Superficial white matter damage in anti-NMDA receptor encephalitis

BackgroundClinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter.MethodsForty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity.ResultsNon-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients.ConclusionsAnti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.

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White matter network damage mediates association between cerebrovascular disease and cognition

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21990980 ◽

2021 ◽

pp. 0271678X2199098

Author(s):

Saima Hilal ◽

Siwei Liu ◽

Tien Yin Wong ◽

Henri Vrooman ◽

Ching-Yu Cheng ◽

...

Keyword(s):

White Matter ◽

Cerebrovascular Disease ◽

Verbal Memory ◽

Visual Memory ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Domain Specific ◽

Epidemiology Of Dementia ◽

Z Scores ◽

White Matter Connectivity

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

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Dysmature superficial white matter microstructure in developmental focal epilepsy

Brain Communications ◽

10.1093/braincomms/fcz002 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 3

Author(s):

Lauren M Ostrowski ◽

Daniel Y Song ◽

Emily L Thorn ◽

Erin E Ross ◽

Sally M Stoyell ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Fine Motor ◽

Epilepsy Syndrome ◽

Healthy Controls ◽

Deep White Matter ◽

White Matter Microstructure ◽

Benign Epilepsy

Abstract Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.

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Alternative Microstructural Measures to Complement Diffusion Tensor Imaging in Migraine Studies with Standard MRI Acquisition

Brain Sciences ◽

10.3390/brainsci10100711 ◽

2020 ◽

Vol 10 (10) ◽

pp. 711

Author(s):

Álvaro Planchuelo-Gómez ◽

David García-Azorín ◽

Ángel L. Guerrero ◽

Rodrigo de Luis-García ◽

Margarita Rodríguez ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Chronic Migraine ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Episodic Migraine ◽

Healthy Controls ◽

Axial Diffusivity ◽

Average Diffusion ◽

Cerebellar Peduncle

The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine (p < 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions (p < 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine.

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Nicotine Effects on White Matter Microstructure in Young Adults

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acy101 ◽

2019 ◽

Vol 35 (1) ◽

pp. 10-21 ◽

Cited By ~ 2

Author(s):

Megan M Kangiser ◽

Alicia M Thomas ◽

Christine M Kaiver ◽

Krista M Lisdahl

Keyword(s):

Working Memory ◽

Young Adults ◽

White Matter ◽

Fractional Anisotropy ◽

Sustained Attention ◽

Verbal Memory ◽

Diffusion Tensor ◽

Memory Performance ◽

Mean Diffusivity ◽

White Matter Microstructure

Abstract Objective Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. Methods Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18–25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. Results Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus—temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. Conclusions Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

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Mapping white matter damage distribution in neuromyelitis optica spectrum disorders with a multimodal MRI approach

Multiple Sclerosis Journal ◽

10.1177/1352458520941493 ◽

2020 ◽

pp. 135245852094149

Author(s):

Laura Cacciaguerra ◽

Maria A Rocca ◽

Loredana Storelli ◽

Marta Radaelli ◽

Massimo Filippi

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Fractional Anisotropy ◽

Neuromyelitis Optica ◽

Mean Diffusivity ◽

Healthy Controls ◽

Neuromyelitis Optica Spectrum Disorders ◽

White Matter Damage ◽

Axial Diffusivity ◽

Spectrum Disorders

Background: The pathogenetic mechanisms sustaining neuroinflammatory disorders may originate from the cerebrospinal fluid. Objective: To evaluate white matter damage with diffusion tensor imaging and T1/T2-weighted ratio at progressive distances from the ventricular system in neuromyelitis optica spectrum disorders and multiple sclerosis. Methods: Fractional anisotropy, mean, axial, and radial diffusivity and T1/T2-weighted ratio maps were obtained from patients with seropositive neuromyelitis optica spectrum disorders, multiple sclerosis, and healthy controls ( n = 20 each group). White matter damage was assessed as function of ventricular distance within progressive concentric bands. Results: Compared to healthy controls, neuromyelitis optica spectrum disorders patients had similar fractional anisotropy, radial and axial diffusivity, increased mean diffusivity ( p = 0.009–0.013) and reduced T1/T2-weighted ratio ( p = 0.024–0.037) in all bands. In multiple sclerosis, gradient of percentage lesion volume and intra-lesional mean and axial diffusivity were higher in periventricular bands. Compared to healthy controls, multiple sclerosis patients had reduced fractional anisotropy ( p = 0.001–0.043) in periventricular bands, increased mean ( p < 0.001), radial ( p < 0.001–0.004), and axial diffusivity ( p = 0.002–0.008) and preserved T1/T2-weighted ratio in all bands. Conclusion: White matter damage is higher at periventricular level in multiple sclerosis and diffuse in neuromyelitis optica spectrum disorders. Fractional anisotropy preservation, associated with increased mean diffusivity and reduced T1/T2-weighted ratio may reflect astrocyte damage.

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18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy

10.1101/19000596 ◽

2019 ◽

Author(s):

Nicolas Nicastro ◽

Patricia Vazquez Rodriguez ◽

Maura Malpetti ◽

William Richard Bevan-Jones ◽

P. Simon Jones ◽

...

Keyword(s):

White Matter ◽

Progressive Supranuclear Palsy ◽

Pet Imaging ◽

Diffusion Tensor ◽

Brain Mri ◽

Mean Diffusivity ◽

White Matter Integrity ◽

Tau Pathology ◽

Cross Sectional ◽

White Matter Changes

ABSTRACTIntroductionProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.ResultsWidespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.

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Age-Related Variations in Regional White Matter Volumetry and Microstructure During the Post-adolescence Period: A Cross-Sectional Study of a Cohort of 1,713 University Students

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2021.692152 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ami Tsuchida ◽

Alexandre Laurent ◽

Fabrice Crivello ◽

Laurent Petit ◽

Antonietta Pepe ◽

...

Keyword(s):

White Matter ◽

University Students ◽

Diffusion Tensor ◽

Brain Mri ◽

Mean Diffusivity ◽

High Angular Resolution ◽

White Matter Volume ◽

Matter Volume ◽

Brain White Matter ◽

Age Related

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

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Abstract P64: Longitudinal Brain Structural Changes After Stroke

Stroke ◽

10.1161/str.52.suppl_1.p64 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Kyle C Kern ◽

Clinton B Wright ◽

Richard Leigh

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Stroke Volume ◽

Brain Atrophy ◽

Structural Changes ◽

Diffusion Tensor ◽

Brain Mri ◽

Mean Diffusivity ◽

Intracranial Volume ◽

Post Stroke

Background: Stroke causes focal and diffuse structural brain changes that may contribute to subsequent cognitive decline and dementia. We hypothesize that MRI structural measures can detect continued cerebral degeneration over the first year after stroke. We identify predictors for progression of brain atrophy, leukoaraiosis and diffusion tensor imaging (DTI) metrics. Methods: Patients with ischemic stroke were enrolled prospectively in an observational study that included serial brain MRI. Patients underwent MRI FLAIR and DTI at the time of acute stroke and were followed for at least 9 months with multiple MRIs between 30 days and 15 months post-stroke. We used FLAIR to measure brain atrophy as the percent brain parenchymal fraction (BPF) of the total intracranial volume (TICV) and white matter hyperintensity volume (WMHV) as a percentage of TICV. DTI was used to calculate Peak Skeletonized Mean Diffusivity (PSMD), a global measure of white matter integrity previously validated in cerebral small vessel disease. Longitudinal changes in BPF, WMHV or PSMD were measured from 30 days post-stroke onward using linear regression models that included age, stroke volume, baseline BPF and WMHV as predictors. Results: Twenty-six patients had a median of 4 follow-ups over 9-15 months. Median age was 74 years (range 51-84) and 38% were women. Mean stroke volume was 4.5cc (0 - 30cc). Mean BPF was 78% (72 - 86%) and mean baseline WMHV was 1.1% (0.1 - 3.9%). BPF was associated with age and declined by 0.7% per year (t(111) = 2.7, p = 0.007). Progression was associated with baseline BPF (t(111) = -3.4, p < 0.001). WMHV in the non-stroke hemisphere was associated with age and increased by 0.10% per year (t(87) = -5.8, p < 0.001). Accumulation was associated with age (t(87) = 5.8, p < 0.001). PSMD was associated with baseline WMHV and had a relative increase of 1.9% per year in the non-stroke hemisphere and 4.5% in the stroke hemisphere (t(174) = -2.1, p = 0.03). Progression was associated with age (t(174) = 2.3, p = 0.03) and stroke volume (t(174) = 2.4, p = 0.02). Conclusions: During the months after ischemic stroke, BPF, WMHV and PSMD can detect persistent structural changes that may reflect later phases of stroke injury or ongoing contributions of aging, silent ischemia, or neurodegeneration.

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Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function

The Neuroradiology Journal ◽

10.1177/1971400916682753 ◽

2017 ◽

Vol 31 (1) ◽

pp. 83-89 ◽

Cited By ~ 7

Author(s):

Maria M D’Souza ◽

SP Gorthi ◽

Kunal Vadwala ◽

Richa Trivedi ◽

C Vijayakumar ◽

...

Keyword(s):

Cognitive Function ◽

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Surrogate Marker ◽

Mean Diffusivity ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Damage ◽

Vessel Disease

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

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Axonal loss of white matter in migraine without aura: A tract-based spatial statistics study

Cephalalgia ◽

10.1177/0333102412466964 ◽

2012 ◽

Vol 33 (1) ◽

pp. 34-42 ◽

Cited By ~ 48

Author(s):

Dahua Yu ◽

Kai Yuan ◽

Wei Qin ◽

Ling Zhao ◽

Minghao Dong ◽

...

Keyword(s):

White Matter ◽

Spatial Statistics ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Internal Capsule ◽

Brain Regions ◽

Axonal Loss ◽

Healthy Controls ◽

Posterior Limb ◽

Tract Based Spatial Statistics

Aim Multiple diffusion tensor imaging (DTI) derived indices may help to deduce the pathophysiological type of white matter (WM) changes and provide more specific biomarkers of WM neuropathology in the whole brain of migraine patients without aura (MWoA). Methods Twenty MWoA and 20 age-, education- and gender-matched healthy volunteers participated in this study. Tract-based spatial statistics (TBSS) was employed to investigate the WM abnormalities in MWoA by integrating multiple indices, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Results Compared with healthy controls, MWoA showed significantly lower FA, MD and AD in multiple brain regions, whereas no difference in RD was observed. Specifically, the overlap among the lower FA, MD, and AD was found in the genu, body, and splenium part of the corpus callosum (CC), the right anterior limb of the internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC) in MWoA compared with healthy controls. Additionally, some of the above WM findings were significantly correlated with duration and headache frequency in MWoA. Conclusion Given that decreased AD may suggest axonal loss, our findings may reveal axonal loss in MWoA.

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