Methods: We prospectively enrolled consecutive patients with acute ischemic stroke. Whole blood viscosities at a low or high shear rate were measured using a scanning capillary tube viscometer, and were referred to as diastolic blood viscosity (DBV) and systolic blood viscosity (SBV), respectively. Correlations between blood viscosity and acute stroke etiology or chronic radiological manifestations of cerebralsmallvesseldisease were investigated. The temporal profiles of blood viscosity at the onset of stroke and follow-up at 1 and 5 weeks were investigated. Results: Of the 127 patients admitted with acute ischemic stroke, 63 patients were included in the final analyses. DBV at the onset of stroke was significantly higher in small artery occlusion (SAO) stroke than in other stroke subtypes ( p = 0.037). DBV showed a significant positive correlation with the number of chronic lacunes ( r = 0.274, p = 0.030). The temporal profiles of DBV in SAO stroke showed a transient decrease due to the hydration therapy after 1 week and recurrent elevation at 5 week follow-up ( p = 0.009).
Background: Lacunae, brain atrophy, white matter hyperintensity, enlarged perivascular space and microbleed are magnetic resonance imaging (MRI) markers of cerebralsmall-vesseldisease (cSVD). Studies have reported that higher blood pressure variability (BPV) predicted cardiovascular risk in hypertensive patients; however, the association between BPV and the total MRI burden of cSVD has not been investigated. In this study, we aimed to explore this relationship between BPV and cSVD MRI burden.
individuals with these risk factors never experience a stroke. This may suggest that patients who do develop a stroke are more vulnerable to risk factors than those who do not. Consequently, they may also have a higher risk of developing other (cerebro)vascular diseases. A possible marker of the brain’s vulnerability to vascular risk factors is cerebralsmallvesseldisease (SVD). In the elderly, SVD has convincingly been related to vascular risk factors and accelerated cognitive and motor decline. 5–7
Vascular cognitive impairment (VCI), or cognitive decline due to vascular pathology, is the second most common cause of dementia after Alzheimer's disease and it is a major health concern for the aging populations. In most of the VCI cases, smallvesseldisease is the underlying cerebral pathology (Pantoni, 2010). Cerebralsmallvesseldisease (cSVD) is an umbrella term used for the various disease subtypes where the small vessels in the brain are affected. The term embraces the whole spectrum of related clinical and imaging abnormalities (Pantoni, 2010). The disease itself can be undetected for many years, and so far, there is no available treatment specific for cSVD. There are currently several studies investigating the effects of lifestyle changes and manipulation of vascular risk factors on cSVD; however, the results remain inconclusive (the largest treatment study up to date: the Secondary Prevention of Small Subcortical Strokes (SPS3) study, Benavente et al., 2011; for reviews see Bath & Wardlaw, 2015; Dichgans & Zietemann, 2012).This is in part due to inadequate understanding of the disease pathophysiology. It is therefore of great importance to understand the disease mechanisms to facilitate early diagnosis, optimisation of prevention strategies and provide management of the disease. Furthermore, the pathology of cSVD very often co-occurs with Alzheimer's disease (AD), and both diseases share common risk factors. It is difficult to differentiate the contribution of vascular pathology from Alzheimer pathology; however, for managing and treating cSVD this differentiation is crucial (Wardlaw et al., 2013b).
Hitherto, to our knowledge, the G283R variant has neither been documented as a pathogenic variant nor has it been reported as a benign variant. However, we surmise that this variant is pathogenic, considering that a heterozygous mis- sense substitution at the same position (G283E) has been reported in an individual with cerebralsmallvesseldisease, cognitive impairment, and gait disturbance. 9 In that publica- tion, functional analysis suggested that the mutant gene might cause disease through defective trimerization with the wild type. 9 Although functional analysis was not performed in our case, we suppose that G283R may possibly have similar mo- lecular characteristics as G283E and may have similar pathogenicity.
Abstract: Objective: To evaluate whether hyperhomocysteinemia and cognitive status, vascular endothelial cell ac- tive factor levels, and endothelial progenitor cell (EPC) function are associated with cerebralsmallvesseldisease (CSVD). Methods: A total of 97 patients with CSVD were retrospectively analyzed. According to their plasma homo- cysteine (Hcy) concentrations, the patients were divided into three groups: group A (Hcy <15 μmol/L, n=32), group B (15 μmol/L ≤ Hcy <20 μmol/L, n=44), or group C (Hcy ≥20 μmol/L, n=21). The cognitive functions of the patients in the three groups were evaluated using the Montreal Cognitive Assessment (MoCA) Scale and the Minimum Mental State Examination Scale (MMSE). The vascular endothelial cell active factor levels, including serum intercellular adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1), were measured. The number, proliferation, migration, and adhesion of the EPCs in the peripheral blood of the patients in the three groups were also compared. Results: The MoCA and MMSE scores were the highest in group A and lowest in group C (all P<0.05). The serum ICAM-1 and ET-1 levels were the highest in group C, and the lowest in group A (all P<0.05). The number, proliferation, migration, and adhesion of the EPCs in group B and C were lower than they were in group A, and all the indictors in group C were lower than those in group B (P<0.05). Conclusion: Cognitive impairment, the disturbance of vascular endothelial cell active factors, and a decrease in the number, proliferation, migration and adhesion of EPCs are found in patients with CSVD complicated with hyperhomocysteinemia.
With the development of neuroimaging techniques for the diagnosis of brain pathology, practitioners and researchers are increasingly able to early diagnose cerebrovascular changes, predict, prevent and monitor the effectiveness of the treatment. Enlarged perivascular spaces of the brain is an important neuroimaging indicator of vascular changes, in particular the pathology of cerebralsmallvesseldisease and the risk of lacunar strokes [1, 2]. In addition, EPVS may reflect changes in large vessels - there is a relationship between arterial pulsatility and EPVS that allows identification of individuals at increased risk of territorial stroke [3, 4]. The study of EPVS «in space and time» is a promising predictor of clinical and biological changes.
Cerebralsmallvesseldisease (CSVD) is a neurodegener- ative condition affecting the small blood vessels of the brain. In contrast to cerebral large vessels, small vessels are not visualized by contemporary imaging methods and therefore cerebralsmallvesseldisease is used to de- scribe the parenchyma lesions rather than the underlying smallvessel alterations . The neuroimaging correlates of CSVD include lacunar infarcts, white matter hyperin- tensities, enlarged perivascular spaces, microbleeds, and brain atrophy . CSVD is a neuroradiological diagnosis and the above findings may occur in adults with or with- out a history of clinically manifest stroke or dementia . However, the presence and severity of CSVD neuro- imaging correlates are associated with risk factor burden, baseline cognition and function, and prognosis with re- spect to recurrent stroke and cognitive decline [4–6].
This podcast begins and closes with Dr. Robert Gross, Editor-in- Chief, briefly discussing highlighted articles from the October 31, 2017, issue of Neurology. In the first segment, Dr. Matthew Elliot talks with Dr. Hugh Markus about his paper on multimodal MRI markers and dementia risk in cerebralsmallvesseldisease. In the second part of the podcast, Dr. Brian Eckerle focuses his interview with Dr. Charles Pollack on dabigatran reversal in patients with uncontrolled bleeding or receiving surgery.
related zebrafish foxc1 morphant phenotypes, and (c) the exten- Patients with cerebralsmall-vesseldisease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2 –/– mutants displayed brain vascular phenotypes. Together, these results extend the genetic
Abstract: Cerebralsmallvesseldisease (CSVD) is a group of pathological processes with multifarious etiology and pathogenesis that are involved into the small arteries, arterioles, venules, and capillaries of the brain. CSVD mainly contains lacunar infarct or lacunar stroke, leukoaraiosis, Binswanger’s disease, and cerebral microbleeds. CSVD is an important cerebral microvascular pathogenesis as it is the cause of 20% of strokes worldwide and the most com- mon cause of cognitive impairment and dementia, including vascular dementia and Alzheimer’s disease (AD). It has been well identified that CSVD contributes to the occurrence of AD. It seems that the treatment and prevention for cerebrovascular diseases with statins have such a role in the same function for AD. So far, there is no strong evidence-based medicine to support the idea, although increasing basic studies supported the fact that the treatment and prevention for cerebrovascular diseases will benefit AD. Furthermore, there is still lack of evidence in clinical application involved in specific drugs to benefit both AD and CSVD.
A quarter of ischemic strokes (≈30 000 per year in the UK) are lacunar or small subcortical in type (Fig. 1) (1). These usually cause mild to moderate neurological deficit with low early mor- tality, but can be physically disabling and have a high long-term risk of recurrence and cognitive impairment (5,6). Lacunar stroke is associated with subclinical abnormalities that contribute to the burden of brain damage causing insidious physical and cognitive deficits and vascular dementia (7), and increasing the societal impact beyond that expected from the small size of the infarct alone (3). These abnormalities are easily detected on magnetic resonance imaging (MRI) brain imaging, and include lacunar or small subcortical infarction, lacunes, white matter hyperintensi- ties (WMH) (8) and microbleeds (9). Although they may present after a clinically-overt event, most lacunes (10), subcortical grey or white matter hyperintensities and microbleeds develop ‘silently’. When numerous, all three are associated with cognitive impairment, doubling the risk of dementia and trebling the risk of stroke (11,12). Together with lacunar stroke, these features are collectively known as cerebralsmallvesseldisease (SVD; Fig. 1) (2). Small haemorrhages can also present with lacunar stroke (13); and an as yet unknown proportion of large haemorrhages are also now recognized to have SVD as the major underlying pathology (Fig. 1).
Cerebralsmall-vesseldisease (CSVD) is a syn- drome encompassing clinical, cognitive, radio- logical and pathological features that result from lesions in and around small blood vessels in the brain; capillaries, venules, arterioles and small arteries up to 200 μm in diameter . CSVD accounts for the etiology of 1/4 of acute ischemic strokes [2, 3] and it has been recog- nized as serious disease for the past 15 years . Despite this, its basic causes and risk fac- tors remain somewhat unclear. Diabetes, hyperlipoidemia, hypertension and old age, which are major risk factors for cerebrovascu- lar disease [5-8] in general, could also be fac- tors for CSVD; particularly, age and hyperten- sion are thought to be important for CSVD. Khan et al.  studied the vascular risk factors
Purpose: Cerebralsmallvesseldisease (SVD) is known to be associated with ischemic stroke, intracerebral hemorrhage (ICH), and cognitive impairment. In this retrospective observational study, we explored SVD markers on MRI relevant to spontaneous ICH. Materials and Methods: The ICH group consisted of 150 consecutive patients with a first primary parenchymal ICH, and the con- trol group consisted of 271 age- and sex-matched individuals who underwent brain MRI in a health care center. We compared ce- rebral microbleeds (CMBs), white matter hyperintensities (WMHs), enlarged perivascular space (EPVS), and lacunae in the ICH and control groups.
The diagnosis of cerebralsmallvesseldisease (SVD) is difficult because there is no consensus on clinical criteria and therefore, imaging is important for diagnosis. Most patients undergo brain imaging by computed tomography (CT), which is able to detect ischemic strokes, hemorrhages and brain atrophy and may also indicate white matter changes. Magnetic resonance imaging (MRI) remains the key neuroimaging modality and is preferred to CT in vascular cognitive impairment (VCI) because it has higher sensitivity and specificity for detecting pathological changes. These modalities for imaging morphology permit to detect vascular lesions traditionally attributed to VCI in subcortical areas of the brain, single infarction or lacunes in strategic areas (thalamus or angular gyrus), or large cortical- subcortical lesions reaching a critical threshold of tissue loss. In SVD multiple punctuate or confluent lesions can be seen in the white matter by MRI and were called leukoaraiosis. Another major neuroimaging finding of smallvesseldisease in VCI are microhemorrhages. However, while CT and MRI are able to detect morphologic lesions, these modalities cannot determine functional consequences of the underlying pathological changes.
Cerebralsmallvesseldisease (SVD) is the most common pa- thology underlying vascular dementia. Characteristic MRI appearances include white matter hyperintensities (WMH), la- cunar infarcts, cerebral microbleeds (CMBs), and diﬀuse white matter damage on diﬀusion tensor imaging (DTI). Each is in- dividually associated with cognition, but how these associations result in dementia is incompletely understood. 1,2 A popular hy- pothesis is that cognitive impairment results from disconnection of cortical-subcortical and cortical-cortical connections, 3–5 lead- ing to disruption of large-scale brain networks underlying cog- nitive domains aﬀected by SVD, such as executive function and processing speed. 3 This hypothesis implies that network con- nectivity will mediate associations between conventional SVD brain pathologies and cognitive impairment.
These results correspond to three classes of vessels, namely: vascular bed feeding arteries and arterioles in the ranges D ∈ (190 µm, 210 µm) and D ∈ (30 µm, 50 µm). The present sensitivity study aimed at analysing the model predictions for several conditions of hyper- tensive remodelling, that is, considering scenarios with different MAP and pressure pulses (PP = SBP–DBP). The sensitivities for the differential SBP and DBP are found to be larger when modifying the lumen radius of the vessels, followed by the arterial wall thickness and the peripheral resistance, and finally the peripheral compliance. When the alterations are directed towards Figure 2 Results of the simulations for the two considered scenarios: normotensive (N) and hypertensive (H). Pulsatile arterial pressure (mean between brackets) is displayed at selected arterial vessels covering medium-sized arteries and small-sized arteries. Vessels have been picked up in both centrencephalic and cortical areas. The MAP, SBP and DBP at the same arterial vessels are also reported in table 1 for the normotensive (N) and hypertensive (H) cases. BA, basilar artery; BrA, brachial artery; DBP, diastolic pressure; DMSA, distal medial striate artery; ICA, internal carotid artery; LsA, lenticulostriate artery; MAP, mean arterial pressure; MCA, middle cerebral artery; PCA, posterior cerebral artery; PfA, prefrontal artery; PPB, posterior parietal branch; SBP, systolic blood pressure; TB, terminal branch.
Patients with cSVD represent a clinically and aetiologically relatively homogeneous population (7). It is a disease of the small perforating end arteries in the brain (5,9). cSVD manifests itself as a number of often coexisting conditions, which may be additive in their negative effect on the patient‟s long term prognosis (1). These conditions include white matter ischaemic lesions (WML), microbleeds, dilated or enlarged perivascular spaces (EPVS), infarcts in a lacunar territory either with a concomitant clinical stroke syndrome or clinically „silent‟, plus other silent subcortical infarcts (1,10-12). All of these can be seen on magnetic resonance imaging (MRI) and can be considered structural markers of underlying cSVD. This study primarily aims to evaluate the use of a functional MRI (fMRI) marker in patients with cSVD.
Multiple mechanisms underlying WMH such as incomplete infarct, chronic hypoperfusion and venous collagenous have been proposed, but evidence for each is limited. In a pathology study (n=15), no incomplete infarct was found in WMH. 29 Though many cross- sectional studies have found low cerebral blood ﬂ ow (CBF) to be associated with higher WMH burden, the causality between low CBF and WMH is unclear. 35 A lon- gitudinal study (n=575) showed that more severe base- line WMH predated CBF decline over time rather than falling CBF predating WMH progression. 36 In a post- mortem study, some non-in ﬂ ammatory, periventricular venulopathy was observed in periventricular WMH, sug- gesting that venous collagenosis might cause tissue damage by vasogenic oedema and impede ISF circula- tion. 31 However, this theory remains to be con ﬁ rmed in in vivo studies. Impaired BBB was noted in WMH areas in autopsies, 29 30 which was corroborated by studies using cerebrospinal ﬂ uid (CSF)/plasma albumin ratio 37 and MRI. 38–41 It is hypothesised that the disrupted BBB would result in leakage of ﬂ uid, plasma components and cells and eventually lead to perivascular in ﬂ ammation, demyelination and gliosis. Indeed, the formation of WMH is likely to be multifactorial. Hypoperfusion, venous pathologies and BBB impairment might all play critical roles in WMH initiation or progression and inter- act with each other, but which one is the key initial factor remains unknown.
atherosclerosis in the carotid artery, which can be ob- tained via ultrasonography. Both IMT and carotid plaque are more prevalent in patients with dementia and AD than in cognitively healthy individuals . Moreover, both measures are related to increased cognitive decline in patients with AD . Additionally, several population- based studies have shown that individuals with the highest IMT measures have an increased risk of incident demen- tia, including AD [32,43,44]. Carotid plaque scores were also associated with an increased risk of AD in one study, but this association lacked statistical significance . An- other marker of pre-clinical large vesseldisease is calcifi- cation volume in the atherosclerotic plaque, which can be assessed using computed tomography (CT). Although cal- cification is only part of the plaque, it is a suitable measure of the underlying plaque burden . CT has the disad- vantage of radiation exposure, but CT measures of athero- sclerotic calcification are more observer-independent than ultrasonography measures. Few studies have investigated the relation between CT-derived atherosclerotic calcifica- tion and dementia, but some studies found that larger cal- cification volumes in the coronary arteries, aortic arch, and carotid arteries relate to worse cognitive performance [46,47]. Moreover, larger calcification volume was associ- ated with smaller brain tissue volumes and worse micro- structural integrity of the white matter, which are both factors related to an increased risk of AD . Mecha- nisms linking carotid large vesseldisease to AD include sub-clinical cerebralsmallvesseldisease (see below), hy- poperfusion, or shared etiology [3,4,6].