Cerebrovascular Diseases (Cerebrovasc Dis )

Publisher: S. Karger (Firm), Karger

Description

A rapidly-growing field, cerebrovascular research is unique in that it involves a variety of specialties such as neurology, internal medicine, surgery, radiology, epidemiology, cardiology, hematology, psychology and rehabilitation. ëCerebrovascular Diseasesí is a new international forum which meets the growing need for sophisticated, up-to-date scientific information on clinical data, diagnostic testing, and therapeutic issues, dealing with all aspects of stroke and cerebrovascular diseases. It contains original contributions, reviews of selected topics and clinical investigative studies, recent meeting reports and work-in-progress as well as discussions on controversial issues. All aspects related to clinical advances are considered, while purely experimental work appears if directly relevant to clinical issues.

Impact factor 3.70

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    Impact factor
  • 5-year impact
    3.21
  • Cited half-life
    5.50
  • Immediacy index
    0.48
  • Eigenfactor
    0.02
  • Article influence
    1.12
  • Website
    Cerebrovascular Diseases website
  • Other titles
    Cerebrovascular diseases (Basel, Switzerland: Online)
  • ISSN
    1421-9786
  • OCLC
    44717733
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Karger

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  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Intracerebral hemorrhage (ICH), a subtype of stroke associated with high mortality and disability, accounts for 13% of all strokes. Basic and clinical research has contributed to our understanding of the complex pathophysiology of neuronal injury in ICH. Outcome rates, however, remain stable, and questions regarding acute management of ICH remain unanswered. Newer research is aiming at matching measured levels of serum proteins, enzymes, or cells to different stages of brain damage, suggesting that blood biomarkers may assist in acute diagnosis, therapeutic decisions, and prognostication. This paper provides an overview on the most promising blood biomarkers and their potential role in the diagnosis and management of spontaneous ICH. Summary: Information was collected from studies, reviews, and guidelines listed in PubMed up to November 2013 on blood biomarkers of nontraumatic ICH in humans. We describe the potential role and limitations of GFAP, S100B/RAGE, and ApoC-III as diagnostic biomarkers, β- Amyloid as a biomarker for etiological classification, and 27 biomarkers for prognosis of mortality and functional outcome. Within the group of prognostic markers we discuss markers involved in coagulation processes (e.g., D-Dimers), neuroendocrine markers (e.g., copeptin), systemic metabolic markers (e.g., blood glucose levels), markers of inflammation (e.g., IL-6), as well as growth factors (e.g., VEGF), and others (e.g., glutamate). Some of those blood biomarkers are agents of pathologic processes associated with hemorrhagic stroke but also other diseases, whereas others play more distinct pathophysiological roles and help in understanding the basic mechanisms of brain damage and/or recovery in ICH. Key Messages: Numerous blood biomarkers are associated with different pathophysiological pathways in ICH, and some of them promise to be useful in the management of ICH, eventually contributing additional information to current tools for diagnosis, therapy monitoring, risk stratification, or intervention. Up to date, however, no blood biomarker of ICH has been studied sufficiently to find its way into clinical routine yet; well-designed, large-scale, clinical studies addressing relevant clinical questions are needed. We suggest that the effectiveness of biomarker research in ICH might be improved by international cooperation and shared resources for large validation studies, such as provided by the consortium on stroke biomarker research (http://stroke-biomarkers. com/page.php?title=Resources). © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 12/2014; 38(6):395-409.
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    ABSTRACT: Background: Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma ≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. Methods: 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. Results: Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p = 0.039), especially in older patients (29/46 (63.04%) patients ≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients <60 years of age with 3 plaques; p < 0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26 ± 14 vs. 32 ± 18 mm; p = 0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p = 0.048). Conclusions: This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 12/2014; 38(6):410-417.
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    ABSTRACT: Background: Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions that often result in intracerebral hemorrhage (ICH), seizures, and neurological deficits. Carriers of the same genetic mutation can present with variable symptoms and severity of disease, suggesting the influence of modifier factors. Evidence is emerging that inflammation and immune response play a role in the pathogenesis of CCM. The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence the severity of familial CCM1 disease, as manifested by ICH and greater brain lesion count. Methods: Hispanic CCM1 patients (n = 188) harboring the founder Q455X 'common Hispanic mutation' (CHM) in the KRIT1 gene were analyzed at baseline. Participants were enrolled between June 2010 and March 2014 either through the Brain Vascular Malformation Consortium (BVMC) study or through the Angioma Alliance organization. Clinical assessment and cerebral susceptibility-weighted magnetic resonance imaging were performed to determine ICH as well as total and large (≥5 mm in diameter) lesion counts. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 830 variants in 56 inflammatory and immune response genes for association with ICH and residuals of log-transformed total or large lesion count adjusted for age at enrollment and gender. Variants were analyzed individually or grouped by sub-pathways or whole pathways. Results: At baseline, 30.3% of CCM1-CHM subjects had ICH, with a mean ± standard deviation (SD) of 60.1 ± 115.0 (range 0-713) for total lesions and 4.9 ± 8.7 (range 0-104) for large lesions. The heritability estimates explained by all autosomal variants were 0.20 (SE = 0.31), 0.81 (SE = 0.17), and 0.48 (SE = 0.19), for ICH, total lesion count, and large lesion count, respectively. TGFBR2 rs9823731 was significantly associated with ICH as well as with the total and large lesion counts (p ≤ 0.017). Further, IL-4 rs9327638, CD14 rs778588, IL-6R rs114660934 and MSR1 rs62489577 were associated with two markers of disease severity. Finally, the whole pathway was associated with total lesion count (p = 0.005) with TLR-4 rs10759930, CD14 rs778588, IL-6R rs114660934 and IGH rs57767447 mainly bearing this association. Eicosanoid signaling, extracellular pattern recognition, and immune response sub-pathways were also associated with the total lesion count. Conclusions: These results suggest that polymorphisms in inflammatory and immune response pathways contribute to variability in CCM1 disease severity and might be used as predictors of disease severity. In particular, TGFBR2 rs9823731 was associated with all three markers of CCM1 disease severity tested, suggesting that TGFBR2 might be a key participant in the mechanism underlying CCM1 disease severity and phenotype variability. However, further longitudinal studies in larger sample sizes are needed to confirm these findings. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 12/2014; 38(6):433-440.
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    ABSTRACT: Background: Although the echolucent plaque in carotid stenosis is associated with future ischemic stroke, the predictive value of echogenicity in small and medium size carotid plaques on vascular events has not been thoroughly examined. Thus, we prospectively tested the hypothesis that plaque echogenicity of carotid atheroma can predict the future total cardiovascular events in patients with vascular risk factors. Methods: Ultrasound assessment of carotid intima-media complex thickness (IMT) and plaque echogenicity using integrated backscatter (IBS) analysis was performed in 596 patients aged 40 or more, with any history of vascular events or with at least 1 risk factor, who were enrolled between 2001 and 2006 in the Osaka Follow-up Study for Carotid Atherosclerosis, part 2 (OSACA2). We followed the incidence of total cardiovascular events including cerebrovascular events, coronary heart disease (CHD), and peripheral artery disease (PAD) for 6.4 years. We divided the patients into two groups according to the IBS index above (echorich plaques) and under (echolucent plaque) the median value, and calculated the hazard ratios (HR) of the echolucent group compared with the echogenic group in the risk of cardiovascular events. Results: Among 596 patients, carotid stenosis was found only in 87 patients. During the follow-up period, we observed 121 cardiovascular events including 63 cerebrovascular events, 45 CHD cases, and 13 PAD cases. The patients with incident cardiovascular events had larger plaque thickness and lower IBS index than those without incident vascular events. The relative risk of vascular events for echolucent versus echorich plaques was 1.45 (95% confidence interval [CI] 0.99-2.13, p = 0.058) after adjustment for risk factors and plaque thickness. In patients with plaque size above the median value (>2.1 mm), the relative risk of vascular events for echolucent plaques was 1.72 (95% CI 1.06-2.85, p = 0.029), but this association was not observed in patients with plaque size <2.0 mm. Conclusions: The association between echogenicity of carotid plaque and incident vascular events is dependent on the plaque size. Echolucent medium-to-large plaques, but not small plaques, are associated with the risk of future total cardiovascular events. This finding suggests that measurement of echolucency in medium-to-large carotid plaques may improve selection of patients at high risk for total vascular events. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):354-361.
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    ABSTRACT: Background and Purpose: A recent surgery may be one of the trigger factors precipitating stroke and transient ischemic attack (TIA). While stroke in cardiac and carotid surgery has been well studied, less is known on stroke risk after surgery outside the heart and brain supplying arteries. We tested the hypothesis that preceding non-neurosurgical, non-cardiothoracic, and non-carotid surgery and other interventions temporarily increase the risk of stroke and transient ischemic attack (TIA) and investigated the risk related to different time periods between interventions and stroke/TIA. Methods: In the Ludwigshafen Stroke Study, a population-based stroke registry, we assessed surgery and other interventions within the year preceding stroke and TIA. The risk factor profiles of patients with and without prior intervention were compared and rate ratios (RR) were calculated for different time periods with 91-365 days before stroke and TIA serving as reference period. Results: In 2006 and 2007, 803 patients without and 116 patients with non-neurosurgical, non-cardiothoracic, and non-carotid intervention within the preceding year were identified. Elective (n = 21) and posttraumatic orthopedic (n = 14), eye (n = 14), and visceral surgery (n = 11) dominated. Interventions within 0-30 days (n = 34; RR 4.72; 95% confidence interval (CI) 2.70-8.26) but not within 31-60 or 61-90 days before stroke/TIA were observed more often than in the reference period. Interventions were more common within day 8-30 before stroke/TIA (RR 3.26; 95% CI 1.66-6.39), particularly common within the preceding week (RR 9.52; 95% CI 3.77-24.1) and most common in the preceding 2 days (RR 27.1; 95% CI 5.97-123) as compared to the reference period. Atrial fibrillation (AF) but not other risk factors was more common in patients with interventions within 30 days (n = 15; 44.1%) as compared to patients with more antecedent interventions (n = 19; 23.2%, p = 0.022) and those without surgery (n = 222; 27.6%, p = 0.031). Interventions within 30 days before stroke/TIA, were associated with total ischemic stroke (RR 6.11; 95% CI 3.32-11.2), first-ever in a lifetime ischemic stroke (RR 5.62; 95% CI 2.83-11.1) and recurrent ischemic stroke (RR 7.50; 95% CI 2.88-19.6). Conclusion: Recent non-cardiothoracic, non-carotid, and non-neurosurgical interventions are associated with an increased risk of stroke lasting for about 1 month and being particularly high within the first days. AF may be among the mechanisms linking interventions and stroke besides induction of a procoagulant state and interruption of medication. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):370-376.
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    ABSTRACT: Background: A wide variety of racial and ethnic disparities in stroke epidemiology and treatment have been reported. Race-ethnic differences in initial stroke severity may be one important determinant of differences in the outcome after stroke. The overall goal of this study was to move beyond ethnic comparisons in the mean or median severity, and instead investigate ethnic differences in the entire distribution of initial stroke severity. Additionally, we investigated whether age modifies the relationship between ethnicity and initial stroke severity as this may be an important determinant of racial differences in the outcome after stroke. Methods: Ischemic stroke cases were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project. National Institutes of Health Stroke Scale (NIHSS) was determined from the medical record or abstracted from the chart. Ethnicity was reported as Mexican American (MA) or non-Hispanic white (NHW). Quantile regression was used to model the distribution of NIHSS score by age category (45-59, 60-74, 75+) to test whether ethnic differences exist over different quantiles of NIHSS (5 percentile increments). Crude models examined the interaction between age category and ethnicity; models were then adjusted for history of stroke/transient ischemic attack, hypertension, atrial fibrillation, coronary artery disease, and diabetes. Results were adjusted for multiple comparisons. Results: There were 4,366 ischemic strokes, with median age 72 (IQR: 61-81), 55% MA, and median NIHSS of 4 (IQR: 2-8). MAs were younger, more likely to have a history of hypertension and diabetes, but less likely to have atrial fibrillation compared to NHWs. In the crude model, the ethnicity-age interaction was not statistically significant. After adjustment, the ethnicity-age interaction became significant at the 85th and 95th percentiles of NIHSS distribution. MAs in the younger age category (45-59) were significantly less severe by 3 and 6 points on the initial NIHSS than NHWs, at the 85th and 95th percentiles, respectively. However, in the older age category (75+), there was a reversal of this pattern; MAs had more severe strokes than NHWs by about 2 points, though not reaching statistical significance. Conclusions: There was no overall ethnic difference in stroke severity by age in our crude model. However, several potentially important ethnic differences among individuals with the most severe strokes were seen in younger and older stroke patients that were not explained by traditional risk factors. Age should be considered in future studies when looking at the complex distributional relationship between ethnicity and stroke severity. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):362-369.
  • Cerebrovascular Diseases 11/2014; 38(5):393-394.
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    ABSTRACT: Background: Normal aging is associated with a decline in cognitive abilities, particularly in the domains of psychomotor speed and executive functioning. However, 'aging,' per se, is not a cause of cognitive decline but rather a variable that likely captures multiple accumulating biological changes over time that collectively affect mental abilities. Recent work has focused on the role of cerebrovascular disease as one of the biological changes. In the current study, we examined whether lobar microbleeds - magnetic resonance imaging (MRI) signal voids due to hemosiderin deposits secondary to cerebral amyloid angiopathy - are associated with cognitive decline in normal aging. Previous studies that reported a relationship between the presence of lobar microbleeds and decreased cognitive abilities have been primarily cross-sectional. Here, we used a retrospective longitudinal design to examine whether the presence of lobar microbleeds is associated with the rate of cognitive decline among non-demented older adults. Methods: Participants came from an ongoing longitudinal community-based aging study, in which subjects are evaluated at 18-24 months intervals and received a full medical, neurological, and neuropsychological examination at each of the follow-up visits. Gradient echo MRI scans were available on 197 non-demented participants (mean age: 84.15 ± 5.02 years). Microbleeds were rated visually on axial view and divided into subcortical (basal ganglia, cerebellum) and lobar (frontal, temporal, parietal, occipital lobe) regions, and confirmed with coronal and sagittal views to exclude artifacts. Cognition was assessed with a neuropsychological battery, providing summary scores for memory, language, executive, and visuospatial abilities. Using general estimating equations (GEE), we compared cognition cross-sectionally between individuals with 2 or more (n = 11) and fewer than 2 (n = 186) lobar microbleeds and examined longitudinal cognitive change beginning 9.47 ± 3.13 years before the MRI scan. Results: Subjects with 2 or more lobar microbleeds had worse executive functioning at the visit closest to the MRI scan (β = -0.044; p < 0.001) and had a faster decline in executive function over time (β = -0.072; p = 0.012) than subjects with fewer than 2 lobar microbleeds. The two groups were similar in age at scan date, education, ethnicity, sex distribution, and cognitive performance at first visit. Conclusions: Lobar microbleeds, a marker of cerebral amyloid angiopathy, are associated with an accelerated rate of executive function decline. The presence of cerebral amyloid angiopathy may be an important source of cognitive decline in aging. Future work should examine how cerebral amyloid angiopathy interacts with neurodegenerative processes, such as Alzheimer's disease. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):377-383.
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    ABSTRACT: Background: Isolated posterior fossa parenchymal lesions associated with cerebral venous thrombosis (CVT) are rare. Posterior fossa lesions are an independent predictor of death in CVT. We aim to describe the characteristics and outcome of patients with CVT and isolated posterior fossa lesions and assess the safety of anticoagulation in patients with posterior fossa lesions associated with CVT. Methods: We retrieved data from all patients with posterior fossa parenchymal lesions in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort related to clinical features, therapy and outcome. Fisher's exact test was used to evaluate associations. To assess the safety of anticoagulation in CVT patients with posterior fossa lesions we considered all patients with a lesion in this topography, either isolated or with concomitant supratentorial lesions, and compared the rate of new intracranial haemorrhages on repeated imaging with the remaining cohort. Results: Out of 624 patients, 12 had isolated posterior fossa lesions and 14 had posterior fossa lesion with accompanying supratentorial lesions. The lateral sinus was most frequently occluded (n = 11). Involvement of the superior sagittal sinus was significantly less frequent compared to the remaining patients of the cohort (p = 0.013). None of the patients with isolated posterior fossa lesion died but 3 remained dependent on follow-up. Poor outcome (modified Rankin Scale ≥3) was more frequent in patients with any posterior fossa lesion, even when on anticoagulation (29.2% vs. 11.9%; OR 3.04; 95% CI 1.2-7.6; p = 0.018). Of the 24 anticoagulated patients with a posterior fossa lesion, 3 (12.5%) had new haemorrhages on repeated imaging, compared with 30 out of 495 anticoagulated patients (6.1%) without posterior fossa lesions (p = 0.19). Conclusions: We describe the largest series of CVT patients with associated posterior fossa lesions. When compared to anticoagulated CVT patients without posterior fossa lesions, CVT patients with posterior fossa lesions on full anticoagulation did not have a significant increase in the rate of new intracranial haemorrhages. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):384-388.
  • Cerebrovascular Diseases 11/2014; 38(5):391-392.
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    ABSTRACT: Background: Space-occupying malignant stroke of the middle cerebral artery (MCA) is associated with a high mortality rate of up to 80% under conservative treatment. Although there is convincing evidence that decompression craniectomy can significantly reduce mortality rate and improve neurological outcome in young patients (<60 years), many surgeons are still hesitant to recommend hemicraniectomy for stroke patients. Summary: This review addresses some major issues that appear to be an obstacle to decompression craniectomy, in particular, indicating surgery for patients >60 years or with infarcts of the dominant hemisphere. Furthermore, it emphasizes technical issues such as timing and size of the craniectomy, additional temporal lobectomy, and resection of the temporal muscle, as well as duraplasty and cranioplasty. According to the current literature, decompression craniectomy in older patients can increase survival without most severe disabilities, although, most survivors need assistance in most bodily needs. Involvement of the dominant hemisphere results in aphasia that might partly recover in younger patients, although, considering the neuropsychological deficits caused by infarctions of the nondominant hemisphere, involvement of the dominant hemisphere does not pose as a contraindication for decompression craniectomy. Furthermore, there is convincing evidence that surgery should be performed within 48 h after the onset of symptoms and the size of the craniectomy should be at least 12 cm as a minimum. An additional lobectomy or the resection of the temporal muscle, however, can only be part of individual treatment options. Conceding the weak evidence, it is recommended to close the dura by some form of a duraplasty avoiding cerebrospinal fluid leakages or scarring between the cortex and the scalp leading to injuries during reimplantation of the bone-flap. Complications associated with decompression surgery (hemorrhages, infections, 'sinking skin-flap syndrome', cerebrospinal fluid leakages, hydrocephalus, seizures), with the infarction itself, or with those that occur during the ICU course (cardiac and pulmonary complications) appear acceptable and are mostly treatable, especially considering the fatal course of conservative treatment. Key Message: This review summarizes the current state of the literature about decompression craniectomy of patients with malignant stroke addressing, in particular, critical surgical issues, and thus, help surgeons to make decisions confidently for/or against performing surgery. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):313-323.
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    ABSTRACT: Background: Elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with both coronary artery and cerebrovascular diseases. The clinical diagnosis of neurovascular events, specifically transient ischemic attack can be challenging, although there is disagreement among vascular trained neurologists regarding this. Currently, there is no single accurate biomarker for the diagnosis of acute brain ischemia. Aim: We studied the relationship between Lp-PLA2 mass and activity levels and the diagnosis of acute brain ischemia in the acute phase among patients evaluated in the emergency department following transient focal neurological symptoms. Methods: Patients evaluated in our academic center for transient neurological symptoms of possible ischemic mechanism were enrolled with informed consent. Lp-PLA2 mass and activity levels were performed by DiaDexus, Inc. Results: 100 patients were enrolled: 58 were ischemic (30 stroke, 28 TIA), 10 were unknown, and 28 were non-ischemic. Blood samples were collected after a median delay of 23 h (IQR: 17, 36) after symptom onset. The median levels of Lp-PLA2 activity level for ischemic (stroke and TIA) versus non-ischemic events were 186.5 nmol/ml/min (IQR = 153, 216.3) and 169 nmol/ml/min (IQR = 137, 212.5), respectively. The median levels of Lp-PLA2 mass level for ischemic versus non-ischemic events were 202 ng/ml (IQR = 171.6, 226.1) and 192 ng/ml (167.8, 230). The differences in median Lp-PLA2 mass and activity levels were not statistically significant in the ischemic versus non-ischemic patients. Vessel imaging revealed a symptomatic stenosis in 14 patients (10 intracranial and 4 cervical). The median Lp-PLA2 mass and activity levels among patients with a symptomatic stenosis were not significantly higher than the levels measured in TIA/stroke patients without stenosis. Conclusion: The results of our study do not support the early measurement of Lp-PLA2 mass or activity levels for confirming an ischemic etiology in patients experiencing minor or transient focal neurological events. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):324-327.
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    ABSTRACT: Background: Microvasculature plays a key role in stroke pathophysiology both during initial damage and extended neural repair. Moreover, angiogenesis processes seem to be a promising target for future neurorestorative therapies. However, dynamic changes of microvessels after stroke still remain unclear, and MRI follow-up could be interesting as an in vivo biomarker of these. Methods: The aim of this study is to characterize the microvascular plasticity 25 days after ischemic stroke using both in vivo microvascular 7T-MRI (vascular permeability, cerebral blood volume (CBV), vessel size index (VSI), vascular density) and quantification of angiogenic factor expressions by RT-qPCR in a transient middle cerebral artery occlusion rat model. CBV and VSI (perfused vessel caliber) imaging was performed using a steady-state approach with a multi gradient-echo spin-echo sequence before and 2 min after intravenous (IV) injection of ultrasmall superparamagnetic iron particles. Vascular density (per mm(2)) was derived from the ratio [ΔR2/(ΔR2*)(2/3)]. Blood brain barrier leakage was assessed using T1W images before and after IV injection of Gd-DOTA. Additionally, microvessel immunohistology was done. Results: 3 successive stages were observed: 1) 'Acute stage' from day 1 to day 3 post-stroke (D1-D3) characterized by high levels of angiopoietin-2 (Ang2), vascular endothelial growth factor receptor-2 (VEGFR-2) and endothelial NO synthase (eNOS) that may be associated with deleterious vascular permeability and vasodilation; 2) 'Transition stage' (D3-D7) that involves transforming the growth factors β1 (TGFβ1), Ang1, and tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains 1 (Tie1), stromal-derived factor-1 (SDF-1), chemokine receptor type 4 (CXCR-4); and 3) 'Subacute stage' (D7-D25) with high levels of Ang1, Ang2, VEGF, VEGFR-1 and TGFβ1 leading to favorable stabilization and maturation of microvessels. In vivo MRI appeared in line with the angiogenic factors changes with a delay of at least 1 day. All MRI parameters varied over time, revealing the different aspects of the post-stroke microvascular plasticity. At D25, despite a normal CBV, MRI revealed a limited microvessel density, which is insufficient to support a good neural repair. Conclusions: Microvasculature MRI can provide imaging of different states of functional (perfused) microvessels after stroke. These results highlight that multiparametric MRI is useful to assess post-stroke angiogenesis, and could be used as a biomarker notably for neurorestorative therapy studies. Additionally, we identified that endogenous vessel maturation and stabilization occur during the 'subacute stage'. Thus, pro-angiogenic treatments, such as cell-based therapy, would be relevant during this subacute phase of stroke. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(5):344-353.
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    ABSTRACT: Background: Intracranial arterial stenosis (ICAS) is a major cause of ischemic stroke in Asians. Despite the clinical importance of ICAS, the literature on the natural history of ICAS has been less enlightening. The aims of our study were to evaluate a long-term natural course of symptomatic and asymptomatic ICAS. Methods: 102 subjects (37 symptomatic and 65 asymptomatic) underwent follow-up MR angiography (MRA) with a median time interval between initial and follow-up MRA of 5.7 years (range 3.6-8.5 years). For each patient, the extent of stenosis of five arteries (both middle cerebral arteries, both intracranial internal carotid arteries, and basilar artery) was classified according to five grades, by consensus: normal, mild (signal reduction <50%), moderate (signal reduction ≥50%), severe (focal signal loss with the presence of a distal signal), and occlusion. Because the sample size was too small to adjust for multiple confounders, we applied the propensity score. Results: Mean (Standard deviation) age at initial MRA was 63.5 (9.6) and 54% were men. The progression rate of ICAS differed significantly between symptomatic and asymptomatic patients (22 vs. 8%, p < 0.01), indicating a 3-fold risk of progression for symptomatic stenosis compared with asymptomatic stenosis [odds ratio (OR) 3.27, 95% confidence interval (CI) 1.08-9.95]. After adjustment for propensity score, the OR was 4.84 (95% CI, 1.40-16.7). In the matched cohort, the relative risk of stenosis progression was 5.20 for symptomatic stenosis (95% CI 1.00-27.23) compared with asymptomatic stenosis. Conclusion: We found a greater risk of progression for symptomatic stenosis compared with asymptomatic stenosis. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2014; 38(4):290-296.