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.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Purchase Online Access to this article for 24 hours
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).
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.
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.
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.
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.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Neurology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 1
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
The Rational Clinical Examination
Evidence Summary and Review 2
The Rational Clinical Examination
Other Radiological Modes Including MRI. A comprehensive review of all radiological modes...
All results at
and access these and other features:
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.