Transcriptome Sequencing Identifies Potential Biomarker for White Matter Lesions Diagnosis in the Hypertension Population.

Hypertension is confirmed to be one of the major risk factors of leukoaraiosis (LA). However, the pathogenesis of LA is not completely understood and there is no reliable indicator for the early diagnosis of LA in the hypertensive population. This study was designed to explore the potential biomarker for LA diagnosis in patients with hypertension. And it serves as the basis for the further study of LA mechanism. In this study, This study included 110 subjects, including 50 in the LA group and 60 in the control group. First, we performed transcriptome sequencing and quantitative PCR (qPCR) in four samples from the LA group, and three from the control group (seven people) to identify relevant long non-coding RNAs (long ncRNAs or lncRNA). The 103 samples were used for qPCR validation of relevant lncRNAs and the results were consistent with the sequencing. In-depth bioinformatics analysis were performed on differentially expressed (DE) lncRNAs and mRNAs. Go-functional enrichment analysis was performed on DE mRNAs. Some DE mRNA were enriched to biological processes associated with LA, And some lncRNAs related to DE mRNAs were traceable through cis/trans analysis, suggesting that they might be regulated in some way. Additionally, potential biomarkers for LA diagnosis in the hypertension population were identified via RT-qPCR and receive operating characteristic curve (ROC) analysis of lncRNA. One lncRNA, AC020928.1, has been demonstrated to be potential biomarkers for LA diagnosis in the hypertension population. The results of the present study indicated that the lncRNA may have an important role in the pathogenesis of LA and may be a novel target for further research. As the relationship between lncRNAs and LA is just beginning to be unraveled, their specific mechanisms require further investigation.

Degenerative dementia with proximal radial and lower vertical spatial neglect.

A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.

[White matter hyperintensities in ageing: Pathophysiology, associated cognitive disorders and prevention]. / Hypersignaux de la substance blanche chez la personne âgée : physiopathologie, troubles cognitifs associés et pistes de prévention.

White matter hyperintensities (WMH), also known as leukoaraïosis are very common neuroradiological manifestations in the elderly. The main risk factors for WMH are age and high blood pressure. The vascular origin of these lesions is classically accepted and WMH are considered as one feature of the small vessel disease. WMH may be associated with clinical symptoms, depending notably on their importance according to age. They are associated with increased mortality, strokes and changes in cognition with a higher risk of dementia (vascular dementia or Alzheimer's disease). Modification of vascular risk factors could have a beneficial effect, but few evidences from controlled trials are available.

Radiomics from magnetic resonance imaging may be used to predict the progression of white matter hyperintensities and identify associated risk factors.

OBJECTIVE: The progression of white matter hyperintensities (WMH) varies considerably in adults. In this study, we aimed to predict the progression and related risk factors of WMH based on the radiomics of whole-brain white matter (WBWM). METHODS: A retrospective analysis was conducted on 141 patients with WMH who underwent two consecutive brain magnetic resonance (MR) imaging sessions from March 2014 to May 2018. The WBWM was segmented to extract and score the radiomics features at baseline. Follow-up images were evaluated using the modified Fazekas scale, with progression indicated by scores ≥ 1. Patients were divided into progressive (n = 65) and non-progressive (n = 76) groups. The progressive group was subdivided into any WMH (AWMH), periventricular WMH (PWMH), and deep WMH (DWMH). Independent risk factors were identified using logistic regression. RESULTS: The area under the curve (AUC) values for the radiomics signatures of the training sets were 0.758, 0.749, and 0.775 for AWMH, PWMH, and DWMH, respectively. The AUC values of the validation set were 0.714, 0.697, and 0.717, respectively. Age and hyperlipidemia were independent predictors of progression for AWMH. Age and body mass index (BMI) were independent predictors of progression for DWMH, while hyperlipidemia was an independent predictor of progression for PWMH. After combining clinical factors and radiomics signatures, the AUC values were 0.848, 0.863, and 0.861, respectively, for the training set, and 0.824, 0.818, and 0.833, respectively, for the validation set. CONCLUSIONS: MRI-based radiomics of WBWM, along with specific risk factors, may allow physicians to predict the progression of WMH. KEY POINTS: • Radiomics features detected by magnetic resonance imaging may be used to predict the progression of white matter hyperintensities. • Radiomics may be used to identify risk factors associated with the progression of white matter hyperintensities. • Radiomics may serve as non-invasive biomarkers to monitor white matter status.

COL4A1 Mutation as a Cause of Familial Recurrent Intracerebral Hemorrhage.

The COL4A1 mutation is a very rare monogenic cause of small vessel disease related to recurrent intracerebral hemorrhage. We report a family in which the index case presented with two intracerebral hemorrhages in the basal ganglia with severe periventricular leukoaraiosis and a cataract and vascular tortuosity in the ophthalmological study. His twin brother also had severe leukoaraiosis and multiple subcortical microhemorrhages as well as a congenital cataract and vascular tortuosity in the retina. The older sister had a porencephalic cyst and involvement of the periventricular white matter and intracerebral hemorrhage. In single-gene testing, all three were found to have the same COL4A1 mutation. Intracerebral subcortical hemorrhages or microhemorrhages and severe subcortical leukoaraiosis in familial cases may be related to COL4 mutations.

Generalized chorea associated with subcortical leukoaraiosis of Binswanger type: a case report.

Binswanger disease (BD) involves injuries to the brain small vessels, resulting to gradually progressive subcortical ischemia. This disorder manifests with dementia, gait abnormalities, upper motor signs and parkinsonism, and presents as extensive, confluent, bilateral cerebral white matter hyperintensities in the MRI. Cases of BD typically manifests with vascular risk factors, such as hypertension and multiple strokes. We report a unique case of a Filipino patient whom we have diagnosed with BD presenting with no cardinal signs of parkinsonism, but with generalized choreiform movement disorder and without a history of hypertension and symptomatic strokes. To our knowledge, this is the first report presenting an adult patient with subcortical leukoaraiosis of Binswanger type associated with a hyperkinetic movement disorder.

Pooled cohort risk equation and subclinical cerebrovascular diseases.

BACKGROUND AND PURPOSE: In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) introduced a novel pooled cohort risk (PCR) model for atherosclerotic cardiovascular disease. In this study, we evaluated the relationship between the PCR score and cerebral large- and small-vessel diseases (cLVD and cSVD) in a healthy population, METHODS: We assessed consecutive health check-up volunteers from 2006 to 2013. We calculated the estimated 10-year atherosclerotic cardiovascular disease risk as the PCR score based on the 2013 ACC/AHA guidelines. We evaluated both cSVD/cLVD, including the prevalence of cLVD, lacunes and cerebral microbleed (CMB), and the volume of white matter hyperintensity (WMH). In addition to PCR score, the risk factors that were associated with outcome variables at P < 0.10 in univariate analysis were included for further multivariable linear or regression analyses. RESULTS: A total of 2720 participants were evaluated (mean age, 57 years, male sex, 54%). In multivariable analysis, PCR score was associated with WMH volume [ß = 0.361; 95% confidence interval (CI), 0.320-0.402, P < 0.001], cLVD [adjusted odds ratio (aOR), 1.66; 95% CI, 1.29-2.16, P < 0.001], lacunes (aOR, 1.80; 95% CI, 1.52-2.14, P < 0.001) and CMBs (aOR, 1.75; 95% CI, 1.40-2.19, P < 0.001). Furthermore, PCR score also showed dose-response tendencies according to the burden of cLVD, WMH, lacunes and CMB. CONCLUSIONS: A higher PCR score based on the ACC/AHA guidelines is closely associated with a higher prevalence and burden of cLVD and cSVD.

White matter hypointensities and hyperintensities have equivalent correlations with age and CSF ß-amyloid in the nondemented elderly.

INTRODUCTION: T1- and T2-weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1-weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM-hyper) volume from FLAIR and white matter hypointensity (WM-hypo) volume from T1-weighted images and compared their associations with age and cerebrospinal fluid (CSF) ß-amyloid and tau. METHODS: A total of 56 nondemented participants (68-94 years) were recruited and gave informed consent. All participants went through MR imaging on a GE 1.5T scanner and of these 47 underwent lumbar puncture for CSF analysis. WM-hypo was calculated using FreeSurfer analysis of T1 FSPGR 3D, and WM-hyper was calculated with the Lesion Segmentation Toolbox in the SPM software package using T2-FLAIR. RESULTS: WM-hyper and WM-hypo were strongly correlated (r = .81; parameter estimate (p.e.): 1.53 ± 0.15; p < .0001). Age was significantly associated with both WM-hyper (r = .31, p.e. 0.078 ± 0.030, p = .013) and WM-hypo (r = .42, p.e. 0.055 ± 0.015, p < .001). CSF ß-amyloid levels were predicted by WM-hyper (r = .33, p.e. -0.11 ± 0.044, p = .013) and WM-hypo (r = .42, p.e. -0.24 ± 0.073, p = .002). CSF tau levels were not correlated with either WM-hyper (p = .9) or WM-hypo (p = .99). CONCLUSIONS: Strong correlations between WM-hyper and WM-hypo, and similar associations with age, abnormal ß-amyloid, and tau suggest a general equivalence between these two imaging markers. Our work supports the equivalence of white matter hypointensity volumes derived from FreeSurfer for evaluating leukoaraiosis. This may have particular utility when T2-FLAIR is low in quality or absent, enabling analysis of older imaging data sets.

Structural and functional MRI correlates of T2 hyperintensities of brain white matter in young neurologically asymptomatic adults.

OBJECTIVES: Although white matter hyperintensities (WMHs) are quite commonly found incidentally, their aetiology, structural characteristics, and functional consequences are not entirely known. The purpose of this study was to quantify WMHs in a sample of young, neurologically asymptomatic adults and evaluate the structural and functional correlations of lesion load with changes in brain volume, diffusivity, and functional connectivity. METHODS: MRI brain scan using multimodal protocol was performed in 60 neurologically asymptomatic volunteers (21 men, 39 women, mean age 34.5 years). WMHs were manually segmented in 3D FLAIR images and counted automatically. The number and volume of WMHs were correlated with brain volume, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) data. Diffusion parameters measured within WMHs and normally appearing white matter (NAWM) were compared. RESULTS: At least 1 lesion was found in 40 (67%) subjects, median incidence was 1 lesion (interquartile range [IQR] = 4.5), and median volume was 86.82 (IQR = 227.23) mm3. Neither number nor volume of WMHs correlated significantly with total brain volume or volumes of white and grey matter. Mean diffusivity values within WMHs were significantly higher compared with those for NAWM, but none of the diffusion parameters of NAWM were significantly correlated with WMH load. Both the number and volume of WMHs were correlated with the changes of functional connectivity between several regions of the brain, mostly decreased connectivity of the cerebellum. CONCLUSIONS: WMHs are commonly found even in young, neurologically asymptomatic adults. Their presence is not associated with brain atrophy or global changes of diffusivity, but the increasing number and volume of these lesions correlate with changes of brain connectivity, and especially that of the cerebellum. KEY POINTS: • White matter hyperintensities (WMHs) are commonly found in young, neurologically asymptomatic adults. • The presence of WMHs is not associated with brain atrophy or global changes of white matter diffusivity. • The increasing number and volume of WMHs correlate with changes of brain connectivity, and especially with that of the cerebellum.

Can the trail making test black and white predict white matter hyperintensity on MRI?

White matter hyperintensity (WMH) in the general population has clinical importance. However, MRI (magnetic resonance imaging) is not suitable for screening purposes due to high cost and restricted availability. We hypothesized that performance on the trail making test black & white (TMT-B&W) may correlate with WMH and provide a screening tool for patients with WMH. Intergroup comparisons between WMH (+) (a Fazekas score of ≥2) and WMH (-) (<2) were performed for time variables in type A, B, B-A, B/A, B*A and errors in type A and B. To determine an ideal cutoff value and confirm the diagnostic performance of TMT-B&W on the presence of WMH (+), the area under the receiver operating characteristics curve (AUC) was analyzed. Multiple linear regression analysis was used, adjusting for age and education, to correlate the normalized WMH volumes and TMT-B&W performance. We show that higher WMH correlates with a significant increase in completion time for type A (p < 0.001) and B (p = 0.006) TMT-B&W. In AUC analysis, the optimal cutoff time to complete type A was 75 s [sensitivity, 66.7%; specificity, 67.2%; %; p = 0.001; AUC, 0.729; 95% confidence interval (CI), 0.600-0.858]. Additionally, there were significant correlations between normalized WMH volume and TOTAL-A (B = 0.233, p = 0.016) and errors in type A (B = 0.353, p < 0.001). We identified the correlation between the performance in TMT-B&W and WMH burden, and propose its potential clinical utility in predicting brain WMH burden.

Daily Living Activities and Cognition in Aged Patients: Effect of Acute Systemic Diseases and Stroke on Leukoaraiosis.

BACKGROUND: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExLA) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leukoaraiosis (L-A). METHODS: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial patients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conducted within and between groups with nonparametric techniques. RESULTS: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one. CONCLUSION: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in order to achieve the best possible treatment.

Electrocardiographic left atrial abnormality and silent vascular brain injury: The Northern Manhattan Study.

HYPOTHESIS: We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort. METHODS: PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors. RESULTS: Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 µV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 µV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01-0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94-1.81), but not with all subclinical infarcts. CONCLUSION: Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis.

Microvascular complications of diabetes worsen long-term functional outcomes after acute ischemic stroke.

Objective This study was performed to evaluate the potential predictors of poor outcomes associated with diabetes-specific microvascular pathologies and to analyze their influence on clinical outcomes by adjusting for other well-known prognostic factors in patients with acute ischemic stroke. Methods We analyzed 1389 consecutive adult patients with acute ischemic stroke and explored the relationship among clinical characteristics, laboratory measurements, imaging findings, and 6-month functional outcomes. Results The final study population comprised 216 patients with both acute ischemic stroke and diabetes mellitus who were followed up for 6 months. A multiple logistic regression analysis of poor outcomes revealed the following independent predictors: leukoaraiosis severity [odds ratio (OR), 7.38; 95% confidence interval (CI), 1.40-38.86, per 1-point increase), diabetic nephropathy (OR, 10.66; 95% CI, 1.10-103.43), and the admission National Institutes of Health stroke scale score (OR, 2.58; 95% CI, 1.36-4.92 per 1-point increase). In this model, admission hyperglycemia and intracerebral hemorrhagic transformation were not independent prognostic predictors. Conclusion Microvascular complications (such as nephropathy) caused by diabetes mellitus predict an unfavorable clinical outcome after acute ischemic stroke. Diabetic nephropathy may partly affect post-stroke prognosis by means of exacerbating leukoaraiosis.

The degree of leukoaraiosis predicts clinical outcomes and prognosis in patients with middle cerebral artery occlusion after intravenous thrombolysis.

Leukoaraiosis (LA) is common in elderly patients with ischemic stroke on magnetic resonance imaging. In this study, we investigate whether the degree of LA is associated with clinical outcomes and prognosis of patients with middle cerebral artery occlusion following intravenous thrombolytic. Ninety-seven patients were recruited and divided into three groups based on the degree of LA (no, mild and moderate to severe LA) by the Fazekas scale. Clinical outcomes, recurrent stroke, Fugl-Meyer rating scale (FMS) and complications of intravenous thrombolysis were assessed. The association between the degree of LA and functional outcomes was analyzed by multivariable logistic regression model. Patients enrolled were divided into three groups: 26 patients with no LA, 43 patients with mild LA and 28 patients with moderate to severe LA. Impressively, the patients with mild LA were better in early neurological recovery and 90-day FMS score than patients in the other two groups. Multivariate logistic analysis revealed that moderate to severe LA was an independent predictor of poor functional outcome (OR: 10.482; 95% CI: 1.442-76.181; P = .020). Moreover, the patients with moderate to severe LA have a higher rate of hemorrhagic transformation and recurrent stroke as compared with two other groups during 90-day follow-up. Different degrees of LA differentially affect clinical outcome and prognosis in patients with middle cerebral artery occlusion following intravenous thrombolytic. Moderate to severe LA is a risk factor of poor prognosis. Mild LA is associated with early neurological recovery and good motor functional outcome.

The association of uric acid with leukoaraiosis.

Objective To explore the possible correlation between uric acid levels and leukoaraiosis (LA). Methods This cross-sectional study enrolled patients who presented with some neurological discomfort (e.g. dizziness, headache, mild cognitive impairment). Potential demographic and clinical risk factors associated with LA, including sex, age, hypertension, diabetes mellitus, smoking, alcohol consumption, dyslipidaemia, plasma fibrinogen, D-dimer, uric acid, and homocysteine, were investigated using univariate and multivariate logistic regression analyses. Results A total of 268 patients were enrolled in the study and divided into the LA group ( n = 164) and the non-LA group ( n = 104). Compared with the non-LA group, uric acid was significantly higher in the LA group (mean ± SD: 356.49 ± 121.85 µmol/l versus 289.96 ± 102.98 µmol/l). Multivariate logistic regression analyses showed that uric acid was an independent risk factor for LA (odds ratio 1.285; 95% confidence interval 1.062, 1.556). Conclusion Hyperuricaemia was an independent risk factor for leukoaraiosis in Chinese patients.

Leukoaraiosis is a predictor of futile recanalization in acute ischemic stroke.

Futile recanalization occurs when successful recanalization fails to improve clinical outcome in acute ischemic stroke patients. Predictors of futile recanalization are still debated and may help in selecting patients for reperfusion strategies. We aim to determine whether leukoaraiosis may be useful in predicting futile recanalization in acute ischemic stroke patients treated by endovascular mechanical thrombectomy. We included in the analysis patients with acute ischemic stroke due to anterior circulation large vessel occlusion undergoing endovascular mechanical thrombectomy obtaining complete vessel recanalization. Demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale score, time from symptoms onset to recanalization, Alberta Stroke Program Early CT Score, and leukoaraiosis graded on a 4-point van Swieten scale were collected. We dichotomized patients into those with moderate-severe leukoaraiosis (2-4) versus those with absent-slight leukoaraiosis (0, 1). Outcome measures were symptomatic intracranial hemorrhage, and modified Rankin scale score at 90 days. The relationships among radiological parameters and clinical data with outcome measures were studied with univariate and multivariable analyses. Sixty-eight patients were identified. Recanalization was futile in 32.4% of cases. On multivariable logistic regression analysis, the presence of moderate-severe LA was independent predictors of FR (P = 0.01). Furthermore, higher NIHSS score at baseline (P < 0.01) end endovascular mechanical thrombectomy alone treatment (P < 0.01) resulted associated with futile recanalization. Our results showed that the presence of moderate-severe leukoaraiosis is associated with poor outcome in recanalized patients.

Cognitive reserve moderates long-term cognitive and functional outcome in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical symptoms has been modest, however, and thus the outcome may be affected by various host factors. We investigated the predictive value of educational and occupational attainments as proxy measures of cognitive reserve on long-term cognitive and functional outcome in patients with different degrees of WMH. METHODS: In the Leukoaraiosis and Disability (LADIS) study, 615 older individuals with WMH were evaluated with brain MRI and detailed clinical and neuropsychological assessments at 3-year follow-up. A prolonged follow-up of functional and cognitive status was administered with a structured telephone interview after up to 7 years. RESULTS: Higher levels of educational and occupational attainment were strongly related to baseline cognitive scores and predicted a slower rate of decline at 3-year follow-up in measures of processing speed, executive functions and memory independently of WMH volume and other confounders. The deleterious effect of WMH on processing speed and memory was moderated by education and occupation. Education mitigated the relation of WMH volume on 7-year cognitive status. Moreover, higher education and occupational attainments were related to favourable outcome at 7-year follow-up as defined by sustained functional independence and lower mortality. CONCLUSIONS: The results support the presumption that cognitive reserve plays a significant role as a buffer against the clinical manifestations of SVD and may in part explain high individual variability in outcome.

The Influence of Age in the Relationship between Cerebral Small Vessel Disease and Edentulism. The Atahualpa Project.

BACKGROUND: The association between edentulism and cerebral small vessel disease is controversial. We aimed to assess this relationship in community-dwelling older adults living in rural Ecuador. METHODS: MRI was performed in 311 (81%) of 385 individuals ≥60 years enrolled in the Atahualpa Project. Participants were classified in 2 groups according to whether they have severe edentulism (<10 remaining teeth) or not. Using multivariate logistic regression and exposure effect models, we assessed whether edentulism correlated with severity of white matter hyperintensities (WMHs), after adjusting for relevant confounders. RESULTS: Mean age of participants was 70 ± 8 years (57% women). Severe edentulism was noticed in 152 (49%) individuals and moderate-to-severe WMHs in 81 (26%). In univariate analyses, moderate-to-severe WMHs were more common among edentulous individuals (OR 1.88, 95% CI 1.13-3.16, p = 0.015). Such difference became non-significant in the logistic regression model (OR 1.65, 95% CI 0.91-2.99, p = 0.098); in this model, the single relevant covariate was age. A weighted exposure effect model revealed no association of severe edentulism with moderate-to-severe WMH (average exposure effect: 0.73, 95% CI -0.01 to 0.16, p = 0.10). CONCLUSION: The relationship between edentulism and diffuse subcortical damage of vascular might be explained by the high prevalence of both variables in older adults.

Severe White Matter Hyperintensity Is Associated with Early Neurological Deterioration in Patients with Isolated Pontine Infarction.

OBJECTIVE: Pontine infarction is a common type of brain stem infarction and early neurological deterioration (END). We evaluated the possibility of severe white matter hyperintensity (WMH) as a predictor of END in isolated pontine infarction. METHODS: We recruited 2 types of patients with isolated pontine infarction within 24 h from symptom onset. END was defined as an increase of ≥1 point on the motor National Institutes of Health Stroke Scale (NIHSS) or ≥2 points on the total NIHSS score within 72 h from admission. We graded WMH using Fazekas scale, which is dichotomized into mild (grades 0-1) and moderate to severe (grades 2-3) on fluid-attenuated inversion recovery images. RESULTS: A total of 82 patients with an isolated pontine infarction were selected. END was detected in 23 patients (28%). Severe periventricular and subcortical WMH (PVWMH and SCWMH, respectively) were more frequent in deteriorating patients (p = 0.001 and p = 0.019, respectively). A logistic regression analysis revealed that both severe PVWMH (OR 6.17; 95% CI 1.93-19.75, p = 0.002) and SCWMH (OR 3.19; 95% CI 1.10-9.23, p = 0.032) remained independent predictors of END. CONCLUSIONS: Both severe PVWMH and SCWMH were useful to predict END in patients with isolated pontine infarction.

White Matter Changes and Cognitive Decline in a Ten-Year Follow-Up Period: A Pilot Study on a Single-Center Cohort from the Leukoaraiosis and Disability Study.

AIMS: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. METHODS: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. RESULTS: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (ß = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. CONCLUSION: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years.