The Impact of Intracortical Lesions on Volumes of Subcortical Structures in Multiple Sclerosis

Abstract

BACKGROUND AND PURPOSE: Recent studies showed thalamic atrophy in the early stages of MS. We investigated the impact of intracortical lesions on the volumes of subcortical structures (especially the thalamus) compared with other lesions in MS. MATERIALS AND METHODS:Seventy-one patients with MS were included. The volumes of intracortical lesions and white matter lesions were identified on double inversion recovery and FLAIR, respectively, by using 3D Slicer. Volumes of white matter T1 hypointensities and subcortical gray matter, thalamus, caudate, putamen, and pallidum volumes were calculated using FreeSurfer. Age, MS duration, and the Expanded Disability Status Scale score were assessed. RESULTS:Patients with intracortical lesions were older (P ¼ .003), had longer disease duration (P , .001), and higher Expanded Disability Status Scale scores (P ¼ .02). The presence of intracortical lesions was associated with a significant decrease of subcortical gray matter volume (P ¼ .02). In our multiple regression model, intracortical lesion volume was the only predictor of thalamic volume (R 2 ¼ 0.4, b* ¼ -0.28, P ¼ .03) independent of white matter lesion volume and T1 hypointensity volume. White matter lesion volume showed an impact on subcortical gray matter volume in patients with relapsing-remitting MS (P ¼ .04) and those with disease duration of ,5 years (P ¼ .04) and on thalamic volume in patients with Expanded Disability Status Scale scores of ,4.0 (P ¼ .01). By contrast, intracortical lesion volume showed an impact on subcortical gray matter and thalamic volumes in the secondary-progressive MS subgroup (P ¼ .02 and P , .001) in patients with a long-standing disease course (P , .001 and P ¼ .001) and more profound disability (P , .001 and P , .001).CONCLUSIONS: Thalamic atrophy was explained better by intracortical lesions than by white matter lesion and T1 hypointensity volumes, especially in patients with more profound disability. ABBREVIATIONS: DIR ¼ double inversion recovery; EDSS ¼ Expanded Disability Status Scale; iCL ¼ intracortical lesion; ICV ¼ intracranial volume; PPMS ¼ primary-progressive MS; RRMS ¼ relapsing-remitting MS; SPMS ¼ secondary-progressive MS; T1H ¼ T1 hypointensities; WMH ¼ white matter hypointensities; WML ¼ white matter lesions; SGMS ¼ subcortical grey matter structures; b* ¼ standartized regression coefficients

Volume changes of thalamus, hippocampus and cerebellum are associated with specific CSF profile in MS

“…We completed our analysis investigating also other possible clinical and MRI variables associated to the volume loss of the thalamus, cerebellar cortex and hippocampus: in line with previous data, 35 we observed a relationship between the volume at T0 and volume change at T24 of these structures and both GM and WM lesion load and disease progression.…”

Predictors of multiple sclerosis progression: A systematic review of conventional magnetic resonance imaging studies

“…Abnormalities in the gray matter, whether deep or cortical, including atrophy or lesion in the cortex, can predict the progression of disability among patients with MS. Several studies have shown a strong correlation between cortical lesion and EDSS score [32][33][34][35][36][37][38] with cortical lesion volume being a predictor of neurologic disability progression during follow-up [35]. Gray matter atrophy has also been identified as a predictor of higher EDSS scores [34,39,40].…”

The Development of Subcortical Gray Matter Atrophy in Multiple Sclerosis: One Size Does Not Fit All

“…Indeed, if inflammation in the white matter, related to the formation of WMLs, is recognized as the major driving force for deep gray matter atrophy in early phases and a relapsing-remitting course, 7 less is known about the mechanisms sustaining the enduring subcortical volume loss in chronic disease stages and a progressive course, when neuroinflammation in the white matter becomes less pronounced, as well as its impact on subcortical atrophy and disease progression. 5 In this light, the correlation between cortical lesions and deep gray matter atrophy, reported by Kalinin et al, 6 may reflect a second-order disconnection effect via thalamocortical radiations and corticothalamic tracts, and/or it may represent an epiphenomenon related to the prominent primary involvement of gray matter (both cortical and subcortical, simultaneously), which is known to characterize chronic disease stages and progressive phenotypes. 1 Understanding the pathogenic processes underlying subcortical gray matter (primarily thalamic) atrophy in different phases of the disease would be critical in the determination of treatment strategies, potentially informing therapeutic choices with the aim of preventing the occurrence of thalamic damage and its detrimental consequences in terms of brain network economy and clinico-cognitive functioning.…”

“…4 However, despite its pathophysiologic and clinical relevance, what drives this typical pattern of neurodegeneration in MS remains partially unclear, probably including a combination of primary local neuroinflammatory and neurodegenerative pathologic processes and secondary effects from remote injury in other parts of the brain (mainly white matter) via anterograde/retrograde degeneration and/or spreading of inflammation along axonal pathways. 5 The study by Kalinin et al, 6 published in a recent issue of the American Journal of Neuroradiology, explores the impact of purely intracortical lesions compared with white matter lesions (WMLs) on the volumes of deep gray matter structures in a cohort of patients with relapsing-remitting MS (RRMS, n ¼ 54), secondary-progressive MS (SPMS, n ¼ 12), and primary-progressive MS (PPMS, n ¼ 5). They found that patients with intracortical lesions had longer disease duration, greater disability, and more deep gray matter atrophy.…”