White Matter Signal Abnormalities Research Articles

Characterization of MRI White Matter Signal Abnormalities in the Pediatric Population.

(1) Background and Purpose: The aim of this study was to retrospectively characterize WMSAs in an unselected patient cohort at a large pediatric neuroimaging facility, in order to learn more about the spectrum of the underlying disorders encountered in everyday clinical practice. (2) Materials and Methods: Radiology reports of 5166 consecutive patients with standard brain MRI (2006-2018) were searched for predefined keywords describing WMSAs. A neuroradiology specialist enrolled patients with WMSAs following a structured approach. Imaging characteristics, etiology (autoimmune disorders, non-genetic hypoxic and ischemic insults, traumatic white matter injuries, no final diagnosis due to insufficient clinical information, "non-specific" WMSAs, infectious white matter damage, leukodystrophies, toxic white matter injuries, inborn errors of metabolism, and white matter damage caused by tumor infiltration/cancer-like disease), and age/gender distribution were evaluated. (3) Results: Overall, WMSAs were found in 3.4% of pediatric patients scanned at our and referring hospitals within the ten-year study period. The majority were found in the supratentorial region only (87%) and were non-enhancing (78% of CE-MRI). WMSAs caused by autoimmune disorders formed the largest group (23%), followed by "non-specific" WMSAs (18%), as well as non-genetic hypoxic and ischemic insults (17%). The majority were therefore acquired as opposed to inherited. Etiology-based classification of WMSAs was affected by age but not by gender. In 17% of the study population, a definite diagnosis could not be established due to insufficient clinical information (mostly external radiology consults). (4) Conclusions: An "integrated diagnosis" that combines baseline demographics, including patient age as an important factor, clinical characteristics, and additional diagnostic workup with imaging patterns can be made in the majority of cases.

Evolution of the intracranial features of congenital cytomegalovirus on MRI

To describe the evolution of the intracranial features of congenital cytomegalovirus (cCMV) on magnetic resonance imaging (MRI). Sixteen infants with polymerase chain reaction (PCR)-confirmed cCMV who had undergone at least two MRI examinations of the brain were identified. Two paediatric neuroradiologists reviewed the baseline studies retrospectively for intracranial features of cCMV, including white matter signal abnormalities, subependymal cysts, malformations of cortical development, and intracranial calcification. The subsequent MRI studies were then reviewed and directly compared to the baseline examinations. White matter signal abnormalities were seen on all 16 baseline studies (100%); these persisted on all subsequent examinations but were patchier, more focal, and associated with an interval reduction in white matter volume. Subependymal cysts were present on 11 (69%) of the baseline scans; these almost universally regressed (in 10 of the 11 cases [91%]), with no new cysts appreciable on subsequent imaging. Malformations of cortical development, exclusively in the form of polymicrogyria, were seen in six (38%) patients and persisted, unchanged, on subsequent imaging. Intracranial calcification was seen in a minority of baseline studies (4 [25%]) and remained stable on subsequent scans. Children with cCMV who present later in life without an established or suspected underlying pathology can pose a challenge to the assessing radiologist. The radiological sequelae of cCMV can be non-specific; in some cases, white matter signal abnormalities and focal loss of white matter volume may be the only intracranial features. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.

Underlying cerebrovascular pathology in Subjective Cognitive Decline: A systematic review and meta‐analysis

AbstractBackgroundSubjective cognitive decline (SCD) implies self‐reported cognitive complaints in absence of objective cognitive impairment. SCD has been postulated as an early marker of Alzheimer’s Disease (AD). However, longitudinal studies have linked SCD to future vascular dementia. Thus, we conducted a systematic review and meta‐analysis aiming to synthesise and analyse the available data on the association between SCD and the presence of underlying cerebrovascular pathology measured by MRI.MethodOur study was performed following the PRISMA statement. The search strategy included terms for “subjective cognitive decline” and “white matter signal abnormalities”. It was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin by December 8th, 2021. Two authors screened the studies in a 2‐stepwise approach. Primary studies including cognitively unimpaired adults with subjective cognitive complaints meeting the SCD‐I criteria for SCD that evaluated cerebrovascular pathology based on white matter signal abnormalities (WMSA) on MR images were selected. Study quality was assessed using the FLC 3.0 tool. Meta‐analysis comparing case‐control mean difference of WMSA was performed.ResultOf 240 articles identified, 16 research articles were selected. Of those, 8 case‐control studies were selected for the meta‐analysis. The sample size of the SCD group across the studies ranged from 8 to 906 participants, with age ranged from 40 to 84 years. All eight studies comprised a total of 2.637 SCD individuals. Study quality was deemed moderate (n=6) to high (n=10). The meta‐analysis showed a significant overall effect‐size between the mean WMSA burden of SCD and the controls, that was not significantly heterogeneous (Q(gl=7)=14.20; p=0,04; I2=42,5%). SCD was significantly associated with higher CVP burden based on neuroimaging measures.ConclusionThis is the first study to synthesise and analyse the current evidence on the association between SCD and WMSA. Our findings show the usefulness of SCD as a marker of underlying cerebrovascular pathology. Thus, the potential role of SCD as a preclinical stage of vascular cognitive impairment needs further investigation. Changes in lifestyle (e.g. exercise, diet, smoking cessation), cognitive stimulation or pharmacotherapy may be key to avoid an evolution towards cognitive deterioration in SCD.

Vascular health is associated with locus coeruleus‐related entorhinal tau deposition

AbstractBackgroundAutopsy studies reported that the locus coeruleus (LC) is one of the first sites of tau accumulation. In addition, LC‐mediated norepinephrine (NE) signaling is thought to play a role in blood‐brain‐barrier maintenance and neurovascular coupling through its projections to the microvasculature, suggesting that the NE‐LC system interacts with cerebrovascular disease and Alzheimer’s disease (AD) pathology. Since vascular risk factors are prevalent in older individuals and contribute to vascular pathology, a common co‐pathology of AD, understanding interrelationships among vascular health, tau and LC integrity as early as possible, can guide prevention.MethodWe included 124 individuals (Table1) from the Harvard Aging Brain Study with MRI and 18F‐Flortaucipir and 11C‐Pittsburgh‐Compound‐B PET‐imaging within one year of each other. LC‐MRI signal intensity was extracted from 5 maximum‐intensity voxels and normalized to pontine tegmentum. White matter signal abnormalities (WMSA intracranial volume adjusted) were obtained from FreeSurfer6. PET measures were partial‐volume corrected. The Framingham‐Risk‐Score (FRS‐CVD, likelihood of a cardiovascular event in 10 years) was calculated. Structural Equation Models were used to test hypothetic models (1: WMSA mediate the relationship between FRS‐CVD and LC, leading to entorhinal (EC) tau; 2: FRS‐CVD is associated with WMSA and LC, and the LC influences WMSA, both leading to EC tau) against the null model (independent paths of LC and WMSA between FRS‐CVD and EC tau;Figure1). Models were bootstrapped (n = 2000). Model fit measures determined which model described the data best (CFI >0.90, RMSEA <0.08, SRMR <0.08). Age and sex were included as covariates.ResultModels null and 2 had poor fit. Model‐1 had an excellent fit, suggesting that a higher likelihood of a cardiovascular event in ten years is positively associated with WMSA, WMSA is associated with LC intensity, which in turn is associated with EC tau (Table2). Posthoc, global Aβ (DVR) was added as covariate in model‐1, this did not change the model‐fit or outcomes.ConclusionPrevious work demonstrated that LC‐intensity correlates strongly with entorhinal tau. Our findings now suggest that presence of increased cardiovascular risk is associated with lower LC‐intensity through its effects on white‐matter damage, emphasizing the importance of mitigating risk factors earlier in life.

Cerebrovascular damage in subjective cognitive decline: A systematic review and meta-analysis.

Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer's Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers. This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed. Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD. Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.

Chronic Active Epstein-Barr Virus Infection With Central Nervous System Involvement in Children: A Clinical Study of 22 Cases.

To analyze the clinical features, treatment, and prognosis of chronic active Epstein-Barr virus infection (CAEBV) with central nervous system (CNS) involvement in children. Patients with CAEBV admitted to Beijing Children's Hospital, Capital Medical University, were enrolled in this study from January 2017 to December 2020. They were divided into a CNS group and a non-CNS group based on the presence of CNS involvement. Twenty-two patients developed CNS disease, accounting for 23.9% (22/92) of CAEBV patients in the same period. Of these, only 2 of 22 patients presented initially with neurologic symptoms in the CNS group, and they all improved after treatment. Cerebrospinal fluid (CSF) examination demonstrated normal protein concentration and cell number in all patients with CNS involvement. Only 7 patients were positive for CSF EBV-DNA. Twenty-one patients had neuroimaging abnormalities, such as white matter signal abnormalities, encephalography or calcification. In the CNS group, 7 (31.8%) patients died, including 5 who died of active hemophagocytic lymphohistiocytosis, 1 died of unrelated causes, and 1 died of respiratory failure caused by pulmonary lymphoproliferative disease progression after transplantation. The 3-year overall survival was lower in the CNS group than in the non-CNS group (63.6% ± 11.9% versus 86.9% ± 4.1%, P = 0.027). Hemophagocytic lymphohistiocytosis (HLH) is an independent risk factor for CNS involvement in patients with CAEBV (OR = 2.946, 95% CI: 1.042-8.335, P = 0.042). Compared with the non-CNS group, blood EBV-DNA loads and CD4+/CD8+ ratio of T lymphocytes in the CNS group were higher (P < 0.001), while fibrinogen levels and natural killer (NK)-cell activity were lower (P = 0.047). Children with CAEBV were more likely to develop CNS diseases with low NK-cell activity (NK-cell activity < 14.00%, P = 0.023) or high alanine aminotransferase (ALT) levels (ALT levels > 40 U/L, P = 0.032). CAEBV with CNS involvement has nonspecific clinical manifestations, laboratory data, neuroimaging but has a worse prognosis. Blood fibrinogen levels and NK-cell activity in CAEBV children with CNS involvement are lower than in those without CNS involvement. In contrast, blood EBV-DNA loads and CD4+/CD8+ ratio of T lymphocytes are higher. Children with CAEBV who presented with HLH, NK-cell activity <14.00%, serum ALT >40 U/L and high-blood EBV-DNA loads are prone to develop CNS diseases.

Case Report: Fortuitous discovery of a white matter signal abnormality in the context of Leopard syndrome

Multiple Lentigines syndrome is an autosomal dominant inherited disorder of variable expressivity also known by the acronym LEOPARD syndrome. A rare disease with multiple congenital anomalies, mainly characterized by skin, facial and cardiac anomalies. Other malformations can be encountered, in particular cerebral and dysmorphic. We report the case of a 40-year-old female patient known for a Leopard syndrome, who in the context of bilateral hypoacusis, the cerebral MRI carried out finds a lesion in flair hypersignal at the asymptomatic left occipital level, we do not note any evolution of this lesion after 10 years this could correspond to "unidentified shiny object: OFU". In conclusion, LEOPARD syndrome is a disease with a multi-systemic involvement, the discovery of a lesion corresponding to an OFU" is possible.

Classification of white matter lesions and characteristics of small vessel disease markers.

Radiological markers for cerebral small vessel disease (SVD) may have different biological underpinnings in their development. We attempted to categorize SVD burden by integrating white matter signal abnormalities (WMSA) features and secondary presence of lacunes, microbleeds, and enlarged perivascular spaces. Data were acquired from 610 older adults (aged > 40 years) who underwent brain magnetic resonance imaging exam as part of a health checkup. The WMSA were classified individually by the number and size of non-contiguous lesions, distribution, and contrast. Age-detrended lacunes, microbleeds, and enlarged perivascular space were quantified to further categorize individuals. Clinical and laboratory values were compared across the individual classes. Class I was characterized by multiple, small, deep WMSA but a low burden of lacunes and microbleeds; class II had large periventricular WMSA and a high burden of lacunes and microbleeds; and class III had limited juxtaventricular WMSA and lacked lacunes and microbleeds. Class II was associated with older age, diabetes, and a relatively higher neutrophil-to-lymphocyte ratio. Smoking and higher uric acid levels were associated with an increased risk of class I. The heterogeneity of SVD was categorized into three classes with distinct clinical correlates. This categorization will improve our understanding of SVD pathophysiology, risk stratification, and outcome prediction. • Classification of white matter signal abnormality (WMSA) features was associated with different characteristic of lacunes, microbleeds, and enlarged perivascular space and clinical variability. • Class I was characterized by multiple, small, deep WMSA but a low burden of lacunes and microbleeds. Class II had large periventricular WMSA and a high burden of lacunes and microbleeds. Class III had limited juxtaventricular WMSA and lacked lacunes and microbleeds. • Class II was associated with older age, diabetes, and higher neutrophil-to-lymphocyte ratio. Smoking and higher uric acid levels were associated with an increased risk of class I.

Ischemic Stroke With Hemorrhagic Conversion in a Case of Lyme Neuroborreliosis

Lyme disease is an infectious tick-borne illness predominant in northeastern and midwestern United States. The clinical presentation varies significantly and only a few cases develop Lyme neuroborreliosis (LNB), which makes diagnosis difficult. A 59-year-old male visiting from Michigan presented to a hospital in Florida with an ischemic stroke with aphasia and acute confusion for two days. He had imaging that noted a subacute infarct in the left parietal lobe along with multiple areas of white matter signal abnormalities and CSF serology positive for Borrelia burgdorferi IgM and IgG antibodies. The patient was placed on ceftriaxone for 30 days and showed significant clinical improvement. We present a case of ischemic stroke with hemorrhagic conversion and an incidental finding of LNB.

A nationwide survey of monocarboxylate transporter 8 deficiency in Japan: Its incidence, clinical course, MRI and laboratory findings

BackgroundMonocarboxylate transporter 8 (MCT8) deficiency is an X-linked recessive developmental disorder characterized by initially marked truncal hypotonia, later athetotic posturing, and severe intellectual disability caused by mutations in SLC16A2, which is responsible for the transport of triiodothyronine (T3) into neurons. We conducted a nationwide survey of patients with MCT8 deficiency to clarify their current status. MethodsPrimary survey: In 2016–2017, we assessed the number of patients diagnosed with MCT8 deficiency from 1027 hospitals. Secondary survey: in 2017–2018, we sent case surveys to 31 hospitals (45 cases of genetic diagnosis), who responded in the primary survey. We asked for: 1) perinatal history, 2) developmental history, 3) head MRI findings, 4) neurophysiological findings, 5) thyroid function tests, and 5) genetic test findings. ResultsWe estimated the prevalence of MCT8 deficiency to be 1 in 1,890,000 and the incidence of MCT8 deficiency per million births to be 2.12 (95 % CI: 0.99–3.25). All patients showed severe psychomotor retardation, and none were able to walk or speak. The significantly higher value of the free T3/free T4 (fT3/fT4) ratio found in our study can be a simple and useful diagnostic biomarker (Our value 11.60 ± 4.14 vs control 3.03 ± 0.38). Initial white matter signal abnormalities on head MRI showed recovery, but somatosensory evoked potentials (SEP) showed no improvement, suggesting that the patient remained dysfunctional. ConclusionFor early diagnosis, including in mild cases, it might be important to consider the clinical course, early head MRI, SEP, and fT3/fT4 ratio.

Clinical, radiologic, and pathologic features of the globular glial tauopathy subtype of frontotemporal lobar degeneration in right temporal variant frontotemporal dementia with salient features of Geschwind syndrome

ABSTRACT Globular Glial Tauopathy (GGT) is a rare form of Frontotemporal Lobar Degeneration (FTLD) consisting of 4-repeat tau globular inclusions in astrocytes and oligodendrocytes. We present the pathological findings of GGT in a previously published case of a 73-year-old woman with behavioral symptoms concerning for right temporal variant frontotemporal dementia with initial and salient features of Geschwind syndrome. Clinically, she lacked motor abnormalities otherwise common in previously published GGT cases. Brain MRI showed focal right anterior temporal atrophy (indistinguishable from five FTLD-TDP cases) and subtle ipsilateral white matter signal abnormalities. Brain autopsy showed GGT type III and Alzheimer’s neuropathologic changes. .

Case Report: A Novel EIF2B3 Pathogenic Variant in Central Nervous System Hypomyelination/Vanishing White Matter

Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants in EIF2B3: the previously known pathogenic variant c c.260C>T (p.Ala87Val) and the novel variant c.673C>T (p.Arg225Trp). Based on the American College of Medical Genetics (ACMG) recommendations, we classified p.Arg225Trp as likely pathogenic. We report a novel variant in a patient with CACH/VWM and highlight the importance of genetic testing in patients with leukodystrophies.

Brain Imaging Abnormalities in Mixed Alzheimer's and Subcortical Vascular Dementia.

A large proportion of Alzheimer's disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity. To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD. We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures. Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD). These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Early MRI diagnosis of Sturge Weber Syndrome type 1 in infants

Patients with Sturge-Weber syndrome type 1 (SWS1) have a port-wine birthmark (PWB) as cutaneous hallmark. Up to 35% of neonates with a high risk PWB develop SWS1. Clinical manifestations are severe and often progressive. Especially early onset seizures are associated with worse neurocognitive outcome. Identification of pre-symptomatic SWS1 patients is hampered because brain MRI in the first months of life does not always show the for SWS1 characteristic leptomeningeal capillary malformation (LMC).Identification of sensitive and specific MRI predictors for early SWS1 diagnosis.In this retrospective single centre study, we included 24 SWS1 patients and 20 controls. We studied specificity and sensitivity for SWS1 diagnosis of LMC and indirect MRI signs such as choroid plexus (CP) size and thickness, abnormal white matter signal, lobar cerebral atrophy, ischemia and cortical calcifications.In SWS1 patients CP thickness and CP thickness ratio on non-contrast brain MRI was significantly increased. The optimal cut-off value of 5.6 mm on the affected side corresponded with a sensitivity of 91.7% and a specificity of 100% for confirmation of SWS1 diagnosis. In 21% of children aged ≤3 months with a later confirmed SWS1 diagnosis, LMC on initial MRI could not be discerned but CP thickness ≥5.6 mm on the affected side confirmed SWS1 diagnosis.In this study, CP size ratio and thickness were found to be sensitive and specific signs additional to earlier described criteria to support SWS1 diagnosis in neonates and infants which need to be confirmed in other series.

Neuroimaging Findings in Parechovirus Encephalitis: A Case Series of Pediatric Patients

BackgroundHuman parechovirus infection can cause parechovirus encephalitis in neonates and should be considered as a differential diagnosis in the emergency department. Neuroimaging features of parechovirus encephalitis have been described in neonates and young infants, but there is a paucity of literature regarding magnetic resonance imaging brain injury patterns in older children. We aim to present three cases of parechovirus encephalitis, showing distinctive magnetic resonance imaging brain patterns of injury in two newborns and, for the first time, in an adolescent. MethodsWe conducted a retrospective review of parechovirus encephalitis cases in our pediatric hospital. Clinical information and neuroimaging findings are described in detail. ResultsClassical neuroimaging findings in neonatal parechovirus encephalitis include restricted diffusion of the subcortical and periventricular white matter with frontoparietal predominance, in association with corpus callosum signal abnormality and bilateral swollen thalami. Parechovirus encephalitis in the adolescent appeared with an additional pattern of white matter signal abnormality in the corona radiata in continuity with the corticospinal tracts. ConclusionsParechovirus encephalitis should be considered in the differential diagnosis when magnetic resonance imagingdemonstrates white matter injury with typical (sunburst type) distribution in the deep and periventricular white matter in both neonates and adolescents, especially in those with comorbidities or therapy that lead to an immunosuppressive status.

The canonical pattern of Alzheimer's disease atrophy is linked to white matter hyperintensities in normal controls, differently in normal controls compared to in AD

White matter signal abnormalities (WMSA), either hypo- or hyperintensities in MRI imaging, are considered a proxy of cerebrovascular pathology and contribute to, and modulate, the clinical presentation of Alzheimer's disease (AD), with cognitive dysfunction being apparent at lower levels of amyloid and/or tau pathology when lesions are present. To what extent the topography of cortical thinning associated with AD may be explained by WMSA remains unclear. Cortical thickness group difference maps and subgroup analyses show that the effect of WMSA on cortical thickness in cognitively normal participants has a higher overlap with the canonical pattern of AD, compared to AD participants. (Age and sex-matched group of 119 NC (AV45 PET negative, CDR = 0) versus 119 participants with AD (AV45 PET-positive, CDR > 0.5). The canonical patterns of cortical atrophy thought to be specific to Alzheimer's disease are strongly linked to cerebrovascular pathology supporting a reinterpretation of the classical models of AD suggesting that a part of the typical AD pattern is due to co-localized cortical loss before the onset of AD.

Association of Plasma Oligomerized Amyloid-β and Cerebral White Matter Lesions in a Health Screening Population.

Cerebral white matter lesions (WML) are related to a higher risk of vascular and Alzheimer's dementia. Moreover, oligomerized amyloid-β (OAβ) can be measured from blood for dementia screening. We aimed to investigate the relationship of plasma OAβ levels with clinical and radiological variables in a health screening population. WML, other volumetric parameters of magnetic resonance images, cognitive assessment, and plasma OAβ level were evaluated. Ninety-two participants were analyzed. The majority of participants' clinical dementia rating was 0 or 0.5 (96.7%). White matter hyperintensities (WMH) increased with age, but OAβ levels did not (r2 = 0.19, p < 0.001, r2 = 0.03, p = 0.10, respectively). No volumetric data, including cortical thickness/hippocampal volume, showed any significant correlation with OAβ. Log-WMH volume was positively correlated with OAβ (r = 0.24, p = 0.02), and this association was significant in the periventricular area. White matter signal abnormalities from 3D-T1 images were also correlated with the OAβ in the periventricular area (p = 0.039). Multivariate linear regression showed that log-WMH values were independently associated with OAβ (B = 0.879 (95% confidence interval 0.098 -1.660, p = 0.028)). Higher tertiles of WMH showed higher OAβ levels than lower tertiles showed (p = 0.044). Using a cutoff of 0.78 ng/mL, the high OAβ group had a larger WMH volume, especially in the periventricular area, than the low OAβ group (p = 0.036). Both WML and plasma OAβ levels can be early markers for neurodegeneration in the healthcare population. The lesions, especially in the periventricular area, might be related to amyloid pathogenesis, which strengthens the importance of WML in the predementia stage.

Sepsis-Related Brain MRI Abnormalities Are Associated With Mortality and Poor Neurological Outcome in Pediatric Sepsis

BackgroundIt is not known whether brain magnetic resonance imaging (MRI) abnormalities in pediatric sepsis are associated with clinical outcomes. Study objectives were to (1) determine the prevalence and type of sepsis-related neuroimaging abnormalities evident on clinically indicated brain MRI in children with sepsis and (2) test the association of these abnormalities with mortality, new disability, length of stay (LOS), and MRI indication. MethodsRetrospective cohort study of 140 pediatric patients with sepsis and a clinically indicated brain MRI obtained within 60 days of sepsis onset at a single, large academic pediatric intensive care unit (PICU). Two radiologists systematically reviewed the first post-sepsis brain MRI and determined which abnormalities were sepsis-related. Outcomes compared in patients with versus without sepsis-related MRI abnormalities. ResultsPICU mortality was 7%. Thirty patients had one or more sepsis-related MRI abnormality, yielding a prevalence of 21% (95% confidence interval 15%, 28%). Among those, 53% (16 of 30) had sepsis-related white matter signal abnormalities; 53% (16 of 30) sepsis-related ischemia, infarction, or thrombosis; and 27% (eight of 30) sepsis-related posterior reversible encephalopathy. Patients with one or more sepsis-related MRI abnormality had increased mortality (17% vs 5%; P = 0.04), new neurological disability at PICU discharge (32% vs 11%; P = 0.03), and longer PICU LOS (median 18 vs 11 days; P = 0.04) compared with patients without. ConclusionsIn children with sepsis and a clinically indicated brain MRI, 21% had a sepsis-related MRI abnormality. Sepsis-related MRI abnormalities were associated with increased mortality, new neurological disability, and longer PICU LOS.

Cerebrovascular disease and depressive symptomatology in individuals with subjective cognitive decline: A community‐based study

AbstractBackgroundSubjective cognitive decline (SCD) may be the first sign of Alzheimer’s disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. In this study, we investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We hypothesized three different scenarios, where depressive symptomatology would co‐exist, contribute to, or be a consequence of SCD (Figure).MethodWe recruited 225 cognitively unimpaired individuals from a prospective community‐based study (mean age (SD) = 54.64 (10.18); age range 35 – 77 years; 55% women; 102 individuals without any subjective cognitive complaint, 123 individuals with one or more complaints). SCD was assessed with a scale of 9 memory and non‐memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. We used magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD) to assess cerebrovascular disease. We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD.ResultsWe found that SCD was associated with higher cerebrovascular disease (WMSA: r=0.210, p&lt;0.002; MD: r=0.216, p=0.001), older age (r=0.373, p&lt;0.001), and increased depressive symptomatology (r=0.340, p&lt;0.001). In turn, depressive symptomatology was not associated with cerebrovascular disease (WMSA: r=0.003, p&lt;0.961; MD: r=0.076, p&lt;0.321) or age (r=0.069, p&lt;0.030). We also studied whether abnormalities in white matter MD in SCD may be due to cerebrovascular disease. Results showed that variability in MD was mediated by WMSA burden (p=0.026), presumably reflecting cerebrovascular disease.ConclusionIn our community‐based cohort, depressive symptomatology co‐exists with SCD and reflects emotional factors, but does not reflect cerebrovascular disease. In addition, depressive symptomatology did not influence the capacity of SCD to predict underlying cerebrovascular disease. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD.

MRI correlates of neuropsychiatric symptom progression in pre‐dementia GRN and C9orf72 mutation carriers

AbstractBackgroundFrontotemporal dementia (FTD) patients with mutations in the C9orf72 or the GRN genes frequently exhibit neuropsychiatric symptoms (NPS), which may precede the onset of dementia. We hypothesized that the burden and progression of NPS in pre‐dementia mutation carriers are associated with structural abnormalities detectable in brain MRI.MethodWe analyzed data from 42 participants before onset of dementia (11 C9orf72+ mutation carriers, 8 GRN+ mutation carriers, and 23 non‐carrier family members (NCs); mean±SD age: 46y±11, 50y±9, and 53y±8 respectively) recruited through the University of British Columbia FTD Study. Participants were assessed longitudinally for NPS with Neuropsychiatric Inventory (NPI), Frontal Behavioural Inventory (FBI) and Iowa Scale of Personality Change (ISPC) (mean follow‐up: 8.4y). Participants also underwent 1.5T MRI at the first and third annual visits (mean interval: 28±8m). If a participant developed FTD during the follow‐up (N=2), we only analyzed observations collected before the conversion. We processed T1‐weighted MRI to calculate annualized volumetric changes in the grey‐matter, the white‐matter and the hypointense white‐matter signal‐abnormalities (WMSA), within the entire brain and lobar region‐of‐interests. We applied a random‐slope model to the NPI, FBI and ISPC scores to estimate subject‐specific slopes of their progression. Then, we applied a linear model to evaluate the association between the estimated slopes and the MRI measures, among the genetic groups. Covariates included sex, age, baseline assessment scores, baseline WMSA and total white‐matter volumes.ResultThere were non‐significant baseline group differences in the MRI or NPS measures. Overall, a higher rate of frontal lobar WMSA accumulation was associated with a higher rate of NPI score increase. However, GRN+ carriers had a faster progression of NPS compared to NCs, and the higher NPI slope was associated with a higher rate of frontal lobar white‐matter volume loss. The FBI and ISPC slopes were not significantly associated with the MRI measures.ConclusionPrior to the onset of FTD, the emergence of NPS in mutation carriers may be correlated with the degree of frontal lobar white‐matter lesions. In GRN+ carriers, the progression of NPS, as represented by NPI score increases, may also be associated with frontal white‐matter volume loss.