The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.
MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.
they wrote.
Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.
This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.
The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.
Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.
The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.
A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.
The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.
In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.
In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.
Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.
Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.
The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.