Neurology

Multiple Sclerosis

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Detection and Monitoring of Multiple Sclerosis: Past, Present, and Future

patient care perspectives by Eric C. Klawiter, MD, MSc

Overview

Consistent progress has been made in the identification of pharmacogenomic markers of disease-modifying therapy response in multiple sclerosis (MS), but predicting patient response to disease-modifying therapy in advance remains a major clinical challenge. Drug efficacy monitoring may allow for the early identification of nonresponsive patients and the optimization of treatment formulation, dosage, and schedule of administration in individual patients.

Expert Commentary

Eric C. Klawiter, MD, MSc

Associate Neurologist
Massachusetts General Hospital
Associate Professor of Neurology
Harvard Medical School
Boston, MA

“A novel imaging biomarker that has the potential to be incorporated into the diagnostic criteria for MS to improve specificity is the central vein sign.”

Eric C. Klawiter, MD, MSc

MS is considered both a clinical and radiologic diagnosis, meaning that both clinical and radiologic features of MS are required to make the diagnosis. However, even with our current diagnostic criteria, some patients are misdiagnosed in the clinic, which shows that there is room for improvement in our ability to correctly diagnose MS.

It is clear that magnetic resonance imaging (MRI) is the most sensitive tool for detecting the pathology of MS, both for diagnostic purposes and for monitoring treatment response. From a diagnostic perspective, a novel imaging biomarker that has the potential to be incorporated into the diagnostic criteria for MS to improve specificity is the central vein sign. In the classic periventricular lesion of MS, a high percentage of these lesions will have a vein that runs through the center of the lesion. The finding is not readily apparent unless you acquire a specialized MRI sequence that is sensitive at detecting veins. In cases of nonspecific white matter changes that occur in diseases other than MS, there is a much lower percentage of lesions with this central vein sign. There is still work to do related to validating this particular biomarker, but the potential is there to improve the diagnostic certainty of MS.

Another promising area with recent strides is in our ability to detect cortical gray matter disease. This would be useful in terms of adding certainty to the diagnosis of MS and for monitoring disease progression, particularly in the progressive phases of the disease, where we tend to see less robust inflammatory white matter disease activity.

An additional untapped MRI tool for detecting changes in MS relates to developing quantitative markers in the spinal cord, including atrophy. We have made strides in adopting some of the quantitative markers used in clinical trials for evaluating outcomes such as whole brain atrophy, cortical gray matter atrophy, and thalamic atrophy in the clinic, and further progress will depend on our ability to standardize the MRI acquisitions and automate the analyses.

References

Caldano N, Raoul W, Rispens T, Bertolotto A. Drug efficacy monitoring in pharmacotherapy of multiple sclerosis with biological agents. Ther Drug Monit. 2017;39(4):350-355. doi:10.1097/FTD.0000000000000393

Rae-Grant A, Day GS, Marrie RA, et al. Comprehensive systematic review summary: disease-modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology [published correction appears in Neurology. 2019;93(17):769]. Neurology. 2018;90(17):789-800. doi:10.1212/WNL.0000000000005345

Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology [published correction appears in Neurology. 2019;92(2):112]. Neurology. 2018;90(17):777-788. doi:10.1212/WNL.0000000000005347

Saslow L, Li DKB, Halper J, et al. An international standardized magnetic resonance imaging protocol for diagnosis and follow-up of patients with multiple sclerosis: advocacy, dissemination, and implementation strategies. Int J MS Care. 2020;22(5):226-232. doi:10.7224/1537-2073.2020-094

Sati P, Oh J, Constable RT, et al; NAIMS Cooperative. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12(12):714-722. doi:10.1038/nrneurol.2016.166

Van Schependom J, Guldolf K, D’hooghe MB, Nagels G, D’haeseleer M. Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in. Transl Neurodegener. 2019;8:37. doi:10.1186/s40035-019-0178-4

Eric C. Klawiter, MD, MSc

Associate Neurologist
Massachusetts General Hospital
Associate Professor of Neurology
Harvard Medical School
Boston, MA

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