Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis

Mahajan, Kedar R; Nakamura, Kunio; Cohen, Jeffrey A.; Trapp, Bruce D.; Ontaneda, Daniel

doi:10.1002/ana.25743

Cited by 40 publications

(57 citation statements)

References 36 publications

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“…These findings add to the growing evidence that the two imaging findings may reflect different aspects of MS‐related brain injury 20 . More recently, a postmortem histologic‐imaging study by Mahajan et al has shown that thalamic volume atrophy may be better explained by WM lesions and subsequent afferent and efferent axonal/neuronal loss than thalamic demyelinating lesions, 26 a finding which may further explain our result.…”

Section: Discussionsupporting

confidence: 57%

Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T

Park

Thongkham

Sadigh

et al. 2020

Journal of Neuroimaging

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BACKGROUND AND PURPOSE: The comparative detection rates of deep gray matter (GM) multiple sclerosis (MS) lesions using double inversion recovery (DIR) and fluid-attenuated inversion-recovery (FLAIR) on 3T MR imaging remain unknown. We aimed to assess the detectability of cortical and deep GM MS lesions using DIR and FLAIR on 3T clinical exams and evaluate the relationship between deep GM lesions and brain atrophy. METHODS: One hundred fifty consecutive MS patients underwent routine brain MRI that included 3D DIR and 2D T2 FLAIR on the same 3T scanner. Three neuroradiologists independently reviewed all exams for cortical and deep GM lesions. Statistical parametric mapping (SPM) and FMRIB software library (FSL)-FIRST pipelines were used to determine normalized whole brain and deep GM volumes. RESULTS: A total of 65 cortical and 98 deep lesions were detected on DIR versus 24 and 20, respectively, on FLAIR. Among all 150 patients, the number and percentage of patients with GM lesions on DIR and FLAIR were as follows: cortical 43 (28.7%) versus 24 (16.0%) (P < .001), thalamus 47 (31.3%) versus 20 (13.3%) (P < .001), putamen 10 (6.7%) versus 3 (2.0%) (P = .02), globus pallidus 9 (6.0%) versus 3 (1.3%) (P = .02), and caudate 5 (3.3%) versus 1 (0.7%) (P = .125). Presence of deep GM lesions weakly correlated with deep GM volume fractions. CONCLUSION: Deep GM MS lesions can be detected using routine clinical brain MRI including DIR and FLAIR at 3T. Future studies to optimize these sequences may improve the detection rates of cortical and deep GM lesions. The presence of GM lesions showed weak correlation with GM atrophy.

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Section: Discussionsupporting

confidence: 57%

Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T

Park

Thongkham

Sadigh

et al. 2020

Journal of Neuroimaging

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“…As non-lesioned brain volumes within six weeks after stroke are assumed to be similar to those before the stroke (Egorova et al, 2019), this finding suggests that larger thalamic volumes prior to stroke could provide a neuroprotective effect. Thalamic atrophy was recently associated with loss of extrinsic and intrinsic connectivity between the thalamus and the rest of the brain, suggesting that thalamic measures may serve as an index of global brain function (Mahajan et al, 2020). Future research using longitudinal datasets with greater spatial specificity could relate changes in specific thalamic nuclei to sensorimotor recovery to identify targets for neuroprotective or early stroke therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Thalamic atrophy was recently associated with loss of extrinsic and intrinsic connectivity between the thalamus and the rest of the brain, suggesting that thalamic measures may serve as an index of global brain function. 26 Future research using longitudinal datasets with greater spatial specificity could relate changes in specific thalamic nuclei to sensorimotor recovery to identify targets for neuroprotective or early stroke therapies.…”

Section: Discussionmentioning

confidence: 99%

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Liew¹,

Zavaliangos‐Petropulu²,

Schweighofer³

et al. 2020

Preprint

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Background: Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Subcortical regions play critical roles in the control and regulation of sensorimotor circuits. Identifying relationships between sensorimotor behavior and non-lesioned subcortical volumes will reveal new neural targets for improving outcomes. Methods: We pooled high-resolution T1-weighted MRI brain scans and behavioral data in 828 individuals with unilateral stroke from 28 cohorts worldwide (age: median 63, interquartile range 19 years; 516 males, 312 females). Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behavior to non-lesioned subcortical volumes. We analyzed subacute (≤90 days) and chronic (≥180 days) stroke; sub-analyses in chronic stroke were performed on class of sensorimotor deficit (impairment, activity limitations) and side of lesioned hemisphere, with exploratory analyses in early stroke (≤21 days) and across time (Bonferroni-corrected, p<0.004). Results: Worse sensorimotor behavior was associated with a smaller ipsilesional thalamic volume in both subacute (n=274, d=0.46) and early stroke (n=179; d=0.68). In chronic stroke (n=404), worse sensorimotor behavior was associated with smaller ipsilesional putamen (d=0.52) and nucleus accumbens (d=0.39) volumes, and a larger ipsilesional lateral ventricle volume (d=-0.42), representing atrophy. In chronic stroke, worse sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n=256) was associated with a smaller ipsilesional putamen (d=0.72), and larger lateral ventricle (d=-0.41), while several measures of activity limitations (n=116) showed no significant relationships. Side of lesion (left=214, right=190) had no impact. The full cohort (n=828) revealed associations of sensorimotor behavior with the ipsilesional nucleus accumbens (d=0.23), putamen (d=0.33), thalamus (d=0.33), and lateral ventricle (d=-0.23). Discussion: This analysis identified significant relationships between sensorimotor behavior and key subcortical regions at different times post-stroke. While further longitudinal studies are needed, these findings may represent brain imaging markers of resilience and reserve and provide putative neuroanatomical targets for improving sensorimotor outcomes post-stroke.

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“…Thalamic lesions occur in two main types, subependymal or perivascular, and are present in 42-97% of patients (33)(34)(35). Imaging investigation in the thalamus have focused mainly on volumetric assessment (e.g., T1-or T2-weighted images, ultrahigh field) and overall measures of thalamic integrity [e.g., susceptibility-weighted imaging (SWI), magnetization transfer ratio (MTR), magnetic resonance spectroscopy, diffusion tensor imaging (DTI)].…”

Section: Imaging Of the Thalamus In Multiple Sclerosismentioning

confidence: 99%

Thalamic Injury and Cognition in Multiple Sclerosis

Amin

Ontaneda

2021

Front. Neurol.

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Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.

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Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis

Cited by 40 publications

References 36 publications

Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T

Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Thalamic Injury and Cognition in Multiple Sclerosis

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