What drives MRI-measured cortical atrophy in multiple sclerosis?

Popescu, Veronica Adriana; Klaver, Roel; Voorn, Pieter; Graaf, Yvon Galis-de; Knol, Dirk L.; Twisk, Jos W. R.; Versteeg, Adriaan; Schenk, Geert J.; Valk, Paul van der; Barkhof, Frederik; Vries, Helga E. de; Vrenken, Hugo; Geurts, Jeroen J. G.

doi:10.1177/1352458514562440

Cited by 97 publications

(81 citation statements)

References 33 publications

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“…The detailed methodology has been described recently 31, 32. Only autopsies with very short postmortem delay (≤7 hours) were included.…”

Section: Methodsmentioning

confidence: 99%

“…Hence, only normal‐appearing GM was sampled as part of the standardized autopsy procedure. In the normal‐appearing cortical GM, myelin, axons, and dendrites were measured in relative optical density units 32. We also determined the average cortical thickness per tissue block 31.…”

Section: Methodsmentioning

confidence: 99%

“…GEEs also work with unbalanced designs, that is, when missing data occur at random. Accordingly, it has already proved useful in a similar context, namely for the analysis of the histopathological substrate of cortical atrophy in MS 32. One GEE analysis was run per histopathological measurement as explanatory variable.…”

Section: Methodsmentioning

confidence: 99%

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Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

Righart

Biberacher

Jonkman

et al. 2017

Annals of Neurology

108

119

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ObjectiveIn multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown.MethodsUsing a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors.ResultsPatients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin.InterpretationThe T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529

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“…The detailed methodology has been described recently 31, 32. Only autopsies with very short postmortem delay (≤7 hours) were included.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

Righart

Biberacher

Jonkman

et al. 2017

Annals of Neurology

108

119

View full text Add to dashboard Cite

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“…MRI-based atrophy measures have been assumed to reflect a neurodegenerative process. This assumption was recently confirmed using combined post-mortem whole-brain in situ MRI imaging and histopathology in brain donors with chronic MS (Popescu et al, 2015). Neuronal and axonal pathology were identified as the predominant substrates of MRI-measured cortical volume.…”

Section: Neuroimagingmentioning

confidence: 73%

Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward

Benedict

DeLuca

Enzinger

et al. 2017

J Int Neuropsychol Soc

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The neuropsychological aspects of multiple sclerosis (MS) have evolved over the past three decades. What was once thought to be a rare occurrence, cognitive dysfunction is now viewed as one of the most disabling symptoms of the disease, with devastating effects on patients' quality of life. This selective review will highlight major innovations and scientific discoveries in the areas of neuropathology, neuroimaging, diagnosis, and treatment that pertain to our understanding of the neuropsychological aspects of MS. Specifically, we focus on the recent discovery that MS produces pathogical lesions of gray matter (GM) that have consequences for cognitive functions. Methods for imaging these GM lesions in MS are discussed along with multimodal imaging studies that integrate structural and functional imaging methods to provide a better understanding of the relationship between cognitive test performance and functional reserve. Innovations in the screening and comprehensive assessment of cognitive disorders are presented along with recent research that examines cognitive dysfunction in pediatric MS. Results of innovative outcome studies in cognitive rehabilitation are discussed. Finally, we highlight trends for potential future innovations over the next decade. (JINS, 2017, 23, 832-842)

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“…Reports on the spatial distribution of cortical GM atrophy are much sparse, but in the past years several studies consistently showed that especially the temporal lobe, precentral cortical areas, and medial parietal lobe are involved [35]. Although the pathophysiological background of brain atrophy in the context of MS pathology is complex and not completely understood, several hypotheses have been postulated [18]: they include primary damage of the GM [36], but also secondary damage due to axonal transection by lesions [37]. Multiple MRI studies consistently reported associations between whole-brain GM loss and increases of lesion load; however, recent reports suggest that the association between GM atrophy and WM pathology may be different depending on anatomical region and disease course [38,39].…”

Section: Measuring Remyelination and Neuronal Repairmentioning

confidence: 99%