Primary <scp>P</scp>rogressive <scp>M</scp>ultiple <scp>S</scp>clerosis <scp>E</scp>volving <scp>F</scp>rom <scp>R</scp>adiologically <scp>I</scp>solated <scp>S</scp>yndrome

Kantarci, Orhun H.; Lebrun, C.; Síva, Aksel; Keegan, Mark; Azevedo, Christina; Inglese, Matilde; Tintoré, Mar; Newton, Braeden D.; Durand‐Dubief, Françoise; Amato, Maria Pia; Stefano, Nicola De; Sormani, Maria Pia; Pelletier, Daniel; Okuda, Darin T.

doi:10.1002/ana.24564

Cited by 145 publications

(118 citation statements)

References 27 publications

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“…One possible explanation could be periods of asymptomatic inflammation at younger age, before clinical onset and diagnosis. Direct evolution from a radiologically isolated syndrome to symptomatic PPMS has been recently reported 23. Consistent with the concept of an earlier, more inflammatory disease phase, we found that the proportion of patients with active lesions is greatest in the youngest PPMS patients and decreases gradually with older age, a pattern that is well known from RMS 24.…”

Section: Discussionsupporting

confidence: 90%

Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study

Miller

Lublin

Sormani

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692).MethodsMagnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease‐burden covariates.ResultsBaseline normalized brain volume was predictive of disability worsening: Risk of 3‐month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, P = 0.0339; log‐rank test: P = 0.0297). Moreover, on‐study brain volume loss was significantly associated with disability worsening (P = 0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (P < 0.0001). Despite low inflammatory activity at baseline (13% of patients had gadolinium‐enhancing lesions) and throughout the study (mean 0.5 new/enlarging T2 lesions and 172 mm3 T2 lesion volume increase per year), baseline T2 lesion volume was substantial (mean 10 cm3). Lower normalized brain volume at baseline correlated with higher baseline T2 volume and older age (both P < 0.0001).InterpretationBaseline brain volume and the rate of ongoing brain atrophy are significantly associated with disability worsening in primary progressive multiple sclerosis. Brain volume loss is significantly related to baseline T2 lesion volume, but partially independent of new lesion activity, which might explain the limited efficacy of anti‐inflammatory treatment.

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Section: Discussionsupporting

confidence: 90%

Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study

Miller

Lublin

Sormani

et al. 2018

Ann Clin Transl Neurol

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“…A number of independent observational cohort studies have shown that within 5 years after initial RIS detection, up to 30% of RIS patients will develop a symptomatic demyelinating event and nearly two-thirds will progress radiologically with new lesions on MRI. [7][8][9][10][11][12] Notably, nearly 10% of RIS patients have been found to develop not an acute clinical onset but a progressive clinical course fulfilling criteria for primary progressive MS. 12,13 RIS who evolved to primary progressive MS were significantly older, more commonly men, and had a higher spinal cord lesion load compared to RIS patients who developed an acute demyelinating symptom. 13 Which RIS patients are at higher risk of future demyelinating event?…”

Section: Clinical Relevance Of Rismentioning

confidence: 99%

Radiologically isolated syndrome: An update on a rare entity

Labiano-Fontcuberta

Benito‐León

2016

Mult Scler

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Our understanding of radiologically isolated syndrome (RIS) is evolving, as new data emerge on the clinical characterization and the pathophysiological nature of this rare entity. This topical review aims to (1) outline state-of-the-art clinical and magnetic resonance imaging findings of RIS research; (2) raise the main obstacles to RIS research; (3) discuss the most controversial issues of current RIS findings; and (4) highlight potential strategies for upcoming research studies.

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“…This is supported by findings from the long-term follow-up of individuals with radiologically isolated syndrome, suggesting the presence of a presymptomatic phase in patients with PPMS [25]. Among the 34 % of patients with radiologically isolated syndrome who developed an initial clinical event related to demyelination within the CNS over a 5-year follow-up period, 11.7 % fulfilled the criteria for PPMS [25].…”

Section: Progressive Ms Phenotypementioning

confidence: 53%

Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis

2016

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Identifying effective therapies for the treatment of progressive forms of multiple sclerosis (MS) is a highly relevant priority and one of the greatest challenges for the global MS community. Better understanding of the mechanisms involved in progression of the disease, novel trial designs, drug repurposing strategies, and new models of collaboration may assist in identifying effective therapies. In this review, we discuss various therapies under study in phase II or III trials, including antioxidants (idebenone); tyrosine kinase inhibitors ( m a s i t i n i b ) ; s p h i n g o s i n e r e c e p t o r m o d u l a t o r s (siponimod); monoclonal antibodies (anti-leucine-rich repeat and immunoglobulin-like domain containing neurite outgrowth inhibitor receptor-interacting protein-1, natalizumab, ocrelizumab, intrathecal rituximab); hematopoetic stem cell therapy; statins and other possible neuroprotective agents (amiloride, riluzole, fluoxetine, oxcarbazepine); lithium; phosphodiesterase inhibitors (ibudilast); hormone-based therapies (adrenocorticotrophic hormone and erythropoietin); T-cell receptor peptide vaccine (NeuroVax); autologous T-cell immunotherapy (Tcelna); MIS416 (a microparticulate immune response modifier); dopamine antagonists (domperidone); and nutritional supplements, including lipoic acid, biotin, and sunphenon epigallocatechin-3-gallate (green tea extract). Given ongoing and planned clinical trial initiatives, and the largest ever focus of the global research community on progressive MS, future prospects for developing targeted therapeutics aimed at reducing disability in progressive forms of MS appear promising.

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Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome

Cited by 145 publications

References 27 publications

Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study

Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study

Radiologically isolated syndrome: An update on a rare entity

Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis

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