In 2018, the distinguishing pathological features of white matter lesions in patients with progressive multiple sclerosis (MS) were refined, and serological and MRI biomarkers of clinical worsening and evolution to progressive MS were identified. We also saw therapeutic advances in progressive MS with the emergence of new neuroprotective strategies and putative markers of neurodegeneration.
Key advances
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A pathological study showed that substantial white matter lesion activity, in the form of mixed active–inactive, smouldering and slowly expanding lesions, persists and correlates with disease severity in patients with long-standing progressive multiple sclerosis (MS)1.
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Levels of serum neurofilament light chain, a marker of neuroaxonal damage, were found to be higher in progressive MS than in relapsing MS, to correlate with current and future clinical disability, and to predict accelerated brain and spinal cord atrophy4.
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In patients with relapse-onset MS, a high cortical lesion count at disease onset predicted conversion to secondary progressive MS5, and in patients with primary progressive MS, baseline grey matter damage was predictive of clinical worsening after 15 years6.
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Integration of MRI measures into the clinical evaluation of patients with MS would allow earlier prognostication of long-term clinical outcomes6, leading to possible improvements in treatment decision-making and optimization of overall costs.
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In a phase II trial in patients with progressive MS, ibudilast treatment was associated with slower progression of brain atrophy but also had some adverse effects10; this study provides the impetus for future trials of neuroprotection in progressive MS.
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References
Luchetti, S. et al. Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis. Acta Neuropathol. 135, 511–528 (2018).
Frischer, J. M. et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann. Neurol. 78, 710–721 (2015).
Disanto, G. et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann. Neurol. 81, 857–870 (2017).
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Fox, R. J. et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. N. Engl. J. Med. 379, 846–855 (2018).
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M.A.R. has received speaker’s honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. M.F. has received compensation for consulting services and/or speaking activities from Biogen Idec, Merck Serono, Novartis and Teva Pharmaceutical Industries, and receives research support from Biogen Idec, Merck Serono, Novartis, Teva Pharmaceutical Industries, Roche, the Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
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Rocca, M.A., Filippi, M. Targeting progression in multiple sclerosis — an update. Nat Rev Neurol 15, 62–64 (2019). https://doi.org/10.1038/s41582-018-0127-3
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DOI: https://doi.org/10.1038/s41582-018-0127-3
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