Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective

Abstract

agnetic resonance imaging (MRI) is central in the diagnostic workup of patients with suspected multiple sclerosis (MS) given its high sensitivity to detect disease dissemination in space and over time and its substantial, albeit imperfect, ability to exclude other mimics of MS. From 2001 until 2017, great effort was expended providing successive iterations of the McDonald criteria to define imaging features typical of MS in patients presenting with clinically isolated syndrome (CIS). 1 However, diagnosis of primary progressive (PP) MS remains challenging and is only possible retrospectively based on clinical assessment.Identification of imaging features associated with PPMS and features that predict evolution from relapsing-remitting (RR) MS to secondary progressive (SP) MS is an important unmet need. Given the advent of effective therapies for RRMS that may reduce development of SPMS and limit disability worsening in progressive MS (PMS), 2 the need for such imaging indicators is all the greater.Diagnosis of PMS is limited by difficulties in distinguishing accumulating disability due to inflammatory disease activity from that attributable to degenerative processes associated with SPMS. Moreover, there are no accepted clinical criteria for diagnosing SPMS. 3,4 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 PMS. MethodsIn this review, we report the conclusions of the "Diagnosis of Progressive MS: The Imaging Perspective" workshop held in Milan,

Characteristics of secondary progressive multiple sclerosis: Disease activity and provision of care in Germany – A registry-based/multicentric cohort study

“…It is worth noting that 'MRI activity' (new T2 lesions) in patients aged over 55-60 is likely to be confounded by lesions that are not MSassociated but are due to the increasing number of comorbidities (especially cerebrovascular) in elderly populations (e.g. hypertension) (Filippi et al, 2020;Guisset et al, 2020). Insufficient reproducibility of longitudinal MRI findings (especially beyond approval studies) has long been known as a problem in MRI follow-up investigations among clinical neurologists (Molyneux et al, 1999).…”

Chronic active lesions: a new MRI biomarker to monitor treatment effect in multiple sclerosis?

“…Since the accumulation of chronic active lesions may represent one of the contributors to clinical disability in PMS [9], the demonstration of a beneficial effect of ocrelizumab in limiting chronic inflammation, demyelination, and axonal loss could further support the use of this drug in limiting clinical worsening in these patients.…”

“…dynamic contrast enhancement [DCE]), chronic active lesions, ~9.4% of all chronic lesions, showed no contrastenhancement, thus they lack substantially abnormal bloodbrain barrier permeability that typically characterizes acute lesions [7]. Iron rim lesions are also characterized by a more limited lesional repair and have been described in all MS phenotypes although with heterogeneous reported rates: clinically isolated syndrome/relapsing-remitting (RR) MS from 6% to 53%, PMS from 7% to 62% [3,4,8,9]. By evaluating the longitudinal evolution of iron rim lesions over up to 7 years, a recent study with the longest follow-up currently available showed that such lesions are characterized by a slow rate of increase in size in the first years after their formation and then stabilize.…”

“…Chronic active lesions seem to represent one of the most relevant pathological substrates associated with more severe clinical disability, progressive disease course, and brain atrophy and contributing to disability progression in MS, also in the absence of overt inflammatory activity [6,9]. Accordingly, the investigation of the potential beneficial effects of disease-modifying treatments (DMTs) on the occurrence, accumulation and microstructural features of chronic active lesions may represent a rewarding strategy to understand whether specific therapeutic interventions may limit this compartmentalized chronic inflammation in MS.…”

New Prospects for Ultra-High-Field Magnetic Resonance Imaging in Multiple Sclerosis

“…Magnetic resonance imaging can also support the identification of mechanisms behind disease progression, including paramagnetic rim lesions, subpial demyelination, distinct spinal cord pathology, and brain and spinal cord atrophy. 44 …”