Neurological Review |

Imaging Cortical Damage and Dysfunction in Multiple Sclerosis

Massimo Filippi, MD; Maria A. Rocca, MD; Mark A. Horsfield, PhD; Simon Hametner, MD; Jeroen J. G. Geurts, PhD; Giancarlo Comi, MD; Hans Lassmann, MD
JAMA Neurol. 2013;70(5):556-564. doi:10.1001/jamaneurol.2013.1954.
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In line with pathological investigations, in vivo magnetic resonance imaging has consistently shown both focal and diffuse damage in the cerebral cortex of patients with multiple sclerosis. Cortical injury tends to progress over time and is only partially related to white matter abnormalities. This review summarizes the main findings from studies using both conventional and modern quantitative magnetic resonance–based techniques for the assessment of cortical damage and dysfunction in patients with multiple sclerosis.

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Figure 1. Pathological findings in an acute multiple sclerosis case with severe cortical involvement. A, Proteolipid protein immunohistochemical (IHC) staining shows macrophages in the cortex containing myelin degradation products (arrows), indicating active demyelination. B, Immunohistochemical staining for 2′3′-cyclic-nucleotide 3′-phosphodiesterase shows macrophages containing early myelin degradation products (arrows), indicating early active demyelination. C, CD3 IHC staining reveals cortical parenchymal infiltration of T lymphocytes (arrows). D, Glial fibrillary acidic protein IHC staining shows severe cortical protoplasmic astrogliosis with reactive astrocytes (arrows). Scale bars represent 100 μm or 25 μm (insets).

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Figure 2. Comparison of cortical lesion detection and classification using 3- and 7-T magnetic resonance imaging. A and B, Three-Tesla T1-weighted magnetization-prepared rapid acquisition with gradient echo (A) and double inversion recovery (B) sequences disclosed a juxtacortical lesion (arrow). C, Seven-Tesla fast low-angle shot–T2*-weighed imaging categorized the lesion as type 1 (arrow). Adapted from Nielsen et al20 with permission.

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Figure 3. Cortical lesions in multiple sclerosis using double inversion recovery sequences. A and B, Increased cortical multiple sclerosis lesion visibility on double inversion recovery short echo time (A) and long echo time (B) T2-weighted magnetic resonance images. C, Multislab 3-dimensional fluid-attenuated inversion recovery image. D, Multislab 3-dimensional double inversion recovery image showing a cortical lesion (arrow) that is not visible on the other, more conventional, magnetic resonance sequences. White matter lesions around the ventricles are visible on all sequences. Adapted from Geurts et al17 with permission.

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Figure 4. Distribution of regions of significant cortical and subcortical atrophy (P < .05, familywise error corrected) (blue) and T2 visible lesions (red) in patients with multiple sclerosis (MS) with cognitive impairment vs cognitive preservation according to the clinical phenotype. A, Relapsing remitting MS. B, Secondary progressive MS. C, Primary progressive MS. Orange circles identify regions with a correspondence between the presence of T2 visible lesions and cortical atrophy. The comparison between patients with cognitive impairment vs cognitive preservation in the 3 clinical phenotypes, analyzed separately, shows several areas with significant tissue loss in the former groups. Differences between patients with cognitive impairment vs cognitive preservation are more prominent when considering patients with secondary progressive MS. The analysis of regional distribution of T2 visible lesions shows that while in patients with relapsing-remitting MS and secondary progressive MS there is a correspondence between location of focal white matter lesions and cortical atrophy, in primary progressive MS such an association is not found. Images are oriented in neurological convention. From Riccitelli et al66 with permission.

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Figure 5. Areas showing increased activation in patients with primary progressive multiple sclerosis with cognitive preservation in comparison with those with cognitive impairment (A-C) and vice versa (D-G) during the analysis of the 2-back task (random effect analysis, analysis of variance, P < .05, corrected for multiple comparisons). Compared with patients with cognitive impairment, patients with cognitive preservation have more significant activations of the head of the left caudate nucleus, left prefrontal cortex, and left inferior parietal lobule. Conversely, compared with patients with cognitive preservation, those with cognitive impairment have more significant activations of the bilateral secondary sensorimotor cortex, bilateral cerebellum, and right insula. The color-encoded activations have been superimposed on a rendered brain and normalized into the standard Montreal Neurological Institute space (neurological convention). From Rocca et al74 with permission.




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