Degree Of White Matter Lesions Research Articles

SERS “hot spot” enhance-array assay for misfolded SOD1 correlated with white matter lesions and aging

Misfolding of superoxide dismutase-1 (SOD1) has been correlated with many neurodegenerative diseases, such as Amyotrophic lateral sclerosis's and Alzheimer's among others. However, it is unclear whether misfolded SOD1 plays a role in another neurodegenerative disease of white matter lesions (WMLs). In this study, a sensitive and specific method based on SERS technique was proposed for quantitative detection of misfolded SOD1 content in WMLs. To fabricate the double antibodysandwich substrates for SERS detection, gold nanostars modified with capture antibody were immobilized on glass substrates to prepare active SERS substrates, and then SERS probes conjugated with a Raman reporter and a specific target antibody were coupled with active SERS substrates. This SERS substrates had been employed for quantitative detection of misfolded SOD1 levels in WMLs and exhibited excellent stability, reliability, and accuracy. Moreover, experimental results indicated that the level of misfolded SOD1 increased with the increase in age and the degree of WMLs. Hence, misfolded SOD1 may be a potential blood marker for WMLs and aging. Meanwhile, SERS-based gold nanostars have great clinical application potential in the screening, diagnosis and treatment of WMLs.

Neurofilament Light Chain Is a Promising Biomarker in Alcohol Dependence.

Background: Alcohol dependence, a global public health problem, leads to structural and functional damage in the brain. Alcohol dependence patients present complex and varied clinical manifestations and live with general complaints existing in contemporary society, making most people with alcohol dependence hard to identify. Therefore, it is important to find potential biomarkers for the diagnosis and evaluation of alcohol dependence. In the study, we explored potential biomarkers for the diagnosis and monitoring of diseases and evaluated brain structural changes in alcohol dependence patients.Methods: Enzyme-linked immunosorbent assay (ELSA) was employed to detect the expression of serum nucleotide-binding oligomerization domain containing 3 (NLRP3) and single-molecule array (Simoa) assay was used to detect the expression of serum neurofilament light (NfL) in 50 alcohol dependence patients and 50 controls with no drinking history. Alcohol consumption was measured by standard drinks. Neuropsychological assessments, including the Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9), were conducted to evaluate cognitive function and psychological state. The degree of white matter lesions (WMLs) was rated using the Fazekas scale based on magnetic resonance imaging analysis. White matter structure was quantified using the voxel-based morphometry method. The correlations between NLRP3 levels, NfL levels, neuropsychological dysfunction, the degree of WMLs, and white matter volume (WMV) were analyzed in alcohol dependence patients.Results: Serum NLRP3 and NfL levels were higher in the alcohol dependence group. NLRP3 levels were irrelevant to monthly alcohol assumption as well as to the MoCA, PSQI, GAD-7, PHQ-9, and Fazekas scale scores and WMV. NfL levels were positively correlated with the PSQI and PHQ-9 scores as well as the degree of WMLs and negatively correlated with the MoCA scores and WMV. No associations were evident between NfL and monthly alcohol assumption and GAD-7 scores in the alcohol dependence group.Conclusion: This study supports the potential value of serum NfL as a non-invasive biomarker in alcohol dependence. The association with neuropsychological dysfunction and degree of WMLs has implications to use NfL as a promising biomarker to assess the severity of brain damage as well as the progression and prognosis of alcohol dependence.

Blood Pressure Rhythm and Blood Pressure Variability as Risk Factors for White Matter Lesions: A Cross-Sectional Study.

BackgroundWhite matter lesions are common in the elderly. The aim of this study was to explore the correlation between blood pressure rhythm and blood pressure variability with white matter lesions.Material/MethodsA total of 144 subjects aged 40 to 80 years underwent MRI scanning to assess the degree of white matter lesions using the Fazekas scale. The regional cerebral blood flow was detected by brain perfusion imaging, and an ambulatory blood pressure monitor was used to measure the circadian blood pressure rhythm. Odds ratio and the 95% confidence interval was computed using logistics regression analysis. The relationship between various factors and blood pressure was calculated by curve simulation.ResultsWith the increase of white matter lesions, the regional cerebral blood flow at the lesion decreased gradually. Systolic blood pressure day/night difference ratio (OR=0.815, 95% CI 0.729–0.910), diastolic blood pressure day/night difference ratio (OR=0.895, 95% CI 0.831–0.964), systolic blood pressure coefficient of variation (OR=1.589, 95% CI 1.273–1.983), and diastolic blood pressure coefficient of variation (OR=1.363, 95% CI 1.150–1.616) were significantly associated with Fazekas score (P<0.05 for all).ConclusionsGreater blood pressure variability and blood pressure rhythm disorders were associated with lower regional cerebral blood flow in patients with white matter lesions.

Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion

BackgroundSubcortical ischemic vascular dementia, one of the major subtypes of vascular dementia, is characterized by lacunar infarcts and white matter lesions caused by chronic cerebral hypoperfusion. In this study, we used a mouse model of bilateral common carotid artery stenosis (BCAS) to investigate the role of B-cell translocation gene 2 (BTG2), an antiproliferation gene, in the white matter glial response to chronic cerebral hypoperfusion.MethodsBtg2−/− mice and littermate wild-type control mice underwent BCAS or sham operation. Behavior phenotypes were assessed by open-field test and Morris water maze test. Brain tissues were analyzed for the degree of white matter lesions and glial changes. To further confirm the effects of Btg2 deletion on proliferation of glial cells in vitro, BrdU incorporation was investigated in mixed glial cells derived from wild-type and Btg2−/− mice.ResultsRelative to wild-type mice with or without BCAS, BCAS-treated Btg2−/− mice exhibited elevated spontaneous locomotor activity and poorer spatial learning ability. Although the severities of white matter lesions did not significantly differ between wild-type and Btg2−/− mice after BCAS, the immunoreactivities of GFAP, a marker of astrocytes, and Mac2, a marker of activated microglia and macrophages, in the white matter of the optic tract were higher in BCAS-treated Btg2−/− mice than in BCAS-treated wild-type mice. The expression level of Gfap was also significantly elevated in BCAS-treated Btg2−/− mice. In vitro analysis showed that BrdU incorporation in mixed glial cells in response to inflammatory stimulation associated with cerebral hypoperfusion was higher in Btg2−/− mice than in wild-type mice.ConclusionBTG2 negatively regulates glial cell proliferation in response to cerebral hypoperfusion, resulting in behavioral changes.

Cochlear implantation in children with white matter lesions: Prediction of hearing outcomes by multiple regression analysis.

Brain magnetic resonance imaging (MRI) white matter lesions have been reported in some preoperative cochlear implant children. However, the role of white matter lesions in predicting the hearing outcome is yet unclear. The present study investigated the outcomes of cochlear implantation (CI) in 40 children with white matter lesions.The data from children with white matter lesions were reviewed in this retrospective study. Based on brain MRI, the patients were divided into 3 groups: mild, moderate, and severe. The children were treated with unilateral CI and monitored for a follow-up period of at least 3 years. The main outcome measures were category of auditory performance (CAP) and speech intelligibility rating (SIR). MRI white matter lesions, age at implant, gender, physical impairment, and cognitive impairment were obtained from a research database to assess the correlation with long-term CAP and SIR outcome by multiple regression analysis.The data of children with white matter lesions were reviewed (18 females and 23 males). The mean age at implantation was 31.6 months. Strikingly, all children obtained better CAP and SIR scores. The age at implantation, brain white matters lesions on MRI, and cognitive and physical disabilities were associated with CAP and SIR scores. Multiple regression established a weak correlation between the degree of white matter lesions on brain MRI and long-term CAP and SIR, while cognitive impairment strongly accounted for long-term CAP and SIR outcome.The majority of the children with brain white matter lesions obtained a satisfactory postoperative effect. The cognitive impairment before CI is a major factor, and such factor should be considered.

Cochlear implantation in prelingually deaf children with white matter lesions.

White matter lesions (WMLs) are the most common central nervous system changes observed during cochlear implant evaluation. However, its clinical significance in cochlear implantation (CI) remains unclear. The purpose of this study is to explore the effects of WMLs on hearing and speech rehabilitation of prelingually deaf children after CI. The data of forty-five children with WMLs who received CI from 2011 to 2014 were retrospectively reviewed. All patients underwent magnetic resonance imaging examination preoperatively. The categories of auditory performance (CAP) and speech intelligibility rating (SIR) scales were used to evaluate changes in the auditory and speech abilities of the patients, and the Fazekas scale was adopted to assess the extent of WMLs. The degree of WMLs was divided into four grades (none, mild, moderate, severe). We assessed hearing and speech abilities at the following time points: 6, 12, 24, 36, 48 and 60-months post-operation. No significant differences in CAP scores were observed between WMLs groups and the control group at 12months post-CI (p = 0.099), but marked between-group differences were found at 6, 24, 48- and 60-months post-CI. (p < 0.05). Similarly, no significant differences in the SIR scores were observed at 6months post-CI (p = 0.087), but marked between-group differences were found at 12, 24, 48- and 60- months post-CI. (p < 0.05). Analysis of stratified group results revealed improvements in hearing and speech development for all the subgroups, including the severe WMLs subgroup following CI. However, hearing and speech ability of the severe WMLs subgroup was much slower than that of other groups. The auditory and speech abilities of prelingually deaf children with WMLs and those without WMLs can improve after CI. Therefore, WMLs should not be considered a contraindication for CI. However, the decision to perform CI in such patients needs a comprehensive evaluation because the post-surgery effects on children with severe WMLs are not ideal.

Utility of a diffusion-weighted arterial spin labeling (DW-ASL) technique for evaluating the progression of brain white matter lesions

PurposeTo investigate the utility of diffusion-weighted arterial spin labeling (DW-ASL) for detecting the progression of brain white matter lesions. Materials and methodsA total of 492 regions of interest (ROIs) in 41 patients were prospectively analyzed. DW-ASL was performed using the diffusion gradient prepulse of five b-values (0, 25, 60, 102, and 189) before the ASL readout. We calculated the water exchange rate (Kw) with post-processing using the ASL signal information for each b-value. The cerebral blood flow (CBF) was also calculated using b0 images. Using the signal information in FLAIR (fluid-attenuated inversion recovery) images, we classified the severity of white matter lesions into three grades: non-lesion, moderate, and severe. In addition, the normal Kw level was measured from DW-ASL data of 60 ROIs in five control subjects. The degree of variance of the Kw values (Kw-var) was calculated by squaring the value of the difference between each Kw value and the normal Kw level. All patient's ROIs were divided into non-progressive and progressive white matter lesions by comparing the present FLAIR images with those obtained 2 years before this acquisition. ResultsCompared to the non-progressive group, the progressive group had significantly lower CBF, significantly higher severity grades in FLAIR, and significantly greater Kw-var values. In a receiver operator characteristic curve analysis, a high area under the curve (AUC) of 0.89 was obtained with the use of Kw-var. In contrast, the AUCs of 0.59 for CBF and 0.72 for severity grades in FLAIR were obtained. ConclusionsThe DW-ASL technique can be useful to detect the progression of brain white matter lesions. This technique will become a clinical tool for patients with various degrees of white matter lesions.

Analysis of correlation between cerebral perfusion and KIM score of white matter lesions in patients with Alzheimer's disease.

PurposeThis study aimed to characterize white matter lesions (WMLs) and regional cerebral perfusion, and evaluate their correlations with cognitive deficits in Alzheimer’s disease (AD) patients.Patient and methodsOne hundred and twenty-eight patients with AD (AD group) and 75 subjects without AD (control group) were recruited. The medical information was collected from each subject. Montreal cognitive assessment (MoCA) was employed for the assessment of cognition. Cranial MRI was performed, and the KIM scoring system was used to evaluate the white matter hyperintensity. The CT perfusion (CTP) imaging was employed to assess the whole cerebral perfusion, and the region of interest (ROI) was selected to determine the blood perfusion at different parts.ResultsThe education level and MoCA score in AD group were significantly lower than in control group (P<0.001). The KIM score of juxtaventricular WML (JVWMLs) was significantly different between two groups (P<0.05) and AD group showed a higher incidence of severe JVWML and periventricular WML (PVWMLs); in AD group, the total KIM score and KIM scores of JVWMLs, PVWMLs and deep WML (DWMLs) showed negative relationships with the MoCA score (P<0.001). As compared to control group, the blood perfusion of either whole brain or different parts in the AD group reduced significantly (P<0.05). In the AD group, there was a negative correlations of blood perfusion at JVWM and PVWM with corresponding KIM scores (P<0.05 or 0.01). In the AD group, the blood perfusions of the whole brain, JVWMLs, PVWMLs and deep WML were negatively related to MoCA score (P<0.05).ConclusionIn conclusion, the cognitive deficits in the AD patients are associated with the degree of WMLs, especially the JVWML, PVWML and DWML as well as with the reduced perfusion of JVWM, PVWM and deep WM.

Transient increase in CSF GAP-43 concentration after ischemic stroke

BackgroundCerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer’s disease patients; however, patients suffering from stroke have not been studied previously.MethodsThe concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0–1, 2–4, 7–9, 3 weeks, and 3–5 months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging.ResultsIncreased GAP-43 concentration was detected from day 7–9 to 3 weeks after stroke, compared to day 1–4 and to levels in the control group (P = 0.02 and P = 0.007). At 3–5 months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (rs = 0.65, P = 0.001).ConclusionsThe transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer’s disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.

Brain MR Imaging Findings in Woodhouse-Sakati Syndrome

Woodhouse-Sakati syndrome is a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, and progressive extrapyramidal signs. The disease is caused by biallelic pathogenic variants in the DCAF17 gene. The purpose of this study was to describe the spectrum of brain MR imaging abnormalities in Woodhouse-Sakati syndrome. We reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome (12 males, 14 females; age range, 16-45 years; mean age, 26.6 years). Follow-up studies were conducted for 6 patients. All patients had abnormal MR imaging findings. The most common abnormalities were a small pituitary gland (76.9%), pronounced basal ganglia iron deposition (73%), and white matter lesions in 69.2%. White matter lesions showed frontoparietal and periventricular predominance. All white matter lesions spared subcortical U-fibers and were nonenhanced. Prominent perivascular spaces (15.3%) and restricted diffusion in the splenium of the corpus callosum (7.6%) were less frequent findings. Follow-up studies showed expansion of white matter lesions with iron deposition further involving the red nucleus and substantia nigra. Older age was associated with a more severe degree of white matter lesions (P < .001). Small pituitary gland, accentuated iron deposition in the globus pallidus, and nonenhancing frontoparietal/periventricular white matter lesions were the most noted abnormalities seen in our cohort. The pattern and extent of these findings were observed to correlate with older age, reflecting a possible progressive myelin destruction and/or axonal loss. The presence of pituitary hypoplasia and white matter lesions can further distinguish Woodhouse-Sakati syndrome from other neurodegenerative diseases with brain iron accumulation subtypes.

Prediction of white matter lesions and subcortical atrophy for cognitive impairment in patients with ischemic stroke

Objective To investigate the predictive role of cerebral white matter lesions (WML) and subcortical atrophy on cognitive function in patients with acute ischemic stroke (AIS) after 3 months. Methods 233 cases of AIS patients admitted to hospital continuously from September 2016 to March 2018 were enrolled and all of them underwent brain MRI.The degree of WML on FLAIR was evaluated according to the Fazekas grading standard.The linear measurement of subcortical atrophy on T1WI was carried out on the subcortical brain atrophy index, including EVANS ratio (ER), inverse cella media index (iCMI), caudate head index (CHI) and basal cistern index (BCI). Demographic, clinical and imaging data of all patients were also recorded.Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were conducted at 3 months after AIS.The patients were divided into normal cognitive function (NCI) group and post stroke cognitive impairment (PSCI) group according to evaluation results of MMSE and MoCA.Multivariate logistic regression analysis was used to screen the independent risk factors of cognitive impairment. Results Univariate analysis showed that age (t=-4.233, P=0.000), sex (χ2=7.501, P=0.006), education (H=21.188, P=0.000), NHISS score (H=5.791, P=0.016), history of atrial fibrillation (χ2=6.484, P=0.011), TIA (χ2= 9.015, P=0.003), smoking history (χ2=6.943, P=0.008), Fazekas WML score (χ2=27.885, P=0.000), EVANS ratio (H=31.129, P=0.000), inverse cella media index (H=9.434, P=0.002), caudate head index (H=15.148, P=0.000), basal cistern index (t=-1.979, P=0.049) and baseline cognitive function (χ2=136.994, P=0.000) were related to cognitive impairment in patients with AIS after 3 months (P<0.05). Multivariate logistic regression analysis showed that WML score (OR=3.416, P=0.047, 95%CI: 1.017-11.482), EVANS ratio (OR=1.245, P=0.038, 95%CI: 1.012-1.531) and caudate head index (OR=1.187, P=0.040, 95%CI: 1.008-1.397) were risk factors for cognitive impairment in AIS patients after 3 months adjusting for age, education, disease severity and baseline cognitive function. Conclusion WML, EVANS ratio and caudate head index can predict short-term cognitive function in patients with AIS. Key words: White matter lesions; Subcortical atrophy; Acute ischemic stroke; Cognitive impairment

White matter lesions and cognitive impairment may be related to recovery from unilateral spatial neglect after stroke

BackgroundUnilateral spatial neglect (USN) is frequently found in ischemic stroke patients. Because USN is related to poor functional outcomes, evaluating recovery from USN after stroke is critical. MethodsPatients with acute ischemic stroke with lesions in the right cerebral hemisphere on MRI and exhibiting left USN were administered the Behavior Inattention Test (BIT) at 1 and 3weeks after admission. BIT improvement was defined as a ≥1-point increase in ≥4 of the 6 BIT subtests from 1 to 3weeks, or a total BIT score ≥131 at 3weeks. Factors associated with improvement of left USN were analyzed. ResultsEighteen patients (8 men; mean age, 70±12years) were enrolled in this study. BIT was performed at 5.3±0.7 and 18.2±0.7days after admission. Twelve patients were classified to the improvement (I) group, and 6 to the non-improvement (NI) group. BIT scores increased substantially from 76.6±40.5 in the acute phase to 109.2±43.3 in the subacute phase. The I group displayed higher BIT scores than the NI group in both acute and subacute phases (P<0.01 each). The degree of white matter lesions on the Fazekas scale was lower in the I group (0.6±0.7) than in the NI group (1.7±1.2, P=0.028). Increased BIT scores correlated significantly with increased Mini Mental State Examination scores (r=0.487, P=0.040). ConclusionsAmelioration of left USN might be related to white matter lesions and cognitive impairment. Sample size in the current study was small, limiting the generalizability of results, and larger studies are warranted in the future.

The Association Between Leukoaraiosis and Poor Outcome in Intracerebral Hemorrhage Is Not Mediated by Hematoma Growth

The significance of white matter lesions (WMLs) in intracerebral hemorrhage (ICH) remains unclear. We investigated the effects of WML on initial hematoma volume, hematoma growth, intraventricular extension, and clinical outcome in patients with spontaneous ICH. Computed tomography scans of 262 patients included in a placebo arm of a prospective, multicenter trial were used for a semi-quantitative analysis of white matter changes. A logistic regression analysis was used to explore the effects on hematoma volume, volume changes, intraventricular hemorrhage, and clinical outcome after 90 days. The degree of WML was not associated with initial hematoma volume, absolute and relative hematoma growth, hematoma growth >33% or >6 mL, or with intraventricular extension. WML significantly increased the odds for poor outcome after 90 days (adjusted OR 1.4, 95% CI 1.1-1.8, P = .02). WMLs were not associated with initial hematoma volume, hematoma growth, or intraventricular extension. WMLs were associated with poor outcome independently.

Association between the extent of white matter damage and early cognitive impairment following acute ischemic stroke.

White matter (WM) injury following acute ischemic stroke (AIS) is associated with cognitive decline. Establishing relationships between the specific cognitive tests used to assess post-AIS cognition and various clinical indices of WM injury severity and distribution may aid in prognosis and early treatment decisions. We enrolled 62 patients with AIS to Weifang People's Hospital between September 2014 and August 2015. WM lesion severity and distribution were examined by computed tomography (CT) and magnetic resonance imaging (MRI). The Blennow scale was used for scoring the distribution and degree of WM lesions (WMLs) on CT images, the Fazekas scale for scoring periventricular and deep WMLs on MRI, and the Cholinergic Pathways Hyperintensities Scale (CHIPS) for scoring MRI manifestation of cholinergic fiber damage. The 8-domain Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function. Mean ± standard deviation scores on the Blennow scale was 1.6±0.5; Fazekas scale, 3.4±0.8; and CHIPS, 65.7±12.5. The proportion of patients with a MoCA score <26 (indicating cognitive dysfunction) was significantly higher in subgroups with Blennow scale score >2, Fazekas scale score >4, and CHIPS score >51 (all P<0.001). The MoCA score was negatively correlated with Blennow scale score (r=−0.326, P=0.002), Fazekas scale score (r=−0.404, P=0.031), and CHIPS score (r=−0.234, P=0.042). Thus, the degree and distribution of whole-brain, deep, and cholinergic WMLs were associated with cognitive impairment. The Blennow scale, Fazekas scale, and CHIPS all provide good predictive efficacy of post-AIS cognitive dysfunction.

White matter lesions reduce number of brain metastases in different cancers: a high-resolution MRI study.

Brain metastases are major complications of common cancers. Tumor type and proneness to the CNS are thought to define the number and size of brain metastases. It is not known if intrinsic vascular factors can also have an effect. Restricted perfusion due to cerebral small vessel disease is frequent in elderly patients and causes white matter lesions (WML). The aim of this analysis was to evaluate a possible negative effect of WML and patient age on the number and size of brain metastases (BM) of different tumor entities. Pre-therapeutic 3T brain magnetic resonance imaging (MRI) of 200 patients with BM were analyzed. Location, size and number of BM (NoM) were determined. T2 hyperintensive WML were scored according to Fazekas-Score (grade I-III). Patients with WML grade 1 (NoM: 5.59; p = 0.009) and grade 2 (NoM: 3.68; p = 0.002) had significantly less BM than patients without WML (NoM: 6.99). This effect was present in subgroups of different tumors: NSCLC (p = 0.05), other tumors than NSCLC (p = 0.048). Age (≤65 or >65 years) was positively correlated with the degree of WML but not with number (pNoM = 0.832) or mean diameter (pmDM = 0.662) of brain metastases. While patient age did not appear to be relevant, increasing WML were associated with lower number of brain metastases in different tumor types.

Animal Models of Vascular Dementia: Translational Potential At the Present Time and In 2050

ABSTRACT: Vascular dementia is a heterogeneous syndrome, and includes subcortical ischemic vascular dementia. For translational research, subcortical ischemic vascular dementia is an appropriate target since this is the most prevalent subtype and exhibits relatively uniform clinical and neuropathological changes. These changes consist of hypertensive arteriolar changes, lacunar infarctions, hypertensive hemorrhage and white matter lesions. Among various species, rodents are most frequently used, but their small volume of white matter may impede analysis of white matter lesions. Primate models have a larger volume, but the degree of white matter lesions is inconsistent. Animal models should accommodate the effect of aging and comorbidities, and in the case of primate models, low accessibility should be overcome by repeated and quantitative examinations using modern neuroimaging techniques and functional measures, especially for memory and motor function. There is no model that replicates all features of subcortical ischemic vascular dementia and, therefore, rodent and primate models should be selected appropriately for translational research.

Abstract T P360: Risk Factors Underlying Recurrent Subclinical Subcortical Cerebrovascular Lesions in Elderly Patients

Background and Purpose: Subclinical subcortical cerebrovascular lesions (SSCLs) are very common in elderly people. Accumulation of SSCLs may have additive or even synergic effects to the coexisting brain lesions such as Alzheimer’s pathology or symptomatic cerebrovascular lesions in elderly patients, but the mechanisms underlying the recurrence of SSCLs remains to be clarified. The present study was conducted to elucidate the contributing risk factors to the recurrent SSCLs. Subjects and Methods: The present study was based on 96 cases (55 men and 41women) with subcortical lesions, including 49 cases with symptomatic lacunar infarction, 36 cases with asymptomatic lacunar infarction, and 11 cases with symptomatic intracerebral hemorrhage. The mean age was 70.9 years. MRI studies were repeated with an average interval of 416 (248-822) days. Numbers of lacunar infarcts (LIs) and microbleeds (MBs) were counted in all MR slices, and the degree of white matter lesions (WMLs) was evaluated according the Fazekas’ categories, and those parameters were compared between the baseline and follow-up images. Laboratory studies included high sensitivity CRP (hsCRP), interleukin-6 (IL-6), serum lipid profile, glucose and brain natriuretic peptide (BNP). Results: The number of LIs increased in 16 cases whereas unchanged in 80 cases. The number of MBs increased in 16 cases, whereas unchanged in 80 cases. There was a deterioration in the degree of WMLs in 7 cases, whereas no change in 89 cases. Those with recurrent LIs had significantly greater number of LIs in the baseline MRI (p&lt;0.005), and those with recurrent MBs had greater numbers of LIs and MBs at baseline MRI (p&lt;0.005). Those who showed deterioration in WMLs had greater number of MBs and higher total cholesterol, LDL-cholesterol and lower HDL-cholesterol at baseline. Six cases showed combined recurrent vascular lesions, and had significantly elevated hsCRP and IL-6, and greater number of LIs and MB at baseline as compared with those with recurrence in single vascular lesions. Conclusion: The present result suggest that multiple subcortical vascular lesions are already a strong risk for the recurrence, and chronic inflammation may have additional risk for the combined vascular lesions.

Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke.

BACKGROUNDCerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML).METHODSA total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed.RESULTSPatients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test).CONCLUSIONSSeveral CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

Automated Walks using Machine Learning for Segmentation

This paper describes an automated algorithm for segmentation of brain structures (CSF, white matter, and gray matter) in MR images. We employ machine learning, i.e. k-Nearest Neighbors, of features derived from k-means, Canny edge detection, and Tourist Walks to fully automate the seeding process of the Random Walker algorithm. We test our methods on a dataset of 12 diabetes patients with atrophy and varying degrees of white matter lesions provided by the MRBrainS13 Challenge, and find encouraging segmentation performance.

Cognitive Dysfunction and Dementia in Primary Sjögren’s Syndrome

Background. Primary Sjögren's syndrome (PSS) is a frequent systemic autoimmune disease. In this study, we aimed to explore the cognitive impairment and the correlations with brain MRI. Methods. Twenty-five patients (mean age 55 ± 11.8 years, 21 females) with PSS were prospectively selected and tested with a French translation of the Brief Repeatable Battery for Neuropsychological Examination. The results were compared with the scores for 25 matched patients with multiple sclerosis (MS) and 25 controls. Brain lesions were assessed by brain MRI using the Wahlund classification. Results. Fifteen of the 25 PSS patients (60%) presented with cognitive disorders versus 19/25 MS patients (76%). Five patients had dementia in the PSS group. Speed of information processing, attention, immediate and long-term memory, and executive functions were frequently impaired. The mean duration of cognitive complaints was 5.6 ± 6.1 years, and the mean duration of PSS was 15.8 ± 14.0 years. A trend towards a correlation was found between the severity of cognitive impairment and the degree of white matter lesions (WML) (P = 0.03, rho = 0.43). Conclusion. Cognitive impairment—mild or dementia—exists in patients with PSS. Further MRI studies are needed to better understand the precise neural basis of cognitive impairment in PSS patients.