Cerebral White Matter Hyperintensities Research Articles

Journal Club: Relationship between carotid arterial properties and cerebral white matter hyperintensities.

White matter hyperintensities (WMH) are generally diagnosed on brain MRI and are associated with risk of stroke, dementia, death, and functional impairment.1,2 Their progression appears to be insidious, and the detection of preclinical disease could provide the opportunity to aggressively manage risk factors (i.e., reduced thresholds to begin hypertension treatment, lowering blood pressure targets), increase monitoring frequency, and begin secondary prevention strategies in the case of silent infarcts (i.e., initiation of antiplatelet therapy with silent strokes, CT angiography as needed). Given that most people do not receive neuroimaging in the presymptomatic stage, an inexpensive, noninvasive test could help to identify those at risk. To date, potential vascular markers of cerebrovascular disease have focused on central arterial stiffness3; however, directly assessing the carotid arteries may be more relevant to cerebrovascular disease as this vessel serves as the primary conduit responsible for delivering blood to the brain.

White matter hyperintensities and vascular risk factors in monozygotic twins

Cerebral white matter hyperintensities (WMHs) have been associated with vascular risk factors, both of which are under genetic influence. We examined in a monozygotic twin sample whether the association between vascular risk and WMHs is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age = 70 ± 7 years), including 94 complete pairs. Regional WMH load was estimated using an automated algorithm. Vascular risk was summarized with the Framingham score. The within–twin pair correlation for total WMHs was 0.76 and for Framingham score was 0.77. Within participants, Framingham score was associated with total and periventricular WMHs (r = 0.32). Framingham score in 1 twin was also associated with total WMHs in the co-twin (r = 0.26). Up to 83% of the relation between both traits could be explained by shared genetic effects. In conclusion, monozygotic twins have highly similar vascular risk and WMH burden, confirming a genetic background for these traits. The association between both traits is largely driven by overlapping genetic factors.

Blood-ocular barrier disruption in patients with acute stroke

Prompted by the unexpected finding of gadolinium leakage into ocular structures (GLOS) in acute stroke patients, we studied the frequency and nature of this finding in 167 patients. Patients were selected who had an MRI with gadolinium at baseline and another MRI with fluid-attenuated inversion recovery (FLAIR) imaging at 2 and/or 24 hours later. GLOS was detected as lack of vitreous and/or aqueous fluid suppression on postcontrast FLAIR images. GLOS, evident on postcontrast FLAIR MRI, occurred in 127/167 (76%) patients: 86/109 (79%) patients treated with tissue plasminogen activator and 41/58 (71%) who were untreated. At 2 hours after administration of the contrast, GLOS was more common in the aqueous chamber alone, occurring in 67% of patients, compared to the vitreous chamber alone, seen in 6% of patients; it occurred in both chambers in 27% of patients. At 24 hours, GLOS was present in 121/162 (75%) patients, always involving the vitreous chamber, but also affecting the aqueous chamber in 6% of cases. Vitreous GLOS at 24 hours was associated with increasing age (p = 0.002) and a higher burden of cerebral white matter hyperintensities (p = 0.017). Patients with rapid diffuse GLOS, defined as GLOS involving both chambers at 2 hours, had larger infarcts (p = 0.022) and a higher degree of blood-brain barrier permeability (p = 0.025). We found GLOS to be common in patients with acute stroke; delayed GLOS was a marker for chronic vascular disease. The mechanism for acute GLOS remains uncertain but may be a remote effect of acute cerebral injury on the blood-ocular barrier.

Abstract WP403: Patent Foramen Oval (PFO) Shunting is Associated With White Matter Hyperintensity (WMH) in Stroke Patients

Background: Clinical trials report PFO closure to decrease the long-term risk of recurrent paradoxical stroke. We previously found that PFO is not just a back door to clotting, but may increase the risk of chronic neurovascular injury via venous arterial mixing resulting in elevated oxidative mediators. In this study, we prospectively explore the relationship of PFO shunting and chronic WMH, a surrogate for chronic neurovascular injury, compared to non-PFO-related cryptogenic stroke (CS). Method: PFO and non-PFO CS patients were consecutively recruited in accordance with IRB (n=81 PFO; n=98 non-PFO CS). WMHs were scored by vascular neurologist blinded to patient outcome. Result: Compared to CS without PFO, PFO pts had increased WMH burden as measured by Scheltens scale. WMH burden was independently associated with PFO after adjusting for age, gender, NIHSS and disease status (odds ratio: 1.19, p = 0.003). Moreover, in pts s/p PFO closure, WMH score was significantly higher in those with residual shunting as compared with complete closure (Figure 1, 1 vs 8.25, p = 0.038). Conclusion: Our results suggest an important association between PFO-related blood shunting and chronic neurovascular injury as measured by cerebral WMH. Studies in a larger patient cohort are ongoing to investigate the mechanistic relationship between PFO shunting and WMH.

Abstract TP163: Left Ventricular Systolic Dysfunction is Associated With Larger Burden of White Matter Hyperintensity

Background and Purpose: Pathogenesis of cerebral white matter hyperintensity (WMH) is unclear, though it has been known to be the major pathology. Diffuse cerebral hypoperfusion related to low cardiac output from left ventricular systolic dysfunction may be a possible contributor, which has not been validated yet in patients with ischemic stroke. Methods: We recruited consecutive patients with first-ever stroke patients within 7 days of symptom onset. Left ventricular systolic function was evaluated with ejection fraction from echocardiography. WMH volume was measured quantitatively with semi-automated methods. Sensitivity analysis was performed with the Fazekas scale in both periventricular and subcortical areas. Results: A total of 862 patients (mean age 66 years, male 61%) were included, and the median volume of WMH was 3.70 [1.44-11.21] mL. The WMH volumes were negatively correlated with ejection fraction (Pearson correlation efficient = -0.182, P < 0.001). In multivariate analysis, lower ejection fraction [β = -0.045, standard error (SE) = 0.008, P < 0.001], older age (β = 0.056, SE = 0.005, P < 0.001), and frequent diabetes (β = 0.308, SE = 0.133, P = 0.021) were significantly associated with WMH volumes. Sensitivity analysis revealed that low ejection fraction remained significant in the periventricular WMH volumes ( P = 0.039), but not in the subcortical WMH volumes ( P = 0.565). Conclusions: Left ventricular systolic dysfunction is associated with the extent of WMH, especially in periventricular area. These results indicate that cardiac dysfunction may have potential role in the pathogenesis of cerebral WMH

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.

Association between Red Blood Cells Omega-3 Polyunsaturated Fatty Acids and White Matter Hyperintensities: The MAPT Study.

The association between circulating biomarkers of red blood cells (RBC) omega-3 polyunsaturated fatty acids (PUFAs) and cerebral white matter hyperintensities (WMH) on the brain MRI remains yet unclear. We investigated the cross-sectional and prospective associations of RBC omega-3 PUFAs with WMH in dementia-free older adults with subjective memory complaints. Participants were 234 older adults with assessments for both PUFA and MRI near to baseline; among them, 79 also had an MRI assessment at 3-year follow-up. The measurement of WMH volume was obtained by an automated segmentation algorithm. We related individual or combinational baseline RBC omega-3 PUFAs levels with baseline WMH volumes and WMH evolution over 3 years. We carried out multiple (cross-sectional) and mixed-effect (prospective analysis, with random effects at participant's level) linear regressions with adjustment for age, sex, time interval between date of blood draw for measurement of fatty acids and date of brain MRI, the status of APOE e4 carrier, body mass index, and vascular risk factors. Associations were considered significant at p ≤ 0.006 to take into account multiplicity (8 comparisons). None of the eight RBC omega-3 PUFAs tested was significantly associated with WMH at both cross-sectional and prospective analyses. We did not find any association between omega-3 PUFAs and WMH in non-demented older adults with memory complaints. A longer longitudinal study with data on omega-3 PUFAs and WMH would contribute important information to this field.

Increased Rather than Decreased Small Vessel Pulsatility in Patients with Progressing Cerebral White Matter Hyperintensities.

Increased Rather than Decreased Small Vessel Pulsatility in Patients with Progressing Cerebral White Matter Hyperintensities.

Whole genome sequence analyses of brain imaging measures in the Framingham Study

ObjectiveWe sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program.MethodsWe performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants.ResultsWe detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10−8) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10−8). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10−4) and in 17q25 for WMH (rs7214628, p = 2.0 × 10−3) were confirmed. Gene-based tests detected associations (p ≤ 2.3 × 10−6) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease– (UNC5D) and Parkinson disease–associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways.ConclusionsWhole genome sequence–wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.

Relationship between the severity of cerebral white matter hyperintensities and sympathetic nervous activity in older adults.

White matter hyperintensities (WMH), visualized on brain magnetic resonance imaging, represent an abnormality related to the development of geriatric syndromes. Recently, it has been found that low sympathetic nervous activity might be associated with physical and cognitive dysfunction in older adults. Therefore, we investigated the relationship between the severity of cerebral WMH and sympathetic nervous activity, measured by the heart rate variability. We carried out a cross-sectional study of 39 older patients. Holter recording was carried out for 30 min. From the RR intervals on the electrocardiogram, the standard deviation of the normal-to-normal intervals, the standard deviation of all normal-to-normal intervals in all the five segments of the entire recording, low frequency (LF), high frequency (HF) and LF/HF were calculated. In regard to the WMH, periventricular hyperintensities and deep white matter hyperintensities (DWMH) were rated according to the Fazekas classification. The WMH were also rated semiquantitatively according to the methods developed by Junque (periventricular hyperintensities) and de Groot (DWMH). The LF/HF showed significant negative correlations with the total and regional periventricular hyperintensities, as well as DWMH. Multiple regression analysis showed that the negative associations remained significant between the LF/HF and DWMH (total, temporal, occipital). Furthermore, fall risk index significantly correlated with the LF/HF, total and the occipital DWMH. The severity of the DWMH was associated with the LF/HF and the fall risk, one of the important geriatric syndromes, suggesting that WMH, sympathetic nervous dysfunction and geriatric syndrome are interrelated to each other. Geriatr Gerontol Int 2018; 18: 569-575.

Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-aged Adults in the Framingham Study

ImportanceNonalcoholic fatty liver disease (NAFLD) is a common condition that is most often asymptomatic. It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment. However, it is not known whether NAFLD is associated with structural brain measures in humans.ObjectiveTo assess the association between prevalent NAFLD and brain magnetic resonance imaging (MRI) measures.Design, Setting, and ParticipantsThe cross-sectional association between NAFLD and brain MRI measures was assessed from November 6, 2002, to March 16, 2011, in 766 individuals from the Offspring cohort of the Framingham Study. Participants were included if they did not have excessive alcohol intake and were free of stroke and dementia. Data analysis was conducted from December 30, 2015, to June 15, 2016.ExposuresNonalcoholic fatty liver disease was assessed by multidetector computed tomographic scans of the abdomen.Main Outcomes and MeasuresLinear or logistic regression models were used to evaluate the cross-sectional association between NAFLD and brain MRI measures, adjusting for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, hypertension, current smoking, high-density lipoprotein and low-density lipoprotein cholesterol levels, lipid treatment, type 2 diabetes, cardiovascular disease, physical activity, insulin resistance, C-reactive protein levels, and plasma homocysteine values. Brain MRI measures included total cerebral brain volume, hippocampal and white matter hyperintensity volumes, and presence or absence of covert brain infarcts.ResultsOf the 766 individuals in the study sample (410 women and 356 men; mean [SD] age at the time of brain MRI, 67 [9] years), 137 (17.9%) had NAFLD. Nonalcoholic fatty liver disease was significantly associated with smaller total cerebral brain volume even after adjustment for all the covariates included in the study (β [SE], –0.26 [0.11]; P = .02). Differences in total cerebral brain volume between those with and without NAFLD corresponded to 4.2 years of brain aging in the general sample and to 7.3 years in individuals younger than 60 years of age. No statistically significant associations were observed between NAFLD and hippocampal or white matter hyperintensity volumes or covert brain infarcts.Conclusions and RelevanceNonalcoholic fatty liver disease is associated with a smaller total cerebral brain volume, independent of visceral adipose tissue and cardiometabolic risk factors, pointing to a possible link between hepatic steatosis and brain aging.

Bullseye's representation of cerebral white matter hyperintensities

Background and purposeVisual rating scales have limited capacities to depict the regional distribution of cerebral white matter hyperintensities (WMH). We present a regional-zonal volumetric analysis alongside a visualization tool to compare and deconstruct visual rating scales. Materials and methods3D T1-weighted, T2-weighted spin-echo and FLAIR images were acquired on a 3T system, from 82 elderly participants in a population-based study. Images were automatically segmented for WMH. Lobar boundaries and distance to ventricular surface were used to define white matter regions. Regional-zonal WMH loads were displayed using bullseye plots. Four raters assessed all images applying three scales. Correlations between visual scales and regional WMH as well as inter and intra-rater variability were assessed. A multinomial ordinal regression model was used to predict scores based on regional volumes and global WMH burdens. ResultsOn average, the bullseye plot depicted a right-left symmetry in the distribution and concentration of damage in the periventricular zone, especially in frontal regions. WMH loads correlated well with the average visual rating scores (e.g. Kendall's tau [Volume, Scheltens]=0.59 CI=[0.53 0.62]). Local correlations allowed comparison of loading patterns between scales and between raters. Regional measurements had more predictive power than global WMH burden (e.g. frontal caps prediction with local features: ICC=0.67 CI=[0.53 0.77], global volume=0.50 CI=[0.32 0.65], intra-rater=0.44 CI=[0.23 0.60]). ConclusionRegional-zonal representation of WMH burden highlights similarities and differences between visual rating scales and raters. The bullseye infographic tool provides a simple visual representation of regional lesion load that can be used for rater calibration and training.

Association of Cardiac Hemodynamic Factors With Severity of White Matter Hyperintensities in Chronic Valvular Heart Disease

The cerebral white matter hyperintensity (WMH) is frequently noted in patients with chronic heart disease. Long-term alteration of cardiac hemodynamics might have an influence on the mechanism of cerebral WMH. To investigate the association between chronically altered cardiac hemodynamics and severity of cerebral WMH in patients with chronic valvular heart disease. This cross-sectional analysis identified 303 consecutive patients at a tertiary referral center between 2008 and 2016 who were 50 years or older, and diagnosed with severe chronic valvular heart disease and underwent cardiac catherization, echocardiography, and received brain magnetic resonance imaging. Among these patients, 71 with other demonstrated cardiac disease, central nervous system disease, and/or without sufficient catheterization data were excluded, and the remaining 232 patients were included in further analyses. The site and mechanism of valve diseases, as well as clinical and medication profiles, were reviewed. Cardiac catheterization parameters such as right atrial (RA) mean pressure, right ventricular pressure, and aortic mean pressure were obtained. Comprehensive echocardiographic hemodynamic markers such as left ventricular (LV) ejection fraction, LV mass index, LV end diastolic volume, cardiac index, and E/e' ratio were also obtained. White matter hyperintensity volume was quantitatively evaluated using volumetric analysis. This study included 232 patients (103 men [44.4%] and 129 women [55.6%]; mean [SD] (range) age, 65.6 [8.8] (51-88) years) in the final analysis. The mean (SD) WMH volume was 5.93 (7.14) mL (median [interquartile range], 4.33 [1.33-8.62] mL), and mean (SD) RA pressure was 10.0 (4.7) mm Hg. From the catheterization data, 147 patients (63.4%) were classified as having a disease involving the mitral valve; 93 (40.1%), aortic valve; 37 (15.9%), tricuspid valve; and 4 (1.7%), pulmonary valve. In multivariate linear regression analysis, adjusting the type and mechanism of valve disease and clinical, echocardiographic, and/or other catheterization parameters, WMH volume was linearly associated with mean RA pressure (B coefficient, 0.702; 95% CI, 0.373-1.031; P = .001), along with age (B coefficient, 0.145; 95% CI, 0.029-0.261; P = .01) and mean aortic pressure (B coefficient, 0.112; 95% CI, 0.034-0.190; P = .005). Mean RA pressure was independently associated with the WMH volume in chronic valvular heart disease. Chronically altered RA hemodynamics might have a distinct influence on the pathomechanism underlying the development of WMH.

Development of an automatic retinal image analysis (ARIA) for screening cerebral small vessel disease in the community

Background: Cerebral white matter hyperintensity (WMH) on MRI of elderly subjects is associated with an increased risk for incident stroke and dementia. WMH is considered a manifestation of sporadic small vessel disease (SVD). Since it commonly harbors in the brain for years before clinical symptoms appear, this subclinical phase provides a therapeutic window for exploring preventive treatments. However, currently there is no economical, convenient and sensitive screening tool for WMH.

Location of Cerebral Microbleeds And Their Association with Carotid Intima-media Thickness: A Community-based Study

To assess whether high cerebral microbleeds (CMBs) are associated with carotid intima-media thickness (CIMT), a marker of systemic atherosclerosis, we cross-sectionally evaluated participants from a community-based study, the I-Lan Longitudinal Aging Study. The participants’ demographics and cardiovascular risk factors were determined by questionnaire and/or laboratory measurements. CIMT was measured by ultrasonography. CMBs were assessed by susceptibility-weighted-imaging on 3 T MRI. Of the 962 subjects [62.5(8.6) years, 44.2% men] included, CMBs were found in 134(14.0%) subjects. Among the subjects with identified CMB’s, 85(63.4%) had deep or infratentorial (DI) and 49(36.6%) had strictly lobar(SL) CMBs. After the results were adjusted for age and sex, the analysis revealed that hypertension, hyperlipidemia, obesity, and higher triglyceride levels correlated with DI but not SL CMBs. The subjects with DI CMBs also had a higher mean CIMT and higher prevalence of top quartile CIMT. The multivariate analysis demonstrated that high CIMT (top quartile) significantly predicted the presence of DI CMBs (odds ratio = 2.1; 95% confidence interval = 1.3–3.4; P = 0.004), independent of age, sex, cardiovascular risk factors, and other cerebral small vessel diseases, lacune, and white matter hyperintensity. There was no association between CIMT and SL CMBs. Our results support that there are distinct pathogenesis in DI and SL CMBs.

Cystatin C, a potential marker for cerebral microvascular compliance, is associated with white-matter hyperintensities progression.

Cerebral white matter hyperintensities (WMHs) are central MRI markers of the brain aging process, but the mechanisms for its progression remain unclear. In this study, we aimed to determine whether the baseline serum cystatin C level represented one mechanism underlying WMH progression, and whether it was associated with the long-term progression of cerebral WMH volume in MRI. 166 consecutive individuals who were ≥50 years of age and who underwent initial/follow-up MRI evaluations within an interval of 34–45 months were included. Serum cystatin C level, glomerular-filtration rate (GFR), and other laboratory parameters were measured at their initial evaluation and at the end of follow-up. Cerebrovascular risk factors, medications, and blood-pressure parameters were also reviewed. WMH progression rate was measured by subtracting WMH volume at baseline from that at the follow-up using volumetric analysis, divided by the MRI intervals. At baseline, WMH volume was 9.61±13.17 mL, mean GFR was 77.3±22.8 mL/min, and mean cystatin C level was 0.92±0.52 mg/L. After 37.9±3.4 months, the change in WMH volume was 3.64±6.85 mL, the progression rate of WMH volume was 1.18±2.28 mL/year, the mean ΔGFR was 2.4±7.9 mL/min, and the mean Δcystatin C was 0.03±0.34 mg/L. The progression rate of WMH volume was linearly associated with cystatin C level (B coefficient = 0.856; 95% confidence interval [CI] 0.174−1.538; P = 0.014), along with the baseline WMH volume (B = 0.039; 95% CI 0.019−0.059; P<0.001), after adjusting for the conventional vascular risk factors, laboratory parameters, medication profiles, and GFR. Especially, patients with a baseline level of cystatin C ≥1.00 mg/L exhibited a much higher progression rate of WMH as compared with those with a baseline level of cystatin C <1.00 mg/L (1.60±1.91 mL/year vs. 0.82±1.63 mL/year, P = 0.010). We concluded that serum cystatin C level is independently associated with the long-term progression rate of the cerebral WMH volume. Therefore, serum cystatin C level might predict the progression of cerebral WMH.

Cerebral white matter hyperintensity is associated with intracranial atherosclerosis in a healthy population

Background and aimsCerebral white matter hyperintensity (WMH) is commonly found in ischemic stroke patients, especially when accompanied by intracranial atherosclerosis (ICAS). However, the relationship between WMH and ICAS in a healthy population has not been evaluated. MethodsA total of 3159 healthy subjects who underwent health checkups, including brain magnetic resonance imaging and angiography, were enrolled. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels on magnetic resonance angiography. Volumes of WMH were quantitatively rated. ResultsEighty-two (2.6%) subjects had ICAS. The mean age of the cohort was 56 years, and the median volume of WMH was 1.02 [0.20–2.60] mL. In a multivariate analysis, ICAS [β = 0.331, 95% confidence interval (CI) = 0.086 to 0.576, p = 0.008] was significantly associated with WMH volumes after adjusting confounders. Age (β = 0.046, 95% CI = 0.042 to 0.050, p < 0.001), hypertension (β = 0.113, 95% CI = 0.017 to 0.210, p = 0.021), and diabetes (β = 0.154, 95% CI = 0.043 to 0.265, p = 0.006) were also significant, independently of ICAS. The ICAS (+) group had more frequent vascular risk factors including hypertension, diabetes, and statin use, than the ICAS (−) group, and these tendencies increased when WMH was accompanied by ICAS. ConclusionsICAS is associated with larger WMH volume in a healthy population. Close observation of this group and strict control of vascular risk factors are needed.

White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm3, p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.

Quantitative and qualitative MRI evaluation of cerebral small vessel disease in an elderly population: a longitudinal study.

Background Cerebral white matter hyperintensities (WMHs), lacunes, and microbleeds are seen on magnetic resonance imaging (MRI) in small vessel disease (SVD). Purpose To assess SVD on MRI and its evolution over five years in an elderly population and to investigate whether relative cerebral blood flow (rCBF) at baseline was related to the progression of white matter (WM) lesions. Material and Methods In a population-based study, 406 participants aged 75 years underwent morphological MRI of the brain and 252 of them again at age 80 years. At age 75 years, a perfusion scan was also done. WMHs were evaluated qualitatively (visual scoring) and quantitatively (CASCADE software). Lacunes and microbleeds were counted. Results A significant progression of the WMH score and WMH volume occurred over five years ( P < 0.0001). New lacunes were seen in 10%. Participants with new lacunes at age 80 years showed a more pronounced increase in WMHs (P < 0.0001). Microbleeds were present in 14% at age 75 years. The visual WMH score was significantly associated with the presence of microbleeds ( P < 0.0001). There was no relationship between total WM rCBF and WMH volume at age 75 years, and no significant associations between regional or total rCBF at age 75 years and changes in WMH volume over five years. The total WM and GM volume decreased significantly between the ages of 75 and 80 years ( P < 0.0001). Conclusion MRI manifestations of SVD progressed over five years in an elderly population (age range = 75-80 years). rCBF was not associated with WMH volume or progression of WMH volume.

High neutrophil to lymphocyte ratio is associated with white matter hyperintensity in a healthy population

High neutrophil to lymphocyte ratio (NLR) is correlated with the occurrence, morbidity and mortality of cerebrovascular disease as a marker of systemic inflammation. However, its effect on cerebral white matter hyperintensity (WMH) is unclear. We investigated high NLR burden as a surrogate marker of WMH volume in a healthy population. Healthy subjects with voluntary health check-ups between January 2006 and December 2013, including brain MRI and laboratory examination, were collected. WMH volumes were rated quantitatively. A total of 2875 subjects were enrolled, and the mean volume of WMH was 2.63±6.26mL. In multivariate linear regression analysis, NLR [β=0.191, 95% confidence interval (CI)=0.104 to 0.279, P<0.001] remained significant after adjusting for confounders. Age (β=0.049, 95% CI=0.045 to 0.054, P<0.001), hypertension (β=0.191, 95% CI=0.101 to 0.281, P<0.001), diabetes (β=0.153, 95% CI=0.045 to 0.261, P=0.006), and extracranial atherosclerosis (β=0.348, 95% CI=0.007 to 0.688, P=0.045) were also significant independently from NLR. Additionally, the high NLR group (NLR≥1.52) was related to male sex, hypertension, diabetes, current smoking, extracranial atherosclerosis, silent brain infarct, and high WMH volumes. In conclusion, high NLR is associated with larger WMH volumes in a healthy population. Assessment of NLR may be helpful in detecting cerebral WMH burdens in high risk groups.