Impact of the 2017 McDonald Criteria Revision on Time to Diagnosis and Long-Term Disability in Primary Progressive Multiple Sclerosis’s patients

The clinical course of relapsing multiple sclerosis (RMS) has become milder over recent decades [1]. Longitudinal cohort studies have consistently demonstrated a temporal delay in the attainment of disability milestones among patients diagnosed in more recent years [2–3-4]. Although this improvement results from a complex interplay of multiple factors, the most significant contributor is undoubtedly the widespread adoption of disease-modifying therapies (DMTs). Another key factor is the progressive reduction in diagnostic latency following the introduction of the McDonald diagnostic criteria for MS [6] and their subsequent revisions [7–8]. These criteria have enabled earlier diagnosis of relapsing MS (RMS), often in milder forms, allowing for the earlier initiation of DMTs, which in turn has contributed to a reduction in both relapse rates and long-term disability. A large multicenter study involving 785 patients with clinically isolated syndrome (CIS) demonstrated that the 2017 revision of the criteria allowed for a significantly shorter median time to diagnosis of relapsing-remitting MS (RRMS) compared to the 2010 version (3.2 months vs. 13.0 months) [9]. However, the diagnostic performance of the 2017 criteria in primary progressive MS (PPMS) remains less clearly established. Due to its unique clinical presentation and the frequent presence of diagnostic confounders, PPMS has been defined by separate diagnostic criteria since the year 2001. The first diagnostic criteria for PPMS required evidence of dissemination in space (DIS)—demonstrated by MRI or abnormal visual evoked potentials—and dissemination in time (DIT), established either through MRI findings or sustained disability progression over one year. The 2005 revision made mandatory the determination- retrospective or prospective- of one year of disease progression (retrospectively or prospectively determined) and added the need for at least one of the following: a positive brain MRI, a positive spinal cord MRI, or positive cerebrospinal fluid (CSF) findings. The 2010 revision introduced the MAGNIMS neuroimaging criteria for DIS in the brain, nowdefined by the presence of one or more T2 lesions in at least one MS-characteristic region (periventricular, juxtacortical, or infratentorial). In the most recent 2017 revision of the McDonald criteria, the diagnostic criteria for PPMS remained essentially unchanged from the 2010 version, with the exception of the elimination of the distinction between symptomatic and asymptomatic MRI lesions and the inclusion of cortical lesions in the assessment. More recently, the conventional classification of MS into discrete phenotypes has been challenged by a conceptual shift toward viewing the disease as a continuum of neuroinflammation and neurodegeneration [10]. From disease onset, both progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) contribute—albeit to varying degrees—to the accumulation of irreversible neurological disability in patients with MS. [11]
To date, however, there is a paucity of real-world, multicenter data evaluating whether the 2017 revision has led to a reduced diagnostic latency in PPMS and whether this has translated into improved long-term outcomes. The aim of our project is to address this gap by analyzing real-world data from the Italian MS and Related Disorders Register (RISM). Specifically, we seek to determine whether the implementation of the 2017 criteria has resulted in a measurable reduction in diagnostic latency for PPMS, and to compare the risk of reaching predefined disability milestones in patient cohorts diagnosed in different epochs. The findings of this study may help identify unmet needs in the diagnostic and therapeutic management of PPMS, with implications for optimizing care in this challenging MS phenotype

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