Search

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Occupational exposure to hypobaria (low atmospheric pressure) is a risk factor for reduced white matter integrity, increased white matter hyperintensive burden, and decline in cognitive function. We tested the hypothesis that a discrete hypobaric exposure will have a transient impact on cerebral physiology. Cerebral blood flow, fractional anisotropy of water diffusion in cerebral white matter, white matter hyperintensity volume, and concentrations of neurochemicals were measured at baseline and 24 hr and 72 hr postexposure in N = 64 healthy aircrew undergoing standard US Air Force altitude chamber training and compared to N = 60 controls not exposed to hypobaria. We observed that hypobaric exposure led to a significant rise in white matter cerebral blood flow (CBF) 24 hr postexposure that remained elevated, albeit not significantly, at 72 hr. No significant changes were observed in structural measurements or gray matter CBF. Subjects with higher baseline concentrations of neurochemicals associated with neuroprotection and maintenance of normal white matter physiology (glutathione, N-acetylaspartate, glutamate/glutamine) showed proportionally less white matter CBF changes. Our findings suggest that discrete hypobaric exposure may provide a model to study white matter injury associated with occupational hypobaric exposure., (© 2019 Wiley Periodicals, Inc.)

Introduction: Quantitative longitudinal magnetic resonance imaging and spectroscopy (MRI/S) is used to assess progress of brain disorders and treatment effects. Understanding the significance of MRI/S changes requires knowledge of the inherent technical and physiological consistency of these measurements. This longitudinal study examined the variance and reproducibility of commonly used quantitative MRI/S measurements in healthy subjects while controlling physiological and technical parameters., Methods: Twenty-five subjects were imaged three times over 5 days on a Siemens 3T Verio scanner equipped with a 32-channel phase array coil. Structural (T1, T2-weighted, and diffusion-weighted imaging) and physiological (pseudocontinuous arterial spin labeling, proton magnetic resonance spectroscopy) data were collected. Consistency of repeated images was evaluated with mean relative difference, mean coefficient of variation, and intraclass correlation (ICC). Finally, a "reproducibility rating" was calculated based on the number of subjects needed for a 3% and 10% difference., Results: Structural measurements generally demonstrated excellent reproducibility (ICCs 0.872-0.998) with a few exceptions. Moderate-to-low reproducibility was observed for fractional anisotropy measurements in fornix and corticospinal tracts, for cortical gray matter thickness in the entorhinal, insula, and medial orbitofrontal regions, and for the count of the periependymal hyperintensive white matter regions. The reproducibility of physiological measurements ranged from excellent for most of the magnetic resonance spectroscopy measurements to moderate for permeability-diffusivity coefficients in cingulate gray matter to low for regional blood flow in gray and white matter., Discussion: This study demonstrates a high degree of longitudinal consistency across structural and physiological measurements in healthy subjects, defining the inherent variability in these commonly used sequences. Additionally, this study identifies those areas where caution should be exercised in interpretation. Understanding this variability can serve as the basis for interpretation of MRI/S data in the assessment of neurological disorders and treatment effects.

Background: Repetitive hypobaric exposure in humans induces subcortical white matter change, observable on magnetic resonance imaging (MRI) and associated with cognitive impairment. Similar findings occur in traumatic brain injury (TBI). We are developing a swine MRI-driven model to understand the pathophysiology and to develop treatment interventions., Methods: Five miniature pigs (Sus scrofa domestica) were repetitively exposed to nonhypoxic hypobaria (30,000 feet/FIO 2 100%/transcutaneous PO 2 >90%) while under general anesthesia. Three pigs served as controls. Pre-exposure and postexposure MRIs were obtained that included structural sequences, dynamic contrast perfusion, and diffusion tensor quantification. Statistical comparison of individual subject and group change was performed utilizing a two-tailed t test., Findings: No structural imaging change was noted on T2-weighted or three-dimensional fluid-attenuated inversion recovery imaging between MRI 1 and MRI 2. No absolute difference in dynamic contrast perfusion was observed. A trend (p = 0.084) toward increase in interstitial extra-axonal fluid was noted. When individual subjects were examined, this trend toward increased extra-axonal fluid paralleled a decrease in contrast perfusion rate., Discussion/impact/recommendations: This study demonstrates high reproducibility of quantitative noninvasive MRI, suggesting MRI is an appropriate assessment tool for TBI and hypobaric-induced injury research in swine. The lack of fluid-attenuated inversion recovery change may be multifactorial and requires further investigation. A trend toward increased extra-axonal water content that negatively correlates with dynamic contrast perfusion implies generalized axonal injury was induced. This study suggests this is a potential model for hypobaric-induced injury as well as potentially other axonal injuries such as TBI in which similar subcortical white matter change occurs. Further development of this model is necessary., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Introduction: Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability., Methods: There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values., Results: Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots., Discussion: Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.McGuire SA, Boone GRE, Sherman PM, Tate DF, Wood JD, Patel B, Eskandar G, Wijtenburg SA, Rowland LM, Clarke GD, Grogan PM, Sladky JH, Kochunov PV. White matter integrity in high-altitude pilots exposed to hypobaria. Aerosp Med Hum Perform. 2016; 87(12):983-988.

Objective: Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI)., Methods: Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas-based stereotactic frame., Results: Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p < 0.001/count p < 0.001) when compared to DOC, whereas PHY were not significantly different than U2P., Interpretation: This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. Ann Neurol 2014;76:719-726., (© 2014 American Neurological Association.)