used to quantify the association between Lp(a) levels and risk of PAD, stroke and CAD outcomes. During 212,981 person-years at risk, a total of 2365 CAD, 284 ischemic stroke and 596 PAD events occurred in 18,720 participants. Lp(a) was associated with PAD and CAD outcomes but not with ischemic stroke (HR per 2.7 fold increase in Lp(a) of 1.37, 95% CI 1.25-1.50, 1.13, 95% CI 1.04-1.22 and 0.91, 95%CI 0.79-1.03 respectively). LDL-C levels did not modify these associations. Conclusion Lp(a) levels were associated with future PAD and CAD events. The association between Lp(a) and cardiovascular disease was not modified by LDL-C levels. PMID:23065826
Torén, Kjell; Bergdahl, Ingvar A; Nilsson, Tohr; Järvholm, Bengt
Objectives A growing number of epidemiological studies are showing that ambient exposure to particulate matter air pollution is a risk factor for cardiovascular disease; however, whether occupational exposure increases this risk is not clear. The aim of the present study was to examine whether occupational exposure to particulate air pollution increases the risk for ischaemic heart disease and cerebrovascular disease. Methods The study population was a cohort of 176 309 occupationally exposed Swedish male construction workers and 71 778 unexposed male construction workers. The definition of exposure to inorganic dust (asbestos, man‐made mineral fibres, dust from cement, concrete and quartz), wood dust, fumes (metal fumes, asphalt fumes and diesel exhaust) and gases and irritants (organic solvents and reactive chemicals) was based on a job‐exposure matrix with focus on exposure in the mid‐1970s. The cohort was followed from 1971 to 2002 with regard to mortality to ischaemic heart disease and cerebrovascular disease. Relative risks (RR) were obtained by the person‐years method and from Poisson regression models adjusting for baseline values of blood pressure, body mass index, age and smoking habits. Results Any occupational particulate air pollution was associated with an increased risk for ischemic heart disease (RR 1.13, 95% CI 1.07 to 1.19), but there was no increased risk for cerebrovascular disease (RR 0.97, 95% CI 0.88 to 1.07). There was an increased risk for ischaemic heart disease and exposure to inorganic dust (RR 1.07, 95% CI 1.03 to 1.12) and exposure to fumes (RR 1.05, 95% CI 1.00 to 1.10), especially diesel exhaust (RR 1.18, 95% CI 1.13 to 1.24). There was no significantly increased risk for cerebrovascular disease and exposure to inorganic dust, fumes or wood dust. Conclusions Occupational exposure to particulate air pollution, especially diesel exhaust, among construction workers increases the risk for ischaemic heart disease. PMID
López-Liria, Remedios; Fernández-Alonso, Melodie; Vega-Ramírez, Francisco A; Salido-Campos, M Ángeles; Padilla-Góngora, David
INTRODUCTION. Bronchopneumonia is a frequent complication in the first days after a cerebrovascular disease and is linked with a higher rate of mortality. It occurs in patients with an altered level of consciousness or tussigenic reflex, and could be prevented with an early dysphagia rehabilitation programme. AIMS. To review the scientific literature on the treatment and rehabilitation of patients with dysphagia after suffering a stroke, published between 2002 and 2012. DEVELOPMENT. A search conducted in the PubMed, Cochrane, PEDro, CINAHL and ENFISPO databases yielded 15 papers that fulfilled eligibility criteria and the initial aims of the study, providing information about 3,212 patients. The different protocols and techniques for re-education in dysphagia are described and include compensatory strategies, orofacial regulation therapy, music therapy, sensory stimulation, lip muscle, tongue, pharynx, larynx and respiratory tract training, Mendelsohn manoeuvre, neuromuscular electrical stimulation, repetitive transcranial magnetic stimulation and acupuncture. CONCLUSIONS. The studies examined in this research claim that the treatment of dysphagia following a stroke can improve the function of deglutition (coordination, speed, volume), quality of life and people's social relationships. Further work needs to be carried out to establish or define what kind of therapies, techniques, exercises or manoeuvres are the most effective in dysphagia. Generally agreed treatment or rehabilitation protocols also need to be drawn up within units that address stroke in an integrated manner.
Hage, Ziad A; Alaraj, Ali; Arnone, Gregory D; Charbel, Fady T
Imaging techniques available to the physician treating neurovascular disease have substantially grown over the past several decades. New techniques as well as advances in imaging modalities continuously develop and provide an extensive array of modalities to diagnose, characterize, and understand neurovascular pathology. Modern noninvasive neurovascular imaging is generally based on computed tomography (CT), magnetic resonance (MR) imaging, or nuclear imaging and includes CT angiography, CT perfusion, xenon-enhanced CT, single-photon emission CT, positron emission tomography, magnetic resonance angiography, MR perfusion, functional magnetic resonance imaging with global and regional blood oxygen level dependent imaging, and magnetic resonance angiography with the use of the noninvasive optional vessel analysis software (River Forest, Ill). In addition to a brief overview of the technique, this review article discusses the clinical indications, advantages, and disadvantages of each of those modalities.
Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu
Abstract Long-term studies demonstrating the effect of pioglitazone use on primary prevention of ischemic cerebrovascular disease in older people with type 2 diabetes mellitus are lacking. This study investigated the relationship between pioglitazone use and first attack of ischemic cerebrovascular disease in Taiwan. We conducted a case-control study using the database of the Taiwan National Health Insurance Program. There were 2359 type 2 diabetic subjects aged ≥65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to 2011 as the case group and 4592 sex- and age-matched, randomly selected type 2 diabetic subjects aged ≥65 years without ischemic cerebrovascular disease as the control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic cerebrovascular disease associated with pioglitazone use was measured by the multivariable unconditional logistic regression model. After adjustment for confounding factors, the multivariable logistic regression analysis disclosed that the adjusted ORs of first attack of ischemic cerebrovascular disease associated with cumulative duration of using pioglitazone were 3.34 for <1 year (95% CI 2.59–4.31), 2.53 for 1 to 2 years (95% CI 1.56–4.10), 2.20 for 2 to 3 years (95% CI 1.05–4.64), and 1.09 for ≥3 years (95% CI 0.55–2.15), respectively. Our findings suggest that pioglitazone use does not have a protective effect on primary prevention for ischemic cerebrovascular disease among older people with type 2 diabetes mellitus during the first 3 years of use. Whether using pioglitazone for >3 years would have primary prevention for ischemic cerebrovascular disease needs a long-term research to prove. PMID:27495077
Marchant, Natalie L.; Reed, Bruce R.; DeCarli, Charles S.; Madison, Cindee M.; Weiner, Michael W.; Chui, Helena C.; Jagust, William J.
The present study evaluated cerebrovascular disease (CVD), β-amyloid (Aβ), and cognition in clinically normal elderly adults. Fifty-four participants underwent MRI, PIB-PET imaging, and neuropsychological evaluation. High white matter hyperintensity burden and/or presence of infarct defined CVD status (CVD−: N = 27; CVD+: N = 27). PIB-PET ratios of Aβ deposition were extracted using Logan plotting (cerebellar reference). Presence of high levels of Aβ in prespecified regions determined PIB status (PIB−: N = 33; PIB+: N = 21). Executive functioning and episodic memory were measured using composite scales. CVD and Aβ, defined as dichotomous or continuous variables, were unrelated to one another. CVD+ participants showed lower executive functioning (P = 0.001) when compared to CVD− individuals. Neither PIB status nor amount of Aβ affected cognition (Ps ≥ .45), and there was no statistical interaction between CVD and PIB on either cognitive measure. Within this spectrum of normal aging CVD and Aβ aggregation appear to be independent processes with CVD primarily affecting cognition. PMID:22048124
Graziano, Ana P; Sancilio, Andrea; Bugalter, Mariela; Barbosa, Walter; Rodríguez, Facundo; Montali, César; García Munitis, Pablo
Stroke in childhood is considered rare. It may be ischemic or hemorrhagic. Its presentation is often acute and it is a leading cause of mortality in pediatrics. The aim of our work is to present the general features of stroke of 18 patients under 15 years of age admitted to the Hospital El Cruce, between July 2009 and June 2014, and their clinical outcome a year later. We observed a predominance of male patients and the median age of 5 years. The main clinical features were hemiparesis, seizures, headache and vomiting and sensory impairment. The most frequent type was ischemic and the middle cerebral artery territory was the most commonly involved. Twelve patients had no sequelae. The signs and symptoms were guiding stroke, neuroimaging studies were essential for diagnosis and patients evolved favorably with low number of recurrence and death.
Dalal, P. M.; Shah, P. M.; Aiyar, R. R.; Kikani, B. J.
Cerebral angiographic findings in ischaemic stroke are described and discussed in detail. Though the Indian patients studied had altogether different social customs, living standards, and dietary habits from Western people, the relative incidence of various cerebral vascular lesions did not differ significantly. Irrespective of the poor nutritional status of the patients, thrombosis associated with atherosclerosis was chiefly responsible for a non-embolic cerebral infarction. Atherothrombosis in the young normotensive persons not showing any evidence of arteritis, diabetes mellitus, or hypercholesterolaemia was also identified. The grave risks involved in cerebral angiography in cases of acute stroke are re-emphasized. As to prognosis, the nutritional status, the type and territory of an ictal lesion, and the blood levels of sugar and cholesterol had no significant influence on the immediate survival-after a non-embolic cerebral infarction. However, a significantly greater number of deaths were encountered in the hypertensive patients. Female patients and patients with a large cerebral infarction had a poor prognosis. PMID:5676713
Bowers, Karen J.; deVeber, Gabrielle A.; Ferriero, Donna M.; Roach, E. Steve; Vexler, Zinaida S.; Maria, Bernard L.
Cerebrovascular disease in children manifests in many forms, all of which have devastating and long-lasting effects. Recent advances in diagnostic imaging have revealed that this condition is much more common in the pediatric population than previously believed, affecting as many as 1 in 1500 neonates and 1 in 3000 children. The underlying mechanisms that cause stroke—ischemic stroke, sinovenous thrombosis, and hemorrhagic stroke—are only beginning to be understood; however, progress has been made toward better understanding the mechanisms of disease, particularly in the fields of genetics, inflammation, and thrombus formation. Furthermore, new imaging techniques, and better understanding of how to use imaging in managing stroke, have enabled practitioners to more quickly and accurately identify cerebrovascular disease type in children, which is key to mitigation of negative outcomes. The 2010 Neurobiology of Disease in Children symposium, held in conjunction with the 39th annual meeting of the Child Neurology Society, aimed to (1) describe clinical issues surrounding childhood stroke, including diagnosis and acute care; (2) discuss recent advances in the understanding of the pathogenesis of childhood stroke; (3) review current management of and therapies for childhood stroke, including controversial therapies; and (4) establish research directions for investigators. This article summarizes the speakers’ presentations and includes an edited transcript of question-and-answer sessions. PMID:21778188
Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau
In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature. PMID:24659966
Gorelick, P B; Caplan, L R; Langenberg, P; Hier, D B; Pessin, M; Patel, D; Taber, J
We compared clinical and arteriographic features in 106 patients with symptomatic unilateral carotid territory occlusive disease to determine the frequency and distribution of occlusive arterial lesions in asymptomatic vessels. Among black patients who were predominantly from Chicago, young, and female, there were fewer transient ischemic attacks and myocardial infarcts, less claudication, and more asymptomatic lesions of the supraclinoid internal carotid artery, anterior cerebral artery stem, and the middle cerebral artery stem. Among white patients predominantly from New England, elderly, and male, there was more frequent and severe occlusive asymptomatic disease at extracranial carotid and vertebral artery sites. Knowledge of the distribution of asymptomatic lesions will help guide evaluation and treatment strategies for patients with occlusive cerebrovascular disease.
Hinduja, Archana; Limaye, Kaustubh; Ravilla, Rahul; Sasapu, Appalnaidu; Papanikolaou, Xenofon; Wei, Lai; Torbey, Michel; Waheed, Sarah
Objectives Patients with multiple myeloma (MM) are at increased risk of arterial thrombosis. Our aim was to determine the risk factors, mechanisms and outcome of strokes in these patients. Methods We conducted a retrospective matched case–control study from our database of MM patients enrolled in Total Therapy (TT) 2, TT3a and TT3b protocols who developed a vascular event (transient ischemic attack, ischemic stroke, or intracerebral hemorrhage) from October 1998 to January 2014. Cases were matched for age-matched selected controls. Baseline demographics, risk factors, MM characteristics, laboratory values, and mortality of cases were compared to those of controls. Multivariate logistic regression analysis identified risk factors associated with stroke. Ischemic strokes (IS) were classified with modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results Of 1,148 patients, 46 developed a vascular event (ischemic stroke, 33; transient ischemic attack, 11; hypertensive intracerebral hemorrhage, 2). Multivariate logistic regression analysis determined renal insufficiency (odds Ratio, 3.528; 95% CI, 1.36–9.14; P = 0.0094) and MM Stages I and II (odds Ratio, 2.770, 95% CI, 1.31–5.81; p = 0.0073) were independent predictors of stroke. In our study, strokes attributable to hypercoagulability, atrial fibrillation and small-vessel occlusion were common mechanisms. After a stroke, 78% of patients were discharged to home or a rehabilitation facility and 4% to a long-term nursing facility; in-hospital mortality was 15%. Despite suffering a stroke no significant differences in survival were observed. Conclusion In our cohort of multiple myeloma patients, renal failure and MM Stages I and II had increased risk of stroke. PMID:27902730
Wang, Dandan; Wang, Jing; Jin, Cheng; Ji, Ruijun; Wang, Anxin; Li, Xin; Gao, Xiang; Wu, Shouling; Zhou, Yong; Zhao, Xingquan
Asymptomatic extracranial artery stenosis (ECAS) is a well-known risk factor for stroke events, but it remains unclear whether it has the same role in predicting cardiovascular and cerebrovascular diseases, especially in China. We investigated the potential associations between ECAS, carotid plaque and carotid intima-media thickness and the new occurrence of cardiovascular and cerebrovascular diseases in the study. Out of 5440 study participants, 364 showed an asymptomatic ECAS at baseline, and 185 had come up to the final vascular events (brain infarction, intracerebral hemorrhage, subarachnoid hemorrhage, coronary heart disease and death due to the vascular diseases). During the follow- up. ECAS, carotid plaque and its instability and increased CIMT have associated with vascular events significantly (P < 0.05). After adjusting relevant vascular risk factors, ECAS still has a strong relationship with the new occurrence of vascular events, especially the brain infarction (HR: 2.101; 95% CI: 1.027–4.298; P = 0.042). We observed a clear relationship between ECAS and the new occurrence of cardiovascular and cerebrovascular disease, especially the brain infarction event. Carotid plaque and its instability and increased CIMT have all relevant with the occurrence of vascular events. Our findings provide direct evidence for the importance of ECAS in vascular events occurrence. PMID:27650877
Roldan, Carlos A.; Schevchuck, Oleksandr; Tolstrup, Kirsten; Roldan, Paola C.; Macias, Leonardo; Qualls, Clifford R.; Greene, Ernest R.; Hayek, Reyaad; Charlton, Gerald; Sibbitt, Wilmer L.
Background Lambl’s excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets’ coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. Methods 77 patients with systemic lupus erythematosus (SLE) (71 women, age 37±12 years) and 26 age-and-sex matched healthy controls (22 women, age 34±11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, transesophageal echocardiography (TEE), carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. Results On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39% and 43%), stroke/TIA (35% and 43%), cerebromicroembolism (41% and 42%), or cerebral infarcts (36% and 43%) (all p≥0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA [1(1.3%) and 2(2.5%), respectively, p=1.0] during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors
Roldan, Carlos A.; Sibbitt, Wilmer L.; Qualls, Clifford R.; Jung, Rex E.; Greene, Ernest R.; Gasparovic, Charles M.; Hayek, Reyaad; Charlton, Gerald A.; Crookston, Kendall
Objective To determine whether Libman-Sacks endocarditis is a pathogenic factor for cerebrovascular disease (CVD) in systemic lupus erythematosus (SLE). Background A cardioembolic pathogenesis of SLE CVD manifested as 1) neuropsychiatric SLE (NPSLE) including stroke and transient ischemic attacks (TIA), 2) neurocognitive dysfunction, and 3) MRI focal brain lesions has not been established. Methods A 6-year study of 30 patients with acute NPSLE (27 women, age 38±12 years), 46 age-and-sex matched SLE controls without NPSLE (42 women, age 36±12 years), and 26 age-and-sex matched healthy controls (22 women, age 34±11 years) who underwent clinical and laboratory evaluations, TEE, carotid duplex, transcranial Doppler, neurocognitive testing, and brain MRI/MRA. NPSLE patients were re-evaluated after 4.5 months of therapy. All patients were followed clinically for a median of 52 months. Results Libman-Sacks vegetations (87%), cerebromicroembolism (27% with 2.5 times more events per hour), neurocognitive dysfunction (60%), and cerebral infarcts (47%) were more common in NPSLE than in SLE (28%, 20%, 33%, and 0%) and healthy controls (8%, 0%, 4%, and 0%, respectively) (all p≤0.009). Patients with vegetations had 3 times more cerebromicroemboli per hour, lower cerebral blood flow, more stroke/TIA and overall NPSLE events, neurocognitive dysfunction, cerebral infarcts, and brain lesion load than those without (all p≤0.01). Libman-Sacks vegetations were independent risk factors of NPSLE (OR=13.4, p<0.001), neurocognitive dysfunction (OR=8.0, p=0.01), brain lesions (OR=5.6, p=0.004), and all 3 outcomes combined (OR=7.5, p<0.001). Follow-up re-evaluations in 18 (78%) of 23 surviving NPSLE patients demonstrated improvement of vegetations, microembolism, brain perfusion, neurocognitive dysfunction, and lesion load (all p≤0.04). Finally, patients with vegetations had reduced event free survival time to stroke/TIA, cognitive disability, or death (p=0.007). Conclusion The
Villela, Paolo Blanco; Klein, Carlos Henrique; de Oliveira, Gláucia Maria Moraes
Background Cerebrovascular and hypertensive diseases are among the main causes of death worldwide. However, there are limited data about the trends of these diseases over the years. Objective To evaluate the temporal trends in mortality rates and proportional mortality from cerebrovascular and hypertensive diseases according to sex and age in Brazil between 1980 and 2012. Methods We evaluated the underlying causes of death between 1980 and 2012 in both sexes and by age groups for circulatory diseases (CD), cerebrovascular diseases (CBVD), and hypertensive diseases (HD). We also evaluated death due to all causes (AC), external causes (EC), and ill-defined causes of death (IDCD). Data on deaths and population were obtained from the Department of Information Technology of the Unified Health System (Departamento de Informática do Sistema Único de Saúde, DATASUS/MS). We estimated crude and standardized annual mortality rates per 100,000 inhabitants and percentages of proportional mortality rates. Results With the exception of EC, the mortality rates per 100,000 inhabitants of all other diseases increased with age. The proportional mortality of CD, CBVD, and HD increased up to the age range of 60-69 years in men and 70-79 years in women, and reached a plateau in both sexes after that. The standardized rates of CD and CBVD declined in both sexes. However, the HD rates showed the opposite trend and increased mildly during the study period. Conclusion Despite the decline in standardized mortality rates due to CD and CBVD, there was an increase in deaths due to HD, which could be related to factors associated with the completion of the death certificates, decline in IDCD rates, and increase in the prevalence of hypertension. PMID:27355586
Kolmos, Mia; Krawcyk, Rikke Steen; Kruuse, Christina
Objectives: Exercise improves endothelial dysfunction, the key manifestation of cardiovascular and cerebrovascular disease, and is recommended in both cardiovascular and cerebrovascular rehabilitation. Disagreement remains, however, on the role of intensity of exercise. The purpose of this review was to gather current knowledge on the effects of high-intensity training versus moderate-intensity continuous exercise on endothelial function in cardiovascular and cerebrovascular patients. Methods: A systematic review was performed in PubMed database, Embase and Cochrane libraries and on PEDro using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were restricted to cardiovascular and cerebrovascular patients, and healthy subjects as general reference. Interventions comprised of high-intensity training alone, high-intensity training compared to moderate-intensity continuous exercise, or no training, with endothelial function as outcome measure. Endothelial function was measured either physiologically by flow-mediated dilatation and/or by systemic biomarkers. Data were analyzed descriptively due to non-comparability for a meta-analysis to be performed. Results: A total of 20 studies were included in the review. Although there was great heterogenecity in design, population and exercise protocols, all studies found high-intensity training to be safe. High-intensity training was equal to moderate-intensity continuous exercise through improvement in endothelial function in 15 of the 20 selected studies, as measured by flow-mediated dilatation, nitric oxide bioavailability and circulating biomarkers. Only a few studies examined high-intensity training in cerebrovascular patients, none with endothelial function as outcome. Conclusion: High-intensity training is promising as a time-efficient exercise strategy in cardiovascular rehabilitation, but data on endothelial effects in cerebrovascular rehabilitation are warranted. Agreement on a
Murray, Alison D; Staff, Roger T; McNeil, Christopher J; Salarirad, Sima; Ahearn, Trevor S; Mustafa, Nazahah; Whalley, Lawrence J
The cognitive reserve hypothesis explains the disparity between clinical and pathological phenotypes and why, in two individuals with the same extent of neuropathology, one may be demented while the other remains cognitively intact. We examined the balance between brain magnetic resonance imaging measures of the two most common pathologies associated with brain ageing, cerebrovascular disease and Alzheimer's disease, and parameters of cerebral reserve in well-characterized participants born in 1936, for whom childhood intelligence is known. Brain magnetic resonance imaging was carried out at 1.5T using fluid attenuation inversion recovery and T(1)-weighted volumetric sequences in 249 participants. Cerebrovascular disease was quantified by measuring brain white matter hyperintensities on fluid attenuation inversion recovery images using Scheltens' scale and Alzheimer's disease was measured from volumetric data using FreeSurfer to extract whole brain volume and hippocampal volumes in turn. The effect of these measures of brain burden on life-long cognitive ageing from the age of 11 to 68 years was compared with the effect of educational attainment and occupational grade using structural equation modelling. Complete brain burden and reserve data were available in 224 participants. We found that educational attainment, but not occupation, has a measurable and positive effect, with a standardized regression weight of +0.23, on late life cognitive ability in people without cognitive impairment aged 68 years, allowing for the influence of childhood intelligence and the two most common subclinical brain pathological burdens in the ageing brain. In addition, we demonstrate that the magnitude of the contribution of education is greater than the negative impact of either neuropathological burden alone, with standardized regression weights of -0.14 for white matter hyperintensities and -0.20 for hippocampal atrophy. This study illustrates how education counteracts the
Su, K P; Hsu, C Y; Hsieh, S C; Shen, W W
Delusions associated with cerebrovascular diseases have been sporadically reported. Although both psychiatrists and neurologists attempted to link delusions with anatomical locations of the brain lesion, comorbid psychiatric and neurological disorders make the interpretation of delusions difficult. The purpose of the present paper is to report the clinical features and magnetic resonance imaging (MRI) characteristics in patients with delusional disorder due to diffuse cerebrovascular diseases, and to redefine the concept of 'vascular delusion'. The clinical features and MRI findings were reviewed retrospectively in a series of seven patients with 'delusional disorder due to cerebrovascular disease' as defined in Diagnostic and Statistical Manual of Mental Disorders (DSMIV). The average age of onset is 64. No patient had a prior personal or family history of major psychiatric illness. The illness is presented as acute, subacute or stepwise course. Hypertension was present in all patients. Two had diabetes mellitus, and one had atrial fibrillation. Three had clinical evidence of previous cerebrovascular attacks, only one showed minor neurological deficits. Three had diffuse cortical slow wave in electroencephalogram. No patient had significant cognitive impairment but had multiple cortical and subcortical cerebrovascular lesions in MRI, with white-matter lesions (WML) in bilateral frontal areas. Delusional disorder due to diffuse cerebrovascular change is characterized by late-onset, stepwise course, and comorbid medical and neurological diseases. The results of vascular changes in the present study did not establish a cause-effect relationship and should be considered as multifactorial in pathogenesis. The findings suggested the hypothesis of neural circuit theory. Further studies in larger numbers of patients and newer neuroimaging techniques are needed to expand the knowledge learned from these findings.
Agnoli, A; Denaro, A; Ruggieri, S
Chronic cerebro-vascular disorders could be considered in a broad sense as a large body of knowledge in which three main categories of clinical disturbances have to be be considered: 1) Pathological aging that manifest itself with light short term memory impairment associated with a mild parkinsonian symptomatology or pseudobulbar signs. 2) Senile dementia Alzheimer type and multi infarct dementia. 3) Chronic cerebro-vascular disorders as defined by the Ad Hoc Committee (Paris, 1980). At present the therapy of chronic cerebro-vascular disorders is based on two main groups of drugs and can be divided into: 1) A treatment of prevention or secondary prevention which tends to correct or modify the different risk factors. 2) A treatment that seeks to control and modify the neurological and neuropsychological after effects and the disorders of the higher nervous activities which result from the lesion.
Giraudo, Maria Teresa; Fasanelli, Francesca; Lenzo, Giulia; Galli, Matteo; Sieri, Sabina; Pala, Valeria; Masala, Giovanna; Bendinelli, Benedetta; Tumino, Rosario; Frasca, Graziella; Chiodini, Paolo; Mattiello, Amalia; Panico, Salvatore
Background A consistent association has been reported between low socioeconomic status (SES) and cardiovascular events (CE), whereas the association between SES and cerebrovascular events (CBVD) is less clear. The aim of this study was to investigate the association between SES (measured using education) and CE/CBVD in a cohort study, as well as to investigate lifestyle and clinical risk factors, to help to clarify the mechanisms by which SES influences CE/CBVD. Material and Methods We searched for diagnoses of CE and CBVD in the clinical records of 47,749 members of the EPICOR cohort (average follow-up time: 11 years). SES was determined by the relative index of inequality (RII). Results A total of 1,156 CE and 468 CBVD were found in the clinical records. An increased risk of CE was observed in the crude Cox model for the third tertile of RII compared to the first tertile (hazard ratio [HR] = 1.39; 95% confidence interval [CI] 1.21–1.61). The increased risk persisted after adjustment for lifestyle risk factors (HR = 1.19; 95%CI 1.02–1.38), clinical risk factors (HR = 1.35; 95%CI 1.17–1.56), and after full adjustment (HR = 1.17; 95%CI 1.01–1.37). Structural equation model showed that lifestyle rather than clinical risk factors are involved in the mechanisms by which education influences CE. No significant association was found between education and CBVD. A strong relationship was observed between education and diabetes at baseline. Conclusion The most important burden of inequality in CE incidence in Italy is due to lifestyle risk factors. PMID:27711245
Brickman, Adam M.; Reitz, Christiane; Luchsinger, José A.; Manly, Jennifer J.; Schupf, Nicole; Muraskin, Jordan; DeCarli, Charles; Brown, Truman R.; Mayeux, Richard
Objective To determine the association of blood pressure (BP) level and longterm fluctuation in BP with cerebrovascular disease. Design Participants received structural MRI and BP measurements in 3, 24 month intervals prior to scanning. We derived the mean and standard deviation (SD) of the mean BP for each participant over the 3 intervals and divided them into four groups defined as above and below the group median (≤ 96.48 mmHg or >96.48mmHg) and further subdivided by the median standard deviation (below SD ≤ 7.21 mmHg or above SD > 7.21 mmHg). This scheme yielded four groups representing the full range of BP and fluctuations in BP. We examined differences in white matter hyperintensity (WMH) volume and brain infarctions across these groups. Setting The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from northern Manhattan. Participants 686 non-demented older adults who received structural MRI and had BP measurements over three study visits. Results WMH volume increased across the four groups in a linear fashion with the lowest WMH volume in the lowest mean/lowest SD group and the highest in the highest mean/highest SD group (F(3,610)=27.43, p=0.0017). Frequency of infarction also increased monotonically across groups (from 22% to 41%; p-for-trend=0.004). Conclusions Compared to individuals with low BP with low fluctuations in BP, the risk of cerebrovascular disease increases with increasing BP and BP fluctuation. Given that cerebrovascular disease is associated with disability, findings suggest that interventions should focus on longterm fluctuating BP as well as elevated BP. PMID:20457955
Nahab, Fadi; Takesaka, Jennifer; Mailyan, Eugene; Judd, Lilith; Culler, Steven; Webb, Adam; Frankel, Michael; Choi, Dennis; Helmers, Sandra
Background: There are limited data on factors associated with 30-day readmissions and the frequency of avoidable readmissions among patients with stroke and other cerebrovascular disease. Methods: University HealthSystem Consortium (UHC) database records were used to identify patients discharged with a diagnosis of stroke or other cerebrovascular disease at a university hospital from January 1, 2007 to December 31, 2009 and readmitted within 30 days to the index hospital. Logistic regression models were used to identify patient and clinical characteristics associated with 30-day readmission. Two neurologists performed chart reviews on readmissions to identify avoidable cases. Results: Of 2706 patients discharged during the study period, 174 patients had 178 readmissions (6.4%) within 30 days. The only factor associated with 30-day readmission was the index length of stay >10 days (vs <5 days; odds ratio [OR] 2.3, 95% CI [1.4, 3.7]). Of 174 patients readmitted within 30 days (median time to readmission 10 days), 92 (53%) were considered avoidable readmissions including 38 (41%) readmitted for elective procedures within 30 days of discharge, 27 (29%) readmitted after inadequate outpatient care coordination, 15 (16%) readmitted after incomplete initial evaluations, 8 (9%) readmitted due to delayed palliative care consultation, and 4 (4%) readmitted after being discharged with inadequate discharge instructions. Only 5% of the readmitted patients had outpatient follow-up recommended within 1 week. Conclusions: More than half of the 30-day readmissions were considered avoidable. Coordinated timing of elective procedures and earlier outpatient follow-up may prevent the majority of avoidable readmissions among patients with stroke and other cerebrovascular disease. PMID:23983857
Zeng, Mingfei; Pan, Linmei; Qi, Shunmei; Cao, Yuntai; Zhu, Huaxu; Guo, Liwei; Zhou, Jing
Recent studies have focused more on Chinese medicine used for the treatment of cerebrovascular disease. The current review covers researches on the pharmacokinetics of Chinese medicine, providing a convenient reference for researchers to increase efficiency of drug discovery, by compiling and discussing the pharmacokinetics of four classical Chinese medicines for therapy of cerebrovascular disease containing: Panax notoginseng, Salvia miltiorrhiza, Ligusticum Chuanxiong and Gardenia. It also helps to eliminate side effect as far as possible from inappropriate Chinese medicine usage. Current integrative and comprehensive review of Chinese medicine for cerebrovascular disease including 1) the absorption of some constituents is limited such as ginsenosides Rg1 and Rb1. It may be affected by gastric juice, first-pass effect, etc. 2) The interactions between Chinese medicine and prescription can occur. Borneol and carbomer would enhance the absorption of R1 and Rg1 in vivo by increasing adjacent cell transport ability. 3) The distribution of active constituents in brain is important for cerebrovascular disease. BBB protects brain from xenobiotic. Intranasal, intra-tympanic administration is a promising alternative to conventional administration to reach brain for ligustrazine. 4) Renal excretion is the uppermost route of these Chinese medicines. But biliary, fecal and urinary excretion are the other major routes. Theoretical and practical aspects are described with pharmacokinetic examples. In the end, this paper also discusses recent development of bio-analysis of Chinese medicine.
Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina
Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N(G) -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.
Piriyawat, Paisith; Smajsová, Miriam; Smith, Melinda A; Pallegar, Sanjay; Al-Wabil, Areej; Garcia, Nelda M; Risser, Jan M; Moyé, Lemuel A; Morgenstern, Lewis B
To provide a scientific rationale for choosing an optimal stroke surveillance method, the authors compared active surveillance with passive surveillance. The methods involved ascertaining cerebrovascular events that occurred in Nueces County, Texas, during calendar year 2000. Active methods utilized screening of hospital and emergency department logs and routine visiting of hospital wards and out-of-hospital sources. Passive means relied on International Classification of Diseases, Ninth Revision (ICD-9), discharge codes for case ascertainment. Cases were validated by fellowship-trained stroke neurologists on the basis of published criteria. The results showed that, of the 6,236 events identified through both active and passive surveillance, 802 were validated to be cerebrovascular events. When passive surveillance alone was used, 209 (26.1%) cases were missed, including 73 (9.1%) cases involving hospital admission and 136 (17.0%) out-of-hospital strokes. Through active surveillance alone, 57 (7.1%) cases were missed. The positive predictive value of active surveillance was 12.2%. Among the 2,099 patients admitted to a hospital, passive surveillance using ICD-9 codes missed 73 cases of cerebrovascular disease and mistakenly included 222 noncases. There were 57 admitted hospital cases missed by active surveillance, including 13 not recognized because of human error. This study provided a quantitative means of assessing the utility of active and passive surveillance for cerebrovascular disease. More uniform surveillance methods would allow comparisons across studies and communities.
Spinelli, Mariacarmela; Demitri, Christian; Sannino, Alessandro; Peruzzotti-Jametti, Luca; Bacigaluppi, Marco; Comi, Giancarlo; Corea, Francesco
The field of neurovascular ultrasound is growing rapidly with new applications. While ultrasound contrast agents were initially used to overcome poor transcranial bone windows for identification of cerebral arteries, newgeneration microbubbles in combination with innovative contrast-specific ultrasound techniques now enable potential therapeutic procedures. This article will provide a review of recent and emerging developments along with patents in ultrasound technology and contrast-specific therapeutic techniques for cerebrovascular patients.
Ferrándiz, Juan; Abellán, Juan J.; Gómez-Rubio, Virgilio; López-Quílez, Antonio; Sanmartín, Pilar; Abellán, Carlos; Martínez-Beneito, Miguel A.; Melchor, Inmaculada; Vanaclocha, Hermelinda; Zurriaga, Óscar; Ballester, Ferrán; Gil, José M.; Pérez-Hoyos, Santiago; Ocaña, Ricardo
Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case–control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991–1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors—calcium and magnesium—on mortality from cerebrovascular (ICD-9 430–438) and ischemic heart (ICD-9 410–414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the
Ferrandiz, Juan; Abellan, Juan J; Gomez-Rubio, Virgilio; Lopez-Quilez, Antonio; Sanmartin, Pilar; Abellan, Carlos; Martinez-Beneito, Miguel A; Melchor, Inmaculada; Vanaclocha, Hermelinda; Zurriaga, Oscar; Ballester, Ferran; Gil, Jose M; Perez-Hoyos, Santiago; Ocana, Ricardo
Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case-control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991-1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors--calcium and magnesium--on mortality from cerebrovascular (ICD-9 430-438) and ischemic heart (ICD-9 410-414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the effect of
Cruse, Belinda; Cysique, Lucette A; Markus, Romesh; Brew, Bruce J
The widespread use of highly active antiretroviral therapy (HAART) in HIV-infected individuals mostly in developed countries has dramatically improved their prognosis. In such advantaged regions of the world, therefore, many patients are now transitioning from middle into older age, with altered patterns of disease. While previously a rare complication of HIV infection, cerebrovascular disease (particularly that associated with atherosclerosis) is becoming relatively more important in this treated group of individuals. This review summarises the evidence regarding the shifting epidemiology of cerebrovascular diseases affecting HIV-infected individuals. While outlining the association between HIV infection and AIDS and cerebrovascular disease, as well as opportunistic diseases and HIV-associated vasculopathies, the current evidence supporting an increase in atherosclerotic disease in treated HIV-infected individuals is emphasised and a management approach to ischaemic stroke in HIV-infected individuals is presented. Evidence supporting the important role of HAART and HIV infection itself in the pathogenesis of atherosclerotic disease is discussed, together with preventative approaches to this increasingly important disease process as the population ages. Finally, a discussion regarding the significant association between cerebrovascular disease and HIV-associated neurocognitive disorder is presented, together with possible mechanisms behind this relationship.
Gusev, E I; Skvortsova, V I; Chukanova, E I
One hundred and eighty-seven patients with different stages of cerebrovascular insufficiency (CI) have been examined. A diagnosis of CI was based on the results of neurological and neuropsychological study, ultrasonic dopplerography, rheo- and encephalography, electrocardiography, brain MRI and eyegrounds examination. Neurological scales were used for neurological status assessment and further data processing. The study aimed at evaluation of tolerability and clinical efficacy of the medication and complications in CI course. Semax treatment resulted in significant clinical improvement, stabilization of the disease progress and reduced a risk of stroke and transitory ischemic attacks in the disease course. The drug is featured by minor percent of side-effects and is well tolerated by patients, including those of older age groups.
Guo, Hao; Li, Lei; Hou, Jin-Cai; Liu, Jian-Xun
Remaining organic and functional damage of ischemia cardio-cerebrovascular disease is always a main trouble puzzling the clinicians. After the discovery of endothelial progenitor cells (EPCs), researchers realize that postnatal angiogenesis is an important biological process, which play a key role to repair the ischemia tissue and improve the function. So a new concept which names therapeutic angiogenesis supply a new treament way for the ischemia cardio-cerebrovascular disease. Traditional Chinese medicine (TCM) has accumulated rich experience on treating the ischemia disease, studies found that many Chinese medicine prescriptions and effective ingredients can increase the therapeutic angiogenesis, howerer the mechanisms were not the same, they mainly manifest in regular the secretion of angiogenic factors, increase the proliferation and differentiation etc. In this paper, we review recent studies, summary the Chinese medicine prescriptions and effective ingredients which can increase the therapeutic angiogenesis, and analyze the differernt pathway. We view to provide reference for the later researchers.
Wong, Caine W.; Quaranta, Vito; Glenner, George G.
A synthetic peptide (Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr), homologous to the amino terminus of a protein purified from cerebrovascular amyloid (β protein), induced antibodies in BALB/c mice that were used immunohistochemically to stain not only amyloid-laden cerebral vessels but neuritic plaques as well. These findings suggest that the amyloid in neuritic plaques shares antigenic determinants with β protein of cerebral vessels. Since the amino acid compositions of plaque amyloid and cerebrovascular amyloid are similar, it is likely that plaque amyloid also consists of β protein. This possibility suggests a model for the pathogenesis of Alzheimer disease involving β protein.
Objectives: The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) was designed to evaluate the conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for primary prevention of Alzheimer's dementia (AD). On 17 December 2004, after the Adenoma Prevention with Celecoxib (APC) trial reported increased cardiovascular risks with celecoxib, the ADAPT Steering Committee suspended treatment and enrollment. This paper reports on cardiovascular and cerebrovascular events in ADAPT. Design: ADAPT is a randomized, placebo-controlled, parallel chemoprevention trial with 1–46 mo of follow-up. Setting: The trial was conducted at six field sites in the United States: Baltimore, Maryland; Boston, Massachusetts; Rochester, New York; Seattle, Washington; Sun City, Arizona; and Tampa, Florida. Participants: The 2,528 participants were aged 70 y and older with a family history of AD. Interventions: Study treatments were celecoxib (200 mg b.i.d.), naproxen sodium (220 mg b.i.d.), and placebo. Outcome measures: Outcome measures were deaths, along with nonfatal myocardial infarction (MI), stroke, congestive heart failure (CHF), transient ischemic attack (TIA), and antihypertensive treatment recorded from structured interviews at scheduled intervals. Cox proportional hazards regression was used to analyze these events individually and in several composites. Results: Counts (with 3-y incidence) of participants who experienced cardiovascular or cerebrovascular death, MI, stroke, CHF, or TIA in the celecoxib-, naproxen-, and placebo-treated groups were 28/717 (5.54%), 40/713 (8.25%), and 37/1070 (5.68%), respectively. This yielded a hazard ratio (95% confidence interval [CI]) for celecoxib of 1.10 (0.67–1.79) and for naproxen of 1.63 (1.04–2.55). Antihypertensive treatment was initiated in 160/440 (47.43%), 147/427 (45.00%), and 164/644 (34.08%). This yielded hazard ratios (CIs) of 1.56 for celecoxib (1.26–1.94) and 1.40 for naproxen (1.12–1
Proietti, Marco; Mairesse, Georges H; Goethals, Peter; Scavee, Christophe; Vijgen, Johan; Blankoff, Ivan; Vandekerckhove, Yves; Lip, Gregory Yh
Background Cerebrovascular disease confers a major healthcare burden worldwide and is a major cause of death and disability. Several well-established risk factors, such as atrial fibrillation (AF), are associated with cerebrovascular disease and antithrombotic therapy reduces risk. Design This study was a subgroup analysis from the Belgian Heart Rhythm Week, a nationwide AF awareness programme. Methods We studied subjects screened between 2012 and 2014 with available data on clinical risk factors and antithrombotic treatment. Results Of the 38,034 subjects eligible for this analysis, 1513 (4.0%) reported a positive clinical history for cerebrovascular disease. Logistic regression analysis found that age, hypertension, diabetes mellitus, history of vascular disease, history of heart failure and history of AF (all p < 0.001) were independently associated with cerebrovascular disease. Among subjects with history of cerebrovascular disease and AF, 1.7% were taking oral anticoagulant drugs only, while both oral anticoagulant drugs and aspirin were used in 61.5% of subjects, aspirin in 4.3% of patients and no antithrombotic therapy in 32.5% of subjects. Among those subjects without AF, the corresponding figures were 0.8, 9.5, 2.0 and 87.6%, respectively. Conclusions The prevalence of cerebrovascular disease in this contemporary population screening project was higher than that reported in the general population and was associated with the major known stroke risk factors. Sub-optimal antithrombotic therapy management was evident, with a low use of oral anticoagulant drugs among patients with AF and a low use of aspirin among subjects without AF.
Hartmann, A.; Tsuda, Y.
Regional cerebral blood flow (rCBF) in 90 patients with CBF decreased due to vascular diseases was studied by using the xenon 133 inhalation technique and a 32-detector setup. Whereas 30 patients received their standard basic therapy only and were regarded as controls, 30 others received 3 x 2 mg/day of an ergot alkaloid (co-dergocrine mesylate), and 30 others received 3 x 400 mg pentoxifylline (slow-release formulation)/day orally. Therapy was performed for eight weeks and CBF measured before start of treatment, after a four-week treatment period, and at the end of the study. CBF did not change significantly in the control group; both the pentoxifylline and the ergot alkaloid group presented with a significant increase in the CBF. This positive effect was significantly more pronounced in the pentoxifylline group and affected more ischemic than other brain tissues. In addition, symptoms like sleep disturbances, vertigo, and tinnitus improved significantly during the pentoxifylline observation period.
Background Diseases of the circulatory system (CVD) are the most common causes of death in developed countries. However, the prevalence of CVD varies between countries; for example, the mortality rate in Russia is about four times higher than in Western Europe. In a recent retrospective cohort study it was unexpectedly found that CVD mortality is lower among "Aussiedler" (ethnic Germans from the former Soviet Union) compared to the German population. Methods This is a case-control study, nested into a recent cohort study of migrants from the former Soviet Union. Relatives of cases and controls themselves were interviewed by telephone using a standardized questionnaire. To estimate relative risks via the odds ratio (OR), a conditional logistic regression procedure was performed. Results Commonly known risk factors for CVD were identified as relevant to Aussiedler. The best multivariate model for CVD includes five risk factors: consumption of alcohol, smoking, diabetes, cholesterol and consumption of sweets. For alcohol consumption and smoking, OR = 3.68 (95% CI, 1.58-8.58) and OR = 3.07 (95% CI, 1.42-6.62), respectively. For diabetes mellitus and high cholesterol values, OR = 3.29 (95% CI, 1.50-7.39) and OR = 2.32 (95% CI, 1.11-4.88), respectively. The almost complete abdication of sweets is associated with a protective effect, OR = 0.34 (95% CI, 0.18-0.64). The prevalence of risk factors is somewhat different to that of the autochthon German population and partly explains the differences in CVD mortality between both groups. Conclusions The reported lower prevalences of known risk factors of CVD such as alcohol consumption, high cholesterol, diabetes and smoking (in women) could contribute to a lower risk of CVD. PMID:22413759
Ebrahimi, Ali P.
Background: Blood vessel mechanics has traditionally been of interest to researchers and clinicians. Changes in mechanical properties of arteries have been associated with various diseases. Objective: To provide a comprehensive review directed towards understanding the basic biomechanical properties of cerebral arteries under normal and diseased conditions. Methods: Literature review supplemented by personal knowledge. Results: The mechanical properties of vascular tissue may depend on several factors including macromolecular volume fraction, molecular orientation, and volume or number of cells such as smooth muscle cells. Mechanical properties of a blood vessel have been characterized using different methods such as in vitro tensile testing, non-invasive ultrasound examination, and mathematical models. Experiments are complicated by the variation in properties and content of materials that make up the vessel wall and more challenging as the size of the vessel of interest decreases. Therapeutic interventions aiming to alter the mechanical response are either pharmaceutical: including calcium channel blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and β-blockers; or, mechanical interventions such as angioplasty, stent placement, mechanical thrombectomy, or embolization procedures. Conclusion: It is apparent from the literature that macromolecular and cellular mechanics of blood vessels are not fully understood. Therefore, further studies are necessary to better understand contribution of these mechanisms to the overall mechanics of the vascular tissue. PMID:22518247
Slivka, A; Levy, D E; Lapinski, R H
Intravenous heparin is frequently used to treat thromboembolic disease, but the consequences of stopping heparin have not been studied systematically. To determine whether discontinuing heparin poses a clinical risk, we examined the charts of 378 patients treated with heparin for transient ischaemic attack (TIA), reversible ischaemic neurological deficit, or ischaemic stroke from October 1979 to June 1985. Clinical deterioration, or a new TIA or stroke was more likely (p = 0.01) during the 24 hours after heparin was stopped in patients not already on aspirin or warfarin (10/143, 7%) than in patients receiving aspirin or warfarin before heparin withdrawal (3/215, 1%). Stopping heparin in patients not receiving aspirin or warfarin appears to expose them to an increased risk for TIA, stroke, or clinical deterioration. PMID:2614427
[The group study of diagnostic efficacy of cerebro-vascular disease by I-123 IMP SPECT images obtained with ring type SPECT scanner--the ROC analysis on the diagnosis of perfusion defect and redistribution].
Machida, K; Matsumoto, T; Honda, N; Mamiya, T; Takahashi, T; Takishima, T; Kamano, T; Tamaki, S; Iinuma, T A; Tateno, Y
We performed two image reading experiments in order to investigate the diagnostic capability of I-123 IMP SPECT obtained by the ring type SPECT scanner in cerebro-vascular disease. Fourteen physicians diagnosed SPECT images of 55 cases with reference to clinical neurological informations, first without brain XCT images and second with XCT images. Each physician detected perfusion defects and redistributions of I-123 IMP and assigned a confidence level of abnormality for these SPECT findings by means of five rating method. From results obtained by ROC analysis, we concluded as follows: (1) Generally, I-123 IMP SPECT is a stable diagnostic modality in the diagnosis of cerebro-vascular disease and the image reading of XCT had no effects on the diagnosis of SPECT on the whole of physician, (2) However, there were unnegligible differences among individuals in the detectability of findings and the effect of XCT image reading, (3) Detectability of redistribution of I-123 IMP was lower than that of perfusion defect and inter-observer variation in the diagnostic performance for redistribution was larger than that of perfusion defect. The results suggest that it is necessary to standardize diagnostic criteria among physicians for redistribution of I-123 IMP.
Background The contribution of cerebrovascular function to cognitive performance is gaining increased attention. Transcranial doppler (TCD) is portable, reliable, inexpensive and extremely well tolerated by young and clinical samples. It enables measurement of blood flow velocity in major cerebral arteries at rest and during cognitive tasks. Methods We systematically reviewed evidence for associations between cognitive performance and cerebrovascular function in children (0-18 years), as measured using TCD. A total of 2778 articles were retrieved from PsychInfo, Pubmed, and EMBASE searches and 25 relevant articles were identified. Results Most studies investigated clinical groups, where decreased blood flow velocities in infants were associated with poor neurological functioning, and increased blood flow velocities in children with Sickle cell disease were typically associated with cognitive impairment and lower intelligence. Studies were also identified assessing autistic behaviour, mental retardation and sleep disordered breathing. In healthy children, the majority of studies reported cognitive processing produced lateralised changes in blood flow velocities however these physiological responses did not appear to correlate with behavioural cognitive performance. Conclusion Poor cognitive performance appears to be associated with decreased blood flow velocities in premature infants, and increased velocities in Sickle cell disease children using TCD methods. However knowledge in healthy samples is relatively limited. The technique is well tolerated by children, is portable and inexpensive. It therefore stands to make a valuable contribution to knowledge regarding the underlying functional biology of cognitive performance in childhood. PMID:24602446
Carta, Mauro Giovanni; Pala, Andrea Norcini; Finco, Gabriele; Musu, Mario; Moro, Maria Francesca
Introduction : Depression and cerebrovascular atherosclerosis often occur in comorbidity showing neuropsychological impairment and poor response to antidepressant treatment. Objective is to evaluate if new antidepressant vortioxetine may be a potential treatment option. Mechanism of Action : Vortioxetine has 5-HT3, 5-HT7 and 5-HT1D antagonists, 5-HT1B partial agonist and a 5-HT1A agonist and serotonin transporter inhibitor property. Efficacy and safety in Major Depressive Disorders and in cognitive impairment : The majority of trials (one of them in older people) showed efficacy for vortioxetine against placebo and no differences against other active treatments. The Adverse Effects ranged from 15.8% more to 10.8% less than placebo. In the elderly, only nausea was found higher than placebo. Effects on arterial blood pressure and cardiac parameters including the ECG-QT segment were similar to placebo. Elderly depressive patients on vortioxetine showed improvement versus placebo and other active comparators in Auditory Verbal Learning Test and Digit Symbol Substitution Test scores. The inclusion criteria admitted cases with middle cerebrovascular disease. Conclusion : The mechanism of action, the efficacy on depression and safety profile and early data on cognitive impairment make Vortioxetine a strong candidate for use in depression associated with cerebrovascular disease. This information must be supported by future randomized controlled trials. PMID:25893002
Meguro, Kenichi; Tanaka, Naofumi; Nakatsuka, Masahiro; Nakamura, Kei; Satoh, Masayuki
The concept and diagnosis for mixed dementia is not simple, since it is difficult to identify the type and regions of cerebrovascular disease (CVD) responsible for causing dementia. An investigation is needed to confirm the presence of mixed dementia, those who met the criteria for Alzheimer's disease (AD) and those for vascular dementia (VaD). According to the community-based stroke, dementia, and bed-confinement prevention in Kurihara, northern Japan (Kurihara Project), the prevalence of dementia and dementing diseases was surveyed in 2008-2010. Five hundred and ninety people finally agreed to participate (47.0%), and 73 (12.4%) people were diagnosed with dementia according to the DSM-IV. Using MRI, intensive evaluations on CVDs were performed for the 49 dementia patients associated with CVDs (mixed dementia, VaD, and AD with CVD). For the mixed dementia group, all had left subcortical strategic CVDs. These included the caudate head and thalamus. For the VaD group, all patients had at least cortical CVDs or subcortical strategic CVDs. The AD with CVD group had non-strategic CVDs in cortical, subcortical, or other areas in 5 or 6 patients each. Two extreme concepts regarding CVD and dementia are possible. One is that there is no concept for mixed dementia or VaD. An alternative is that the vascular factor should be considered as primary. Our data showed an importance of cortical and subcortical "strategic" areas, the latter included thalamus and caudate head.
Wang, Hui; Sun, Wei; Ji, Yue; Shi, Jing; Xuan, Qinkao; Wang, Xiuzhi; Xiao, Junjie; Kong, Xiangqing
Although the mortality of cerebrovascular disease (CVD) has been steadily declined in the European Union (EU), CVD remains among the major causes of death in EU. As risk factors such asobesity and diabetes mellitus are increasing, the trends of European CVD mortality remains unknown. To understand the variation in CVD mortality of different EU countries, we studied the trends in CVD mortality in EU countries over the last three decades between males and females. Age- and sex-specific mortality rates between 1980 and 2011 were calculated by data from the WHO mortality database. Joinpoint software was used to calculate annual percentage changes and to characterize trends in mortality rates over time. Our study showed that between 1980 and 2011, CVD mortality significantly decreased in both men and women across all age groups. The specific mortality trends varied largely between EU countries. The plateau trend was observed in little regions at different age groups, however, the EU as a whole displayed declined trend CVD mortality. During the last three decades, CVD mortality decreased substantially in the entire population of EU. However, despite this overall decline in CVD mortality, several areas were identified as having no change in their CVD mortality rates at different period. The whole EU needs to establish strict prevention measures toreduce the incidence of CVD risk factors. PMID:25550927
Takahashi, Hidetoshi; Iinuma, Shin; Honma, Masaru; Iizuka, Hajime
Psoriasis is a chronic inflammatory skin disease, which may be associated with metabolic syndrome accompanied by cardio- and cerebrovascular diseases. We investigated the relation between serum C-reactive protein (CRP) and cardio- and cerebrovascular diseases in Japanese psoriasis vulgaris patients. Ninety-seven psoriasis vulgaris patients and 79 healthy controls were assessed for serum CRP levels by immunoturbidimetry. The data were analyzed in terms of Psoriasis Area and Severity Index (PASI) scores, and comorbidity of cardio- and cerebrovascular disease and metabolic syndrome. Serum CRP levels in psoriasis vulgaris patients were significantly higher than those of healthy controls. There was no significant difference between male and female CRP levels in either psoriasis or healthy controls. No correlation was detected between PASI scores and serum CRP levels, either. Psoriasis with cardio- and cerebrovascular disease showed significantly higher CRP levels compared with those without the diseases. Furthermore, psoriasis with metabolic syndrome showed significantly higher serum CRP levels than those without the metabolic syndrome. In conclusion, serum CRP level is increased in psoriasis, and may be a useful marker for the prediction of the future risk of cardio- and cerebrovascular disease.
Dobson, Scott R; Holden, Kenton R; Nietert, Paul J; Cure, Joel K; Laver, Joseph H; Disco, Deborah; Abboud, Miguel R
We conducted a retrospective study to determine whether the presence of moyamoya collaterals influenced the risk of recurrence of cerebrovascular events (CVEs: stroke or transient ischemic attack) in patients with sickle cell disease placed on chronic transfusions after a stroke. Forty-three patients with homozygous sickle cell anemia (HbSS) and 1 with HbSO(Arab) (16 females, 28 males) who had suffered strokes while under the age of 18 were studied. All patients had been on transfusions aimed at maintaining the sickle hemoglobin (HbS) level below 30%. They were followed for a mean of 6.6 years (2.2 to 20.4 years). The presence of collaterals was diagnosed based on either magnetic resonance angiography or conventional angiography. Eighteen (41%) of the 44 patients suffered recurrent CVEs. Nineteen (43%) (6 females, 13 males) patients had moyamoya collaterals. Eleven (58%) of these 19 experienced 21 total recurrent CVEs, including 4 strokes in 4 patients (21%). In comparison, 7 (28%) of 25 patients without moyamoya collaterals experienced 9 recurrent CVEs (P <.05) with only 1 recurrent stroke (4%). Moyamoya patients were also more likely to have 2 recurrent CVEs (42% vs 8%, P <.05) as well as poorer neuropsychological testing results. A proportional hazards regression analysis indicated that patients with moyamoya were more than twice as likely to incur a subsequent CVE (hazard ratio, 2.40; 95% confidence interval, 0.85, 6.75). We conclude that up to 41% of patients with sickle cell disease experience recurrent CVEs after an initial stroke despite chronic transfusions and that the risk of recurrence is significantly higher for those who have moyamoya collaterals.
Simonetto, Cristoforo; Schöllnberger, Helmut; Azizova, Tamara V.; Grigoryeva, Evgenia S.; Pikulina, Maria V.; Eidemüller, Markus
A detailed analysis of cerebrovascular diseases (CeVD) for the cohort of workers at Mayak Production Association (PA) is presented. This cohort is especially suitable for the analysis of radiation induced circulatory diseases, due to the detailed medical surveillance and information on several risk factors. The risk after external, typically protracted, gamma exposure is analysed, accounting for potential additional internal alpha exposure. Three different endpoints have been investigated: incidence and mortality from all cerebrovascular diseases and incidence of stroke. Particular emphasis was given to the form of the dose-response relationship and the time dependence of the radiation induced risk. Young attained age was observed to be an important, aggravating modifier of radiation risk for incidence of CeVD and stroke. For incidence of CeVD, our analysis supports a dose response sub-linear for low doses. Finally, the excess relative risk per dose was confirmed to be significantly higher for incidence of CeVD compared to CeVD mortality and incidence of stroke. Arguments are presented for this difference to be based on a true biological effect. PMID:25933038
Ongali, Brice; Nicolakakis, Nektaria; Tong, Xing-Kang; Aboulkassim, Tahar; Imboden, Hans; Hamel, Edith
The co-administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II (AngII) receptor blockers (ARB) that bind angiotensin type 1 receptors (AT1R) may protect from Alzheimer's disease (AD) better than each treatment taken alone. We tested the curative potential of the non brain-penetrant ACEi enalapril (3 mg/kg/day) administered for 3 months either alone or in combination with the brain penetrant ARB losartan (10 mg/kg/day) in aged (∼15 months) transgenic mice overexpressing a mutated form of the human amyloid-β protein precursor (AβPP, thereafter APP mice). We studied cerebrovascular function, protein levels of oxidative stress markers (superoxide dismutases SOD1, SOD2 and the NADPH oxidase subunit p67phox), amyloid-β (Aβ) pathology, astrogliosis, cholinergic innervation, AT1R and angiotensin IV receptor (AT4R) levels, together with cognitive performance. Both treatments normalized cerebrovascular reactivity and p67phox protein levels, but they did not reduce the cerebrovascular levels of SOD1. Combined treatment normalized cerebrovascular SOD2 levels, significantly attenuated astrogliosis, but did not reduce the increased levels of cerebrovascular AT1R. Yet, combined therapy enhanced thioflavin-S labeled Aβ plaque burden, a tendency not significant when Aβ1 - 42 plaque load was considered. None of the treatments rescued cognitive deficits, cortical AT4R or cholinergic innervation. We conclude that both treatments normalized cerebrovascular function by inhibiting the AngII-induced oxidative stress cascade, and that the positive effects of the combined therapy on astrogliosis were likely due to the ability of losartan to enter brain parenchyma. However, enalapril did not potentiate, and may even dampen, the reported cognitive benefits of losartan, raising caution when selecting the most appropriate antihypertensive therapy in AD patients.
Matsumoto, K; Ohta, T; Iwatsuka, T; Hashimoto, S; Fukutomi, K
The relation of variables obtained from a baseline examination to death from ischemic heart disease (IHD), cerebro-vascular disease (CVD) and sudden death (SUD) was analyzed in a case-control study. From questionnaire survey of approximately 180,000 subjects who underwent baseline health examinations in 1971-1986 at Aichi prefectural center of health care, 148 deaths were selected for this study. The number of cases on IHD, CVD and SUD was 36, 60, and 52, respectively. Mean age of cases was 54.8 years old and the mean follow up interval between baseline examination and death was 3.7 years. Four controls matched according to year of baseline examination, age and sex were chosen arbitrarily for each case, and odds ratios for the three diseases were estimated. In some of the matched sets, odds ratios at a follow up examination were compared with that at the first examination. The results were as follows: 1) Variables showing positive relationships to death from each of the three diseases were hypertension, high fasting blood sugar, abnormality of cardio-thoracic ratio, ST-T abnormality in ECG, left ventricular hypertrophy in ECG. The odds ratio for ST-T abnormality in ECG was significant for all three causes of death. 2) High total cholesterol showed a significant positive relation only to death from IHD. As to death from CVD and SUD, albuminuria and sclerotic changes in fundus oculi were positively and significantly related. Risk factors differed for deaths from the three diseases. 3) In death from IHD and CVD, odds ratio at the second examination was apt to be higher than that at baseline examination. In death from SUD, however, odds ratios at the first and the second examination showed no significant difference.
Stoeter, P; Ortega-Suhrkamp, E; Voigt, K
Although cerebral angiography should be approached with caution in the diagnosis of inflammatory cerebro-vascular disease there are some characteristic angiographic findings which may be helpful for classification and differential diagnosis. The proximal cerebral arteries are favourably affected by basal meningitis and thrombangiitis obliterans with resulting stenoses and occlusions. Whereas those inflammations originating from neighbouring skull structures mostly involve the intracavernous parts of the carotid artery, the tuberculous and mycotic arteritis prefer the supraclinoid carotid siphon. Peripheral vascular changes are found in luetic endangiitis, necrotizing and toxic angiitis and in collagenoses. Simultaneous involvement of the temporal arteries is of great diagnostic importance demonstrating the systemic character of the inflammatory process; in Horton's arteritis it can be a pathognomonic finding. Infectious endocarditis, some mycoses and malaria may lead to embolic occlusion of cerebral vessels. Mycotic aneurysms mostly have a broad base or a fusiform shape and do not prefer the localizations of congenital aneurysms. Angiographically, abscesses, tuberculomas and viral encephalitis may result in circumscribed hypervascularized areas. The characteristic angiographic findings are exemplified and discussed on the basis of 8 cases of inflammatory cerebro-vascular disease (tuberculosis, pneumococcal and unspecific bacterial meningitis, syphilis, mycosis, Takayasu-syndrome, panarteritis nodosa, temporal arteritis).
Buletsa, B A; Fatula, M I; Fabri, Z I
A total of 417 patients with cerebral circulatory disorders were examined in two biogeochemical regions of the UkrainianCarpathian Mountains. The first one is a region with iodine insufficiency; the second one is a region where the people use table salt in excess. It has been established that iodine insufficiency and excessive iodine concentration in the body of man are risk factors of the development of cerebrovascular disease. Besides, in persons with abnormal iodine metabolism, cerebrovascular diseases run a graver course than in those with normal content in the body of these trace elements.
Gao, Yong-Zhe; Zhang, Jun-Jian; Liu, Hui; Wu, Guang-Yao; Xiong, Li; Shu, Min
Hemodynamic disturbance in cerebral blood flow (CBF) is common in both Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to investigate the different patterns of regional cerebral blood flow (rCBF) change and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance, separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2 inhalation. The ASL results showed that, rCBF was significantly lower in both the bilateral frontal and temporal lobes in AD group and lower in left frontal and temporal white matter in patients with VaD. CVR calculated by rCBF was impaired more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed to demonstrate significant difference in MFV and CVR between the two groups. It is concluded that the different patterns detected by ASL in resting rCBF change and cerebrovascular reactivity in response to carbogen inhalation may serve as a potential marker to distinguish AD and VaD.
Gebel, James M
The beneficial effects of antiplatelet therapy for secondary prevention in patients with prior cardiovascular or cerebrovascular events, including stroke, transient ischemic attack, and myocardial infarction, have been demonstrated repeatedly over the past decade. It is increasingly apparent that pathophysiologic differences between patients with different types of prior vascular events have an important effect on treatment outcomes. Several large, important trials of antiplatelet therapies, including MATCH, CHARISMA, ESPRIT, and TRITON-TIMI 38, underscore the heterogeneity of the efficacy and safety of antiplatelet agents in patients with recent cerebrovascular disease, compared with patients with recent acute coronary syndromes. Trial data therefore support an individualized approach to antithrombotic therapy for secondary vascular-event prevention that is appropriate for any probable future vascular events and actively reduces the impact of modifiable risk factors common to all vascular events. The potential for benefit in reducing recurrent vascular events must be weighed against the increased risk of bleeding and of patient non-responsiveness to treatment. A number of other factors also need to be considered, including drug interactions, patient compliance, and adverse-effect profiles. Overall, there is now a substantial body of clinical trial evidence that supports the need to carefully individualize antiplatelet therapy and other risk-reducing strategies on the basis of each patient's pathology and specific needs.
Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya
Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals.
Barone, Frank C; Gustafson, Deborah; Crystal, Howard A; Moreno, Herman; Adamski, Mateusz G; Arai, Ken; Baird, Alison E; Balucani, Clotilde; Brickman, Adam M; Cechetto, David; Gorelick, Philip; Biessels, Geert Jan; Kiliaan, Amanda; Launer, Lenore; Schneider, Julie; Sorond, Farzaneh A; Whitmer, Rachel; Wright, Clinton; Zhang, Zheng Gang
As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international
Li, Weili; Cheng, Ruilian
To investigate the fall efficiency and its influence factors of the hospitalized geriatric patients with cerebrovascular diseases. The Modified Fall Efficacy Scale (MFES), Morse Fall Risk Assessment Scales (MFS), Berg Balance Scale (BBS) and Tinetti Gait Analysis (TGA) were adopted and the combined ways of questionnaires and observation were utilized to investigate the 113 hospitalized geriatric patients with cerebrovascular diseases. The fall efficiency of the geriatric patients with cerebrovascular diseases were 7.85±2.57 scores. The two projects "walking up and down stairs" and "taking public transport means" have got the lowest scores; The two projects "stretching out the hand to the box or the drawer for taking something" and "sitting up and down to the chair" have got the highest scores. It was found that there were three factors which had significant influences on the fall efficiency, they were myodynamia of the right upper extremity, Berg balance functions and gait. For the sake of helping the geriatric patients with cerebrovascular diseases to establish the self-confidence of preventing the falls, the medical workers need to take further psychological counseling for the patients and befittingly and specifically to improve the fall efficiency of patients so as to effectively prevent the occurring of the fall on the basis of improving the balance ability and gait of patients.
Lessa, I; Silva, M R
Social inequalities and the excess (%) in mortality by cerebrovascular diseases (CVD) unregistered in the official death statistics were studied in Salvador, Brazil, 1988. In an ecological spacial (aggregate) desing, all death mentioning CVD as basic and as associated cause of death were reviewed and distributed, according to their addresses by 66 geographical zones. The mortality rates by CVD (basic+associated) ranged from 22.94 to 376.62/10,000 adults. The mortality fraction not included in the official statistics was 29.1% for Salvador with means between 16.12 and 33.72% in the group of zones of very low to those in the high mortality levels. Seven out of 16 zones included in the 4th quantil showed exceptionally high mortality rates (above those of Salvador + 1.64 x standard deviation corrected by the zones population). The authors discuss possible explanations for the social differences in the mortality profile.
Sato, Naoyuki; Shimamura, Munehisa; Morishita, Ryuichi
Gene therapy provides a potential strategy for the treatment of cardiovascular disease such as peripheral arterial disease, myocardial infarction, restenosis after angioplasty, and vascular bypass graft occlusion. Currently, more than 20 clinical studies of gene therapy for cardiovascular disease are in progress. Although cerebrovascular gene therapy has not proceeded to clinical trials, in contrast to cardiovascular gene therapy, there have been several trials in experimental models. Three major potential targets for cerebrovascular gene therapy are vasospasm after subarachnoid hemorrhage (SAH), ischemic cerebrovascular disease, and restenosis after angioplasty, for which current therapy is often inadequate. In experimental SAH models, strategies using genes encoding a vasodilating protein or decoy oligodeoxynucleotides have been reported to be effective against vasospasm after SAH. In experimental ischemic cerebrovascular disease, gene therapy using growth factors, such as Brain-derived neurotrophic factor (BDNF), Fibroblast growth factor-2 (FGF-2), or Hepatocyte growth factor (HGF), has been reported to be effective for neuroprotection and angiogenesis. Nevertheless, cerebrovascular gene therapy for clinical human treatment still has some problems, such as transfection efficiency and the safety of vectors. Development of an effective and safe delivery system for a target gene will make human cerebrovascular gene therapy possible.
Bhargava, Seema; Ali, Arif; Kankra, Mamta; Das, Sabari; Manocha, Anjali; Gupta, Flora; Srivastava, Lalit Mohan
Data from studies examining lipid peroxidation as a mechanism involved with hyperhomocysteinemia (HHcy)-induced vascular remodeling in patients with occlusive vascular disease have been contradictory. It has not yet been studied in Indians within the context of atherogenesis. Therefore, we measured the levels of homocysteine (Hcy), malondialdehyde (MDA) as a measure of lipid peroxides (LPOs), and total antioxidant status (TAS) in the serum of 167 patients with occlusive vascular disease [coronary artery disease (CAD) = 43; cerebrovascular disease (CVD) = 82; peripheral vascular disease (PVD) = 42]. Each of these groups was further divided into groups of individuals with or without HHcy. In the case of CAD and CVD, patients with HHcy had significantly higher LPOs than those without HHcy (p = 0.009, 0.001, respectively). TAS was significantly lower in CVD patients with HHcy than in those without (p = 0.014). In patients with CAD or CVD, Hcy directly correlated with LPOs (p = 0.002, 0.001, respectively). Lipid peroxidation is a significant mechanism in HHcy-induced vascular remodeling in CAD and CVD, but not in PVD, probably because it is not relevant in thrombosis (38 of 42 patients of PVD had deep-vein thrombosis). To explain the significantly lower TAS in CVD, we hypothesized that CVD patients present very early with grave symptoms, whereas CAD and PVD occur over a longer period of time. Therefore, when CVD presents, TAS is still overwhelmed by HHcy-induced oxidative stress. Hence, adjuvant therapy with antioxidants would benefit patients with CVD.
Anazodo, Udunna C.; Shoemaker, J. K.; Suskin, Neville; Ssali, Tracy; Wang, Danny J. J.; St. Lawrence, Keith S.
Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control. PMID:26779011
Aizer, Ayal A; Du, Rose; Wen, Patrick Y; Arvold, Nils D
Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983-2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42-0.93 %) versus 0.16 % (95 % CI 0.055-0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25-6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50-1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients.
Kim, Julia; Schweizer, Tom A.; Fischer, Corinne E.; Munoz, David G.
Background: The pathophysiology behind psychosis in patients with Alzheimer’s disease (AD) remains unknown. Recently, vascular risk factors have been recognized as important modifiers of the clinical presentation of AD. Objective: The purpose of our study is to investigate the mechanism through which vascular risk factors mediate psychosis and whether or not it involves cerebrovascular lesions. Methods: Data was provided by the National Alzheimer’s Coordinating Centre. The Uniform Data Set was used to collect information on subject-reported history of vascular risk factors, clinician-reported state of cognitive performance, and presence of psychosis based on the Neuropsychiatric Inventory Questionnaire (NPI-Q). The Neuropathology Data Set was used to evaluate the presence of vascular lesions and the severity of AD pathology. Subjects with high probability of AD based on the NIA/AA Reagan criteria were included in the analysis. Results: We identified 1,459 patients with high probability of AD and corresponding NPI-Q scores. We confirmed the association between hypertension and diabetes on psychosis, specifically in delusions and the co-occurrence of delusions and hallucinations. Furthermore, the presence of white matter rarefaction based on pathological evaluation was associated with hallucinations. A history of vascular risk factors was positively associated with vascular lesions. However, vascular lesions in the presence of vascular risk factors did not increase the likelihood of psychosis. Furthermore, vascular lesions were not associated with greater cognitive or functional impairments in this group with severe AD pathology. Conclusion: Vascular risk factors and vascular lesions are independently associated with psychosis in patients with severe AD. However, vascular lesions are not the mechanism through which vascular risk factors mediate psychosis. PMID:27662301
Kholmogorov, N A; Shprakh, V V; Miriutova, N F
Treatment of patients at the early stages of cerebrovascular diseases with the use of sodium chloride baths resulted in the improvement of morphological and functional characteristics of brain vessels. Combination of sodium chloride baths with impulse currents and magnetic fields caused regression of neurologic and neuropsychotic disturbances in 80% of the patients. Beneficial therapeutic effects persisted especially long when the patients received the above treatment during 21-24 days.
Harada, K; Uozumi, T; Kurisu, K; Sumida, M; Nakahara, A; Migita, K
Five cases of cerebro-vascular diseases with carotid-basilar anastomosis were evaluated. Case 1: a 73-year-old female was diagnosed as having subarachnoid hemorrhage due to a ruptured aneurysm of the right internal carotid artery-posterior communicating artery bifurcation and demonstrated that a left proatlantal intersegmental artery. Case 2: a 38-year-old female showed intraventricle hemorrhage due to arteriovenous malformation and showed left primitive hypoglossal artery. Case 3: 73-year-old female was diagnosed as having subarachnoid hemorrhage due to a ruptured basilar top aneurysm and demonstrated that a right primitive hypoglossal artery. Case 4: a 29-year-old male with unruptured aneurysm of the left internal carotid artery-posterior communicating artery bifurcation, and right trigeminal artery was detected incidentally by magnetic resonance angiography (MRA). Furthermore, right proatlantal intersegmental artery was detected by conventional angiography. Case 5: a 76-year-old male was diagnosed as having subarachnoid hemorrhage due to a ruptured aneurysm of the anterior communicating artery. MRA showed the aneurysm and a primitive trigeminal artery. No clinical symptom related with carotid-basilar anastomosis was detected. Magnetic resonance angiography (MRA) was useful for diagnosis of asymptomatic carotid-basilar anastomosis. Especially, axial view of MRA by time of flight method detected two cases of a primitive trigeminal artery. And coronal view of MRA by phase contrast method is useful for diagnosis of primitive proatlantal intersegmental artery. More asymptomatic persistent carotid-basilar anastomosis may be detected by MRA.
Introduction of multislice CT (MSCT) has revolutionizing the diagnosis of cerebro-vascular disease. Newly developed 32-slice MSCT enabled us to acquire isotropic volumetric data of whole brain with the resolution of 0.5-mm. CT perfusion is one of the promising application for the diagnosis of early-staged cerebral ischemia. However, it can be hazardous in terms of ionic radiation because of multiplied exposure to the same level. A new quantum denoising filter was developed in order to solve this problem. It is possible to reduce more than 80% of dose using the filter in combination with lower kv/lower mA technique. This filter can also aids to improve the detection of early CT signs, which is important for the diagnosis of cerebral ischemia. Detection of the penumbra can be made by revealing the absence of early CT sign and low perfusion area in CT perfusion. Isotropic volumetric data provided by MSCA can also be an ideal source data for the high-quality 3D-CT angiography. Improved temporal resolution of MSCT in obtaining volumetric data made it possible separated visualization of arteries and veins on single 3D-CTA image. The technique to visualize brain surface using isotropic data and volume rendering algorithm was also reported.
Guo, Yu-Jiao; Wang, De-Wang; Meng, Ling; Wang, Yong-Qing
Several reports describing anaphylactic shock following treatment of cardiovascular and cerebrovascular diseases with Chinese herbal injections were described. Our analysis of these reports showed that anaphylactic shock caused by traditional Chinese medicine (TCM) injections for the treatment of cardiovascular and cerebrovascular diseases is common but also sometimes fatal. Therefore, we proposed the following four suggestions for improving the clinical safety of delivering Chinese herbal injections and reducing the occurrence of allergic shock. First, patients with cardiovascular and cerebrovascular diseases are at high risk, so they should only be given TCM injections after a doctor's diagnosis and approval. Second, people in allergic groups can suffer anaphylactic shock, so vigilance is important in the treatment of all age groups, although even more caution should be exercised when treating children or elderly people. In fact, TCM injections may not be appropriate for those age groups, so that they should be carefully considered before treatment. Third, no significant gender differences have been noted in patients with anaphylactic shock, so all patients should be carefully monitored, irrespective of gender. Fourth, the timeframe in which different drugs cause anaphylactic shock varies; thus, patients should be observed as long as possible. PMID:26000291
Liu, Yin; Liu, Jun; Liu, Huanghui; Liao, Yunjie; Cao, Lu; Ye, Bin; Wang, Wei
Objective The aim of this study was to investigate focal iron deposition level in the brain in patients with ischemic cerebrovascular disease and its correlation with cerebral small vessel disease imaging markers. Patients and methods Seventy-four patients with first-ever transient ischemic attack (median age: 69 years; 30 males and 44 females) and 77 patients with positive ischemic stroke history (median age: 72 years; 43 males and 34 females) were studied retrospectively. On phase image of susceptibility-weighted imaging and regions of interest were manually drawn at the bilateral head of the caudate nucleus, lenticular nucleus (LN), thalamus (TH), frontal white matter, and occipital white matter. The correlation between iron deposition level and the clinical and imaging variables was also investigated. Results Iron deposition level at LN was significantly higher in patients with previous stroke history. It linearly correlated with the presence and number of cerebral microbleeds (CMBs) but not with white matter hyperintensity and lacunar infarct. Multiple linear regression analysis showed that deep structure CMBs were the most relevant in terms of iron deposition at LN. Conclusion Iron deposition at LN may increase in cases of more severe ischemia in aged patients with transient ischemic attack, and it may be an imaging marker for CMB of ischemic origin. PMID:27574434
Smith, Eric E; Saposnik, Gustavo; Biessels, Geert Jan; Doubal, Fergus N; Fornage, Myriam; Gorelick, Philip B; Greenberg, Steven M; Higashida, Randall T; Kasner, Scott E; Seshadri, Sudha
Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians.
Su, C L; Chang, S F; Hung, T P
Cerebrovascular disease (CVD) is predominantly a disease of the elderly, and its morbidity effects increase with advancing age. In Taiwan, the increasing proportion of the elderly, as a result of medical progress and improved health care in the past 30 years, is largely responsible for the apparent increase in the number of CVD deaths. From 1963 to 1981, CVD was the leading cause of death. The crude mortality rate (CMR) and age-specific mortality rate (ASMR) of CVD by sex were derived from vital statistical data from 1959 to 1989 in Taiwan. The age-adjusted mortality rate (AAMR) using the standard world population of WHO and the cumulative mortality rate (CUMR) from birth to less than 80 years of age were calculated. Before 1983, the total number of CVD deaths had increased steadily for 30 years. In 1989, the CMR was 76.6/100,000 in men and 67.7/100,000 in women. The highest AAMR was 158.5/100,000 in 1973 for men and 130.2/100,000 in 1972 for women, and the lowest AAMR was 91.3/100,000 in 1989 for men and 81.1/100,000 in 1972 for women. The highest CUMR was 26.3% in 1968 for men and 20.8% in 1972 for women, and the lowest CUMR was 14.5% in 1989 for men and 13.6% in 1989 for women. The AAMR and CUMR for both sexes reached a maximum in 1972 and began to decline thereafter. The declines in AAMR and CUMR were averaging 2%/yr for both sexes after 1972 and were averaging 5%/yr for men and 4%/yr for women after 1983. This declining trend in CVD deaths in Taiwan began later and has been slower than similar trends in Japan and the U.S.
Zuo, Feng-Tong; Liu, Hui; Wu, Hui-Jun; Su, Na; Liu, Jie-Qiong; Dong, Ai-Qin
Abstract Background: There are limited data on the effect of dual antiplatelet treatment with clopidogrel plus aspirin in patients with ischemic cerebrovascular disease and intracranial and extracranial arteriostenosis. The aim of our study was to evaluate the efficacy and safety of aspirin plus clopidogrel in the treatment of ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis. Methods: Patients with clinically evident acute cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis (greater than 50%) who were unsuitable or reluctance to perform stent implantation were enrolled in this study. We randomly assigned these patients to receive clopidogrel (75 or 50 mg) plus aspirin (100 mg) or aspirin (100 mg) once daily through 90 days, and followed them for 90 days. We examined the main endpoints including the recurrence of stroke, death from cardiovascular causes, and bleeding events. Results: In all, 200 patients were recruited and followed for 90 days. Ischemic stroke occurred in 6 patients (9.1%) treated with 50 mg clopidogrel and aspirin, 6 patients (9.1%) receiving 75 mg clopidogrel and aspirin, whereas 19 patients (27.9%) in the aspirin group (aspirin alone vs copidogrel 50 mg plus aspirin; 95% confidence intervals 1.704–23.779, P < 0.05; aspirin alone vs copidogrel 75 mg plus aspirin; 95% confidence intervals 1.190–13.240, P < 0.05). There were more hemorrhagic events among recipients (3 patients [2.3%]) in the copidogrel plus aspirin group than aspirin recipients (0 patient [0%]), including 1 subcutaneous hemorrhage in the group of 50 mg clopidogrel and aspirin, doubling the number of nasal and gum bleeding in the group of 75 mg clopidogrel and aspirin (P > 0.05). No intracranial hemorrhage and gastro-intestinal hemorrhage occurred in these 3 groups. Conclusion: Accordingly, 50 mg clopidogrel plus aspirin, and 75 mg clopidogrel plus aspirin
Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD) and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli), there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli) playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels). That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events. PMID:27314040
Ramasamy, Mouli; Varadan, Vijay K.
Hypertension and hypertension associated cerebrovascular and cardiovascular diseases are on a rise. At-least 970 million people in the world and Seventy percent of the American adults are affected by high blood pressure, also known as hypertension. Even though blood pressure monitoring systems are readily available, the number of people being affected has been increasing. Most of the blood pressure monitoring systems require cumbersome approaches. Even the noninvasive techniques have not lowered the number of people affected nor did at-least increase the user base of these systems. Uncontrolled or untreated hypertension may lead to various cerebrovascular disorders including stroke, hypertensive crisis, lacunar infarcts intracerebral damage, microaneurysm, and cardiovascular disorders including heart failure, myocardial infraction, and ischemic heart disease. Hypertension is rated as the one of the most important causes of premature death in spite of the technical advances in biomedical technology. This paper briefs a review of the widely adopted blood pressure monitoring methods, research techniques, and finally, proposes a concept of implementing nanosensors and wireless communication for real time non-invasive blood pressure monitoring.
Patel, S S
Increased risk of cerebrovascular accident in diabetes cannot be fully explained by traditional risk factors. Epidemiological studies show that postprandial hyperglycemia is strongly associated with cerebrovascular events and cerebrovascular-associated mortality. Postprandial hyperglycemia contributes to vascular damage by several mechanisms such as endothelial dysfunction, arthrosclerosis, oxidative stress, inflammation, and hypercoagulability. Hyperglycemia has deleterious effects on the vascular endothelium and leads to the development of cerebrovascular disease. Thus, an important strategy to reduce cerebrovascular risk in patients with diabetes is to reduce postprandial hyperglycemia. Glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and α-glucosidase inhibitors predominantly reduce postprandial plasma glucose levels. Among all of these, α-glucosidase inhibitors reduces postprandial hyperglycemia by delaying carbohydrate absorption from the intestine and this mechanism provides glycemic control without exacerbating coexisting cerebrovascular risk factors. Good glycemic control is proven to reduce the risk of cardiovascular complications, but equivalent evidence for cerebrovascular risk reduction is lacking. This review examines the evidences that postprandial hyperglycemia plays a major role in vascular damage, along with the complex interplay between hyperglycemia and coexisting risk factors. Furthermore, the mechanism by which α-glucosidase inhibitors may prevent this vascular damage as well as risk of hypoglycemia with α-glucosidase inhibitors are examined. Thus, this review suggests that α-glucosidase inhibitors are useful in reducing the risk of cerebrovascular events in patients with diabetes.
Carpiniello, Bernardo; Pinna, Federica; Tuveri, Raffaella
Delusional infestation is an aspecific psychiatric condition manifested either as a primary psychotic disorder or a secondary disorder induced by a wide range of very different medical conditions. Both primary and secondary delusional infestations seem to respond to typical and atypical antipsychotics. The latter are considered the first-line treatment although the use of second-generation antipsychotics featuring a higher metabolic, cardiovascular, and renal tolerability is preferable in secondary cases, which often occur in patients with multiple, severe medical conditions. We report a case of a 72-year-old patient affected by delusional infestation associated with severe renal failure, metabolic syndrome, hypertensive cardiopathy, and chronic cerebrovascular disease.
Carpiniello, Bernardo; Pinna, Federica; Tuveri, Raffaella
Delusional infestation is an aspecific psychiatric condition manifested either as a primary psychotic disorder or a secondary disorder induced by a wide range of very different medical conditions. Both primary and secondary delusional infestations seem to respond to typical and atypical antipsychotics. The latter are considered the first-line treatment although the use of second-generation antipsychotics featuring a higher metabolic, cardiovascular, and renal tolerability is preferable in secondary cases, which often occur in patients with multiple, severe medical conditions. We report a case of a 72-year-old patient affected by delusional infestation associated with severe renal failure, metabolic syndrome, hypertensive cardiopathy, and chronic cerebrovascular disease. PMID:22174718
Zhou, Quan; Dong, Yang; Chen, WenLi; Lin, Xueying; Xing, Da; Huang, Li
Cerebrovascular disease is one of the leading causes of death, and approximately 50% of survivors have a residual neurologic deficit and greater than 25% require chronic care. Cerebrovascular reserve capacity (CVRC) describes how far cerebral perfusion can increase from a baseline value after stimulation. High blood pressure is the most important independent risk factor for stroke and other vascular diseases. The incidence of stroke in the hypertensive is six times higher than in the patient with normal blood pressure. CVRC in the hypertensive was even lower than in control patients. MR perfusion weighted imaging (MR PWI) with the well-established acetazolamide (ACZ) stimulation test has been used for assessing brain function. The aim of this work is to assess the cerebrovascular reserve capacity by MR PWI with "ACZ" tolerance test in spontaneous hypertensive rat (SHR) and to identify its value in evaluating the CVRC. Experimental animal including 3 groups: Wistar-Kyoto rats (WKY) (12-week-old) as control group, SHR (12-week-old and 20-week-old) as experimental group. MR PWI was performed respectively before and after acetazolamide administrated orally in 3 groups on a clinical 1.5 Tesla GE Signa MR fx/i whole-body MR system. The ROI was chosen in the bilateral frontal lobe to measure the value of rCBV, rCBF and MTT. The results showed that before ACZ-test, there was statistic differences between the WKY and SHR(12-week-old), and between SHR(12-week-old) and SHR(20-week-old) in the values of rCBV and rCBF (P>0.05), and after ACZ-test, there were statistic differences between WKY and SHR (20-week-old), and between SHR(12-week-old) and SHR(20-week-old) in the rCBV value (P<0.05). It is concluded that the method of MRI PWI combined with the "ACZ stress test" can provide more qualitative and half-quantitative information on the cerebral perfusion to evaluate the CVRC in SHR.
Turin, Tanvir Chowdhury; Shahana, Nahid; Wangchuk, Lungten Z; Specogna, Adrian V; Al Mamun, Mohammad; Khan, Mudassir Azeez; Choudhury, Sohel Reza; Zaman, M Mostafa; Rumana, Nahid
Similar to most populations, South Asian countries are also witnessing the dramatic transitions in health during the last few decades with the major causes of adverse health shifting from a predominance of nutritional deficiencies and infectious diseases to chronic diseases such as cardio and cerebrovascular disease (CVD). We summarized the available information of the burden of CVD and risk factors in the South Asian populations. The prevalence of conventional cardiovascular has been increasing among all South Asian populations. Extensive urbanization, shift in dietary pattern and sedentary daily life style is contributing towards the worsening of the CVD risk factor scenario. The burdens of the chronic cardiovascular risk factors are much prevalent in the South Asian populations. These are also rising alarmingly which ought to influence the already existed heavy CVD burden. Similar to the rest of the world, management for the conventional cardiovascular risk factors is very important for the prevention of CVD in South Asia.
Zheng, Shan; Wang, Minzhen; Wang, Shigong; Tao, Yan; Shang, Kezheng
Panel studies show a consistent association between increase in the cardiovascular hospitalizations with air pollutants in economically developed regions, but little evidence in less developed inland areas. In this study, a time-series analysis was used to examine the specific effects of major air pollutants [particulate matter less than 10 microns in diameter (PM10), sulfur dioxide (SO2), and nitrogen dioxides (NO2)] on daily hospital admissions for cardio-cerebrovascular diseases in Lanzhou, a heavily polluted city in China. We examined the effects of air pollutants for stratified groups by age and gender, and conducted the modifying effect of seasons on air pollutants to test the possible interaction. The significant associations were found between PM10, SO2 and NO2 and cardiac disease admissions, SO2 and NO2 were found to be associated with the cerebrovascular disease admissions. The elderly was associated more strongly with gaseous pollutants than younger. The modifying effect of seasons on air pollutants also existed. The significant effect of gaseous pollutants (SO2 and NO2) was found on daily hospital admissions even after adjustment for other pollutants except for SO2 on cardiac diseases. In a word, this study provides the evidence for the detrimental short-term health effects of urban gaseous pollutants on cardio-cerebrovascular diseases in Lanzhou. PMID:23358231
Sim, John J; Shi, Jiaxiao; Al-Moomen, Rushdy; Behayaa, Hind; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J
Plasma renin activity (PRA) may be a surrogate for vascular damage. The authors hypothesize that PRA is associated with cardiovascular and cerebrovascular disease (CED). A cross-sectional study (January 1, 1998, to December 31, 2009) was performed on hypertensive individuals 18 years and older using multivariable logistic regression models to estimate odds ratios (ORs) for ischemic heart disease (IHD), congestive heart failure (CHF), and CED based on PRA quartiles controlling for age, sex, race, diabetes mellitus (DM), and medication use. Among 7887 individuals (60% women; 34% whites, 23% blacks, and 19% Hispanics; and 29% with DM), the adjusted ORs (95% CI) for IHD were 0.94 (0.80-1.10), 1.09 (0.92-1.29), and 1.18 (1.00-1.39); for CHF were 1.23 (0.99-1.53), 1.27 (1.01-1.61), and 1.41 (1.13-1.77); and for CED were 0.95 (0.78-1.17), 0.77 (0.61-0.97), and 0.97 (0.78-1.20) for the second, third, and fourth quartiles compared with the first quartile. Higher PRA was associated with greater likelihood for prevalent IHD and CHF but not CED in this large ethnically diverse population of hypertensive individuals.
Takahashi, Hiroto; Xia, Peng; Cui, Jiankun; Talantova, Maria; Bodhinathan, Karthik; Li, Wenjun; Holland, Emily A.; Tong, Gary; Piña-Crespo, Juan; Zhang, Dongxian; Nakanishi, Nobuki; Larrick, James W.; McKercher, Scott R.; Nakamura, Tomohiro; Wang, Yuqiang; Lipton, Stuart A.
Stroke and vascular dementia are leading causes of morbidity and mortality. Neuroprotective therapies have been proposed but none have proven clinically tolerated and effective. While overstimulation of N-methyl-d-aspartate-type glutamate receptors (NMDARs) is thought to contribute to cerebrovascular insults, the importance of NMDARs in physiological function has made this target, at least in the view of many in ‘Big Pharma,’ ‘undruggable’ for this indication. Here, we describe novel NitroMemantine drugs, comprising an adamantane moiety that binds in the NMDAR-associated ion channel that is used to target a nitro group to redox-mediated regulatory sites on the receptor. The NitroMemantines are both well tolerated and effective against cerebral infarction in rodent models via a dual allosteric mechanism of open-channel block and NO/redox modulation of the receptor. Targeted S-nitrosylation of NMDARs by NitroMemantine is potentiated by hypoxia and thereby directed at ischemic neurons. Allosteric approaches to tune NMDAR activity may hold therapeutic potential for cerebrovascular disorders. PMID:26477507
Hartmann, Sara E; Waltz, Xavier; Kissel, Christine K; Szabo, Lian; Walker, Brandie L; Leigh, Richard; Anderson, Todd J; Poulin, Marc J
Acute hypoxia increases cerebral blood flow (CBF) and ventilation (V̇e). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (V̄p; index of CBF), and V̇e during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. V̄p and V̇e sensitivity to hypoxia was reduced in Older by ∼60% (P < 0.02). COPD patients exhibited similar V̄p and V̇e responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic V̇e response but selectively decreased the V̄p sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia.
Roe, Annie J; Zhang, Shucha; Bhadelia, Rafeeque A; Johnson, Elizabeth J; Lichtenstein, Alice H; Rogers, Gail T; Rosenberg, Irwin H; Smith, Caren E; Zeisel, Steven H; Scott, Tammy M
Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism.Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology.Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean ± SD age: 73 ± 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilution-multiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small- and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology.Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower high-density lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile
Suzuki, T; Saitoh, E; Tani, M; Nabeta, R; Daikuya, S; Hirose, H; Wakayama, I; Fujiwara, T
We experienced H-reflex may be evoked with supramaximal stimulation in patients with cerebrovascular disease (CVD). In this study, we investigated the relationship between the characteristic appearances of H-reflex and F-wave with increased stimulus intensity and neurological signs. We examined the H-reflex and F-wave of the affected arm with increased stimulus intensity during muscle relaxation in 31 patients (17 males and 14 females) with hemiparesis caused by CVD. Mean patient age was 56.0 (range 30-82) years. 30 healthy subjects, mean age of 56.2 (range 28-80) were investigated using the same method as controlled group. H-reflex and F-wave with increased stimulus intensity after the median nerve stimulation at the wrist were recorded from the opponence pollicis muscle on the affected side in patients with CVD or right arm in the healthy subjects. Appearance patterns of the H-reflex and F-wave with increased stimulus intensity was separated into four types. Type 1: F-wave appeared with increased stimulus intensity, but there was no H-reflex. Type 2: H-reflex and F-wave both appeared with increased stimulus intensity, but the F-wave followed disappearance of the H-reflex with increased stimulus intensity. Type 3: H-reflex and F-wave both appeared with increased stimulus intensity, but the F-wave appeared during the H-reflex with increased stimulus intensity. Type 4: Only the H-reflex appeared with increased stimulus intensity, but there was no F-wave. Neurological findings including muscle tone and tendon reflex were also evaluated. Findings on muscle tone and tendon reflex were classified into increased (markedly, moderately and slightly), normal and decreased. Results were analyzed as follows; 1) The characteristic appearances of H-reflex and F-wave in the healthy subjects and 2) The relationship between characteristic appearances of waves with increased stimulus intensity and neurological signs in patients with CVD. 1) Pattern of the H-reflex and F-wave with
A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project--1981-86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage.
Bamford, J; Sandercock, P; Dennis, M; Burn, J; Warlow, C
The age and sex specific incidence rates for cerebral infarction, primary intracerebral haemorrhage and subarachnoid haemorrhage in a population of approximately 105,000 are presented. Over four years 675 patients with a first-ever stroke were registered with the Oxfordshire Community Stroke Project. The pathological diagnosis was confirmed by computerised tomography (CT) scan, necropsy or lumbar puncture (cases of subarachnoid haemorrhage only) in 78% of cases and a further 17% were diagnosed according to the Guy's Hospital Stroke Diagnostic Score. The proportion of all first-ever strokes by pathological type was: cerebral infarction 81% (95% confidence interval 78-84), primary intracerebral haemorrhage 10% (8-12), subarachnoid haemorrhage 5% (3-7) and uncertain type 5% (3-7). These proportions are similar to other community-based studies. The overall 30 day case fatality rate was 19% (16-22), that for cerebral infarction being 10% (7-13), primary intracerebral haemorrhage 50% (38-62) and subarachnoid haemorrhage 46% (29-63). One year post stroke 23% (19-27) with cerebral infarction were dead and 65% (60-70) of survivors were functionally independent. The figures for primary intracerebral haemorrhage were 62% (43-81) dead and 68% (50-86) of survivors functionally independent and for subarachnoid haemorrhage were 48% (24-72) dead and 76% (56-96) of survivors functionally independent. There are important differences between these rates and those from other sources possibly due to more complete case ascertainment in our study. Nevertheless, the generally more optimistic early prognosis in our study, particularly for cases of cerebral infarction, has important implications for the planning of clinical trials and for the expected impact that any treatment might have on the general population. PMID:2303826
López-Liria, Remedios; Ferre-Salmerón, Rocío; Arrebola-López, Clara; Granados-Valverde, Rocío; Gobernado-Cabero, Miguel Ángel; Padilla-Góngora, David
Introduccion. El estudio de la eficacia en los tratamientos de rehabilitacion aplicados a pacientes con secuelas tras una enfermedad cerebrovascular (ECV) resulta decisivo en la actualidad para planificar su abordaje desde la sanidad publica y mejorar las directrices de evaluacion y tratamiento existentes. Objetivo. Describir las caracteristicas que presentan los pacientes que han sufrido ECV atendidos por las unidades moviles de rehabilitacion-fisioterapia (UMRF) y como influyen estos tratamientos sobre su recuperacion funcional. Pacientes y metodos. Estudio descriptivo prospectivo en 124 pacientes derivados a las UMRF de la provincia de Almeria entre 2008 y 2011. Se analizaron variables (pre y postratamiento) como las caracteristicas y antecedentes personales, indice de Barthel, escala de espasticidad de Ashworth modificada, dolor (hombro) y escala neurologica canadiense. Resultados. La muestra final estuvo compuesta por 106 participantes (edad media: 73,72 años). El proceso discapacitante fue isquemico en un 77,4%, y la hipertension, el factor de riesgo mas prevalente (81%). La media del indice de Barthel inicial fue de 31,04, y la media del indice final, de 57,62 (t = –11,75; p < 0,001). La escala canadiense mostro una evolucion favorable en el nivel de conciencia, orientacion y lenguaje (p < 0,001). El 56,2% de los pacientes recibio alta por mejoria, sin precisar rehabilitacion ambulatoria adicional. Conclusiones. Los resultados obtenidos reflejan una importante mejora funcional en los pacientes tratados en las UMRF. La rehabilitacion domiciliaria se plantea como una herramienta necesaria para las personas con mayor vulnerabilidad clinica y sin acceso a los cuidados ambulatorios, que logra los beneficios de tratamientos que son efectivos.
Background High LDL-cholesterol (LDL-C) and glucose levels are risk factors for ischemic heart disease (IHD) in middle-aged diabetic individuals; however, the risk among the elderly, especially the very elderly, is not well known. The aim of this study was to identify factors that predict IHD and cerebrovascular attack (CVA) in the elderly and to investigate their differences by age. Methods We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) with 5.5 years of follow-up. A total of 4,014 patients with type 2 diabetes and without previous IHD or CVA (1,936 women; age 67.4 ± 9.5 years, median 70 years; <65 years old, n = 1,261; 65 to 74 years old, n = 1,731; and ≥ 75 years old, n = 1,016) were recruited on a consecutive outpatient basis from 40 hospitals throughout Japan. Lipids, glucose, and other factors related to IHD or CVA risk, such as blood pressure (BP), were investigated using the multivariate Cox hazard model. Results One hundred fifty-three cases of IHD and 104 CVAs (7.8 and 5.7/1,000 people per year, respectively) occurred over 5.5 years. Lower HDL-cholesterol (HDL-C) and female gender were correlated with IHD in patients ≥75 years old (hazard ratio (HR):0.629, P < 0.01 and 1.132, P < 0.05, respectively). In contrast, systolic BP (SBP), HbA1C, LDL-C and non-HDL-C were correlated with IHD in subjects <65 years old (P < 0.05), and the LDL-C/HDL-C ratio was correlated with IHD in all subjects. HDL-C was correlated with CVA in patients ≥75 years old (HR: 0.536, P < 0.01). Kaplan-Meier estimator curves showed that IHD occurred more frequently in patients <65 years old in the highest quartile of the LDL-C/HDL-C ratio. In patients ≥75 years old, IHD and CVA were both the most frequent among those with the lowest HDL-C levels. Conclusions IHD and CVA in late elderly diabetic patients were predicted by HDL-C. LDL-C, HbA1C, SBP and non-HDL-C are risk factors for
Zhang, F; Slungaard, A; Vercellotti, G M; Iadecola, C
Recent evidence indicates that elevated plasma levels of homocysteine are a risk factor for ischemic cerebrovascular diseases. However, little is known about cerebrovascular effects of homocysteine. Homocysteine could impair cerebrovascular function by metal-catalyzed production of activated oxygen species. We studied whether homocysteine, in the presence of Cu2+, alters reactivity of cerebral circulation and, if so, whether this effect depends on O-2 generation. In halothane-anesthetized rats the parietal cortex was exposed and superfused with Ringer solution. Cerebrocortical blood flow (CBF) was monitored by a laser-Doppler probe. With Ringer solution superfusion, CBF increased with hypercapnia (+134 +/- 7%; PCO2 = 50-60 mmHg) and topical application of 10 microM ACh (+35 +/- 3%), the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 500 microM; +66 +/- 6%), or 1 mM papaverine (+100 +/- 6%; n = 5). Superfusion with 40 microM Cu2+ alone did not perturb resting CBF or responses to hypercapnia, ACh, SNAP, or papaverine (P > 0.05, n = 5). However, superfusion of homocysteine-Cu2+ reduced resting CBF (-28 +/- 4%) and attenuated (P < 0.05) responses to hypercapnia (-31 +/- 9%), ACh (-73 +/- 6%), or SNAP (-48 +/- 4%), but not papaverine. The effect was observed only at 1 mM homocysteine. Cerebrovascular effects of homocysteine-Cu2+ were prevented by coadministration of superoxide dismutase (SOD; 1,000 U/ml; n = 5). SOD alone did not affect resting CBF or CBF reactivity (n = 5). The observation that homocysteine-Cu2+ attenuates the response to hypercapnia, ACh, and SNAP, but not the NO-independent vasodilator papaverine, suggests that homocysteine-Cu2+ selectively impairs NO-related cerebrovascular responses. The fact that SOD prevents such impairment indicates that the effect of homocysteine is O-2 dependent. The data support the conclusion that O-2, generated by the reaction of homocysteine with Cu2+, inhibits NO-related cerebrovascular responses by scavenging NO
Park, Jae-Hyun; Seo, Sang Won; Kim, Changsoo; Kim, Sook Hui; Kim, Geon Ha; Kim, Sung Tae; Jeon, Seun; Lee, Jong Min; Oh, Seung Jun; Kim, Jae Seung; Choe, Yearn Seong; Lee, Kyung-Han; Shin, Ji Soo; Kim, Chi Hun; Noh, Young; Cho, Hanna; Yoon, Cindy W; Kim, Hee Jin; Ye, Byoung Seok; Ewers, Michael; Weiner, Michael W; Lee, Jae-Hong; Werring, David J; Na, Duk L
Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.
Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial magnetic resonance imaging (MRI) indicators of cerebrovascular disease (CVD). Cross-sectional inves...
Crowson, Cynthia S.; Makol, Ashima; Ytterberg, Steven R.; Saitta, Antonino; Salvarani, Carlo; Matteson, Eric L.; Warrington, Kenneth J.
Objective To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. Methods A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. Results The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. Conclusion In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects. PMID:26901431
Shibuya, Seiji; Murahashi, Makoto; Inoue, Masahiko; Jimi, Takahiro; Wakayama, Yoshihiro
The double contrast pharyngogram by use of computed radiography (DCP-CR) has been found to be useful in detection of asymptomatic swallowing dysfunction. Following the DCP-CR examination, we investigated the incidence of aspiration pneumonia in 143 patients with chronic cerebrovascular disease (CVD) for 3 years and the effects of ACE inhibitors on the prevention of pneumonia. Aspiration pneumonia occurred in 29 out of 143 patients, and more frequently in the elderly chronic CVD patients with multiple brain lesions. Aspiration pneumonia was confirmed in 26 out of 85 patients (30.6%) with abnormal barium adhesion to the pharyngeal wall on the double contrast pharyngogram image by DCP-CR; whereas pneumonia occurred in 3 out of 58 patients (5.2%) with normal findings of DCP-CR pharyngogram. Among chronic CVD patients with abnormal findings of DCP-CR pharyngogram, the incidence of aspiration pneumonia was significantly lower in the patients treated with ACE inhibitors than in those treated with other antihypertensive agents or without antihypertensive agents (chi 2 value = 7.163, p < 0.05). Accordingly, ACE inhibitors may prevent the aspiration pneumonia and reduce the incidence of aspiration pneumonia in the chronic CVD patients with abnormal DCP-CR pharyngogram images.
Nonaka, K.; Imaizumi, Y.
It has been suggested that maternal nutrition, and fetal and infant growth have an important effect on the risk of cardiovascular disease in adult life. We investigated the population-based distribution of deaths from cerebrovascular diseases (ICD9 codes 430, 431, or 434) in Japan in 1986-1994 as a function of birth month, by examining death-certificate records. For a total of 853 981 people born in the years 1900-1959, the distribution of the number of deaths according to the month of birth was compared with the distribution expected from the monthly numbers of all births for each sex and for the corresponding birth decade. For those born between 1920 and 1949, there were significant discrepancies between the actual numbers of deaths from subarachnoid hemorrhage (ICD9 430) and the numbers expected, and these differences were related to the month of birth. Those born in summer, June-September, consistently had an elevated risk of death, particularly men, where the excess risk was 8%-23%. This tendency was also observed, less distinctly but significantly, for deaths from intracerebral hemorrhage (ICD9 431), but was not observed for those dying from occlusion of the cerebral arteries (ICD9 434). The observation that the risk of dying from subarachnoid hemorrhage was more than 10% higher among those born in the summer implies that at least one in ten deaths from subarachnoid hemorrhage has its origin at a perinatal stage. Although variations in hypertension in later life, which could possibly be ''programmed'' during the intra-uterine stages, could be an explanation for this observation, the disease-specific nature of the observation suggests the involvement of aneurysm formation, which is a predominant cause of subarachnoid hemorrhage.
Kaufmann, Tim A S; Wong, Kai C; Schmitz-Rode, Thomas; Steinseifer, Ulrich
Understanding circulatory autoregulation is essential for improving physiological control of rotary blood pumps and support conditions during cardiopulmonary bypass (CPB). Cerebral autoregulation (CAR), arguably the most critical, is the body's intrinsic ability to maintain sufficient cerebral blood flow (CBF) despite changes in aortic perfusion pressure. It is therefore imperative to include this mechanism into computational fluid dynamics (CFD), particle image velocimetry (PIV), or mock circulation loop (MCL) studies. Without such inclusions, potential losses of CBF are overestimated. In this study, a mathematical model to mimic CAR is implemented in a MCL- and PIV-validated CFD model. A three-dimensional model of the human vascular system was created from magnetic resonance imaging records. Numerical flow simulations were performed for physiological conditions and CPB. The inlet flow was varied between 4.5 and 6 L/min. Arterial outlets were modeled using vessel-specific, flow-dependent cerebrovascular resistances (CVRs), resulting in a variation of the pressure drop between 0 and 80mmHg. CBF is highly dependent on the level of CAR during CPB. By varying the CVR parameters up to the beginning of plateau phase, it can be regulated between 0 and 80% of physiological CBF. So while implementing autoregulation, CBF remains unchanged during a simulated native cardiac output of 5L/min or CPB support of 6L/min. Neglecting CAR, constant backflow from the brain occurs for some cannula positions. Using flow-dependent CVR, CBF returns to its baseline at a rate of recovery of 0.25s. Results demonstrate that modeling of CAR by flow-dependent CVR delivers feasible results. The presented method can be used to optimize physiological control of assist devices dependent upon different levels of CAR representing different patients.
Lee, Jennifer K.; Brady, Ken M.; Chung, Shang-En; Jennings, Jacky M.; Whitaker, Emmett E.; Aganga, Devon; Easley, Ronald B.; Heitmiller, Kerry; Jamrogowicz, Jessica L.; Larson, Abby C.; Lee, Jeong-Hoo; Jordan, Lori C.; Hogue, Charles W.; Lehmann, Christoph U.; Bembea, Mela M.; Hunt, Elizabeth A.; Koehler, Raymond C.; Shaffner, Donald H.
Aim Improved survival after cardiac arrest has placed greater emphasis on neurologic resuscitation. The purpose of this pilot study was to evaluate the relationship between cerebrovascular autoregulation and neurologic outcomes after pediatric cardiac arrest. Methods Children resuscitated from cardiac arrest had autoregulation monitoring during the first 72 hours after return of circulation with an index derived from near-infrared spectroscopy in a pilot study. The range of mean arterial blood pressure (MAP) with optimal vasoreactivity (MAPOPT) was identified. The area under the curve (AUC) of the time spent with MAP below MAPOPT and MAP deviation below MAPOPT was calculated. Neurologic outcome measures included placement of a new tracheostomy or gastrostomy, death from a primary neurologic etiology (brain death or withdrawal of support for neurologic futility), and change in the Pediatric Cerebral Performance Category score (ΔPCPC). Results Thirty-six children were monitored. Among children who did not require extracorporeal membrane oxygenation (ECMO), children who received a tracheostomy/gastrostomy had greater AUC during the second 24 hours after resuscitation than those who did not (P=0.04; n=19). Children without ECMO who died from a neurologic etiology had greater AUC during the first 48 hours than did those who lived or died from cardiovascular failure (P=0.04; n=19). AUC below MAPOPT was not associated with ΔPCPC when children with or without ECMO were analyzed separately. Conclusions Deviation from the blood pressure with optimal autoregulatory vasoreactivity may predict poor neurologic outcomes after pediatric cardiac arrest. This experimental autoregulation monitoring technique may help individualize blood pressure management goals after resuscitation. PMID:25046743
Guimarães de Andrade, O; Partezani Rodrigues, R A
This study tries to identify the roles family members have in the care of an elderly person experiencing the effects of cerebral-vascular disease in the home and the main strategies to employ in the treatment of such a patient. The theoretical methodological procedure was based on a psychological project, a historical drawing about a theme, in which five subjects who were caretakers drew two achromatic pictures narrating corresponding stories individually in their homes. This form of expression allowed the project designers to have an interpretation of the daily situations involved in the care of these patients. In the first analysis phase, we drew the conclusion that caretakers construct their own particular knowledge system regarding the care of the elderly patient in their home. We verified that this construction started with a network relating common, daily elements which are interwoven in the treatment process occurring within a specific social milieu which as a result generates strategies that rely heavily on common sense knowledge in the manner of carrying out this social function.
Goltz, L; Bodechtel, U; Siepmann, T
Whereas statins and acetylsalicylic acid (ASA) are considered gold standard for secondary prevention following myocardial infarction or atherotrombotic stroke, there are inconsistent data on the use of these drugs for primary prevention in patients with increased cardiovascular risk. Some meta-analyses indicated that the use of statins and ASA for primary prevention of cardiovascular disease can reduce the risk of cardiovascular events such as ischemic stroke or myocardial infarction. However, the effects of primary prevention with statins and ASA on mortality varied in the data included in these meta-analyses. Therefore the guidelines of the German College of General Practitioners and Family Physicians recommend primary prevention with statins and ASA only in those patients who have a 10-year risk of cardiovascular events which exceeds 20 %. Divergently, primary prevention with ASA is not recommended by the European Society of Cardiology. Observational studies suggested that treatment success of primary prevention with statins and ASA depends on various factors such as adherence to medication and prescription behavior of physicians. This review summarizes the current literature on primary prevention of cardiovascular events with ASA and statins.
Schmidt, Wolf; Endres, Matthias; Dimeo, Fernando; Jungehulsing, Gerhard J
The burden of cerebrovascular disease (CVD) is huge and therapeutic options are limited. Physical activity is effective in preventing coronary heart and peripheral artery disease both experimentally and clinically. It is likely that the protective effects of exercise can be extended to both CVD and cognitive impairment. The pleiotropic protective and preventive mechanisms induced by physical activity include increased perfusion as well as mechanisms of collateral recruitment and neovascularization mediated by arterio- and angiogenesis. Physical activity increases the bioavailability of nitric oxide, bone marrow-derived CD34+ cells and growth factors, all of which promote neovascularization. Additionally, shear stress is discussed as a potential mechanism for vessel growth. Moreover, physical activity plays a role in endothelial function and cerebral autoregulation in small- and large-artery CVD. The vascular niche hypothesis highlights the complex interactions of neuro- and angiogenesis for regenerative and repair mechanisms in the human brain. Experimental and clinical studies demonstrate the positive impact of prior physical activity on stroke lesion size and on outcome after stroke. Clinical trials are necessary to further address the impact of physical activity on primary and secondary stroke prevention, outcome and cognitive function.
Gavurová, Beáta; Kováč, Viliam; Vagašová, Tatiana
Non-communicable diseases represent one of the greatest challenges for health policymakers. The main objective of this study is to analyse the development of standardised mortality rates for cerebrovascular disease, which is one of the most common causes of deaths, in relation to income inequality in individual regions of the Slovak Republic. Direct standardisation was applied using data from the Slovak mortality database, covering the time period from 1996 to 2013. The standardised mortality rate declined by 4.23% in the Slovak Republic. However, since 1996, the rate has been higher by almost 33% in men than in women. Standardised mortality rates were lower in the northern part of the Slovak Republic than in the southern part. The regression models demonstrated an impact of the observed income-related dimensions on these rates. The income quintile ratio and Gini coefficient appeared to be the most influencing variables. The results of the analysis highlight valuable baseline information for creating new support programmes aimed at eliminating health inequalities in relation to health and social policy.
Hicks, M E; Kreipke, D L; Becker, G J; Edwards, M K; Holden, R W; Jackson, V P; Bendick, P J; Kuehn, D S
Three hundred sixty-one patients underwent intraarterial digital subtraction angiography for definite or probable occlusive vascular disease of the carotid arteries. Examinations were performed with 65-cm-long, 4-F aortic catheters. A transbrachial approach was used. Images were good or excellent in nearly all cases. No postprocedural neurologic deficits or hematomas occurred. Permanent pulse deficit occurred in two patients, and temporary deficit occurred in three patients, an improvement over the frequency found in previous transbrachial series using 6-8-F catheters. While these results establish the efficacy of this technique, they also indicate a possible greater relative safety in men than in women.
Nishigaki, H; Adachi, I; Komori, T; Tatsu, Y; Hisada, Y; Sueyoshi, K; Narabayashi, I
99mTc-HM-PAO cerebral SPECT and whole body scintigraphy (WBS) were performed in 5 patients without cerebro-vascular disease (CVD) (Group 1), 31 patients with CVD but not hemiparesis (Group 2) and 18 patients with CVD and hemiparesis (Group 3). Four ROIs were drawn manually around the whole body (WB), brain (Br), right and left thigh (Th). We calculated some ratios: the total counts in the brain over the total counts in the whole body (Br/WB), the total counts in the thigh over the total counts in the whole body (Th/WB) and the mean counts in the thigh over the mean counts in the brain (Th/Br). The Br/WB was 6.9 +/- 1.8%, rt-Th/WB was 4.9 +/- 2.1%, lt-Th/WB was 5.1 +/- 1.3% and Th/Br was 0.46 +/- 0.17 in group 1. Whole body scintigraphies in group 1 revealed clear and similar images between right and left thigh. The Br/WB was 6.7 +/- 1.4%, Th/WB of paretic side was 4.6 +/- 1.0%, Th/WB of non-paretic side was 5.8 +/- 1.2% and Th/Br was 0.47 +/- 0.18 in group 3. The Th/WB in non paretic side was significantly higher than that in paretic side (p < 0.01). The thigh images in group 3 revealed clearly different between paretic and non-paretic thigh. In conclusion we could acquire the clear thigh images with 99mTc-HM-PAO. It was possible that we evaluated not only cerebral perfusion but also muscle atrophy and/or perfusion in patients with CVD using 99mTC-HM-PAO.
Li, Xin-Gang; Ma, Ning; Wang, Bo; Li, Xiao-Qing; Mei, Sheng-Hui; Zhao, Kun; Wang, Yong-Jun; Li, Wei; Zhao, Zhi-Gang; Sun, Shu-Sen; Miao, Zhong-Rong
The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0.018; ADP-induced platelet-fibrin clot strength (MAADP): P = 0.030]. The concentrations of clopidogrel active metabolite had no significant difference (P = 0.281). Sixteen CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12 + 13) showed lower methylation status, which correlated with a strong association with increased risk of clinical events. Changes of MAADP and ADP% were also associated with methylation levels of CpG 11 and CpG 12 + 13. Hypomethylation of the P2Y12 promoter is associated with a higher platelet reactivity and increased risk of ischemic events in our patients. Methylation analysis of peripheral blood samples might be a novel molecular marker to help early identification of patients at high risk for clinical ischemic events. PMID:27686864
Pagliano, F M; Galbiati, G C
The efficacy and safety of two different regimens of dihydroergocristine, in the treatment of patients with chronic cerebro-vascular disease, were compared in this double-blind study. Forty out-patients, 11 males and 29 females, aged 55-80 years were randomly assigned to treatment with 6 or 20 mg dihydroergocristine, daily, for 3 months. The Sandoz Clinical Assessment for Geriatrics (SCAG) scale was used to assess the efficacy of treatment. Both doses induced a statistically significant improvement (P < 0.01) in total SCAG scores after both 45 and 90 days of treatment. The higher dose produced a significantly greater improvement in total SCAG scores than did the lower dose after both 45 and 90 days. There were no statistically or clinically significant changes in any of the laboratory parameters after either treatment; neither were there any statistically significant changes in blood-pressure or pulse-rate except in the case of standing systolic pressure which decreased significantly (P < 0.01) in the 20 mg group. The only adverse event reported was a case of mild gastric pain at the end of treatment with 20 mg dihydroergocristine.
Takeuchi, Nobuyuki; Takezako, Nobuhiro; Shimonishi, Yuko; Usuda, Shigeru
[Purpose] This study evaluated effects of a high-intensity linear polarized near-infrared ray irradiation for mitigation of muscle hypertonia. [Subjects] The subjects were 20 patients with cerebrovascular disease. [Methods] Subjects were randomly allocated to an intervention or control group. The intervention group received irradiation of the triceps surae. Passive range of motion and passive resistive joint torque of ankle dorsiflexion were measured before and after the intervention in knee extended and flexed positions. [Results] In the knee extended position, the mean changes in passive range of motion were 2.70° and −0.50° in the intervention and control groups, respectively, and the mean changes in passive resistive joint torque were −1.42 and −0.26 N·m in the intervention and control groups, respectively. In the knee flexed position, the mean changes in passive range of motion were 3.70° and 0.70° in the intervention and control groups, respectively, and the mean changes in passive resistive joint torque were −2.38 and −0.31 N·m in the intervention and control groups, respectively. In both knee positions, the mean changes in the two indices were greater in the intervention group than in the control group. [Conclusion] High-intensity linear polarized near-infrared ray irradiation increases passive range of motion and decreases passive resistive joint torque. PMID:26834360
Bazilevich, S N; Odinak, M M; Dyskin, D E; Krasakov, I V; Fokin, V A; P'ianov, I V; Dekan, V S; Okol'zin, A V; Pozdniakov, A V; Stanzhevskiĭ, A A
The results of the dynamic study of patients with epileptic seizures in chronic and acute cerebral vascular pathology are presented. Various methods of structural and functional neurovisualization--magnetic resonance tomography using perfusion- and diffusion-weighted imaging, proton magnetic resonance spectroscopy, positron emission tomography, single photon emission computed tomography were used. Based on the results obtained in the study, the authors discuss etiopathogenetic variants of the development of these seizures and new possible approaches to the complex treatment besides the administration of antiepileptic medications.
Gungor, Levent; Terzi, Murat; Onar, Musa Kazim
Aphasia causes significant disability and handicap among stroke survivors. Language therapy is recommended for aphasic patients, but not always available. Piracetam, an old drug with novel properties, has been shown to have mild beneficial effects on post-stroke aphasia. In the current study, we investigated the effects of 6 months treatment with…
Güngör, Levent; Terzi, Murat; Onar, Musa Kazim
Aphasia causes significant disability and handicap among stroke survivors. Language therapy is recommended for aphasic patients, but not always available. Piracetam, an old drug with novel properties, has been shown to have mild beneficial effects on post-stroke aphasia. In the current study, we investigated the effects of 6 months treatment with piracetam on aphasia following stroke. Thirty patients with first-ever ischemic strokes and related aphasia were enrolled in the study. The scores for the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), and Gülhane Aphasia Test were recorded. The patients were scheduled randomly to receive either 4.8 g piracetam daily or placebo treatment for 6 months. At the end of 24 weeks, clinical assessments and aphasia tests were repeated. The level of improvement in the clinical parameters and aphasia scores was compared between the two groups. All patients had large lesions and severe aphasia. No significant difference was observed between the piracetam and placebo groups regarding the improvements in the NIHSS, BI and mRS scores at the end of the treatment. The improvements observed in spontaneous speech, reading fluency, auditory comprehension, reading comprehension, repetition, and naming were not significantly different in the piracetam and placebo groups, the difference reached significance only for auditory comprehension in favor of piracetam at the end of the treatment. Piracetam is well-tolerated in patients with post-stroke aphasia. Piracetam taken orally in a daily dose of 4.8 g for 6 months has no clear beneficial effect on post-stroke language disorders.
Tomassoni, Daniele; Amenta, Francesco; Amantini, Consuelo; Farfariello, Valerio; Di Cesare Mannelli, Lorenzo; Nwankwo, Innocent E.; Marini, Carlotta; Tayebati, Seyed Khosrow
Oxidative stress is an imbalance between the production of free radicals and antioxidant defense mechanisms, potentially leading to tissue damage. Oxidative stress has a key role in the development of cerebrovascular and/or neurodegenerative diseases. This phenomenon is mainly mediated by an enhanced superoxide production by the vascular endothelium with its consequent dysfunction. Thioctic, also known as alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid), is a naturally occurring antioxidant that neutralizes free radicals in the fatty and watery regions of cells. Both the reduced and oxidized forms of the compound possess antioxidant ability. Thioctic acid has two optical isomers designated as (+)- and (−)-thioctic acid. Naturally occurring thioctic acid is the (+)-thioctic acid form, but the synthetic compound largely used in the market for stability reasons is a mixture of (+)- and (−)-thioctic acid. The present study was designed to compare the antioxidant activity of the two enantiomers versus the racemic form of thioctic acid on hydrogen peroxide-induced apoptosis in a rat pheochromocytoma PC12 cell line. Cell viability was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and free oxygen radical species (ROS) production was assessed by flow cytometry. Antioxidant activity of the two enantiomers and the racemic form of thioctic acid was also evaluated in spontaneously hypertensive rats (SHR) used as an in vivo model of increased oxidative stress. A 3-h exposure of PC12 cells to hydrogen peroxide (H2O2) significantly decreased cell viability and increased levels of intracellular ROS production. Pre-treatment with racemic thioctic acid or (+)-enantiomer significantly inhibited H2O2-induced decrease in cell viability from the concentration of 50 μmol/L and 20 μmol/L, respectively. Racemic thioctic acid and (+)-salt decreased levels of intracellular ROS, which were unaffected by (−)-thioctic acid. In the brain of SHR
Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia.
Okada, Kaoru; Kurita, Akira; Takase, Bonpei; Otsuka, Toshiaki; Kodani, Eitaro; Kusama, Yoshiki; Atarashi, Hirotsugu; Mizuno, Kyoichi
Music therapy (MT) has been used in geriatric nursing hospitals, but there has been no extensive research into whether it actually has beneficial effects on elderly patients with cerebrovascular disease (CVD) and dementia. We investigated the effects of MT on the autonomic nervous system and plasma cytokine and catecholamine levels in elderly patients with CVD and dementia, since these are related to aging and chronic geriatric disease. We also investigated the effects of MT on congestive heart failure (CHF) events.Eighty-seven patients with pre-existing CVD were enrolled in the study. We assigned patients into an MT group (n = 55) and non-MT group (n = 32). The MT group received MT at least once per week for 45 minutes over 10 times. Cardiac autonomic activity was assessed by heart rate variability (HRV). We measured plasma cytokine and catecholamine levels in both the MT group and non-MT group. We compared the incidence of CHF events between these two groups. In the MT group, rMSSD, pNN50, and HF were significantly increased by MT, whereas LF/HF was slightly decreased. In the non-MT group, there were no significant changes in any HRV parameters. Among cytokines, plasma interleukin-6 (IL-6) in the MT group was significantly lower than those in the non-MT group. Plasma adrenaline and noradrenaline levels were significantly lower in the MT group than in the non-MT group. CHF events were less frequent in the MT group than in the non-MT group (P < 0.05). These findings suggest that MT enhanced parasympathetic activities and decreased CHF by reducing plasma cytokine and catecholamine levels.
Pulling, T. Michael; Rosenberg, Jarrett; Marks, Michael P.; Steinberg, Gary K.; Zaharchuk, Greg
Background and Purpose Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to middle cerebral artery (STA MCA) bypass in Moyamoya patients. This study was undertaken to determine whether pre-operative MR imaging and/or cerebrovascular reserve (CVR) assessment using reference standard stable xenon enhanced computed tomography (xeCT) could predict such complications. Materials and Methods Among all adult patients receiving direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xeCT examination, we identified index cases (patients with >15 ml post-operative infarcts) and control cases (patients without post-operative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated using the Mann Whitney test. Univariate and multivariate generalized linear model regression were employed to test predictors of post-operative infarct. Results Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95±55 ml. Four of six index cases (67%), but no control patients, had pre-operative acute infarcts. Baseline CBF was similar, but CVR was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median CVR was 0.4% (range: −38.0% to 16.6%) in index vs. 26.3% (range: −8.2% to 60.5%) in control patients (p=0.003). Multivariate analysis demonstrated that the presence of a small pre-operative infarct (regardless of location) and impaired CVR were independent, significant predictors of severe post-operative ischemic injury. Conclusion Acute infarcts and impaired CVR on pre operative imaging are independent risk factors for severe ischemic complications following STA MCA bypass in Moyamoya disease. PMID:26564435
Hromadnikova, Ilona; Kotlabova, Katerina; Hympanova, Lucie; Krofta, Ladislav
Aims To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 32 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-33a-5p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-208a-3p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in placental tissues, compared between groups (35 gestational hypertension, 80 preeclampsia, 35 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in placental tissues affected by pregnancy-related complications have been carried out. Results The expression profile of microRNAs was different between pregnancy-related complications and controls. The up-regulation of miR-499a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Preeclamptic pregnancies delivering after 34 weeks of gestation and IUGR with abnormal values of flow rate in the umbilical artery demonstrated up-regulation of miR-1-3b. Preeclampsia and IUGR requiring termination of gestation before 34 weeks of gestation were associated with down-regulation of miR-26a-5p, miR-103a-3p and miR-145-5p. On the other hand, some of microRNAs (miR-16-5p, miR-100-5p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-143-3p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, and miR-574-3p) were only down-regulated or showed a trend to down-regulation just in intrauterine growth restriction pregnancies requiring the delivery before 34 weeks of gestation. Conclusion
Lapi, Francesco; Piccinni, Carlo; Simonetti, Monica; Levi, Miriam; Lora Aprile, Pierangelo; Cricelli, Iacopo; Cricelli, Claudio; Fanelli, Andrea
Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case-control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31-365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person-years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95% CI 1.04-2.24; OR = 1.62; 95% CI 1.02-2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95% CI 1.05-4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.
Frisoni, G; Scheltens, P; Galluzzi, S; Nobili, F; Fox, N; Robert, P; Soininen, H; Wahlund, L; Waldemar, G; Salmon, E
Neuroimaging is a mainstay in the differential diagnosis of patients with cognitive impairment. The often equivocal clinical pictures, the prognostic uncertainty of the earliest stages of mild cognitive impairment, and the subtle brain changes mean that neuroimaging techniques are of potentially great incremental diagnostic value. A number of methods, ranging from very simple subjective visual ratings to highly sophisticated computerised tools, have been developed, which allow rating of structural and functional brain changes. The choice of the method is not obvious, and current guidelines provide no indications on which tools should be preferred. In this paper, we give indications for tools with demonstrated accuracy for detecting regional atrophy, cerebrovascular disease, and regional brain function, and discuss these according to increasing technological complexity, ranging from those with high feasibility that can be used at the patient's bedside to highly technological ones that require trained personnel and specific hardware and software. PMID:14570828
Symptom profiles of subsyndromal depression in disease clusters of diabetes, excess weight, and progressive cerebrovascular conditions: a promising new type of finding from a reliable innovation to estimate exhaustively specified multiple indicators–multiple causes (MIMIC) models
Francoeur, Richard B
Addressing subsyndromal depression in cerebrovascular conditions, diabetes, and obesity reduces morbidity and risk of major depression. However, depression may be masked because self-reported symptoms may not reveal dysphoric (sad) mood. In this study, the first wave (2,812 elders) from the New Haven Epidemiological Study of the Elderly (EPESE) was used. These population-weighted data combined a stratified, systematic, clustered random sample from independent residences and a census of senior housing. Physical conditions included progressive cerebrovascular disease (CVD; hypertension, silent CVD, stroke, and vascular cognitive impairment [VCI]) and co-occurring excess weight and/or diabetes. These conditions and interactions (clusters) simultaneously predicted 20 depression items and a latent trait of depression in participants with subsyndromal (including subthreshold) depression (11≤ Center for Epidemiologic Studies Depression Scale [CES-D] score ≤27). The option for maximum likelihood estimation with standard errors that are robust to non-normality and non-independence in complex random samples (MLR) in Mplus and an innovation created by the author were used for estimating unbiased effects from latent trait models with exhaustive specification. Symptom profiles reveal masked depression in 1) older males, related to the metabolic syndrome (hypertension–overweight–diabetes; silent CVD–overweight; and silent CVD–diabetes) and 2) older females or the full sample, related to several diabetes and/or overweight clusters that involve stroke or VCI. Several other disease clusters are equivocal regarding masked depression; a couple do emphasize dysphoric mood. Replicating findings could identify subgroups for cost-effective screening of subsyndromal depression. PMID:28003768
Reider, Nadia; Cohen, Jeffrey; Stuve, Olaf; Trojano, Maria; Cutter, Gary; Reingold, Stephen; Sorensen, Per Soelberg
Background: Findings regarding the prevalence of vascular comorbidities in multiple sclerosis (MS) are conflicting. Objective: The objective of this review is to estimate the incidence and prevalence of vascular comorbidities and predisposing comorbidities in persons with MS and to assess the quality of the included studies. Methods: The PubMed, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched. One reviewer abstracted data using a standardized data collection form, while the second reviewer verified the abstraction. Included studies were assessed qualitatively. Quantitatively, we assessed studies using the I2 statistic, and conducted meta-analyses for population-based studies only. Results: The prevalence of hypertension and hyperlipidemia exceeded 10% in the MS population and increased with age. While the prevalence of ischemic heart disease, congestive heart failure, and stroke were less than 5% overall, the prevalence of these conditions exceeded expectations when compared to the general population. Cardiac valvular disease, however, affected the MS population less often than expected. Problems with study quality were common. Conclusion: Despite the relatively high prevalence of some vascular comorbidities in the MS population, important gaps exist in our understanding of their epidemiology. Most of our knowledge is based on studies conducted in a small number of regions. PMID:25533300
Lin, Ro-Ting; Lin, Cheng-Kuan; Christiani, David C; Kawachi, Ichiro; Cheng, Yawen; Verguet, Stéphane; Jong, Simcha
Cardiovascular and cerebrovascular diseases (CVDs) related to overwork are common in Asia, as is death from overwork, known as karoshi. Japan was the first country in the world to introduce criteria for recognizing overwork-related CVDs in 1961. Taiwan followed Japan in putting in place new policies and then updating these in 2010. We aimed to investigate the effect of introducing the new criteria for recognizing overwork-related CVDs in both countries. We defined the baseline period as the 5 years before launch of the new criteria, then collected data to 5 years after the new criteria. We applied a Poisson regression model to analyze the longitudinal change in rates of overwork-related CVDs before and after, adjusting for indicators of working conditions. Implementation of the new criteria was associated with a 2.58-fold increase in the rate of overwork-related CVDs (p-value < 0.05). However, the examined policy framework in Taiwan still appears to miss a substantial number of cases compared to that are captured by a similar policy framework used to capture overwork-related CVD rates in Japan by a factor of 0.42 (p-value < 0.05). Accordingly, we make a case for enhancements of Taiwan's system for reporting and recognizing overwork-related diseases and deaths.
TITLE: Cerebrovascular injury in blast loading PRINCIPAL INVESTIGATOR: Kenneth L. Monson, PhD...SUBTITLE Cerebrovascular injury in blast loading 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0295 5c. PROGRAM ELEMENT NUMBER 6...and pH control. 15. SUBJECT TERMS Blast brain injury; cerebrovascular injury and dysfunction; shock tube 16. SECURITY CLASSIFICATION OF: 17
Driver, Ian D; Andoh, Jamila; Blockley, Nicholas P; Francis, Susan T; Gowland, Penny A; Paus, Tomáš
Current functional MRI (fMRI) approaches assess underlying neuronal activity through monitoring the related local variations in cerebral blood oxygenation, blood volume and blood flow. This vascular response is likely to vary across brain regions and across individuals, depending on the composition of the local vascular bed and on the vascular capacity to dilate. The most widely used technique uses the blood oxygen level dependent (BOLD) fMRI signal, which arises from a complex combination of all of these factors. The model of handedness provides a case where one brain region (dominant motor cortex) is known to have a stronger BOLD response over another (non-dominant motor cortex) during hand motor task performance. We predict that this is accompanied by a higher vascular reactivity in the dominant motor cortex, when compared with the non-dominant motor cortex. Precise measurement of end-tidal CO2 and a novel sinusoidal CO2 respiratory challenge were combined with the high sensitivity and finer spatial resolution available for fMRI at 7 T to measure BOLD cerebrovascular reactivity (CVR) in eight healthy male participants. BOLD CVR was compared between the left (dominant) and right (non-dominant) primary motor cortices of right-handed adults. Hemispheric asymmetry in vascular reactivity was predicted and observed in the primary motor cortex (left CVR = 0.60 ± 0.15%/mm Hg; right CVR = 0.47 ± 0.08%/mm Hg; left CVR > right CVR, P = 0.04), the first reported evidence of such a vascular difference. These findings demonstrate a cerebral vascular asymmetry between the left and right primary motor cortex. The origin of this asymmetry largely arises from the contribution of large draining veins. This work has implications for future motor laterality studies that use BOLD, and it is also suggestive of a vascular plasticity in the human primary motor cortex.
Detweiler, Mark B; Warf, Carlena
An increasing amount of literature suggests the positive effects of nature in healthcare. The extended life expectancy in the US and the consequent need for long-term care indicates a future need for restorative therapy innovations to reduce the expense associated with long-term care. Moving carefully selected stroke patients' sessions to the peaceful setting of a dementia wander garden, with its designed paths and natural stimuli, may be beneficial. Natural settings have been shown to improve attention and reduce stress--both important therapy objectives in many post-stroke rehabilitation programs. In this case study, using the dementia wander garden for restorative therapy of a non-dementia patient was a novel idea for the restorative therapy group, which does not have a horticultural therapy program. The dementia wander garden stage of the post-stroke rehabilitation helped the patient through a period of treatment resistance. The garden provided both an introduction to the patient's goal of outdoor rehabilitation and a less threatening environment than the long-term care facility hallways. In part because the patient was less self-conscious about manifesting his post-stroke neurological deficits, falling, and being viewed as handicapped when in the dementia wander garden setting, he was able to resume his treatment plan and finish his restorative therapy. In many physical and mental rehabilitation plans, finding a treatment modality that will motivate an individual to participate is a principal goal. Use of a dementia wander garden may help some patients achieve this goal in post-stroke restorative therapy.
Cooper, Leroy L.; Woodard, Todd; Sigurdsson, Sigurdur; van Buchem, Mark A.; Torjesen, Alyssa A.; Inker, Lesley A.; Aspelund, Thor; Eiriksdottir, Gudny; Harris, Tamara B.; Gudnason, Vilmundur; Launer, Lenore J.; Mitchell, Gary F.
Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment Susceptibility – Reykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized β: −0.071±0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: −0.029; 95% CI: −0.043, −0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: −0.042; 95% CI: −0.087, 0.003; P=0.07) and explained approximately 41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage. PMID:26573713
Hughson, Richard Lee; Shoemaker, Joel Kevin; Blaber, Andrew Philip; Arbeille, Philippe; Greaves, Danielle Kathleen
Cardiovascular and Cerebrovascular Control on Return from ISS (CCISS) will study the effects of long-duration spaceflight on crew members' heart functions and their blood vessels that supply the brain. Learning more about the cardiovascular and cerebrovascular systems could lead to specific countermeasures that might better protect future space travelers. This experiment is collaborative with the Canadian Space Agency.
Benyó, Zoltán; Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál
The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation.
Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál
The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. PMID:26825517
Qureshi, Adnan I
Imaging of head and neck vasculature continues to improve with the application of new technology. To judge the value of new technologies reported in the literature, it is imperative to develop objective standards optimized against bias and favoring statistical power and clinical relevance. A review of the existing literature identified the following items as lending scientific value to a report on imaging technology: prospective design, comparison with an accepted modality, unbiased patient selection, standardized image acquisition, blinded interpretation, and measurement of reliability. These were incorporated into a new grading scheme. Two physicians tested the new scheme and an established scheme to grade reports published in the medical literature. Inter-observer reliability for both methods was calculated using the kappa coefficient. A total of 22 reports evaluating imaging modalities for cervical internal carotid artery stenosis were identified from a literature search and graded by both schemes. Agreement between the two physicians in grading the level of scientific evidence using the new scheme was excellent (kappa coefficient: 0.93, p<0.0001). Agreement using the established scheme was less rigorous (kappa coefficient: 0.39, p<0.0001). The weighted kappa coefficients were 0.95 and 0.38 for the new and established schemes, respectively. Overall agreement was higher for the newer scheme (95% versus 64%). The new grading scheme can be used reliably to categorize the strength of scientific knowledge provided by individual studies of vascular imaging. The new method could assist clinicians and researchers in determining appropriate clinical applications of newly reported technical advances.
Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis
Militana, Adam R; Donahue, Manus J; Sills, Allen K; Solomon, Gary S; Gregory, Andrew J; Strother, Megan K; Morgan, Victoria L
The goal of this pilot study is to use complementary MRI strategies to quantify and relate cerebrovascular reactivity, resting cerebral blood flow and functional connectivity alterations in the first week following sports concussion in college varsity athletes. Seven college athletes (3F/4M, age = 19.7 ± 1.2 years) were imaged 3-6 days following a diagnosed sports related concussion and compared to eleven healthy controls with no history of concussion (5M/6F, 18-23 years, 7 athletes). Cerebrovascular reactivity and functional connectivity were measured using functional MRI during a hypercapnia challenge and via resting-state regional partial correlations, respectively. Resting cerebral blood flow was quantified using arterial spin labeling MRI methods. Group comparisons were made within and between 18 regions of interest. Cerebrovascular reactivity was increased after concussion when averaged across all regions of interest (p = 0.04), and within some default-mode network regions, the anterior cingulate and the right thalamus (p < 0.05) independently. The FC was increased in the concussed athletes within the default-mode network including the left and right hippocampus, precuneus and ventromedial prefrontal cortex (p < 0.01), with measures being linearly related to cerebrovascular reactivity in the hippocampus in the concussed athletes. Significant resting cerebral blood flow changes were not detected between the two groups. This study provides evidence for increased cerebrovascular reactivity and functional connectivity in the medial regions of the default-mode network within days of a single sports related concussion in college athletes. Our findings emphasize the utility of complementary cerebrovascular measures in the interpretation of alterations in functional connectivity following concussion.
Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease: Clinical correlations With Neurobehavioral Data in Cross-Sectional and After 18 Months Follow-ups.
Wu, Ming-Kung; Lu, Yan-Ting; Huang, Chi-Wei; Lin, Pin-Hsuan; Chen, Nai-Ching; Lui, Chun-Chung; Chang, Wen-Neng; Lee, Chen-Chang; Chang, Ya-Ting; Chen, Sz-Fan; Chang, Chiung-Chih
Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to fiber tract integrity, we predefined 11 major association tracts and calculated tract specific fractional anisotropy (FA) values. Eighty-five patients with AD underwent neurobehavioral assessments including the minimental state examination (MMSE) and 12-item neuropsychiatric inventory twice with a 1.5-year interval to represent major outcome factors. In the cross-sectional data, total cholesterol, low-density lipoprotein, vitamin B12, and homocysteine levels correlated variably with WM FA values. After entering the biomarkers and WM FA into a regression model to predict neurobehavioral outcomes, only fiber tract FA or homocysteine level predicted the MMSE score, and fiber tract FA or age predicted the neuropsychiatric inventory total scores and subdomains of apathy, disinhibition, and aberrant motor behavior. In the follow-up neurobehavioral data, the mean global FA value predicted the MMSE and aberrant motor behavior subdomain, while age predicted the anxiety and elation subdomains. Cerebrovascular risk biomarkers may modify WM microstructural organization, while the association with fiber integrity showed greater clinical significance to the prediction of neurobehavioral outcomes both cross-sectionally and longitudinally.
Hirsch, Sven; Reichold, Johannes; Schneider, Matthias; Székely, Gábor; Weber, Bruno
The cerebrovascular system continuously delivers oxygen and energy substrates to the brain, which is one of the organs with the highest basal energy requirement in mammals. Discontinuities in the delivery lead to fatal consequences for the brain tissue. A detailed understanding of the structure of the cerebrovascular system is important for a multitude of (patho-)physiological cerebral processes and many noninvasive functional imaging methods rely on a signal that originates from the vasculature. Furthermore, neurodegenerative diseases often involve the cerebrovascular system and could contribute to neuronal loss. In this review, we focus on the cortical vascular system. In the first part, we present the current knowledge of the vascular anatomy. This is followed by a theory of topology and its application to vascular biology. We then discuss possible interactions between cerebral blood flow and vascular topology, before summarizing the existing body of the literature on quantitative cerebrovascular topology. PMID:22472613
Carvalho, Janessa O.; Tommet, Doug; Crane, Paul K.; Thomas, Michael L.; Claxton, Amy; Habeck, Christian; Manly, Jennifer J.
Objectives. To evaluate the effects of vascular conditions and education quality on cognition over time in White and African American (AA) older adults. Method. We investigated cross-sectional and longitudinal racial differences in executive functioning (EF) and memory composites among Whites (n = 461) and AAs (n = 118) enrolled in a cohort study. We examined whether cerebrovascular risk factors and Shipley Vocabulary scores (a proxy for education quality) accounted for racial differences. Results. On average, AAs had lower quality of education and more cerebrovascular risk factors including hypertension, diabetes, and obesity. AAs had lower mean EF and memory at baseline, but there were no group differences in rates of decline. Cross-sectional racial differences in EF and memory persisted after controlling for vascular disease, but disappeared when controlling for Shipley Vocabulary. Discussion. Quality of education appears to be more important than cerebrovascular risk factors in explaining cross-sectional differences in memory and EF performance between White and AA older adults. Further investigation is needed regarding the relative contribution of education quality and cerebrovascular risk factors to cognitive decline among ethnically/racially diverse older adults. PMID:25098527
Knoefel, Janice; Bhaskar, Kiran
The prevalence of dementia is increasing in our aging population at an alarming rate. Because of the heterogeneity of clinical presentation and complexity of disease neuropathology, dementia classifications remain controversial. Recently, the National Plan to address Alzheimer’s Disease prioritized Alzheimer’s disease-related dementias to include: Alzheimer’s disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and mixed dementias. While each of these dementing conditions has their unique pathologic signature, one common etiology shared among all these conditions is cerebrovascular dysfunction at some point during the disease process. The goal of this comprehensive review is to summarize the current findings in the field and address the important contributions of cerebrovascular, physiologic, and cellular alterations to cognitive impairment in these human dementias. Specifically, evidence will be presented in support of small-vessel disease as an underlying neuropathologic hallmark of various dementias, while controversial findings will also be highlighted. Finally, the molecular mechanisms shared among all dementia types including hypoxia, oxidative stress, mitochondrial bioenergetics, neuroinflammation, neurodegeneration, and blood–brain barrier permeability responsible for disease etiology and progression will be discussed. PMID:26174330
Rudenko, A Iu; Bashkirova, L M
The central goal of the investigation was to study Solcoseryl (SolcoSwitzerland) therapeutic efficacy for patients suffering from early or chronic cerebrovascular diseases complicated with different forms of paroxysms. 29 patients were examined. (14 of them were with vegetovascular dystonia, 7 with discirculatory encephalopathy of degree of 1 and 8 with discirculatory encephalopathy of degree of II). The authors revealed Solcoseryl to be positive in decreasing incidence and duration of vegetovascular fits, complaints, pathologic symptoms.
Cooper, Leroy L.; Mitchell, Gary F.
Background Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. Summary Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery. Aortic stiffening thereby impairs a protective mechanism that shields the peripheral microcirculation from excessive pulsatility within downstream target organs. Beyond midlife, aortic stiffness increases rapidly and exposes the cerebral microcirculation to abnormal pulsatile mechanical forces that are associated with microvascular damage and remodeling in the brain. Aortic stiffening and high-flow pulsatility are associated with alterations in the microvasculature of the brain; however, a mechanistic link between aortic stiffness and memory has not been established. We showed that in a community-based sample of older individuals, cerebrovascular resistance and white matter hyperintensities - markers of cerebrovascular remodeling and damage - mediated the relation between higher aortic stiffness and lower performance on memory function tests. These data suggest that microvascular and white matter damage associated with excessive aortic stiffness contribute to impaired memory function with advancing age. Key Messages Increasing evidence suggests that vascular etiologies - including aortic stiffness and microvascular damage - contribute to memory impairment and the pathogenesis of dementia, including Alzheimer's disease. Interventions that reduce aortic stiffness may delay memory decline among older individuals. PMID:27752478
Beyond Volume: Hospital-Based Healthcare Technology for Better Outcomes in Cerebrovascular Surgical Patients Diagnosed With Ischemic Stroke: A Population-Based Nationwide Cohort Study From 2002 to 2013.
Kim, Jae-Hyun; Park, Eun-Cheol; Lee, Sang Gyu; Lee, Tae-Hyun; Jang, Sung-In
We examined whether the level of hospital-based healthcare technology was related to the 30-day postoperative mortality rates, after adjusting for hospital volume, of ischemic stroke patients who underwent a cerebrovascular surgical procedure. Using the National Health Insurance Service-Cohort Sample Database, we reviewed records from 2002 to 2013 for data on patients with ischemic stroke who underwent cerebrovascular surgical procedures. Statistical analysis was performed using Cox proportional hazard models to test our hypothesis. A total of 798 subjects were included in our study. After adjusting for hospital volume of cerebrovascular surgical procedures as well as all for other potential confounders, the hazard ratio (HR) of 30-day mortality in low healthcare technology hospitals as compared to high healthcare technology hospitals was 2.583 (P < 0.001). We also found that, although the HR of 30-day mortality in low healthcare technology hospitals with high volume as compared to high healthcare technology hospitals with high volume was the highest (10.014, P < 0.0001), cerebrovascular surgical procedure patients treated in low healthcare technology hospitals had the highest 30-day mortality rate, irrespective of hospital volume. Although results of our study provide scientific evidence for a hospital volume/30-day mortality rate relationship in ischemic stroke patients who underwent cerebrovascular surgical procedures, our results also suggest that the level of hospital-based healthcare technology is associated with mortality rates independent of hospital volume. Given these results, further research into what components of hospital-based healthcare technology significantly impact mortality is warranted.
Modeling the Relationships Among Late-Life Body Mass Index, Cerebrovascular Disease, and Alzheimer's Disease Neuropathology in an Autopsy Sample of 1,421 Subjects from the National Alzheimer's Coordinating Center Data Set.
Alosco, Michael L; Duskin, Jonathan; Besser, Lilah M; Martin, Brett; Chaisson, Christine E; Gunstad, John; Kowall, Neil W; McKee, Ann C; Stern, Robert A; Tripodis, Yorghos
The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum. The sample included 1,421 subjects from the National Alzheimer's Coordinating Center's Uniform Data Set and Neuropathology Data Set with diagnoses of normal cognition (NC; n = 234), mild cognitive impairment (MCI; n = 201), or AD dementia (n = 986). ADNP was defined as moderate to frequent neuritic plaques and Braak stageIII-VI. Ischemic Injury Scale (IIS) operationalized CVD. Joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score. Subject-specific random intercept for BMI was the predictor for ADNP due to minimal BMI change (p = 0.3028). Analyses controlling for demographic variables and APOE ɛ4 showed lower late-life BMI predicted increased odds of ADNP in the overall sample (p < 0.001), and in subjects with CDR of 0 (p = 0.0021) and 0.5 (p = 0.0012), but not ≥1.0 (p = 0.2012). Although higher IIS predicted greater odds of ADNP (p < 0.0001), BMI did not predict IIS (p = 0.2814). The current findings confirm lower late-life BMI confers increased odds for ADNP. Lower late-life BMI may be a preclinical indicator of underlying ADNP.
Montagne, Axel; Gauberti, Maxime; Macrez, Richard; Jullienne, Amandine; Briens, Aurélien; Raynaud, Jean-Sébastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit; Docagne, Fabian; Defer, Gilles; Vivien, Denis; Maubert, Eric
Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuroinflammation.
TAKAGI, Yasushi; MIYAMOTO, Susumu
Moyamoya disease is a cerebrovascular occlusive disease characterized by progressive stenosis or by occlusion at the terminal portion of the bilateral internal carotid arteries. The unusual vascular network (moyamoya vessels) at the base of the brain with this disease as collateral channels is developed in this disease. Social independence because of cognitive impairment has recently been recognized as an important unsolved social issue with adult moyamoya disease. The patients with cognitive impairment have difficulty in proving their status because the standard neuroradiological and neuropsychological methods to define cognitive impairment with moyamoya disease are not determined. These patients with cognitive impairment should be supported by social welfare as psychologically handicapped persons. Thus Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN study) is planned. In this study, we want to establish a standard finding of the cognitive impairment in patients with moyamoya disease. PMID:25739435
Takagi, Yasushi; Miyamoto, Susumu
Moyamoya disease is a cerebrovascular occlusive disease characterized by progressive stenosis or by occlusion at the terminal portion of the bilateral internal carotid arteries. The unusual vascular network (moyamoya vessels) at the base of the brain with this disease as collateral channels is developed in this disease. Social independence because of cognitive impairment has recently been recognized as an important unsolved social issue with adult moyamoya disease. The patients with cognitive impairment have difficulty in proving their status because the standard neuroradiological and neuropsychological methods to define cognitive impairment with moyamoya disease are not determined. These patients with cognitive impairment should be supported by social welfare as psychologically handicapped persons. Thus Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN study) is planned. In this study, we want to establish a standard finding of the cognitive impairment in patients with moyamoya disease.
Background Although the mechanisms underlying the beneficial effects of estrogen on cerebrovascular function are well known, the age-dependent deleterious effects of estrogen are largely unstudied. It was hypothesized that age and sex interact in modulating cerebrovascular reactivity to vasopressin (VP) by altering the role of prostanoids in vascular function. Methods Female (F) Sprague–Dawley rats approximating key stages of “hormonal aging” in humans were studied: premenopausal (mature multigravid, MA, cyclic, 5–6 months) and postmenopausal (reproductively senescent, RS, acyclic, 10–12 months). Age-matched male (M) rats were also studied. Reactivity to VP (10−12–10−7 M) was measured in pressurized middle cerebral artery segments in the absence or presence of selective inhibitors of COX-1 (SC560, SC, 1 μM) or COX-2 (NS398, NS, 10 μM). VP-stimulated release of PGI2 and TXA2 were measured using radioimmunoassay of 6-keto-PGF1α and TXB2 (stable metabolites, pg/mg dry wt/45 min). Results In M, there were no changes in VP-induced vasoconstriction with age. Further, there were no significant differences in basal or in low- or high-VP-stimulated PGI2 or TXA2 production in younger or older M. In contrast, there were marked differences in cerebrovascular reactivity and prostanoid release with advancing age in F. Older RS F exhibited reduced maximal constrictor responses to VP, which can be attributed to enhanced COX-1 derived dilator prostanoids. VP-induced vasoconstriction in younger MA F utilized both COX-1 and COX-2 derived constrictor prostanoids. Further, VP-stimulated PGI2 and TXA2 production was enhanced by endogenous estrogen and decreased with advancing age in F, but not in M rats. Conclusions This is the first study to examine the effects of age and sex on the mechanisms underlying cerebrovascular reactivity to VP. Interestingly, VP-mediated constriction was reduced by age in F, but was unchanged in M rats. Additionally, it was observed
Di Pasquale, G.; Andreoli, A.; Pinelli, G.; Grazi, P.; Manini, G.; Tognetti, F.; Testa, C.
A prospective cardiologic evaluation was performed in 83 consecutive patients with transient cerebral ischemia or mild stroke and without symptoms or electrocardiographic signs of ischemic heart disease. Patients were studied with an electrocardiographic exercise test; a positive test was followed by exercise Thallium-201 myocardial scintigraphy. Results were compared to those obtained in a group of 83 age and sex-matched healthy subjects submitted to the same study protocol. Asymptomatic coronary artery disease was detected in 28% of cerebrovascular patients with adequate electrocardiographic exercise test. A scintigraphic perfusion defect of variable extension was found in 19 of them. In the control group the electrocardiographic exercise test was positive in only 6% (p less than 0.01). Our results support the concept that: asymptomatic ischemic heart disease is often associated with cerebrovascular disease; therefore cerebral ischemic attacks may be a marker of coronary artery disease, an active investigation of the heart should be considered in cerebrovascular patients in order to plan optimal, comprehensive management.
Shumann, M U; Mirzai, S; Samii, M; Vorkapic, P
A patient with the coincidental occurrence of a right internal carotid artery (ICA) stenosis and asymptomatic ipsilateral infraclinoidal ICA aneurysm is presented. CBF measurements including testing of the cerebrovascular reserve capacity (CRC) demonstrated a compromise of cerebral blood flow (CBF) within the anterior circulation of the affected side. We treated the patient in one operation by aneurysm clipping and subsequent carotid endarterectomy (CEA). 10 months later she presented with an occlusion of the contralateral ICA. CBF measurements showed sufficient resting flow and CRC on both sides. One year later repeat measurements disclosed a lowered resting CBF and diminished CRC on the affected side. Extracranial/Intracranial (EC/IC) artery bypass improved both symptoms and CBF/CRC values. The authors propose to treat symptomatic ICA stenosis and concurrent silent ipsilateral intracranial aneurysms at once if the patient is eligible for aneurysm surgery. CBF measurements should be performed before surgery. In a medically compromised patient carotid endarterectomy alone appears to be justifiable. In cases of symptomatic aneurysm and concurrent ICA stenosis a CEA can be added to aneurysm clipping to improve the hemodynamic situation for a better postoperative management. Xenon/CT investigations are suitable to provide important cerebral blood flow information. Together with angiography and clinical judgment it allows to identify patients with hemodynamic insufficiency. These are suitable candidates for an operative procedure to augment cerebral blood flow and to improve symptoms.
Miller, S.; Richmond, I.; Borgos, J.; Mitra, K.
Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions, including mild traumatic brain injury, microgravity induced intracranial pressure (ICP) increases, mild cognitive impairment, and Alzheimer's disease. Near infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of the interrogated cerebral volume that is useful in identifying trends and changes in oxygen supply to cerebral tissue and has been used to monitor cerebrovascular function during surgery and ventilation. In this study, CO2-inhalation-based hypercapnic breathing challenges were used as a tool to simulate CBF dysregulation, and NIRS was used to monitor the CBF autoregulatory response. A breathing circuit for the selective administration of CO2-compressed air mixtures was designed and used to assess CBF regulatory responses to hypercapnia in 26 healthy young adults using non-invasive methods and real-time sensors. After a 5 or 10 minute baseline period, 1 to 3 hypercapnic challenges of 5 or 10 minutes duration were delivered to each subject while rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs were continuously monitored. Change in rSO2 measurements from pre- to intrachallenge (ΔrSO2) detected periods of hypercapnic challenges. Subjects were grouped into three exercise factor levels (hr/wk), 1: 0, 2:>0 and <10, and 3:>10. Exercise factor level 3 subjects showed significantly greater ΔrSO2 responses to CO2 challenges than level 2 and 1 subjects. No significant difference in ΔPETCO2 existed between these factor levels. Establishing baseline values of rSO2 in clinical practice may be useful in early detection of CBF changes.
Vasilj, Ivan; Cavaljuga, Semra; Lucić, Tomo; Kvesić, Ferdo
Cerebro-vascular insult is defined as sudden focal neurological deficit, caused by a cerebro-vascular disease lasting more then 24 hours. In this paper result of a retrospective epidemiological study of cerebro-vascular insult hospitalized and died patients from West Hercegovina Canton, was given. The study was done in Clinical hospital Mostar, for the period from 1998 to 2002. The source of the data was this hospital medical documentation. This hospital serves a total of 88,257 population of West Hercegovina Canton. A total of 393 insult cases were analyzed, out of which were 189 or 48.1% of male and 204 or 51.9% female patients. Hospital lethality found for that period was 37.4% (147 patients died out of 393 treated). Out of a total number of exited patients 37.1% (70 out of 189) were male and 37.7% (77 out of 204) were female patients. The highest lethality among both sexes was above the age of 65 years of life (37.4%), while the least was among patients between 30 to 49 years of life (25.0%).
Hulette, Christine M; Ervin, John F; Edmonds, Yvette; Antoine, Samantha; Stewart, Nicolas; Szymanski, Mari H; Hayden, Kathleen M; Pieper, Carl F; Burke, James R; Welsh-Bohmer, Kathleen A
We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared with brains of nondemented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: nondemented subjects without significant AD type pathology ("Normal"; n = 20), nondemented subjects with frequent senile plaques at autopsy ("Preclinical AD"; n = 20), and subjects with frontotemporal dementia ("FTD"; n = 10). The groups were matched for sex and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex, and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. Smooth muscle actin expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of nondemented subjects suggest that increased SMA expression might represent a physiological response to neurodegeneration that could prevent or delay overt expression dementia in AD.
Liebeskind, David S
Crowdsourcing, an unorthodox approach in medicine, creates an unusual paradigm to study precision cerebrovascular health, eliminating the relative isolation and non-standardized nature of current imaging data infrastructure, while shifting emphasis to the astounding capacity of big data in the cloud. This perspective envisions the use of imaging data of the brain and vessels to orient and seed A Million Brains Initiative™ that may leapfrog incremental advances in stroke and rapidly provide useful data to the sizable population around the globe prone to the devastating effects of stroke and vascular substrates of dementia. Despite such variability in the type of data available and other limitations, the data hierarchy logically starts with imaging and can be enriched with almost endless types and amounts of other clinical and biological data. Crowdsourcing allows an individual to contribute to aggregated data on a population, while preserving their right to specific information about their own brain health. The cloud now offers endless storage, computing prowess, and neuroimaging applications for postprocessing that is searchable and scalable. Collective expertise is a windfall of the crowd in the cloud and particularly valuable in an area such as cerebrovascular health. The rise of precision medicine, rapidly evolving technological capabilities of cloud computing and the global imperative to limit the public health impact of cerebrovascular disease converge in the imaging of A Million Brains Initiative™. Crowdsourcing secure data on brain health may provide ultimate generalizability, enable focused analyses, facilitate clinical practice, and accelerate research efforts.
Liebeskind, David S.
Crowdsourcing, an unorthodox approach in medicine, creates an unusual paradigm to study precision cerebrovascular health, eliminating the relative isolation and non-standardized nature of current imaging data infrastructure, while shifting emphasis to the astounding capacity of big data in the cloud. This perspective envisions the use of imaging data of the brain and vessels to orient and seed A Million Brains Initiative™ that may leapfrog incremental advances in stroke and rapidly provide useful data to the sizable population around the globe prone to the devastating effects of stroke and vascular substrates of dementia. Despite such variability in the type of data available and other limitations, the data hierarchy logically starts with imaging and can be enriched with almost endless types and amounts of other clinical and biological data. Crowdsourcing allows an individual to contribute to aggregated data on a population, while preserving their right to specific information about their own brain health. The cloud now offers endless storage, computing prowess, and neuroimaging applications for postprocessing that is searchable and scalable. Collective expertise is a windfall of the crowd in the cloud and particularly valuable in an area such as cerebrovascular health. The rise of precision medicine, rapidly evolving technological capabilities of cloud computing and the global imperative to limit the public health impact of cerebrovascular disease converge in the imaging of A Million Brains Initiative™. Crowdsourcing secure data on brain health may provide ultimate generalizability, enable focused analyses, facilitate clinical practice, and accelerate research efforts. PMID:27921034
expressed as mean ± SD. There was no statistical treament for data on the 24 pigs (Table 1); only percentage values were calculated. All applied...new, promising field for use of liposomes as a vehicle is in the treatment of cerebrovascular disease through gene therapy (Saito et al., 2004; Shi...brain by means of liposomes. Tohoku J. Exp. Med. 136:219-229. Toyoda, K., Chu, Y., Heistad, D. D. (2003). Gene therapy for cerebral vascular disease
In a long-term double-blind cross-over design 26 patients with amnestic syndrome due to cerebro-vascular insufficiency were submitted to vincamine-cromesilate (Vincaryl) and placebo treatment. The efficiency of vincamine was proved by mildly ameliorated psychometric patterns, biochemically by decreased cholesterol level and ophthalmodynamographically by slight increase of pulsation capacity. By means of EMG, ECG and EEG clinic side effects were excluded.
Cho, Eunice E; Drazic, Jelena; Ganguly, Milan; Stefanovic, Bojana; Hynynen, Kullervo
Blood–brain barrier (BBB) disruption can be achieved with ultrasound (US) and circulating microbubble (MB) contrast agent. Using dorsal US sonication and Definity, an MB contrast agent, responses of the cortical cerebral vasculature to BBB opening were observed with varying acoustic peak negative pressure (0.071 to 0.25 MPa) under two-photon microscope. Wistar rats with a craniotomy were sonicated with a single piezoelectric transducer following the intravenous injection of Texas Red for visualization of vasculature and leakage from BBB opening. Based on time-dependent intensity change in the extravascular area, the leakage was classified into three types: fast, sustained, and slow. Fast leakage was characterized by a rapid increase to peak intensity during sonication, but a decrease afterwards, occurring at all pressures and vessels sizes analyzed in our study. Sustained leakage was indicated by a similar, immediate increase to peak intensity but one that remained elevated for the duration of imaging, occurring at low-to-intermediate pressures. Slow leakage began 5 to 15 minutes after sonication, dominating at low pressures, and was more prevalent among smaller vessels than fast and sustained leakage. Our study showed the possibility of controlling leakage type and vessel size in US-induced BBB opening through varying acoustic pressure. PMID:21505473
Agyare, Edward K; Jaruszewski, Kristen M; Curran, Geoffry L; Rosenberg, Jens T; Grant, Samuel C; Lowe, Val J; Ramakrishnan, Subramanian; Paravastu, Anant K; Poduslo, Joseph F; Kandimalla, Karunya K
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid beta (Aβ) proteins within the walls of the cerebral vasculature with subsequent aggressive vascular inflammation leading to recurrent hemorrhagic strokes. The objective of the study was to develop theranostic nanovehicles (TNVs) capable of a) targeting cerebrovascular amyloid; b) providing magnetic resonance imaging (MRI) contrast for the early detection of CAA; and c) treating cerebrovascular inflammation resulting from CAA. The TNVs comprised of a polymeric nanocore made from Magnevist (MRI contrast agent) conjugated chitosan. The nanocore was also loaded with cyclophosphamide (CYC), an immunosuppressant shown to reduce the cerebrovascular inflammation in CAA. Putrescine modified F(ab')2 fragment of anti-amyloid antibody, IgG4.1 (pF(ab')24.1) was conjugated to the surface of the nanocore to target cerebrovascular amyloid. The average size of the control chitosan nanoparticles (conjugated with albumin and are devoid of Magnevist, CYC, and pF(ab')24.1) was 164±1.2 nm and that of the TNVs was 239±4.1 nm. The zeta potential values of the CCNs and TNVs were 21.6±1.7 mV and 11.9±0.5 mV, respectively. The leakage of Magnevist from the TNVs was a modest 0.2% over 4 days, and the CYC release from the TNVs followed Higuchi's model that describes sustained drug release from polymeric matrices. The studies conducted in polarized human microvascular endothelial cell monolayers (hCMEC/D3) in vitro as well as in mice in vivo have demonstrated the ability of TNVs to target cerebrovascular amyloid. In addition, the TNVs provided contrast for imaging cerebrovascular amyloid using MRI and single photon emission computed tomography. Moreover, the TNVs were shown to reduce pro-inflammatory cytokine production by the Aβ challenged blood brain barrier (BBB) endothelium more effectively than the cyclophosphamide alone.
Betzen, Christian; White, Robin; Zehendner, Christoph M; Pietrowski, Eweline; Bender, Bianca; Luhmann, Heiko J; Kuhlmann, Christoph R W
N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was observed via in-cell Western. The functionality of the expressed NMDA-R was determined by measuring DiBAC fluorescence in ROS-preexposed cells upon stimulation with the specific agonist NMDA. Finally, the effects on barrier integrity were evaluated using the ECIS system to detect changes in monolayer impedance upon NMDA-R stimulation after exposure to ROS. The expression of NR1 significantly (p<0.001) increased 72 h after 30 min exposure to superoxide (+33.8+/-7.5%), peroxynitrite (+84.9+/-10.7%), or hydrogen peroxide (+92.8+/-7.6%), resulting in increased cellular response to NMDA-R stimulation and diminished monolayer impedance. We conclude that oxidative stress upregulates NMDA-R on cerebrovascular endothelium and thus heightens susceptibility to glutamate-induced BBB disruption.
Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M
Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases. PMID:25833341
Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M
Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases.
Nus, Meritxell; Ruperto, Mar; Sánchez-Muniz, Francisco J
Nuts have been included in human diets for ages. They are very appreciated and used as a central component of sweets and desserts. However, during the last decades, scientific interest in those foods has increased enormously as many epidemiologic studies show protective effects of nut consumption on coronary heart disease in different population groups. To date, many clinical trials have analyzed the positive effects of nuts consumption (almond, walnut, pistachio, Macadamia nut, and pecan) on the lipid profile, decreasing total and low density lipoproteins (LDL) cholesterol. However, whether these effects are only due to their fatty acid composition or to any other bioactive compounds, such as tocopherols, phytosterols and phytoestrogens, it is still unknown. This paper, aims to review comparative composition aspects of nuts, such as the positive effects on body weight, lipoprotein metabolism, and protection against cardiovascular and cerebrovascular diseases. The inclusion of 25 g/day of nuts, mainly raw, into a prudent diet seems to be recommended. Further investigations, as actual information is still scarce, in order to dilucidate the relationship between nuts consumption and vascular diseases are proposed.
Gavett, Brandon E.; John, Samantha E.; Gurnani, Ashita S.; Bussell, Cara A.; Saurman, Jessica L.
Background Dementia severity can be modeled as the construct δ, representing the “cognitive correlates of functional status.” Objective We recently validated a model for estimating δ in the National Alzheimer’s Coordinating Center’s Uniform Data Set; however, δ’s association with neuropathology remains untested. Methods We used data from 727 decedents evaluated at Alzheimer’s Disease (AD) Centers nationwide. Participants spoke English, had no genetic abnormalities, and were pathologically diagnosed with AD as a primary or contributing etiology. Clinical data from participants’ last visit prior to death were used to estimate dementia severity (δ). Results A structural equation model using age, education, race, and apolipoprotein E (APOE) genotype (number of ε2 and ε4 alleles) as predictors and latent AD pathology and cerebrovascular disease (CVD) pathology as mediators fit the data well (RMSEA = 0.031; CFI = .957). AD pathology mediated the effects of age and APOE genotype on dementia severity. An older age at death and more ε2 alleles were associated with less AD pathology and, in turn, with less severe dementia. In contrast, more ε4 alleles were associated with more pathology and more severe dementia. Although age and race contributed to differences in CVD pathology, CVD pathology was not related to dementia severity in this sample of decedents with pathologically confirmed AD. Conclusions Using δ as an estimate of dementia severity fits well within a structural model in which AD pathology directly affects dementia severity and mediates the relationship between age and APOE genotype on dementia severity. PMID:26444761
Todo, Tsuyoshi; Alexander, Michael; Stokol, Colin; Lyden, Patrick; Braunstein, Glenn; Gewertz, Bruce
Cervical pain caused by the elongation of the styloid process (Eagle syndrome) is well known to otolaryngologists but is rarely considered by vascular surgeons. We report two patients with cerebrovascular symptoms of Eagle syndrome treated in our medical center in the past year. Case 1: an 80-year-old man with acromegaly presented with dizziness and syncope with neck rotation. The patient was noted to have bilateral elongated styloid processes impinging on the internal carotid arteries. After staged resections of the styloid processes through cervical approaches, the symptoms resolved completely. Case 2: a 57-year-old man presented with acute-onset left-sided neck pain radiating to his head immediately after a vigorous neck massage. Hospital course was complicated by a 15-minute transient ischemic attack resulting in aphasia. Angiography revealed bilateral dissections of his internal carotid arteries, with a dissecting aneurysm on the right. Both injuries were immediately adjacent to the bilateral elongated styloid processes. Despite immediate anticoagulation therapy, he experienced aphasia and right hemiparesis associated with an occlusion of his left carotid artery. He underwent emergent catheter thrombectomy and carotid stent placement, with near-complete resolution of his symptoms. Elongated styloid processes characteristic of Eagle syndrome can result in both temporary impingement and permanent injury to the extracranial carotid arteries. Although rare, Eagle syndrome should be considered in the differential diagnosis in patients with cerebrovascular symptoms, especially those induced by positional change.
Claassen, Jurgen A H R; Diaz-Arrastia, Ramon; Martin-Cook, Kristin; Levine, Benjamin D; Zhang, Rong
Cerebrovascular disease may contribute to the development and progression of Alzheimer's disease (AD). This study investigated whether impairments in cerebral hemodynamics can be detected in early-stage AD. Nine patients with mild AD and eight cognitively normal controls matched for age underwent brain magnetic resonance imaging and neuropsychological evaluation, followed by assessment of steady-state cerebral blood flow velocity (CBFV, transcranial Doppler), blood pressure (BP, Finapres), and cerebrovascular resistance index (BP/CBFV). Cerebral hemodynamics were quantified using spectral and transfer function analysis of BP and CBFV in rest, during standing up after squat, and during repeated squat-stand maneuvers. Compared to controls, AD patients had lower CBFV and higher cerebrovascular resistance index, unexplained by brain atrophy. Low-frequency variability of BP was enhanced, suggesting impaired arterial baroreflex function. However, CBFV variability was reduced despite enhanced BP variability, and dynamic cerebral autoregulation was not impaired. In conclusion, despite a distinct pattern of altered cerebral hemodynamics, AD patients may have normal autoregulation. However, the challenges for autoregulation in AD are higher, as our data show enhanced BP fluctuations. Increased cerebral vasoconstriction or reduced vasomotion also may attenuate CBFV variability.
Increased accumulation of the cardio-cerebrovascular disease treatment drug tanshinone in Salvia miltiorrhiza hairy roots by the enzymes 3-hydroxy-3-methylglutaryl CoA reductase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
Shi, Min; Luo, Xiuqin; Ju, Guanhua; Yu, Xiaohong; Hao, Xiaolong; Huang, Qiang; Xiao, Jianbo; Cui, Lijie; Kai, Guoyin
Tanshinone is widely used for treatment of cardio-cerebrovascular diseases with increasing demand. Herein, key enzyme genes SmHMGR (3-hydroxy-3-methylglutaryl CoA reductase) and SmDXR (1-deoxy-D-xylulose 5-phosphate reductoisomerase) involved in the tanshinone biosynthetic pathway were introduced into Salvia miltiorrhiza (Sm) hairy roots to enhance tanshinone production. Over-expression of SmHMGR or SmDXR in hairy root lines can significantly enhance the yield of tanshinone. Transgenic hairy root lines co-expressing HMGR and DXR (HD lines) produced evidently higher levels of total tanshinone (TT) compared with the control and single gene transformed lines. The highest tanshinone production was observed in HD42 with the concentration of 3.25 mg g(-1) DW. Furthermore, the transgenic hairy roots showed higher antioxidant activity than control. In addition, transgenic hairy root harboring HMGR and DXR (HD42) exhibited higher tanshinone content after elicitation by yeast extract and/or Ag(+) than before. Tanshinone can be significantly enhanced to 5.858, 6.716, and 4.426 mg g(-1) DW by YE, Ag(+), and YE-Ag(+) treatment compared with non-induced HD42, respectively. The content of cryptotanshinone and dihydrotanshinone was effectively elevated upon elicitor treatments, whereas there was no obvious promotion effect for the other two compounds tanshinone I and tanshinone IIA. Our results provide a useful strategy to improve tanshinone content as well as other natural active products by combination of genetic engineering with elicitors.
Haupt, Walter F; Pawlik, Gunter; Thiel, Alexander
Results of somatosensory evoked potential (SEP) and brainstem auditory evoked potential (BAEP) examinations performed early in the clinical course of patients with acute cerebrovascular disease correlate statistically significantly with outcome regardless of type and localization of the primary lesion. The prognostic value of serial examinations of SEP and BAEP has not been studied yet. The authors examined a group of 215 patients suffering from acute stroke requiring neurocritical care composed of 75 supratentorial and 36 infratentorial ischemic strokes, 58 supratentorial and 18 infratentorial hemorrhages, and 28 aneurysmatic subarachnoid hemorrhages prospectively using spinal and cortical SEP and BAEP according to routine procedures on admission as well as after 1 and 2 weeks. The findings were correlated to outcome at 4 weeks. Statistical assessment was performed using standard methods of contingency analysis. In all groups, SEP findings were significantly correlated with outcome at initial and all subsequent examinations, similar correlations were also found for BAEP. However, after partialling out the prognostic information gained from the initial examination of SEP and BAEP, the follow-up examinations rendered only a marginal increase in prognostic information. Therefore, the initial examination of evoked potentials supplies valuable prognostic information, however, serial examinations of evoked potentials during the first weeks of disease improve the prognostic information only marginally.
Li, Qian; Cui, Jing; Fang, Chen; Zhang, Xiaowen; Li, Liang
Chronic cerebrovascular hypoperfusion is a high-risk factor for Alzheimer's disease (AD) as it is conducive to beta amyloid (Aβ) over-production. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family widely expressed in the central nervous system. The structure of the rat BDNF gene is complex, consisting of eight non-coding exons (I-VIII) and one coding exon (IX). The BDNF gene is transcribed from multiple promoters located upstream of different 5' non-coding exons to produce a heterogeneous population of BDNF mRNAs. S-adenosylmethionine (SAM) produced in the methionine cycle is the primary methyl donor and the precursor of glutathione. In this study, a cerebrovascular hypoperfusion rat model and an Aβ intrahippocampal injection rat model were used to explore the expression profiles of all BDNF transcripts in the hippocampus with chronic cerebrovascular hypoperfusion or Aβ injection as well as with SAM treatment. We found that the BDNF mRNAs and protein were down-regulated in the hippocampus undergoing chronic cerebrovascular hypoperfusion as well as Aβ treatment, and BDNF exons IV and VI played key roles. SAM improved the low BDNF expression following these insults mainly through exons IV and VI. These results suggest that SAM plays a neuroprotective role by increasing the expression of endogenous BDNF and could be a potential target for AD therapy.
Nakamoto, Beau K; Jahanshad, Neda; McMurtray, Aaron; Kallianpur, Kalpana J; Chow, Dominic C; Valcour, Victor G; Paul, Robert H; Marotz, Liron; Thompson, Paul M; Shikuma, Cecilia M
HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.
Liu, Peiying; Li, Yang; Pinho, Marco; Park, Denise C; Welch, Babu G; Lu, Hanzhang
Cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or constrict, has been shown to provide valuable information in the diagnosis and treatment evaluation of patients with various cerebrovascular conditions. CVR mapping is typically performed using hypercapnic gas inhalation as a vasoactive challenge while collecting BOLD images, but the inherent need of gas inhalation and the associated apparatus setup present a practical obstacle in applying it in routine clinical use. Therefore, we aimed to develop a new method to map CVR using resting-state BOLD data without the need of gas inhalation. This approach exploits the natural variation in respiration and measures its influence on BOLD MRI signal. In this work, we first identified a surrogate of the arterial CO2 fluctuation during spontaneous breathing from the global BOLD signal. Second, we tested the feasibility and reproducibility of the proposed approach to use the above-mentioned surrogate as a regressor to estimate voxel-wise CVR. Third, we validated the "resting-state CVR map" with a conventional CVR map obtained with hypercapnic gas inhalation in healthy volunteers. Finally, we tested the utility of this new approach in detecting abnormal CVR in a group of patients with Moyamoya disease, and again validated the results using the conventional gas inhalation method. Our results showed that global BOLD signal fluctuation in the frequency range of 0.02-0.04Hz contains the most prominent contribution from natural variation in arterial CO2. The CVR map calculated using this signal as a regressor is reproducible across runs (ICC=0.91±0.06), and manifests a strong spatial correlation with results measured with a conventional hypercapnia-based method in healthy subjects (r=0.88, p<0.001). We also found that resting-state CVR was able to identify vasodilatory deficit in patients with steno-occlusive disease, the spatial pattern of which matches that obtained using the conventional gas method (r
Background Cerebrovascular diseases are the second leading cause of death worldwide and one of the health conditions which demand the highest level of social services. The aim of this study was to estimate the social cost of non-professional (informal) care provided to survivors of cerebrovascular accidents (CVA) with some type of disability in Spain. Methods We obtained data from the 2008 Survey on Disability, Independent Living and Dependency (EDAD-08) on the main characteristics of individuals who provide informal care to survivors of CVAs in Spain. We estimated the cost of substituting informal care in favor of formal care provided by professional caregivers (proxy good method) and performed a statistical analysis of the relationship between degree of dependency and number of care hours provided using ordinary least squares regression. Results The number of disabled people diagnosed with CVA totaled 1,975 (329,544 people when extrapolating to the national population using the elevation factor provided by EDAD-08). Of these, 1,221 individuals (192,611 people extrapolated to the national population) received at least one hour of informal care per week. The estimated hours of informal care provided in 2008 amounted to 852 million. The economic valuation of the time of informal care ranges from 6.53 billion euros (at 7.67 euros/hour) to 10.83 billion euros (when calculating each hour of care at 12.71 euros). The results of our statistical analysis highlight the importance of degree of dependency in explaining differences in the number of hours of informal care provided. Conclusions The results of our study reveal the high social cost of cerebrovascular accidents in Spain. In addition, evidence is presented of a correlation between higher degree of dependency in CVA survivors and greater number of hours of care received. An integral approach to care for CVA survivors requires that the caregivers’ role and needs be taken into account. PMID:24308349
Urbanova, Barbora; Tomek, Ales; Mikulik, Robert; Magerova, Hana; Horinek, Daniel; Hort, Jakub
There has been a growing interest in vascular impairment associated with Alzheimer’s disease (AD). This interest was stimulated by the findings of higher incidence of vascular risk factors in AD. Signs of vascular impairment were investigated notably in the field of imaging methods. Our aim was to explore ultrasonographic studies of extra- and intracranial vessels in patients with AD and mild cognitive impairment (MCI) and define implications for diagnosis, treatment, and prevention of the disease. The most frequently studied parameters with extracranial ultrasound are intima-media thickness in common carotid artery, carotid atherosclerosis, and total cerebral blood flow. The transcranial ultrasound concentrates mostly on flow velocities, pulsatility indices, cerebrovascular reserve capacity, and cerebral microembolization. Studies suggest that there is morphological and functional impairment of cerebral circulation in AD compared to healthy subjects. Ultrasound as a non-invasive method could be potentially useful in identifying individuals in a higher risk of progression of cognitive decline. PMID:24478651
Mey, Lilli; Hörmann, Mareike; Schleicher, Nadine; Reuter, Peter; Dönges, Simone; Kinscherf, Ralf; Gassmann, Max; Gerriets, Tibo; Al-Fakhri, Nadia
Cerebral ischemia is encompassed by cerebrovascular apoptosis, yet the mechanisms behind apoptosis regulation are not fully understood. We previously demonstrated inhibition of endothelial apoptosis by vascular endothelial growth factor (VEGF) through upregulation of poly(ADP-ribose)-polymerase (PARP) expression. However, PARP overactivation through oxidative stress can lead to necrosis. This study tested the hypothesis that neuropilin-1 (NP-1), an alternative VEGF receptor, regulates the response to cerebral ischemia by modulating PARP expression and, in turn, apoptosis inhibition by VEGF. In endothelial cell culture, NP-1 colocalized with VEGF receptor-2 (VEGFR-2) and acted as its coreceptor. This significantly enhanced VEGF-induced PARP mRNA and protein expression demonstrated by receptor-specific inhibitors and VEGF-A isoforms. NP-1 augmented the inhibitory effect of VEGF/VEGFR-2 interaction on apoptosis induced by adhesion inhibition through the αV-integrin inhibitor cRGDfV. NP-1/VEGFR-2 signal transduction involved JNK and Akt. In rat models of permanent and temporary middle cerebral artery occlusion, the ischemic cerebral hemispheres displayed endothelial and neuronal apoptosis next to increased endothelial NP-1 and VEGFR-2 expression compared to non-ischemic cerebral hemispheres, sham-operated or untreated controls. Increased vascular superoxide dismutase-1 and catalase expression as well as decreased glycogen reserves indicated oxidative stress in the ischemic brain. Of note, protein levels of intact PARP remained stable despite pro-apoptotic conditions through increased PARP mRNA production during cerebral ischemia. In conclusion, NP-1 is upregulated in conditions of imminent cerebrovascular apoptosis to reinforce apoptosis inhibition and modulate VEGF-dependent PARP expression and activation. We propose that NP-1 is a key modulator of VEGF maintaining cerebrovascular integrity during ischemia. Modulating the function of NP-1 to target PARP could help to
Ellis, Michael J.; Ryner, Lawrence N.; Sobczyk, Olivia; Fierstra, Jorn; Mikulis, David J.; Fisher, Joseph A.; Duffin, James; Mutch, W. Alan C.
Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies. In order to provide an accurate assessment of CVR, these sequences must be combined with a reliable, reproducible vasoactive stimulus that can manipulate CBF. Although CVR imaging currently plays a crucial role in the diagnosis and management of many cerebrovascular diseases, only recently have studies begun to apply this assessment tool in patients with concussion. In order to evaluate the quality, reliability, and relevance of CVR studies in concussion, it is important that clinicians and researchers have a strong foundational understanding of the role of CBF regulation in health, concussion, and more severe forms of TBI, and an awareness of the advantages and limitations of currently available CVR measurement techniques. Accordingly, in this review, we (1) discuss the role of CVR in TBI and concussion, (2) examine methodological considerations for MRI-based measurement of CVR, and (3) provide an overview of published CVR studies in concussion patients. PMID:27199885
Arends, Maarten; Wanner, Christoph; Hughes, Derralynn; Mehta, Atul; Oder, Daniel; Watkinson, Oliver T; Elliott, Perry M; Linthorst, Gabor E; Wijburg, Frits A; Biegstraaten, Marieke; Hollak, Carla E
Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; P<0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40; P<0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (P<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.
Pinto, Antonio; Tuttolomondo, Antonino; Di Raimondo, Domenico; Fernandez, Paola; Licata, Giuseppe
Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of
Munot, Pinki; Saunders, Dawn E.; Milewicz, Dianna M.; Regalado, Ellen S.; Ostergaard, John R.; Braun, Kees P.; Kerr, Timothy; Lichtenbelt, Klaske D.; Philip, Sunny; Rittey, Christopher; Jacques, Thomas S.; Cox, Timothy C.
Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features. This study involved the analysis of neuroimaging of 13 patients with heterozygous missense mutations in ACTA2 disrupting Arg179. All patients had persistent ductus arteriosus and congenital mydriasis, and variable presentation of pulmonary hypertension, bladder and gastrointestinal problems associated with this mutation. Distinctive cerebrovascular features were dilatation of proximal internal carotid artery, occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries, and absent basal ‘moyamoya’ collaterals. Patterns of brain injury supported both large and small vessel disease. Key differences from moyamoya disease were more widespread arteriopathy, the combination of arterial ectasia and stenosis and, importantly, absence of the typical basal ‘moyamoya’ collaterals. Evaluation of previously published cases suggests some of these features are also seen in the ACTA2 mutations disrupting Arg258. The observation that transition from dilated to normal/stenotic arterial calibre coincides with where the internal carotid artery changes from an elastic to muscular artery supports the hypothesis that abnormal smooth muscle cell proliferation caused by ACTA2 mutations is modulated by arterial wall components. Patients with persistent ductus arteriosus or congenital mydriasis with a label of ‘moyamoya’ should be re-evaluated to ensure the distinctive neuroimaging features of an ACTA2 mutation have not been overlooked. This diagnosis has prognostic and genetic implications, and mandates surveillance of other organ systems, in particular the aorta, to prevent life-threatening aortic dissection
Macgowan, Christopher K; Stoops, Sarah Joy; Zhou, Yu-Qing; Cahill, Lindsay S; Sled, John G
Genetic and surgical mouse models are commonly used to study cerebrovascular disease, but their size makes invasive hemodynamic testing technically challenging. The purpose of this study was to demonstrate a noninvasive measurement of cerebrovascular impedance and wave reflection in mice using high-frequency ultrasound in the left common carotid artery (LCCA), and to examine whether microvascular changes associated with hypercapnia could be detected with such an approach. Ten mice (C57BL/6J) were studied using a high-frequency ultrasound system (40 MHz). Lumen area and blood flow waveforms were obtained from the LCCA and used to calculate pulse-wave velocity, input impedance, and reflection amplitude and transit time under both normocapnic and hypercapnic (5% CO2) ventilation. With hypercapnia, vascular resistance was observed to decrease by 87%±12%. Although the modulus of input impedance was unchanged with hypercapnia, a phase decrease indicative of increased total arterial compliance was observed at low harmonics together with an increased reflection coefficient in both the time (0.57±0.08 versus 0.68±0.08, P=0.04) and frequency domains (0.62±0.08 versus 0.73±0.06, P=0.02). Interestingly, the majority of LCCA blood flow was found to pass into the internal carotid artery (range=76% to 90%, N=3), suggesting that hemodynamic measurements in this vessel are a good metric for intracerebral reactivity in mouse. PMID:25515209
Ojemann, R.G.; Crowell, R.M.; Heros, R.
This book is a concise and practical description of the current treatment of these conditions at the Massachusetts General Hospital. It is clearly written and has excellent reproductions of roentgenograms, as well as detailed and explicit drawings. One of its strengths is that it presents a unified approach that has been used over a number of years with very satisfactory results.
Chen, Junhui; Chen, Lei; Zhang, Chunlei; He, Jianqing; Li, Peipei; Zhou, Jingxu; Zhu, Jun; Wang, Yuhai
Angiographically occult cerebrovascular malformation (AOVM) is a type of complex cerebrovascular malformation that is not visible on digital subtraction angiography (DSA). Vascular malformation coexisting with glioma is clinically rare, and glioma coexisting with AOVM is even more rare. To the best of our knowledge, the present study is the first to report glioma coexisting with AOVM in the literature. The present study reports a rare case of glioma coexisting with AOVM in a 30-year-old male patient. Computed tomography (CT) scan revealed calcification, hemorrhage and edema in the right frontal lobe. CT angiography revealed a vascular malformation in the right frontal lobe, which was not observed on DSA. Finally, glioma coexisting with AOVM was confirmed by 2.0T magnetic resonance imaging and postoperative pathological examination. The present patient had a positive outcome and no neurological dysfunctions during the 6-month follow-up subsequent to surgery. PMID:27698825
Sigmundsdottir, Linda; Tchan, Michel C; Knopman, Alex A; Menzies, Graham C; Batchelor, Jennifer; Sillence, David O
Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity.
Lam, Virginie; Hackett, Mark; Takechi, Ryusuke
A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB) is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms. PMID:27999412
Kuriyama, Kana; Watenpaugh, D. E.; Hargens, Alan R.; Ueno, T.; Ballard, R. E.; Fortney, S. M.
Reduced orthostatic tolerance is commonly observed after space flight, occasionally causing presyncopal conditions. Although the cerebrovascular system may play an important role in presyncope, there have been few reports concerning cerebral hemodynamics during presyncope. The purpose of this study was to investigate cerebrovascular responses during presyncope induced by lower body negative pressure (LBNP). Seven healthy male volunteers were exposed to LBNP in steps of -10 mmHg every 3 min until presyncopal symptoms were detected. Blood pressure (BP) and heart rate (HR) were measured with a finger cuff. Cerebral tissue oxy- and deoxy- hemoglobin (Hb) concentrations were estimated using near infrared spectroscopy (NIRS). Cerebral blood flow (CBF) velocity at the middle cerebral artery was measured with Transcranial Doppler Sonography (TCD). We focused on the data during the 2 min before endpoint. BP marked a gradual decrease (91 to 86 mmHg from 2 min to 30 sec before endpoint), which was accelerated along with HR decrease during the final 30 sec (86 to 71 mmHg). Cerebral oxy-Hb concentration decreases as presyncope is approached while total-Hb concentration remains fairly constant. TCD reveals a decrease in the CBF velocity. The TCD and NIRS results suggest that CBF decreases along with the BP decrease. Cerebrovascular responses during presyncope are closely related to cardiovascular responses.
Sachdev, Anil; Sharma, Rachna; Gupta, Dhiren
Cerebrovascular complications are being frequently recognized in the pediatric intensive care unit in the recent few years. The epidemiology and risk factors for pediatric stroke are different from that of the adults. The incidence of ischemic stroke is almost slightly more than that of hemorrhagic stroke. The list of diagnostic causes is increasing with the availability of newer imaging modalities and laboratory tests. The diagnostic work up depends on the age of the child and the rapidity of presentation. Magnetic resonance imaging, computerized tomography and arteriography and venography are the mainstay of diagnosis and to differentiate between ischemic and hemorrhagic events. Very sophisticated molecular diagnostic tests are required in a very few patients. There are very few pediatric studies on the management of stroke. General supportive management is as important as the specific treatment. Most of the treatment guidelines and suggestions are extrapolated from the adult studies. Few guidelines are available for the use of anticoagulants and thrombolytic agents in pediatric patients. So, our objective was to review the available literature on the childhood stroke and to provide an insight into the subject for the pediatricians and critical care providers. PMID:21253346
Gault, Judith; Sarin, Hemant; Awadallah, Nabil A; Shenkar, Robert; Awad, Issam A
Cerebrovascular malformations affect more than 3% of the population, exposing them to a lifetime risk of hemorrhagic stroke, seizures, and focal neurological deficits. Cerebral cavernous malformations (CCMs) exhibit an immature vessel wall, a brittle hemorrhagic tendency, and epileptogenesis, whereas arteriovenous malformations (AVMs) lack capillary beds and manifest apoplectic bleeding under high-flow conditions. There are also more benign venous anomalies, capillary malformations, and lesions with mixed and transitional features. Advances have been made toward understanding the natural history, radiological and pathological correlates, and clinical management. Yet, mechanisms of lesion genesis and clinical manifestations remain largely unknown, and the clinical behavior in individual patients is highly unpredictable. Lesion pathogenesis likely involves abnormal assembly or maintenance of blood vessels, resulting in dysmorphic vessel phenotypes. Familial CCM disease is in part caused by mutations in a cytoskeletal-related protein that is likely integral to interendothelial cell connectivity and maturation of the vascular wall. Rare familial forms of AVM disease have been correlated with two different transforming growth factor-beta receptor components, possibly causing disturbance in signaling during vascular assembly. Relevance of these mechanisms to the more common and otherwise identical sporadic CCM and AVM lesions is being explored. In this report, basic mechanisms of vasculogenesis and angiogenesis and how they possibly relate to the common cerebrovascular malformation lesions are reviewed. Novel concepts are discussed related to the cellular, molecular, and genetic substrates in CCM and AVM as well as to how this knowledge can be applied to predict, explain, and possibly modify clinical disease manifestations.
Yezhuvath, Uma S.; Lewis-Amezcua, Kelly; Varghese, Rani; Xiao, Guanghua; Lu, Hanzhang
Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to dilate and is an important marker for brain vascular reserve. It may provide a useful addition to the traditional baseline blood flow measurement when assessing vascular factors in brain disorders. Blood-oxygenation-level-dependent MRI under CO2 inhalation offers a non-invasive and quantitative means to estimate CVR in humans. In this study, we investigated several important methodological aspects of this technique with the goal of optimizing the experimental and data processing strategies for clinical use. Comparing 4 min of 5% CO2 inhalation (less comfortable) to a 1 min inhalation (more comfortable) duration, it was found that the CVR values were 0.31 ±0.05%/mmHg (N = 11) and 0.31 ±0.08%/mmHg (N = 9), respectively, showing no significant differences between the two breathing paradigms. Therefore, the 1 min paradigm is recommended for future application studies for patient comfort and tolerability. Furthermore, we have found that end-tidal CO2 recording was useful for accurate quantification of CVR because it provided both timing and amplitude information regarding the input function to the brain vascular system, which can be subject-dependent. Finally, we show that inter-subject variations in CVR are of physiologic origin and affect the whole brain in a similar fashion. Based on this, it is proposed that relative CVR (normalized against the CVR of the whole brain or a reference tissue) may be a more sensitive biomarker than absolute CVR in clinical applications as it minimizes inter-subject variations. With these technological optimizations, CVR mapping may become a useful method for studies of neurological and psychiatric diseases. PMID:19388006
Jansen, J.; Rozeboom, W.; Penning, C.; Evenhuis, H. M.
Background: Epidemiological information on age-related cardiovascular disease in people with intellectual disability (ID) is scarce and inconclusive. We compared prevalence and incidence of cerebrovascular accident and myocardial infarction over age 50 in a residential population with ID to that in a general practice population. Method: Lifetime…
Donahue, Manus J.; Dethrage, Lindsey; Faraco, Carlos C.; Jordan, Lori C.; Clemmons, Paul; Singer, Robert; Mocco, J; Shyr, Yu; Desai, Aditi; O’Duffy, Anne; Riebau, Derek; Hermann, Lisa; Connors, John; Kirshner, Howard; Strother, Megan K.
Background and Purpose A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial (IC) stenosis is cerebrovascular reactivity (CVR) mapping using non-invasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated. Methods In sequence with structural and angiographic imaging, blood-oxygenation-level-dependent (BOLD) carbogen-induced CVR scans were performed in patients with symptomatic IC stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted (CBFw) pseudo-continuous arterial spin labeling (pCASL) CVR. Subjects were stratified for four sub-studies: to evaluate relationships between (i) carbogen and hyercarbic normoxic (HN) CVR in healthy tissue (n=10), (ii) carbogen CBF CVR and BOLD CVR in IC stenosis patients (n=57), (iii) carbogen CVR and clinical measures of disease in patients with asymmetric IC atherosclerotic (n=31) and moyamoya (n=29) disease, and (iv) the CVR scan and immediate and longer-term complications (n=92). Results Non-invasive BOLD carbogen-induced CVR values correlate with (i) lobar HN gas stimuli in healthy tissue (R=0.92; P<0.001), (ii) carbogen-induced CBF CVR in IC stenosis patients (R=0.30–0.33; P<0.012), and (iii) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population. Conclusions Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with IC vasculopathy. PMID:24938845
Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Angina Pectoris; Death, Sudden, Cardiac; Cerebrovascular Disorders; Peripheral Vascular Diseases; Coronary Disease; Diabetes Mellitus, Non-insulin Dependent; Diabetes Mellitus
Haeren, R H L; Vink, H; Staals, J; van Zandvoort, M A M J; Dings, J; van Overbeeke, J J; Hoogland, G; Rijkers, K; Schijns, O E M G
Introduction Adequate functioning of the blood–brain barrier (BBB) is important for brain homoeostasis and normal neuronal function. Disruption of the BBB has been described in several neurological diseases. Recent reports suggest that an increased permeability of the BBB also contributes to increased seizure susceptibility in patients with epilepsy. The endothelial glycocalyx is coating the luminal side of the endothelium and can be considered as the first barrier of the BBB. We hypothesise that an altered glycocalyx thickness plays a role in the aetiology of temporal lobe epilepsy (TLE), the most common type of epilepsy. Here, we propose a protocol that allows intraoperative assessment of the cerebrovascular glycocalyx thickness in patients with TLE and assess whether its thickness is decreased in patients with TLE when compared with controls. Methods and analysis This protocol is designed as a prospective observational case–control study in patients who undergo resective brain surgery as treatment for TLE. Control subjects are patients without a history of epileptic seizures, who undergo a craniotomy or burr hole surgery for other indications. Intraoperative glycocalyx thickness measurements of sublingual, cortical and hippocampal microcirculation are performed by video microscopy using sidestream dark-field imaging. Demographic details, seizure characteristics, epilepsy risk factors, intraoperative haemodynamic parameters and histopathological evaluation are additionally recorded. Ethics and dissemination This protocol has been ethically approved by the local medical ethical committee (ID: NL51594.068.14) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Informed consent is obtained before study enrolment and only coded data will be stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. Trial registration number
In spite of some data being added to our knowledge of the effect of antiplatelets in secondary prevention of brain ischemic lesion in recent years, the main reasons to perform a second European Stroke Prevention Study (ESPS 2), which started in 1987-1988, were: (a) clarify the relative roles of aspirin (ASA) and dipyridamole (DP) alone or in combination; (b) confirm the efficacy of small doses of ASA and, so doing, decrease the number of drop-outs due to ASA side effects; (c) join information to the effect of antiplatelets in complete stroke. General characteristics of the sample of 6602 patients are presented and compared with other major trials and series. The patients in the four treatment arms (aspirin, dipyridamole, aspirin + dipyridamole and placebo) are compared. The more relevant features and risk factors known to influence long term prognosis are described and discussed. The small proportion of patients included with TIA (23.7%) and the comparability among treatment groups are stressed. No relevant differences have been found, among groups, on the sex or age distribution, prevalence of hypertension, diabetes, previous vascular events or atrial fibrillation, nor in the characteristics of the accident leading to the inclusion in trial.
Carotid Stenosis; Constriction, Pathologic; Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical
Nash, Kevin M.; Shah, Zahoor A.
Ginkgo biloba extract is an alternative medicine available as a standardized formulation, EGb 761®, which consists of ginkgolides, bilobalide, and flavonoids. The individual constituents have varying therapeutic mechanisms that contribute to the pharmacological activity of the extract as a whole. Recent studies show anxiolytic properties of ginkgolide A, migraine with aura treatment by ginkgolide B, a reduction in ischemia-induced glutamate excitotoxicity by bilobalide, and an alternative antihypertensive property of quercetin, among others. These findings have been observed in EGb 761 as well and have led to clinical investigation into its use as a therapeutic for conditions such as cognition, dementia, cardiovascular, and cerebrovascular diseases. This review explores the therapeutic mechanisms of the individual EGb 761 constituents to explain the pharmacology as a whole and its clinical application to cardiovascular and neurological disorders, in particular ischemic stroke. PMID:26604665
Bianciardi, Marta; Toschi, Nicola; Polimeni, Jonathan R; Evans, Karleyton C; Bhat, Himanshu; Keil, Boris; Rosen, Bruce R; Boas, David A; Wald, Lawrence L
The influence of cardiac activity on the viscoelastic properties of intracranial tissue is one of the mechanisms through which brain-heart interactions take place, and is implicated in cerebrovascular disease. Cerebrovascular disease risk is not fully explained by current risk factors, including arterial compliance. Cerebrovascular compliance is currently estimated indirectly through Doppler sonography and magnetic resonance imaging (MRI) measures of blood velocity changes. In order to meet the need for novel cerebrovascular disease risk factors, we aimed to design and validate an MRI indicator of cerebrovascular compliance based on direct endogenous measures of blood volume changes. We implemented a fast non-gated two-dimensional MRI pulse sequence based on echo-planar imaging (EPI) with ultra-short repetition time (approx. 30-50 ms), which stepped through slices every approximately 20 s. We constrained the solution of the Bloch equations for spins moving faster than a critical speed to produce an endogenous contrast primarily dependent on spin volume changes, and an approximately sixfold signal gain compared with Ernst angle acquisitions achieved by the use of a 90° flip angle. Using cardiac and respiratory peaks detected on physiological recordings, average cardiac and respiratory MRI pulse waveforms in several brain compartments were obtained at 7 Tesla, and used to derive a compliance indicator, the pulsatility volume index (pVI). The pVI, evaluated in larger cerebral arteries, displayed significant variation within and across vessels. Multi-echo EPI showed the presence of significant pulsatility effects in both S0 and [Formula: see text] signals, compatible with blood volume changes. Lastly, the pVI dynamically varied during breath-holding compared with normal breathing, as expected for a compliance indicator. In summary, we characterized and performed an initial validation of a novel MRI indicator of cerebrovascular compliance, which might prove useful
Antenatal intrauterine cerebrovascular events were found to play an important role in the pathogenesis of perinatal brain damage. Changes in placental vascular resistance, cardiac contractibility, vessel compliance, and blood viscosity alter the normal dynamics of fetal cerebral circulation. The circulatory mechanisms described in animal fetuses also operate in the human fetus. The isthmus of the aorta represents a watershed area reflecting the redistribution of blood during increased peripheral resistance and hypoxia. The fetal cerebrovascular system acts locally within the skull and interacts with the other components of fetal circulation to compensate by redistribution of blood in case of shortage in resources. The introduction of various sonographic techniques and the collection of data from the arterial and venous cerebral circulation have improved our understanding of the regulatory mechanisms involved in fetal cerebral hemodynamic events. Anatomical and physiological considerations of cerebral vasculature in health and disease are relevant in the research of variations in fetal brain blood perfusion. Changes in flow characteristics in fetal cerebral vasculature can be used for clinical decisions. However, caution is advised before applying research data into practice. The clinical utility is well established in situations of fetal compromise such as growth restriction and anemia.
... news/fullstory_164453.html Study Links Celiac Disease, Anorexia Chances of being diagnosed with eating disorder were ... face a heightened risk of being diagnosed with anorexia, a new study suggests. The Swedish researchers found ...
Andrade, Susan E.; Harrold, Leslie R.; Tjia, Jennifer; Cutrona, Sarah L.; Saczynski, Jane S.; Dodd, Katherine S.; Goldberg, Robert J.; Gurwitz, Jerry H.
Purpose To perform a systematic review of the validity of algorithms for identifying cerebrovascular accidents (CVAs) or transient ischemic attacks (TIAs) using administrative and claims data. Methods PubMed and Iowa Drug Information Service (IDIS) searches of the English language literature were performed to identify studies published between 1990 and 2010 that evaluated the validity of algorithms for identifying CVAs (ischemic and hemorrhagic strokes, intracranial hemorrhage and subarachnoid hemorrhage) and/or TIAs in administrative data. Two study investigators independently reviewed the abstracts and articles to determine relevant studies according to pre-specified criteria. Results A total of 35 articles met the criteria for evaluation. Of these, 26 articles provided data to evaluate the validity of stroke, 7 reported the validity of TIA, 5 reported the validity of intracranial bleeds (intracerebral hemorrhage and subarachnoid hemorrhage), and 10 studies reported the validity of algorithms to identify the composite endpoints of stroke/TIA or cerebrovascular disease. Positive predictive values (PPVs) varied depending on the specific outcomes and algorithms evaluated. Specific algorithms to evaluate the presence of stroke and intracranial bleeds were found to have high PPVs (80% or greater). Algorithms to evaluate TIAs in adult populations were generally found to have PPVs of 70% or greater. Conclusions The algorithms and definitions to identify CVAs and TIAs using administrative and claims data differ greatly in the published literature. The choice of the algorithm employed should be determined by the stroke subtype of interest. PMID:22262598
Ungprasert, Patompong; Crowson, Cynthia S; Matteson, Eric L
A higher incidence of cardiovascular disease (CVD) has been observed in several chronic inflammatory diseases. However, data on sarcoidosis are limited.In this study, 345 patients with incident sarcoidosis in Olmsted County (Minnesota, USA) during 1976-2013 were identified based on comprehensive medical record review. 345 sex- and age-matched comparators were also identified from the same underlying population. Medical records were individually reviewed for CVD, including coronary artery disease, congestive heart failure, atrial fibrillation, cerebrovascular accident, transient ischaemic attack, peripheral arterial disease and abdominal aortic aneurysm. Cox proportional hazards models with adjustment for age, sex, calendar year and cardiovascular risk factors were used to compare the rate of development of CVD between cases and comparators.The prevalence of CVD before the index date was not significantly different between the two groups. Adjusting for age, sex and calendar year, the risk of incident CVD after the index date was significantly elevated among patients with sarcoidosis with an adjusted hazard ratio of 1.57 (95% CI 1.15-2.16). Adjustment for cardiovascular risk factors yielded an adjusted hazard ratio of 1.65 (95% CI 1.08-2.53). Significantly increased risk was also observed for several types of CVD, including coronary artery disease, congestive heart failure, atrial fibrillation and cerebrovascular accident.Increased incidence of CVD among patients with sarcoidosis was demonstrated in this population-based cohort, even after controlling for baseline traditional atherosclerotic risk factors.
Hynes, Brian G; Rodés-Cabau, Josep
Transcatheter aortic valve implantation (TAVI) has revolutionized the care of high-risk patients with severe calcific aortic stenosis. Those considered at high or prohibitive risk of major adverse outcomes with open surgical aortic valve replacement may now be offered an alternative less-invasive therapy. Despite the rapid evolution and clinical application of this new technology, recent studies have raised concerns about adverse cerebrovascular event rates in patients undergoing TAVI. In this review, we explore the current data both in relation to procedure-related silent cerebrovascular ischemic events, as well as clinically apparent stroke. The timing of neurological events and their prognostic implications are also examined. Finally, potential mechanisms of TAVI-related cerebrovascular injury are described, in addition to efforts to minimize their occurrence.
De Ley, G
In order to gain more insight into the pathophysiology of extracerebral cerebrovascular occlusion, the cerebral hemodynamic behaviour after uni- or bilateral carotid occlusion was investigated. In Wistar rats, acute occlusion of one common carotid artery leads to a moderate bilateral lowering of the resting hemispheric brain blood flow; no interhemispheric perfusion asymmetry is observed. During hypercapnia, however, a manyfold increase of the hemispheric blood flow is seen at the intact side, whereas blood flow increase at the side of the occlusion is suppressed indicating that the cerebrovascular reserve at the side of the occlusion is largely used to preserve resting hemispheric perfusion. During the days (1, 5, 15 and 30) following the occlusion, resting hemispheric blood flow is progressively restored rather rapidly (bilateral normalization on the fifth day) whereas restoration of the cerebrovascular reserve (hemispheric blood flow increase in hypercapnia) proceeds more slowly and a nearly normal hypercapnic response is reached on day thirty. Spontaneously Hypertensive Rats (SHR) show structural abnormalities of their blood vessels during the development of hypertension, leading to impaired adaptation possibilities of the cerebral vasculature after unilateral common carotid occlusion. This is indicated by the striking comparability of the compensation of hemispheric cerebral blood flow (in normo- and hypercapnia) of SH rats five days after unilateral carotid occlusion with the cerebral hemodynamic status of normotensive animals already seen 24 hours after the same occlusion. Consecutive bilateral common carotid occlusion shows that survival rate increases by increasing the interval between both occlusions. This survival relation is much more unfavorable in SH rats. The parallelism between the restoration of the measured CO2-reactivity of the blood flow in the involved hemisphere after unilateral carotid occlusion and the evolution of survival rate after
Heo, Jae-Hyeok; Im, Dong-Gyu; Lee, Seung-Hyeon; Ahn, Jin-Young
Background: Microbleeds (MBs) are observed frequently in Alzheimer's disease (AD) and suggested to play a crucial role in the pathophysiology, but their clinical significance remains unclear. Materials and Methods: The study recruited 100 patients with AD who were diagnosed at the memory clinic in Seoul Medical Center in 2014. For each patient, baseline characteristics, neuropsychological tests, cerebrovascular risk factors, medial temporal lobe atrophy (MTLA), and severity of small vessel disease (SVD) according to the existence of MBs were evaluated. Results: The prevalence of MBs in patients with AD was 33%. The percentage of male gender, the severity of SVD and MTLA were significantly increased in MB(+) group. The MB(+) group showed more severe MTLA and SVD than MB(−) group. Conclusions: These results suggested that MBs might reflect the burden of amyloid and ischemic vascular pathology. PMID:27994360
Lucareli, Paulo Roberto Garcia; Greve, Julia Maria D’Andrea
INTRODUCTION There is still no consensus among different specialists on the subject of kinematic variation during the hemiparetic gait, including the main changes that take place during the gait cycle and whether the gait velocity changes the patterns of joint mobility. One of the most frequently discussed joints is the knee. OBJECTIVES This study aims to evaluate the variables found in the angular kinematics of knee joint, and to describe the alterations found in the hemiparetic gait resulting from cerebrovascular injury. METHODS This study included 66 adult patients of both genders with a diagnosis of either right or left hemiparesis resulting from ischemic cerebrovascular injury. All the participants underwent three-dimensional gait evaluation, an the angular kinematics of the joint knee were selected for analysis. RESULTS The results were distributed into four groups formed based on the median of the gait speed and the side of hemiparesis. CONCLUSIONS The relevant clinical characteristics included the important mechanisms of loading response in the stance, knee hyperextension in single stance, and reduction of the peak flexion and movement amplitude of the knee in the swing phase. These mechanisms should be taken into account when choosing the best treatment. We believe that the findings presented here may aid in preventing the occurrence of the problems found, and also in identifying the origin of these problems. PMID:18719753
Latka, M.; Turalska, M.; Kolodziej, W.; Latka, D.; West, B.
We employ complex continuous wavelet transforms to develop a consistent mathematical framework capable of quantifying both cerebrospinal compensatory reserve and cerebrovascular pressure--reactivity. The wavelet gain, defined as the frequency dependent ratio of time averaged wavelet coefficients of intracranial (ICP) and arterial blood pressure (ABP) fluctuations, characterizes the dampening of spontaneous arterial blood oscillations. This gain is introduced as a novel measure of cerebrospinal compensatory reserve. For a group of 10 patients who died as a result of head trauma (Glasgow Outcome Scale GOS =1) the average gain is 0.45 calculated at 0.05 Hz significantly exceeds that of 16 patients with favorable outcome (GOS=2): with gain of 0.24 with p=4x10-5. We also study the dynamics of instantaneous phase difference between the fluctuations of the ABP and ICP time series. The time-averaged synchronization index, which depends upon frequency, yields the information about the stability of the phase difference and is used as a cerebrovascular pressure--reactivity index. The average phase difference for GOS=1 is close to zero in sharp contrast to the mean value of 30^o for patients with GOS=2. We hypothesize that in patients who died the impairment of cerebral autoregulation is followed by the break down of residual pressure reactivity.
Sleiman, Katarzyna; Zimny, Anna; Kowalczyk, Edyta; Sąsiadek, Marek
Summary Background Cerebrovascular diseases are the most common neurological disorders. Most of them are arterial strokes, mainly ischemic, less often of hemorrhagic origin. Changes in the course of cerebral venous thrombosis are less common causes of acute cerebrovascular events. Clinical and radiological presentation of arterial and venous strokes (especially in emergency head CT) may pose a diagnostic problem because of great resemblance. However, the distinction between arterial and venous stroke is important from a clinical point of view, as it carries implications for the treatment and determinates patient’s prognosis. Case Report In this article, we present cases of two young women (one with an acute venous infarction, the second with an arterial stroke) who presented with similar both clinical and radiological signs of acute vascular incident in the cerebral cortex. We present main similarities and differences between arterial and venous strokes regarding the etiology, clinical symptoms and radiological appearance in various imaging techniques. Conclusions We emphasize that thorough analysis of CT (including cerebral vessels), knowledge of symptoms and additional clinical information (e.g. risk factors) may facilitate correct diagnosis and allow planning further diagnostic imaging studies. We also emphasize the importance of MRI, especially among young people, in the differential diagnosis of venous and arterial infarcts. PMID:24505227
Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-β (Aβ)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer’s disease (AD) and Down’s syndrome. Moreover, Aβ-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Aβ domain of the amyloid precursor protein (APP) such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic Aβ variants or an unaltered Aβ42/Aβ40 ratio favor vascular Aβ deposition over parenchymal plaques, but higher than critical levels of Aβ40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels. PMID:19468344
Bondar, R. L.; Kassam, M. S.; Stein, F.; Dunphy, P. T.; Fortney, S.; Riedesel, M. L.
BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve. METHODS: Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14% of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation
Nivethitha, L.; Mooventhan, A.; Manjunath, N. K.; Bathala, Lokesh; Sharma, Vijay K.
Background: Pranayama techniques are known to produce variable physiological effects on the body. We evaluated the effect of the two commonly practiced Pranayama techniques on cerebral hemodynamics. Materials and Methods: Fifteen healthy male volunteers, trained in Yoga and Pranayama, were included in the study. Mean age was 24 years (range 22–32 years). Study participants performed 2 Pranayamas in 2 different orders. Order 1 (n = 7) performed Bhastrika (bellows breaths) followed by Kumbhaka (breath retention) while order 2 (n = 8) performed Kumbhaka followed by Bhastrika. Both breathing techniques were performed for 1 min each. Continuous transcranial Doppler (TCD) monitoring was performed during the breathing techniques. TCD parameters that were recorded included peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MFV), and pulsatility index (PI) of the right middle cerebral artery at baseline, 15, 30, 45, and 60 s. Results: Significant reductions in EDV (3.67 ± 6.48; P < 0.001) and MFV (22.00 ± 7.30; P < 0.001) with a significant increase in PI (2.43 ± 0.76; P < 0.001) were observed during Bhastrika. On the contrary, a significant increase in PSV (65.27 ± 13.75; P < 0.001), EDV (28.67 ± 12.03; P < 0.001), and MFV (43.67 ± 12.85; P < 0.001) with a significant reduction in PI (0.89 ± 0.28; P < 0.01) was observed only during Kumbhaka. Conclusion: Bhastrika and Kumbhaka practices of Pranayama produce considerable and opposing effects on cerebral hemodynamic parameters. Our findings may play a potential role in designing the Pranayama techniques according to patients’ requirements. PMID:28149083
Little, Mark P; Zablotska, Lydia B; Brenner, Alina V; Lipshultz, Steven E
High-dose ionizing radiation is associated with circulatory disease. Risks from lower-dose fractionated exposures, such as from diagnostic radiation procedures, remain unclear. In this study we aimed to ascertain the relationship between fractionated low-to-medium dose radiation exposure and circulatory disease mortality in a cohort of 13,568 tuberculosis patients in Massachusetts, some with fluoroscopy screenings, between 1916 and 1961 and follow-up until the end of 2002. Analysis of mortality was in relation to cumulative thyroid (cerebrovascular) or lung (all other circulatory disease) radiation dose via Poisson regression. Over the full dose range, there was no overall radiation-related excess risk of death from circulatory disease (n = 3221; excess relative risk/Gy -0.023; 95% CI -0.067, 0.028; p = 0.3574). Risk was somewhat elevated in hypertensive heart disease (n = 89; excess relative risk/Gy 0.357; 95% CI -0.043, 1.030, p = 0.0907) and slightly decreased in ischemic heart disease (n = 1950; excess relative risk/Gy -0.077; 95% CI -0.130, -0.012; p = 0.0211). However, under 0.5 Gy, there was a borderline significant increasing trend for all circulatory disease (excess relative risk/Gy 0.345; 95% CI -0.032, 0.764; p = 0.0743) and for ischemic heart disease (excess relative risk/Gy 0.465; 95% CI, -0.032, 1.034, p = 0.0682). Pneumolobectomy increased radiation-associated risk (excess relative risk/Gy 0.252; 95% CI 0.024, 0.579). Fractionation of dose did not modify excess risk. In summary, we found no evidence of radiation-associated excess circulatory death risk overall, but there are indications of excess circulatory death risk at lower doses (<0.5 Gy). Although consistent with other radiation-exposed groups, the indications of higher risk at lower doses are unusual and should be confirmed against other data.
Lunetta, Kathryn L; Erlich, Porat M; Cuenco, Karen T; Cupples, L Adrienne; Green, Robert C; Farrer, Lindsay A; Decarli, Charles
Magnetic resonance imaging (MRI) traits can serve as more specific measures of degenerative or cerebrovascular brain injury than can be ascertained through personal history, risk factors, clinical signs, or symptoms. They are potentially useful intermediate phenotypes for genetic studies of Alzheimer disease (AD). Recent studies have estimated heritability of white matter hyperintensity (WMH) among cognitively normal family members to be between 0.55 and 0.73. Persons discordant for AD are expected to have substantially different MRI phenotype distributions; our goal was to determine whether MRI traits in siblings discordant for AD are heritable. We measured cerebral atrophy, medial temporal atrophy (MTA), WMH, and a rating of cerebrovascular disease (CVR) via MRI in 815 participants from 424 families of the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study. Residual heritability after adjustment for covariates ranged from 0.17 (P=0.009) for MTA to 0.57 (P=10(-7)) for CVR. The number of APOE-epsilon4 alleles was significantly associated with WMH (P=0.01) and CVR (P=0.005) but not cerebral atrophy (P=0.25) or MTA (P=0.83). Heritability remained significant and high after adjusting for APOE genotype, suggesting that a substantial proportion of the additive genetic variation in these MRI traits is explained by other genes. In the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study of AD-discordant siblings, MRI traits are heritable and are potential endophenotypes for genetic association studies.
Nicholls, E S; Peruga, A; Restrepo, H E
Despite subregional differences, mortality profiles have undergone major changes in most countries of the Americas. While the proportion of deaths caused by noncommunicable diseases, particularly cardiovascular diseases, has increased, overall age-adjusted mortality rates attributable to all cardiovascular disease are declining in 13 of the 15 countries selected for the present study. About half the countries showed decreasing mortality rates for ischaemic heart disease; the other half had increasing rates. The mortality rates for cerebrovascular disease and hypertensive disease declined in all but four countries. The ischaemic heart disease/cerebrovascular disease mortality ratio increased as a consequence of a greater decline in deaths due to cerebrovascular disease, except in two countries that exhibited a greater decline for ischaemic heart disease. With few exceptions the male-to-female mortality ratios increased for all cardiovascular disease, ischaemic heart disease and cerebrovascular disease, reflecting a greater decline in female mortality. In general there was a decline in all cardiovascular disease mortality for almost every age group in the North American, Southern Cone, English-speaking Caribbean, and Andean subregions, while there were increases in the Central American and Latin Caribbean subregions. The magnitude of the changes was related to the initial level of mortality and the date of onset of the decline. Change began earlier and the declines were largest in the countries with the highest initial mortality levels, whereas in the countries that initially had comparatively low values the mortality rates are still increasing. Insufficient information is available to permit elucidation of the determinants of the changes reported. There has been speculation about the possible role of factors such as demographic and sociocultural changes, changes in lifestyle and subsequently in the prevalence of risk factors for cardiovascular disease, and the
Vasilevko, Vitaly; Passos, Giselle F; Quiring, Daniel; Head, Elizabeth; Kim, Richard C; Fisher, Mark; Cribbs, David H
Age-related cerebrovascular dysfunction contributes to ischemic stroke, intracerebral hemorrhages (ICHs), microbleeds, cerebral amyloid angiopathy (CAA), and cognitive decline. Importantly, there is increasing recognition that this dysfunction plays a critical secondary role in many neurodegenerative diseases, including Alzheimer's disease (AD). Atherosclerosis, hypertension, and CAA are the most common causes of blood-brain barrier (BBB) lesions. The accumulation of amyloid beta (Aβ) in the cerebrovascular system is a significant risk factor for ICH and has been linked to endothelial transport failure and blockage of perivascular drainage. Moreover, recent anti-Aβ immunotherapy clinical trials demonstrated efficient clearance of parenchymal amyloid deposits but have been plagued by CAA-associated adverse events. Although management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA. Thus, there is a critical need for new strategies that improve BBB function and limit the development of β-amyloidosis in the cerebral vasculature.
Prinz, Vincent; Endres, Matthias
The introduction of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, i.e., statins, constitutes a milestone in the prevention of cardio- and cerebrovascular disease. The effects of statins extend far beyond their effects on cholesterol levels: pleiotropic effects include vasoprotective mechanisms, comprising improved endothelial function, increased bioavailability of nitric oxide, immunomodulatory and antiinflammatory properties, stabilization of atherosclerotic plaques, as well as antioxidant and stem cell-regulating capacities. Large clinical trials have clearly demonstrated that statins reduce the risk of myocardial infarction and stroke. Recent experimental and clinical data have demonstrated that in addition to risk reduction, statins may also improve outcome after stroke and myocardial infarction, even when statins were administered after the event. Moreover, abrupt discontinuation of statin therapy after acute cardio- or cerebrovascular events may impair vascular function and increase morbidity and mortality. Beyond stroke, statin treatment also has been shown to provide protective effects in critically ill patients, e.g., after major surgery, sepsis, or in patients at high-vascular risk. However, although large randomized controlled trials are missing, ongoing trials will clarify the impact of acute statin treatment in these conditions. Although evidence is presently limited, acute statin therapy is emerging as a new therapeutic avenue for the treatment of the critically ill. Until now, statins were only available as oral drugs. An IV formulation may be warranted for acute treatment of severely ill patients, for example, those who are unable to swallow or scheduled for surgery. Hydrophilic statins would be suitable for an IV formulation and have been safely tested in healthy volunteers.
Wiggers, Giulia Alessandra; Furieri, Lorena Barros; Briones, Ana María; Avendaño, María Soledad; Peçanha, Franck Maciel; Vassallo, Dalton Valentim; Salaices, Mercedes; Alonso, María Jesús
Mercury (Hg) has many harmful vascular effects by increasing oxidative stress, inflammation and vascular/endothelial dysfunction, all of which may contribute to cerebrovascular diseases development. We aimed to explore the effects of chronic low-mercury concentration on vascular function in cerebral arteries and the mechanisms involved. Basilar arteries from control (vehicle-saline solution, im) and mercury chloride (HgCl2)-treated rats for 30 days (first dose 4.6μg/kg, subsequent dose 0.07μg/kg/day, im, to cover daily loss) were used. Vascular reactivity, protein expression, nitric oxide (NO) levels and superoxide anion (O2(-)) production were analyzed. HgCl2 exposure increased serotonin contraction and reduced the endothelium-dependent vasodilatation to bradykinin. After NO synthase inhibition, serotonin responses were enhanced more in control than in mercury-treated rats while bradykinin-induced relaxation was abolished. NO levels were greater in control than Hg-treated rats. Tiron and indomethacin reduced vasoconstriction and increased the bradykinin-induced relaxation only in HgCl2-treated rats. Vascular O2(-) production was greater in mercury-treated when compared to control rats. Protein expressions of endothelial NO synthase, copper/zinc (Cu/Zn), Manganese (Mn) and extracellular-superoxide dismutases were similar in cerebral arteries from both groups. Results suggest that Hg treatment increases cerebrovascular reactivity by reducing endothelial negative modulation and NO bioavailability; this effect seems to be dependent on increased reactive oxygen species and prostanoids generation. These findings show, for the first time, that brain vasculature are also affected by chronic mercury exposure and offer further evidence that even at small concentration, HgCl2 is hazardous and might be an environmental risk factor accounting for cerebral vasospasm development.
Regan, Rosemary E; Fisher, Joseph A; Duffin, James
Background and Purpose Cerebrovascular reactivity (CVR), measures the ability of the cerebrovasculature to respond to vasoactive stimuli such as CO2. CVR is often expressed as the ratio of cerebral blood flow change to CO2 change. We examine several factors affecting this measurement: blood pressure, stimulus pattern, response analysis and subject position. Methods Step and ramp increases in CO2 were implemented in nine subjects, seated and supine. Middle cerebral artery blood flow velocity (MCAv), and mean arterial pressure (MAP) were determined breath-by-breath. Cerebrovascular conductance (MCAc) was estimated as MCAv/MAP. CVR was calculated from both the relative and absolute measures of MCAc and MCAv responses. Results MAP increased with CO2 in some subjects so that relative CVR calculated from conductance responses were less than those calculated from CVR calculated from velocity responses. CVR measured from step responses were affected by the response dynamics, and were less than those calculated from CVR measured from ramp responses. Subject position did not affect CVR. Conclusions (1) MAP increases with CO2 and acts as a confounding factor for CVR measurement; (2) CVR depends on the stimulus pattern used; (3) CVR did not differ from the sitting versus supine in these experiments; (4) CVR calculated from absolute changes of MCAv was less than that calculated from relative changes. PMID:25328852
Shenkar, Robert; Elliott, J. Paul; Diener, Katrina; Gault, Judith; Hu, Ling-Jia; Cohrs, Randall J.; Phang, Tzulip; Hunter, Lawrence; Breeze, Robert E.; Awad, Issam A.
OBJECTIVE We sought to identify genes with differential expression in cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs), and control superficial temporal arteries (STAs) and to confirm differential expression of genes previously implicated in the pathobiology of these lesions. METHODS Total ribonucleic acid was isolated from four CCM, four AVM, and three STA surgical specimens and used to quantify lesion-specific messenger ribonucleic acid expression levels on human gene arrays. Data were analyzed with the use of two separate methodologies: gene discovery and confirmation analysis. RESULTS The gene discovery method identified 42 genes that were significantly up-regulated and 36 genes that were significantly down-regulated in CCMs as compared with AVMs and STAs (P = 0.006). Similarly, 48 genes were significantly up-regulated and 59 genes were significantly down-regulated in AVMs as compared with CCMs and STAs (P = 0.006). The confirmation analysis showed significant differential expression (P < 0.05) in 11 of 15 genes (angiogenesis factors, receptors, and structural proteins) that previously had been reported to be expressed differentially in CCMs and AVMs in immunohistochemical analysis. CONCLUSION We identify numerous genes that are differentially expressed in CCMs and AVMs and correlate expression with the immunohistochemistry of genes implicated in cerebrovascular malformations. In future efforts, we will aim to confirm candidate genes specifically related to the pathobiology of cerebrovascular malformations and determine their biological systems and mechanistic relevance. PMID:12535382
Providência, Rui; Gonçalves, Lino; Ferreira, Maria João
Cerebrovascular disease has long been the leading cause of death in Portugal. Despite improvements in the treatment of hypertension and the resulting decrease in associated mortality, the progressive aging of the population and increased prevalence of atrial fibrillation have prevented the incidence of stroke from falling as much as desired. The authors review the evidence on the situation in Portugal and propose an intervention plan.
position with the head in a stereotaxic frame. The skin was incised over the sutura sagittalis (30 mm in length), and the skull was exposed between the... sutura coronalis and the s. lambdoidea. The dermis, subdermal layers, periosteum and muscle over the parasagittal regions were removed; the bone was...electrodes was as follows: 3 mm lateral to the sutura sagittalis; 3 mm anterior to the coronal suture; 3 mm anterior to the lambdoid suture. These
MacKay, Christina M; Skow, Rachel J; Tymko, Michael M; Boulet, Lindsey M; Davenport, Margie H; Steinback, Craig D; Ainslie, Philip N; Lemieux, Chantelle C M; Day, Trevor A
One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology.
Lee, Wen-Hsien; Hsu, Po-Chao; Chu, Chun-Yuan; Su, Ho-Ming; Lee, Chee-Siong; Yen, Hsueh-Wei; Lin, Tsung-Hsien; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung
Background Atherothrombotic diseases including cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial disease (PAD), contribute to the major causes of death in the world. Although several studies showed the association between polyvascular disease and poor cardiovascular (CV) outcomes in Asian population, there was no large-scale study to validate this relationship in this population. Methods and Results This retrospective cohort study included patients with a diagnosis of CVD, CAD, or PAD from the database contained in the Taiwan National Health Insurance Bureau during 2001–2004. A total of 19954 patients were enrolled in this study. The atherothrombotic disease score was defined according to the number of atherothrombotic disease. The study endpoints included acute coronary syndrome (ACS), all strokes, vascular procedures, in hospital mortality, and so on. The event rate of ischemic stroke (18.2%) was higher than that of acute myocardial infarction (5.7%) in our patients (P = 0.0006). In the multivariate Cox regression analyses, the adjusted hazard ratios (HRs) of each increment of atherothrombotic disease score in predicting ACS, all strokes, vascular procedures, and in hospital mortality were 1.41, 1.66, 1.30, and 1.14, respectively (P≦0.0169). Conclusions This large population-based longitudinal study in patients with atherothrombotic disease demonstrated the risk of subsequent ischemic stroke was higher than that of subsequent AMI. In addition, the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score. PMID:24647769
Goldberg, P; Gueguen, A; Schmaus, A; Nakache, J; Goldberg, M
STUDY OBJECTIVE—Although perceived health status is an indicator widely used in epidemiological studies, its relation to various diseases is not well known. The objective of this study is to examine these relations in detail. DESIGN—Marginal models used for a longitudinal study of the association between three health scales and 47 diseases among 12 164 men and 44 diseases among 4415 women. SETTING—French Gazel cohort during the period from 1991 to 1996. MAIN RESULTS—The general health status scale was significantly associated with 43 diseases among men, and 31 among women. Some of these significantly associated diseases were physical (for example, cancer and cerebrovascular accident) and others, psychological (for example, depression). The mental fatigue scale was more specifically associated with psychological disorders, including sleep problems, depression, and nervous diseases. Moreover, modifications in subjects' assessment of their health from one year to the next were generally associated with modifications in reported diseases. CONCLUSION—Although the mechanism that relates the presence of a disease to perceived health status remains in question, these results show clearly that there is a close association between these two domains that justifies the use of perceived health as a proxy for self reported diseases. Keywords: marginal model; health scale; self rated disease PMID:11238577
Intracerebral haemorrhage is the most dramatic, even if not the most frequent among cerebrovascular emergencies. However the improved treatment of arterial hypertension has decreased its frequency. Modern neuroradiological methods have led to an easier diagnosis, but the best choice for treatment (medical or surgical) is still debated. Decision must be based upon different factors, the most important of which are clinical condition volume, and location of haemorrhage. If the general prognosis has been improved by the transfer to specialized Units, wherein such are available, the benefit of surgery, while indispensable in some cases, has yet to be demonstrated by prospective studies. The problem is far different in subarachnoïd haemorrhage due to rupture of a vascular malformation: the necessity of a rapid treatment by surgery or embolization is largely admitted except for those patients in a bad clinical conditions.
LaPelusa, Michael B.; Charvat, Jacqueline M.; Lee, Lesley R.; Wear, Mary L.; Van Baalen, Mary
The development of atherosclerosis is strongly associated with an increased risk for cerebrovascular accidents (CVA), including stroke and transient ischemic attacks (TIA). Certain unique occupational exposures that individuals in the NASA astronaut corps face, specifically high-performance aircraft training, SCUBA training, and spaceflight, are hypothesized to cause changes to the cardiovascular system. These changes, which include (but are not limited to) oxidative damage as a result of radiation exposure and circadian rhythm disturbance, increased arterial stiffness, and increased carotid-intima-media thickness (CIMT), may contribute to the development of atherosclerosis and subsequent CVA. The purpose of this study was to review cases of CVA in the NASA astronaut corps and describe the comorbidities and occupational exposures associated with CVA.
Judd, B.W.; Meyer, J.S.; Rogers, R.L.; Gandhi, S.; Tanahashi, N.; Mortel, K.F.; Tawaklna, T.
Cerebral blood flow (CBF) was measured by the /sup 133/Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses to situational demands and predisposes to cerebral ischemia. Loss of cerebral vasomotor responsiveness among MID patients, which is a biologic marker of cerebrovascular disease, provides confirmatory evidence of the vascular etiology of MID and assists in separating MID from AD patients.
Thust, Stefanie C.; Chong, Wui Khean Kling; Gunny, Roxana; Mazumder, Asif; Poitelea, Marius; Welsh, Anna; Ederies, Ash
Background Paediatric cerebrovascular CT angiography (CTA) can be challenging to perform due to variable cardiovascular physiology between different age groups and the risk of movement artefact. This analysis aimed to determine what proportion of CTA at our institution was of diagnostic quality and identify technical factors which could be improved. Materials and methods a retrospective analysis of 20 cases was performed at a national paediatric neurovascular centre assessing image quality with a subjective scoring system and Hounsfield Unit (HU) measurements. Demographic data, contrast dose, flow rate and triggering times were recorded for each patient. Results Using a qualitative scoring system, 75% of studies were found to be of diagnostic quality (n=9 ‘good’, n=6 ‘satisfactory’) and 25% (n=5) were ‘poor’. Those judged subjectively to be poor had arterial contrast density measured at less than 250 HU. Increased arterial opacification was achieved for cases performed with an increased flow rate (2.5-4 mL/s) and higher intravenous contrast dose (2 mL/kg). Triggering was found to be well timed in nine cases, early in four cases and late in seven cases. Of the scans triggered early, 75% were poor. Of the scans triggered late, less (29%) were poor. Conclusions High flow rates (>2.5 mL/s) were a key factor for achieving high quality paediatric cerebrovascular CTA imaging. However, appropriate triggering by starting the scan immediately on contrast opacification of the monitoring vessel plays an important role and could maintain image quality when flow rates were lower. Early triggering appeared more detrimental than late. PMID:25525579
Ogoh, Shigehiko; Nakahara, Hidehiro; Ueda, Shinya; Okazaki, Kazunobu; Shibasaki, Manabu; Subudhi, Andrew W; Miyamoto, Tadayoshi
In normoxic conditions, a reduction in arterial carbon dioxide tension causes cerebral vasoconstriction, thereby reducing cerebral blood flow and modifying dynamic cerebral autoregulation (dCA). It is unclear to what extent these effects are altered by acute hypoxia and the associated hypoxic ventilatory response (respiratory chemoreflex). This study tested the hypothesis that acute hypoxia attenuates arterial CO2 tension-mediated regulation of cerebral blood flow to help maintain cerebral O2 homeostasis. Eight subjects performed three randomly assigned respiratory interventions following a resting baseline period, as follows: (1) normoxia (21% O2); (2) hypoxia (12% O2); and (3) hypoxia with wilful restraint of the respiratory chemoreflex. During each intervention, 0, 2.0, 3.5 or 5.0% CO2 was sequentially added (8 min stages) to inspired gas mixtures to assess changes in steady-state cerebrovascular CO2 reactivity and dCA. During normoxia, the addition of CO2 increased internal carotid artery blood flow and middle cerebral artery mean blood velocity (MCA Vmean), while reducing dCA (change in phase = -0.73 ± 0.22 rad, P = 0.005). During acute hypoxia, internal carotid artery blood flow and MCA Vmean remained unchanged, but cerebrovascular CO2 reactivity (internal carotid artery, P = 0.003; MCA Vmean, P = 0.031) and CO2-mediated effects on dCA (P = 0.008) were attenuated. The effects of hypoxia were not further altered when the respiratory chemoreflex was restrained. These findings support the hypothesis that arterial CO2 tension-mediated effects on the cerebral vasculature are reduced during acute hypoxia. These effects could limit the degree of hypocapnic vasoconstriction and may help to regulate cerebral blood flow and cerebral O2 homeostasis during acute periods of hypoxia.
Pala, Laura; Monami, Matteo; Ciani, Silvia; Dicembrini, Ilaria; Pasqua, Alessandro; Pezzatini, Anna; Francesconi, Paolo; Cresci, Barbara; Mannucci, Edoardo; Rotella, Carlo Maria
Background and Aims. The secretion of several adipocytokines, such as adiponectin, retinol-binding protein 4 (RBP4), adipocyte fatty acid binding protein (aFABP), and visfatin, is altered in subjects with abdominal adiposity; these endocrine alterations could contribute to increased cardiovascular risk. The aim of the study was to assess the relationship among adiponectin, RBP4, aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A case-control study, nested within a prospective cohort, on 2945 subjects enrolled for a diabetes screening program was performed. We studied 18 patients with incident fatal or nonfatal IHD (Ischemic Heart Disease) or CVD (Cerebrovascular Disease), compared with 18 matched control subjects. Circulating adiponectin levels were significantly lower in cases of IHD with respect to controls. Circulating RBP4 levels were significantly increased in CVD and decreased in IHD with respect to controls. Circulating aFABP4 levels were significantly increased in CVD, while no difference was associated with IHD. Circulating visfatin levels were significantly lower in cases of both CVD and IHD with respect to controls, while no difference was associated with CVD. Conclusions. The present study confirms that low adiponectin is associated with increased incidents of IHD, but not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and RBP4 in the development of cardiovascular disease. PMID:21869928
Sethi, S K; Sarm, P S A
Fatal bilateral cerebro-vascular accident with variable atrio-ventricular blocks, atrial fibrillation and refractory tachy-arrhythmias in a previously healthy 75-years-old hypertensive female is presented.
Schreiber, W G; Gückel, F; Stritzke, P; Schmiedek, P; Schwartz, A; Brix, G
We have developed a new method for estimation of regional CBF (rCBF) and cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2 patients with acute stroke underwent dynamic susceptibility-weighted contrast enhanced MRI. Using principles of indicator dilution theory and deconvolution analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit time (MTT) were calculated. In patients with ICA occlusion/stenosis, cerebrovascular reserve capacity was assessed by the rCBF increase after acetazolamide stimulation. Mean gray and white matter rCBF values in normals were 67.1 and 23.7 mL x 100 g(-1) x min(-1), respectively. Before acetazolamide stimulation, six of eight patients with ICA occlusions showed decreased rCBF values; and in seven patients increased MTT values were observed in tissue ipsilateral to the occlusion. After acetazolamide stimulation, decreased cerebrovascular reserve capacity was observed in five of eight patients with ICA occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8 mL x 100 g(-1) x min(-1). In peri-infarct tissue, rCBF and MTT were higher than in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical information on the hemodynamic state of brain tissue in patients with occlusive cerebrovascular disease or acute stroke.
Kioumourtzoglou, Marianthi-Anna; Seals, Ryan M; Gredal, Ole; Mittleman, Murray A; Hansen, Johnni; Weisskopf, Marc G
Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disease of unknown etiology. We investigated the association between ALS diagnosis and prior cardiovascular disease (CVD), and CVD-specific, hospital admissions in the Danish population. We conducted a population based nested case-control study, including 3182 Danish residents diagnosed with ALS at age ≥20 years (1982-2009) and 100 randomly selected controls for each case, matched on age, gender and vital status. We estimated odds ratios (OR) associated with CVD, and CVD-specific hospital admissions, adjusting for socioeconomic and marital status, region of residence and past diabetes and obesity diagnoses. The estimated adjusted OR for any CVD admission at least three years prior to the date of ALS diagnosis was 1.15 (95% CI 1.04-1.27). Our results varied across cause-specific admissions; for atherosclerosis the OR was 1.36 (95% CI 1.02-1.80) and for ischemic heart disease 1.14 (95% CI 0.99-1.31), while we observed no association with hypertensive and cerebrovascular diseases. Adjusting for or stratifying by COPD status, a cigarette-smoking correlate, did not change our results. In conclusion, in our population based study we found evidence for a moderately elevated association with CVD that was stronger for specific conditions, such as atherosclerosis. Our findings may have important implications for ALS pathogenesis.
Fujita, K; Yamasaki, S; Tamaki, N; Fujita, S; Shirakata, S; Matsumoto, S
Cerebro-vascular accident is an uncommon but formidable complication of pregnancy. Faced with these cases, the neurosurgeon and obstetrician might differ in the planning of the treatment, when the interests of mother and child appear to conflict between them. From our clinical data of 5 cases and review of the literatures, the following points should be considered for the management of a cerebro-vascular accident during pregnancy. (1) The possibility of cerebro-vascular accident should be considered in any pregnant patients with neurological symptoms, and full investigation should be done if clini-indicated. (2) Aneurysm and angioma are most often encountered in pregnant patients with a cerebro-vascular accident. (3) Unless labour begins during investigation, a cerebral lesion should be treated before delivery, irrespective of the stage of pregnancy and the method of treatment should be decided primarily on neurosurgical grounds. (4) The time of onset of cerebro-vascular accident may be related to the hemodynamic and hormonal change. It occurs more frequently after the second trimester, when the blood volume and cardiac output reach their peak. (5) Pregnancy per se does not influence the mortality from a cerebro-vascular accident in pregnant patients.
Meairs, S; Beyer, J; Hennerici, M
Although recent studies have demonstrated the potential value of compounded data for improvement in signal-to-noise ratio and speckle contrast for three-dimensional (3-D) ultrasonography, clinical applications are lacking. We investigated the potential of six degrees-of-freedom (6-DOF) scanhead position and orientation measurement (POM) devices for registration of in vivo multiplanar, irregularly sampled ultrasound (US) images to a regular 3-D volume space. The results demonstrate that accurate spatial and temporal registration of four-dimensional (4-D) US data can be achieved using a 6-DOF scanhead tracking system. For reconstruction of arbitrary, irregularly sampled US data, we introduce a technique based upon a weighted, ellipsoid Gaussian convolution kernel. Volume renderings of 3-D and 4-D compounded in vivo US data are presented. The results, although restricted to the field of cerebrovascular disease, will be of value to other applications of 3-D sonography, particularly those in which compounding of data through irregular sampling may provide superior information on tissue or vessel structure.
Del Brutto, Oscar H; Mera, Robertino M; Macias, Jorge; Morales, Gabriela; Zambrano, Mauricio
All studies attempting to find an association between vitamin D deficiency and cerebrovascular diseases have been conducted at latitudes far away from the Equator, where living conditions, cardiovascular risk factors, and sunshine exposure are different from tropical regions. We aimed to assess cerebrovascular correlates of vitamin D deficiency in community-dwelling older adults living in Atahualpa, a village located in rural coastal Ecuador. Out of 267 individuals enrolled in the neuroimaging substudy of the Atahualpa Project, 220 (82%) signed the informed consent. Mean age of participants was 70·9 ± 7·8 years, and 126 (57%) were women. Fifty-four (25%) persons have vitamin D levels <20 ng/ml, 47 (21%) had ischemic strokes, and 53 (24%) had moderate-to-severe white matter hyperintensities of presumed vascular origin. Exposure effect models constructed with vitamin D deficiency as the exposure, white matter hyperintensities and ischemic stroke as the outcomes, and confounders--age, gender, body mass index, physical activity, blood pressure, fasting glucose, total cholesterol, ionized calcium, phosphorus, intact parathormone, and serum creatinine--as independent variables revealed a significant association of vitamin D deficiency with white matter hyperintensities (P = 0·006) but not with ischemic strokes (P = 0·359). This study shows an association of vitamin D deficiency with diffuse subcortical brain damage in older adults living in a tropical region. Lack of awareness of the importance of vitamin D deficiency might be one of the factors influencing the high prevalence of white matter hyperintensities of presumed vascular origin in underserved Latin American populations.
Koscielny, J; Jung, E M; Mrowietz, C; Kiesewetter, H; Latza, R
In the Aachen study the prevalence of arterial disease was established in 346 out of a cohort of 2821 subjects between 45 and 65 years of age. Rheological variables and risk factor profile for patients with peripheral occlusive arterial disease (POAD), coronary heart disease (CHD) and cerebrovascular insufficiency (CI) in comparison to a control group are given. Significantly elevated are hematocrit in males, plasma viscosity, erythrocyte aggregation and fibrinogen. It is evident that plasma viscosity is the rheological parameter most often elevated in patients with arterial disease (70.8%). In patients with CI (80.6%) plasma viscosity is elevated about four times more often than in healthy subjects. While 85.8% of healthy volunteers show no or only one elevated rheological parameter only 44.5% of the patients have this constellation. Risk factors are bundled in patients compared to healthy volunteers. 84.2% of the healthy volunteers have no or only one risk factor whereas patients with OAD show this constellation in only 30.9% (32.4% in POAD, 16.1% in CI and 32.4% in CHD).
Ethell, Douglas W; Cameron, D Joshua
Zebrafish are a powerful tool to study developmental biology and pathology in vivo. The small size and relative transparency of zebrafish embryos make them particularly useful for the visual examination of processes such as heart and vascular development. In several recent studies transgenic zebrafish that express EGFP in vascular endothelial cells were used to image and analyze complex vascular networks in the brain and retina, using confocal microscopy. Descriptions are provided to prepare, treat and image zebrafish embryos that express enhanced green fluorescent protein (EGFP), and then generate comprehensive 3D renderings of the cerebrovascular system. Protocols include the treatment of embryos, confocal imaging, and fixation protocols that preserve EGFP fluorescence. Further, useful tips on obtaining high-quality images of cerebrovascular structures, such as removal the eye without damaging nearby neural tissue are provided. Potential pitfalls with confocal imaging are discussed, along with the steps necessary to generate 3D reconstructions from confocal image stacks using freely available open source software.
Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane
Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316
Xu, Zhen; Tito, Antonio; Rui, Yan-Ning; Zhang, Sheng
Polyglutamine (polyQ) diseases are a family of dominantly transmitted neurodegenerative disorders caused by an abnormal expansion of CAG trinucleotide repeats in the protein-coding regions of the respective disease-causing genes. Despite their simple genetic basis, the etiology of these diseases is far from clear. Over the past two decades, Drosophila has proven to be successful in modeling this family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. Additionally, it has been valuable in probing the pathogenic mechanisms, in identifying and evaluating disease modifiers, and in helping elucidate the normal functions of disease-causing genes. Knowledge learned from this simple invertebrate organism has had a large impact on our understanding of these devastating brain diseases. PMID:26257024
Karasek, R; Baker, D; Marxer, F; Ahlbom, A; Theorell, T
The association between specific job characteristics and subsequent cardiovascular disease was tested using a large random sample of the male working Swedish population. The prospective development of coronary heart disease (CHD) symptoms and signs was analyzed using a multivariate logistic regression technique. Additionally, a case-controlled study was used to analyze all cardiovascular-cerebrovascular (CHD-CVD) deaths during a six-year follow-up. The indicator of CHD symptoms and signs was validated in a six-year prospective study of CHD deaths (standardized mortality ratio 5.0; p less than or equal to .001). A hectic and psychologically demanding job increases the risk of developing CHD symptoms and signs (standardized odds ratio 1.29, p less than 0.25) and premature CHD-CVD death (relative risk 4.0, p less than .01). Low decision latitude-expressed as low intellectual discretion and low personal schedule freedom-is also associated with increased risk of cardiovascular disease. Low intellectual discretion predicts the development of CHD symptoms and signs (SOR 1.44, p less than .01), while low personal schedule freedom among the majority of workers with the minimum statutory education increases the risk of CHD-CVD death (RR 6.6, p less than .0002). The associations exist after controlling for age, education, smoking, and overweight. PMID:7246835
Dee, T H; Schiffman, G; Sottile, M I; Rytel, M W
Many patients die from pneumococcal disease despite the availability of effective antimicrobial agents. Immunologic studies including detection, typing, and quantitation of serum pneumococcal capsular polysaccharide (PCP) antigen by counterimmunoelectrophoresis (CIE), quantitation of PCP antibody by radioimmunoassay (RIA), and quantitation of serum complement components C3, C4, and C3PA and serum immunoglobulins IgG, IgM, and IgA by the radial immunodiffusion technique of Mancini were performed with the sera of 18 patients. Five patients died (group I), and 13 survived (group II) pneumococcal infection. Both groups were comparable in age, underlying disease, and leukopenia on admission. All patients of group I and 10 of 13 (77%) of group II patients were bacteremic. Two patients in each group had an extrapulmonary focus infection. PCP antigen was detected in the sera of all group I and nine of 13 group II patients. PCP antigen levels were larger than or equal to 15 microng/ml in four of five group I and two of 13 group II patients (p = 0.022). Levels of antibody to PCP exceeded 100 ng/ml of antibody nitrogen (AbN) in 10 of 12 group II and one of five group I patients (p = 0.027) during the course of illness. All group I patients and three of 12 group II patients had decreased levels of one or more complement components on admission (p less than 0.01). One or more complement components remained decreased until death in four group I patients but returned to normal or elevated levels in all group II patients. No difference in serum immunoglobulin concentrations were found.
Gauthier, Sebastien A; Sahoo, Susmita; Jung, Sonia S; Levy, Efrat
The use of murine cerebrovascular endothelial and smooth muscle cells has not been widely employed as a cell culture model for the investigation of cellular mechanisms involved in cerebral amyloid angiopathy (CAA). Difficulties in isolation and propagation of murine cerebrovascular cells and insufficient yields for molecular and cell culture studies have deterred investigators from using mice as a source for cerebrovascular cells in culture. Instead, cerebrovascular cells from larger mammals are preferred and several methods describing the isolation of endothelial and smooth muscle cells from human, canine, rat, and guinea pig have been published. In recent years, several transgenic mouse lines showing CAA pathology have been established; consequently murine cerebrovascular cells derived from these animals can serve as a key cellular model to study CAA. Here, we describe a procedure for isolating murine microvessels that yields healthy smooth muscle and endothelial cell populations and produce sufficient material for experimental purposes. Murine smooth muscle cells isolated using this protocol exhibit the classic "hill and valley" morphology and are immunoreactive for the smooth muscle cell marker α-actin. Endothelial cells display a "cobblestone" pattern phenotype and show the characteristic immunostaining for the von Willebrand factor and the factor VIII-related antigen. In addition, we describe methods designed to preserve these cells by storage in liquid nitrogen and reestablishing viable cell cultures. Finally, we compare our methods with protocols designed to isolate and maintain human cerebrovascular cell cultures.
Smith, M Z; Nagy, Z; Esiri, M M
Recent findings from our and other laboratories indicate that cell cycle-related phenomena may play a key role in the formation of Alzheimer-type pathology and neuronal cell death in both Alzheimer's and cerebro-vascular diseases. In this study we examine the expression patterns of cyclins A, B1, D1 and E in neuronal nuclei in the hippocampus in autopsied healthy elderly individuals, Alzheimer's disease patients and subjects suffering from cerebrovascular disease with and without co-existing Alzheimer's disease. Nuclear cyclin B1 and cyclin E expression was detected in hippocampal neurones in each subject category. However, cyclin B1 expression was significantly elevated in the CA1 of patients suffering from cerebro-vascular disease alone, while cyclin E expression was significantly higher in the CA4 subfield in patients suffering from mixed Alzheimer's and cerebro-vascular diseases compared to subjects in other categories. We hypothesize that cell cycle re-entry may occur in healthy elderly people leading to age-related cell death and mild Alzheimer-type pathology in the hippocampus. However, in pathological conditions, the cell cycle arrest may lead either to the development of severe Alzheimer-related pathology or to excess apoptotic cell death as in vascular dementia.
Escalona, A Olloqui; Pradel, Z Galve; Pisón, J López; Oguiza, A García; Montañés, N Clavero; Delgado, R Pérez; Hidalgo, M Lafuente; Guelbenzu, S; Segura, J L Peña
We present the case of a 13 year-old patient diagnosed with fibromuscular dysplasia (FMD) by angiographic study, with "string of beads" image of internal carotid, after undergoing two ischemic strokes in nine days. Conservative treatment with acetylsalicylic acid at antiaggregant doses was decided. Twenty months later the clinical progress is favorable without presenting any new episodes. FMD is a very uncommon cause of stroke in childhood. Little is known about its etiology. In spite of it usually being an asymptomatic disease, it must be considered in cases of repeated or inexplicable strokes. Its prognosis and treatment is controversial, due to the limited number of pediatric patients with this pathology.
Ishizuka, Toshiaki; Niwa, Atsuko; Tabuchi, Masaki; Ooshima, Kana; Higashino, Hideaki
Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.
Myburgh, J A; Upton, R N; Grant, C; Martinez, A
Infusions of catecholamines are frequently administered to patients receiving propofol or isoflurane anaesthesia. Interactions between these drugs may affect regional circulations, such as the brain. The aim of this animal (sheep) study was to determine the effects of ramped infusions of adrenaline, noradrenaline (10, 20, 40 micrograms/min) and dopamine (10, 20, 40 micrograms/kg/min) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR) and cerebral metabolic rate for oxygen (CMRO2). These measurements were made under awake physiological conditions, and during continuous propofol (15 mg/min) or 2% isoflurane anaesthesia. All three catecholamines significantly and equivalently increased mean arterial pressure from baseline in a dose-dependent manner in the three cohorts (P < 0.001). In the awake cohort (n = 8), dopamine (P < 0.01) significantly increased CBF from baseline whilst adrenaline and noradrenaline did not (P > 0.05). Under propofol (n = 6) and isoflurane (n = 6), all three catecholamines significantly increased CBF (P < 0.001). Dopamine caused the greatest increase in CBF, and was associated with significant increases in ICP (awake: P < 0.001; propofol P < 0.05; isoflurane P < 0.001) and CVR (isoflurane P < 0.05). No significant changes in CMRO2 were demonstrated. Under propofol and isoflurane anaesthesia, the cerebrovascular effects of catecholamines were significantly different from the awake, physiological state, with dopamine demonstrating the most pronounced effects, particularly under propofol. Dopamine-induced hyperaemia was associated with other cerebrovascular changes. In the presence of an equivalent effect on mean arterial pressure, the exaggerated cerebrovascular effects under anaesthesia appear to be centrally mediated, possibly induced by propofol- or isoflurane-dependent changes in blood-brain barrier permeability, thereby causing a direct influence on the cerebral vasculature.
Byard, Roger W
A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42-year-old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left-sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman.
Murray, C J; Lopez, A D
As part of the Global Burden of Disease Study, three scenarios of future mortality and disability were identified. The scenarios were based on future health status as a function of projected changes in key socioeconomic variables that influence health status. Regression equations for mortality rates for nine cause-of-death clusters were developed by region based on gross domestic product per person, average number of years of education, time (as a proxy for technological change), and smoking intensity. Life expectancy at birth was projected, in all three scenarios, to increase for women (to about 90 years in established market economies by 2020), with far smaller gains in male life expectancy. Worldwide, annual mortality from communicable maternal, perinatal, and nutritional disorders (group 1 causes) is expected to decline from 17.2 million to 10.3 million in 2020 in the baseline model. Also expected is a very large increase in deaths from non-communicable diseases (group 2 causes) from 28.1 million in 1990 to 49.7 million in 2020. Deaths from injuries (group 3) are projected to increase from 5.1 million to 8.4 million. Diarrheal diseases, perinatal disorders, measles, and malaria are expected to decline dramatically as causes of death in the 1990-2020 period, while lung cancer, stomach cancer, war injuries, liver cancer, and HIV are expected to move up five or more places in the ranking. In 2020, the 10 leading causes of disability-adjusted life-years (in descending order) are projected to be ischemic heart disease, unipolar major depression, road traffic accidents, cerebrovascular disease, chronic obstructive pulmonary disease, lower respiratory infections, tuberculosis, war injuries, diarrheal diseases, and HIV. Tobacco-attributable mortality is projected to increase from 3.0 million in 1990 to 8.4 million in 2020 (9% of the worldwide mortality burden).
Background Most neurodegenerative diseases are age-related disorders; however, how aging predisposes the brain to disease has not been adequately addressed. The objective of this study is to determine whether expression of proteins in the cerebromicrovasculature related to inflammation, oxidative stress and neurotoxicity is altered with aging. Methods Brain microvessels are isolated from Fischer 344 rats at 6, 12, 18 and 24 months of age. Levels of interleukin (IL)-1β and IL-6 RNA are determined by RT-PCR and release of cytokines into the media by ELISA. Vessel conditioned media are also screened by ELISA for IL-1α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α, (TNFα), and interferon γ (IFNγ). Immunofluorescent analysis of brain sections for IL-1β and IL-6 is performed. Results Expression of IL-1β and IL-6, both at RNA and protein levels, significantly (p < 0.01) decreases with age. Levels of MCP-1, TNFα, IL-1α, and IFNγ are significantly (p < 0.05-0.01) lower in 24 month old rats compared to 6 month old animals. Immunofluorescent analysis of brain vessels also shows a decline in IL-1β and IL-6 in aged rats. An increase in oxidative stress, assessed by increased carbonyl formation, as well as a decrease in the antioxidant protein manganese superoxide dismutase (MnSOD) is evident in vessels of aged animals. Finally, addition of microvessel conditioned media from aged rats to neuronal cultures evokes significant (p < 0.001) neurotoxicity. Conclusions These data demonstrate that cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging and suggest that the microvasculature may contribute to functional changes in the aging brain. PMID:20937133
MacDonald, Matthew Ethan; Frayne, Richard
Cerebrovascular imaging is of great interest in the understanding of neurological disease. MRI is a non-invasive technology that can visualize and provide information on: (i) the structure of major blood vessels; (ii) the blood flow velocity in these vessels; and (iii) the microcirculation, including the assessment of brain perfusion. Although other medical imaging modalities can also interrogate the cerebrovascular system, MR provides a comprehensive assessment, as it can acquire many different structural and functional image contrasts whilst maintaining a high level of patient comfort and acceptance. The extent of examination is limited only by the practicalities of patient tolerance or clinical scheduling limitations. Currently, MRI methods can provide a range of metrics related to the cerebral vasculature, including: (i) major vessel anatomy via time-of-flight and contrast-enhanced imaging; (ii) blood flow velocity via phase contrast imaging; (iii) major vessel anatomy and tissue perfusion via arterial spin labeling and dynamic bolus passage approaches; and (iv) venography via susceptibility-based imaging. When designing an MRI protocol for patients with suspected cerebral vascular abnormalities, it is appropriate to have a complete understanding of when to use each of the available techniques in the 'MR angiography toolkit'. In this review article, we: (i) overview the relevant anatomy, common pathologies and alternative imaging modalities; (ii) describe the physical principles and implementations of the above listed methods; (iii) provide guidance on the selection of acquisition parameters; and (iv) describe the existing and potential applications of MRI to the cerebral vasculature and diseases. The focus of this review is on obtaining an understanding through the application of advanced MRI methodology of both normal and abnormal blood flow in the cerebrovascular arteries, capillaries and veins.
In 1958, Minamata Disease was suggested to be organic mercury compounds intoxication. This suggestion was based on Hunter and Russel's report on occupational exposure to methylmercury. This report is known to have established the typical symptoms of methyl mercury intoxication. However, it has been widely believed since the official recognition of Minamata Disease (1956) that, at the moment of outbreak, no reports were available on organic mercury formation from inorganic mercury in acetaldehyde production from acetylene, or on organic mercury intoxication among workers in acetaldehyde production from acetylene. However, this was not the case. The formation of organic mercury from inorganic mercury used as a catalyst was reported by Vogt and Nieuwland in 1921. In 1930, Zangger reported several cases of organic mercury intoxication among workers in acetaldehyde production from acetylene. Soon after, Koelsch reported that the cases were methyl- and/or ethylmercury intoxication, and that such cases had been common since 1916. These reports were already available at the time of the Minamata Disease outbreak. However, Zangger's report, the most important of these three was not referred to until 1987, notwithstanding its listing in the references of Kurland et al.. Zangger's report was not referred to not by investigators, but by a lawyer. If these reports had been referred to at the outbreak of Minamata Disease, the number of victims in Minamata would have been minimized, and Minamata Disease in Niigata would have been prevented.
Protocol for a systematic review of the diagnostic and prognostic utility of tests currently available for the detection of aspirin resistance in patients with established cardiovascular or cerebrovascular disease
Background The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed “aspirin resistance”. These patients may in turn be at a higher risk of future vascular events. The proportion of “resistant” patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151). Methods Relevant studies will be sought from bibliographic databases. Trials registers will be searched for ongoing studies. Reference lists will be checked and subject experts contacted. There will be no date or language restrictions. Standard reviewing methodology to minimise bias will be employed. Any prospective studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included, as will studies reporting prognostic models. Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines, and suitable criteria for assessing quality of prognostic studies. Data on test accuracy measures, relative risks, odds or hazard ratios will be extracted and meta-analysed, where possible, using a random-effects model to account for between-study heterogeneity. Where appropriate, the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses. If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population, the potential for a cost-effectiveness analysis will be considered and, if possible, an economic model constructed. This
Lee, Sohee; Kang, Bok-Man; Shin, Min-Kyoo; Min, Jiwoong; Heo, Chaejeong; Lee, Yubu; Baeg, Eunha; Suh, Minah
Repeated stress is one of the major risk factors for cerebrovascular disease, including stroke, and vascular dementia. However, the functional alterations in the cerebral hemodynamic response induced by chronic stress have not been clarified. Here, we investigated the in vivo cerebral hemodynamic changes and accompanying cellular and molecular changes in chronically stressed rats. After 3 weeks of restraint stress, the elicitation of stress was verified by behavioral despair in the forced swimming test and by physical indicators of stress. The evoked changes in the cerebral blood volume and pial artery responses following hindpaw electrical stimulation were measured using optical intrinsic signal imaging. We observed that, compared to the control group, animals under chronic restraint stress exhibited a decreased hemodynamic response, with a smaller pial arterial dilation in the somatosensory cortex during hindpaw electrical stimulation. The effect of chronic restraint stress on vasomodulator enzymes, including neuronal nitric oxide synthase (nNOS) and heme oxygenase-2 (HO-2), was assessed in the somatosensory cortex. Chronic restraint stress downregulated nNOS and HO-2 compared to the control group. In addition, we examined the subtypes of cells that can explain the environmental changes due to the decreased vasomodulators. The expression of parvalbumin in GABAergic interneurons and glutamate receptor-1 in neurons were decreased, whereas the microglial activation was increased. Our results suggest that the chronic stress-induced alterations in cerebral vascular function and the modulations of the cellular expression in the neuro-vasomodulatory system may be crucial contributing factors in the development of various vascular-induced conditions in the brain. PMID:26778944
Rivera-Rivera, Leonardo A; Schubert, Tilman; Turski, Patrick; Johnson, Kevin M; Berman, Sara E; Rowley, Howard A; Carlsson, Cynthia M; Johnson, Sterling C; Wieben, Oliver
Cerebral blood flow, arterial pulsation, and vasomotion may be important indicators of cerebrovascular health in aging and diseases of aging such as Alzheimer's disease. Noninvasive markers that assess these characteristics may be helpful in the study of co-occurrence of these diseases and potential additive and interacting effects. In this study, 4D flow MRI was used to measure intra-cranial flow features with cardiac-gated phase contrast MRI in cranial arteries and veins. Mean blood flow and pulsatility index as well as the transit time of the peak flow from the middle cerebral artery to the superior sagittal sinus were measured in a total of 104 subjects comprising of four groups: (a) subjects with Alzheimer's disease, (b) age-matched controls, (c) subjects with mild cognitive impairment, and (d) a group of late middle-aged with parental history of sporadic Alzheimer's disease. The Alzheimer's disease group exhibited: a significant decrease in mean blood flow in the superior sagittal sinus, transverse sinus, middle cerebral artery, and internal carotid arteries; a significant decrease of the peak and end diastolic blood flow in the middle cerebral artery and superior sagittal sinus; a faster transmission of peak flow from the middle cerebral artery to the superior sagittal sinus and increased pulsatility index along the carotid siphon.
Sigmundsdottir, Linda; Tchan, Michel C.; Knopman, Alex A.; Menzies, Graham C.; Batchelor, Jennifer; Sillence, David O.
Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity. PMID:25319043
Wang, Molin; Spiegelman, Donna; Kuchiba, Aya; Lochhead, Paul; Kim, Sehee; Chan, Andrew T; Poole, Elizabeth M; Tamimi, Rulla; Tworoger, Shelley S; Giovannucci, Edward; Rosner, Bernard; Ogino, Shuji
A fundamental goal of epidemiologic research is to investigate the relationship between exposures and disease risk. Cases of the disease are often considered a single outcome and assumed to share a common etiology. However, evidence indicates that many human diseases arise and evolve through a range of heterogeneous molecular pathologic processes, influenced by diverse exposures. Pathogenic heterogeneity has been considered in various neoplasms such as colorectal, lung, prostate, and breast cancers, leukemia and lymphoma, and non-neoplastic diseases, including obesity, type II diabetes, glaucoma, stroke, cardiovascular disease, autism, and autoimmune disease. In this article, we discuss analytic options for studying disease subtype heterogeneity, emphasizing methods for evaluating whether the association of a potential risk factor with disease varies by disease subtype. Methods are described for scenarios where disease subtypes are categorical and ordinal and for cohort studies, matched and unmatched case-control studies, and case-case study designs. For illustration, we apply the methods to a molecular pathological epidemiology study of alcohol intake and colon cancer risk by tumor LINE-1 methylation subtypes. User-friendly software to implement the methods is publicly available.
Svaldi, Diana O; Joshi, Chetas; Robinson, Meghan E; Shenk, Trey E; Abbas, Kausar; Nauman, Eric A; Leverenz, Larry J; Talavage, Thomas M
Cerebrovascular reactivity (CVR) is impaired following brain injury, increasing susceptibility to subsequent injury. CVR was tracked in football and non-collision athletes throughout one season. CVR transiently decreased in football athletes during the first half of the season. Results indicate the brain adapts slowly to increases in loading, increasing risk for injury.
Colon, E J; de Weerd, J P; Notermans, S L; Vingerhoets, H M
Of our patients who underwent quantitative Doppler sonography (Haemato-Tacho-Graphy), 382 underwent carotid angiography and 61 vertebral artery angiography. The reliability of the method proved to be between 90 and 95 percent for carotid as well as for vertebral arteries. The HTG proved to be a useful addition to angiography in patients with extracranial cerebro-vascular stenosis.
Oswald, W D; Fleischmann, U M; Keuchel, I
The question on which level of evaluation treatment effects have to be based on, proves the relevance of independent psychological measurements. The Nuremberg Gerontopsychological Inventory NAI is introduced as a symptomatic-oriented approach for the assessment of therapeutically induced changes. It contains four distinct ways of treatment evaluations: (1) the level of assessment of cognitive functioning; (2) subject-rated well-being; (3) observer-rated activities-of-daily-living (e.g. by a nurse), and (4) examiner-rated personality traits. For all test procedures, norm scores as well as detailed test characteristics are computed. Interrelations between the independent data levels proved to be essential for a valid estimation of treatment effects.
Diluna, Michael L; Amankulor, Nduka M; Johnson, Michele H; Gunel, Murat
Faciogenital dysplasia, also known as Aarskog-Scott syndrome (AAS), is an X-linked dominant congenital disorder characterized by multiple facial, musculoskeletal, dental, neurological and urogenital abnormalities, ocular manifestations, congenital heart defects, low IQ and behavioral problems. Here we describe an unusual presentation of dysplastic carotid artery, basilar artery malformation or occlusion and posterior circulation aneurysm in a 13-year-old male with AAS.
Perez-Lazaro, C; Santos-Lasaosa, S; Velazquez-Benito, A; Bellosta-Diago, E; Tejero-Juste, C; Iniguez-Martinez, C
Introduccion. El ictus es una de las principales causas de invalidez y mortalidad en nuestra sociedad, con importantes repercusiones socioeconomicas y sanitarias. La asistencia precoz puede mejorar el pronostico de los pacientes. Actualmente, existen tratamientos en fase aguda, que consiguen reperfundir el tejido isquemico en riesgo y revertir la sintomatologia, pero son pocos los pacientes que se benefician, por el retraso en su atencion, debido a la falta de reconocimiento de los sintomas y la escasa percepcion de gravedad. Objetivo. Analizar el conocimiento de la poblacion de nuestra area de salud sobre el ictus. Sujetos y metodos. La muestra analizada ha sido la poblacion del sector III de la provincia de Zaragoza, con seleccion aleatoria. La herramienta utilizada ha sido una encuesta telefonica estructurada (total de 583). Resultados. Un 63,5% de los encuestados desconoce los sintomas del ictus, y un 48%, los factores de riesgo vascular. Solo un 9% reconoce al menos dos sintomas y dos factores de riesgo. En cuanto a la actitud, un 56% actuaria correctamente frente a un 44% que no. El analisis multivariante mostro que los factores mas relacionados con el conocimiento fueron el nivel cultural y la edad joven. Vivir en un pueblo y sexo femenino se relacionaron con la mejor actitud. Conclusiones. El conocimiento del ictus es escaso, con una baja percepcion de urgencia. Los factores que implican un mejor conocimiento son la edad joven y el nivel cultural alto.
Kim, Jae-Hyun; Park, Eun-Cheol; Lee, Sang Gyu; Lee, Tae-Hyun; Jang, Sung-In
Abstract We examined whether the level of hospital-based healthcare technology was related to the 30-day postoperative mortality rates, after adjusting for hospital volume, of ischemic stroke patients who underwent a cerebrovascular surgical procedure. Using the National Health Insurance Service-Cohort Sample Database, we reviewed records from 2002 to 2013 for data on patients with ischemic stroke who underwent cerebrovascular surgical procedures. Statistical analysis was performed using Cox proportional hazard models to test our hypothesis. A total of 798 subjects were included in our study. After adjusting for hospital volume of cerebrovascular surgical procedures as well as all for other potential confounders, the hazard ratio (HR) of 30-day mortality in low healthcare technology hospitals as compared to high healthcare technology hospitals was 2.583 (P < 0.001). We also found that, although the HR of 30-day mortality in low healthcare technology hospitals with high volume as compared to high healthcare technology hospitals with high volume was the highest (10.014, P < 0.0001), cerebrovascular surgical procedure patients treated in low healthcare technology hospitals had the highest 30-day mortality rate, irrespective of hospital volume. Although results of our study provide scientific evidence for a hospital volume/30-day mortality rate relationship in ischemic stroke patients who underwent cerebrovascular surgical procedures, our results also suggest that the level of hospital-based healthcare technology is associated with mortality rates independent of hospital volume. Given these results, further research into what components of hospital-based healthcare technology significantly impact mortality is warranted. PMID:26986122
Pulicherla, K K; Verma, Mahendra Kumar
Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.
Dhande, Isha S; Zhu, Yaming; Braun, Michael C; Hicks, M John; Wenderfer, Scott E; Doris, Peter A
Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg/kg/day po) (n = 8) or vehicle (saline) (n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with vehicle-treated controls, MMF-treated SHR-A3 rats had improved survival and lower neurological deficit scores (1.44 vs. 0.125; P < 0.02). Gross morphology of the brain revealed cerebral edema in 8 of 9, and microbleeds and hemorrhages in 5 of 9 vehicle-treated rats. These lesions were absent in MMF-treated rats. Brain CD68 expression, indicating macrophage/microglial activation, was upregulated in vehicle-treated rats with microbleeds and hemorrhages but was undetectable in the brains of MMF-treated rats. MMF also prevented renal injury in SHR-A3 rats, evidenced by reduced proteinuria (albumin:creatinine) from 7.52 to 1.05 mg/mg (P < 0.03) and lower tubulointerstitial injury scores (2.46 vs. 1.43; P < 0.01). Salt loading resulted in a progressive increase in BP, which was blunted in rats receiving MMF. Our findings provide evidence that abnormal immune activation predisposes to cerebrovascular and renal injury in stroke-prone SHR-A3 rats.
Bragin, Denis E.; Statom, Gloria; Nemoto, Edwin M.
SUMMARY We previously suggested that the discrepancy between the critical cerebral perfusion pressures (CPP) of 30 mmHg, obtained by increasing intracranial pressure (ICP), and 60 mmHg, obtained by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP  and that the determination of the critical CPP by the static cerebral blood flow (CBF) autoregulation curve is not valid with intracranial hypertension. Here we demonstrated that critical CPP, measured by induced dynamic ICP reactivity (iPRx) and cerebrovascular reactivity (CVRx), accurately identifies the critical CPP in the hypertensive rat brain which differs from that obtained by the static autoregulation curve. Step changes in CPP from 70 to 50 and 30 mmHg were made by increasing ICP using an artificial cerebrospinal fluid reservoir connected to the cisterna magna. At each CPP, a transient 10-mmHg rise in arterial pressure was induced by bolus i.v. dopamine. iPRx and iCVRx were calculated as ΔICP/ΔMAP and as ΔCBF/ΔMAP, respectively. The critical CPP at high ICP, obtained by iPRx and iCVRx, is 50 mmHg, where compromised capillary flow, transition of blood flow to non-nutritive microvascular shunts, tissue hypoxia and BBB leakage begin to occur, which is higher than the 30 mmHg determined by static autoregulation. PMID:27165917
Chen, J L; Wang, Y C; Wang, J Y
1. The response of cerebral blood vessels to hyperosmolar agents in vivo remains controversial, and little is known about the effect of glycerol on cerebral vessels. In this study we investigated the cerebrovascular response to intravenous administration of glycerol (1 g/kg, infused over 25 min) in dogs under pentobarbital anaesthesia. 2. intracranial pressure, systemic arterial pressure, mean arterial blood pressure, serum osmolarity and packed cell volume were continuously monitored, and blood gases were checked frequently. Through a parietal cranial window, pial vessel diameter was measured by means of a surgical microscope and a video image-analyser. 3. Pial vessel diameter increased gradually with a maximum at 30 min after the beginning of glycerol infusion. The maximum increase in diameter in small (less than or equal to 100 microns) vessels was 14.3%, whereas that in large (greater than 100 microns) vessels was 10.3%. There was only a slight increase (less than 4%) in pial vessel diameter in vehicle-infused animals. The intracranial pressure decreased drastically after glycerol infusion, whereas the mean arterial blood pressure remained constant. There were correlations between the rise in serum osmolarity, fall in packed cell volume and vasodilatation, indicating that glycerol caused vasodilatation accompanied by plasma volume expansion. 4. Our data suggest that glycerol produces cerebral vasodilatation, which might be beneficial in cerebral ischaemia and vasospasm, in addition to its intracranial pressure-reducing effect on normal or oedematous brain. The degree of vasodilatation was not sufficient to affect the predominant intracranial pressure drop resulting from cerebral dehydration.
Spencer, Matthew D.; Tyndall, Amanda V.; Davenport, Margie H.; Argourd, Laurie; Anderson, Todd J.; Eskes, Gail A.; Friedenreich, Christine M.; Hogan, David B.; Leigh, Richard; Meshi, Bernard; Smith, Eric E.; Wilson, Ben J.; Wilton, Stephen B.; Poulin, Marc J.
The primary purpose of this Brain in Motion (BIM) sub-study was to determine the 6-month stability of resting blood flow velocity and cerebrovascular responsiveness to a euoxic hypercapnic challenge in a group of physically inactive community dwelling men and men aged ≥55 yrs (range 55–92 yrs). At baseline and 6 months later 88 women (65±6 yr) and 78 men (67±7 yr) completed a hypercapnic challenge (step changes from resting end-tidal PCO2 ((PETCO2) to +1, +5 and +8 mmHg above rest) while cerebral blood flow velocity was assessed using transcranial Doppler ultrasound. Peak velocity of the middle cerebral artery (MCAv) was increased (p<0.05) at the second visit during rest (51±2 vs. 52±4); however, these differences were abolished (p>0.05) when MCAv was normalized to PETCO2. During hypercapnia, MCAv tended to be increased at follow-up, but this finding was absent when MCAv/PETCO2 was compared across time. Cerebrovascular reactivity (i.e., ΔMCAv/ΔPETCO2) was similar (p>0.05) between testing occasions regardless of the approach taken (i.e., considering only the lower step [from +1 to +5 mmHg]; the upper step [+5 to +8 mmHg]; or the complete test taken together). In conclusion, this study has shown that cerebral blood flow and cerebrovascular responsiveness to acute euoxic hypercapnia are stable in older, healthy adults over a 6-month period. Modest changes in MCAv over time must be viewed in the context of underlying differences in PETCO2, an important finding with implications for future studies considering cerebral blood flow velocity. PMID:26599343
Weinstock, Peter; Prabhu, Sanjay P; Flynn, Katie; Orbach, Darren B; Smith, Edward
OBJECT Despite the availability of multiplanar imaging, understanding relational 3D anatomy for complex cerebrovascular lesions can be difficult. A 3D printed model allows for instantaneous visualization of lesional anatomy from all perspectives, with the added ability to simulate operative approaches with tactile feedback. The authors report their experience with customized 3D printed models of pediatric cerebrovascular lesions as an educational and clinical tool for patients, trainees, and physicians. METHODS Via an "in-house" 3D print service, magnetic resonance imaging (MRI) and computerized tomography (CT) studies of pediatric patients with arteriovenous malformations (AVMs) were processed with specialized software, and regions of interest were selected by the surgical/endovascular team. Multiple models for each patient were then printed on a 3D printer, with each construct designed to illustrate different aspects of the specific lesion. Intraoperative validation of model fidelity was performed using perioperative imaging, surgical filming, and post hoc analysis of models with intraoperative photography. RESULTS Four cases involving pediatric patients (ages 0-16 years) were studied for initial proof of principle. Three of the patients had AVMs and one had a vein of Galen malformation (VOGM). The VOGM was embolized successfully and the AVMs were resected without complication. In the AVM cases, intraprocedural imaging and photography were performed and verified millimeter-level fidelity of the models (n = 5, 98% concordance, range 94%-100% with average of < 2 mm variation in the largest AVM [6-cm diameter]). The use of 3D models was associated with a 30-minute reduction in operative time (12%) in 2 cases when they were compared with matched controls as a feasibility study. CONCLUSIONS Patient-specific 3D printed models of pediatric cerebrovascular conditions can be constructed with high fidelity. This proof-of-principle series demonstrates, for the first time
Alsayouf, Hamza; Zamel, Khaled M; Heyer, Geoffrey L; Khuhro, A Latif; Kahwash, Samir B; de los Reyes, Emily C
Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation (MTHFR TT) has been linked to an increased risk for stroke, coronary artery disease, and migraine headaches. The authors analyzed the potential link between MTHFR 677C>T homozygosity and childhood stroke. A true association might facilitate screening, recurrence risk stratification, and treatment in patients with cerebrovascular disease. They performed a retrospective chart review of children tested for the MTHFR 677C>/T mutation; 533 patients underwent MTHFR testing, and 8% were homozygous for the MTHFR 677C>T mutation. There was no difference in the cohort compared with the prevalence in the general population. This suggests that the MTHFR 677 C>T polymorphism played a minimal role or no role in stroke risk. However, the data suggest that the MTHFR TT genotype may influence migraine susceptibility in children because there was a higher proportion of migraine patients (28.6%) with the MTHFR TT homozygous genotype.
Leslie, R D; Hawa, M
Immune-mediated diseases affect up to 5% of the population and are a major cause of morbidity and mortality. These diseases can be organ specific, such as insulin-dependent diabetes (IDDM) and non-organ specific, such as Rheumatoid Arthritis (RA). Identical and non-identical twins have been used to establish whether these diseases are determined by genetic or environmental factors. The results of these studies have been collated in a new section of the Mendel Institute in Rome. Diseases included in these studies included IDDM, RA, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS) and Myasthenia. Striking differences in concordance rates between identical and non-identical twins in all these studies suggest that genetic factors are important in causing these diseases. All the diseases are known to be associated with HLA genes on chromosome 6 which may account for some or all of the genetic susceptibility. However, in the majority of pairs the affected twin has an unaffected co-twin. These observations suggest that non-genetically determined factors, probably environmental factors and not somatic mutations, are critical. The study of unaffected co-twins, who are at high disease-risk, has allowed the identification of changes which precede and predict the clinical disease. The immune-mediated destruction in many of these diseases is probably caused by T-lymphocytes. Twin studies have shown the importance of genetic factors in determining T-cell responses. Identical twins should, therefore, provide the perfect test bed to assess the role of T-cells in immune-mediated diseases.
Sarti, C; Vartiainen, E; Torppa, J; Tuomilehto, J; Puska, P
At the beginning of the 1970s, the mortality rates from cerebrovascular disease in Finland were among the highest in the world. In addition, the levels of the main known risk factors for cardiovascular disease, such as high blood pressure, elevated serum cholesterol level and cigarette smoking, were by international comparisons very high. Within Finland, higher mortality from both stroke and ischemic heart disease was observed in the eastern part of the country, where the levels of the risk factors mentioned were higher than in the western regions. Official mortality statistics show that deaths from stroke in Finland declined steeply in the 1970s, and continued to decline, although at a slower pace, during the 1980s. Furthermore, the decline in stroke mortality was greater in eastern Finland than in the western part of the country, such that the gap observed between east and west Finland in stroke mortality has now almost disappeared. These findings are supported by the trends observed from the North Karelia stroke register and from the FINMONICA stroke register. A cohort study has demonstrated that high blood pressure, high blood cholesterol level and cigarette smoking are risk factors for fatal stroke in the male population of eastern Finland. In women, only high blood pressure was found to be a risk factor for fatal stroke, while for cigarette smoking and high blood cholesterol levels the risk, though increased, was not statistically significant. A national strategy has been developed to control and reduce the main cardiovascular risk factors in Finland. The North Karelia project, started in Finland in 1972, was the first program of its type aimed at the reduction of risk factors in a whole population. Arterial blood pressure and total blood cholesterol levels have decreased significantly during the last 20 years in both men and women. The prevalence of cigarette smoking has been reduced only in men. The changes in risk factors that have occurred parallel the
Capone, Christine; Burjonrappa, Sathyaprasad
Blunt cerebrovascular injuries (BCVI) carry significant morbidity if not diagnosed and treated early. A high index of clinical suspicion is needed to recognize the injury patterns associated with this condition and to order the requisite imaging studies needed to diagnose it accurately. We report of BCVI associated with a congenital cervical spine malformation after blunt trauma. We recommend inclusion of cervical spine malformations to the current Eastern Association for the Surgery of Trauma screening criteria for BCVI and explain our rationale for the same.
Perneczky, Robert; Wagenpfeil, Stefan; Lunetta, Kathryn L; Cupples, L Adrienne; Green, Robert C; DeCarli, Charles; Farrer, Lindsay A; Kurz, Alexander
Functional imaging and neuropathological studies suggest that individuals with higher education have better cognitive performance at the same level of brain pathology than less educated subjects. No in vivo studies are available that directly test how education modifies the effect of structural pathology on cognition in Alzheimer's disease (AD). The present study therefore aimed to measure this effect using data from a large multi-center study. 270 patients with AD underwent cognitive testing using the Mini Mental State Examination (MMSE), apolipoprotein E (APOE) genotyping, and cerebral magnetic resonance imaging. A linear regression analysis was used to examine the relation of medial temporal lobe atrophy (MTA), as a proxy of AD pathology, to MMSE score, adjusting for age, gender, APOE, cerebrovascular disease, ethnicity, education, and disease duration. An interaction term for MTA and education was introduced to test the hypothesis that education modifies the effect of MTA on cognition. There was a significant inverse association between MTA and cognition. Most interestingly, the interaction term between education and MTA was significant suggesting that education modifies the relation of MTA to cognition. At any level of pathology, cognition remained higher for better educated individuals.
Durgan, David J; Crossland, Randy F; Lloyd, Eric E; Phillips, Sharon C; Bryan, Robert M
Obstructive sleep apnea (OSA) is associated with cerebrovascular diseases. However, little is known regarding the effects of OSA on the cerebrovascular wall. We tested the hypothesis that OSA augments endothelin-1 (ET-1) constrictions of cerebral arteries. Repeated apneas (30 or 60 per hour) were produced in rats during the sleep cycle (8 hours) by remotely inflating a balloon implanted in the trachea. Four weeks of apneas produced a 23-fold increase in ET-1 sensitivity in isolated and pressurized posterior cerebral arteries (PCAs) compared with PCAs from sham-operated rats (EC50=10−9.2 mol/L versus 10−10.6 mol/L; P<0.001). This increased sensitivity was abolished by the ET-B receptor antagonist, BQ-788. Constrictions to the ET-B receptor agonist, IRL-1620, were greater in PCAs from rats after 2 or 4 weeks of apneas compared with that from sham-operated rats (P=0.013). Increased IRL-1620 constrictions in PCAs from OSA rats were normalized with the transient receptor potential channel (TRPC) blocker, SKF96365, or the Rho kinase (ROCK) inhibitor, Y27632. These data show that OSA increases the sensitivity of PCAs to ET-1 through enhanced ET-B activity, and enhanced activity of TRPCs and ROCK. We conclude that enhanced ET-1 signaling is part of a pathologic mechanism associated with adverse cerebrovascular outcomes of OSA. PMID:25425077
Dearborn, Jennifer L.; Schneider, Andrea L. C.; Sharrett, A. Richey; Mosley, Thomas H.; Bezerra, Daniel C; Knopman, David S.; Selvin, Elizabeth; Jack, Clifford R.; Coker, Laura H.; Alonso, Alvaro; Wagenknecht, Lynne E.; Windham, Beverly G.; Gottesman, Rebecca F.
Background and purpose The term “metabolic syndrome” (MetS) describes the clustering of risk factors found in many individuals with obesity. Due to their pathophysiology, we hypothesized that two features of MetS, central obesity and insulin resistance (IR), would be associated with cerebrovascular changes on MRI, and specifically with incident lacunar disease and not white matter hyperintensity progression (WMH). Methods Risk factors were defined at study baseline in 934 participants in the Atherosclerosis Risk in Communities (ARIC) study who completed two brain MRIs approximately ten years apart. WMH progression and incident lacunes between the two MRIs were determined. An IR score for each participant was created using principal component analysis of 11 risk factors, including (among others): insulin, HOMA-IR, body mass index (BMI) and waist circumference. MetS (presence/absence), using standard clinical definitions, and IR score at the first MRI, were independent variables, evaluated in multivariate logistic regression to determine odds of WMH progression (Q5 vs. Q1–4) and incident lacunes. Results MetS (adjusted OR 1.98; 95% confidence interval (CI) 1.28, 3.05) and IR score (adjusted OR per 1-standard deviation increase: 1.33, 95% CI 1.05, 1.68) were associated with incident lacunes but not with WMH progression. Insulin, HOMA-IR and BMI were not associated with incident lacunes or WMH progression in separate models. Conclusions The IR score and central obesity are associated with incident lacunar disease but not WMH progression in individuals. Central obesity and IR may be important risk factors to target to prevent lacunar disease. PMID:26451022
Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J
The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Zhang Chong; Villa-Uriol, Maria-Cruz; De Craene, Mathieu; and others
Purpose: The objective of this study is to investigate the feasibility of detecting and quantifying 3D cerebrovascular wall motion from a single 3D rotational x-ray angiography (3DRA) acquisition within a clinically acceptable time and computing from the estimated motion field for the further biomechanical modeling of the cerebrovascular wall. Methods: The whole motion cycle of the cerebral vasculature is modeled using a 4D B-spline transformation, which is estimated from a 4D to 2D+t image registration framework. The registration is performed by optimizing a single similarity metric between the entire 2D+t measured projection sequence and the corresponding forward projections of the deformed volume at their exact time instants. The joint use of two acceleration strategies, together with their implementation on graphics processing units, is also proposed so as to reach computation times close to clinical requirements. For further characterizing vessel wall properties, an approximation of the wall thickness changes is obtained through a strain calculation. Results: Evaluation on in silico and in vitro pulsating phantom aneurysms demonstrated an accurate estimation of wall motion curves. In general, the error was below 10% of the maximum pulsation, even in the situation when substantial inhomogeneous intensity pattern was present. Experiments on in vivo data provided realistic aneurysm and vessel wall motion estimates, whereas in regions where motion was neither visible nor anatomically possible, no motion was detected. The use of the acceleration strategies enabled completing the estimation process for one entire cycle in 5-10 min without degrading the overall performance. The strain map extracted from our motion estimation provided a realistic deformation measure of the vessel wall. Conclusions: The authors' technique has demonstrated that it can provide accurate and robust 4D estimates of cerebrovascular wall motion within a clinically acceptable time, although it
Low, P. A.; Novak, V.; Spies, J. M.; Novak, P.; Petty, G. W.
Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.
Lai, Chao-Lun; Wu, Ching-Fen; Kuo, Raymond Nien-Chen; Yang, Yen-Yun; Chen, Ming-Fong; Chan, K Arnold; Lai, Mei-Shu
The clinical outcomes of different limus-based drug-eluting stents (DES) in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and everolimus-eluting stent (EES), using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group). Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan.
Nunes, Karine Vila Real; Ignotti, Eliane; Hacon, Sandra de Souza
The aim of this study was to analyze the association between the exposure to fine particulate matter and circulatory disease mortality rates in the elderly living in the Brazilian Amazon. An ecological study of circulatory disease, acute myocardial infarction and cerebrovascular disease mortality rates in micro areas of the Brazilian Amazon was carried out. The environmental exposure indicator used was percentage hours of PM(2.5) concentrations > 25µg/m(3) divided by the total number of estimated hours of PM(2.5) in 2005. The association between exposure and circulatory disease mortality rates was strongest in the oldest age group. No significant statistical association was found between cerebrovascular disease mortality rates and exposure. Circulatory disease mortality rates in the elderly living in the Amazon have been influenced by atmospheric pollution from emissions caused by forest fires.
Uys, A S; Malan, L; van Rooyen, J M; Steyn, H S; Reimann, M; Ziemssen, T
Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; β = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.
Kawauchi, Chikara; Kadoi, Yuji; Hinohara, Hiroshi; Kunimoto, Fumio; Saito, Shigeru
The present study compared cerebrovascular CO2 reactivity in diabetic patients on different treatment modalities under sedative doses of propofol. Fifteen patients with diabetes mellitus (on three different antidiabetic treatment modalities) who required mechanical ventilation during intensive care therapy were studied, sedation during mechanical ventilation being maintained using propofol. As controls, 6 patients without diabetes were monitored. A 2.5-MHz pulsed transcranial Doppler probe was attached to the head of the patient at the right temporal window for continuous measurement of mean blood flow velocity in the middle cerebral artery (Vmca). After establishing baseline values of Vmca and cardiovascular hemodynamics, end-tidal CO2 was decreased by increasing ventilatory frequency by 5-8 breaths.min(-1). Values for absolute and relative CO2 reactivity in insulintreated patients were lower than those in the other three groups (absolute CO2 reactivity [means +/- SD]: control, 3.1 +/- 0.6 cm.s(-1).mmHg(-1), diet, 3.8 +/- 1.4 cm.s(-1) x mmHg(-1); oral antidiabetic drug 3.2 +/- 0.9 cm x s(-1) x mmHg(-1); insulin, 1.1 +/- 0.6 cm x s(-1) x mmHg(-1); P = 0.002).The present study shows that insulin-treated diabetic patients probably have lower cerebrovascular CO2 reactivity under propofol anesthesia than control patients or diabetics treated with dietary therapy or oral hypoglycemics.
Zhang, Bei; Chen, Lei; Choi, Jeong June; Hennig, Bernhard; Toborek, Michal
Environmental polychlorinated biphenyls (PCBs) are frequently bound onto nanoparticles (NPs). However, the toxicity and health effects of PCBs assembled onto nanoparticles are unknown. The aim of this study was to study the hypothesis that binding PCBs to silica NPs potentiates PCB-induced cerebrovascular toxicity and brain damage in an experimental stroke model. Mice (C57BL/6, males, 12-week-old) were exposed to PCB153 bound to NPs (PCB153-NPs), PCB153, or vehicle. PCB153 was administered in the amount of 5 ng/g body weight. A group of treated animals was subjected to a 40 min ischemia, followed by a 24 h reperfusion. The blood-brain barrier (BBB) permeability, brain infarct volume, expression of tight junction (TJ) proteins, and inflammatory mediators were assessed. As compared to controls, a 24 h exposure to PCB153-NPs injected into cerebral vasculature resulted in significant elevation of the BBB permeability, disruption of TJ protein expression, increased proinflammatory responses, and enhanced monocyte transmigration in mouse brain capillaries. Importantly, exposure to PCB153-NPs increased stroke volume and potentiated brain damage in mice subjected to ischemia/reperfusion. A long-term (30 days) oral exposure to PCB153-NPs resulted in a higher PCB153 content in the abdominal adipose tissue and amplified adhesion of leukocytes to the brain endothelium as compared to treatment with PCB153 alone. This study provides the first evidence that binding to NPs increases cerebrovascular toxicity of environmental toxicants, such as PCB153. PMID:23081707
Connolly, John G; Bykov, Katsiaryna; Gagne, Joshua J
Thiazolidinediones, a class of medications indicated for the treatment of type 2 diabetes mellitus, reduce inflammation and have been shown to provide a therapeutic benefit in animal models of Parkinson disease. We examined the association between treatment with thiazolidinediones and the onset of Parkinson disease in older individuals. We performed a cohort study of 29,397 Medicare patients enrolled in state pharmaceutical benefits programs who initiated treatment with thiazolidinediones or sulfonylureas during the years 1997 through 2005 and had no prior diagnosis of Parkinson disease. New users of thiazolidinediones were propensity score matched to new users of sulfonylureas and followed to determine whether they were diagnosed with Parkinson disease. We used Cox proportional hazards models to compare time to diagnosis of Parkinson disease in the propensity score-matched populations. To assess the association with duration of use, we performed several analyses that required longer continuous use of medications. In the primary analysis, thiazolidinedione users had a hazard ratio for a diagnosis of Parkinson disease of 1.09 (95% confidence interval: 0.71, 1.66) when compared with sulfonylurea users. Increasing the duration-of-use requirements to 10 months did not substantially change the association; the hazard ratios ranged from 1.00 (95% confidence interval: 0.49, 2.05) to 1.17 (95% confidence interval: 0.60, 2.25). Thiazolidinedione use was not associated with a longer time to diagnosis of Parkinson disease than was sulfonylurea use, regardless of duration of exposure.
Zhang, Xiakun; Zhang, Shuyu; Wang, Chunling; Wang, Baojian; Guo, Pinwen
The effects of cold air on cardiovascular and cerebrovascular diseases were investigated in an experimental study examining blood pressure and biochemical indicators. Zhangye, a city in Gansu Province, China, was selected as the experimental site. Health screening and blood tests were conducted, and finally, 30 cardiovascular disease patients and 40 healthy subjects were recruited. The experiment was performed during a cold event during 27-28 April 2013. Blood pressure, catecholamine, angiotensin II (ANG-II), cardiac troponin I (cTnI), muscle myoglobin (Mb) and endothefin-1 (ET-1) levels of the subjects were evaluated 1 day before, during the 2nd day of the cold exposure and 1 day after the cold air exposure. Our results suggest that cold air exposure increases blood pressure in cardiovascular disease patients and healthy subjects via the sympathetic nervous system (SNS) that is activated first and which augments ANG-II levels accelerating the release of the norepinephrine and stimulates the renin-angiotensin system (RAS). The combined effect of these factors leads to a rise in blood pressure. In addition, cold air exposure can cause significant metabolism and secretion of Mb, cTnI and ET-1 in subjects; taking the patient group as an example, ET-1 was 202.7 ng/L during the cold air exposure, increased 58 ng/L compared with before the cold air exposure, Mb and cTnI levels remained relatively high (2,219.5 ng/L and 613.2 ng/L, increased 642.1 ng/L and 306.5 ng/L compared with before the cold air exposure, respectively) 1-day after the cold exposure. This showed that cold air can cause damage to patients' heart cells, and the damage cannot be rapidly repaired. Some of the responses related to the biochemical markers indicated that cold exposure increased cardiovascular strain and possible myocardial injury.
Lienkamp, Soeren S
Modern sequencing technology is revolutionizing our knowledge of inherited kidney disease. However, the molecular role of genes affected by the rapidly rising number of identified mutations is lagging behind. Xenopus is a highly useful, but underutilized model organism with unique properties excellently suited to decipher the molecular mechanisms of kidney development and disease. The embryonic kidney (pronephros) can be manipulated on only one side of the animal and its formation observed directly through the translucent skin. The moderate evolutionary distance between Xenopus and humans is a huge advantage for studying basic principles of kidney development, but still allows us to analyze the function of disease related genes. Optogenetic manipulations and genome editing by CRISPR/Cas are exciting additions to the toolbox for disease modelling and will facilitate the use of Xenopus in translational research. Therefore, the future of Xenopus in kidney research is bright.
Kennedy, L J; Barnes, A; Short, A; Brown, J J; Seddon, J; Fleeman, L; Brkljacic, M; Happ, G M; Catchpole, B; Ollier, W E R
There are many millions of dogs worldwide, and these dogs have many different functions. The most obvious use is providing companionship, but there are also many working dogs, including guide dogs for the blind, hearing dogs, guard dogs and farm dogs, to mention a few. The health and welfare of these dogs is of great concern to dog owners, dog breeders and to those who use dogs in their work. Dogs spontaneously develop many diseases that are very similar to their human counterparts. Dogs may, therefore, provide exceptional animal models for such diseases. Identifying genetic markers in the dog may be easier than in humans, and may then provide useful information about genes that can be transferred to humans. This study looked for associations between DLA and two autoimmune diseases of the dog, diabetes and hypothyroidism. DLA associations were found for both of these diseases.
Vasilj, Ivan; Cavaljuga, Semra; Lucić, Tomo; Kvesić, Ferdo
Analysis of a cerebro-vascular insult hospitalised cases from West Herzegovina Canton as a retrospective epidemiological study was done in Clinical hospital Mostar for the period from 1998 to 2002. The major source of data was medical documentation of this hospital, the only hospital for the treatment of 88,257 inhabitants from this Canton. The study included a total of 393 cerebro-vascular insult cases from this Canton treated in the Clinical hospital Mostar. Among them 189 (48.1%) were male patients, while 204 (51.9%) cases were female. The majority of the cases were above 50 years of life. Majority of treated female patients were older then 65, while among male patients the majority were between 50 and 65 years old. The least number of cases was under 50 years in both groups. During the same period risk factors research for entire FBiH was performed on the sample of 2,750 national insurance holders. Out of them 1.7% was found to suffer of cerebro vascular insult.
Liu, Pengchong; Xi, Qi; Ahmed, Abu; Jaggar, Jonathan H.; Dopico, Alejandro M.
Binge drinking is associated with increased risk for cerebrovascular spasm and stroke. Acute exposure to ethanol at concentrations obtained during binge drinking constricts cerebral arteries in several species, including humans, but the mechanisms underlying this action are largely unknown. In a rodent model, we used fluorescence microscopy, patch-clamp electrophysiology, and pharmacological studies in intact cerebral arteries to pinpoint the molecular effectors of ethanol cerebrovascular constriction. Clinically relevant concentrations of ethanol elevated wall intracellular Ca2+ concentration and caused a reversible constriction of cerebral arteries (EC50 = 27 mM; Emax = 100 mM) that depended on voltage-gated Ca2+ entry into myocytes. However, ethanol did not directly increase voltage-dependent Ca2+ currents in isolated myocytes. Constriction occurred because of an ethanol reduction in the frequency (-53%) and amplitude (-32%) of transient Ca2+-activated K+ (BK) currents. Ethanol inhibition of BK transients was caused by a reduction in Ca2+ spark frequency (-49%), a subsarcolemmal Ca2+ signal that evokes the BK transients, and a direct inhibition of BK channel steady-state activity (-44%). In contrast, ethanol failed to modify Ca2+ waves, a major vasoconstrictor mechanism. Selective block of BK channels largely prevented ethanol constriction in pressurized arteries. This study pinpoints the Ca2+ spark/BK channel negative-feedback mechanism as the primary effector of ethanol vasoconstriction.
Semplicini, A; Inverso, G; Realdi, A; Macchini, L; Maraffon, M; Puato, M; Zanardo, M; Tirrito, C; Amodio, P; Schiff, S; Mapelli, D; Manara, R
Hypertension causes cognitive impairment, involving mainly executive functions, but the effect of blood pressure (BP) control on the different cognitive domains is still debated. We correlated executive function, attention and memory with BP control and cerebrovascular damage in 60 undemented middle-aged hypertensives at baseline and after 6-year follow-up. At first evaluation, the patients with poor BP control had higher score of white matter lesions, reduced cerebrovascular reserve capacity and greater carotid intima-media thickness (IMT) than those with good BP control. Performance on executive tests correlated with IMT and with performance on attention tests, which was impaired by low diastolic BP. At long-term follow-up, performance in attention and executive tests improved in spite of the minor improvement of BP control, increased IMT and worse memory. Low diastolic BP has a negative effect on attention, which affects executive performance at first cross-sectional examination. This confounding effect has to be taken into consideration when planning studies on cognitive function. Longitudinal studies are required to unravel the effect of BP control on cognitive function, as only long-term antihypertensive treatment improves both attention and executive performance.
Morris, Alan W. J.; Carare, Roxana O.; Schreiber, Stefanie; Hawkes, Cheryl A.
Cerebral amyloid angiopathy (CAA), the accumulation of β-amyloid (Aβ) peptides in the walls of cerebral blood vessels, is observed in the majority of Alzheimer’s disease (AD) brains and is thought to be due to a failure of the aging brain to clear Aβ. Perivascular drainage of Aβ along cerebrovascular basement membranes (CVBMs) is one of the mechanisms by which Aβ is removed from the brain. CVBMs are specialized sheets of extracellular matrix that provide structural and functional support for cerebral blood vessels. Changes in CVBM composition and structure are observed in the aged and AD brain and may contribute to the development and progression of CAA. This review summarizes the properties of the CVBM, its role in mediating clearance of interstitial fluids and solutes from the brain, and evidence supporting a role for CVBM in the etiology of CAA. PMID:25285078
Slatina, Enes; Music, Miralem; Babic, nermina; Pleho –Kapic, Amna; Dervisevic, Senad; Salibasic, Mirhan; Mujaric, ekrema
Introduction: The intention of this work is to research whether the link between the barometer pressure and the cerebrovascular insult (CVI) exists. The stroke is the first cause of non-traumatic disability and third illness by mortality in the majority of available relevant literature. Goals: Goal of the sudy was to research all the cases of the patients who suffered from the acute stroke in the Canton of Sarajevo and those who were treated in the pre-hospital phase by Emergency Medical Institute staff and their working diagnosis was established as CVI ac. Material and methods: The criteria in the research were established for inclusion and exclusion of cases. The days with and without CVI cases were compared with the meteorological data obtained from the Hydro-meteorological Institute of Federation of Bosnia and Herzegovina . Since the approval was requested and obtained from the Hydro-meteorological Institute, all the meteorological data could be compared. The meteorological data comprise the barometer pressure measuring every day at 7 h, 14 h and 21 h. Results and discussion: In the retrospective study, there will be followed, during three years (2004, 2005 and 2006), the cases of the patients who suffered from the stroke, and, the emergency medical care was offered to them by the side of the Emergency Medical Institute of Canton of Sarajevo staff. All the cases in the Canton of Sarajevo were followed regardless of the place of incidence: whether the help was offered in Institute’s outpatient departments, patient’s flat or at public place. Due to the extensiveness of data (in the analysis comprising three years, there was the total of 1930 cases), the test of normal distribution was used. Since it was about the pre-hospital research, the acute stroke was looked at generally without division by types. The certain diagnostics by types can only be established in the hospital. Conclusion: The results in the research indicate that the extreme values of barometer
Blais, Claudia; Germain, Marc; Delage, Gilles; Grégoire, Yves
Background The association between antigens A and B and arterial thrombosis, such as coronary heart disease, cerebrovascular disease or peripheral vascular disease, is still unclear. We evaluated the association between blood groups and thrombotic events in a cohort of blood donors from the province of Quebec, Canada. Material and methods Among all whole blood donors aged ≥18 years in Quebec between June 1990 and March 2009, a study sample with known blood groups was linked with the provincial hospitalisation and death records to count vascular events. All hospital admissions and deaths with codes for primary and relevant secondary diagnoses of coronary, cerebrovascular or peripheral diseases, including coronary heart disease interventions, were included. Cox regression was used to evaluate the hazard ratio associated between blood groups and these events adjusted for other baseline characteristics. Results Among the blood donors, 64,686 had a known blood group and were linked with the provincial health databases. The mean age of these donors was 38 years. The Cox multivariate adjusted hazard ratio for coronary, cerebrovascular or peripheral diseases was 1.19 (95% confidence interval: 1.01–1.40) for subjects with blood group AB compared to those with blood group O. There were no statistically significant associations with other blood groups. Only among women aged ≥40 years did those with blood group A have a higher hazard ratio for coronary heart disease (1.40 [1.01–1.92]) than those with blood group O, after adjusting for other characteristics. Discussion When compared to blood group O, only blood group AB was associated with a higher risk of hospitalisation or death because of thrombotic events such as coronary, cerebrovascular or peripheral diseases. However, the associations differed according to age and sex because only females aged ≥40 years with blood group A had a higher risk of coronary heart disease. PMID:27177404
Schumacher, Kurt R; Stringer, Kathleen A; Donohue, Janet E; Yu, Sunkyung; Shaver, Ashley; Caruthers, Regine L; Zikmund-Fisher, Brian J; Fifer, Carlen; Goldberg, Caren; Russell, Mark W
For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster "virtually" online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media's role in participation compared with other referral modalities. A novel, internet-based survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases.
Yamaguchi, T; Matsushima, Y; Takada, Y; Niimi, Y; Umezu, R; Fukuyama, Y; Yamaguchi, M; Inaba, Y
The cause of Moyamoya disease is still unknown. We made a research about the factors closely related to Moyamoya disease through a case-control study. The number of cases studied was 66. Controls were selected from among patients' friends, matched as to sex, age and residential area. Questionnaires were sent to the cases and the respective controls by mail. The questions were about past history, developmental history, school records, habitual factors, dietary habits and pets. The first symptoms and age at onset were also surveyed in the cases. The response rate was 84.8% (56 cases) of the cases and 76.5% (101 cases) out of the 132 controls. There was no significant difference in the prevalence of tonsillitis, conjunctivitis, otitis media, and bronchitis. Odds ratio of fever of unknown origin is 2.793 and X2 is 7.213. Diseases whose odds ratio was over 1 were herpes, appendicitis, bronchitis, asthma, anemia, dental caries, head injury and drug allergy. But all of them were not significantly prevalent. Odds ratios of school records were 4-9 and X2 were 4-17 from elementary to junior high school. Odds ratio of western dishes was 2.709 and X2 was 5.189. There was no significant difference as to pets kept. We could not find overt relationships between Moyamoya disease and diseases of head and neck like tonsillitis.
Yaghi, Shadi; Rostanski, Sara K.; Boehme, Amelia K.; Martin-Schild, Sheryl; Samai, Alyana; Silver, Brian; Blum, Christina A.; Jayaraman, Mahesh V.; Siket, Matthew S.; Khan, Muhib; Furie, Karen L.; Elkind, Mitchell S. V.; Marshall, Randolph S.; Willey, Joshua Z.
IMPORTANCE Neurological worsening and recurrent stroke contribute substantially to morbidity associated with transient ischemic attacks and strokes (TIA-S). OBJECTIVE To determine predictors of early recurrent cerebrovascular events (RCVEs) among patients with TIA-S and National Institutes of Health Stroke Scale scores of 0 to 3. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted at 2 tertiary care centers (Columbia University Medical Center, New York, New York, and Tulane University Medical Center, New Orleans, Louisiana) between January 1, 2010, and December 31, 2014. All patients with neurologist-diagnosed TIA-S with a National Institutes of Health Stroke Scale score of 0 to 3 who presented to the emergency department were included. MAIN OUTCOMES AND MEASURES The primary outcome (adjudicated by 3 vascular neurologists) was RCVE: neurological deterioration in the absence of a medical explanation or recurrent TIA-S during hospitalization. RESULTS Of the 1258 total patients, 1187 had no RCVEs and 71 had RCVEs; of this group, 750 patients (63.2%) and 39 patients (54.9%), respectively, were aged 60 years or older. There were 505 patients with TIA-S at Columbia University; 31 (6.1%) had RCVEs (15 patients had neurological deterioration only, 11 had recurrent TIA-S only, and 5 had both). The validation cohort at Tulane University consisted of 753 patients; 40 (5.3%) had RCVEs (24 patients had neurological deterioration only and 16 had both). Predictors of RCVE in multivariate models in both cohorts were infarct on neuroimaging (computed tomographic scan or diffusion-weighted imaging sequences on magnetic resonance imaging) (Columbia University: not applicable and Tulane University: odds ratio, 1.75; 95% CI, 0.82–3.74; P = .15) and large-vessel disease etiology (Columbia University: odds ratio, 6.69; 95% CI, 3.10–14.50 and Tulane University: odds ratio, 8.13; 95% CI, 3.86–17.12; P < .001). There was an increase in the percentage of
Vance, Ansar Z; Sivapatham, Thinesh
Background Advantages of radial access over brachial/axillary or femoral access have been well described for several decades and include decreased cost, patient preference, and decreased major access site complications. Despite these advantages, radial access is rarely employed or even considered for neurointerventional procedures. This attitude should be reconsidered given several recent large, randomized, controlled trials from the cardiovascular literature proving that radial access is associated with statistically lower costs, decreased incidence of myocardial infarctions, strokes, and even decreased mortality. Radial access is now considered the standard of care for percutaneous coronary interventions in most US centers. Although radial access has been described for neurovascular procedures in the past, overall experience is limited. The two major challenges are the unique anatomy required to access the cerebral vasculature given very acute angles between the arm and craniocervical vessels and limitations in available technology. Methods We present a simplified approach to radial access for cerebrovascular procedures and provide a concise step-by-step approach for patient selection, ultrasound-guided single-wall access, recommended catheters/wires, and review of patent hemostasis. Additionally, we present a complex cerebrovascular intervention in which standard femoral access was unsuccessful, while radial access was quickly achieved to highlight the importance of familiarity with the radial approach for all neurointerventionalists. Results We have found that the learning curve is not too steep and that the radial access approach can be adopted smoothly for a large percentage of diagnostic and interventional neuroradiologic procedures. Conclusions Radial access should be considered in all patients undergoing a cerebrovascular procedure. PMID:26659807
Parshin, D. V.; Ufimtseva, I. V.; Cherevko, A. A.; Khe, A. K.; Orlov, K. Yu; Krivoshapkin, A. L.; Chupakhin, A. P.
The present paper discusses the method of identification (diseased/healthy) human cerebral vessels by using of mathematical model. Human cerebral circulation as a single tuned circuit, which consists of blood flow, elastic vessels and elastic brain gel tissue is under consideration. Non linear Van der Pol-Duffing equation is assumed as mathematical model of cerebrovascular circulation. Hypothesis of vascular pathology existence in some position of blood vessel, based on mathematical model properties for this position is formulated. Good reliability of hypothesis is proved statistically for 7 patients with arterial aneurysms.
Kulczyński, Bartosz; Gramza-Michałowska, Anna
Cardiovascular diseases are the leading cause of death worldwide. Literature data indicate that, due to these diseases, approximately 17.5 million people died in 2012. Types of cardiovascular disease include ischemic heart disease, cerebrovascular disease, peripheral vascular disease, congenital heart disease, rheumatic heart disease, cardiomyopathy and arrhythmia. Proper nutrition is an important factor in reducing the risk of cardiovascular events. An interesting element of our diets is spices. For thousands of years, they have been used in the treatment of many diseases: bacterial infections, coughs, colds, and liver diseases. Many studies also demonstrate their antioxidant, chemopreventive, anti-inflammatory and immunomodulatory properties. This paper focuses on discussing the importance of selected spices (garlic, cinnamon, ginger, coriander and turmeric) in the prevention and treatment of cardiovascular diseases.
Preskorn, Sheldon H.; Raichle, Marcus E.; Hartman, Boyd K.
External detection of the annihilation radiation produced by water labeled with oxygen-15 was used to measure cerebrovascular permeability and cerebral blood flow in six rhesus monkeys. Use of oxygen-15 also permitted assessment of cerebral metabolic rate in two of the monkeys. Amitriptyline produced a dose-dependent, reversible increase in permeability at plasma drug concentrations which are therapeutic for depressed patients. At the same concentrations the drug also produced a 20 to 30 percent reduction in cerebral metabolic rate. At higher doses normal autoregulation of cerebral blood flow was suspended, but responsivity to arterial carbon dioxide was normal.
Mueller, NT; Odegaard, AO; Gross, MD; Koh, WP; Yuan, JM; Pereira, MA
Purpose To examine whether menarcheal age was inversely associated with CVD mortality in Singaporean Chinese women. Methods 34,022 Chinese women aged 45–74 at enrollment (1993–1998), with complete data on study variables, were followed prospectively through 2009 for primary cause of death due to CVD, including coronary heart disease (CHD) and cerebrovascular disease (CERE). Hazard ratios (HRs) for CVD mortality were computed across menarcheal age categories and adjusted for potential confounders and BMI. Results Over 460,374 person-years of follow-up, 1,852 women died from CVD; 998 of them from CHD and 557 from CERE. There was a significant interaction between menarcheal age and smoking (p<0.05). In nonsmokers, menarcheal age was inversely associated with risk for CVD and CHD mortality. HRs (and 95% CI) for CVD mortality across menarcheal age categories (≤12, 13–14, 15–16, ≥17) were: 1.06 (0.87–1.29), 1 (referent), 0.89 (0.79–1.00), and 0.80 (0.69–0.93), respectively (ptrend<0.001); HRs for CHD mortality were: 1.06 (0.80–1.34), 1 (referent), 0.76 (0.65–0.90), and 0.72 (0.58–0.88), respectively (ptrend<0.001). In nonsmokers there was no association between menarcheal age and CERE mortality. Among smokers, menarcheal age was not associated with CVD, CHD or CERE mortality. Conclusion Menarcheal age was inversely associated with risk of CVD mortality in nonsmoking Chinese women. PMID:22939833
El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype
Background Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. Objectives To evaluate the efficacy and safety of ERT for AFD. Materials and methods For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. Results 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0
Corriveau, Roderick A; Bosetti, Francesca; Emr, Marian; Gladman, Jordan T; Koenig, James I; Moy, Claudia S; Pahigiannis, Katherine; Waddy, Salina P; Koroshetz, Walter
The World Health Organization reports that 47.5 million people are affected by dementia worldwide. With aging populations and 7.7 million new cases each year, the burden of illness due to dementia approaches crisis proportions. Despite significant advances in our understanding of the biology of Alzheimer's disease (AD), the leading dementia diagnosis, the actual causes of dementia in affected individuals are unknown except for rare fully penetrant genetic forms. Evidence from epidemiology and pathology studies indicates that damage to the vascular system is associated with an increased risk of many types of dementia. Both Alzheimer's pathology and cerebrovascular disease increase with age. How AD affects small blood vessel function and how vascular dysfunction contributes to the molecular pathology of Alzheimer's are areas of intense research. The science of vascular contributions to cognitive impairment and dementia (VCID) integrates diverse aspects of biology and incorporates the roles of multiple cell types that support the function of neural tissue. Because of the proven ability to prevent and treat cardiovascular disease and hypertension with population benefits for heart and stroke outcomes, it is proposed that understanding and targeting the biological mechanisms of VCID can have a similarly positive impact on public health.
Bishop, Stephen C; Woolliams, John A
This paper considers the application of genetic and genomic techniques to disease resistance, the interpretation of data arising from such studies and the utilisation of the research outcomes to breed animals for enhanced resistance. Resistance and tolerance are defined and contrasted, factors affecting the analysis and interpretation of field data presented, and appropriate experimental designs discussed. These general principles are then applied to two detailed case studies, infectious pancreatic necrosis in Atlantic salmon and bovine tuberculosis in dairy cattle, and the lessons learnt are considered in detail. It is concluded that the rate limiting step in disease genetic studies will generally be provision of adequate phenotypic data, and its interpretation, rather than the genomic resources. Lastly, the importance of cross-disciplinary dialogue between the animal health and animal genetics communities is stressed. PMID:26339300
Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai; Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M.; Bentzen, Søren M.
Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.
flow; weight training ; cerebrovascular control PRESERVATION OF CEREBRAL PERFUSION is essential for maintaining consciousness. Heavy resistance exercise...cardiovascular and cerebrovascular regulatory mechanisms. Subjects also received famil- iarization training with the experimental protocol and procedures...increases in the power of MCAv LF oscillations was induced by breathing through an inspiratory threshold device and was associated with an improvement in
Mountz, James M; Liu, Hong-Gang; Deutsch, Georg
Nuclear medicine imaging can play an important role in the diagnosis of stroke risk, the differential diagnosis of vascular and parenchymal cerebral abnormalities, and the understanding and management of poststroke recovery. Radionuclide brain-imaging methods can assess hemodynamic, vascular, and metabolic status before and after stroke. Several techniques, including vasodilatory stress imaging with regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT), oxygen extraction methods with positron emission tomography (PET), and spectroscopic imaging with magnetic resonance spectroscopic imaging, offer ways to distinguish vascular from parenchymal dysfunction and to determine whether any observed abnormalities in cerebral blood flow are primary or secondary disease manifestations. The value of radionuclide imaging in assessing the efficacy of several interventional surgical procedures is presented. Data from several imaging modalities bearing on the controversial issue of luxury perfusion and reperfusion injury are analyzed, including some of the discrepancies between animal and human clinical data. Imaging evidence for white matter disease and microangiopathy is analyzed, including a quantitative rCBF pattern analysis that distinguishes between typical Alzheimer's disease and microangiopathy by using multivariate analysis of variance curve profile analysis, which shows results of significant differences in the circumferential cortical blood flow profiles at P =.01. Microangiopathy showed rCBF reduction in the frontal and frontotemporal regions as compared with the more typical reduction in posterior temporal-parietal rCBF diminution characteristic of Alzheimer's disease. Several functional neuroimaging approaches to the study of cerebral poststroke reorganization are analyzed in the context of 2 major models of recovery: the resolution of diaschisis and reorganization in spared brain. Research on these issues is presented with SPECT, PET
Wang, Li; Zheng, Gang; Zhao, Tiezhu; Guo, Chao; Li, Lin; Lu, Guangming
Arterial spin labeling (ASL) technique is a kind of perfusion functional magnetic resonance imaging method that is based on endogenous contrast, and it can measure cerebral blood flow (CBF) noninvasively. The ASL technique has advantages of noninvasiveness, simplicity and relatively lower costs so that it is more suitable for longitudinal studies compared with previous perfusion methods, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), CT and the contrast agent based magnetic resonance perfusion imaging. This paper mainly discusses the current clinical applications of ASL in brain diseases as cerebrovascular diseases, brain tumors, Alzheimer's disease and epilepsy, etc.
Wagner, Steven; Craici, Iasmina
Hypertensive pregnancy disorders affect approximately 6 to 8 % of otherwise normal pregnancies. A growing body of evidence links these disorders with the future development of hypertension, coronary disease, cerebrovascular disease, and peripheral arterial disease. Larger studies associating hypertensive pregnancy to future development of renal disease have been lacking until recently, with publication of several compelling studies in the last 5 years. In this review, we will focus on the recent evidence associating hypertensive pregnancy disorders with the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD), as well as the development of microalbuminuria. We will also attempt to answer whether these renal risks are due to direct effects of hypertension during pregnancy, or whether they are due to shared environmental and genetic risk factors.
Heart Diseases; Cardiovascular Diseases; Acute Myocardial Infarction; Unstable Angina; Chronic Stable Angina; Ischemic Stroke; Cerebrovascular Accident; Subarachnoid Hemorrhage; Transient Ischemic Attack; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Sudden Coronary Death; Ventricular Arrhythmia; Sudden Death; Cardiac Arrest; Heart Failure
Brooks, D J
Positron emission tomography (PET) and single photon emission tomography (SPECT) provide sensitive means for quantifying the loss of nigrostriatal dopaminergic fibres in Parkinson's disease and for detecting the presence of dopaminergic dysfunction in asymptomatic at-risk relatives and patients with isolated tremor. Functional imaging can also be used to follow the rate of disease progression objectively, determine the efficacy of putative neuroprotective agents, and monitor the viability of transplants of fetal tissue. Additionally, in vivo pharmacological changes associated with development of treatment complications (fluctuations, dyskinesias) can be studied. Loss of dopaminergic projections produces profound changes in resting and activated brain metabolism. PET and SPECT activation studies have suggested that the akinesia of Parkinson's disease is associated with failure to activate the supplementary motor and dorsal pre-frontal areas. Activation of these cortical areas is restored towards normal by the use of dopaminergic medication, striatal transplantation with fetal mesencephalic tissue, and pallidotomy. The aim of this chapter is to review the insight which functional imaging has given us into the pathophysiology of parkinsonism.
Selvin, S; Shaw, G; Schulman, J; Merrill, D W
Maps transformed so as to have constant density of residential population were used to analyze the spatial distribution of disease in three specific areas. Each area had received recent attention because of suspected environmental pollution. The area adjacent to the Rocky Flats Facility (CO) was examined to identify any association between possible plutonium releases and increases in lung cancer or leukemia incidence. The industrial area of northern Contra Costa County (CA) was studied to explore a relationship between petrochemical industrial emissions and histologic-specific lung cancers. Finally, a suspected increase in the risk of congenital cardiac defects possibly related to pollution of the Santa Clara County (CA) water supply was investigated. No evidence of elevated risk of disease was found to be associated with either the Rocky Flats Facility or the polluted water of Santa Clara County. An increase in lung cancer, found by other investigators in earlier years, was shown to persist in association with industrial emissions in Contra Costa County.
Selvin, S.; Shaw, G.; Schulman, J.; Merrill, D.W.
Maps transformed so as to have constant density of residential population were used to analyze the spatial distribution of disease in three specific areas. Each area had received recent attention because of suspected environmental pollution. The area adjacent to the Rocky Flats Facility (CO) was examined to identify any association between possible plutonium releases and increases in lung cancer or leukemia incidence. The industrial area of northern Contra Costa County (CA) was studied to explore a relationship between petrochemical industrial emissions and histologic-specific lung cancers. Finally, a suspected increase in the risk of congenital cardiac defects possibly related to pollution of the Santa Clara County (CA) water supply was investigated. No evidence of elevated risk of disease was found to be associated with either the Rocky Flats Facility or the polluted water of Santa Clara County. An increase in lung cancer, found by other investigators in earlier years, was shown to persist in association with industrial emissions in Contra Costa County.
Millar, David J.; Richard-Londt, Angela
Human amyloid deposits always contain the normal plasma protein serum amyloid P component (SAP), owing to its avid but reversible binding to all amyloid fibrils, including the amyloid β (Aβ) fibrils in the cerebral parenchyma plaques and cerebrovascular amyloid deposits of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). SAP promotes amyloid fibril formation in vitro, contributes to persistence of amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore developed (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrospinal fluid (CSF), in patients with AD. Here we report that, after introduction of transgenic human SAP expression in the TASTPM double transgenic mouse model of AD, all the amyloid deposits contained human SAP. Depletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these amyloid deposits crucially validates the strategy of the forthcoming ‘Depletion of serum amyloid P component in Alzheimer's disease (DESPIAD)’ clinical trial of CPHPC. The results also strongly support clinical testing of CPHPC in patients with CAA. PMID:26842068
Wilke, M.; Eiffert, H.; Christen, H.; Hanefeld, F.
As part of an ongoing study aiming to define the clinical spectrum of neuroborreliosis in childhood, we have identified four patients with unusual clinical manifestations. Two patients suffered from a primarily chronic form of neuroborreliosis and displayed only non-specific symptoms. An 11 year old boy presented with long standing symptoms of severe weight loss and chronic headache, while the other patient had pre-existing mental and motor retardation and developed seizures and failure to thrive. Two further children who presented with acute hemiparesis as a result of cerebral ischaemic infarction had a cerebrovascular course of neuroborreliosis. One was a 15 year old girl; the other, a 5 year old boy, is to our knowledge the youngest patient described with this course of illness. Following adequate antibiotic treatment, all patients showed substantial improvement of their respective symptoms. Laboratory and magnetic resonance imaging findings as well as clinical course are discussed and the relevant literature is reviewed. PMID:10869004
Abe, A.; Ueda, T.; Ueda, M.; Nogoshi, S.; Nishiyama, Y.; Katayama, Y.
Summary This study evaluated the recoveries of cerebrovascular reserves (CVR) after applying percutaneous transluminal angioplasty (PTA) to patients with symptomatic middle cerebral artery (MCA) stenosis of varying severity. The patients were submitted to single photon emission computed tomography (SPECT) to obtain their regional cerebral blood flows at resting stage (rCBFrest) and acetazolamide-challenged CBF in five regions of interest (ROIs), including the MCA, on the ipsilateral and contralateral sides of the hemisphere. rCVR values were then calculated from these CBF data to evaluate the CVR recoveries after PTA treatment. When the PTA effects were statistically analyzed of the patients dichotomized into more severe (n=9) and less severe (n=5) groups, distinctly significant ROI-specific PTA effectiveness was observed for CVR rather than CBF values in the patients of the severer group. PMID:22681739
Shimada, A; Kuwamura, M; Awakura, T; Umemura, T; Takada, K; Ohama, E; Itakura, C
The distributions of senile plaques (SP) and cerebrovascular amyloidosis (CA) were studied by employing thioflavin S and modified Bielschowsky stains, and beta-protein immunohistochemistry on serial sections of the brains of aged dogs older than 10 years. Mature and perivascular plaques, both of which contained compact amyloid deposits, always showed a close topographic relationship to CA. In contrast, the majority of diffuse plaques showed no topographic relationship to CA. Cell bodies of neurons and/or glia were almost always involved in the diffuse plaques. In addition, beta-protein immunohistochemistry demonstrated amyloid deposits on the periphery of occasional neurons. These findings suggest that different mechanisms may be involved in the development of the different subtypes of SP in the brains of aged dogs.
Skrobot, Olivia A; Attems, Johannes; Esiri, Margaret; Hortobágyi, Tibor; Ironside, James W; Kalaria, Rajesh N; King, Andrew; Lammie, George A; Mann, David; Neal, James; Ben-Shlomo, Yoav; Kehoe, Patrick G; Love, Seth
There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate
Turner, Martin R; Goldacre, Raph; Talbot, Kevin; Goldacre, Michael J
Objective To use an unbiased method to test a previously reported association between cerebral arteriovenous malformation (AVM) embolisation and the subsequent development of amyotrophic lateral sclerosis (ALS). Methods A hospital record linkage database was used to create cohorts of individuals coded as having cerebral and peripheral vessel AVMs, stroke (separately for haemorrhagic and ischaemic), transient ischaemic attack (TIA) and subarachnoid haemorrhage (SAH). The rate ratio for subsequent ALS was compared to a reference cohort. Results An increased rate ratio for ALS was found in relation to prior AVM (2.69; p=0.005), all strokes (1.38; p<0.001), and TIA (1.47; p<0.001). Conclusions Cerebrovascular injury from a variety of causes, rather than the presence of AVM or the associated embolisation procedure per se, may be a risk factor for ALS within the context of a more complex multiple-hit model of pathogenesis. PMID:26260352
Gan'shina, T S; Kurza, E V; Kurdyumov, I N; Maslennikov, D V; Mirzoyan, R S
Experiments on nonlinear rats subjected to global transient cerebral ischemia revealed the ability of glutamic acid to improve cerebral circulation. Consequently, the excitatory amino acid can produce adverse (neurotoxic) and positive (anti-ischemic) effects in cerebral ischemia. The cerebrovascular effect of glutamic acid in cerebral ischemia is attenuated on the background action of the MNDA receptor blocker MK-801 (0.5 mg/kg intravenously) and eliminated by bicuculline. When glutamic acid is combined with the non-competitive MNDA receptor antagonist MK-801, neither one nor another drug shows its vasodilator effect. The results are indicative of the interaction between excitatory and inhibitory systems on the level of cerebral vessels and once again confirm our previous conclusion about the decisive role of GABA(A) receptors in brain vessels in the implementation of anti-ischemic activity of endogenous compounds (melatonin) and well-known pharmacological substances (mexidol, afobazole), and new chemical compounds based on GABA-containing lipid derivatives.
Rempfler, Markus; Schneider, Matthias; Ielacqua, Giovanna D; Xiao, Xianghui; Stock, Stuart R; Klohs, Jan; Székely, Gábor; Andres, Bjoern; Menze, Bjoern H
We introduce a probabilistic approach to vessel network extraction that enforces physiological constraints on the vessel structure. The method accounts for both image evidence and geometric relationships between vessels by solving an integer program, which is shown to yield the maximum a posteriori (MAP) estimate to a probabilistic model. Starting from an overconnected network, it is pruning vessel stumps and spurious connections by evaluating the local geometry and the global connectivity of the graph. We utilize a high-resolution micro computed tomography (μCT) dataset of a cerebrovascular corrosion cast to obtain a reference network and learn the prior distributions of our probabilistic model and we perform experiments on in-vivo magnetic resonance microangiography (μMRA) images of mouse brains. We finally discuss properties of the networks obtained under different tracking and pruning approaches.
Kuebler, W M; Kisch-Wedel, H; Kemming, G I; Meisner, F; Bruhn, S; Koehler, C; Flondor, M; Messmer, K; Zwissler, B
Although inhaled nitric oxide (NO(i)) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO(i) have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO(i) in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO(i) increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO(i) in the cerebral vasculature, which may occur preferentially in the venous compartment.
Rempfler, Markus; Schneider, Matthias; Ielacqua, Giovanna D.; ...
We introduce a probabilistic approach to vessel network extraction that enforces physiological constraints on the vessel structure. The method accounts for both image evidence and geometric relationships between vessels by solving an integer program, which is shown to yield the maximum a posteriori (MAP) estimate to the probabilistic model. Starting from an over-connected network, it is pruning vessel stumps and spurious connections by evaluating the local geometry and the global connectivity of the graph. We utilize a high-resolution micro computed tomography (µCT) dataset of a cerebrovascular corrosion cast to obtain a reference network and learn the prior distributions of ourmore » probabilistic model. As a result, we perform experiments on micro magnetic resonance angiography (µMRA) images of mouse brains and discuss properties of the networks obtained under different tracking and pruning approaches.« less
Rempfler, Markus; Schneider, Matthias; Ielacqua, Giovanna D.; Xiao, Xianghui; Stock, Stuart R.; Klohs, Jan; Szekely, Gabor; Andres, Bjoern; Menze, Bjoern H.
We introduce a probabilistic approach to vessel network extraction that enforces physiological constraints on the vessel structure. The method accounts for both image evidence and geometric relationships between vessels by solving an integer program, which is shown to yield the maximum a posteriori (MAP) estimate to the probabilistic model. Starting from an over-connected network, it is pruning vessel stumps and spurious connections by evaluating the local geometry and the global connectivity of the graph. We utilize a high-resolution micro computed tomography (µCT) dataset of a cerebrovascular corrosion cast to obtain a reference network and learn the prior distributions of our probabilistic model. As a result, we perform experiments on micro magnetic resonance angiography (µMRA) images of mouse brains and discuss properties of the networks obtained under different tracking and pruning approaches.
Lapcević, Mirjana; Vuković, Mira
Risk factors (RF) of chronic noncontiguous diseases (CND) are mutual and cannot be observed individually since there is an inter-reaction (interaction of RF in various combinations), what makes so-called personality risk profile for development of particular disease. Almost all CND belong to the group of preventable diseases, because their course may be influenced and changed through RF modification and reduction. Bad habits also contribute to CND incidence. CND prevention is the first priority of primary health care physicians. The main objective of our study was to detect RF in patients during everyday activities of general practitioner, to estimate the risk of CND within the existing RF combination, to show the results of 12-week active monitoring of population with RF of CND, and with already present CND; while the secondary goal was to assess how much population is interested in active collaboration as well as to evaluate the qualification of general medicine teams for work based on defined methodology. The study was multicentric, prospective and interventional. The study included 2086 subjects, aged from 25-64 years, and it was carried out in 17 health centers throughout Serbia in the period January-April 2002. The subjects were selected by method of open clinical experiment. Thereafter, 12-week medical intervention was initiated involving non-pharmacological and pharmacological treatment. The first control was scheduled after 8, and the second after 12 months of intervention. Congruence chi2 test, ANOVA for repeated measurements and Logistic regression were used for statistical data processing. Out of a total of 2086 subjects, the following proportion of them reported specific diagnosis in their medical histories: 77% of them reported arterial hypertension (HTA), 68%--increased body mass (BMI > or = 27Kg/m2), 66%--hyperlipoproteinemia (HLP), 34%--diabetes mellitus (DM), 56%--inadequate physical activity (PA), and 23%--cigarette smoking (CS). On the basis of
Esnault, Pierre; Cardinale, Mickaël; Boret, Henry; D'Aranda, Erwan; Montcriol, Ambroise; Bordes, Julien; Prunet, Bertrand; Joubert, Christophe; Dagain, Arnaud; Goutorbe, Philippe; Kaiser, Eric; Meaudre, Eric
OBJECTIVE Blunt cerebrovascular injuries (BCVIs) affect approximately 1% of patients with blunt trauma. An antithrombotic or anticoagulation therapy is recommended to prevent the occurrence or recurrence of neurovascular events. This treatment has to be carefully considered after severe traumatic brain injury (TBI), due to the risk of intracranial hemorrhage expansion. Thus, the physician in charge of the patient is confronted with a hemorrhagic and ischemic risk. The main objective of this study was to determine the incidence of BCVI after severe TBI. METHODS The authors conducted a prospective, observational, single-center study including all patients with severe TBI admitted in the trauma center. Diagnosis of BCVI was performed using a 64-channel multidetector CT. Characteristics of the patients, CT scan results, and outcomes were collected. A multivariate logistic regression model was developed to determine the risk factors of BCVI. Patients in whom BCVI was diagnosed were treated with systemic anticoagulation. RESULTS In total, 228 patients with severe TBI who were treated over a period of 7 years were included. The incidence of BCVI was 9.2%. The main risk factors were as follows: motorcycle crash (OR 8.2, 95% CI 1.9-34.8), fracture involving the carotid canal (OR 11.7, 95% CI 1.7-80.9), cervical spine injury (OR 13.5, 95% CI 3.1-59.4), thoracic trauma (OR 7.3, 95% CI 1.1-51.2), and hepatic lesion (OR 13.3, 95% CI 2.1-84.5). Among survivors, 82% of patients with BCVI received systemic anticoagulation therapy, beginning at a median of Day 1.5. The overall stroke rate was 19%. One patient had an intracranial hemorrhagic complication. CONCLUSIONS Blunt cerebrovascular injuries are frequent after severe TBI (incidence 9.2%). The main risk factors are high-velocity lesions and injuries near cervical arteries.
Flück, Daniela; Siebenmann, Christoph; Keiser, Stefanie; Cathomen, Adrian; Lundby, Carsten
Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAv mean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26 ± 4 years (mean ± s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAv mean was not altered. Hypercapnic CVR was decreased at HA0 (1.16% ± 0.16%/mm Hg, mean ± s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13% ± 0.18% and 2.96% ± 0.10%/mm Hg) and HA22 (3.32% ± 0.12% and 3.24% ± 0.14%/mm Hg) compared with SL (1.98% ± 0.22% and 2.38% ± 0.10%/mm Hg; P < 0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAv mean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude.
Flück, Daniela; Siebenmann, Christoph; Keiser, Stefanie; Cathomen, Adrian; Lundby, Carsten
Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAvmean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26±4 years (mean±s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAvmean was not altered. Hypercapnic CVR was decreased at HA0 (1.16%±0.16%/mm Hg, mean±s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13%±0.18% and 2.96%±0.10%/mm Hg) and HA22 (3.32%±0.12% and 3.24%±0.14%/mm Hg) compared with SL (1.98%±0.22% and 2.38%±0.10%/mm Hg; P<0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAvmean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude. PMID:25806704
Wert, S M
One of the earliest attempts at risk sharing between a managed-care organization and a pharmaceutical company is the infectious disease management program developed since late 1993 by Intergroup of Arizona and Eli Lilly and Company (Indianapolis, Indiana) in conjunction with the Center for Pharmaceutical Economics at The University of Arizona (Tucson, Arizona) and other entities. In the first phase of the program, protocols were built around eight infectious disease states, and it was recognized that second-line antibiotics were often prescribed when more economical first-line antibiotics would be equally effective. The second phase of the program emphasized developing treatment algorithms focused on patient outcomes, using merged medical and pharmacy claims databases to determine the effects of the antibiotic changes. To implement the program successfully, some significant shifts in corporate, medical, and patient mind-sets had to be addressed. A primary goal was to encourage a movement from a rebate, volume-driven, cost structure to a shared-risk, appropriate-use, reimbursement method in which both managed-care and the pharmaceutical company incentives could mesh as far as possible. Over the long term, it is hoped that this project will lay the groundwork for other disease management programs for high-impact, frequently occurring diseases.
Lee, Heyne; Pienaar, Ilse S
The vertebrate blood-brain barrier (BBB) is critical for ensuring the maintenance of brain homeostasis, whilst protecting the brain against toxic insults. Various pathological events disrupt BBB integrity, holding several important clinical implications. In instances where the normal mechanisms controlling passage of substances into the brain are compromised, these could sensitize or even worsen endogenous pathological conditions. Recognition has grown recently that patients diagnosed with Parkinson's disease (PD) present with concurrent medical problems, including cerebrovascular lesions. However, cerebrovascular disturbances may also result from PD-related disease processes; the pathological mechanisms which could entail interaction between environment-derived and genetic factors. The current review addresses the accumulation of studies aimed at better understanding the series of processes affecting the neurovascular unit in human Parkinsonism, due in part to the BBB presenting as a formidable opponent in the effective delivery of therapeutics that have shown promise as therapeutic strategies for treating aspects of PD when tested in vitro.
Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing
Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. This article is protected by
Yang, Changbin; Gao, Yuan; Greaves, Danielle K.; Villar, Rodrigo; Beltrame, Thomas; Fraser, Katelyn S.
The hypothesis that cerebrovascular autoregulation was not impaired during head-up tilt (HUT) that followed brief exposures to varying degrees of prior head-down tilt (HDT) was tested in 10 healthy young men and women. Cerebral mean flow velocity (MFV) and cardiovascular responses were measured in transitions to a 60-s period of 75° HUT that followed supine rest (control) or 15 s HDT at −10°, −25°, and −55°. During HDT, heart rate (HR) was reduced for −25° and −55°, and cardiac output was lower at −55° HDT. MFV increased during −10° HDT, but not in the other conditions even though blood pressure at the middle cerebral artery (BPMCA) increased. On the transition to HUT, HR increased only for −55° condition, but stroke volume and cardiac output transiently increased for −25° and −55°. Total peripheral resistance index decreased in proportion to the magnitude of HDT and recovered over the first 20 s of HUT. MFV was significantly less in all HDT conditions compared with the control in the first 5-s period of HUT, but it recovered quickly. An autoregulation correction index derived from MFV recovery relative to BPMCA decline revealed a delay in the first 5 s for prior HDT compared with control but then a rapid increase to briefly exceed control after −55° HDT. This study showed that cerebrovascular autoregulation is modified by but not impaired by brief HDT prior to HUT and that cerebral MFV recovered quickly and more rapidly than arterial blood pressure to protect against cerebral hypoperfusion and potential syncope. PMID:25749443
Hung, Chia-Wei; Chen, Yu-Chih; Hsieh, Wan-Ling; Chiou, Shih-Hwa; Kao, Chung-Lan
Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.
Tarazona, Monica Jidid Mateus; Mota, Amanda Nascimento Cavalleiro de Macedo; Gripp, Alexandre Carlos; Unterstell, Natasha; Bressan, Aline Lopes
Bullous pemphigoid (BP) is an autoimmune, acquired, cutaneous disease caused by the production of autoantibodies against hemidesmosomes' components in the basement membrane. The estimated incidence in Europe ranges from 7 to 43 cases per million inhabitants per year. Several studies have reported an association between BP and neurological disorders (ND). Our cohort of Bullous pemphigoid and ND is the first in Brazil and showed a significantly high prevalence of neurological and/or psychiatric diseases, especially cerebrovascular accident (CVA) and dementia, in agreement with the prevalence reported in several studies published in the medical literature in recent years. PMID:25831008
Van Cauwelaert, P; Muylaert, P; Tombeur, J; Alleman, J; Fornhoff, M
In 99 of 2250 consecutive C.B.P. cases, signs of cerebro-vascular disease (C.V.D.) were recorded in 87 (3.9%) on admission and in 12 post-operatively. The detection of C.V.D. by auscultation alone is very incomplete. There were 17 post-C.B.P. neurologic deficits (P.O.N.D.) (0.75%): 15 strokes (0.67%) and 2 T.I.A.'s. 26 patients (out of 87 detected on admission) were treated by carotid endarterectomy (C.E.) either pre-by-pass or simultaneously. There were no complications. The remaining 61 patients, who were not treated, had 4 strokes and 1 T.I.A. after their C.B.P. The most probable cause of these deficits was pre-existing C.V.D. Could more extensive pre-operative investigation, and treating the serious lesions by C.E., improve the P.O.N.D. incidence? The published series on simultaneous C.E. + C.B.P. are not yet conclusive. We favour C.E. done before the C.P.B. procedure except in very serious coronary disease when simultaneous operation is preferred.
Dong, Kai; Huang, Xiaoqin; Zhang, Qian; Yu, Zhipeng; Ding, Jianping; Song, Haiqing
Abstract Chronic kidney disease (CKD) is gradually recognized as an independent risk factor for cardiovascular and cardio-/cerebrovascular disease. This study aimed to examine the association of the estimated glomerular filtration rate (eGFR) and clinical outcomes at 3 months after the onset of ischemic stroke in a hospitalized Chinese population. Totally, 972 patients with acute ischemic stroke were enrolled into this study. Modified of Diet in Renal Disease (MDRD) equations were used to calculate eGFR and define CKD. The site and degree of the stenosis were examined. Patients were followed-up for 3 months. Endpoint events included all-cause death and newly ischemic events. The multivariate logistic model was used to determine the association between renal dysfunction and patients’ outcomes. Of all patients, 130 patients (13.4%) had reduced eGFR (<60 mL/min/1.73 m2), and 556 patients had a normal eGFR (≥90 mL/min/1.73 m2). A total of 694 patients suffered from cerebral artery stenosis, in which 293 patients only had intracranial artery stenosis (ICAS), 110 only with extracranial carotid atherosclerotic stenosis (ECAS), and 301 with both ICAS and ECAS. The patients with eGFR <60 mL/min/1.73m2 had a higher proportion of death and newly ischemic events compared with those with a relatively normal eGFR. Multivariate analysis revealed that a baseline eGFR <60 mL/min/1.73 m2 increased the risk of mortality by 3.089-fold and newly ischemic events by 4.067-fold. In further analysis, a reduced eGFR was associated with increased rates of mortality and newly events both in ICAS patients and ECAS patients. However, only an increased risk of newly events was found as the degree of renal function deteriorated in ICAS patients (odds ratio = 8.169, 95% confidence interval = 2.445–14.127). A low baseline eGFR predicted a high mortality and newly ischemic events at 3 months in ischemic stroke patients. A low baseline eGFR was also a strong independent
Ortega Calvo, M; Villadiego Sánchez, J M
Superficial thoracic wall and dorsal vein of the penis phlebitis are uncommon diseases. Both are known as Mondor's disease. Two cases have been diagnosed in a short period of time in a Southern. Spain primary care clinics.
Money, John; And Others
Described in a family in which the youngest boy has early infantile autism, Addison's disease, and moniliasis and two older boys have autoimmune disease with hypoparathyroidism, Addison's disease, moniliasis, and either alopecia totalis or diabetes mellitus, while the oldest boy and parents are symptom free. (KW)
Arteaga, Daniel F; Strother, Megan K; Faraco, Carlos C; Jordan, Lori C; Ladner, Travis R; Dethrage, Lindsey M; Singer, Robert J; Mocco, J; Clemmons, Paul F; Ayad, Michael J; Donahue, Manus J
'Vascular steal' has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients (n=40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree<50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant (P<0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.
Oziel, M.; Hjouj, M.; Gonzalez, C. A.; Lavee, J.; Rubinsky, B.
Monitoring changes in non-ionizing radiofrequency electromagnetic waves as they traverse the brain can detect the effects of stimuli employed in cerebrovascular autoregulation (CVA) tests on the brain, without contact and in real time. CVA is a physiological phenomenon of importance to health, used for diagnosis of a number of diseases of the brain with a vascular component. The technology described here is being developed for use in diagnosis of injuries and diseases of the brain in rural and economically underdeveloped parts of the world. A group of nine subjects participated in this pilot clinical evaluation of the technology. Substantial research remains to be done on correlating the measurements with physiology and anatomy. PMID:26898944
Oziel, M.; Hjouj, M.; Gonzalez, C. A.; Lavee, J.; Rubinsky, B.
Monitoring changes in non-ionizing radiofrequency electromagnetic waves as they traverse the brain can detect the effects of stimuli employed in cerebrovascular autoregulation (CVA) tests on the brain, without contact and in real time. CVA is a physiological phenomenon of importance to health, used for diagnosis of a number of diseases of the brain with a vascular component. The technology described here is being developed for use in diagnosis of injuries and diseases of the brain in rural and economically underdeveloped parts of the world. A group of nine subjects participated in this pilot clinical evaluation of the technology. Substantial research remains to be done on correlating the measurements with physiology and anatomy.
Fierstra, Jorn; Conklin, John; Krings, Timo; Slessarev, Marat; Han, Jay S; Fisher, Joseph A; Terbrugge, Karel; Wallace, M Christopher; Tymianski, Michael; Mikulis, David J
Epileptic seizures are a common presentation in patients with newly diagnosed brain arteriovenous malformations, but the pathophysiological mechanisms causing the seizures remain poorly understood. We used magnetic resonance imaging-based quantitative cerebrovascular reactivity mapping and conventional angiography to determine whether seizure-prone patients with brain arteriovenous malformations exhibit impaired cerebrovascular reserve or morphological angiographic features predictive of seizures. Twenty consecutive patients with untreated brain arteriovenous malformations were recruited (10 with and 10 without epileptic seizures) along with 12 age-matched healthy controls. Blood oxygen level-dependent MRI was performed while applying iso-oxic step changes in end-tidal partial pressure of CO(2) to obtain quantitative cerebrovascular reactivity measurements. The brain arteriovenous malformation morphology was evaluated by angiography, to determine to what extent limitations of arterial blood supply or the presence of restricted venous outflow and tissue congestion correlated with seizure susceptibility. Only patients with seizures exhibited impaired peri-nidal cerebrovascular reactivity by magnetic resonance imaging (0.11 ± 0.10 versus 0.25 ± 0.07, respectively; P < 0.001) and venous drainage patterns suggestive of tissue congestion on angiography. However, cerebrovascular reactivity changes were not of a magnitude suggestive of arterial steal, and were probably compatible with venous congestion in aetiology. Our findings demonstrate a strong association between impaired peri-nidal cerebrovascular reserve and epileptic seizure presentation in patients with brain arteriovenous malformation. The impaired cerebrovascular reserve may be associated with venous congestion. Quantitative measurements of cerebrovascular reactivity using blood oxygen level-dependent MRI appear to correlate with seizure susceptibility in patients with brain arteriovenous malformation.
Willie, C K; Colino, F L; Bailey, D M; Tzeng, Y C; Binsted, G; Jones, L W; Haykowsky, M J; Bellapart, J; Ogoh, S; Smith, K J; Smirl, J D; Day, T A; Lucas, S J; Eller, L K; Ainslie, P N
There is considerable utility in the use of transcranial Doppler ultrasound (TCD) to assess cerebrovascular function. The brain is unique in its high energy and oxygen demand but limited capacity for energy storage that necessitates an effective means of regional blood delivery. The relative low cost, ease-of-use, non-invasiveness, and excellent temporal resolution of TCD make it an ideal tool for the examination of cerebrovascular function in both research and clinical settings. TCD is an efficient tool to access blood velocities within the cerebral vessels, cerebral autoregulation, cerebrovascular reactivity to CO(2), and neurovascular coupling, in both physiological states and in pathological conditions such as stroke and head trauma. In this review, we provide: (1) an overview of TCD methodology with respect to other techniques; (2) a methodological synopsis of the cerebrovascular exam using TCD; (3) an overview of the physiological mechanisms involved in regulation of the cerebral blood flow; (4) the utility of TCD for assessment of cerebrovascular pathology; and (5) recommendations for the assessment of four critical and complimentary aspects of cerebrovascular function: intra-cranial blood flow velocity, cerebral autoregulation, cerebral reactivity, and neurovascular coupling. The integration of these regulatory mechanisms from an integrated systems perspective is discussed, and future research directions are explored.
Miners, James Scott; Kehoe, Patrick; Love, Seth
Neprilysin (NEP), which degrades amyloid-β (Aβ), is expressed by neurons and cerebrovascular smooth muscle cells (CVSMCs). NEP immunolabeling is reduced within cerebral blood vessels of Alzheimer's disease (AD) patients with cerebral amyloid angiopathy (CAA). We have now measured NEP enzyme activity in leptomeningeal and purified cerebral cortical blood vessel preparations from control and AD patients with and without CAA. Measurements were adjusted for smooth muscle actin (SMA) to control for variations in CVSMC content. NEP activity was reduced in CAA, in both controls and AD. In leptomeningeal vessels, NEP activity was related to APOE genotype, being highest in ε2-positive and lowest in ε4-positive brains. To assess the role of NEP in protecting CVSMCs from Aβ toxicity, we measured cell death in primary human adult CVSMCs exposed to Aβ(1-40) , Aβ(1-42) or Aβ(1-40(Dutch variant)) . Aβ(1-42) was most cytotoxic to CVSMCs. Aβ(1-42) -mediated cell death was increased following siRNA-mediated knockdown or thiorphan-mediated inhibition of NEP activity; conversely Aβ(1-42) -mediated cytotoxicity was reduced by the addition of somatostatin and NEP over-expression following transfection with NEP cDNA. Our findings suggest that NEP protects CVSMCs from Aβ toxicity and protects cerebral blood vessels from the development and complications of CAA.
Moss, Heather E
The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk.
Oberoi, Sukhvinder Singh; Harish, Yashoda; Hiremath, Shivalingaswamy; Puranik, Manjunath
Background: Periodontal deterioration has been reported to be associated with systemic diseases such as cardiovascular disease (CVD), diabetes mellitus, respiratory disease, liver cirrhosis, bacterial pneumonia, nutritional deficiencies, and adverse pregnancy outcomes. Aim: The present study assessed the periodontal disease among patients with systemic conditions such as diabetes, CVD, and respiratory disease. Materials and Methods: The study population consisted of 220 patients each of CVD, respiratory disease, and diabetes mellitus, making a total of 660 patients in the systemic disease group. A control group of 340 subjects were also included in the study for comparison purpose. The periodontal status of the patients with these confirmed medical conditions was assessed using the community periodontal index of treatment needs (CPITNs) index. Results: The prevalence of CPITN code 4 was found to be greater among the patients with respiratory disease whereas the mean number of sextants with score 4 was found to be greater among the patients with diabetes mellitus and CVD. The treatment need 0 was found to be more among the controls (1.18%) whereas the treatment need 1, 2, and 3 were more among the patients with respiratory disease (100%, 97.73%, and 54.8%), diabetes mellitus (100%, 100% and 46.4%), and CVD (100%, 97.73%, and 38.1%), in comparison to the controls (6.18%). Conclusion: From the findings of the present study, it can be concluded that diabetes mellitus, CVD, and respiratory disease are associated with a higher severity of periodontal disease. PMID:28298829
Montoye, Henry J.
A physically more active life, while not being related to atherosclerosis, could enable some individuals to live longer with atherosclerosis before dying from or showing symptoms of coronary heart disease. (MJB)
Pillai, Jay J; Zacà, Domenico
The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion
Wang, Ruikang K; Hurst, Sawan
Optical micro-angiography (OMAG) was developed to achieve volumetric imaging of the microstructures and dynamic cerebrovascular blood perfusion in mice with capillary level resolution and high signal-to-background ratio. In this paper, we present a high-speed and high-sensitivity OMAG imaging system by using an InGaAs line scan camera and broadband light source at 1.3 mum wavelength for enhanced imaging depth in tissue. We show that high quality imaging of cerebrovascular blood perfusion down to capillary level resolution with the intact skin and cranium are obtained in vivo with OMAG, without the interference from the blood perfusion in the overlaying skin. The results demonstrate the potential of 1.3 mum OMAG for high-speed and high-sensitivity imaging of blood perfusion in human and small animal studies.
Dgedge, M.; Novoa, A.; Macassa, G.; Sacarlal, J.; Black, J.; Michaud, C.; Cliff, J.
OBJECTIVE: To classify the causes of death in Maputo City, Mozambique, using the methods of the Global Burden of Disease study, in order to provide information for health policy-makers and to obtain a baseline for future studies in Maputo City and provincial capitals. METHODS: Data were taken from the Maputo City death register and autopsy records for 1994. FINDINGS: A total of 9011 deaths were recorded in the death register, representing a coverage of approximately 86%. Of these, 8114 deaths (92%) were classified by cause. Communicable, maternal, perinatal, and nutritional disorders accounted for 5319 deaths; noncommunicable diseases for 1834; and injuries for 961. The 10 leading causes of registered deaths were perinatal disorders (1643 deaths); malaria (928); diarrhoeal diseases (814); tuberculosis (456); lower respiratory infections (416); road-traffic accidents (371); anaemia (269); cerebrovascular diseases (269); homicide (188); and bacterial meningitis (178). CONCLUSIONS: Infectious diseases of all types, injuries, and cerebrovascular disease ranked as leading causes of death, according to both the autopsy records and the city death register. AIDS-related deaths were underreported. With HIV infection increasing rapidly, AIDS will add to the already high burden of infectious diseases and premature mortality in Maputo City. The results of the study indicate that cause of death is a useful outcome indicator for disease control programmes. PMID:11436477
Chen, H C; Chang, J M; Tsai, J H; Lai, Y H
Medullary cystic disease of the kidney is characterized by progressive tubulointerstitial disease with medullary cyst formation and secondary glomerular sclerosis. We treated a patient with chronic renal failure and investigated the family history of renal disease. The patient, an 18-year-old woman, was admitted due to poor appetite and fatigue for several months. Findings on physical examination were normal except for a pale conjunctiva. Urinalysis revealed only mild proteinuria with clear sediment. The hemogram showed normocytic normochromic anemia with hemoglobin 86 g/L. The patient was azotemic and her creatinine clearance rate was 10.7 mL/min. Renal sonography showed contraction of both kidneys with a marked increase in cortical echogenicity. One small cyst was found in the medullary area. Computed tomography (CT) and magnetic resonance imaging revealed several medullary cysts. Percutaneous renal biopsy showed focal and periglomerular sclerosis, marked tubular atrophy, and interstitial fibrosis. Ten of her family members were examined for renal function, and by sonography and CT. Five had medullary cysts, and three of the five showed abnormal renal function. Medullary cystic disease should be considered in the differential diagnosis of patients with renal disease and a positive family history.
Allan, Philip D; Faulkner, James; O’Donnell, Terrence; Lanford, Jeremy; Wong, Lai-kin; Saleem, Saqib; Woolley, Brandon; Lambrick, Danielle; Stoner, Lee; Tzeng, Yu-Chieh
We investigated if hemodynamic variability, cerebral blood flow (CBF) regulation, and their interrelationships differ between patients with transient ischemic attack (TIA) and controls. We recorded blood pressure (BP) and bilateral middle cerebral artery flow velocity (MCAv) in a cohort of TIA patients (n = 17), and age-matched controls (n = 15). Spontaneous fluctuations in BP and MCAv were characterized by spectral power analysis, and CBF regulation was assessed by wavelet phase synchronization analysis in the very low- (0.02–0.07 Hz), low- (0.07–0.20 Hz), and high-frequency (0.20–0.40 Hz) ranges. Furthermore, cerebrovascular CO2 reactivity was assessed as a second metric of CBF regulation by inducing hypercapnia with 8% CO2 inhalation followed by hyperventilation driven hypocapnia. We found that TIA was associated with higher BP power (group effect, P < 0.05), but not MCAv power (P = 0.11). CBF regulation (assessed by wavelet phase synchronization and CO2 reactivity) was intact in patients (all P ≥ 0.075) across both hemispheres (all P ≥ 0.51). Pooled data (controls and affected hemisphere of patients) showed that BP and MCAv power were positively correlated at all frequency ranges (R2 = 0.20–0.80, all P < 0.01). Furthermore, LF phase synchronization index was a significant determinant of MCAv power (P < 0.05), while VLF and HF phase synchronization index, and TIA were not (all P ≥ 0.50). These results indicate that CBF stability and control is maintained in TIA patients, but BPV is markedly elevated. BPV attenuation may be an important therapeutic strategy for enhancing secondary stroke prevention in patients who suffer a TIA. PMID:26537345
Abenoza, P; Sibley, R K
A 1-week-old baby boy presented with hepatosplenomegaly, coarse facial features, and cloudy corneas. A metabolic storage disease was considered and he underwent cutaneous and liver biopsy. By light microscopy the skin was normal. Kupffer cells were enlarged and had foamy cytoplasm. Ultrastructural examination of skin and liver demonstrated features compatible with Farber's disease: curvilinear and "banana" bodies, zebra-like structures, and concentric lamellar bodies. A deficiency of lysosomal acid ceramidase was subsequently demonstrated in cultured fibroblasts and in liver tissue corroborating the ultrastructural findings.
Gissel, Matthew; Undas, Anetta; Slowik, Agnieszka; Mann, Kenneth G.; Brummel-Ziedins, Kathleen E.
Introduction More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events. Materials and Methods We studied (1) 100 patients with acute ischemic stroke (n=50) or transient ischemic attack (TIA) (n=50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n=50) or TIA (n=50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI). Results The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p≤0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p<0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced. Conclusion Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors. PMID:20709367
Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen
Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P < 0.001); and, 0.39% and 0.26% (P < 0.001) in advanced MD. Mild to moderate CKD patients had higher risk for MD [adjusted odds ratio (OR), 1.301; 95% confidence interval (CI), 1.200-1.411; P < 0.001] than normal renal function subjects. The association was more pronounced for advanced MD. From all age strata (10 years increase), the presence of CKD in those patients aged less than 40 years had highest OR for all MD (OR = 2.125, 95% CI: 1.417-3.186, P < 0.001). The results were consistent in interaction terms, highlighting the importance of CKD in young age patient for risk of MD. The high risk for MD in mild to moderate CKD patients remains significant after adjustment for personal habits (alcohol drinking and smoking, model 1; OR: 1.371; 95% CI: 1.265-1.486; P < 0.001), comorbidities (dyslipidemia, cerebrovascular disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264-1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218-1.431, P < 0.001). This association was consistent in the subanalysis, excluding those
Bravi, Luca; Rudini, Noemi; Cuttano, Roberto; Giampietro, Costanza; Maddaluno, Luigi; Ferrarini, Luca; Adams, Ralf H.; Corada, Monica; Boulday, Gwenola; Tournier-Lasserve, Elizabeth; Dejana, Elisabetta; Lampugnani, Maria Grazia
Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences. At present, the only recommended treatment of CCM is surgical. Because surgery is often not applicable, pharmacological treatment would be highly desirable. We describe here a murine model of the disease that develops after endothelial-cell–selective ablation of the CCM3 gene. We report an early, cell-autonomous, Wnt-receptor–independent stimulation of β-catenin transcription activity in CCM3-deficient endothelial cells both in vitro and in vivo and a triggering of a β-catenin–driven transcription program that leads to endothelial-to-mesenchymal transition. TGF-β/BMP signaling is then required for the progression of the disease. We also found that the anti-inflammatory drugs sulindac sulfide and sulindac sulfone, which attenuate β-catenin transcription activity, reduce vascular malformations in endothelial CCM3-deficient mice. This study opens previously unidentified perspectives for an effective pharmacological therapy of intracranial vascular cavernomas. PMID:26109568
Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Rossato, Gianluca; Nollo, Giandomenico; Faes, Luca; Porta, Alberto
Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.
Weiss, Robert H; Kim, Kyoungmi
Metabolomics--the nontargeted measurement of all metabolites produced by the body--is beginning to show promise in both biomarker discovery and, in the form of pharmacometabolomics, in aiding the choice of therapy for patients with specific diseases. In its two basic forms (pattern recognition and metabolite identification), this developing field has been used to discover potential biomarkers in several renal diseases, including acute kidney injury (attributable to a variety of causes), autosomal dominant polycystic kidney disease and kidney cancer. NMR and gas chromatography or liquid chromatography, together with mass spectrometry, are generally used to separate and identify metabolites. Many hurdles need to be overcome in this field, such as achieving consistency in collection of biofluid samples, controlling for batch effects during the analysis and applying the most appropriate statistical analysis to extract the maximum amount of biological information from the data obtained. Pathway and network analyses have both been applied to metabolomic analysis, which vastly extends its clinical relevance and effects. In addition, pharmacometabolomics analyses, in which a metabolomic signature can be associated with a given therapeutic effect, are beginning to appear in the literature, which will lead to personalized therapies. Thus, metabolomics holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in kidney disease.
Chen, Yufen; Parrish, Todd B.
The blood-oxygenation-level-dependent (BOLD) signal is dependent on multiple physiological factors such as cerebral blood flow (CBF), local oxygen metabolism (CMRO2) and cerebral blood volume (CBV). Since caffeine affects both CBF and neural activity, its effects on BOLD remain controversial. The calibrated BOLD approach is an excellent tool to study caffeine because it combines CBF and BOLD measures to estimate changes in CMRO2. The present study used the calibrated BOLD approach with 5% CO2 to determine if a 2.5mg/kg intravenous injection of caffeine changes the coupling between CBF and CMRO2 during motor and visual tasks. The results show that caffeine decreases n, the CBF:CMRO2 coupling ratio, from 2.58 to 2.33 in motor (p=0.006) and from 2.45 to 2.23 in visual (p=0.002) areas respectively. The current study also demonstrated that caffeine does not alter cerebrovascular reactivity to CO2. These results highlight the importance of the calibrated BOLD approach in improving interpretation of the BOLD signal in the presence of substances like caffeine. PMID:19000770
Gomonova, I Iu
The problem of unexpected death is challenging for many medical disciplines including forensic medicine. In 2011 the ratio of violent to non-violent deaths was 1:1.7. The structure of non-violent mortality changed due to the rise in the number of deaths from cerebrovascular diseases. International epidemiological studies demonstrated that stroke presently holds the second or third place in the structure of overall mortality in the world's population. The lethality rate attributable to hemorrhagic stroke is estimated at 79.5%. Of special interest for both forensic medical experts and general practitioners is the combination of cerebrovascular disease and the preceding craniocerebral injury. The discrepancy between clinical and pathologo-anatomical diagnoses amounts to 46.5%. According to the data collected by the Russian Centre of Forensic Medical Expertise in 2010, cerebrovascular pathology remained unrecognized in 62.4% of the cases and was erroneously diagnosed as a cerebrocranial injury in 52.2% of the patients. It is believed that forensic medical experts can render assistance to health facilities as regards the improvement of the quality of medical aid and preventive measures provided to the population by means of analysis of available information and the development of relevant recommendations.
Hoogeveen, E K; Kostense, P J; Beks, P J; Mackaay, A J; Jakobs, C; Bouter, L M; Heine, R J; Stehouwer, C D
A high serum total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease. Because it is not known whether the strength of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease, we compared the three separate risk estimates in an age-, sex-, and glucose tolerance-stratified random sample (n=631) from a 50- to 75-year-old general white population. Furthermore, we investigated the combined effect of hyperhomocysteinemia and diabetes mellitus with regard to cardiovascular disease. The prevalence of fasting hyperhomocysteinemia (>14.0 micromol/L) was 25.8%. After adjustment for age, sex, hypertension, hypercholesterolemia, diabetes, and smoking, the odds ratios (ORs; 95% confidence intervals) per 5-micromol/L increment in tHcy were 1.44 (1.10 to 1.87) for peripheral arterial, 1.25 (1.03 to 1.51) for coronary artery, 1.24 (0.97 to 1.58) for cerebrovascular, and 1.39 (1.15 to 1.68) for any cardiovascular disease. After stratification by glucose tolerance category and adjustment for the classic risk factors and serum creatinine, the ORs per 5-micromol/L increment in tHcy for any cardiovascular disease were 1.38 (1.03 to 1.85) in normal glucose tolerance, 1.55 (1.01 to 2.38) in impaired glucose tolerance, and 2.33 (1.11 to 4.90) in non-insulin-dependent diabetes mellitus (P=.07 for interaction). We conclude that the magnitude of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease in a 50- to 75-year-old general population. High serum tHcy may be a stronger (1.6-fold) risk factor for cardiovascular disease in subjects with non-insulin-dependent diabetes mellitus than in nondiabetic subjects.
Drubay, Damien; Caër-Lorho, Sylvaine; Laroche, Pierre; Laurier, Dominique; Rage, Estelle
A significant association has been observed between radon exposure and cerebrovascular disease (CeVD) mortality among French uranium miners, but risk factors for circulatory system diseases (CSD) have not been previously considered. We conducted new analyses in the recently updated (through 2007) French cohort of uranium miners (n = 5,086), which included 442 deaths from CSD, 167 of them from ischemic heart disease (IHD) and 105 from CeVD. A nested case-control study was then set up to collect and investigate the influence of these risk factors on the relationships between mortality from CSD and occupational external gamma ray and internal ionizing radiation exposure (radon and long-lived radionuclides) in this updated cohort. The nested case-control study included miners first employed after 1955, still employed in 1976 and followed up through 2007. Individual information about CSD risk factors was collected from medical files for the 76 deaths from CSD (including 26 from IHD and 16 from CeVD) and 237 miners who had not died of CSD by the end of follow-up. The exposure-risk relationships were assessed with a Cox proportional hazard model weighted by the inverse sampling probability. A significant increase in all CSD and CeVD mortality risks associated with radon exposure was observed in the total cohort [hazard ratios: HRCSD/100 working level months (WLM) = 1.11, 95% confidence interval (1.01; 1.22) and HRCeVD/100 WLM = 1.25 (1.09; 1.43), respectively]. A nonsignificant exposure-risk relationship was observed for every type of cumulative ionizing radiation exposure and every end point [e.g., HRCSD/100WLM = 1.43 (0.71; 2.87)]. The adjustment for each CSD risk factor did not substantially change the exposure-risk relationships. When the model was adjusted for overweight, hypertension, diabetes, hypercholesterolemia and smoking status, the HR/100WLM for CSD, for example, was equal to 1.21 (0.54; 2.75); and when it was adjusted for risk factors selected with the
Dittmar, Michael S; Vatankhah, Bijan; Fehm, Nando P; Schuierer, Gerhard; Bogdahn, Ulrich; Horn, Markus; Schlachetzki, Felix
Middle cerebral artery occlusion (MCAO) in Fischer-344 rats results in a small variance of infarct size. However, complications are frequent especially in aged Fisher-344 rats undergoing endovascular suture occlusion of the middle cerebral artery. Analyzing our experiences with 165 Wistar, 13 Sprague-Dawley and 10 F-344 rats, we compared the incidence of impossible thread advancement and subarachnoid hemorrhage, respectively. Magnetic resonance angiography (MRA) was applied to study the course of the internal carotid artery (ICA) in Fischer and Wistar rats. Finally, we performed a structured review of the literature from 1991 to 2005 evaluating reports on Fischer rats subjected to intraluminal filament MCAO. Complications like fruitless filament advancement or subarachnoid hemorrhage were found to be significantly more frequent in Fischer rats than in other strains. MRA revealed significantly more pronounced kinking of the ICA in F-344 than in Wistar rats. In seven publications available on filament MCAO in F-344 rats, complication rates of 50-100% were reported, corroborating our data. Surgical difficulties accompanied by high complication rates due to their cerebrovascular anatomy make Fischer rats unsuitable for filament MCAO. If the use of Fischer rats for studies on focal cerebral ischemia is indicated, other ischemia models than intraluminal suture occlusion should be chosen.
Talebi, Hossein; Moossavi, Abdollah; Faghihzadeh, Soghrat
Background: Older adults with cerebrovascular accident (CVA) show evidence of auditory and speech perception problems. In present study, it was examined whether these problems are due to impairments of concurrent auditory segregation procedure which is the basic level of auditory scene analysis and auditory organization in auditory scenes with competing sounds. Methods: Concurrent auditory segregation using competing sentence test (CST) and dichotic digits test (DDT) was assessed and compared in 30 male older adults (15 normal and 15 cases with right hemisphere CVA) in the same age groups (60-75 years old). For the CST, participants were presented with target message in one ear and competing message in the other one. The task was to listen to target sentence and repeat back without attention to competing sentence. For the DDT, auditory stimuli were monosyllabic digits presented dichotically and the task was to repeat those. Results: Comparing mean score of CST and DDT between CVA patients with right hemisphere impairment and normal participants showed statistically significant difference (p=0.001 for CST and p<0.0001 for DDT). Conclusion: The present study revealed that abnormal CST and DDT scores of participants with right hemisphere CVA could be related to concurrent segregation difficulties. These findings suggest that low level segregation mechanisms and/or high level attention mechanisms might contribute to the problems. PMID:25679009
Lafreniere, R.G.; Dube, M.P.; Rouleau, G.A.
Unverricht-Luendborg disease (ULD) is a progressive myoclonus epilepsy with an age of onset between 6 and 13 years, myoclonic jerks that progressively worsen, and mental deterioration. ULD shows an autosomal recessive mode of inheritance. The ULD gene has been genetically linked to 21q22.3, and more recently estimated to lie within 0.3 cM of the markers PFKL, D21S25, and D21S154, based on linkage disequilibrium. We have previously identified eight families affected with ULD and shown linkage to 21q22.3. In our efforts to identify the metabolic basis of the disease, we have identified several other families with ULD and are testing them for linkage to 21q22.3 We are also constructing a cosmid and YAC contig of the candidate EPM1 region in 21q22.3 and are in the process of identifying candidate genes therefrom.
Cold, G E; Jensen, F T; Malmros, R
Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed.
Lee, Young-Hoon; Lee, Kun Sei; Jeong, Hyo Seon; Ahn, Hye Mi; Oh, Gyung-Jae
Background This study investigates the perception of the general public regarding the concentration to metropolitan, hospitals of cardiac and cerebrovascular surgeries, and the perceived public need for government policies to resolve this issue. Methods A total of 800 participants were recruited for our telephone interview survey. Quota sampling was performed, adjusting for age and sex, to select by various geographic regions. Sampling with random digit dialing was performed; we called the randomly generated telephone numbers and made three attempts for non-responders before moving on to a different telephone number. Results Our sample population was 818 participants, 401 men (49.0%) and 417 women (51.0%). Our data showed that 85.5% of participants thought that cardiac surgery and neurosurgery patients are concentrated in large hospitals in Seoul. The principle reason for regional patients to want to receive surgery at major hospitals in Seoul was because of poor medical standards associated with regional hospitals (87.7%). We found that a vast majority of participants (97.5%) felt that government policies are needed to even out the clustering of cardiac surgery and neurosurgery patients, and that this clustering may be alleviated if policies that can specifically enhance the quality and the capacity of regional hospitals to carry out surgeries are adopted (98.3%). Conclusion Government policy making must reflect public desiderata, and we suggest that these public health needs may be partially resolved through government-designated cardiac and neurosurgery specialist hospitals in regional areas. PMID:28035297
Weekes, E; Elia, M
The aim of this study was to measure resting energy expenditure (REE) in patients routinely admitted to hospital following a cerebro-vascular accident (CVA). The REE of 15 patients (8 female; 7 male) was measured using indirect calorimetry 24-72 hours after the CVA; 11 patients (7 female; 4 male) were measured again 10-14 days later. Body composition was assessed using skin-fold thickness, near infra-red interactance and bioelectrical impedance techniques. Initial REE in females was 1133 kcal/day (+/-67) and in males 1526 kcal/day (+/-111). There was little or no difference in REE or body composition between the first and second measurements. REE was between 95%-107% of the values predicted by 10 reference tables and equations and up to 118% of that predicted by another. We conclude that the total energy requirements of patients following a stroke are not high, probably because of decreased physical activity and changes in muscular tone subsequent to CVA.
Hughson, R. L.; Shoemaker, J. K.; Blaber, A. P.; Arbeille, Ph.; Zuj, K. A.; Greaves, D. K.
CCISS is a project to study the cardiovascular and cerebrovascular responses of astronauts before, during and after long-duration (>60-day) stays on the International Space Station. The CCISS experiments consist of three phases that are designed to achieve an integrated examination of components responsible for return of blood to the heart, the pumping of blood from the heart and the distribution to the vascular territories including the brain. In this report the data are obtained from the 24-h monitoring of physical activity (Actiwatch on wrist and ankle) and of heart rate (Holter monitor). The data show clear patterns of change in physical activity from predominantly leg-based on Earth to relatively little activity of the ankles with maintained or increased activity of the wrists on ISS. Both on Earth and on ISS the largest changes in heart rate occur during the periods of leg activity. Average heart rate was changed little during the periods of minimal activity or of sleep in comparisons of Earth with in-flight recording both within the first two weeks of flight and the last two weeks. These data clearly show the importance of monitoring heart rate and physical activity simultaneously and show that attempts to derive indicators of autonomic activity from spectral analysis of heart rate variability should not be performed in the absence of knowledge of both variables.
You, Jiang; Volkow, Nora D.; Park, Kicheon; Zhang, Qiujia; Clare, Kevin; Du, Congwu
Occurrence of transient ischemic attacks (TIA) and cerebral strokes is a recognized risk associated with cocaine abuse. Here, we use a rodent model along with optical imaging to study cocaine-induced TIA and the associated dynamic changes in cerebral blood flow velocity (CBFv) and cerebrovasculature. We show that chronic cocaine exposure in mice resulted in marked cortical hypoperfusion, in significant arterial and venous vasoconstriction, and in a sensitized vascular response to an acute cocaine injection. Starting after 10 days of exposure, an acute cocaine challenge to these mice resulted in a TIA, which presented as hemiparalysis and was associated with an abrupt exacerbation of CBFv. The severity of the TIA correlated with the decreases in cortical CBFv such that the greater the decreases in flow, the longer the TIA duration. The severity of TIA peaked around 17–22 days of cocaine exposure and decreased thereafter in parallel to a reorganization of CBFv from superficial to deep cortical layers, along with an increase in vessel density into these layers. Here, we document for the first time to our knowledge evidence of a TIA in an animal model of chronic cocaine exposure that was associated with profound decreases in CBFv, and we revealed that while the severity of the TIA initially increased with repeated exposures, it subsequently improved in parallel to an increase in the vessel density. This suggests that strategies to accelerate cerebrovascular recovery might be therapeutically beneficial in cocaine abusers. PMID:28289715
Saleem, Saqib; Tzeng, Yu-Chieh; Kleijn, W. Bastiaan; Teal, Paul D.
This study sought to determine whether models of cerebrovascular function based on Laguerre-Volterra kernels that account for nonlinear cerebral blood flow (CBF) dynamics can detect the effects of functional cerebral sympathetic blockade. We retrospectively analyzed continuous beat-to-beat blood pressure, middle cerebral blood velocity, and partial-pressure of end-tidal CO2 (PETCO2) recordings from eighteen healthy individuals who were treated with either an oral dose of the α1-adrenergic receptor blocker Prazosin or a placebo treatment. The global principal dynamic modes (PDMs) were analyzed using Laguerre-Volterra kernels to examine the nonlinear system dynamics. Our principal findings were: (1) very low frequency (<0.03 Hz) linear components of first-order kernels for BP and PETCO2 are mutually coupled to CBF dynamics with the ability to separate individuals between control and blockade conditions, and (2) the gains of the nonlinear functions associated with low-pass and ≈0.03 Hz global PDMs for the BP are sensitive to sympathetic blockade. Collectively these results suggest that very low frequency global PDMs for BP may have potential utility as functional biomarkers of sympathetic neurovascular dysfunction which can occur in conditions like autonomic failure, stroke and traumatic brain injury. PMID:28119628
Mahin, L; Chadli, M; Addi, A
Digital diseases of cattle, as defined by the "International Council on Digital Diseases of the Ruminants" were studied on 32 farms with various management systems in Morocco. This study involved 953 cattle without lameness for claw examination and 89 lame cattle for detailed clinical examination and semiological trimming of the eight claws. Claw deformities, interdigital dermatitis and ungular erosion, chronic diffuse aseptic pododermatitis, circumscribed pododermatitis and deep digital diseases were described regarding their prevalence and clinical characteristics, including their distribution on fore and hind limbs, and on antero-medial, antero-lateral, postero-medial and postero-lateral claws. Interrelationships between different digital diseases and relationships between some digital diseases and environmental factors were searched by correlation studies. The results are compared with the characteristics of the same digital diseases in other countries.
Bayliss, George P.; Weinrauch, Larry A.; Gleason, Ray E.; Lee, Annette T.; D'Elia, John A.
Background Diabetic patients on hemodialysis are at high risk of death from cardiovascular disease, and research has suggested that various biologic markers of inflammation, oxidative stress and hemostasis may give added value to clinical information for predicting cardiovascular event (CVE)-free survival. This information could be particularly important in evaluating this population for renal transplant, given the scarcity of organs. We hypothesized that in diabetic patients undergoing renal replacement therapy (RRT) these biologic markers would prove useful in predicting event-free follow-up in a prospective study. Methods One hundred and fifty diabetic (76 type 1, 74 type 2) and 27 non-diabetic stable RRT patients were followed for 0.04–13.69 years for CVE (myocardial infarction, coronary arterial intervention, peripheral arterial bypass or amputation, cerebrovascular accident or carotid artery intervention), cardiac and all-cause mortality. Measured biologic markers of inflammation included the following: Il-6, C reactive protein, fibrinogen; of hemostasis: fibrinogen, plasminogen activator inhibitor (PAI), fibrinolytic activity, von Willebrand factor VII (vWF), platelet-selectin, viscosity and of oxidative stress: advanced glycated end products and antibody to oxidized low-density lipoprotein. For each, upper versus lower tertiles were compared for duration of event-free follow-up. Results Cardiovascular events prior to study entry occurred in 51.3% of DM1, 54.0% of DM2 and 25.9% of DM0 patients. Subsequent cardiovascular events were noted in 31.6% of DM1, 45.9% of DM2 and 11.1% of DM0 patients. All mean levels of biologic markers at baseline were abnormal (P < 0.05). Conclusions In this RRT population, all biologic marker levels except PAI did not improve clinical prediction of events. PMID:26069829
Liao, Kuang-Ming; Lu, Hsueh-Yi
The incidence and prevalence of chronic obstructive pulmonary disease (COPD) is associated with increasing age. Osteoarthritis is also a growing problem in the aging population, and total knee replacement (TKR) is a common surgical procedure for this population. An increasing number of COPD patients are receiving TKR, but few studies have examined the complications and outcomes after TKR in COPD patients. The purpose of this study was to investigate the complications, including mortality, wound infections, hospitalization readmission, pneumonia (PN), and cerebrovascular accidents (CVAs) in patients with COPD after receiving TKR.The National Health Insurance operated by the government is a nationwide health care program with universal coverage in Taiwan. It covers approximately 99% of the total Taiwanese population of 23 million people. In this case-control study, we analyzed the longitudinally linked National Health Insurance Research Database, which consists of a cohort of 1,000,000 randomly selected enrollees retrospectively followed from 1996 to 2010. This study analyzed patients who underwent TKR surgery between January 1, 2004 and December 31, 2009 by identifying the International Classification of Diseases, Ninth Revision, Clinical Modification code. We separated patients into COPD and non-COPD groups. Five study outcomes and complications were measured after TKR, including mortality for 1 and 3 years, wound infections for 1 and 2 years, hospitalization readmission for 30 and 90 days, PN for 30 and 90 days, and CVAs.A total of 3431 patients who underwent TKR surgery were identified, including 358 patients with COPD and 3073 patients without COPD. The COPD group had a higher percentage of 90-day PN (3.7% vs. 1.1%), 30-day readmission (7.0% vs. 4.0%), 30-day CVA (1.7% vs. 0.6%), 90-day CVA (3.9% vs. 2.1%), and 3-year mortality (3.9% vs. 2.1%) than the non-COPD group. COPD was associated with 90-day PN (adjusted hazard ratio[HR)] = 2.12, P = 0.030) after
Akioyamen, Leo; Levine, Mitchell; Sherifali, Diana; O'Reilly, Daria; Frankfurter, Claudia; Pullenayegum, Eleanor; Goeree, Ron; Tsoi, Bernice
Angiotensin receptor blockers (ARBs) are widely used in managing essential hypertension, with considerable evidence available on their short-term efficacy in lowering blood pressure (BP). However, there currently exists limited "pooled" data examining the long-term efficacy of ARB treatment in controlling BP or mitigating cardiovascular and cerebrovascular events. The purpose of this study was to conduct a systematic review and meta-analysis assessing the long-term effects of ARBs as a class on BP control, myocardial infarction, hospitalization for heart failure, cerebrovascular events (ie, stroke), cardiovascular mortality, and all-cause mortality. MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched from inception to March 2015. Two evaluators independently reviewed studies for eligibility. Randomized controlled hypertension trials were included if they reported on ARB efficacy in either BP control (relative to placebo for periods ≥ 6 months) or cardiovascular/cerebrovascular outcomes (relative to non-ARB antihypertensive therapies for periods ≥ 24 months). Studies were pooled with a random-effects model using weighted mean differences (WMDs) and relative risks for continuous and dichotomous outcomes, respectively. A total of 11 articles were included in the narrative synthesis, representing seven unique trials (16,864 participants). Six ARB agents were studied: candesartan, eprosartan, irbesartan, olmesartan, losartan (each represented by one trial arm), and telmisartan (represented by two arms). ARB therapy significantly reduced mean systolic BP (WMD: -4.86; 95% CI: -6.19, -3.53 mm Hg) and diastolic BP (WMD: -2.75; 95% CI: -3.65, -1.86 mm Hg] compared to placebo. The risk of stroke was reduced by 21% in the ARB group compared with alternative antihypertensives (risk ratio: 0.79; 95% CI: 0.66, 0.96). ARBs did not, however, produce statistically significant reductions in the risk of myocardial infarction, heart failure hospitalization, or
1014 patients with benigne gynaecological diseases (functional incontinence of urine with and without displacement, myoma of uterus, ovarian tumors, chronic salpingoophoritis) were examined by means of isotope nephrogram before gynaecological treatment was begun. A group of 156 patients was parallely examined by means of chromocystoscopy and intravenous urography. For judgement of the ING-curves we applicated an extra parameter--the drain value "A"--, through which it was possible to differenciate between emptying disturbances and functional urinary transport disorders. To obtain this value it is necessary to change the position of the patients during examination. Under these conditions approximately 95% of ING-findings conformed with those vaised by intravenous urography. Giving weight to these conditions, we recommend the application of ING in gynaecology as a screening method. Criteria for optimal usage of this method are mentioned.
Nielsen, Philip Rising; Kragstrup, Tue Wenzel; Deleuran, Bent Winding; Benros, Michael Eriksen
Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between hospital admission for an infection and 29 autoimmune diseases. This study shows that infections are risk factors for a broad spectrum of autoimmune diseases in a dose-response and temporal manner, in agreement with the hypothesis that infections are an environmental risk factor contributing to the etiology of autoimmune diseases together with genetic factors.
Peng, Ying Y; Uprichard, James
Anaemia is a condition in which the number of red cells necessary to meet the body's physiological requirements is insufficient. Iron deficiency anaemia and the anaemia of chronic disease are the two most common causes of anaemia worldwide;(1) iron homeostasis plays a pivotal role in the pathogenesis of both diseases. An understanding of how iron studies can be used to distinguish between these diseases is therefore essential not only for diagnosis but also in guiding management. This review will primarily focus on iron deficiency anaemia and anaemia of chronic disease; however, iron overload in anaemia will also be briefly discussed.
Myotonic dystrophy type 1 (Steinert's disease) is a multisystem disorder with autosomal dominant inheritance. This disease is associated with the presence of an abnormal expansion of a cytosine thymine-guanine (CTG) trinucleotide repeat on chromosome 19q13.3. Because of rhythmic complications, the place for systematic electrophysiological study (EPS) has to be discussed.
Myotonic dystrophy type 1 (Steinert's disease) is a multisystem disorder with autosomal dominant inheritance. This disease is associated with the presence of an abnormal expansion of a cytosine thymine-guanine (CTG) trinucleotide repeat on chromosome 19q13.3. Because of rhythmic complications, the place for systematic electrophysiological study (EPS) has to be discussed. PMID:18928563
Snowdon, David A.
Describes a woman who maintained high cognitive test scores until her death at 101 years of age despite anatomical evidence of Alzheimer's disease. The woman was part of a larger "Nun Study" in which 678 sisters donated their brains to teach others about the etiology of aging and Alzheimer's disease. Findings are discussed. (RJM)
Forbus, William R., III
A case study focuses on the characteristics and physical management of a 15-year-old with Prader-Willi Syndrome, a birth defect associated with hypotonia, insatiable appetite, hypogonadism, central nervous system dysfunction, and abnormal growth and development . A literature review addresses studies dealing with behavior modification of obesity…
Five years after their initial derivation from mouse somatic cells, induced pluripotent stem (iPS) cells are an important tool for the study of neurological diseases. By offering an unlimited source of patient-specific disease-relevant neuronal and glial cells, iPS cell-based disease models hold enormous promise for identification of disease mechanisms, discovery of molecular targets and development of phenotypic screens for drug discovery. The present review focuses on the recent advancements in modeling neurological disorders, including the demonstration of disease-specific phenotypes in iPS cell-derived neurons generated from patients with spinal muscular atrophy, familial dysautonomia, Rett syndrome, schizophrenia and Parkinson disease. The ability of this approach to detect treatment effects from known therapeutic compounds has also been demonstrated, providing proof of principle for the use of iPS cell-derived cells in drug discovery. PMID:21936964
Mochizuki, Ronald M.; Richter, Kenneth J.
A case report is presented of a 32 year-old male bodybuilder who sustained an ischemic cerebrovascular accident and showed signs of cardiomyopathy. Although no cause was found, the man had been taking steroids for 16 years. Harmful effects of steroid use are discussed. (IAH)
Grabowski, Gregory; Robertson, Ryan N.; Barton, Blair M.; Cairns, Mark A.; Webb, Sharon W.
Study Design Retrospective comparative study. Objective To compare strict Biffl criteria to more-liberal criteria for computed tomography angiography (CTA) when screening for blunt cerebrovascular injury (BCVI). Methods All CTAs performed for blunt injury between 2009 and 2011 at our institution were reviewed. All patients with cervical spine fractures who were evaluated with CTA were included; patients with penetrating trauma and atraumatic reasons for imaging were excluded. We then categorized the patients' fractures based on the indications for CTA as either within or outside Biffl criteria. For included subjects, the percentage of studies ordered for loose versus strict Biffl criteria and the resulting incidences of BCVI were determined. Results During our study period, 1,000 CTAs were performed, of which 251 met inclusion criteria. Of the injuries, 192 met Biffl criteria (76%). Forty-nine were found to have BCVIs (19.5%). Forty-one injuries were related to fractures meeting Biffl criteria (21.4%), and 8 were related to fractures not meeting those criteria (13.6%). The relative risk of a patient with a Biffl criteria cervical spine injury having a vascular injury compared with those imaged outside of Biffl criteria was 1.57 (p = 0.19). Conclusions Our data demonstrates that although cervical spine injuries identified by the Biffl criteria trend toward a higher likelihood of concomitant BCVI (21.4%), a significant incidence of 13.6% also exists within the non-Biffl fracture cohort. As a result, a more-liberal screening than proposed by Biffl may be warranted. PMID:27781188
Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.
The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association (Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.
Pina-Jover, María; Martinez-Del Villar, María; Lillo-Laguna, Lucía; Jadraque-Rodriguez, Rocío; Martinez-Pastor, Pedro; Jover-Cerda, Jenaro; Gomez-Gosalvez, Francisco
INTRODUCTION. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. PATIENTS AND METHODS. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. RESULTS. None of the 10 patients studied presented any relevant events in the mothers' medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. CONCLUSIONS. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible.
Ock, Minsu; Lee, Jin Yong; Oh, In Hwan; Park, Hyesook; Yoon, Seok Jun; Jo, Min Woo
Disability weight for each disease plays a key role in combining years lived with disability and years of life lost in disability adjusted life year. For the Korean Burden of Disease 2012 study, we have conducted a re-estimation of disability weights for causes of disease by adapting the methodology of a recent Global Burden of Disease study. Our study was conducted through a self-administered web-based survey using a paired comparison (PC) as the main valuation method. A total of 496 physicians and medical college students who were attending in third or fourth grade of a regular course conducted the survey. We applied a probit regression on the PC data and computed the predicted probabilities of each cause of disease from the coefficient estimates of the probit regression. We used 'being dead (1)' and 'full health (0)' as anchor points to rescale the predicted probability of each cause of disease on a scale of 0 to 1. By this method, disability weights for a total of 228 causes of disease were estimated. There was a fairly high correlation between the disability weights of overlapping causes of disease from this study and a previous South Korean study despite the differences in valuation methods and time periods. In conclusion, we have shown that disability weights can be estimated based on a PC by including 'full health' and 'being dead' as anchor points without resorting to a person trade-off. Through developments in the methodology of disability weights estimation from this study, disability weights can be easily estimated and continuously revised.
Disability weight for each disease plays a key role in combining years lived with disability and years of life lost in disability adjusted life year. For the Korean Burden of Disease 2012 study, we have conducted a re-estimation of disability weights for causes of disease by adapting the methodology of a recent Global Burden of Disease study. Our study was conducted through a self-administered web-based survey using a paired comparison (PC) as the main valuation method. A total of 496 physicians and medical college students who were attending in third or fourth grade of a regular course conducted the survey. We applied a probit regression on the PC data and computed the predicted probabilities of each cause of disease from the coefficient estimates of the probit regression. We used 'being dead (1)' and 'full health (0)' as anchor points to rescale the predicted probability of each cause of disease on a scale of 0 to 1. By this method, disability weights for a total of 228 causes of disease were estimated. There was a fairly high correlation between the disability weights of overlapping causes of disease from this study and a previous South Korean study despite the differences in valuation methods and time periods. In conclusion, we have shown that disability weights can be estimated based on a PC by including 'full health' and 'being dead' as anchor points without resorting to a person trade-off. Through developments in the methodology of disability weights estimation from this study, disability weights can be easily estimated and continuously revised. PMID:27775250
Atadzhanov, M; Zumla, A; Mwaba, P
Objective: The aims of this study were (A) to determine inheritance patterns of familial Parkinson's disease in three different geographical areas (Russia, Uzbekistan, and Zambia); (B) compare clinical characteristics of familial with sporadic Parkinson's disease; and (C) assess whether there were ethnic differences in clinical manifestations of the disease. Methods: Fifty two index cases of familial Parkinson's disease in Moscow, 55 in Tashkent, and 27 in Lusaka were selected on the basis of the typical clinical features of Parkinson's disease with a familial history. The sex ratio, transmission patterns, and segregation ratio were determined by pedigree analysis. Results: Familial Parkinson's disease was found in all three countries (30 families in Russia, 12 in Uzbekistan, and seven in Zambia), and appeared more common in Russia. Both autosomal dominant and autosomal recessive patterns of inheritance were seen, but autosomal dominance was more common in all countries. Conclusions: In all three countries men have a higher risk of developing Parkinson's disease than women and there are ethnic differences in clinical manifestations of the disease. The onset of both familial and sporadic Parkinson's disease in Zambian patients occurs at a younger age and is associated with slow progression and a benign course, and generally responds well to levodopa treatment. PMID:15701745
Gowert, Nina S; Donner, Lili; Chatterjee, Madhumita; Eisele, Yvonne S; Towhid, Seyda T; Münzer, Patrick; Walker, Britta; Ogorek, Isabella; Borst, Oliver; Grandoch, Maria; Schaller, Martin; Fischer, Jens W; Gawaz, Meinrad; Weggen, Sascha; Lang, Florian; Jucker, Mathias; Elvers, Margitta
Alzheimer's disease (AD) is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA). Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß) peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS) and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.
Day, Linda Susan; Parnell, Martha M.
The 10-year longitudinal case study describes the history, speech therapy program, and treatment results for an adult male with Wilson's disease, a genetically based metabolic progressive neurological disorder which includes severe speech problems. (DB)
Little, Mark P
Exposure to therapeutic doses of ionizing radiation is associated with damage to the heart and coronary arteries. However, only recently have studies with high-quality individual dosimetry data allowed this risk to be quantified while also adjusting for concomitant chemotherapy, and medical and lifestyle risk factors. At lower levels of exposure the evidence is less clear. In this article I review radiation-associated risks of circulatory disease in groups treated with radiotherapy for malignant and non-malignant disease, and in occupationally- or environmentally-exposed groups receiving rather lower levels of radiation dose, also for medical diagnostic purposes. Results of a meta-analysis suggest that excess relative risks per unit dose for various types of heart disease do not exhibit statistically significant (p>0.2) heterogeneity between studies. Although there are no marked discrepancies between risks derived from the high-dose therapeutic and medical diagnostic studies and from the moderate/low dose occupational and environmental studies, at least for ischemic heart disease and stroke there are indications of larger risks per unit dose for lower dose rate and fractionated exposures. Risks for stroke and other types of circulatory disease are significantly more variable (p<0.0001), possibly resulting from confounding and effect-modification by well known (but unobserved) risk factors. Adjustment for any of mean dose, dose fractionation or age at exposure results in the residual heterogeneity for cerebrovascular disease becoming non-significant. The review provides strong evidence in support of a causal association between both low and high dose radiation exposure and most types of circulatory disease.
I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.
Andreev, A G
Basing on epidemiological, prospective and clinicopsychological data obtained on 1900 industrial workers of Nizhni Novgorod city, the system of psychoprophylaxis and psychotherapy of cerebrovascular diseases has been developed. The system of psychoprophylaxis was used with consideration of the disease stage and phase, psychic and psychosomatic status in risk groups, in subjects with initial and apparent symptoms of cerebrovascular failure. The psychoprophylactic system proved effective in the conditions of a large industrial enterprise.
I started my life as a medical doctor at Amagasaki Prefectural Hospital after graduation from the Faculty of Medicine, Kyoto University in September 1971. I joined the newly established section of nephrology in the second year. The chief was Dr. Kazuro Kanatsu who had just moved from Kyoto University at the time of the campus disturbances. Dr. Kanatsu not only oriented me in clinical nephrology, but also guided me in medical research. I used to go to the laboratory of Dr. Tadao Tamura, Kyoto University once a week to learn renal biopsy study. In 1977, I entered the Department of Pathology, Postgraduate School of my university to learn immunopathology from Prof. Yoshihiro Hamashima. In the second year, I was willingly involved in the research group on murine SLE organized by the newly invited associate professor, Dr. Toshikazu Shirai, who taught young researchers such as myself how to consider, practice and enjoy experiments. In 1982, I went abroad to Prof. Peter Miescher, University of Geneva, who was a friend of Prof. Hamashima and organized immunopathology research groups. In the laboratory of Prof. Shozo Izui, I performed an isoelectric focused study on anti-DNA antibodies in lupus-prone mice and identified the pathogenetic role of the clonal expansion of autoantibodies. After 3 years, I came back to the 3rd Division of Internal Medicine of my university. Meanwhile, Prof. Chuichi Kawai guided me to go back to Prof. Hamashima's Pathology Department, where I helped young doctors publish a series of papers, including studies on SLE and a murine model of IgA glomerulonephritis. Later, I was obliged to leave the Pathology Department, and moved to Himeji National Hospital in 1992 as a clinical nephrologist by the invitation of the Director, Dr. Tamura. At that time I was very much encouraged by Prof. Shirai at Juntendo University, who gave me a letter with an old saying "Jinkan itarutokoro seizan ari". After 3 years, I moved to Kitano Hospital, Osaka, where I learned
Ousmane, Cisse; Lemine, Dadah Samy Mohamed; Fatoumata, Ba; Makhtar, Ba El Hadji; Soda, Diop Marieme; Side, Diagne Ngor; Dieynaba, Sow Adjaratou; Modji, Basse Anna; Kamadore, Touré; Moustapha, Ndiaye; Gallo, Diop Amadou; Mansour, Ndiaye Mouhamadou
Cerebrovascular accident (CVA) is defined as the rapid development of localized or global clinical signs of neurological dysfunction with no apparent cause other than that of vascular origin. A variety of risk factors have been identified and associated with the occurrence of Ischemic CVA, including glucose and lipid metabolism disturbances. We conducted a retrospective study at the Clinic of Neurology, Fann. Our study focused on medical records of patients with ICVA confirmed by imaging, hospitalized from January 1 to December 31 2010. All patients underwent complete lipid profile (total cholesterol, triglycerides, HDL; LDL level was calculated using Friedwald formula), kidney function tests and fasting blood sugar test were performed within 48 hours of admission. Data were analysed using univariate technique and then using bivariate technique tanks to SPSS 16.0 software. We collected 235 files. We here report a case series of patients between ages 10-99 years, with an average age of 67,06 years. Males were 42,55%, sex-ratio was 0,74 in favour of women. 26% of cases had impaired fasting glucose levels during the acute phase of ICVA. The lipid profile showed an increase in total cholesterol level in 52.34% of patients. Low levels of HDL cholesterol were found in 34.47% of patients. Hypertriglyceridemia was only observed in 3% of patients. LDL levels were high in 12,76% of patients. Atherogenicity index was high in 25,53% of patients. Disturbances of blood glucose and lipid profile are often associated with ICVA and should be taken into account to ensure better secondary prevention.
The nephrotic syndrome, glomerulonephritis, disseminated lupus erythematosus and the Fanconi syndrome show characteristic changes with electron microscopy. Experimental studies of animals were carried out to determine the significance of such changes by observing reactions that occur under carefully controlled conditions. A lesion with collagen deposition that was found in the centrolobular region of glomeruli sheds new light on the function of this region. This evidence must be considered in developing an understanding of how the production of urine is controlled. Fluid-filled compartments and various bodies associated with the ultrastructure of tubule cells can be produced under conditions which suggest that these structures play a role in tubular resorption. ImagesFigure 1, 2.Figure 3.Figure 4, 5.Figure 6, 7.Figure 8, 9.Figure 10.Figure 11, 12.Figure 13, 14.Figure 15, 16.Figure 17. PMID:13759386
Clements, Dylan N; Short, Andrea D; Barnes, Annette; Kennedy, Lorna J; Ferguson, John F; Butterworth, Steven J; Fitzpatrick, Noel; Pead, Matthew; Bennett, David; Innes, John F; Carter, Stuart D; Ollier, William E R
Canine osteoarthritis (OA) commonly occurs in association with articular diseases, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament rupture (CCLR). We hypothesized that a common genomic risk for the development of canine joint disease and canine OA would be identified by evaluating the allele frequencies of candidate gene single nucleotide polymorphisms (SNPs) in dogs with OA associated with different articular diseases when compared with a general population of breed-matched dogs. DNA was extracted from blood samples obtained from Labrador Retrievers and Golden Retrievers surgically treated for ED, HD, and CCLR and confirmed to have radiographic evidence of OA. One hundred and thirteen SNPs in 20 candidate genes were genotyped. No significant associations were identified for SNPs or haplotypes in the candidate genes for the diseases evaluated. The candidate gene approach for the study of genetic association is unlikely to be successful for complex canine diseases such as OA without prior trait mapping evaluation.
Wang, Ying-ying; Yang, Jin-sheng
In order to explore characteristics of clinical diseases treated by scraping therapy, summarize laws of clinical application of scraping therapy, and prospect for research direction of scraping therapy in future, collect 437 articles about scraping therapy between 1994-2007 and analyze and summarize the treated diseases and methods of scraping therapy. Results indicate that scraping therapy has been widely applied to commonly encountered diseases and frequently encountered diseases in departments of internal medicine, surgery, gynecology and pediatrics, etc. with more obvious therapeutic effects. Clinically, it can combine with acupuncture and moxibustion, cupping, massage, blood-letting puncture and other methods. In future, the studies on standardization of manipulation and standards for assessment of therapeutic effect, suitable diseases and the mechanisms of scraping therapy, and development of tools and media, etc. of scraping therapy should be strengthened.
Hin, Harold; Bird, Graham; Fisher, Peter; Mahy, Nick; Jewell, Derek
Objectives To provide evidence of underdiagnosis of coeliac disease and to describe the main presenting symptoms of coeliac disease in primary care. Design Case finding in a primary care setting by testing for coeliac disease by using the endomysial antibody test. Setting Nine surgeries in and around a market town in central England, serving a population of 70 000. Participants First 1000 patients screened from October 1996 to October 1997. Outcome measures Determination of endomysial antibody titre of patients fulfilling the study criteria, followed by small intestine biopsy of those with positive results. Results The 30 patients (out of 1000 samples) with positive results on the endomysial antibody test all had histological confirmation on small intestine biopsy. The commonest mode of presentation (15/30) was anaemia of varying severity. Most patients (25/30) presented with non-gastrointestinal symptoms. Specificity of the endomysial antibody test was 30/30. Conclusions Underdiagnosis and misdiagnosis of coeliac disease are common in general practice and often result in protracted and unnecessary morbidity. Serological screening in primary care will uncover a large proportion of patients with this condition and should be made widely available and publicised. Coeliac disease should be considered in patients who have anaemia or are tired all the time, especially when there is a family history of the disease. Key messagesGeneral practitioners currently see many people with undiagnosed coeliac diseaseThe most likely presentation is a combination of microcytic anaemia, past or present, a family history of the disease, and feeling tired all the timeEstimations of endomysial antibody and IgA are reliable diagnostic toolsThe prevalence of coeliac disease in Britain is higher than the accepted figure of 1:1000 populationIncreased awareness of the extra intestinal manifestations of coeliac disease, coupled with a low threshold for serological testing, will uncover a
Fan, Jui-Lin; Subudhi, Andrew W; Evero, Oghenero; Bourdillon, Nicolas; Kayser, Bengt; Lovering, Andrew T; Roach, Robert C
The present study is the first to examine the effect of high-altitude acclimatization and reexposure on the responses of cerebral blood flow and ventilation to CO2. We also compared the steady-state estimates of these parameters during acclimatization with the modified rebreathing method. We assessed changes in steady-state responses of middle cerebral artery velocity (MCAv), cerebrovascular conductance index (CVCi), and ventilation (V(E)) to varied levels of CO2 in 21 lowlanders (9 women; 21 ± 1 years of age) at sea level (SL), during initial exposure to 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon reexposure to altitude following either 7 (POST7) or 21 days (POST21) at low altitude (1,525 m). In the nonacclimatized state (ALT1), MCAv and V(E) responses to CO2 were elevated compared with those at SL (by 79 ± 75% and 14.8 ± 12.3 l/min, respectively; P = 0.004 and P = 0.011). Acclimatization at ALT16 further elevated both MCAv and Ve responses to CO2 compared with ALT1 (by 89 ± 70% and 48.3 ± 32.0 l/min, respectively; P < 0.001). The acclimatization gained for V(E) responses to CO2 at ALT16 was retained by 38% upon reexposure to altitude at POST7 (P = 0.004 vs. ALT1), whereas no retention was observed for the MCAv responses (P > 0.05). We found good agreement between steady-state and modified rebreathing estimates of MCAv and V(E) responses to CO2 across all three time points (P < 0.001, pooled data). Regardless of the method of assessment, altitude acclimatization elevates both the cerebrovascular and ventilatory responsiveness to CO2. Our data further demonstrate that this enhanced ventilatory CO2 response is partly retained after 7 days at low altitude.
El-Tallawy, Hamdy N; Farghaly, Wafaa MA; Shehata, Ghaydaa A; Abdel-Hakeem, Nabil M; Rageh, Tarek A; Badry, Reda; Kandil, Mahmoud R
Background and purpose Stroke is a medical emergency that can cause permanent neurological damage, complications, and disability. We aim to determine the epidemiology of non-fatal cerebrovascular stroke (CVS) and transient ischemic attacks (TIAs) in Al Quseir City, Red Sea, Egypt. Methods The total population (n=33,285) was screened through a door to door study by three specialists of neurology and 15 female social workers (for demographic data collection). All suspected stroke patients were subjected to a full clinical examination, computerized tomography (CT) and/or magnetic resonance imaging (MRI) of their brain, blood sugar, lipogram, serum uric acid, complete blood cells, blood urea, and serum creatinine, as well as evaluated by Barthel Index and Scandinavian Stroke Scale. Carotid doppler, echocardiography, and thyroid functions were done for selected cases. Results CVS was recorded among 130 patients out of 19,848 subjects aged 20 years and more, yielding a total prevalence of 6.55/1,000 population. From June 1, 2010 to May 31, 2011, 36 patients were recorded to have stroke within 1-year, yielding an incidence rate of 1.81/1,000. Prevalence and incidence rates were higher among males than females, and both indices increased steadily with advancing age to reach the highest prevalence (37.02/1,000) and incidence rate (9.5/1,000) among aged persons 60 years and more. Conclusion The prevalence of non-fatal stroke in Al Quseir city (6.55/1,000) was at the lower range of that recorded in developing countries (5–10/1,000) and slightly higher than that recorded in industrialized countries (5/1,000 population). Ischemic stroke is the most common type of stroke. The prevalence of TIAs was 0.15/1,000. PMID:24293992
Tong, Yunjie; Bergethon, Peter R.; Frederick, Blaise d.
Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral vasculature to a dilatory stimulus and is an important indicator of brain vascular reserve. fMRI has been proven to be an effective imaging technique to obtain the CVR map when the subjects perform CO2 inhalation or the breath holding task (BH). However, the traditional data analysis inaccurately models the BOLD using a boxcar function with fixed time delay. We propose a novel way to process the fMRI data obtained during a blocked BH by using the simultaneously collected near infrared spectroscopy (NIRS) data as regressor1. In this concurrent NIRS and fMRI study, 6 healthy subjects performed a blocked BH (5 breath holds with 20s durations intermitted by 40s of regular breathing). A NIRS probe of two sources and two detectors separated by 3 cm was placed on the right side of prefrontal area of the subjects. The time course of changes in oxy-hemoglobin (Δ[HbO]) was calculated from NIRS data and shifted in time by various amounts, and resampled to the fMRI acquisition rate. Each shifted time course was used as regressor in FEAT (the analysis tool in FSL). The resulting z-statistic maps were concatenated in time and the maximal value was taken along the time for all the voxels to generate a 3-D CVR map. The new method produces more accurate and thorough CVR maps; moreover, it enables us to produce a comparable baseline cerebral vascular map if applied to resting state (RS) data.
Robbins, Miriam R
Neurologic diseases can have a major impact on functional capacity. Patients with neurologic disease require individualized management considerations depending on the extent of impairment and impact on functional capacity. This article reviews 4 of the more common and significant neurologic diseases (Alzheimer disease, cerebrovascular accident/stroke, multiple sclerosis, and Parkinson disease) that are likely to present to a dental office and provides suggestions on the dental management of patients with these conditions.
Farrell, Maxwell J.; Berrang-Ford, Lea; Davies, T. Jonathan
Determining the factors that influence the transmission of parasites among hosts is important for directing surveillance of animal parasites before they successfully emerge in humans, and increasing the efficacy of programs for the control and management of zoonotic diseases. Here we present a review of recent advances in the study of parasite sharing, wildlife ecology, and epidemiology that could be extended and incorporated into proactive surveillance frameworks for multi-host infectious diseases. These methods reflect emerging interdisciplinary techniques with significant promise for the identification of future zoonotic parasites and unknown reservoirs of current zoonoses, strategies for the reduction of parasite prevalence and transmission among hosts, and decreasing the burden of infectious diseases.
Popov, Dmitri; Maliev, Slava
Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity
Deen, Jacqueline L; von Seidlein, Lorenz; Clemens, John D
With limited healthcare resources, rational prioritization of healthcare interventions requires knowledge and analysis of disease burden. In the absence of actual disease-burden data from less-developed countries, various types of morbidity and mortality estimates have been made. Besides having questionable reliability, these estimates do not capture the full burden of a disease since they provide only the number of cases and deaths. The modelling methods that include disability are more comprehensive but are difficult to understand, and their reliability is affected by baseline approximations. To provide policy-makers with information needed for rational decision-making, the Diseases of the Most Impoverished (DOMI) Programme of the International Vaccine Institute has used a multidisciplinary approach to describe the burden of disease due to typhoid fever, shigellosis, and cholera. Recognizing the relative advantages and disadvantages of various methodologies, the programme employs passive clinic-based surveillance in defined communities to provide prospective data. The prospective data are complemented with retrospectively-collected information from existing sources, frequently less accurate and complete but readily available for the whole population over extended periods. To create a more complete picture, economic and qualitative studies specific to each disease are incorporated in these prospective studies. The goal is to achieve a more complete and realistic picture by combining the results of these various methodologies, acknowledging the strengths and limitations of each. These projects also build in-country capacity in terms of treatment, diagnosis, epidemiology, and data management.
Haddock, K C
Canine heartworm disease is a mosquito vectored illness resulting from parasitization by the filariid worm Dirofilaria immitis. While presenting some danger to humans, the filariid has its greatest impact on the canine population. In recent years the disease has become established throughout much of the United States, perhaps as the result of diffusion from a suspected hearth in the southeastern coastal plain. While its distribution is known in general terms, much research remains to be done to assess the pattern of distribution as well as the impact of D. immitis on canine populations and their human owners for many locales. The present study provides a review of the literature on the parasite; on its distribution, particularly in the United States; and on the ecology of canine heartworm disease. A pilot study is presented which emphasizes the problems encountered in establishing a data base for observations on the disease at the local level.
Zhao, Jikuang; Wu, Xizheng; Nie, Sheng; Gao, Xiang; Sun, Jie; Li, Keqin; Zhang, Tiefeng; Huang, Yi
Objective CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. Methods A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. Results We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p<0.001) and total cholesterol (TC) (p<0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p>0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08–1.25; p<0.0001, random-effect method). Conclusion Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese. PMID:28138111
Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy
Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647
This contribution describes two recent computational studies related to proteins involved in Parkinson's Disease (PD). The first focuses on the interplay between dopamine and α-synuclein (AS), which plays a central role in PD (unpublished results). The second deals with the protein DJ-1, whose mutations are present in patients suffering from familiar PD . Computational methods are used to investigate the relationship between such mutations and the protein oligomeric state, which may be important for the progression of the disease.
Rodríguez, A. O.
In vivo Magnetic Resonance Spectrocopy (MRS) was applied to study Huntington's disease. Two solvent-suppressed and single-voxel MRS methods were used: PRESS and STEAM. We applied these popular MRS sequences to Huntington's disease patients (HD) and healthy volunteers (HV). We also compared our spectra between HD and HV as well the these two modalities. Spectra results are reported for HD and HV for both MRS schemes.
Speliotes, Elizabeth K.
Sequencing of the human genome has opened up many opportunities to learn about our own genetic susceptibilities to disease. In this Foreword to this issue of Seminars in Liver Disease, I provide some required background to understanding genome-wide association analyses in general, including a list of terms (Table 1) often used in such studies. Five areas of particular significance are then reviewed in detail in the articles that follow. PMID:26676811