Jul 2026· Turkish Journal of Cerebrovascular Diseases· Vol 32, pp. 100-107· 0 citations· 30 references
TL;DR
The association between b-WMHs and stroke remained significant after adjustment for age, sex, and supratentorial WMHs (s‑WMHs), but lost statistical significance when additional vascular risk factors were included.
Abstract
Background: No prior research has determined whether brainstem white matter hyperintensities (b-WMHs) are associated with first-ever stroke. This study aims to investigate whether b-WMHs can predict first-ever stroke.
Methods: This was a retrospective study. Clinical records and magnetic resonance imaging (MRI) scans reviewed to identify patients with and without brainstem white matter hyperintensities (b-WMHs). A total of 180 individuals with b-WMHs and no prior history of stroke, and 205 individuals without b-WMHs, were included. Stroke incidence within a three‑year observation window was determined retrospectively from medical records and confirmed by neuroimaging, following American Heart Association/American Stroke Association (AHA/ASA) guidelines. Predictors of stroke were evaluated using Cox regression analysis.
Results: Within the three‑year observation window, 37 patients (9.6%) experienced a first‑ever stroke, 40.5% in the anterior circulation and 59.5% in the posterior circulation. Stroke incidence was significantly higher among patients with b‑WMHs (13%) compared with those without (6%) (OR, 2.27; 95% CI, 1.12–4.61; P=0.02). In multivariable Cox regression analysis, stroke occurrence was independently associated with hypertension (HR, 5.39; P<0.001), diabetes mellitus (HR, 4.39; P=0.007), hyperhomocysteinemia (HR, 2.66; P=0.004), and atrial fibrillation (HR, 3.00; P<0.01). The association between b‑WMHs and stroke remained significant after adjustment for age, sex, and supratentorial WMHs (s‑WMHs), but lost statistical significance when additional vascular risk factors were included.
Conclusion: Brainstem white matter hyperintensities are associated with first-ever stroke but are not independent risk factors. Further studies are needed to explore the mechanisms linking b-WMHs to stroke risk.
INTRODUCTION
White matter hyperintensities (WMH) are key radiographic biomarkers of cerebral small vessel disease (CSVD) and have been associated with worse outcomes after stroke. Since CSVD may involve blood-brain barrier disruption, we hypothesized that worse outcomes in those with WMH may be mediated through more severe cerebral edema and hemorrhagic transformation (HT).
METHODS
In this retrospective multicenter cohort study, we studied patients from four multinational stroke cohorts who presented within 12 h of anterior circulation large vessel occlusion (LVO) stroke and received at least one follow-up computed tomography (CT) between 12 and 48 h. WMH were rated on baseline CTs using a Fazekas-derived system, with a subset also assessed with Fazekas grading on magnetic resonance imaging (MRI). Automated image analysis measured cerebrospinal fluid displacement (ΔCSF) and lesional-to-contralateral hemispheric CSF volumes (CSF-ratio) as quantitative edema biomarkers. We analyzed the association between WMH presence and edema severity, hemorrhagic transformation, and poor functional outcome (mRS 3-6), adjusting for key covariates, overall and in the subgroup undergoing thrombectomy and those with successful reperfusion.
RESULTS
Of 1290 patients with LVO, 782 were eligible for analysis. Of these, 19% had WMH on CT. Patients with WMH were older, more often female, and had a history of hypertension and higher presenting systolic blood pressure and glucose levels. WMH presence was associated with worse functional outcome, adjusting for age and additional covariates [OR 1.84 (1.06-3.22), p = 0.04] but lower risk of any HT [OR 0.48 (0.25-0.88), p = 0.03]. However, WMH presence by CT or MRI was not associated with edema (ΔCSF, CSF ratio, or midline shift) in the whole population or thrombectomy/reperfusion subgroups. Reperfusion was associated with less edema and improved recovery.
CONCLUSIONS
Presence of CT-graded WMH was associated with worse outcome after LVO stroke, independent of age and other factors. However, this risk appears not to be mediated through greater risk of HT or cerebral edema formation.
Objectives Although MRI is the optimal imaging method for assessing white matter hyperintensity (WMH), it lacks sensitivity to the underlying pathophysiological changes of WMH. This study aims to investigate EEG changes associated with WMH and identify potential EEG biomarkers for WMH-related dementia. Methods This cross-sectional study enrolled 90 subjects: 30 patients with WMH with dementia (WMHD), 30 patients with WMH without dementia (WMH-ND), and 30 age-and sex-matched healthy controls. Brain MRI was used to segment and quantify deep, periventricular, and total WMH volumes (DWMH, PVWMH, TWMH). Resting-state EEG data were recorded for microstate analysis. Four microstate classes (A, B, C, D) were extracted, and their occurrence, mean duration, time coverage, and transition probabilities were calculated. Partial correlation analysis was used to evaluate the associations between microstate features and WMH volume as well as MMSE scores. Based on microstate features, classification prediction models were constructed using machine learning algorithm. Results In the WMHD group, the temporal parameters (occurrence, mean duration, time coverage) of microstate C were decreased (P < 0.05–0.001), while the mean duration of microstates A and B was prolonged (P < 0.05–0.001). The WMH-ND group also showed reduced microstate C temporal parameters (P < 0.001), but exhibited compensatory increases in mean duration and time coverage of microstate D (P < 0.001). Transition probabilities toward microstate C were reduced in both patient groups (P < 0.001), and all transition probabilities toward microstate D were lower in WMHD than in WMH-ND (P < 0.05–0.001). Temporal parameters of microstates A and B and transition probabilities toward them were positively correlated with WMH volume and negatively correlated with MMSE score. Conversely, those of microstate D showed the opposite correlations. For distinguishing WMHD from WMH-ND, support vector machine (SVM) and logistic regression (LR) performed best (accuracy: 76.67%, AUC: 0.84). Classification performance was highest for WMH-ND vs. HC (LR: 79.17%, AUC 0.86), and lowest for WMHD vs. HC (SVM: 68.33%, AUC 0.77). Conclusion Patients with WMH exhibit alterations in EEG microstate features that are significantly correlated with WMH burden and cognitive function. Classification models based on these microstate features show promise for practical application in WMH-related dementia.
Kaiyan Feng, Jiaxin Cai, Jian-Ming Lei et al.· Frontiers in Neuroscience· 0 citations
WMH are common in adults with focal epilepsy, and the frontal lobe is the most frequently affected region, and age, seizure duration, interictal epileptiform discharges, and seizure duration are independent risk factors for greater WMH burden.
Xu Zhang, Wenjie Zhang, Chang Ge et al.· Clinical EEG and Neuroscienc...· 0 citations
Background: Migraine is a common neurological disorder characterized by recurrent headaches that significantly affect quality of life and daily functioning. Brain magnetic resonance imaging (MRI) often demonstrates white matter hyperintensities (WMHs), but their clinical significance remains uncertain. Therefore, this study was conducted to determine the frequency and radiological characteristics of WMHs on MRI in patients with migraine.
Methods: This descriptive cross-sectional study was conducted at Pak Emirates Military Hospital, Rawalpindi. A total of 400 patients aged 18–60 years with migraine diagnosed according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), were included through non-probability consecutive sampling. Brain MRI was performed using T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences. Associations were evaluated using the Chi-square test, and multivariable binary logistic regression analysis was performed to identify independent predictors of WMHs. Data were analyzed using SPSS version 28.
Results: WMHs were significantly more frequent in patients aged >40 years (p<0.001), those with chronic migraine (p=0.01), and those with a migraine duration >5 years (p=0.003). Binary logistic regression demonstrated that age >40 years, chronic migraine, and migraine duration >5 years were independent predictors of WMHs, whereas gender, migraine aura, hypertension, and diabetes mellitus were not independently associated.
Conclusion: WMHs are common MRI findings in patients with migraine, particularly in older patients and those with chronic or long-standing disease. Most lesions are small, mild, and predominantly involve the frontal and deep white matter. These findings may improve the interpretation of MRI findings and contribute to a better understanding of migraine-related brain changes.
Aqeela, K. Nawaz, Sania Saeed et al.· International journal of pat...· 0 citations
BACKGROUND: White matter hyperintensities (WMH) are widely used to assess cerebral small vessel disease but reflect late-stage injury. Diffusion magnetic resonance imaging (MRI) biomarkers have been proposed to capture earlier small vessel disease-related microstructural damage but their temporal progression relative to WMH and risk factors associated with progression remain unexplored. METHODS: We identified 2077 participants from the population-based cohort study of the Mayo Clinic Study of Aging in Olmsted County, Minnesota (aged 50–101 years) collected between 05/2005 and 09/2024 with longitudinal neuroimaging. Using multioutput nonlinear mixed-effects models in those with at least 2 fluid-attenuated inversion recovery-MRI and diffusion MRI scans, we characterized the temporal progression of WMH and 4 diffusion MRI biomarkers: fractional anisotropy of the genu of the corpus callosum, peak width of skeletonized mean diffusivity, free water, and Arteriolosclerosis-score, which were automatically estimated. Models incorporated participant-specific time shifts, correlations between biomarkers, and effects of risk factors (sex, education, APOE ε4 status, cardiometabolic conditions). RESULTS: The study population had a mean age of 78 years, 47% were women, 28% were APOE ε4 allele carriers, and 80% were cognitively unimpaired, with an average follow-up of 5.2 years (SD, 4.3 years) for fluid-attenuated inversion recovery-MRI and 4.3 years (SD, 3.9 years) for diffusion MRI. Arteriolosclerosis-score, fractional anisotropy of the genu of the corpus callosum, free water, and peak width of skeletonized mean diffusivity became abnormal in 50% of the study population 16, 12, 10, and 7 years before WMH become abnormal (half-width of CI <1 year), respectively. Global markers (Arteriolosclerosis-score, free water, peak width of skeletonized mean diffusivity, and WMH) were correlated, indicating shared substrates of widespread white matter injury. Fractional anisotropy of the genu of the corpus callosum, a vascular risk microstructural injury biomarker, was weakly coupled with WMH and had an earlier but more linear worsening across adulthood. Cardiometabolic conditions predicted earlier worsening of all biomarkers. Female participants showed earlier WMH, fractional anisotropy of the genu of the corpus callosum, and Arteriolosclerosis-score abnormalities, whereas male participants exhibited earlier peak width of skeletonized mean diffusivity and free water abnormalities. CONCLUSIONS: Diffusion MRI biomarkers were abnormal at least a decade before WMH become abnormal in the population, revealing a prolonged phase of early small vessel disease and highlighting their potential for small vessel disease prevention.
P. Vemuri, Mingzhao Hu, Emily S. Lundt et al.· Stroke· 0 citations
Objective: White matter hyperintensities (WMH) are among the most common imaging markers of cerebral small vessel disease and may reflect diffuse cerebrovascular vulnerability. This study aimed to investigate the relationship between WMH burden and intracranial aneurysm (IA) rupture.
Materials and Methods: This retrospective observational study included 120 patients with digital subtraction angiography (DSA)-confirmed intracranial aneurysms. Patients were categorized into ruptured (n = 72) and unruptured (n = 48) aneurysm groups. Demographic characteristics, vascular risk factors, aneurysm morphology, and WMH burden were evaluated. WMH severity was assessed using the Fazekas scale on T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences. Multivariate logistic regression analysis was performed to identify factors independently associated with aneurysm rupture.
Results: Hypertension, smoking, anterior communicating artery aneurysms location, higher aspect ratio, and bleb or secondary outpouching were more frequent in ruptured aneurysms. Total WMH score was significantly higher in the ruptured group (median 3 [0–6] vs. 2 [0–5], P = .005). Multivariable analysis demonstrated that AComA location (OR: 2.61, 95% CI: 1.17–5.82, P = .018), presence of bleb or secondary outpouching (OR: 3.38, 95% CI: 1.54–7.40, P = .002), and total WMH score (OR: 1.28, 95% CI: 1.05–1.56, P = .014) were independently associated with aneurysm rupture. No significant association was found between WMH burden and modified Fisher score among patients with ruptured aneurysms.
Conclusions: Increased WMH burden was independently associated with IA rupture. These findings suggest that aneurysm rupture may be influenced not only by local aneurysm morphology but also by diffuse cerebrovascular vulnerability. WMH burden may represent a potential imaging marker associated with aneurysm instability and rupture risk.