Cardiac diastolic dysfunction is associated with cerebral white matter lesions in elderly patients with risk factors for atherosclerosis

Cerebral white matter lesions on magnetic resonance imaging (MRI) are considered to be the result of brain ischemic injury and a risk factor for clinical stroke. The purpose of this study was to elucidate the relationship between the cardiac diastolic function and cerebral white matter lesions in elderly patients with risk factors for atherosclerosis. The study subjects were 55 patients (75 +/- 7 years) with risk factors for atherosclerosis including hypertension, diabetes mellitus, and dyslipidemia. Patients with symptomatic cerebrovascular events were excluded from the study. Cerebral white matter lesions, which were defined as exhibiting high intensity regions on brain MRI, were evaluated with the degrees of periventricular hyperintensity (PVH) according to the Japanese Brain Dock Guidelines of 2003. Peak early diastolic mitral annular velocity (E' velocity) was measured by tissue Doppler echocardiography, and was used as a parameter of cardiac diastolic function. The mean value of E' velocity was decreased due to the cardiac diastolic dysfunction (5.2 +/- 1.4 cm/s). In addition, the E' velocity was inversely correlated with the degree of PVH (rho = -0.701, p < 0.001). Stepwise regression analysis showed that the decrease in the E' velocity (beta coefficient = -0.42, p < 0.001) and the presence of hypertension (beta coefficient = 0.31, p = 0.001) were independent determinants of the degree of PVH. Thus, cardiac diastolic dysfunction is correlated to the severity of cerebral white matter lesions, suggesting the cardio-cerebral connection in elderly patients with risk factors for atherosclerosis.     

Migraine and white matter hyperintensities

Patients with migraine are at increased risk for white matter hyperintensities detected on magnetic resonance imaging. The presence of nonspecific white matter hyperintensities may cause uncertainty for physicians and anxiety for patients. The pathophysiology and long-term consequences of these lesions are unknown. Occasionally, white matter lesions in a migraineur may indicate an underlying disease such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), or central nervous system vasculitis. The ability to distinguish between nonspecific and disease-specific patterns of white matter hyperintensities in migraine sufferers is important for the practicing clinician.     

Current concepts of analysis of cerebral white matter hyperintensities on magnetic resonance imaging

Cerebrovascular disease is common and associated with cognitive deficits and increased risk for dementia. Until recently, only limited attention has focused on advances in imaging techniques to better define and quantify the spectrum of asymptomatic cerebrovascular disease commonly seen on magnetic resonance imaging, such as abnormal white matter signals. Abnormal signals in cerebral white matter, although nonspecific, are increased in prevalence and severity in association with aging and cerebrovascular risk factors among older individuals. The ubiquitous occurrence of these abnormal white matter signals commonly referred to as white matter hyperintensities (WMHs) and the association with cerebrovascular risk and cognitive impairment among older individuals make scientific evaluation of WMHs an important and much needed avenue of research. In this section, we review current methods of WMH analysis. Strengths and limitation of both quantitative and qualitative methods are discussed initially, followed by a brief review of current magnetic resonance imaging segmentation and mapping techniques that make it possible to assess the anatomical location of WMHs. We conclude by discussing future analytic methods designed to better understand the pathophysiology and cognitive consequences of WMHs.     

The Prevalence of Cerebral Damage Varies With Migraine Type: A MRI Study

Studies on the prevalence of MRI signal abnormalities in the brains of migraineurs have yielded controversial results. In order to provide further data on this issue we reviewed the MRI scans of 38 migraine patients without current neurologic symptoms (mean age 35.8 +/- 11.9 years). In addition, we compared the findings in those 24 migraineurs under 50 years without major cerebrovascular risk factors (mean age 30.1 +/- 9.0 years) to that in 14 headache and risk factor free volunteers (mean age 37.8 +/- 5.3 years). Overall, focal areas of hyperintense signal were seen in 15 (39%) patients. They were present on both proton density and T2-weighted spin-echo sequences. Lesion prevalence varied according to the type of headache (18% in migraine without aura, 53% in migraine with typical aura, 38% in basilar migraine). The subset of migraine patients under 50 years exhibited MRI signal abnormalities more than twice as often as controls (33% vs. 14%). Punctate white matter hyperintensities were the predominant finding and were seen in 10 of 15 individuals with MRI lesions. More striking signal abnormalities consisted of symmetrical areas of hyperintensity lateral to the posterior horns in two 24 year old patients and of extensive white matter damage with lacunar infarcts in a 59 year old woman. Our findings confirm a higher prevalence of MRI lesions in a mixed group of migraineurs than in headache free individuals. Signal abnormalities are most often non-specific, however their occurrence relates to the type of migraine.     

Migraine and Cognitive Decline: A Topical Review

Migraine has been linked with an increased risk of stroke and an increased prevalence of clinically silent brain lesions and white‐matter hyperintensities. As it is known that stroke and structural brain lesions are associated with an increased risk of cognitive decline, it has been hypothesized that migraine may be a progressive brain disorder and associated with an increased risk of cognitive impairment. Given the prevalence of migraine in the population, especially among women, and the aging of the population, an association between migraine and cognitive impairment would have substantial public health implications. In this review, we will summarize the existing evidence evaluating the association between migraine and cognitive function. Additionally, we will discuss methodological issues in migraine and cognitive function assessment and elaborate on study design strategies to address this important question.     

Magnetic resonance imaging of the brain in patients with migraine

Magnetic resonance imaging (MRI) was studied in 91 patients with migraine and in 98 controls. Risk factors known to cause MRI lesions were carefully examined. In 36 patients with migraine (39.6%), small foci of high intensity on T2-weighted and proton-density-weighted images were seen in the white matter. Of patients with migraine who were less than 40 years old and without any risk factor, 29.4% showed lesions on MRI; this was significantly higher than the 11.2% for the group of age-matched controls (n = 98). The lesions were distributed predominantly in the centrum semiovale and frontal white matter in young patients, but extended to the deeper white matter at the level of basal ganglia in the older age group. The side of the MRI lesions did not always correspond to the side of usual aura or headache. Migraine-related variables such as type of migraine, frequency, duration or intensity of headache or consumption of ergotamine showed no significant correlation with the incidence of MRI abnormalities. Our data indicated that migraine may be associated with early pathologic changes in the brain.     

Neuroprotection of the developing brain by systemic administration of vasoactive intestinal peptide derivatives

Periventricular leukomalacia (PVL), a necrotic and often cystic lesion of the cerebral white matter occurring in very premature babies, is the leading cause of cerebral palsy in this population. Increased glutamate release and the excitotoxic cascade thus triggered may be critical factors in the development of PVL. The glutamatergic analog ibotenate injected intracerebrally into newborn mice produces white matter cysts that mimic human PVL. Concomitant injection of vasoactive intestinal peptide (VIP), a trophic factor, protects the white matter against excitotoxic lesions. The goal of the present study was to assess the protective properties of systemically injected VIP analogs against ibotenate-induced excitotoxic white matter lesions in newborn mice. VIP analogs were selected on the basis of their low susceptibility to endopeptidases and their potential ability to cross biological membranes. RO-25-1553, a long-lasting cyclic VIP analog, and stearyl-norleucine-VIP, a fatty derivative of VIP, reduced ibotenate-induced white matter cysts by up to 87% and 84%, respectively, when injected i.p. immediately after ibotenate. By comparison, i.p. coadministration of VIP and ibotenate was not protective against the excitotoxic insult. Furthermore, RO-25-1553 and stearyl-norleucine-VIP still induced significant neuroprotection of the developing white matter when injected systemically 8 and 12 h, respectively, after ibotenate, establishing these peptides as therapeutic agents in this murine model. VIP analogs may have therapeutic potential in human premature babies at high risk for PVL.     

Abnormal deep grey matter development following preterm birth detected using deformation-based morphometry

Preterm birth is a leading risk factor for neurodevelopmental and cognitive impairment in childhood and adolescence. The most common known cerebral abnormality among preterm infants at term equivalent age is a diffuse white matter abnormality seen on magnetic resonance (MR) images. It occurs with a similar prevalence to subsequent impairment, but its effect on developing neural systems is unknown. MR images were obtained at term equivalent age from 62 infants born at 24-33 completed weeks gestation and 12 term born controls. Tissue damage was quantified using diffusion-weighted imaging, and deformation-based morphometry was used to make a non-subjective survey of the whole brain to identify significant cerebral morphological alterations associated with preterm birth and with diffuse white matter injury. Preterm infants at term equivalent age had reduced thalamic and lentiform volumes without evidence of acute injury in these regions (t = 5.81, P < 0.05), and these alterations were more marked with increasing prematurity (t = 7.13, P < 0.05 for infants born at less than 28 weeks) and in infants with diffuse white matter injury (t = 6.43, P < 0.05). The identification of deep grey matter growth failure in association with diffuse white matter injury suggests that white matter injury is not an isolated phenomenon, but rather, it is associated with the maldevelopment of remote structures. This could be mediated by a disturbance to corticothalamic connectivity during a critical period in cerebral development. Deformation-based morphometry is a powerful tool for modelling the developing brain in health and disease, and can be used to test putative aetiological factors for injury.     

Multifocal white matter lesions

There is a long differential diagnosis for multifocal white matter lesions on MR. The most common causes are prominent Virchow-Robin spaces, white matter ischemic change, and multiple sclerosis, but many other causes have been reported. Most of these are related to vascular or other demyelinating etiologies, but infectious/inflammatory disease, trauma, and neoplastic and other unusual causes may also be responsible. Typical imaging features of the more common multifocal white matter disorders are outlined, and the rarer causes are discussed briefly. An approach to imaging differential diagnosis is given, with emphasis on the differences between white matter ischemic lesions and multiple sclerosis.     

Leuko-araiosis: description and clinical correlates.

The term leuko-araiosis as predicted by Hachinski may now have outlived its usefulness. Careful delineation of the white matter changes seen in MR imaging by use of the MR characteristics and by the location of the lesions may reduce the apparent heterogeneity of the associate clinical and neuropathological findings. As currently defined, leuko-araiosis is seen in aggregate more commonly in subjects with cerebro-vascular disease or with cerebro-vascular risk factors but it is a common finding associated with aging in otherwise normal, healthy elderly subjects. Its clinical significance as an isolated finding in these populations should therefore be treated cautiously. Its appearance should alert the physician however to seek for and treat potential cerebro-vascular risk factors.     

A method for the analysis of the geometrical relationship between white matter pathology and the vascular architecture of the brain

A novel method for the visual and quantitative analysis of the geometrical relationship between the vascular architecture of the brain and white matter pathology is presented. The cerebro vascular system is implicated in the pathogenesis of many diseases of the cerebral white matter, for example, stroke, microcerebrovascular disease, and multiple sclerosis (MS). In our work, white matter lesions and vessels are depicted using magnetic resonance imaging (MRI) and extracted using image analysis techniques. We focus on measuring distance relationships between white matter lesions and vessels, and distribution of lesions with respect to vessel caliber. Vascular distance maps are generated by computing for each voxel the Euclidean distance to the closest vessel. Analogously, radius maps assign the radius of the closest vessel to each voxel in the image volume. The distance and radius maps are used to analyze the distribution of lesions with respect to the vessels' locations and their calibers. The method was applied to three MS patients to demonstrate its functionality and feasibility. Preliminary findings indicate that larger MS lesions tend to be farther from detected vessels and that the caliber of the vessels nearest to larger lesions tends to be smaller, suggesting a possible role of relative hypoperfusion or hypoxia in lesion formation.     

弥散张量成像在脑白质病变中的应用价值初探

ThisstudyperformedacombinedconventionalanddiffusiontensorMRimagingfrom10multiplesclerosis,10multiplelacunarinfarction,3cysticercosis,1angiitis,1morphinistand10healthycontrolvolunteerstoinvestigatedmorphologicandquantitativeindex.1Subjectsandmethods1.1SubjectsTwenty-fivepatientsandtenhealthycontrolvol-unteersunderwentacombinedconventionalanddiffusiontensorMRimagingduringoneyear.Thepatientsincludetenmultiplesclerosis(7womenand3men)whoseagewasfrom17to48years,themediandurationofthediseasewas1yea…     

Diffusion—tensor magnetic resonance imaging in brain white matter diseases

Objective To evaluate the usefulness of diffusion-tensor MR imaging in brain white matter diseases.Methods A combined conventional and diffusion tensor MRI were obtained from 10 multiple selerosis,10 multiple lacunar infarction,3 cysticercosis,1 angiitis, 1morphinist and 10 healthy control volunteers.After oblaining mean diffusivity (D) and fractional anisotropy images and image coregistration,the corelations of the lesions and the white matter pathways were investigated.D and A values were measured form four big lesions which can be seen in T2WI and compared to contralateral white matter.Also D and AI value of four different anatomic locations of normal-appearing white matter regions were measured in all patients and controls.Results Whereas the lesions of infarction,cysticercosis and angiitis were in and outside the white matter pathways,all plaques of multiple sclerosis were inside the whit matter pathways.The brain white matter lesions by 1 morphinist were beside the lateral ventricle with big pachy appearance,which was partly inside white matter.For MS,D value was higher in lesion than contorl white matter. But for other diseases,D value could be seen higher or lower compared to healthy side.Ai values were lower in all lesions,D valuewas higher and AI was lower in normal appearing brain white matter when comparing MS to other cases or healthy control volunteers.Conclusion Diffusion tensor MR images can determine the correlations of the lesions and brain white matter pathways.The changes of D and AI values can improve specificity in differential diagnoses though quanti6tatively analyzing the tissue damage in lesions and normal-appearing brain white matter.     

尿毒症脑病患者临床特点与危险因素分析

目的:比较尿毒症脑病（uremic encephalopathy,UE）患者与尿毒症患者的临床特点,以明确尿毒症脑病患者的独立危险因素。方法:回顾性分析广州医科大学附属第二医院2014年1月至2019年1月期间入院的符合慢性肾病（chronic kidney disease,CKD）5期诊断标准的患者,其中所有符合尿毒症脑病诊断标准者为尿毒症脑病组,以性别、年龄、发病时长相匹配为原则,选取与尿毒症脑病组的同一期间住院的主要诊断为CKD 5期的非尿毒症脑病患者为非尿毒症脑病组。采用 t检验和卡方检验比较两组患者的临床基线资料、化验与影像学结果;采用Logistic回归分析尿毒症脑病的独立危险因素。 结果:共收集尿毒症脑病组患者70例,非尿毒症脑病组患者70例。尿毒症脑病组患者中存在饮酒史、慢性阻塞性肺疾病和多囊肾病史的比例均较非尿毒症脑病组高（ P<0.05）。两组患者在高血压病、糖尿病、冠心病方面比较,差异均无统计学意义（ P>0.05）;尿毒症脑病组患者中头颅CT或MRI结果显示存在脑软化灶或白质病变的比例均较非尿毒症脑病组高,差异有统计学意义（ P<0.05）。尿毒症脑病组中血中性粒/淋巴细胞比值（NLR）与尿酸（UA）均高于非尿毒症脑病组（ P<0.05）,而血血红蛋白（ALB）与游离T3（FT3）水平均低于非尿毒症脑病组（ P<0.05）。Logistic回归模型分析显示,血NLR、FT3和ALB水平是尿毒症脑病患者的独立危险因素。 结论:头颅影像中常出现的脑软化灶和脑白质病变是尿毒症脑病患者区别于CKD 5期未发生脑病患者的变化特点。NLR、FT3和ALB水平是尿毒症脑病患者的独立危险因素。     

Gray and white matter density changes in monozygotic and same-sex dizygotic twins discordant for schizophrenia using voxel-based morphometry

Global gray matter brain tissue volume decreases in schizophrenia have been associated to disease-related (possibly nongenetic) factors. Global white matter brain tissue volume decreases were related to genetic risk factors for the disease. However, which focal gray and white matter brain regions best reflect the genetic and environmental risk factors in the brains of patients with schizophrenia remains unresolved. 1.5-T MRI brain scans of 11 monozygotic and 11 same-sex dizygotic twin-pairs discordant for schizophrenia were compared to 11 monozygotic and 11 same-sex dizygotic healthy control twin-pairs using voxel-based morphometry. Linear regression analysis was done in each voxel for the average and difference in gray and white matter density separately, in each twin-pair, with group (discordant, healthy) and zygosity (monozygotic, dizygotic) as between subject variables, and age, sex and handedness as covariates. The t-maps (critical threshold value mid R:tmid R: > 6.0, P < 0.05) revealed a focal decrease in gray matter density accompanied by a focal increase in white matter density in the left medial orbitofrontal gyrus and a focal decrease in white matter density in the left sensory motor gyrus in twin-pairs discordant for schizophrenia as compared to healthy twin-pairs. Focal changes in left medial (orbito)frontal and left sensory motor gyri may reflect the increased genetic risk to develop schizophrenia. Focal changes in the left anterior hemisphere may therefore be particularly relevant as endophenotype in genetic studies of schizophrenia.     

MRI in Migraineurs

Forty-six migraineurs and 69 age- and sex-matched controls referred for MRI scans of the brain were evaluated for the incidence of intracranial pathology. Axial long TR/short TE and long TR/long TE and sagittal short TR/short TE scans were performed in all patients. Enhancement with Gd-DTPA was performed in all controls and in nine migraineurs. Six of 46 (13%) of the migraineurs had white matter lesions versus three of 69 (4.3%) of the controls. The white matter lesions in migraineurs were seen in a younger age group than in the controls. These findings agree with recent MRI studies. Ischemia or an immune-based white matter demyelination are possible mechanisms for the white matter lesions.     

White matter atrophy and lesion formation explain the loss of structural integrity of white matter in aging

The importance of macrostructural white matter changes, including white matter lesions and atrophy, in intact brain functioning is increasingly being recognized. Diffusion tensor imaging (DTI) enables measurement of the microstructural integrity of white matter. Loss of white matter integrity in aging has been reported, but whether this is inherent to the aging process itself or results from specific white matter pathology is unknown. In 832 persons aged 60 years and older from the population-based Rotterdam Study, we measured fractional anisotropy (FA) and directional diffusivities in normal-appearing white matter using DTI. All subjects' DTI measures were projected onto a common white matter skeleton to enable robust voxelwise comparison. With increasing age, multiple regions showed significant decreases in FA or increases in axial or radial diffusivity in normal-appearing white matter. However, nearly all of these regional changes were explained by either white matter atrophy or by white matter lesions; each of which related to changes in distinct brain regions. These results indicate that loss of white matter integrity in aging is primarily explained by atrophy and lesion formation and not by the aging process itself. Furthermore, white matter atrophy and white matter lesion formation relate to loss of integrity in distinct brain regions, indicating the two processes are pathophysiologically different.     

White matter lesion extension to automatic brain tissue segmentation on MRI

A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.     

Migrainous Infarction: Aspects on Risk Factors and Therapy

Migraine and stroke are related in more than one way. Migraine with aura is a risk factor for ischemic stroke in women under age 45?years, particularly when combined with other risk factors such as smoking and oral contraceptives. Further, individuals with migraine with aura seem to have more white matter lesions and ischemic infarctions than control patients. Migraine has been correlated to cervical artery dissection, the symptoms of which can mimic migraine. Correspondingly, migraine with aura sometimes is mistaken for stroke. Migrainous infarction is a rare but specific type of ischemic stroke developing during an attack of migraine with aura. It is important to recognize this unusual complication of migraine because the management probably is important. In this review, we will discuss the present knowledge of migrainous infarction, the clinical picture, possible mechanisms, and potential prevention and treatment.     

White matter lesions in migraine and right-to-left shunt: a conventional and diffusion MRI study

Subjects with migraine with aura (MA) have a high prevalence of white matter lesions (WMLs) on magnetic resonance imaging (MRI). Moreover, right-to-left shunt (RILES), mainly due to patent foramen ovale, is frequently associated with MA. The aim of this study was to clarify the relationship between RILES and WML in MA. We enrolled 87 consecutive subjects affected by MA. Patients were screened for migraine characteristics and cerebrovascular risk factors. Transcranial Doppler was used to diagnose RILES and MRI with T2-weighted and diffusion-weighted imaging (DWI) to evaluate presence, number and volume of WMLs. RILES was present in 45% of patients. We did not detect any DWI hyperintense lesion; WMLs were present in 61% of patients on T2-weighted images. Presence of WMLs did not correlate with any migraine clinical feature, whereas the presence, number and volume of WMLs increased with subjects' age. There was no significant difference in the total volume and number of WMLs in the group with and without RILES. In conclusion, RILES does not increase the likelihood of finding WMLs in migraineurs.