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Pathology of Multiple Sclerosis

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Abstract

Multifocal demyelination and neurodegeneration characterized by neuronal, synaptic, and axonal injury are key characteristics of multiple sclerosis (MS). Demyelination involves both white and gray matter regions. Neurodegeneration, mediated by oxidative tissue injury and energy failure, correlates with disability worsening more significantly than white matter (WM) lesions. Magnetic resonance imaging (MRI) is an invaluable tool but has limitations in detecting cortical pathology and discriminating demyelination from axonal pathology. Postmortem in situ MRI with histopathologic correlations can validate demyelination—contrary to popular belief, MRI is not specific for demyelination, as only 55% of T2-only lesions are demyelinated, with axonal pathology also accounting for T2-hyperintensities.

Recently, a subset of patients with “myelocortical MS” has been described, with cerebral WM lesions on MRI but lacking significant cerebral demyelination; they do have cortical and spinal cord demyelination. Characterizing MS histopathology cannot be done in isolation but rather in concert with MRI and clinical history for a more complete picture of the ramifications and impact of the pathology. Here we summarize key findings of focal and diffuse inflammatory and neurodegenerative changes, taking into account the utility and limitations of MRI and the clinical course where applicable.

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Acknowledgments

KRM has received funding from the National MS Society Clinician Scientist Development Award (FAN-1507-05605) and is currently funded by NIH/NINDS K23NS109328. Figures 8.1 and 8.2 were obtained by KRM in the laboratories of Dr. Bruce D. Trapp (Department of Neuroscience) and Dr. Kunio Nakamura (Department of Biomedial Engineering) at the Cleveland Clinic – Lerner Research Institute. The rapid MS postmortem autopsy program has received funding from Sanofi Genzyme.

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Authors and Affiliations

  1. Department of Neuroscience, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Jordon Dunham & Kedar R. Mahajan

  2. Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Kedar R. Mahajan

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  1. Jordon Dunham
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Correspondence to Kedar R. Mahajan .

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  1. University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Amanda L. Piquet

  2. University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Enrique Alvarez

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Dunham, J., Mahajan, K.R. (2021). Pathology of Multiple Sclerosis. In: Piquet, A.L., Alvarez, E. (eds) Neuroimmunology. Springer, Cham. https://doi.org/10.1007/978-3-030-61883-4_8

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  • DOI: https://doi.org/10.1007/978-3-030-61883-4_8

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-61882-7

  • Online ISBN: 978-3-030-61883-4

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