Periventricular Hyperintensities Research Articles

White matter hyperintensities and headache in United States military veterans with mild traumatic brain injury.

The objective of this study was to examine the association between white matter hyperintensities and migraine-like headache in United States military veterans with a history of mild traumatic brain injury. White matter hyperintensities on magnetic resonance imaging (MRI) may be associated with migraine; however, little is currently known about the relationship between white matter hyperintensities and headache following mild traumatic brain injury in military veterans. This cross-sectional study consisted of a retrospective chart review of veterans from a Southeastern Department of Veterans Affairs polytrauma clinic who had a verified history of mild traumatic brain injury. Participants were included if they had undergone an MRI of the brain. Images were reviewed for the presence and severity of periventricular and deep white matter hyperintensities. Headache and migraine-like headache were defined based on responses from the Neurobehavioral Symptom Inventory. This cohort included 83 veterans, mostly consisting of males (78/83 [94%]) with a median (interquartile range [IQR]) age of 36 (13) years, who were a median (IQR) of 9 (8) years since their most recent mild traumatic brain injury. Most of the veterans reported experiencing migraine-like headache (67/83 [81%]). Periventricular white matter hyperintensities were identified on MRI among 35% (29/83) of the cohort, and deep white matter hyperintensities were identified on MRI of 25% (21/83) of the cohort. There was no association between the odds of displaying white matter hyperintensities and the presence of migraine-like headache (periventricular: unadjusted odds ratio [OR] 2.75, 95% confidence interval [CI] 0.71-10.6; deep white matter: OR 0.69, 95% CI 0.208-2.29; all p > 0.05), nor headache severity (periventricular: moderate headache OR 2.92, 95% CI 0.67-12.8; severe headache OR 3.11, 95% CI 0.77-12.6; deep white matter: moderate headache OR 1.44, 95% CI 0.358-5.8; severe headache OR 0.94, 95% CI 0.246-3.62; all p > 0.05). Our findings suggest that neither migraine-like headache nor severity of headache is associated with increased prevalence of white matter hyperintensities in veterans with a history of mild traumatic brain injury.

Obesity with low bone mineral density is a risk for cerebral small-vessel disease in older adults: The Bunkyo Health Study

BackgroundCerebral small-vessel disease (cSVD), a key risk factor for stroke and dementia, has been linked to obesity and low bone mineral density (BMD). While obesity and low BMD are often inversely related, their coexistence may increase cSVD risk. We aimed to assess the prevalence of obesity and low BMD coexistence and its association with increased cSVD prevalence. MethodsThis cross-sectional study used baseline data from the Bunkyo Health Study, which included 1531 community-dwelling adults aged 65–84 years without prior stroke history. All participants underwent dual-energy X-ray absorptiometry and brain magnetic resonance imaging. We defined cSVD as the presence of cerebral lacunar infarcts, cerebral microbleeds, periventricular hyperintensity or deep white matter hyperintensity. Obesity was defined by body mass index. Low BMD was defined as osteoporosis in women and osteopenia/osteoporosis in men. Participants were stratified by sex and classified based on obesity and low BMD presence or absence. ResultsThe prevalence of obesity with low BMD was 8.0 % in women and 7.8 % in men. The overall prevalence of cSVD was 23.2 %. Logistic regression analysis revealed that compared to the non-obese and non-low BMD group, the ORs [95 % CIs] for cSVD in the low BMD group, obesity group, and obesity with low BMD group were 1.55 [1.01–2.38], 1.24 [0.66–2.32], and 2.33 [1.20–4.50] in women, and 0.96 [0.60–1.54], 1.13 [0.65–1.96], and 2.80 [1.38–5.69] in men, respectively. ConclusionThe coexistence of obesity and low BMD, observed in approximately 8 % of older adults, was independently associated with the presence of cSVD.

Subtle signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with reduced cognitive function: results from the Hamburg City Health Study.

Atrial fibrillation is associated with cognitive dysfunction. Atrial cardiomyopathy has been correlated with both entities. We aimed to characterize the association of echocardiographic parameters of atrial cardiomyopathy with cognitive function and cerebral changes. Participants of the population-based Hamburg City Health Study underwent in-depth transthoracic echocardiography and cognitive function testing, the Animal Naming Test (ANT), the Trail Making Test A (TMT-A) and B (TMT-B), 10-word learning test and cerebral magnetic resonance imaging. After excluding individuals with stroke or depression, data from 7852 individuals were available. In multi-variable-adjusted regression analyses, the E/e'-ratio was associated with the level of impairment in the ANT (-0.19 per one standard deviation [SD] increase, 95% confidence interval [CI] -0.36-[-0.01]) and the TMT-A (0.01 per one SD increase, 95% CI 0.003-0.020). Left atrial global peak strain was associated with positive performance in the TMT-A and B (-0.01 per one SD increase [95% CI -0.02-(-0.002)] and -0.02 per one SD increase [95% CI -0.03-(-0.01)], respectively) and the immediate recall of the 10-word learning test (0.11 per one SD increase, 95% CI 0.02-0.20). The E/e'-ratio was positively associated with the total and periventricular white matter hyperintensity load in age- and sex-adjusted regression analyses though statistical significance was lost after multi-variable adjustment. Subclinical echocardiographic signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with impaired performance in cognitive tests in the population. Our data provide evidence of the clinically important cardio-cerebral axis, relating cardiac dysfunction with cognitive performance.

Association of Gait Impairment with Executive Dysfunction and Magnetic Resonance Imaging Brain Findings in Elderly Population.

Objectives: The primary objective was to understand the association between gait impairment and executive dysfunction and magnetic resonance imaging (MRI) brain findings in the elderly Indian population. Also, we aimed to assess the association between executive dysfunction (ED) and MRI brain findings in the elderly Indian population. Materials and methods: This was a prospective observational study conducted in the Department of Neurology at a tertiary care facility in Northwest India for a duration of 1 year between October 2021 and September 2022. Results: Patients with hypertension [odds ratio (OR) 2.85, 95% confidence of interval (CI) 1.59-5.10], raised and/or deranged lipid profile (OR 2.19, 95% CI 1.12-4.30), serum creatinine (Sr. creatinine) (OR 2.16, 95% CI 1.85-2.53) and blood urea (OR 2.27, 95% CI 1.92-2.67) were at increased risk of ED. Smoking tobacco was associated with four times increased risk of ED (OR 3.98, 95% CI 2.18-7.26). Of the tests of frontal assessment battery (FAB), the strength of association was highest for motor Luria (OR 34.81, 95% CI 15.84-76.52), followed by the backward digit span test. Patients with ED had decreased step length, abnormal stride width, abnormal cadence, and decreased velocity. Regarding MRI brain findings, atrophy of the occipital lobe was associated with decreased step length; atrophy of the midbrain and cerebellar atrophy were associated with decreased stride width; and midbrain atrophy was associated with cadence. It was found that the basal ganglia and periventricular hyperintensity were associated with step length. Conclusion: The findings contribute to our understanding of the relationship between ED, brain structural changes, and gait abnormalities, highlighting the potential role of smoking, glycemic control (and related risk factors) and brain regions involved in gait control.

White matter lesions as a prognostic marker of recurrence in cryptogenic stroke with high-risk patent foramen ovale

PurposeA high-risk patent foramen ovale (PFO) could be the cause of cryptogenic stroke, and an atrial septal aneurysm (ASA) increases the risk of stroke recurrence in cryptogenic stroke patients with a patent foramen ovale (PFO). Factors related to stroke recurrence according to PFO characteristics have not been fully evaluated. MethodsData from a multicenter, observational registry of ischemic stroke patients undergoing transesophageal echocardiography were used for this study. Patients were classified into three groups: high-risk PFO, PFO with large shunt (≥20 microbubbles) or ASA; right-to-left shunt (RLS), RLS including PFO with <20 microbubbles or without ASA, or pulmonary arteriovenous fistula; and negative RLS. Cox proportional hazards regression analysis was used to explore the factors related to stroke recurrence in these three groups. ResultsIn total, 586 patients (185 females; 65.5±13.2 years) were analyzed. In cryptogenic stroke (329 patients) with median follow-up of 4.2 (interquartile range, 1.0–6.1) years, 55 patients had stroke recurrence. The negative RLS, RLS, and high-risk PFO groups included 179, 90, and 60 patients, in which stroke recurrence occurred in 5.3%, 2.5%, and 4.6% per person-year, respectively. In patients with high-risk PFO, the National Institutes of Health stroke scale score (hazard ratio [HR] 1.257 [1.034-1.530]) and periventricular hyperintensity (HR 3.369 [1.103-10.294]) were predictors of stroke recurrence on multivariable Cox hazards analysis, but no factors were related to stroke recurrence in the RLS and negative RLS groups. ConclusionPeriventricular hyperintensity was shown to predict recurrent stroke in patients with a high-risk PFO.

Dopamine transporter availability based on white matter hyperintensity during early to mid-stage Parkinson's disease and multiple system atrophy: a case control study.

To evaluate the association of white matter hyperintensity (WMH) with dopamine transporter (DAT) availability in patients with early to mid-stage parkinson's disease (PD) and multiple system atrophy (MSA). The clinical and imaging data of 55 patients were collected, including 38 PD and 17 MSA patients and the clinical features of the two groups were compared. DAT specific binding ratio (SBR) were compared between severe and non-severe WMH groups, and between PD and MSA groups. The relationships of WMH with DAT availability and basic clinical characteristics were analyzed. Multiple linear regression analysis showed that age was the only significant variable showing correlation WMH. Age was the only clinical variable significantly correlated with WMH in PD patients (coefficient for periventricular white matter hyperintensity: 0.430, P = 0.007; coefficient for deep white matter hyperintensity: 0.381, P = 0.018). There was no significant correlation between WMH and SBRs and age in MSA patients. The SBR of the caudate nucleus and anterior putamen was significantly lower in the severe WMH group of patients than in the non-severe WMH group (P < 0.05). The values of the caudate nucleus, anterior putamen, and anterior putamen/posterior putamen were significantly lower in PD patients with than without severe WMH (P < 0.05), and the damage to the striatal DAT in MSA patients with severe WMH was similar to the non-severe patients (P>0.05). Patients with PD and a high WMH score had lower DAT availability. WMH affected the availability of DAT in patients with early to mid-stage PD compared to MSA.

Quantification of white matter hyperintensities in type 1 diabetes and its relation to neuropathy and clinical characteristics

AimsThe aims were to quantify periventricular and deep white matter hyperintensities (WMHs) in adults with type 1 diabetes with different neuropathic phenotypes and to correlate WMH measurements to explanatory factors in diabetes. MethodsWMH measurements were obtained from brain magnetic resonance imaging of 56 adults with type 1 diabetes in subgroups including painful diabetic peripheral neuropathy (DPN), painless DPN, without DPN and 20 healthy controls using Fazekas scale and automatic segmentation analysis. ResultsNo differences in Fazekas assessed WMHs were found (individuals with periventricular lesions: diabetes 66 % vs. controls 40 %, p = 0.063, deep lesions: diabetes 52 % vs. controls 50 %, p = 1.0). Using automatic detection, there were no significant differences in count of periventricular (p = 0.30) or deep (p = 0.31) WMHs. Higher periventricular lesion burden was present in diabetes compared with controls (0.21 % vs. 0.06 %, p = 0.048), which was associated with more severe DPN, increased age, decreased cognitive function, and reduced volumetric and metabolic brain measures (all p < 0.05). ConclusionsOur findings indicate increased burden of periventricular WMHs in diabetes which were associated to DPN severity and measurements reflecting neurodegeneration. Deep WMHs, often considered as chronic ischemic, were not significantly different. Mechanisms reflecting neurodegeneration and accelerated brain aging could be an overlooked aspect of peripheral and central neuropathy.

Kidney Impairment Exacerbates Periventricular White Matter Hyperintensities in Patients with CKD

Kidney Impairment Exacerbates Periventricular White Matter Hyperintensities in Patients with CKD

Dose-dependent Effect of Current Smoking on Enlarged Perivascular Space Identified on Brain MRI.

Cerebral small-vessel disease (CSVD) is a common cause of cognitive decline and stroke. Several studies have shown that smoking is a risk factor for CSVD progression. However, the extent to which smoking exacerbates CSVD lesions remains unclear. In this study, we aimed to clarify the association between total smoking exposure and the severity of CSVD in healthy participants. We analyzed the data of participants aged ≥ 50 years who underwent brain screening. The participants' age, sex, body mass index, alcohol consumption history, and medical history (hypertension, diabetes mellitus, and dyslipidemia) were investigated. Smoking status was assessed in pack-years, and smokers were classified as current or past smokers. CSVD findings on magnetic resonance imaging were used to evaluate the severity of periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and enlarged perivascular spaces (EPVSs). The EPVSs were measured in the basal ganglia and centrum semiovale regions. Multivariable ordinal logistic regression analyses were performed to evaluate the effect of smoking, adjusted for the participants' baseline characteristics. A total of 2,137 participants were included in this study. The mean age of the participants was 58.7 years. The mean pack-years were 20.5 for past smokers and 26.8 for current smokers. Among current smokers, increased pack-years were significantly associated with a high EPVS burden in the basal ganglia (odds ratio: 1.14, 95% confidence interval: 1.00-1.28), whereas no such significant association was found for past smokers. No statistically significant association was found between pack-years and the risks of PVH, DSWMH, or EPVS in the centrum semiovale. Current smoking was associated with a dose-dependent risk of EPVS in the basal ganglia in healthy participants.

Increased extracellular free water is related to white matter hyperintensity burden.

Extracellular free water (FW) has important roles in the occurrence and development of white matter hyperintensity (WMH). To explore the correlations between FW and WMH burden. A prospective analysis was conducted using magnetic resonance imaging (MRI) data from 126 individuals. WMH burden was determined based on WMH volumes and Fazekas scores from deep and periventricular white matter hyperintensity (DWMH and PWMH, respectively) in fluid-attenuated inversion recovery (FLAIR) images. FW values were taken from diffusion tensor imaging (DTI). Univariate analysis showed that FW values were correlated with WMH burden, including WMH volumes and DWMH and PWMH Fazekas scores (P < 0.05). After multivariate analysis, FW values were correlated with WMH volumes and DWMH and PWMH Fazekas scores when adjusted for age and hypertension (P < 0.05). Using MRI, increasing extracellular FW was related to WMH burden.

Association between fibrinogen and white matter lesions and cerebral atrophy in patients with acute ischemic stroke

BackgroundInflammation is a potential mechanism underlying the development of white matter lesions (WMLs) and cerebral atrophy. We aimed to investigate the relationship of fibrinogen levels with WMLs and cerebral atrophy in patients with acute ischemic stroke (AIS). MethodsA total of 701 AIS patients were enrolled. Participants were divided into four groups according to the quartiles of fibrinogen levels: Q1 < 2.58 g/L, Q2: 2.58-3.12 g/L, Q3: 3.12-3.67 g/L, Q4: ≥ 3.67 g/L. White matter hyperintensity (WMH), periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) were defined according to the Fazekas scale. Cerebral atrophy was defined according to global cortical atrophy scores. Univariate and multivariate logistic regression were used to explore the relationship of fibrinogen levels and WMHs, PVH, DWMH and cerebral atrophy. ResultsAmong 701 AIS patients, 498 (71.0 %), 425 (60.6 %), 442 (63.1 %), and 560 (79.9 %) had WMHs, PVH, DWMH and cerebral atrophy, respectively. After adjustment for potential covariates, the highest fibrinogen quartiles were significantly associated with increased risk of WMHs (odds ratio [OR] 1.97, 95 % confidence intervals [CI] 1.10-3.50), PVH (OR 1.85, 95 % CI 1.08-3.16) and cerebral atrophy (OR 2.53, 95 % CI 1.19-5.40) but not DWMH (OR 1.37 95 % CI 0.81-2.31) compared with the lowest fibrinogen quartile. Moreover, the association between elevated fibrinogen levels and the risk of WMLs and cerebral atrophy remained significant as continuous variables. ConclusionsIncreased baseline fibrinogen levels were independently associated with WMHs, PVH and cerebral atrophy in patients with ischemic stroke. Fibrinogen could be the potential blood biomarker of WMLs and cerebral atrophy.

Comorbidity of white matter lesions in parkinson's disease: a study on risk factors and phenotypic differences.

Comorbidity of white matter lesions (WMLs) in idiopathic Parkinson's disease (PD) is becoming increasingly common. To analyze the risk factors and phenotypic differences for the occurrence and severity of WMLs in patients with PD. A total of 123 PD patients underwent clinical, laboratory, and magnetic resonance imaging (MRI) evaluations. PD patients with WMLs were found to have a higher association with age, Modified Hoehn & Yahr stage (H-Y stage), and hypertension. There was a certain correlation between the severity of WMLs and PD phenotypes. 89% of PD patients had periventricular hyperintensities (PVH). Additionally, the score of the modified version of the Scheltens visual rating scale of PVH in the postural instability gait difficulty (PIGD) phenotype of PD was significantly higher than that in the tremor-dominant (TD) phenotype. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in the PIGD group were significantly lower than those in the TD group. Furthermore, compared with the TD group, the serum homocysteine level was significantly higher in the PIGD group. Age, H-Y stage, and hypertension are independent risk factors for WMLs in PD, and the severity of WMLs is related to the phenotype of PD patients. Our study found that PVH is the most common occurrence of WMLs in Parkinson's disease, and the burden of PVH is significantly higher in the PIGD phenotype compared to the TD phenotype of PD. Additionally, the PIGD phenotype is associated with more severe cognitive decline and elevated homocysteine levels.

The relationship between intracranial atherosclerosis and white matter hyperintensity in ischemic stroke patients: a retrospective cross-sectional study using high-resolution magnetic resonance vessel wall imaging.

Both intracranial atherosclerosis and white matter hyperintensity (WMH) are prevalent among the stroke population. However, the relationship between intracranial atherosclerosis and WMH has not been fully elucidated. Therefore, the aim of this study was to investigate the relationship between the characteristics of intracranial atherosclerotic plaques and the severity of WMH in patients with ischemic stroke using high-resolution magnetic resonance vessel wall imaging. Patients hospitalized with ischemic stroke and concurrent intracranial atherosclerosis at Beijing Tsinghua Changgung Hospital, a tertiary comprehensive stroke center, who underwent high-resolution magnetic resonance vessel wall imaging and conventional brain magnetic resonance imaging were continuously recruited from January 2018 to December 2018. Both intracranial plaque characteristics (plaque number, maximum wall thickness, luminal stenosis, T1 hyperintensity, and plaque length) and WMH severity (Fazekas score and volume) were evaluated. Spearman correlation or point-biserial correlation analysis was used to determine the association between clinical characteristics and WMH volume. The independent association between intracranial plaque characteristics and the severity as well as WMH score was analyzed using logistic regression. The associations of intracranial plaque characteristics with total white matter hyperintensity (TWMH) volume, periventricular white matter hyperintensity (PWMH) volume and deep white matter hyperintensity (DWMH) volume were determined using multilevel mixed-effects linear regression. A total of 159 subjects (mean age: 64.0±12.5 years; 103 males) were included into analysis. Spearman correlation analysis indicated that age was associated with TWMH volume (r=0.529, P<0.001), PWMH volume (r=0.523, P<0.001) and DWMH volume (r=0.515, P<0.001). Point-biserial correlation analysis indicated that smoking (r=-0.183, P=0.021) and hypertension (r=0.159, P=0.045) were associated with DWMH volume. After adjusting for confounding factors, logistic regression analysis showed plaque number was significantly associated with the presence of severe WMH [odds ratio (OR), 1.590; 95% CI, 1.241-2.035, P<0.001], PWMH score of 3 (OR, 1.726; 95% CI, 1.074-2.775, P=0.024), and DWMH score of 2 (OR, 1.561; 95% CI, 1.150-2.118, P=0.004). Intracranial artery luminal stenosis was associated with presence of severe WMH (OR, 1.032; 95% CI, 1.002-1.064, P=0.039) and PWMH score of 2 (OR, 1.057; 95% CI, 1.008-1.109, P=0.023). Multilevel mixed-effects linear regression analysis showed that plaque number was associated with DWMH volume (β=0.128; 95% CI, 0.016-0.240; P=0.026) after adjusted for age and sex. In ischemic stroke patients, intracranial atherosclerotic plaque characteristics as measured by plaque number and luminal stenosis were associated with WMH burden.

Associations between semi-quantitative evaluation of intracranial arterial calcification and total cerebral small vessel disease burden score: a retrospective case-control study.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a cause of cognitive impairment, dementia, and stroke. Developing a better understanding of the risk factor of aCSVD is key to reducing the incidence of these conditions. This study investigated the association between intracranial arterial calcification (IAC) and total cerebral small vessel disease (CSVD) burden score. This is a retrospective study, the subjects were transient ischemic attack (TIA) or acute ischemic stroke (AIS) patients. The data of 303 inpatients admitted to our study hospital between December 2018 and July 2020 were analyzed. Four imaging markers of CSVD (lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces) were evaluated by magnetic resonance imaging, and a total CSVD burden score was calculated. The experimental group was divided into four subgroups according to total CSVD burden score (1-4 points). Patients without CSVD (0 points) served as the control group. Head computerized tomography (CT) scans were used to assess ICA, using Babiarz's method. The correlations between IAC and single imaging markers of CSVD were determined using Spearman's rank correlation. Binary logic regression analysis and multivariate ordered logic regression analysis were used to determine the associations between IAC and aCSVD. IAC was positively correlated with total CSVD burden score (r = 0.681), deep white matter hyperintensities (r = 0.539), periventricular white matter hyperintensities (r = 0.570), cerebral microbleeds (r = 0.479), lacunes (r = 0.541), and enlarged perivascular spaces (r = 0.554) (all p < 0.001). After adjusting for the confounding factors of age, diabetes, and hypertension, aCSVD was independently associated with IAC grade 1-2 [odds ratio (OR) = 23.747, 95% confidence interval (CI) = 8.376-67.327] and IAC grade 3-4 (OR = 30.166, 95% CI = 8.295-109.701). aCSVD severity was independently associated with IAC grade 3-4 (OR = 4.697, 95% CI = 1.349-16.346). IAC is associated with the total CSVD burden score and single imaging signs.

Ambient air pollution, covert cerebrovascular disease and cognition: results from the ISSYS study.

Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. A prospective population-based study of 976 stroke-free and non-demented individuals living in Barcelona, Spain, was conducted during 2010-2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate-adjusted models were developed. At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06-4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13-2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17-2.35) or periventricular (OR 1.96; 95% CI 1.10-3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05-1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04-1.79). There was no association between AP and cognition. Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined.

Association of late-life blood pressure change with cerebral small vessel disease in the MIND-China study

ObjectivesThis study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD).MethodsThis study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models.ResultThe mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes.ConclusionsCSVDs are associated with increased exposure to elevated BP later in life.

Seizure Outcome and Predicting Factors in Adult Patients with Phenylketonuria: Single-center Experience

ABSTRACT Objective: Phenylketonuria (PKU) is one of the most common metabolic disorders worldwide. If left untreated, it causes neuropsychiatric sequelae, with seizures being a common occurrence. There is little information about the clinical features of epilepsy, electroencephalography (EEG) findings, and factors related to seizure outcomes in adult patients. We aimed to investigate these variables in adult PKU patients. Methods: We conducted a retrospective search in our database using the keywords “PKU and epilepsy” for the period between 2008 and 2022. Demographic, clinical, EEG, and cranial magnetic resonance imaging (MRI) findings of the patients were extracted from the electronic health records. Scalp EEG and MRI findings were reassessed. Phenylalanine (Phe) levels of the cases were retrieved. The potential correlation between seizure outcome and laboratory findings was analyzed. Results: Ten patients (4 females; aged: 19–55 years) were included. Seizure onset was various. The most common seizure type was bilateral tonic-clonic. Nine patients were on antiseizure medications (ASMs); seven were seizure-free. EEG background activity was slow in four patients, with paroxysmal discharges in eight individuals. The most frequent MRI finding was periventricular white matter hyperintensity. No correlation existed between seizure outcome and clinical, EEG, MRI results, or Phe levels. Seizure freedom was more common in patients with good dietary compliance. Conclusion: Bilateral tonic–clonic seizures were the most common type of seizure, accompanied by frequent paroxysmal activity in EEG. MRI scans revealed periventricular white matter hyperintensity. Seizure freedom was commonly achieved with ASMs, irrespective of blood Phe levels. Nevertheless, dietary compliance may play a role in seizure control.

Diagnostic Accuracy of Posterior/Anterior Periventricular WMH Ratio to Differentiate CAA From Hypertensive Arteriopathy.

Periventricular white matter hyperintensities (PVWMHs) in cerebral amyloid angiopathy (CAA) have been reported posterior predominant using semiautomated segmentation method and logarithmic transformation. We aimed to compare PVWMH extent and posterior/anterior distribution between patients with CAA and patients with hypertensive arteriopathy with radiological tools available in daily practice. We retrospectively analyzed confluent PVWMH directly adjacent to lateral ventricles on axial FLAIR (fluid-attenuated inversion recovery) from 108 patients with CAA and 99 patients with hypertensive arteriopathy presenting with hemorrhage-related symptoms consecutively recruited in our stroke database (Nîmes University Hospital, France) between January 2015 and March 2022. For each of the left (L), right (R), anterior (A), and posterior (P) horns of lateral ventricles, the maximal distance between the outer PVWMH border and ventricle border was measured. The sum of anterior left PVWMH and anterior right PVWMH, and posterior left PVWMH and posterior right PVWMH resulted in anterior and posterior extent, respectively. Compared with hypertensive arteriopathy, patients with CAA were older (median, 77 versus 71; P=0.0010) and less frequently male (46% versus 64%; P=0.012) and had less frequent hypertension (45% versus 63%; P=0.013) and more chronic hemorrhages (P<0.0001). CAA showed slightly more extensive anterior right PVWMH (median, 6.50 versus 5.90 mm; P=0.034), far more extensive (all P<0.0001) posterior left PVWMH (median, 13.95 versus 6.95 mm), posterior right PVWMH (median, 14.15 versus 5.45 mm), posterior (median, 27.95 versus 13.00 mm), and total (median, 39.60 versus 24.65 mm) PVWMH, and higher posterior/anterior ratios (median, 1.82 versus 1.01). Age-/sex-adjusted model predicting CAA incorporating total PVWMH extent and posterior/anterior ratios for the given score (-4.3683+0.0268×PVWMH-T+0.3749×posterior/anterior PVWMH ratio+0.0394×age+0.3046 when female) showed highest area under the curve (0.76 [0.70-0.83]), with a 72% [62.50-80.99] sensitivity and 76% [67.18-84.12] specificity. Values above the optimal threshold of 0.22 for the score showed a crude relative risk of 2.75 (2.26-2.37; P<0.0001). Severe posterior PVWMH and high posterior/anterior PVWMH ratio assessed by radiological tools used in daily practice are associated with probable CAA versus hypertensive arteriopathy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05486897.

Imaging features for the identification of atrial fibrillation in cryptogenic stroke patients

BackgroundWhether specific imaging aspects can be used to identify cryptogenic stroke (CS) patients with high risk of underlying atrial fibrillation (AF) remains unclear. The purpose of this study was to evaluate brain-imaging features in CS patients and their utility as AF predictors.MethodsThe Nordic Atrial Fibrillation and Stroke study was a prospective observational study of CS and transient ischemic attack patients undergoing 12-month cardiac-rhythm monitoring, biomarker and clinical assessments. In this imaging sub-study, brain magnetic resonance imaging and computed tomography scans from 106 patients were assessed for acute and chronic ischemic lesions in relation to AF occurrence and included in a score to predict AF. Receiver operating characteristics (ROC) curve was used to evaluate the discriminative ability of the score and for its dichotomization for predictive model.ResultsAge, periventricular white-matter hyperintensities (PVWMH), acute lesion size, and vessel occlusion were significantly associated with AF. Acute and chronic cortical infarcts as well as chronic cerebellar infarcts were numerically more frequent in the AF group than the non-AF group. A score consisting of six features (0–6 points) was proposed (age ≥ 65 years, chronic cortical or cerebellar lesions, acute cortical lesions, PVWMH ≥ 2 in Fazekas scale, vessel occlusion, and acute lesion size ≥ 10 mm). Area under ROC curve was 0.735 and a score of ≥ 3 points was a predictor of AF.ConclusionsThe suggested score was shown to identify CS patients with an increased risk of underlying AF.

Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy

Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77–9.50]mm2/s × 10−4) compared with presymptomatic mutation-carriers (2.62 [1.96–3.43]mm2/s × 10−4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16–0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08–0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22–0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13–0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = −0.42 [−0.69–0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.