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December 14, 2020

Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective: A Review

Author Affiliations
  • 1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Istituto di Ricovero e di Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
  • 2Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • 3Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • 4Vita-Salute San Raffaele University, Milan, Italy
  • 5Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Location VU University Medical Center (VUmc), Multiple Sclerosis Center Amsterdam, Amsterdam, the Netherlands
  • 6Institutes of Neurology and Healthcare Engineering, University College London, London, United Kingdom
  • 7Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, University College London Institute of Neurology, London, United Kingdom
  • 8National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, United Kingdom
  • 9Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
  • 10Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, Ohio
  • 11Department of Neurology, San Camillo-Forlanini Hospital, Rome, Italy
  • 12Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland
  • 13Department of Neurology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Vall d’Hebron, Autonomous University of Barcelona, Barcelona, Spain
  • 14Division of Neurology, St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
  • 15Translational Neuroradiology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
  • 16Neuroradiology Section, Department of Radiology (IDI), Vall d’Hebron University Hospital and Research Institute (VHIR), Autonomous University of Barcelona, Barcelona, Spain
  • 17MS/Magnetic Resonance Imaging (MRI) Research Group, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada
  • 18Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • 19Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 20Department of Radiology, Mayo Clinic, Rochester, Minnesota
  • 21Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
  • 22Department of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
JAMA Neurol. 2021;78(3):351-364. doi:10.1001/jamaneurol.2020.4689

Importance  Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS.

Observations  Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS. In patients with PPMS and those with relapse-onset MS, location of lesions in critical central nervous system regions (spinal cord, infratentorial regions, and GM) and MRI-detected high inflammatory activity in the first years after diagnosis are risk factors for long-term disability and future progressive disease course. These measures are evaluable in clinical practice. In patients with established MS, GM involvement and neurodegeneration are associated with accelerated clinical worsening. Subpial demyelination and slowly expanding lesions are novel indicators of progressive MS.

Conclusions and Relevance  Diagnosis of PPMS is more challenging than diagnosis of RRMS. No qualitative clinical, immunological, histopathological, or neuroimaging features differentiate PPMS and SPMS; both are characterized by imaging findings reflecting neurodegeneration and are also impacted by aging and comorbidities. Unmet diagnostic needs include identification of MRI markers capable of distinguishing PPMS from RRMS and predicting the evolution of RRMS to SPMS. Integration of multiple parameters will likely be essential to achieve these aims.

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