Gray Matter Matters: A Longitudinal Magnetic Resonance Voxel-Based Morphometry Study of Primary Progressive Multiple Sclerosis

Rothstein, Ted L.

doi:10.3389/fneur.2020.581537

Cited by 11 publications

(5 citation statements)

References 85 publications

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“…Therefore, we have combined the PPMS and SPMS patients into one group. Cortical atrophy proceeds 1.8 times faster in progressive forms of MS compared to RRMS (Eijlers et al, 2018), with losses occurring mainly in cortical GM and the hippocampus (Rothstein, 2020). In our cohort, the average grey matter loss over and above the average value in the controls was 0.26%/year of disease duration for RRMS and 0.38%/ year of disease duration for progressive forms.…”

Section: The Effect Of Disease Typementioning

confidence: 47%

Possible Markers of Venous Sinus Pressure Elevation in Multiple Sclerosis: Correlations with Gender and Disease Progression

Bateman

Lechner‐Scott

Carey

et al. 2021

Multiple Sclerosis and Related Disorders

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Background: In a previous study, multiple sclerosis (MS) was found to be associated with an increase in intracranial arterial pulsation volume and a reduction in venous sinus compliance, affecting pulsation dampening. There was a suggestion that the reduction in compliance of the sagittal sinus in MS was caused by an increase in venous pressure, secondary to transverse sinus stenosis. Some differences were noted depending on the gender of the patients, however, the original study was relatively underpowered for further sub-classification. The purpose of the current study is to enroll a larger number of patients to allow sub-classification on gender and disease type to further evaluate the markers of possible venous pressure alteration. Methods: 103 patients with MS were prospectively recruited from an MS clinic and compared to 50 matched non-MS patients. Using 3DT1 post contrast images, the sagittal sinus cross-sectional area was measured. The narrowest portion of the transverse sinuses was located and the cross sectional areas and wetted circumferences were measured to calculate the minimum hydraulic and effective diameters. The jugular bulb heights were measured. Voxel wise brain morphometry was performed to evaluate atrophy. Statistical analysis was performed using non-parametric methods and was assessed using α≤0.05.Results: Compared to controls, the MS patients' sagittal sinuses were 23% larger in cross-section (p<0.0001), the transverse sinuses had an average effective stenosis of 39% by area (p<0.0001) and there was a 62% increase in jugular bulb height (p=0.0001). The MS patients showed a reduction in normalized grey matter volume of 2.8% (p= 0.0001). Males with MS showed worse outcomes compared to females, with an increased EDSS and grey matter loss and had a 23% larger sagittal sinus area (p=0.02), 22% higher jugular bulb height (p=0.03) but a lower transverse sinus stenosis percentage (19% vs 48%, p<0.0001). Progressive forms of MS also had worse outcomes and had a 19% larger sagittal sinus area (p=0.04) compared to relapsing remitting MS. Conclusion:In this larger cohort, worse outcomes in both males and progressive forms of MS were associated with larger sagittal sinuses. The possible cause of the altered sinus pressure in females was narrower transverse sinuses. In males, higher jugular bulbs may be associated with increased venous sinus pressure.

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Section: The Effect Of Disease Typementioning

confidence: 47%

Possible Markers of Venous Sinus Pressure Elevation in Multiple Sclerosis: Correlations with Gender and Disease Progression

Bateman

Lechner‐Scott

Carey

et al. 2021

Multiple Sclerosis and Related Disorders

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“…(3) Other influences, including environmental (72), economic (73), lifestyle (74), and genetic predisposition factors, may play independent or combined roles in the WM abnormalities seen in MS. Further research on larger populations is needed and should include genetic data analyses. (4) Gray matter structures, including the cerebral cortex and various deep nuclei, are known to affect MS (67). Our analyses are limited to the WM but can extend to evaluate neurite morphology and potential changes in the GM and include more extensions of the NODDI model to explain anisotropy of the orientation dispersion.…”

Section: Discussionmentioning

confidence: 99%

“…While familial MS was associated with more severe T1-lesion volume, there were no clinical status differences between family and sporadic MS patients (66). Whereas, genetic factors can make familial MS patients more inclined to develop the disease than sporadic patients, other factors such as the environmental influence and the subjective (genetic) differences in response to injury seem to be critical for developing a diffuse and perhaps clinically significant development-relevant pathology in MS. Biologic confounders could influence the analysis of GM volumes, including the introduction of disease-modifying therapies, physiologic factors, normal aging, comorbidities, and daily fluctuations in brain volumes (67). The sample size is small and requires validation by encompassing more significant numbers of patients.…”

Section: Figure 4 | (A)mentioning

confidence: 99%

Widespread Disruptions of White Matter in Familial Multiple Sclerosis: DTI and NODDI Study

et al. 2021

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Diffusion tensor imaging (DTI) is a noninvasive, quantitative MRI technique that measures white matter (WM) integrity. Many brain dimensions are heritable, including white matter integrity measured with DTI. Family studies are valuable to provide insights into the interactive effects of non-environmental factors on multiple sclerosis (MS). To examine the contribution of familial factors to the diffusion signals across WM microstructure, we performed DTI and calculated neurite orientation dispersion plus density imaging (NODDI) diffusion parameters in two patient groups comprising familial and sporadic forms of multiple sclerosis and their unaffected relatives. We divided 111 subjects (49 men and 62 women: age range 19–60) into three groups conforming to their MS history. The familial MS group included 30 participants (patients; n = 16, healthy relatives; n = 14). The sporadic group included 41 participants (patients; n = 10, healthy relatives; n = 31). Forty age-matched subjects with no history of MS in their families were defined as the control group. To study white matter integrity, two methods were employed: one for calculating the mean of DTI, FA, and MD parameters on 18 tracts using Tracts Constrained by Underlying Anatomy (TRACULA) and the other for whole brain voxel-based analysis using tract-based spatial statistics (TBSS) on NDI and ODI parameters derived from NODDI and DTI parameters. Voxel-based analysis showed considerable changes in FA, MD, NDI, and ODI in the familial group when compared with the control group, reflecting widespread impairment of white matter in this group. The analysis of 18 tracts with TRACULA revealed increased MD and FA reduction in more tracts (left and right ILF, UNC, and SLFT, forceps major and minor) in familial MS patients vs. the control group. There were no significant differences between the patient groups. We found no consequential changes in healthy relatives of both patient groups in voxel-based and tract analyses. Considering the multifactorial etiology of MS, familial studies are of great importance to clarify the effects of certain predisposing factors on demyelinating brain pathology.

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“…Calculations of total brain and forebrain volumes, and derived percentiles of intracranial volumes of CGM, hippocampus and thalamus for each sample is based upon a NeuroQuant® normative database, which is not made available to its users. Additional details of NeuroQuant® methodology have previously been described elsewhere [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

Rothstein

2023

BMC Neurol

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Objective COVID-19 (SARS-CoV-2) has been associated with neurological sequelae even in those patients with mild respiratory symptoms. Patients experiencing cognitive symptoms such as “brain fog” and other neurologic sequelae for 8 or more weeks define “long haulers”. There is limited information regarding damage to grey matter (GM) structures occurring in COVID-19 “long haulers”. Advanced imaging techniques can quantify brain volume depletions related to COVID-19 infection which is important as conventional Brain MRI often fails to identify disease correlates. 3-dimensional voxel-based morphometry (3D VBM) analyzes, segments and quantifies key brain volumes allowing comparisons between COVID-19 “long haulers” and normative data drawn from healthy controls, with values based on percentages of intracranial volume. Methods This is a retrospective single center study which analyzed 24 consecutive COVID-19 infected patients with long term neurologic symptoms. Each patient underwent Brain MRI with 3D VBM at median time of 85 days following laboratory confirmation. All patients had relatively mild respiratory symptoms not requiring oxygen supplementation, hospitalization, or assisted ventilation. 3D VBM was obtained for whole brain and forebrain parenchyma, cortical grey matter (CGM), hippocampus, and thalamus. Results The results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient’s quality of life and productivity. Conclusion This study contributes to understanding effects of COVID-19 infection on patient’s neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.

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Gray Matter Matters: A Longitudinal Magnetic Resonance Voxel-Based Morphometry Study of Primary Progressive Multiple Sclerosis

Cited by 11 publications

References 85 publications

Possible Markers of Venous Sinus Pressure Elevation in Multiple Sclerosis: Correlations with Gender and Disease Progression

Possible Markers of Venous Sinus Pressure Elevation in Multiple Sclerosis: Correlations with Gender and Disease Progression

Widespread Disruptions of White Matter in Familial Multiple Sclerosis: DTI and NODDI Study

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

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