Occurrence Of Cerebrovascular Disease Research Articles

Quantitative Thermal Stimulation Using Therapeutic Ultrasound to Improve Cerebral Blood Flow and Reduce Vascular Stiffness.

It is important to improve cerebrovascular health before the occurrence of cerebrovascular disease, as it has various aftereffects and a high recurrence rate, even with appropriate treatment. Various medical recommendations for preventing cerebrovascular diseases have been introduced, including smoking cessation, exercise, and diet. However, the effectiveness of these methods varies greatly from person to person, and their effects cannot be confirmed unless they are practiced over a long period. Therefore, there is a growing need to develop more quantitative methods that are applicable to the public to promote cerebrovascular health. Thus, in this study, we aimed to develop noninvasive and quantitative thermal stimulation techniques using ultrasound to improve cerebrovascular health and prevent cerebrovascular diseases. This study included 27 healthy adults in their 20s (14 males, 13 females). Thermal stimulation using therapeutic ultrasound at a frequency of 3 MHz was applied to the right sternocleidomastoid muscle in the supine posture for 2 min at four intensities (2.4, 5.1, 7.2, and 10.2 W/cm2). Diagnostic ultrasound was used to measure the peak systolic velocity (PSV), heart rate (HR), and pulse wave velocity (PWV) in the right common carotid artery (CCA), and the physiological changes were compared between intervention intensities. Compared to pre-intervention (preI), the PSV showed a significant increase during intervention (durI) at intensities of 7.2 W/cm2 and 10.2 W/cm2 (p = 0.010 and p = 0.021, respectively). Additionally, PWV showed a significant decrease for post-intervention (postI) at 7.2 W/cm2 and 10.2 W/cm2 (p = 0.036 and p = 0.035, respectively). However, the HR showed no significant differences at any of the intensities. The results demonstrate that an intervention at 3 MHz with an intensity of 7.2 W/cm2 or more can substantially increase cerebral blood flow and reduce arterial stiffness. Therefore, the use of therapeutic ultrasound of appropriate intensity is expected to improve the cerebral blood flow and reduce vascular stiffness to maintain cerebral blood flow at a certain level, which is closely related to the prevention and treatment of cerebrovascular diseases, thereby improving cerebrovascular health.

Serum uric acid as a predictor of cardio- and cerebro-vascular diseases in maintenance hemodialysis patients.

Background: Hyperuricemia is associated with an increased risk of cardio-and cerebrovascular disease (CVD) in general population. However, in the hemodialysis (HD) patients, low serum uric acid (SUA) increases the risk of mortality. Considering that CVD is the principal cause of death among maintenance HD patients, the present study aimed to determine the predictive value of SUA for CVD outcome in this population.Methods: In this two-year follow-up prospective study, 205 outpatients under maintenance HD were enrolled from March 2017 to 2020. Patients' demographic data, underlying diseases, and the results of serum tests, as well as two-year follow-up results of CVD events and mortality were recorded.Results: A total of 130 (63%) patients were eligible for analysis; 62.9% were male; mean age of participants was 59±13years. At follow-up, coronary artery disease was observed in 43.2%, peripheral artery disease in 26.5%, and cerebrovascular disease in 20.5%; angiography was required in 52.3% and 4.5% died of CVD. SUA was ≤5.4 mg/dL in 52 patients, 5.5-6.1 mg/dL in 19, and ≥6.2 mg/dL in 59 patients with significant difference based on mean age, sex distribution, occurrence of cerebrovascular disease and cardiovascular mortality (P<0.05). Patients with cerebrovascular disease had a significantly lower SUA levels (P=0.006). Logistic regression showed the significant effect of SUA on the occurrence of cerebrovascular disease (P=0.008).Conclusion: Low SUA can predict two-year incidence of cerebrovascular disease in HD patients. However, SUA levels did not show significant predictive effect on two-year coronary events, peripheral artery disease and cardiovascular mortality.

Acute Effects of Metrological Factors on Cerebrovascular Diseases among Type2 Diabetes Patients: case crossover evidence from Beijing, China

Background: Acute effects of metrological factors on cerebrovascular diseases (CBVD) have become a growing public health concern. However, the impact of those factors on CBVD among type 2 diabetes (T2D) patients has not been well studied in the study area. The main aim of this study was to assess the acute effects of metrological factors including temperature, relative humidity and atmospheric pressure on incidence of CBVD among type 2 diabetes patients in Beijing, China. Methods: Data was obtained from 258 large general hospitals from the Beijing Public Health Information Center Cardiovascular Case Database and China. Meteorological Administration covering 16 districts in Beijing from 2014 to 2018. Time-stratified case crossover design with a distributed lag nonlinear model (DLNM) was used by considering 27 lag days on CBVD admissions. Results: Within five years (January 2014–December 2018), a total of 223,216 cases for cerebrovascular disease were collected after excluding nonlocal admissions, of which 9,541 (4.27%), 149,757 (67.09%), 7,444 (3.33%), 31,356 (14.05%), and 23,912 (10.71%) were hospitalized for hemorrhagic stroke, ischemic stroke, atherosclerosis, intracranial aneurysm, and apoplexy sequela, respectively. In short, male participants and elderly individuals (≥65 years) accounted for 57.6% and 61.7%, respectively. Generally, the cumulative exposure-response curve for temperature was almost inverted “V”-shaped, with a slight increase at concentrations of higher than 25°C. The cumulative exposure response curve for relative humidity was almost linear. The cumulative exposure-response curves for atmospheric pressure were V-shaped, which meant that both high and low concentrations of atmospheric pressure may increase the risk of cerebrovascular disease incidence among patients with T2D. Conclusions: The results of this study indicate that both an increase and a decrease in temperature and atmospheric pressure had a significant association with the occurrence of cerebrovascular disease among co morbid patients with diabetes. This study provides evidence of the short term effects of metrological factors on hospital admissions of CBVD among T2D patients. Keywords: Keywords: Admission; Beijing; Cerebrovascular disease; Distributed lag nonlinear model; Metrological factors, Type 2 diabetes

Cerebrovascular Disease after Allogeneic Hematopoietic Stem Cell Transplantation: Incidence, Manifestations, Risk and Clinical Outcome

BackgroundThe incidence, manifestations and risk of cerebrovascular disease (CVD) are not well known in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). CVD, including ischemic or hemorrhagic stroke and posterior reversible encephalopathy syndrome (PRES), are important and potentially life-threatening post-transplant complications. Notably, there are few supporting results to explore these complications. We therefore aim to investigate the incidence, risk factors, and survival of post-transplant CVD.Patients and MethodsWe included in this study 459 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2015. A total 24 patients documented post-transplant ischemic or hemorrhagic stroke and PRES according to clinical neurologic signs and brain MRI. Clinical features, cumulative incidence, risk factors and survival for post-transplant CVD in recipients of HSCT were collected and analyzed.ResultsPost-transplant CVD occurred in 24 (5.2%) of 459 HSCT patients. One patient suffered from PRES initially, and subsequent ischemic stroke two months later. The cumulative incidences at days 100, one year and two years were 0.8%, 2.8% and 3.2% in ischemic stroke (n = 10), and 1.2%, 2.2% and 3.0% in hemorrhagic stroke (n = 10), respectively. In addition, the cumulative incidences of PRES (n = 5) at days 100, one year and two years were 0.2%, 1.2% and 1.2%, respectively. In the multivariate analysis, thrombotic microangiopathy (TMA) prior to CVD (adjusted hazard ratio [HR] 10.30, 95% confidence interval [CI]: 3.37-31.51) and high-dose ara-c (HiDAC) ≥ 3 courses prior to transplant (adjusted HR 4.91, 95% CI: 1.42-16.95) were identified as independent risk factors of post-transplant CVD. There was a trend as a risk factor in patients with grade III-IV acute GVHD (P= 0.094). For patients with post-transplant stroke, there were significantly lower disease-free survival (P= 0.016) and overall survival (P= 0.004).ConclusionThe occurrence of CVD, especially for ischemic or hemorrhagic stroke after allogeneic HSCT, was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of post-transplant CVD play roles to improve outcome. Patients with TMA prior to CVD and treatment of more than three HiDAC courses prior to transplant are at risk of CVD. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of this complication.. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

MBL2 gene polymorphisms are not related to the occurrence of cerebrovascular disease in sickle cell anemia

Objective: This study has as objective to verify whether MBL2 gene polymorphisms are related to the occurrence of cerebrovascular disease (CD) in sickle cell anemia (SCA) patients. Methods: Overall, 259 unrelated SCA patients were enrolled. The patients were divided into three groups: control group, stroke group ad range of risk group. Peripheral blood samples were collected and DNA extraction was performed. All patients were genotyped for exon 1, promoter region -221 and promoter region -550 of MBL2 gene, along with β-globin gene haplotypes. Results: Concerning the genotyping of the MBL2, there was no difference in the frequency of allelic and genotypic variants of the exon 1 and the promoter regions -221 and -550 of the MBL2 gene among the studied groups. Conclusion: Despite the small number of patients, and the lack of association between MBL2 polymorphisms and CD, our study represents an effort to understand the impact of MBL2 polymorphisms in the clinical outcome of patients with SCA.

Neuropsychiatric Disorders in Chronic Kidney Disease

Neuropsychiatric conditions including depression, anxiety disorders, and cognitive impairment are prevalent in patients with chronic kidney disease (CKD). These conditions often make worse the quality of life and also lead to longer hospitalizations and higher mortality. Over the past decades, some hypotheses have tried to explain the connection between CKD and neuropsychiatric disorders. The most common hypothesis is based on the occurrence of cerebrovascular disease and accumulated uremic toxins in adult patients with CKD. However, the lack of a direct association between known vascular risk factors (e.g., diabetes and hypertension) with CKD-related cognitive deficits suggests that other mechanisms may also play a role in the pathophysiology shared by renal and neuropsychiatric diseases. This hypothesis is corroborated by the occurrence of neuropsychiatric comorbidities in pediatric patients with CKD preceding vascular damage, and the inconsistent findings on neuroprotective effects of antihypertensives. The aim of this narrative review was to summarize clinical evidence and potential mechanisms that links CKD and brain disorders, specifically in regard to cognitive impairment, anxiety, and depression.

Incidence of dementia in patients with adult-onset epilepsy of unknown causes

Epilepsy is generally considered to occur most commonly in childhood; however, several epidemiological studies confirmed that its occurrence increases from middle age [ [1] Hauser W.A. Seizure disorders: the changes with age. Epilepsia. 1992; 33: S6-S14 Crossref PubMed Scopus (344) Google Scholar , [2] Olafsson E. Ludvigsson P. Gudmundsson G. Hesdorffer D. Kjartansson O. Hauser W.A. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol. 2005; 4: 627-634 Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar ], and is the third most common neurological disease affecting the elderly, following dementia and cerebrovascular disease (CVD) [ [3] Brodie M.J. Kwan P. Epilepsy in elderly people. BMJ. 2005; 331: 1317-1322 Crossref PubMed Scopus (141) Google Scholar , [4] Werhahn K.J. Epilepsy in the elderly. Dtsch Arztebl Int. 2009; 106: 135-142 PubMed Google Scholar ]. These diseases interact with each other in later life. The leading etiology of elderly-onset epilepsy is CVD [ [5] Hauser W.A. Rowan A.J. Ramsay R.E. Epidemiology of Seizures and Epilepsy in the Elderly. Butterworth-Heinemann, Boston1997: 7-18 Google Scholar , [6] Wallace H. Shorvon S. Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922, and age-specific fertility rates of women with epilepsy. Lancet. 1998; 352: 1970-1973 Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar ], and CVD is a major risk factor for dementia with neurodegenerative disease, especially Alzheimer's disease (AD) [ [7] Petrovitch H. Ross G.W. Steinhorn S.C. Abott R.D. Markesbery W. Davis D. et al. AD lesions and infarcts in demented and non-demented Japanese-American men. Ann. Neurol. 2005; 57: 98-103 Crossref PubMed Scopus (202) Google Scholar , [8] J. Obrien R. Vascular dementia: atherosclerosis, cognition and Alzheimer's disease. Curr. Alzheimer Res. 2011; 8: 341-344 Crossref PubMed Scopus (13) Google Scholar ]. Adult-onset epilepsy is considered as a consequence of structural damage of the central nervous system (CNS), and the existence of AD, a typical neurodegenerative disease, also increases the occurrence of epilepsy [ [9] Scarmeas N. Honig L.S. Choi H. Cantero J. Brandt J. Blacker D. et al. Seizures in Alzheimer disease: who, when, and how common?. Arch. Neurol. 2009; 66: 992-997 Crossref PubMed Scopus (221) Google Scholar ]. This clinical finding is supported by several basic studies using a transgenic mouse model of AD, which demonstrated that deposited amyloid-β (Aβ) causes epileptiform discharges in the cortex, nonconvulsive seizures, and cognitive dysfunction [ [10] Palop J.J. Chin J. Roberson E.D. Wang J. Thwin M.T. Bien-Ly N. et al. Compensatory remodering of inhibitory hippocampal circuits in mouse models in Alzheimer's disease. Neuron. 2007; 55: 697-711 Abstract Full Text Full Text PDF PubMed Scopus (1121) Google Scholar , [11] Huang Y. Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012; 148: 1204-1222 Abstract Full Text Full Text PDF PubMed Scopus (1358) Google Scholar ]. Taking into account the evidence that Aβ deposition starts >10 years before clinical signs of AD appear [ [12] Villemagne V.L. Burnham S. Bourgeat P. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013; 12: 357-367 Abstract Full Text Full Text PDF PubMed Scopus (1410) Google Scholar ], epilepsy may develop earlier than AD. To test this hypothesis, we retrospectively studied the occurrence of AD in patients with adult-onset epilepsy of unknown causes to elucidate whether these patients are more likely to develop AD than control patients. Moreover, to determine whether an atherosclerotic factor affects the occurrence of AD, we also investigated the occurrence of CVD in both groups.

Microbial characteristics in culture-positive sepsis and risk factors of polymicrobial infection in ICU

To investigate the clinical characteristics and pathogenic microorganisms in culture-positive sepsis, to identify its risk factors, and evaluate the prognosis on polymicrobial infection in intensive care unit (ICU). A descriptive retrospective study was conducted. Clinical data of patients aged ≥ 18 years, diagnosed as culture-positive sepsis, and admitted to six ICUs of Guangdong General Hospital from October 12th, 2012 to December 1st, 2014 were enrolled. Based on the number of isolated pathogens, patients were divided into polymicrobial infection group (≥ two pathogens) and monomicrobial infection group (one pathogen) to investigate the clinical characteristics of patients with culture-positive sepsis and the causative pathogens. Multiple logistic regression was conducted to identify the risk factors for polymicrobial infection. Kaplan-Meier curve was plotted to analyze a 90-day survival rate from the onset of positive blood culture. 299 patients with positive blood culture were enrolled. A total of 450 strains of pathogens were isolated including 246 gram-positive cocci (54.67%), 167 gram-negative bacilli (37.11%) and 37 fungi (8.22%). Ninety-one patients had polymicrobial infection, and 208 with monomicrobial infection. Compared with monomicrobial infection group, patients suffering from polymicrobial infection had more advanced age (years: 73.19 ± 18.02 vs. 60.83 ± 18.06, t = -5.447, P = 0.000), also with higher incidence of cerebrovascular diseases [39.56% (36/91) vs. 17.79% (37/208), χ2 = 16.261, P = 0.000] or chronic renal insufficiency [15.38% (14/91) vs. 7.21% (15/208), χ2 = 4.828, P = 0.028], higher incidence of recent hospital stay (≥ 2 days) within 90 days [73.63% (67/91) vs. 61.54% (128/208), χ2 = 4.078, P = 0.043], longer mechanical ventilation duration [days: 4 (0, 17) vs. 1 (0, 6), U = 7673.000, P = 0.006], longer length of hospital stay before blood was drawn for culture [days: 21 (7, 40) vs. 9 (3, 17), U = 6 441.500, P = 0.006], and higher incidence of pre-admission intravenous use of antibiotics [84.62% (77/91) vs. 66.83% (139/208), χ2 = 9.989, P = 0.002]. Multiple logistic regression analysis showed that advanced age [odd ratio (OR) = 1.032, 95% confidential interval (95% CI) = 1.015-1.050, P = 0.000], cerebrovascular diseases (OR = 2.247, 95%CI = 1.234-4.090, P = 0.008), prolonged mechanical ventilation (OR = 1.041, 95% CI = 1.014-1.069, P = 0.003), and recent hospital stay (≥ 2 days) within 90 days (OR = 1.968, 95%CI = 1.079-3.592, P = 0.027) were the independent risk factors for polymicrobial infection. In the polymicrobial infection group, the length of ICU stay [days: 46 (22, 77) vs. 13 (7, 22), U = 3 148.000, P = 0.000] and hospital stay [days: 81 (47, 118) vs. 28 (17, 46), U = 3 620.000, P = 0.000] were significantly longer, and the ICU mortality [65.93% (60/91) vs. 43.75% (91/208), χ2 = 12.463, P = 0.000 ] and hospital mortality [68.13% (62/91) vs. 45.67% (95/208), χ2 = 12.804, P = 0.000] were significantly higher, and on the other hand the 90-day survival rate was significantly lower than that in the monomicrobial infection group (χ2 = 8.513, P = 0.004). The most common pathogen of ICU sepsis is gram-positive cocci. Independent risk factors for polymicrobial infections were found to be advanced age, occurrence of cerebrovascular disease, prolonged mechanical ventilation, and recent hospitalization. Polymicrobial infection is associated with longer length of ICU and hospital stay, as well as higher mortality.

Cardiac valve degeneration in a patient with Sneddon syndrome

Sneddon syndrome--a rare cause of aortic and mitral valve stenosis. Sneddon syndrome is a rare disorder that leads to repeated occurrence of cerebrovascular disease and skin manifestation, defined as livedo racemosa generalisata. The authors report the occurrence of multiple valve degenerations in a 49-year-old patient with Sneddon syndrome, which seemed to have been asymptomatic through a long period of time and was diagnosed as it needed a complex surgical intervention.

Prognostic Value of Chronotropic Incompetence in Elderly Patients Undergoing Exercise Echocardiography

Chronotropic incompetence (CI), defined as failure to achieve less than 80% of age-expected heart rate, is a predictor of mortality and adverse cardiovascular events and may confer a worse prognosis in elderly diabetic individuals. To evaluate the prognostic value of chronotropic incompetence (CI) in elderly diabetic patients considering endpoints with acute myocardial infarction (AMI), cerebrovascular disease (CVD) and overall mortality and compare clinical and echocardiographic characteristics between patients with and without CI. A total of 298 elderly diabetic patients undergoing exercise echocardiography (EE) were studied from January 2001 to December 2010. Of these, 109 were chronotropic incompetent (group 1) and were compared with the chronotropic competent ones (group 2) regarding the occurrence of cardiovascular events, clinical and echocardiographic characteristics. Chronotropic incompetents patients showed a higher frequency of cerebrovascular disease (9.2% vs. 3.2, p = 0.027) and higher mortality was observed in those who had cerebrovascular disease or acute myocardial infarction. The presence of typical angina and dyspnea prior to the performance of EE and male gender were more frequent in group 1. Rest and exercise left ventricular wall motion score index, rate of left ventricle mass and left atrium diameter were higher in chronotropic incompetent individuals. Chronotropic incompetence was independently associated with the occurrence of cerebrovascular disease in elderly diabetic individuals.

Sneddon's syndrome: case report and review of its relationship with antiphospholipid syndrome

The Sneddon's syndrome is a rare disorder characterized by the occurrence of cerebrovascular disease associated with livedo reticularis. The antiphospholipid syndrome is the most frequent type of acquired thrombophilia, defined by the occurrence of thrombosis or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. Approximately 80% of Sneddon's syndrome patients have an antiphospholipid antibody marker. These antibodies may play a pathogenetic role in some cases of Sneddon's syndrome, and many authors consider these two syndromes as the same entity. Although clinical features of antiphospholipid syndrome and Sneddon's syndrome may overlap, there is a distinction between clinical and laboratory evidence suggesting that these two entities are different diseases. A recent finding of coagulopathies, including elevated levels of coagulation factor VII, decreased levels of protein S, and activated protein C in Sneddon's syndrome patients suggested a possible biological link between the vasculopathy and a primary coagulopathy. Moreover, the clinical course seems to be progressive in Sneddon's syndrome patients and includes increase of disability and cognitive deterioration, more arterial involvement, and the antiphospholipid syndrome shows a more benign course. Both syndromes share clinical and laboratory features, and whether Sneddon's syndrome represents a spectrum of antiphospholipid syndrome remains unclear. Sneddon's syndrome patients have a worse prognosis and may represent a subgroup of patients who demands more rigorous follow-up. It is important to recognize the Sneddon's syndrome, particularly because stroke episodes may be prevented through appropriate treatment.

Methotrexate Reduces the Occurrence of Cerebrovascular Events among Taiwanese Psoriatic Patients: A Nationwide Population-based Study

Psoriasis is a chronic inflammatory disease. The aim of this study was to evaluate the effects of methotrexate and retinoid on risks for developing cerebrovascular disease among psoriatic patients. A population-based nested case-control study was conducted using the Taiwanese National Health Insurance database. Cox proportional hazards models were adopted. The hazard ratio (HR) of newly developed cerebrovascular disease was 1.28 (95% confidence interval (CI) = 1.162-1.413; p < 0.0001) for psoriatic vs. non-psoriatic subjects. In terms of the effects of methotrexate or retinoid on the occurrence of cerebrovascular disease, a significant protection effect (HR = 0.50; 95% CI = 0.27-0.92; p = 0.0264) was found for patients with methotrexate prescription. Retinoid prescription showed no protective effect. Further analyses revealed that a low cumulative methotrexate dose is associated with significant protective effect (HR = 0.53; 95% CI = 0.28-1.00; p = 0.0486) while a high cumulative dose was not (HR 0.80; 95% CI = 0.11-5.68; p = 0.8214). These results suggest that psoriatic patients receiving low-dose methotrexate treatment may have reduced risk for developing cerebrovascular disease. Further prospective study should be performed to validate the vasculoprotective effect of this treatment strategy.

Low HDL Cholesterol Is Associated With the Risk of Stroke in Elderly Diabetic Individuals

OBJECTIVETo clarify the relationship between lipid levels and ischemic heart disease (IHD) and cerebrovascular disease (CVD) in diabetic individuals.RESEARCH DESIGN AND METHODSThe Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4,014 type 2 diabetic patients (1,936 women; mean ± SD age 67.4 ± 9.5 years). Lipid and glucose levels and other factors were investigated in relation to occurrence of IHD or CVD.RESULTSIHD and CVD occurred in 1.59 and 1.43% of participants, respectively, over a 2-year period. The relation of lower HDL or higher LDL cholesterol to occurrence of IHD in subjects <65 years old was significant. Lower HDL cholesterol was also significantly related to CVD in subjects ≥65 years old and especially in those >75 years old (n = 1,016; odds ratio 0.511 [95% CI 0.239–0.918]; P < 0.05). Stepwise multiple regression analysis with onset of CVD as a dependent variable showed the same result.CONCLUSIONSLower HDL cholesterol is an important risk factor for not only IHD but also CVD, especially in diabetic elderly individuals.

中枢神経系浸潤を示した侵襲性副鼻腔アスペルギルス症の２例−ｖｏｒｉｃｏｎａｚｏｌｅの効果と血管病変について

We report 2 patients showing invasion of aspergillosis into the central nerve system (CNS). Patient 1, an 81-year-old woman, underwent surgery for sphenoidal sinusitis. She developed cerebral infarction with unconsciousness on 12th postoperative day. CSF examination demonstrated pleocytosis with increased protein and aspergillus antigen. She was diagnosed as having invasion of aspergillosis into the CNS, and was treated with voriconazole. Her clinical manifestations and CSF findings markedly improved. However, the effects of voriconazole gradually attenuated and she demonstrated recurrence of the cerebral infarction. After 2 months, she died of systemic aspergillosis and sepsis. Autopsy studies. Severe atherosclerotic changes with calcification were demonstrated in the bilateral carotid and basilar arteries, and many aspergillus were clustered in the vessel walls. Granulomatous inflammatory lesions with aspergillus were also demonstrated in the area surrounding the chiasm. There were no massive infarcts or bleeding in the brain, but multiple small infarcts were present. Patinet 2, a 64-year-old man, showing bilateral visual loss, was receiving treatment with corticosteroids under a diagnosis of optic neuritis. Two weeks later, he developed cerebral infarction. CSF examination showed pleocytosis with increased protein and aspergillus antigen. He was diagnosed as having invasive aspergillosis from the sphenoidal sinusitis into the CNS. He was treated with voriconazole, and unconsciousness and CSF findings improved transiently. However, he developed a recurrence of the brain infarction and pneumonia and finally died 6 months later. Treatment by voriconazole was definitely effective in both patients, but both patients died of recurrent cerebral infarction, possibly due to resistance for voriconazole, or developing multicellular filamentous biofilms. Voriconazole is recommended as the first choice of antifungal agents for aspergillosis. Aspergillus infection is strongly invasive into arterial vessels. It is important to consider the possible occurrence of cerebrovascular disease when treating invasion of aspergillosis into the CNS.

Cerebrovascular disease associated with antiphospholipid antibodies: more questions than answers

Neurological syndromes occur in a significant number of patients with antiphospholipid antibodies. The optimal management for these patients however remains uncertain.Our study is a descriptive analysis looking retrospectively at 45 patients who presented to the principal tertiary referral centre in the Australian Capital Territory, with either cerebral arterial or venous thrombosis for which there was no obvious cause for their presentation when initially reviewed. The diagnosis was based on the clinical findings made by one of three neurologists attached to our centre. Radiological findings and the presence of either IgM or IgG anticardiolipin antibodies, IgG anti-beta-2 glycoprotein 1 antibodies or a lupus anticoagulant were then documented.In this group of patients three subgroups were identified:1. Individuals that fulfilled the Sapporo Classification Criteria2. Individuals with transiently positive antiphospholipid antibodies and3. Individuals with persistently low positive antiphospholipid antibodies.The most interesting of these three groups are those individuals with transiently positive antiphospholipid antibodies. A potential cause for presentation was identified in only one patient of this group with documented infective endocarditis and bacteraemia. Comparison with the other two groups suggested that there was little in terms of clinical presentation, radiological findings or intercurrent risk factors for thrombotic disease to distinguish between them. With disappearance of antiphospholipid antibodies, the individuals within this group have not had further thrombotic events.Our observations emphasise the problems that continue to exist in relation to the occurrence of cerebrovascular disease in the context of antiphospholipid antibodies and the optimal management of these stratified groups. Our findings also raise an as yet unanswered question as to the signficance of these transiently positive antiphospholipid antibodies. In the absence of significant intercurrent risk factors our findings would suggest that in the group we describe that they are likely to be of clinical significance.

Stroke As a Late Treatment Effect of Hodgkin's Disease

TO THE EDITOR: Bowers et al are commended for their large cohort study on the risk of stroke in long-term survivors of Hodgkin’s disease. This is the first study showing an absolute increased risk of stroke in these young patients, who were not prone to atherosclerotic diseases because of their age. After a median interval of 17.5 years, these patients have an increased relative risk of stroke of 4.3 in comparison with a sibling control group. This observed increased risk is in agreement with the elevated risk of stroke we found in patients irradiated for head and neck tumors. However, the interval before the onset of stroke is longer in the Hodgkin’s population: 17.5 years versus 10.9 years in the head and neck population. This could possibly be explained by differences in underlying pathogenetic mechanisms. In atherosclerotic-naive patients, like in the Hodgkin’s population, irradiation on the neck seems to induce atherosclerotic-like lesions of the carotid artery. In contrast, in the population of older patients with head and neck cancer, radiation therapy (RT) accelerates pre-existing atherosclerotic disease. Both processes can eventually cause stenosis of the carotid artery and thromboembolisms leading to stroke, but the timing of this depends on whether the atherosclerotic process was already initiated before irradiation. In addition, increased thickness of the carotid vascular wall in the older head and neck cancer patients might sooner induce flow disturbances and shear stress, further accelerating the atherosclerotic process. The relatively low-dose of RT used in the treatment of Hodgkin’s disease (median dose, 40 Gy) compared with the dose used for head and neck cancer (60 to 70 Gy) might also contribute to slower progression of the lesions. A limitation of the Bowers study is that stroke was not confirmed by a computed tomography scan. Therefore, the contribution of other causes of cerebrovascular disease, like intracranial hemorrhage, cannot be established, nor can the origin of stroke be ascertained. Hodgkin’s disease patients who receive mantle irradiation are also at risk for cardiac disease, such as valvular diseases, which can also result in stroke in these patients. We agree with the authors that patients who receive irradiation on the neck should be monitored, especially those patients who have an estimated long survival. However, the suggestion of interviewing patients to establish the occurrence of cerebrovascular disease is, in our view, not the most appropriate solution, because the damage has already been done by then. We suggest duplex screening of the carotid arteries as a crucial part of follow-up to identify damage before it is associated with clinical symptoms. The next step is to investigate possible intervention strategies in order to diminish these debilitating late complications in long-term survivors of cancer.

AIDS/HIV Infection and Cerebrovascular Disease

The occurrence of cerebrovascular disease in patients with human immunodeficiency virus (HIV) infection has been reported mainly in advanced stages of the disease and was generally associated with nonbacterial thrombotic endocarditis, opportunistic infections, or tumors, although in recent series a large number of cryptogenic strokes were found, probably related to HIV vasculopathy. Recently a population-based study reported a strong association between acquired immunodeficiency syndrome (AIDS) and both ischemic stroke and intracerebral hemorrhage, with an incidence of 0.2% per year. However, with the advent of highly active retroviral therapy (HAART)-causing immune restoration in HAART-treated patients and avoiding early death and leading to a lengthening of the disease free-survival, an older population was created, which is at higher risk for stroke. Furthermore, recent evidence suggests that accelerated atherosclerosis may be a potential risk for stroke in these patients as it accompanies dyslipidemia and insulin resistance that were found to be more frequent among patients in the HAART regimen. The relationship of HIV infection and stroke is undergoing remarkable changes and epidemiological studies should be performed on aging HIV populations to state the impact of this new information on the incidence of cerebrovascular disease in HIV-infected patients and to identify factors that are associated with its occurrence.

Seasonal Variation in Hospitalization and Case Fatality of Subarachnoid Hemorrhage – A Nationwide Danish Study on 9,367 Patients

Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive. We conducted a nationwide population-based study in Denmark to examine any seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367 patients with SAH and found a modest indication of overall seasonal variation for the risk of hospitalization with this diagnosis. The seasonal pattern, with the highest incidence in January and the nadir in July, was mostly apparent for subjects aged >65 years (peak-to-trough ratio = 1.18; 95% CI 1.04–1.32). There was little difference by sex. The overall 30-day case fatality rate was 38% and showed less seasonal variation. We found evidence of weak seasonal variation in hospitalization for SAH and almost no seasonal variation in a 30-day case fatality rate after SAH.

Polymorphism -238 G/A in Promotor Region of Tumor Necrosis Factor alpha Gene Is a Risk Factor for Ischemic Cerebrovascular Disease in Spanish Population.

Introduction: Cerebrovascular disease (CVD) is a multifactorial disease caused by the interaction of genetic and environmental factors. The atherosclerotic plaque, the pathological hallmark of CVD, is an inflammatory process, where pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα). TNFα secretion shows a high degree of interindividual variability, which is at least partly genetically determined. We have analysed the prevalence of −238 G/A and −308 G/A polymorphisms in the regulatory region of the TNFα gene promoter in CVD.Patients and methods: Genotypic analyses were performed on 308 consecutive unrelated patients diagnosed with ischemic CVD, 147 women and 161 men, mean age 70±0.8 years, who were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment. All included cases were age and sex matched to a control from the same geographic area who had no history of vascular disease. Patients and controls completed a questionnaires including blood pressure, diabetes status, total serum cholesterol level and smoking history. The TNFα variants were detected by PCR using primers containing a single base-pair mismatch to introduce a restriction site into the wild-type nucleotide sequences after amplification. PCR products were digested with NcoI and MspI to detect −308 and −238 variants, respectively. The strength of the association of the polymorphisms with the occurrence of CVD was estimated by calculation of the OR and its 95%CI by exact method. P values less than 0.05 were considered significant. Logistic regression analysis was applied to estimate the risk in a multivariable predictive model with dependent variable (case/control) and all independent variables significant in the bivariate analysis. SPSS 9.0 was used for the statistical analysis.Results: Genotype analysis showed a significant higher prevalence of the G/A and A/A genotypes of −238 G/A TNFα in patients (p< 0.01;OR= 2.16;95%CI= 1.40–3.34). The prevalence of the A allele was also significantly increased in the group of CVD patients than in the controls (13.6% vs 7.0%; p<0.01;OR=2.10;95%CI=1.40–3.17). By contrast, the distribution of −308 genotypes for patients did not differ from their control group (84.9% vs 81.1% and 14.4% vs 16.9%, respectively; p=0.21;OR=0.76;95%CI=0.48–1.20) or in the A allele frequencies (7.9% vs 10.4%; p=0.12;OR=0.73;95%CI=0.48–1.11). When analysis was performed for the two more frequently subtypes of CVD, atherotrombotic subtype showed an higher prevalence of the A allele of -238 G/A polymorphism, as compared with the undetermined etiology (16.5% vs 11.2%;p=0.06;OR=1.86;95%CI= 0.91–3.82). By contrast, the variant −308 G/A did not differ from the different subtypes. Logistic regression analysis showed a independent association of A haplotype of −238 G/A TNFα with CVD. Also hypertension, diabetes mellitus and current smoking status were statistically associated with CVD.Conclusions: Our findings suggest that the A allele of −238 G/A TNFα promoter polymorphism is a genetic risk factor for ischemic CVD in Spanish population. Data on the distribution of genotypes and corresponding allelic frequencies of −238 G/A and −308 G/A TNFα polymorphisms in CVD are scant. The present study is the first to analyses these variants in CVD patients from this geographic area.

Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases

The role of leukocytes in the pathogenesis of cerebrovascular disease, in particular, cerebral ischemic disease has recently become a focus of research, Several studies have reported that a positive correlation between increased functional activities of neutrophils and the risk of cerebral ischemic disease. Granulocyte colony-stimulating factor (G-CSF) is known to be not only a granulocyte proliferating but also a potent activator of mature neutrophils. In this study, we measured the serum G-CSF levels in 143 patients with cerebrovascular diseases and in 100 patients with other diseases, using our established enzyme-linked immunosorbent assay (ELISA) for G-CSF The minimal detection level was 20 pg/ml G-CSF. In patients with cerebral infarction, G-CSF could be detected in 18.3% and in patients with cerebral hemorrhage, it could be detected in 9.8% of analyzed samples. On the other hand, 6% of the patients with other diseases had measurable levels of G-CSF. The differences among these three groups were statistically significant according to the χ2 test (p <0.01). Our findings that there was a significantly high frequency of elevated levels of G-CSF among patients with cerebrovascular diseases, may indicate that the action of G-CSF as a potent activator of neutrophils plays some role in the occurrence of cerebrovascular disease, in particular, cerebral infarction.