Periventricular Hyperintensities Research Articles

Different mechanisms in periventricular and deep white matter hyperintensities in old subjects.

ObjectiveAlthough multiple pieces of evidence have suggested that there are different mechanisms in periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs), the exact mechanism remains uncertain.MethodsWe reviewed clinical and imaging data of old participants from a local She Ethnic group. We assessed the cerebral blood flow of white matter (WM-CBF) on arterial spin-labeling, deep medullary veins (DMVs) visual score on susceptibility-weighted imaging, and index for diffusion tensor image analysis along the perivascular space (ALPS index), indicating glymphatic function on diffusion tensor imaging. Furthermore, we investigated their relationships with volumes of PWMHs and DWMHs.ResultsA total of 152 subjects were included, with an average age of 63 ± 8 years old. We found that higher age and history of hypertension were independently related to higher volumes of both PWMHs and DWMHs (all p < 0.05). Lower ALPS index was independently associated with higher PWMHs volumes (β = 0.305, p < 0.001), and this relationship was accounted for by the indirect pathway via DMVs score (β = 0.176, p = 0.017). Both lower ALPS index and WM-CBF were independent risk factors for higher DWMHs volumes (β = −0.146, p = 0.041; β = −0.147, p = 0.036).ConclusionsOur study indicated that there were different mechanisms in PWMHs and DWMHs. PWMHs were mainly attributed to the damage of veins due to the dysfunction of the glymphatic pathway, while DWMHs could be affected by both ischemia-hypoperfusion and dysfunction of the glymphatic pathway.Advances in knowledgeThe relationship between glymphatic dysfunction and PWMHs might be accounted for by the indirect pathway via venous abnormalities, a glymphatic dysfunction, and lower CBF in white matter were independent risk factors for DWMHs.

Periventricular white matter hyperintensities are associated with gait and balance in patients with minor stroke.

ObjectiveCerebral small vessel disease (CSVD) is associated with gait and balance deficits in older adults. However, the effect of CSVD-related brain injury on post-stroke mobility is unknown. This study aimed to investigate the association of CSVD with gait and balance impairment after a minor stroke.MethodsA total of 273 patients with a minor stroke (NIHSS ≤ 5 points) who were hospitalized at the Affiliated Hospital of Qingdao University were enrolled. The manifestations of white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMB) were statistically analyzed according to magnetic resonance imaging results, and the total burden score of CSVD was calculated. Gait function was assessed by a 6-m walking speed test, and balance function was assessed by the timed-up-and-go (TUG) test. Linear regression analysis was applied to determine the association after adjusting for key variables.ResultsThe correlation results showed that in patients with minor stroke, age, sex, smoking history, and the infarct site were associated with gait speed, and age and the infarct site were associated with the TUG test. In the univariate linear regression model, periventricular white matter hyperintensities (PVWMH), deep white matter hyperintensities (DWMH), and the total burden of CSVD were correlated with gait speed, while only PVWMH correlated with the TUG test. After adjusting for confounders, only PVWMH were independent predictors of gait speed (β = −0.089, p < 0.05) and the TUG test (β = 0.517, p < 0.05).ConclusionsOur study confirmed that CSVD is associated with gait and balance disorders after a minor stroke. PVWMH are independent predictors of gait and balance disorders in patients with minor stroke. These findings should be confirmed in larger prospective studies.

3D finite-element brain modeling of lateral ventricular wall loading to rationalize periventricular white matter hyperintensity locations

Aging-related periventricular white matter hyperintensities (pvWMHs) are a common observation in medical images of the aging brain. The underlying tissue damage is part of the complex pathophysiology associated with age-related microstructural changes and cognitive decline. PvWMH formation is linked to blood–brain barrier dysfunction from cerebral small vessel disease as well as the accumulation of cerebrospinal fluid in periventricular tissue due to progressive denudation of the ventricular wall. In need of a unifying theory for pvWMH etiology, image-based finite-element modeling is used to demonstrate that ventricular expansion from age-related cerebral atrophy and hemodynamic loading leads to maximum mechanical loading of the ventricular wall in the same locations that show pvWMHs. Ventricular inflation, induced via pressurization of the ventricular wall, creates significant ventricular wall stretch and stress on the ependymal cells lining the wall, that are linked to cerebrospinal fluid leaking from the lateral ventricles into periventricular white matter tissue. Eight anatomically accurate 3D brain models of cognitively healthy subjects with a wide range of ventricular shapes are created. For all models, our simulations show that mechanomarkers of mechanical wall loading are consistently highest in pvWMHs locations (p < 0.05). Maximum principal strain, the ependymal cell thinning ratio, and wall curvature are on average 14%, 8%, and 24% higher in pvWMH regions compared to the remaining ventricular wall, respectively. Computational modeling provides a powerful framework to systematically study pvWMH formation and growth with the goal to develop pharmacological interventions in the future.

Age related increase in internal jugular vein size parallels temporal development of periventricular white matter hyperintensities.

Age-related white matter hyperintensities are associated with cognitive impairment and dementia. Venous insufficiency has recently been proposed as a potential mechanism for the development of periventricular white matter hyperintensities based on the neuroanatomic distribution. The current study assesses age related changes of the internal jugular veins and its association with white matter hyperintensities. A retrospective study was performed assessing patients with computed tomography angiography (CTA) and magnetic resonance imaging (MRI) within a 4-week window. The size of the internal jugular veins, straight sinus, vein of Galen and internal cerebral veins were measured on the CT angiography. A normalized neck venous ratio was developed. Burden of white matter hyperintensities were quantified on MRI using periventricular/deep Fazekas scores. Association was assessed using correlation analysis and multrivariate linear modeling, and differences between groups were assessed using t test, ANOVA or Kruskal-Wallis test, using p < 0.05 for significance. One hundred eighty-two patients were included with a mean age of 65.2 ± 16.8 (51.6% females). Age was correlated with the normalized neck venous ratio (rs =0.25, p < 0.001), and, with both, the periventricular Fazekas (rs =0.63, p < 0.001) and the deep Fazekas (rs =0.57, p < 0.001) grades. The periventricular Fazekas score was positively correlated with the normalized neck venous ratio (rs =0.21, p=0.003), but not significant on multivariate analysis accounting for age. The internal jugular veins demonstrate age related increase in size, paralleling the progression of periventricular white matter hyperintensities. Age remains the strongest predictor of white matter hyperintensities. Further work is needed to evaluate any causal role of venous changes on white matter hyperintensities.

Association of sudden sensorineural hearing loss and its prognosis with the brain white matter hyperintensity

Objective:To explore the relationship between white matter hyperintensity（WMH） and sudden sensorineural hearing loss（SSHL） and evaluate the influence of WMH on the prognosis of SSHL. Methods:Fifty hospitalized unilateral SSHL patients and 50 age and gender matched routine physical examination individuals without SSHL history from June 2019 to June 2020 were included for a case-control study. All included subjects underwent 3.0 Tesla cranial magnetic resonance examination, and the Fazekas scale was applied to evaluate periventricular white matter hyperintense（PVWMH） and deep white matter hyperintense（DWMH）. Fazekas score and distribution proportions of Fazekas score was compared between SSHL and control. Ordered logistic regression was used to study the relationship between prognosis of SSHL and WMH. Results:The Fazekas score of WMH in SSHL group was significantly higher than that of control group（PVWMH: P=0.004, DWMH: P=0.010）; There was a significant difference in the distribution proportions of Fazekas scores between SSHL and control（PVWMH: P=0.036, DWMH: P=0.047）; The results of ordered logistic regression showed that patients without WMH（Fazekas=0） is an independent predictor of good prognosis in SSHL（P=0.025, OR=12.779）. Conclusion:The prevalence of WMH in SSHL patients was higher than that of control. SSHL patients without WMH has a better prognosis than those with WMH.

Association Between Enlarged Perivascular Spaces and Cognition in a Memory Clinic Population.

Although enlarged perivascular spaces (EPVS) have been suggested as an emerging measure of small vessel disease (SVD) in the brain, their association with cognitive impairment is not yet clearly understood. We aimed to examine the relationship between each EPVS in the basal ganglia (BG-EPVS) and centrum semiovale (CSO-EPVS) with cognition in a memory clinic population. Participants with a diverse cognitive spectrum were recruited from a university hospital memory clinic. They underwent comprehensive clinical and neuropsychological assessments and brain MRI. BG-EPVS and CSO-EPVS were measured on T2-weighted MRI and then dichotomized into low and high degrees for further analyses. Other SVD markers were assessed using validated rating scales. A total of 910 participants were included in this study. A high degree of BG-EPVS was significantly associated with poorer scores on the executive function domain, but not with other cognitive domains, when age, sex, education, MRI scanner type, and cognitive diagnosis were controlled as covariates. However, the association between BG-EPVS and executive function was no longer significant after controlling for other markers of SVD, such as lacunar infarcts and periventricular white matter hyperintensities, as additional covariates. CSO-EPVS did not have a significant relationship with any cognitive scores, regardless of the covariates. Our findings from a large memory clinic population suggest that EPVS, regardless of the topographical location, may not be used as a specific SVD marker for cognitive impairment, although an apparent association was observed between a high degree of BG-EPVS and executive dysfunction before controlling other SVD markers that share a common pathophysiologic process with BG-EPVS.

Quantitative Analysis of White Matter Hyperintensity: Comparison of Magnetic Resonance Imaging Image Analysis Software

ObjectiveWhite matter hyperintensity (WMH), defined as abnormal signals on magnetic resonance imaging (MRI), is an important clinical indicator of aging and dementia. Although MRI image analysis software can automatically detect WMH, the quantitative accuracy of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) is unknown. Materials and MethodsThis study was a sub-analysis of MRI data from an ongoing hospital-based prospective cohort study (the Gimlet study). Between March 2016 and March 2017, we enrolled patients who visited our memory clinic and agreed to undergo medical assessments of cognitive function and fecal examination to study the gut microbiome. Participants with a history of stroke were excluded. WMH was independently quantitatively analyzed using two MRI imaging analysis software modalities: SNIPER and FUSION. Intraclass correlation coefficients and the mean difference in volume were calculated and compared between modalities. ResultsThe data of 87 patients (49 women, mean age 74.8 ± 7.9 years) were analyzed. Both total WMH and DWMH volumes obtained using FUSION were greater (p < 0.001), and PVH volume was smaller (p < 0.001) than those obtained using SNIPER. Intraclass correlation coefficients for the lesion measurements of WMH, PVH, and DWMH between the different software were 0.726 (p < 0.001), 0.673 (p < 0.001), and 0.048 (p = 0.231), respectively. ConclusionsThere were significant differences in the quantitative data of WMH between the two MRI imaging analysis software modalities. Thus, care should be taken for quantitative assessments of WMH.

Association of Vascular Properties With the Brain White Matter Hyperintensity in Middle-Aged Population.

BackgroundThe periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation.Methods and ResultsA total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold.ConclusionsWe show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.

White matter changes should not exclude patients with idiopathic normal pressure hydrocephalus from shunt surgery

IntroductionWhite matter changes (WMC) on brain imaging can be classified as deep white matter hyperintensities (DWMH) or periventricular hyperintensities (PVH) and are frequently seen in patients with idiopathic normal pressure hydrocephalus (iNPH). Contradictory results have been reported on whether preoperative WMC are associated with outcome after shunt surgery in iNPH patients. The aim of this study was to investigate any association between DWMH and PVH and shunt outcome in patients with iNPH, using magnetic resonance volumetry.MethodsA total of 253 iNPH patients operated with shunt surgery and clinically assessed before and 12 months after surgery were included. All patients were investigated preoperatively with magnetic resonance imaging of the brain. The volumes of DWMH and PVH were quantified on fluid-attenuated inversion recovery images using an in-house semi-automatic volumetric segmentation software (SmartPaint). Shunt outcome was defined as the difference in symptom score between post- and preoperative investigations, measured on the iNPH scale, and shunt response was defined as improvement with ≥ 5 points.ResultsOne year after shunt surgery, 51% of the patients were improved on the iNPH scale. When defining improvement as ≥ 5 points on the iNPH scale, there was no significant difference in preoperative volume of WMC between shunt responders and non-responders. If outcome was determined by a continuous variable, a larger volume of PVH was negatively associated with postoperative change in the total iNPH scale (p < 0.05) and negatively associated with improvement in gait (p < 0.01) after adjusting for age, sex, waiting time for surgery, preoperative level of symptoms, Evans’ index, and disproportionately enlarged subarachnoid space hydrocephalus. The volume of DWMH was not associated with shunt outcome.ConclusionsAn association between outcome after shunt surgery and volume of PVH was seen, but there was no difference between shunt responders and non-responders in the volumes of DWMH and PVH. We conclude that preoperative assessment of WMC should not be used to exclude patients with iNPH from shunt surgery.

Asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery stenoses

Background and purposeSmall vessel diseases (SVDs) are often asymptomatic. However, SVDs significantly influence the prognosis in patients with large vessel diseases (LVDs). We investigated asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery (CA) stenoses, compared to peoples without a past history of neurological disorders, including strokes. MethodsWe retrospectively analyzed the prevalences of various asymptomatic cerebral findings which were intracerebral hemorrhages (ICHs), cortical superficial siderosis, ventricular dilatation (Evans’ index) and SVDs including cerebral microbleeds (CMBs), lacunar infarctions (LIs), deep white matter hyperintensities (WMHs), periventricular hyperintensities (PVHs). The prevalence of each finding was compared using multivariate logistic regression models with adjustment for stroke risk factors. ResultsWe evaluated the findings in 54 patients with severe CA stenosis treated by stenting (CA stenosis group) and 200 adults with health screening tests of the brain and no past history of neurological disorders (control group). Multivariate analyses adjusted for age ≥ 65 years old, female gender, hypertension, hyperlipidemia, diabetes mellitus, alcohol consumption, and smoking index revealed that the prevalences of severe PVHs, severe deep WMHs, asymptomatic deep ICHs, and asymptomatic LIs were significantly higher in the CA stenosis group than the control group. However, there were no significant differences in the prevalences of CMBs, or the remaining asymptomatic findings described above. ConclusionsWith pathological differences between SVD and LVD, asymptomatic SVDs except CMBs and deep ICHs often co-exists severe CA stenosis as a presentative LVD.

HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients.

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is a rare inborn error of leucine degradation and ketone body synthesis, caused by homozygous or compound heterozygous disease-causing variants in HMGCL. To understand the natural history of this disease, we reviewed the biochemical, clinical, and molecular data of 62 patients from 54 different families with confirmed HMG-CoA lyase deficiency (HMGCLD) diagnosis from Saudi Arabia. The majority of the affected individuals were symptomatic. At initial diagnosis, 38 patients (61.29%) presented with hypoglycemia and 49 patients (79.03%) developed metabolic acidosis. In 27 patients (43.54%), the disorder manifested in the neonatal period, mostly within the first days of life, while 35 (56.45%) patients were diagnosed within the first year of life or beyond. All the patients were alive and developed long-term neurological complications during data collection, which may significantly influence their quality of life. Common neurological findings include seizures 17/62 (27.41%), hypotonic 3/62 (4.83%), speech delay 7/62 (11.29%), hyperactivity 4/62 (4.83%), developmental delay 6/62 (9.677%), learning disability 15/62 (24.14%), and ataxic gate 1/62 (1.612%). An MRI of the brain exhibited nonspecific periventricular and deep white matter hyperintense signal changes in 16 patients (25.80%) and cerebral atrophy was found in one (1/62; 1.612%) patient. We identified a founder variant [c.122G>A; p.(Arg41Gln)] in 48 affected individuals (77.41%) in the HMGCL gene. This is the largest cohort of HMGCLD patients reported from Saudi Arabia, signifying this disorder as a likely life-threatening disease, with a high prevalence in the region. Our findings suggest that diagnosis at an early stage with careful dietary management may avoid metabolic crises.

Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus.

Background:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients.Methods:This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, i.e., with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis.Results:Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8+ T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P = 0.019; OR 2.129, 95% confidence interval [CI] 1.313–4.006 and P < 0.001; OR 1.056, 95% CI 1.023–1.098, respectively).Conclusions:Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE.

Abnormal Cerebrovascular Reactivity and Functional Connectivity Caused by White Matter Hyperintensity Contribute to Cognitive Decline

AimsThis study aimed to investigate the relationships of impaired cerebrovascular reactivity (CVR) and abnormal functional connectivity (FC) with white matter hyperintensity (WMH)-related cognitive decline.MethodsA total of 233 WMH subjects were recruited and categorized into WMH-I (n = 106), WMH-II (n = 72), and WMH-III (n = 55) groups according to Fazekas visual rating scale. All participants underwent neuropsychological tests and multimodal MRI scans, including 3D-T1, and resting-state functional magnetic resonance imaging (rs-fMRI). The alterations of CVR maps and FC were further explored.ResultsSubjects with a higher WMH burden displayed a lower CVR in the left medial occipital gyrus (MOG). The FC analysis using MOG as a seed revealed that the FC of the left insula, left inferior parietal lobule, and thalamus changed abnormally as WMH aggravated. After adjusting for age, gender, and education years, the serial mediation analysis revealed that periventricular white matter hyperintensity contributes indirectly to poorer Mini-Mental State Examination (MMSE) scores (indirect effect: β = −0.1248, 95% CI: −0.4689, −0188), poorer Montreal Cognitive Assessment (MoCA) (indirect effect: β = −0.1436, 95% CI: −0.4584, −0.0292) scores, and longer trail making tests A (TMT-A) (indirect effect: β = 0.1837, 95% CI: 0.0069, 0.8273) times, specifically due to the lower CVR of the left MOG and the higher FC of the left insula-MOG.ConclusionThe CVR decline of the left MOG and the abnormal FC of the left insula-MOG attributed to WMH progression were responsible for the poor general cognition (MMSE and MoCA) and information processing speed (TMT-A). The left MOG may act as a connection, which is involved in the processing of cognitive biases by connecting with the left insula-cortical regions in WMH individuals.

Obstructive sleep apnea and white matter hyperintensities: correlation or causation?

Obstructive sleep apnea (apnea) is thought to cause small vessel ischemic episodes in the brain from hypoxic events, postulated as white matter hyperintensities (hyperintensities) identified on MRI which are implicated in cognitive decline. This study sought to evaluate these correlations. A retrospective evaluation of adults who underwent polysomnography (4/1/2016 to 4/30/2017) and a brain MRI prior to apnea diagnosis or within a year post-diagnosis was completed. MRI visual evaluation of hyperintensities using Fazekas scores were collected blind to clinical data. Collated clinical/MRI data were stratified and analyzed using chi-square, fishers t-tests, ANOVA/ANCOVA and linear regression. Stratification by apnea category revealed no significant differences in any variables including hyperintensity measures (Fazekas p=0.1584; periventricular p=0.3238; deep p=0.4618; deep total p=0.1770). Stratification by Fazekas category, periventricular and deep hyperintensities revealed increasing prevalence with age (p=0.0001); however, apnea categories were not significantly associated (Fazekas p=0.1479; periventricular p=0.3188; deep p=0.4503), nor were any individual apnea indicators. Continuous apnea measurements werre not associated with any hyperintensity factor; total deep hyperintensities were not associated with any apnea factors. Continuous BMI was not found to be associated with any apnea or hyperintensity factors. Only hypertension was noted to be associated with Fazekas (p=0.0045), deep (p=0.0010) and total deep (p=0.0021) hyperintensities; however, hypertension was not associated with apnea category (p=0.3038) or any associated factors. These data suggest apneas alone from OSA are insufficient to cause WMH, but other factors appear to contribute to the complex development of small vessel ischemic injury associated with age and cognitive decline.

Silent cerebral ischemia detected by magnetic resonance imaging can predict postoperative delirium after total arch replacement for aneurysm

ObjectiveTo identify whether preoperative magnetic resonance imaging findings of the brain can predict postoperative delirium in patients who undergo arch replacement for aneurysms. MethodsOverall, 193 patients who underwent aortic replacement for the first time at a single institution between April 2014 and September 2020 were enrolled in this retrospective study. After we excluded patients with acute aortic dissection, no preoperative magnetic resonance imaging findings of the brain, and postoperative cerebral infarction, 50 patients were included and divided into 2 groups, according to their confusion scale results: postoperative delirium (group D) and nonpostoperative delirium (group ND). Preoperative magnetic resonance imaging findings of the brain were classified into lacunar stroke, periventricular hyperintensity, and deep subcortical white matter hyperintensity groups; the latter 2 groups were further classified based on the Fazekas scale, grade 0 to 3. ResultsThere were 23 patients (46%) in group D and 27 (54%) in group ND. The mean age was significantly greater in group D than in group ND (75 vs 70 years; P = .007). The mean operative time was significantly longer in group D than in group ND (447 vs 384 minutes; P = .024). As for preoperative magnetic resonance imaging findings of the brain, there were significantly more lacunar stroke cases in group D than in group ND (P = .027). In multivariable logistic regression with stepwise selection, high-grade periventricular hyperintensity was significantly related to postoperative delirium (odds ratio, 9.38; 95% confidence interval, 1.55-56.56; P = .015). ConclusionsSilent cerebral ischemia detected by preoperative magnetic resonance imaging of the brain was a significant risk factor for postoperative delirium.

Association of ankle-brachial index with cognitive decline in patients with lacunar infarction.

Atherosclerosis is an important risk factor for cognitive decline. This study aimed to investigate the relationship of ankle-brachial pressure index (ABI) and brachial-ankle pulse wave velocity (baPWV) with cognitive function in patients with lacunar infarction. We included records of consecutive patients with their first-ever acute stroke and a diagnosis of lacunar infarction through magnetic resonance imaging (MRI) from July 1, 2011 to December 31, 2018. We excluded patients diagnosed with dementia, including strategic single-infarct dementia, before or after stroke onset. Moreover, we excluded patients with one or more microbleeds, severe white matter lesions, or severe medial temporal atrophy on MRI. For ABI, we used the lower ankle side and divided the results into ABI < 1.0 and ABI ≥ 1.0. For baPWV, we used the higher ankle side and divided the results into two groups based on the median value of the participants. We analyzed 176 patients with stroke (age 72.5 ± 11.4 years, 67 females). The median score on the Mini-Mental State Examination (MMSE) was 27. The number of patients with ABI < 1.0 was 19 (10.8%). Univariate analysis revealed that the MMSE score was associated with age, body mass index, education, chronic kidney disease, periventricular hyperintensity, and ABI < 1.0 (p < 0.10), but not baPWV. Multivariate analysis revealed that body mass index (p = 0.039) and ABI < 1.0 (p = 0.015) were independently associated with the MMSE score. For patients with lacunar infarction, a lower ABI, but not a higher PWV, was associated with cognitive decline.

Abstract TP129: Periventricular Hyperintensity On Magnetic Resonance Imaging Predicts Unfavorable Outcomes After Intracerebral Hemorrhage

Background and Purpose: To determine the association between the markers of cerebral small vessel disease (CSVD) and cerebral brain atrophy evaluated by magnetic resonance imaging (MRI) and outcomes after intracerebral hemorrhage (ICH). Methods: Consecutive patients with ICH ≤72 h from onset to door who underwent MRI during the hospitalization were included. We evaluated the CSVD markers as white matter hyperintensities scale (separately scored by periventricular hyperintensity [PVH] and deep and subcortical white matter hyperintensity [DSWMH]), the number of cerebral microbleeds, the number of old lacunes, and enlarged perivascular spaces scale and the degree of cerebral brain atrophy as global cortical atrophy scale. An unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6 at 3 months from onset. We evaluated whether markers of CSVD and cerebral brain atrophy all assessed by MRI could be associated with prognosis of ICH. Results: We screened 361 consecutive patients with ICH, including 231 patients (161 [70%] male, median age 62 years). Of 231 patients, 83 (36%) patients had unfavorable outcomes. PVH, not DSWMH, was independently associated with unfavorable outcomes (odds ratio 2.059, 95% confidence interval 1.029-4.120, p = 0.041, Figure). There were no significant relationships between other CSVD markers and cerebral brain atrophy and prognosis after ICH. Conclusions: Severe PVH on MRI might predict unfavorable outcomes after ICH.

Abstract TMP44: The Novel Predictors Of Poor Functional Outcome In Acute Lacunar Infarction By Using Hierarchical Cluster Analysis Of Clinical Variables

Background: Lacunar infarct (LI) is a heterogeneous disorder of cerebral small vessel. Hierarchical clustering (HC) is useful for exploring potential underlying clinical phenotype in heterogeneous disease. Our aim is to identify the predictive factors of poor functional outcome in LI to classify the subjects into distinct subgroups using HC and compare the clinical variables including clinical outcome among groups. Methods: From October 2012 to April 2020, LI patients within 24 hours from the onset were enrolled. We used a HC k-means clustering algorithm on patients’ baseline data. We also compared clinical outcome among each cluster groups. Results: Among 187 patients (144 male, median age 66 years old, median NIHSS score2), three clusters were identified. Cluster1(58%), mostly comprised of younger patients (p&lt;0.01), had fewer past history of ischemic stroke (p=0.007). The severity of deep subcortical white matter hyperintensity (DSWMH) and periventricular hyperintensity (PVH) were mild, and small number of cerebral microbleeds (MBs) are detected (p&lt;0.001 for each). Cluster2(15%), mostly comprised of older patients (p&lt;0.001), had the highest NIHSS score on admission (p=0.021). Serum D-dimer and Cr levels were relatively higher (p&lt;0.001, p=0.003, respectively). Cluster3(28%), mostly comprised of men, represented the highest number of MBs (p&lt;0.001) and increase of mean IMT (p =0.003). Poor functional outcome defined as mRS at 3 months &gt; 2-6 was 4% of cluster1, 100% of cluster 2 and 12% of cluster 3 (p=0.001). In multivariate logistic regression analysis, the phenotype of cluster was the strongest predictor of poor functional outcome (OR 16.1, 95% CI 6.04-42.9, p&lt;0.001, Figure). Conclusion: Three clusters with different clinical outcome were identified. The phenotype of cluster was the strongest predictive factor of poor functional outcome. Further study to identify whether management of these components provide different clinical outcome was warranted.

Abstract WP14: Association Of Vascular Properties With The Periventricular And Deep White Matter Hyperintensity In Middle-age Population

Introduction: The periventricular white matter is more sensitive to alterations in the hemodynamics of the systemic circulation than the deep white matter due to differences in its vascular supply and relationship to systemic circulation. We hypothesize that periventricular white matter hyperintensity volume (PVWMH) shows greater association than deep white matter hyperintensity (DWMH) volume with vascular property measures of arterial stiffness (AS) and cardiovascular remodeling, important indicators of the systemic circulation. Methods: Participants in the Genetic Study of Atherosclerosis Risk ≥ 50 years of age with brain MRI were selected. Vascular property measures included pulse pressure (PP), hypertension response to exercise (HRE), diastolic brachial artery (BA) diameter, diastolic common carotid artery (CCA) diameter, CCA distensibility coefficient, and left ventricular function. PVWMH and DWMH were measured using semi-automated segmentation approach. The relative associations of these parameters with PVWMH and DWMH volumes as multiple measures within the same individual further nested within families were determined using multilevel linear models. We also determined if differences between PVWMH and DWMH associations were modified by age. Results: 426 participants (age 59.0±6.1 years, 57.5% females, and 39.7% African American) were included. Within the same subject, PVWMH volume showed greater association than DWMH volume with PP (P=0.002), HRE (p=0.04), diastolic BA diameter (p=0.012), and diastolic CCA diameter (p=0.04) independent of age and cardiovascular risk factors. This difference in PVWMH versus DWMH association with vascular properties did not differ at any age threshold. Conclusions: We show for the first time that PVWMH volume has greater association than DWMH volume, independent of age, with vascular property measurements of AS and cardiovascular remodeling. Our findings suggest that changes in the systemic circulation may affect PVWMH and DWMH differently adding to a growing body of literature that PVWMH and DWMH may represent different phenotypes of cerebral small vessel disease.

Novel insights into the genetic profile of hereditary spastic paraplegia in India

The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Patients with HSP phenotype were evaluated for their clinical features, electrophysiological and radiological abnormalities. Genetic analyses were carried out by clinical exome sequencing (n = 52) and targeted sequencing (n = 5). The cohort comprised of 57 probands (M:F 40:17, age: 3.5–49 years). Based on the phenotype, the cohort could be categorized as ‘pure’ (n = 15, 26.3%) and ‘complicated’ (n = 42, 73.7%) HSP. Brain MRI showed thin corpus callosum (n = 10), periventricular hyperintensities (n = 20), cerebral atrophy (n = 3), cerebellar atrophy (n = 3) and diffuse atrophy (n = 4). Sixty-seven variants representing 40 genes were identified including 47 novel variants. Forty-eight patients (84.2%) had variants in genes previously implicated in HSP and other spastic paraplegia syndromes (SPG genes = 24, non-SPG genes = 24); among these 13 had variations in more than one gene and 12 patients (21.0%) had variations in genes implicated in potentially treatable/modifiable metabolic disorders (MTHFR = 8, MTRR = 1, ARG1 = 2 and ABCD1 = 1). In nine patients, no genetic variants implicated in spastic paraplegia phenotype were identified. Thus, the present study from India highlights the phenotypic complexities and spectrum of genetic variations in patients with HSP including those implicated in metabolically modifiable disorders. It sets a platform for carrying out functional studies to validate the causal role of the novel variants and variants of uncertain significance.