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Background: It has been suggested that antiplatelet or anticoagulant drugs elevate the rate of intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (MBs). To investigate the mechanism by which antiplatelet drugs or warfarin may contribute to deep ICH occurrences in patients with deep MBs, we prospectively analyzed deep ICH occurrences in 807 consecutive patients (351 females and 456 males; mean age ± standard deviation 69.8 ± 12.0 years) who were admitted to our hospital with strokes. Methods: Occurrence-free rate curves were generated using the Kaplan–Meier method; deep ICH occurrence–free rates were compared using the log-rank test. The follow-up period was 0.5 to 71 months (mean ± standard deviation 31.6 ± 22.2 months). Results: In patients with deep MBs, the rates (1.0%/year; 6 ICHs in 180 patients) of deep ICH occurrence associated with antiplatelet drugs were not significantly greater than that without the drugs (1.0%/year; 6 ICHs in 167 patients; P = .977). The incidence of deep ICHs associated with warfarin use was not significantly greater than that without warfarin use. Conclusions: Multivariate analysis revealed that the use of antiplatelet drugs or warfarin did not significantly influence the occurrence of deep ICH in patients with deep MBs. Antiplatelet drugs or warfarin did not significantly elevate the rate of deep ICHs in stroke patients with pre-existing deep MBs. [Copyright &y& Elsevier]

Background: Although brain microbleed has been reported to be a risk factor for antiplatelet-associated intracerebral hemorrhage, data on the use of specific antiplatelet agents are lacking. In this study, we examined the associations between specific antiplatelets and brain microbleeds in order to help select antiplatelet agents in patients with microbleeds. Methods: We evaluated 1914 consecutive acute stroke patients, including 412 patients with intracerebral hemorrhage and 1502 patients with ischemic stroke. The associations between the presence of microbleeds and antiplatelet use were evaluated, including specific antiplatelet agents (aspirin, clopidogrel, cilostazol, and ticlopidine). Results: Antiplatelet use was associated with the presence of microbleeds in patients with intracerebral hemorrhage (odds ratio [OR] 2.418; 95% confidence interval [CI] 1.236-4.730; P = .0099), but not in patients with ischemic stroke. The use of a single antiplatelet medication was not associated with the presence of microbleeds. In patients with intracerebral hemorrhage, aspirin (OR 2.160; 95% CI 1.050-4.443; P = .0364) but not clopidogrel, cilostazol, or ticlopidine was associated with microbleeds. In these patients, dividing brain microbleeds into deep microbleeds and lobar microbleeds revealed an association only between antiplatelet use and the presence of deep microbleeds (OR 2.397; 95% CI 1.258-4.567; P = .0079). None of the antiplatelet agents were associated with the presence of deep microbleeds, although aspirin had a trend of association (OR 1.986; 95% CI 1.000-3.946; P = .0501). Conclusions: Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results. [Copyright &y& Elsevier]

It has been questioned whether patients with cerebral microbleeds are at a greater risk for the development of symptomatic intracerebral hemorrhage following thrombolytic therapy in the management of acute ischemic stroke. Thus far, observational studies have not shown a statistically significant increased risk; however, these have been limited by small sample size. The aim is to better quantify the risk of postthrombolysis intracerebral hemorrhage in patients with acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A systematic review of controlled studies investigating the presence of microbleeds on magnetic resonance imaging as a risk factor for intracerebral hemorrhage following thrombolysis in acute stroke patients was conducted. A random effects model meta-analysis was performed. In pooled analysis of five studies totaling 790 participants, the prevalence of microbleeds was 17%. The presence of microbleeds revealed a trend toward an increased risk of postthrombolysis symptomatic intracerebral hemorrhage [odds ratio: 1·98 (95% confidence interval, 0·90 to 4·35; P = 0·09), I2 = 0%]. Adjusted analysis minimizing potential bias resulted in an increased absolute risk of 4·6% for the development of symptomatic intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2·29 (95% confidence interval, 1·01 to 5·17), I2 = 0%] reaching borderline significance ( P = 0·05). A significant relationship between increasing microbleed burden and symptomatic intracerebral hemorrhage ( P = 0·0015) was observed. Isolated analysis of studies using exclusively intravenous tissue plasminogen activator was insignificant. Our data suggest that patients with cerebral microbleeds are at increased risk for symptomatic intracerebral hemorrhage following thrombolysis for acute ischemic stroke. However, current data are insufficient to justify withholding thrombolytic therapy from acute ischemic stroke patients solely of the basis of cerebral microbleed presence. [ABSTRACT FROM AUTHOR]

Background and purpose Cerebral microbleeds ( CMBs) are extravasations of blood from lipohyalinized or amyloid angiopathic cerebral arterioles, and the presence and numbers of CMBs are significantly associated with the development of oral anticoagulation ( OA)-related intracranial haemorrhage ( ICH). The aim of this study was to investigate whether there is a difference in CMBs burden according to CHADS2 scores or CHA2 DS2- VASc scores in non-valvular atrial fibrillation ( NVAF) patients. Methods We included 550 ischaemic stroke patients who had NVAF and who had undergone brain magnetic resonance imaging ( MRI) with gradient-recalled echo ( GRE) T2 sequences from our prospective stroke registry between January 2005 and November 2011. We calculated CHADS2 scores and CHA2 DS2- VASc scores for all patients based on their underlying cardiovascular diseases. The presence, location and number of CMBs were assessed in each patient. We also investigated whether the CMBs were actually associated with the development of ICH during follow-up. Results The mean patient age was 70.4 ± 10.5 years, and 324 (58.9%) patients were men. One-hundred and seventy-three patients (31.5%) had CMBs detected on GRE MRI. Higher CHADS2 scores or CHA2 DS2- VASc scores were strongly associated with the presence and number of CMBs. During follow-up of median 3.1 ± 1.6 years, the presence of CMBs was independently associated with the development of ICH, whilst the CHADS2 scores or CHA2 DS2- VASc scores were not. Conclusions Considering the positive association between the presence of CMBs and OA-related ICH, our results suggest that the increase in ICH in high-risk groups during OA may be related to an increased burden of CMBs. [ABSTRACT FROM AUTHOR]

Microbleeds have been implicated to play a role in many neurovascular and neurodegenerative diseases. The diameter of each microbleed has been used previously as a possible quantitative measure for grading microbleeds. We propose that magnetic susceptibility provides a new quantitative measure of extravasated blood. Recently, a Fourier-based method has been used that allows susceptibility quantification from phase images for any arbitrarily shaped structures. However, when very small objects, such as microbleeds, are considered, the accuracy of this susceptibility mapping method still remains to be evaluated. In this article, air bubbles and glass beads are taken as microbleed surrogates to evaluate the quantitative accuracy of the susceptibility mapping method. We show that when an object occupies only a few voxels, an estimate of the true volume of the object is necessary for accurate susceptibility quantification. Remnant errors in the quantified susceptibilities and their sources are evaluated. We show that quantifying magnetic moment, rather than the susceptibility of these small structures, may be a better and more robust alternative. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A higher incidence of lacunar infarction (LI) has been reported in nonwhite stroke populations. This study examined racial-ethnic differences in the clinical presentation and imaging findings of a racially-ethnically diverse population with acute LIs. Patients with acute LIs were identified over a 3-year period. Baseline clinical characteristics, vascular risk factors, and magnetic resonance imaging findings were analyzed. Comparisons were made between African Americans, Caribbean blacks, Caribbean Hispanics, and non-Hispanic whites. During the study period, 1036 patients with ischemic stroke were admitted, 194 of whom (25%) had a LI. The proportion of LI was the highest in Caribbean blacks (40%) and lowest in non-Hispanic whites (7%), with African Americans (25%) and Caribbean Hispanics (22%) showing a similar frequency. The mean patient age was 62 ± 12 years, and the study group was 55% male. Hypertension (92%) and dyslipidemia (74%) were the most frequent risk factors. The prevalence of hypertension was highest in African Americans and Caribbean blacks, whereas Caribbean Hispanics were more likely to smoke and have dyslipidemia. Despite similar vascular risk factors and a shared genealogy, the proportion of LI differed in African Americans and Caribbean blacks. Conversely, no difference in the prevalence of LI was seen in African Americans and Caribbean Hispanics, even though the 2 groups had differences in vascular risk factors. Our findings suggest that other determinants besides traditional vascular risk factors influence the risk of LI. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA)., Aims: We investigated the proportion of cerebellar ICH and asymptomatic macro- and microbleeds in Dutch-type hereditary CAA (D-CAA), a severe and essentially pure form of CAA., Methods: Symptomatic patients with D-CAA (defined as ≥1 symptomatic ICH) and presymptomatic D-CAA mutation-carriers were included. We assessed magnetic resonance imaging scans for symptomatic (cerebellar) ICH and asymptomatic cerebellar macro- and microbleeds according to the STRIVE-criteria. Location was assessed as superficial-cerebellar (cortex, vermis or juxta-cortical) or deep-cerebellar (white matter, pedunculi cerebelli and gray nuclei)., Results: We included 63 participants (mean age 58 years, 60% women, 42 symptomatic). In total, the 42 symptomatic patients with D-CAA had 107 symptomatic ICH (range 1-7). None of these ICH were located in the cerebellum. Six of 42 (14%, 95%CI 4-25%) symptomatic patients and none of the 21 (0%, 95%CI 0-0%) presymptomatic carriers had ≥ 1 asymptomatic cerebellar macrobleed(s). All macrobleeds were superficially located. Cerebellar microbleeds were found in 40 of 63 (64%, 95%CI 52-76) participants (median 1.0, range 0-159), 81% in symptomatic patients and 29% in presymptomatic carriers. All microbleeds were strictly or predominantly superficially (ratio superficial versus deep 15:1) located., Conclusions: Superficially located asymptomatic cerebellar macrobleeds and microbleeds are common in D-CAA. Cerebellar microbleeds are already present in the presymptomatic stage. Despite the high frequency of cerebellar micro and macrobleeds, CAA pathology did not result in symptomatic cerebellar ICH in patients with D-CAA.

Background: Gait disturbances may appear prior to cognitive dysfunction in the early stage of silent cerebrovascular disease (SCD). Subtle changes in gait characteristics may provide an early warning of later cognitive decline. Our team has proposed a vision-based artificial intelligent gait analyzer for the rapid detection of spatiotemporal parameters and walking pattern based on videos of the Timed Up and Go (TUG) test. The primary objective of this study is to investigate the relationship between gait features assessed by our artificial intelligent gait analyzer and cognitive function changes in patients with SCD., Methods: This will be a multicenter prospective cohort study involving a total of 14 hospitals from Shanghai and Guizhou. One thousand and six hundred patients with SCD aged 60-85 years will be consecutively recruited. Eligible patients will undergo the intelligent gait assessment and neuropsychological evaluation at baseline and at 1-year follow-up. The intelligent gait analyzer will divide participant into normal gait group and abnormal gait group according to their walking performance in the TUG videos at baseline. All participants will be naturally observed during 1-year follow-up period. Primary outcome are the changes in Mini-Mental State Examination (MMSE) score. Secondary outcomes include the changes in intelligent gait spatiotemporal parameters (step length, gait speed, step frequency, step width, standing up time, and turning back time), the changes in scores on other neuropsychological tests (Montreal Cognitive Assessment, the Stroop Color Word Test, and Digit Span Test), falls events, and cerebrovascular events. We hypothesize that both groups will show a decline in MMSE score, but the decrease of MMSE score in the abnormal gait group will be more significant., Conclusion: This study will be the first to explore the relationship between gait features assessed by an artificial intelligent gait analyzer and cognitive decline in patients with SCD. It will demonstrate whether subtle gait abnormalities detected by the artificial intelligent gait analyzer can act as a cognitive-related marker for patients with SCD., Trial Registration: This trial was registered at ClinicalTrials.gov ( NCT04456348 ; 2 July 2020)., (© 2022. The Author(s).)

Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by amyloid β (Aβ) peptide deposition within the walls of medium to small-caliber blood vessels, cerebral microhemorrhage, and blood-brain barrier (BBB) leakage. It is commonly associated with late-stage Alzheimer's disease. BBB dysfunction is indicated as a pathological substrate for CAA progression with hyperpermeability, enhancing the extravasation of plasma components and inducing neuroinflammation, further worsening BBB injury and contributing to cognitive decline. Although significant effort has been made in defining the gene mutations and risk factors involved in microvascular alterations with vascular dementia and Alzheimer's disease, the intra- and intercellular pathogenic mechanisms responsible for vascular hyperpermeability are still largely unknown. The present study aimed to elucidate the transcriptional profile of the cerebral microvessels (BBB) in a murine model with CAA vasculopathy to define potential causes and underlying mechanisms of BBB injury. A comprehensive RNA sequencing analysis was performed of CAA vasculopathy in Tg-SwDI mice at 6 and 18 months in comparison to age-matched wildtype controls to examine how age and amyloid accumulation impact the transcriptional signature of the BBB. Results indicate that Aβ has a critical role in triggering brain endothelial cell and BBB dysfunction in CAA vasculopathy, causing an intense proinflammatory response, impairing oxidative metabolism, altering the coagulation status of brain endothelial cells, and remodeling barrier properties. The proinflammatory response includes both adaptive and innate immunity, with pronounced induction of genes that regulate macrophage/microglial activation and chemokines/adhesion molecules that support T and B cell transmigration. Age has an important impact on the effects of Aβ, increasing the BBB injury in CAA vasculopathy. However, early inflammation, particularly microglia/macrophage activation and the mediators of B lymphocytes' activities are underlying processes of BBB hyperpermeability and cerebral microbleeds in the early stage of CAA vasculopathy. These findings reveal a specific profile of the CAA-associated BBB injury that leads to a full progression of CAA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Situ, Citalan-Madrid, Stamatovic, Keep and Andjelkovic.)

Objectives: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL., Methods: Subjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated., Results: Data from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia ( p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723-0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719-0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551-0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity., Conclusion: The characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Taniguchi, Shindo, Tabei, Onodera, Ando, Urabe, Kimura, Kitagawa, Miyamoto, Takegami, Ihara, Mizuta, Mizuno and Tomimoto.)

Central nervous system (CNS) infections are a major cause of human morbidity and mortality worldwide. Even patients that survive, CNS infections can have lasting neurological dysfunction resulting from immune and pathogen induced pathology. Developing approaches to noninvasively track pathology and immunity in the infected CNS is crucial for patient management and development of new therapeutics. Here, we develop novel MRI-based approaches to monitor virus-specific CD8+ T cells and their relationship to cerebrovascular pathology in the living brain. We studied a relevant murine model in which a neurotropic virus (vesicular stomatitis virus) was introduced intranasally and then entered the brain via olfactory sensory neurons - a route exploited by many pathogens in humans. Using T2*-weighted high-resolution MRI, we identified small cerebral microbleeds as an early form of pathology associated with viral entry into the brain. Mechanistically, these microbleeds occurred in the absence of peripheral immune cells and were associated with infection of vascular endothelial cells. We monitored the adaptive response to this infection by developing methods to iron label and track individual virus specific CD8+ T cells by MRI. Transferred antiviral T cells were detected in the brain within a day of infection and were able to reduce cerebral microbleeds. These data demonstrate the utility of MRI in detecting the earliest pathological events in the virally infected CNS as well as the therapeutic potential of antiviral T cells in mitigating this pathology., Competing Interests: LL, SD, RH, NP, TA, NB, DM, EM, SG, DM, AK No competing interests declared

The structural integrity of the cerebral white matter, including that of the white matter lesions (WML) and of the surrounding normal appearing white matter (NAWM), can be assessed with diffusion tensor imaging (DTI), which is suggested to be of added value in the explanation of cognitive dysfunction in cerebral small vessel disease (SVD). We investigated the value of DTI of NAWM and WML in addition to conventional magnetic resonance imaging (MRI) parameters in the variance of cognitive performance in subjects with SVD. 499 individuals with SVD, 50-85 years, without dementia, underwent MRI scanning, including a DTI sequence. Grey matter, white matter (WM), and WML volume, number of microbleeds, lacunar and territorial infracts, and mean diffusivity (MD) and fractional anisotropy (FA) in NAWM, WML, and total WM were related to cognitive performance in multivariate regression analyses, after adjustment for age, gender, and education. All MRI parameters together accounted for 1-6% of the variance in cognitive function on top of 22-36% already explained by age, gender, and level of education. Both mean MD and FA of the NAWM, WML, and total WM did not substantially contribute to the explained variance of cognitive function, to that already explained by conventional MRI parameters. When considered separately, the MD of the (NA)WM had the strongest association with cognitive performance. In conclusion, DTI of NAWM and WML has limited additional value to conventional MRI parameters in the etiological explanation of the variance in cognitive function among individuals with SVD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cerebrovascular lesions (CVLs) are known to play important roles in the pathophysiology underlying Alzheimer''s disease (AD), especially in elderly AD cases. The present study was conducted to elucidate the relationship between the CVLs and vascular risk factors (VRFs) in elderly Japanese patients with AD. Subjects and methods: The CVLs such as lacunar infarcts, old microbleeds (OMBs), white matter lesions (WMLs), and occlusive vascular lesions on MRI were analyzed in relation to the risk factors in 120 Japanese patients with probable AD. Their mean age was 75.6years. The subjects were divided into two age groups: young-old group (YOG) consisting of 55 cases being younger than 75years and old-old group (OOG) consisting of 65 cases being 75years or older. Results: In overall analysis, 10 cases (8.3%) showed brain atrophy without CVLs on MRI, 46 cases (38.3%) showed WMLs in addition to the brain atrophy, 61 cases (50.8%) showed lacunar lesions, and 3 cases (2.5%) were diagnosed as having a superficial siderosis. Lacunar infarcts and OMBs were more frequently observed in OOG than in YOG, and were also more frequently observed in those with 2 or more VRFs than those with less than 2 VRFs (p<0.05). The WMLs were more pronounced in OOG, and in those with more VRFs. Conclusion: The CVLs including lacunes, WMLs, and OMBs were present more than 90% of elderly Japanese patients with AD. As the severity of CVLs was associated with VRFs and age, VRFs may modify clinical presentation of elderly AD patients. [Copyright &y& Elsevier]

Abstract: Cerebral small vessel disease (CSVD) is a chronically proceeding pathology of small brain vessels associated with white matter lesions, lacunar infarcts, brain atrophy and microbleeds. CSVD leads to slowly increasing cognitive and functional deficits but may also cause stroke-like symptoms, if vessels in critical brain areas are affected. Spontaneously hypertensive stroke-prone rats (SHRSP) exhibit several vascular risk factors, develop infarcts and hemorrhages and therefore represent a relevant model for the study of CSVD. Using this animal model, we recently demonstrated that intravasal accumulations of erythrocytes, we interpreted as stases, stand at the beginning of a pathological vascular cascade. After stases microbleeds occur, which are followed by reactive microthromboses. Bleeds and thromboses finally cause hemorrhagic infarcts. Immunohistochemical stainings show, that plasma proteins like IgG are deposited in the walls of vessels affected by stases. Further, we found small clots and thread-shaped aggregations of thrombocytes as well as thread-shaped structures of von Willebrand-Factor within stases. Thus, we conclude that blood–brain barrier damages occur in the neighborhood of stases and stases seem to be associated with a restricted activation of blood coagulation without formation of obstructive thromboses. Finally, we demonstrate that small vessel damage rarely appears in the cerebellum. Even animals with multiple cerebral infarcts may be free of any cerebellar vascular pathology. [Copyright &y& Elsevier]

Abstract: New guidelines for the diagnosis of vascular cognitive impairment (VCI) represent an important step in the definition of this clinical entity. These guidelines still remain vague in the definition of “vascular” brain lesions causing cognitive decline, because longitudinal correlative imaging studies are still scarce. In this review we explore which abnormalities are likely to contribute to VCI based on a proven vascular etiology, fast progression and their incidence or progression being related to cognitive decline. Among focal changes visible on standard MRI these features apply for coalescent white matter changes. The evidence for lacunes and microbleeds is much less convincing. Microstructural alterations in normal appearing brain tissue which can be detected by new MRI techniques such as magnetization transfer imaging (MTI), diffusion tensor imaging (DTI) and high resolution MR appear to better correlate with cognitive decline, but the etiology of these changes and their histopathological correlates is still incompletely understood as is their evolution over time. New multimodal image processing such as voxel-based lesion-symptom mapping (VLSM) or combinations of DTI and voxel-based analysis will allow to allocate the lesion patterns that show the greatest covariance with clinical outcome. Such data and more longitudinal correlative data on lacunes and microbleeds will increase our pathophysiologic understanding of VCI including the interplay with primary degenerative processes and will lead to refinement of current VCI criteria. [Copyright &y& Elsevier]

Abstract: Subcortical vascular dementia or cerebral small vessel disease is a common cause of disability in the elderly. On magnetic resonance imaging the disease is manifested as white matter lesions, lacunes and microbleeds. Its etiology is complex, with age and hypertension as established risk factors. The heritability of white matter lesions is constantly high over different populations. Linkage studies identified several loci for these lesions however no genes responsible for the linkage signals had been identified so far. Results from genetic association studies using the candidate gene approach support the role of APOE, the renin–angiotensin system, as well as the Notch3 signaling pathway in the development of subcortical vascular dementia. The recent genomegenome wide association study on white matter lesions identified a novel locus on chromosome 17q25 harboring several genes such as TRIM65 and TRIM47 which pinpoints to possible novel mechanisms leading to these lesions. [Copyright &y& Elsevier]

Abstract: Microbleeds are small dot-like lesions which can be appreciated on gradient echo, T2*-weighted magnetic resonance images as hypointensities. They are considered as an expression of small vessel disease on MRI, next to lacunes and white matter hyperintensities (WMH). Microbleeds are relatively common in vascular dementia, with reported prevalences between 35% and 85%. In the context of vascular dementia, microbleeds are mainly thought to result from hypertensive vasculopathy, but the frequent co-occurrence of lobar microbleeds suggests that neurodegenerative pathology and/or cerebral amyloid angiopathy is also of importance. The presence of multiple microbleeds in vascular dementia or in patients with vascular cognitive impairment is related to worse performance on cognitive tests, mainly in psychomotor speed and executive functioning. They may have some predictive value in terms of predicting development of (vascular) dementia, mortality and disability. Data on the occurrence of stroke and post-stroke dementia in patients with microbleeds are to date not available. New definitions and diagnostic criteria for vascular dementia and vascular cognitive impairment are needed and should take into account microbleeds. [Copyright &y& Elsevier]

Background Microbleeds ( MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration ( FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging ( MRI) in post-mortem FTLD brains. Patients and methods The neuropathological and MRI findings in 12 FTLD brains were compared with eight age-matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, the distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central and the occipital level of a cerebral hemisphere. Results Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls ( P = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers ( P < 0.01) and borderline increased in the middle cortical layers ( P = 0.07) of the frontal section. Conclusions Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood-brain barrier. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage is the second most common subtype of stroke. In recent decades our understanding of intracerebral hemorrhage has improved. New risk factors have been identified; more knowledge has been obtained on previously known risk factors; and new imaging techniques allow for in vivo assessment of preclinical markers of intracerebral hemorrhage. In this review the latest developments in research on intracerebral hemorrhage are highlighted from an epidemiologic point of view. Special focus is on frequency, etiologic factors and pre-clinical markers of intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Stroke prevention efforts typically focus on either ischemic or hemorrhagic stroke. This approach is overly simplistic due to the frequent coexistence of ischemic and hemorrhagic cerebrovascular disease. This coexistence, termed 'mixed cerebrovascular disease', offers a conceptual framework that appears useful for stroke prevention strategies. Mixed cerebrovascular disease incorporates clinical and subclinical syndromes, including ischemic stroke, subclinical infarct, white matter disease of aging (leukoaraiosis), intracerebral hemorrhage, and cerebral microbleeds. Reliance on mixed cerebrovascular disease as a diagnostic entity may assist in stratifying risk of hemorrhagic stroke associated with platelet therapy and anticoagulants. Animal models of hemorrhagic cerebrovascular disease, particularly models of cerebral amyloid angiopathy and hypertension, offer novel means for identifying underlying mechanisms and developing focused therapy. Phosphodiesterase (PDE) inhibitors represent a class of agents that, by targeting both platelets and vessel wall, provide the kind of dual actions necessary for stroke prevention, given the spectrum of disorders that characterizes mixed cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular lesions are frequently observed in Alzheimer brains. Not all of them are due to cerebral amyloid angiopathy. Some of them are related to the severity of the degenerative process itself, implying additional vascular factors in the pathogenesis of Alzheimer's dementia. The aim of the study was to investigate the impact of cerebrovascular pathology on brains with frontotemporal lobar degeneration (FTLD). Patients and Methods: Twenty-two brains with autopsy-proven FTLD were compared to 15 brains of age-matched patients without evident cognitive decline, who died from an illness not related to a brain disease. The prevalence and the severity of small ischaemic and haemorrhagic lesions were determined. Vascular risk factors and the use of antithrombotic agents were also recorded. Results: The patients with FTLD were heterogeneous concerning age of onset, disease duration, clinical presentation, genetic background and neuropathological typing. Cerebrovascular risk factors and lesions were overall rare in FTLD brains without differences in their prevalence and severity compared to the controls. Only white matter changes were more prevalent in the FTLD group (p = 0.04) and showed a trend to greater severity (p = 0.08). Conclusions: Cerebrovascular pathology is not contributing to the evolution of the disease process of patients with FTLD. The isolated prevalence of white matter changes should not be considered as a vascular indicator. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: White matter changes (WMC) and microbleeds (MBs) are common in the elderly and in patients with Alzheimer's disease (AD). Objective: To describe the prevalence, anatomical distribution and longitudinal changes of WMC and MBs in normal aging subjects compared to AD patients and to describe current evidence of their effects on the clinical course of AD. Methods: Short literature review. Results: WMC and MBs are more frequent and progress more rapidly in AD patients than in cognitively normal elderly. New MBs occur in up to one quarter of AD cases without any therapeutic intervention. WMC and MBs influence the clinical course of AD. Conclusion: WMC and MBs might represent treatment targets in clinical trials on AD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly. Objective: To analyze β-amyloid (Aβ) species in plasma in order to uncover biological markers that may contribute to improve the diagnosis of CAA in life. Methods: We determined the level of Aβ(1-40), Aβ(N-40), Aβ(1-42) and Aβ(N-42) in plasma of CAA-related ICH patients (n = 29) and healthy controls (n = 21) using xMAP® technology. Hemorrhages were identified and classified using a CT scan and brain MRI. Patients were clinically classified as probable or possible CAA according to the Boston criteria. Results: We found that plasma full-length Aβ(1-42) and truncated fragments Aβ(N-42) were higher in probable CAA patients than in controls (p < 0.001 and p = 0.046, respectively), and full-length Aβ(1-40) was selectively elevated in probable CAA compared to possible cases (p = 0.015) and controls (p = 0.005). In addition, plasma Aβ(N-42) levels were also higher in patients that presented multiple lobar macrohemorrhages compared to patients that had one symptomatic hemorrhagic event (p = 0.022), indicating that a certain degree of CAA severity is necessary to show increased Aβ fragments in peripheral circulation. Conclusion: Our results suggest that specific Aβ fragments in plasma might be considered as potential biomarkers for the diagnosis of CAA. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The underlying pathology of lacunar infarcts, white matter lesions and also of microbleeds is poorly understood. We assessed whether the presence of lacunar infarcts, white matter lesions or microbleeds on MRI was associated with a decrease in cerebrovascular reactivity, and assessed whether this association was similar for lacunar infarcts, white matter lesions and microbleeds. BOLD-fMRI scan with breath-holding at 7T and anatomical scans at 1.5T were available in 49 patients with atherosclerotic disease from the Second Manifestations of ARTerial disease (SMART) study. Microbleeds and lacunar infarcts were scored visually and volumetric assessment of white matter lesions was performed on the 1.5T scan. The percentage of voxels with a significant signal change on breath-holding and the whole brain signal change were calculated as measures of cerebrovascular reactivity. The mean percentage of voxels with a significant signal change was 25.1% (SD 6.6) and the mean percentage whole brain signal change was 1.20% (SD 0.51). Age, gender, and diastolic blood pressure were significantly associated with cerebrovascular reactivity. Cerebrovascular reactivity was lower with increasing age, lower in females compared to males and lower with lower diastolic blood pressure. ANCOVA showed that patients with microbleeds (n=18) had a significantly lower whole brain signal change than patients without microbleeds, with a mean difference of −0.36% (95% CI −0.64 to 0.07), independent of age, sex, systolic and diastolic blood pressure and non-lacunar infarcts. No significant associations were found for presence of lacunar infarcts or white matter lesion volume with whole brain signal change or percentage of voxels with a significant signal change. The results show that presence of microbleeds is associated with an impaired cerebrovascular reactivity in patients with atherosclerotic disease, whereas no significant association was found for the presence of lacunar infarcts or white matter lesions in our study. [Copyright &y& Elsevier]

Although Alzheimer's disease (AD) is basically considered to be a neurodegenerative disorder, cerebrovascular disease is also involved. The role of vascular risk factors and vascular disease in the progression of AD remains incompletely understood. With the development of brain MRI, it is now possible to detect small-vessel disease, whose prevalence and severity increase with age. The first types of small-vessel disease to be described were white matter hyperintensities (WMHs). More recently, small areas of signal loss on T2*-weighted images, also called microbleeds (MBs), have been reported. Cerebral MBs are focal deposits of hemosiderin that indicate prior microhemorrhages around small vessels, related to either ruptured atherosclerotic microvessels or amyloid angiopathy. Consequently, using brain MRI for the detection of microangiopathy may prove useful to improve our understanding of the impact of the vascular burden in AD pathology. The relationship between microangiopathy and the clinical course of AD or the conversion of mild cognitive impairment to AD remains questionable in terms of cognitive or affective symptoms, particularly if we consider MBs. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing interest in cerebral microbleeds (CMBs) and their role in cerebrovascular disease. A few studies have investigated the histopathological correlation between CMBs and neuroimaging findings. We conducted a systematic review in an attempt to characterize the pathological and radiological correlation. Methods: A systematic literature search was conducted for studies in which CMBs were characterized histopathologically and correlated with MRI findings. Results: Five studies met the inclusion criteria, with a total of 18 patients. Hemosiderin deposition was reported in 42 CMBs (49%), while 16 CMBs (19%) were described as old hematomas which stained for iron, 13 (15%) had no associated specific pathology, 11 (13%) contained intact erythrocytes, 1 (1%) was due to vascular pseudocalcification, 1 (1%) was a microaneurysm and 1 (1%) was a distended dissected vessel. Lipofibrohyalinosis was the most prominent associated vascular finding. Amyloid angiopathy was present primarily in patients with dementia. Conclusions: Although histopathological associations have been observed using MRI in patients with CMBs, the findings have yet to be validated and further research is warranted. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Susceptibility-weighted imaging (SWI) is a new method in MR imaging. SWI detects the signal loss created by disturbance of a homogeneous magnetic field; these disturbances can be caused by paramagnetic, ferromagnetic, or diamagnetic substances. There are many neurologic conditions that can benefit from this method. Objective: To assess the role of magnetic susceptibility weighted imaging in evaluation of brain lesions. Methods: The study was conducted on 30 patients with different brain lesions. Routine MRI study and SWI were done to all patients. Results: The study included 30 patients with different brain lesions, including three patients with diffuse axonal injury, six patients with stroke, six patients with brain tumors, six patients with chronic microbleeds, five patients with venous malformations and venous thrombosis and four patients with extra-axial hemorrhage. In all patients SWI proved excellent demonstration of veins as well as bleeds. Conclusion: SWI is valuable in the diagnosis of different brain lesions and should be included in routine assessment of the brain. [Copyright &y& Elsevier]

Abstract: Subcortical vascular dementia (SVD) is a small vessel disease with dementia that exhibits relatively uniform clinical and pathological features and constitutes approximately half of vascular dementia (VaD) cases. This subtype is further classified into Binswanger''s disease and multiple lacunar infarctions. The former is characterized by diffuse white matter lesions, and the latter is characterized by lacunar infarctions. Both of these entities are related to hypertensive small vessel changes. Subcortical vascular dementia may exhibit slowly progressive vascular Parkinsonism and dementia but can be differentiated from Alzheimer''s disease because it is associated with more extensive white matter lesions, less severe hippocampal atrophy and the absence of cerebral amyloid angiopathy (CAA), which may be indicated radiologically by lobar microbleeds, cortical subarachnoid hemorrhage (SAH) and cortical microinfarctions. Cerebral amyloid angiopathy may manifest as dementia and constitute the cortical type counterpart of SVD in small vessel disease with dementia. This paper provides an overview of the clinical features, pathogenesis and treatment for SVD, as well as its relationship to CAA and Alzheimer''s disease. [Copyright &y& Elsevier]

Neuroimaging plays an important role in etiologic research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to unravel causes of neurological disease by performing neuroimaging in a population-based longitudinal setting. In 1995 and 1999 random subsets of the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. We also describe the imaging protocol and post-processing techniques, and highlight the main findings to date. Finally, we make recommendations for future research, which will also be the main focus of investigation in the Rotterdam Scan Study. [ABSTRACT FROM AUTHOR]

There has been little investigation on the association between cognitive impairment and the microbleeds (MBs) frequently seen in subcortical vascular dementia (SVaD). One possible mechanism of cognitive decline in individuals with SVaD could be disruption of cholinergic fibers by vascular lesions. Central cholinergic circuits in human brain can be tested non-invasively by means of a transcranial magnetic stimulation (TMS) protocol named short latency afferent inhibition (SAI) of motor cortex. In the present study, we used this test in SvaD patients with and without MBs. SAI was evaluated in 13 SVaD patients with MBs (MB-positive group) and the data were compared with those from a group of 15 SVaD patients without MBs (MB-negative group) and with those from 20 healthy subjects. Moreover, we studied covariation of individual SAI values with the Mini-Mental State Examination (MMSE) total score and subscores. SAI was significantly reduced in the MB-positive group when compared with the MB-negative group and the control subjects. Total MMSE score, 'attention and calculation' and 'orientation' subscores were significantly lower in the MB-positive group than in the MB-negative group; SAI showed a positive correlation with total MMSE score. Adjustment for age, gender, education, presence of lacunae, severe white matter hyperintensities or severe periventricular hyperintensities did not affect these findings. This study provides novel physiological evidence that MBs have an impact on central cholinergic function that is independent of the extent of associated white matter changes and ischaemic stroke. This finding shows that TMS have potential diagnostic and therapeutic implications. TMS studies may help in evaluating the causes of cognitive impairment in cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02–1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15–12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in other intracerebral haemorrhage types. Ischaemic brain lesions are associated with white matter changes and cerebral microbleeds, suggesting that they result from an occlusive small-vessel arteriopathy. Diffusion-weighted imaging lesions contribute to the overall burden of vascular-related brain damage in intracerebral haemorrhage, and may be a useful surrogate marker of ongoing ischaemic injury from small-vessel damage. [ABSTRACT FROM AUTHOR]

Abstract: Background: To evaluate the presence of ischemic and hemorraghic lesions in brain MRI of patients with Fabry disease (FD). Methods: Brain MRI studies in 46 consecutive patients were evaluated using classic sequences as well as GRE-weighted images, for ischemic lesions and chronic microbleed detection. Of the 36 adult patients (15 males, mean age 31.2years; 21 females, mean age 41.6years). All had signs or symptoms of FD but lacked history of stroke or TIA. Results: Ten patients under 20years of age initially presented a normal MRI. One child developed a hyperintense occipital lesion on T2-weighted imaging during control MRI. Sixteen adult patients (44.4%) had brain MRI evidence of small vessel disease in the basal ganglia, corona radiata, thalamus or brainstem, as well as in the periventricular white matter. Patients with MRI abnormalities were older (45.6 vs 30.9years, p=0.005), with more vascular risk factors (1.2 vs 0.6 p=0.043). Three women (mean age 59.5years) presented deep chronic microbleeds identified by GRE. Moreover, Flair and T2-weighted images revealed white matter disease and deep gray matter involvement. Conclusion: 44.4% of adult patients with FD without clinical history of CVA or prior dialysis had evidence of small vessel disease on MRI and 11% showed cerebral microbleeds. FD is a treatable disorder that should be routinely included in the differential diagnosis of ischemic and microhemorraghic lesions in young adults. [Copyright &y& Elsevier]

This study evaluated the impact of cerebral microbleeds (CMBs) on the health-related quality of life (HRQoL) in 458 Chinese patients with first or recurrent acute ischemic stroke. HRQoL was assessed with the Short Form-36 (SF-36). Univariate analysis showed the presence of lobar CMBs to be negatively correlated with patients' physical functioning (PF; p < 0.01), social function (SF; p < 0.01), and role-emotional (RE; p < 0.05) scores. Subsequent linear regression analysis revealed lobar CMBs to be independently associated with the PF and SF scores ( p < 0.05). The limitations of this study include the exclusion of patients with more severe stroke, the lack of longitudinal assessments, the use of a generic rather than stroke-specific HRQoL scale, and the less than optimal sensitivity of the CMB measurement. The study findings suggest that CMBs have a significant impact on the HRQoL of stroke survivors. [ABSTRACT FROM AUTHOR]

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥55 years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patients. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Patients with cardioembolic ischemic stroke from nonvalvular atrial fibrillation (NVAF) are candidates for long-term anticoagulation. This study examines the prevalence of cerebral microbleeds (MBs) in stroke patients with NVAF. METHODS: A total of 132 consecutive ischemic stroke patients with NVAF admitted to our Stroke Unit were recruited if complete magnetic resonance (MR) imaging studies including T2∗ imaging had been performed within less than 72 hours. National Institutes of Health Stroke Scale scores were documented and cerebrovascular risk factors were monitored. RESULTS: Among 132 patients (mean age 74.1 ± 9.8 years), only 9 (6.8%) had MBs (mean number 6.2) as detected on T2∗ MR images. No statistically significant differences between patients without versus with MBs were observed regarding arterial hypertension, diabetes, hyperlipidemia, and coronary heart disease. However, small vessel disease (SVD) was significantly more frequent in patients with MBs than without MBs (44.4% vs. 12.2%; P < .05) and significantly more patients with MBs experienced repeated strokes (44.4% vs. 14.6%; P < .05). CONCLUSIONS: In contrast to studies reflecting a high incidence of MBs in stroke patients of various subtypes, MBs occurred less frequently in patients with cardioembolic acute ischemic stroke associated with NVAF. In patients with severe SVD or repeated cerebrovascular events, special caution should be taken regarding oral anticoagulation. [ABSTRACT FROM AUTHOR]

Isolated, non-traumatic, cortical subarachnoid haemorrhage (cSAH) is a rare type of cerebrovascular disease caused by various disorders. In a few cases, especially in the elderly, no apparent cause can be identified. We report a case series of patients without apparent cause of cSAH. We aimed to determine whether cerebral amyloid angiopathy (CAA) could be a common cause of cSAH. We retrospectively analysed clinical and radiological data of consecutive patients admitted to a tertiary stroke unit with cSAH. All patients had brain MRI as a part of their initial evaluation and a repeat examination during follow-up. Amongst 25 patients with cSAH, 10 patients had no apparent cause of cSAH (six men and four women; mean age ± SD: 73.8 ± 8.5 years). All patients with no apparent cause presented with single or recurrent focal transient neurological symptoms of short duration. Only one patient experienced headache. cSAH was limited to one or two sulci, mostly the central sulcus. MRI showed the evidence of prior asymptomatic bleeding in 9/10 patients: cortical hemosiderosis (9/10), lobar intracerebral haemorrhage (ICH) (6/10) and cortical microbleeds (9/10). Eight of ten patients met the Boston criteria for probable CAA and 2/10 for possible CAA. During follow-up, three patients had recurrent bleeding: cSAH (2) and lobar ICH (1). Our findings suggest that CAA could be a common cause of cSAH in the elderly with a fairly uniform clinical presentation. In addition to prior cortical bleeding (ICH, MBs), most patients from the present series had evidence of focal cortical hemosiderosis likely corresponding with prior unrecognized cSAH and suggesting that cSAH was a recurrent event. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cerebral microbleeds (CMBs) are common in stroke survivors, although their clinical significance in the development of psychiatric conditions following stroke remains unknown. This study examines the association between post-stroke depression (PSD) symptom severity and CMBs. Methods: Amongst the 4088 patients with acute ischemic stroke who had been admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong, between December 2004 and May 2009, 994 patients were recruited. A psychiatrist administered the Structural Clinical Interview for DSM-IV to all 994 patients and made a diagnosis of PSD three months after the index stroke. PSD symptom severity was assessed with the 15-item Geriatric Depression Scale (GDS). Seventy-eight patients were found to have PSD. The presence and location of CMBs were evaluated with magnetic resonance imaging (MRI). Results: Seventy-eight patients (7.8%) had PSD. CMBs were identified in 20 PSD patients. Relative to the no-CMB group, the mean GDS score of patients with lobar CMBs was significantly higher (12.6±2.6 versus 10.4±2.5, p =0.01 after adjusting for age, sex, global cognitive functions, neurological deficits and white matter hyperintensities). Limitations: Patients with more severe stroke, those who died before the three-month follow-up and those who became depressed later were excluded, as were those unable to give their consent due to dementia or aphasia. These selection biases may limit the generalizability of the findings. Conclusions: The results suggest that lobar CMBs may contribute to PSD symptom severity. The importance of CMBs in the pathogenesis of other psychiatric disorders in stroke survivors and other patient populations warrants further investigation. [Copyright &y& Elsevier]

Abstract: Increasing evidence from neuro and retinal imaging, neuropathology, epidemiology and experimental models suggests that the primary underlying initiating cause of cerebral small vessel disease is the derangement of the blood-brain barrier. This may start some years before the first symptoms, leads to the small vessel structural changes (vessel wall thickening, disorganisation and eventual breakdown) and perivascular changes (oedema, enlarged perivascular spaces, tissue damage interpreted as “infarcts”) and is fundamentally different to traditional “ischaemic” mechanisms, although small vessel occlusion due to thrombus formation on damaged vessel walls may be a late secondary phenomenon. Space limits a detailed discussion of the epidemiology and experimental evidence, so this brief review will focus on neuroimaging evidence and summarise the appearances, risk factors and associations of different components of cerebral small vessel disease as identified on imaging, discuss potential causes and, in particular, the evidence that disordered blood-brain barrier precipitates or worsens progression of cerebral small vessel disease. This mechanism may also play a role in other common disorders of ageing such as Alzheimer''s disease. [Copyright &y& Elsevier]

Abstract: Despite availability of harmonized criteria for the investigation of patients with presumed “vascular cognitive impairment (VCI)” there exists no clear definition of VCI. The challenge lies in the definition of those vascular components being responsible for the cognitive–behavioural decline of elderly patients. We advocate the use of longitudinal brain MRI studies to establish what type and extent of lesion progression parallels cognitive deterioration in elderly patients who often present with a plethora of diffuse and focal brain abnormalities that may or may not contribute to their cognitive phenotype. So far, a temporal relationship between lesion progression and cognitive decline has been established only for two types of “vascular” abnormalities. The most convincing evidence exists for confluent white matter lesions, less, but clearly supportive data are available for lacunes. All other brain abnormalities including microbleeds, loss of brain volume due to vascular processes or ultrastructural brain changes as seen with new imaging techniques need to be further explored in terms of their pathological correlates, rates of progression and their relationship to cognitive functioning. Such data are the pre-requisite to further develop the currently vague concept of VCI to a clearly defined diagnostic entity. [ABSTRACT FROM AUTHOR]

Background: Microsusceptibility changes in the brain are well known to correspond with microbleeds or micrometal fragments in adults, but this phenomenon has not been explored well in children. Objective: To assess imaging and clinical characteristics of children with multiple foci of microsusceptibility changes using susceptibility-weighted imaging (SWI). Materials and methods: Between 2006 and 2008, 12 children with multiple foci of microsusceptibility on SWI without corresponding abnormal signal on conventional MRI were identified and were retrospectively assessed. Results: The locations of foci of microsusceptibility included the cerebral white matter, basal ganglia, brainstem and cerebellar white matter, without any clear systematic anatomic distribution. CT ( n = 5) showed no calcification at the locations corresponding to the microsusceptibility on SWI. Conventional MR imaging showed white matter volume loss ( n = 5), delayed myelination ( n = 2), acute infarction ( n = 1), chronic infarction ( n = 1), meningitis ( n = 1), slight signal abnormality in the white matter ( n = 1) and no abnormal findings ( n = 1). Follow-up SWI ( n = 3) showed no change of the microsusceptibility foci. Interestingly, all children had a history of heart surgery under extracorporeal circulation for congenital heart disease. Conclusion: Multiple foci of microsusceptibility can be seen in the brain on SWI in children with congenital heart disease who underwent heart surgery with extracorporeal circulation. [ABSTRACT FROM AUTHOR]

Most concussions in sports medicine are managed without advanced neurological imaging. However, computed tomography and magnetic resonance imaging are sometimes used in the management of complex sports concussions to identify acute/ delayed intracranial bleeding or other associated pathology. Advances in imaging techniques have led to greater resolution and the identification of pathology of uncertain clinical significance. This report describes the presence of persistent cerebral microhemorrhages identified on magnetic resonance imaging in a collegiate football player who suffered a concussion. The associated risks and clinical significance of cerebral microhemorrhages have not been determined in the young athletic population. This case highlights provocative issues in the management of sports concussions as related to findings on modern neurological imaging and their potential implication on to return-to-play considerations. [ABSTRACT FROM PUBLISHER]

Background: It is well known that silent ischemic brain lesions on diffusion-weighted imaging (DWI) commonly occur after various interventional procedures or surgeries. However, to our knowledge, postoperative new lesions on T2*-weighted gradient-echo imaging (GRE) have never been explored. Methods: This prospective observational study enrolled 19 consecutive patients undergoing cardiac valve surgery. Preoperative and postoperative (within 7 days) GRE and DWI were performed. New GRE lesions were defined as signal loss lesions on postoperative GRE which were not observed on preoperative GRE. Long-term follow-up GRE was performed in a limited number of cases. Results: Twelve patients developed 26 small (<10 mm) new GRE lesions. Of these patients, 1 had a generalized seizure accompanied by confusion and facial weakness with DWI lesions, and 1 showed confusion of short duration without DWI lesions. Long-term follow-up GRE was performed 3 years after surgery in 4 patients. Of the 12 new GRE lesions in these 4 patients, 11 lesions were still observable on long-term follow-up GRE. Conclusions: New cerebral lesions on GRE after cardiac valve surgery are common and are presumed to be rapidly developed microbleeds and mostly asymptomatic. Further studies are needed to investigate the precise nature and clinical implications of new GRE lesions. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Gradient-echo T2*-weighted magnetic resonance imaging (T2*-weighted MRI) is highly sensitive for detecting cerebral microbleeds (CMBs). CMBs have been reported to be a risk factor for future cerebrovascular events and a marker of cerebral small vessel disease in the general population. Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. The relationship between CKD and CMBs, which has not been clarified to date, is examined. [ABSTRACT FROM PUBLISHER]

Neuroimaging with iron-sensitive MR sequences [gradient echo T2* and susceptibility-weighted imaging (SWI)] identifies small signal voids that are suspected brain microbleeds. Though the clinical significance of these lesions remains uncertain, their distribution and prevalence correlates with cerebral amyloid angiopathy (CAA), hypertension, smoking, and cognitive deficits. Investigation of the pathologies that produce signal voids is necessary to properly interpret these imaging findings. We conducted a systematic correlation of SWI-identified hypointensities to tissue pathology in postmortem brains with Alzheimer’s disease (AD) and varying degrees of CAA. Autopsied brains from eight AD patients, six of which showed advanced CAA, were imaged at 3T; foci corresponding to hypointensities were identified and studied histologically. A variety of lesions was detected; the most common lesions were acute microhemorrhage, hemosiderin residua of old hemorrhages, and small lacunes ringed by hemosiderin. In lesions where the bleeding vessel could be identified, β-amyloid immunohistochemistry confirmed the presence of β-amyloid in the vessel wall. Significant cellular apoptosis was noted in the perifocal region of recent bleeds along with heme oxygenase 1 activity and late complement activation. Acutely extravasated blood and hemosiderin were noted to migrate through enlarged Virchow– Robin spaces propagating an inflammatory reaction along the local microvasculature; a mechanism that may contribute to the formation of lacunar infarcts. Correlation of imaging findings to tissue pathology in our cases indicates that a variety of CAA-related pathologies produce MR-identified signal voids and further supports the use of SWI as a biomarker for this disease. [ABSTRACT FROM AUTHOR]

Hyperintensities on T1-weighted magnetic resonance imaging (MRI) in the setting of brain ischemia are usually considered hemorrhagic transformations. Such changes can also be seen due to "incomplete infarction" with selective neuronal loss. Arguments regarding the cause of these T1 hyperintensities have shuttled between gemistocytic astrocyte accumulation, tissue calcification and paramagnetic substance deposition. Susceptibility weighted imaging (SWI), a sensitive modality for detecting paramagnetic agents and blood products, has never been used to resolve this issue. The study was aimed to evaluate the SWI signal changes of T1 hyperintense lesion in stroke patients and understand its usefulness in differentiating a hemorrhagic infarct and an incomplete infarct. All the seven patients with infarct, having hyperintensities on T1 weighted MRI seen over the last one year were subjected to SWI. In none of the patients SWI failed to show any blooming. By doing SWI for T1-weighted hyperintensities, we can differentiate hemorrhagic infarct and a non-hemorrhagic "incomplete infarct". This differentiation will immensely help in planning management strategy and prognostication. [ABSTRACT FROM AUTHOR]

A new iron sensitive MR sequence (susceptibility weighted imaging – SWI) enabling the simultaneous quantitation of regional brain iron levels and brain microbleeds (BMB) has been acquired serially to study dementia. Cohorts of mildly cognitively impaired (MCI) elderly (n = 73) and cognitively normal participants (n = 33) have been serially evaluated for up to 50 months. SWI phase values (putative iron levels) in 14 brain regions were measured and the number of BMB were counted for each SWI study. SWI phase values showed a left putaminal mean increase of iron (decrease of phase values) over the study duration in 27 participants who progressed to dementia compared to Normals (p = 0.035) and stable MCI (p = 0.01). BMB were detected in 9 out of 26 (38%) MCI participants who progressed to dementia and are a significant risk factor for cognitive failure in MCI participants [risk ratio = 2.06 (95% confidence interval 1.37–3.12)]. SWI is useful to measure regional iron changes and presence of BMB, both of which may be important MR-based biomarkers for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

A 65-year-old architect was admitted to our Memory Clinic because of rapidly progressive dementia accompanied by behavioral disorders, which severely restricted his functional independence. The physical examination revealed several focal neurological signs, and neuroimaging confirmed a cerebellar hemorrhage, multiple microbleeds and an ischemic lacunar infarct. Executive functioning was highly impaired. This case report illustrates cerebral amyloid angiopathy as an important entity of vascular dementia and highlights the importance of neuroimaging in patients with suspected vascular cognitive disorders. [ABSTRACT FROM AUTHOR]

Background: To define the cardiovascular risk factors for cerebral microbleeds and to investigate the relationship between microbleeds on the one hand, and the volume of age-related white matter hyperintensities (WMH) and atrophy on the other in an elderly population. Methods: Four hundred and thirty-nine elderly subjects (age range: 72–85; mean: 77) suffering from vascular disease or at high risk for developing this condition were included in this study. For each subject the number and localization of the microbleeds was recorded. Results: The prevalence of microbleeds in this study was 24%. We found age and a history of hypertension to be risk factors for microbleeds. After regional subdivision systolic blood pressure was found to be a risk factor for microbleeds located in the basal ganglia. A history of hypertension was more prevalent in patients with corticosubcortical and basal ganglia microbleeds. Magnetic resonance imaging risk factors associated with one or more microbleeds were total WMH volume, subcortical WMH volume, and periventricular WMH volume. Total WMH volume and periventricular WMH volume were risk factors for corticosubcortical microbleeds and basal ganglia microbleeds. Conclusion: A high prevalence of microbleeds was found in a population of patients suffering from vascular disease or at high risk for developing this condition. Age, hypertension and WMH were the most important risk factors for microbleeds, especially when located in the corticosubcortial junction or in the basal ganglia. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]