Pediatric multiple sclerosis: developments in timely diagnosis and prognostication

ABSTRACT

Introduction

Pediatric-onset (PO) multiple sclerosis (MS) accounts for about 2–10% of the total MS cases. Recently, a greater attention has been given to POMS, with substantial improvements in the understanding of its pathophysiology, in the diagnostic work-up and in the identification of reliable prognosticators associated with long-term disability in these patients.

Areas covered

This review summarizes the most recent updates regarding the pathophysiology of POMS, the current diagnostic criteria and the clinical, neuroradiological and laboratoristic markers that have been associated with disease progression (i.e. occurrence of a second clinical attack at disease onset and accumulation of disability in definite MS).

Expert opinion

The study of POMS, where the clinical onset is closer to the biological onset of MS, may contribute to better understand how the different pathological processes impact brain maturation and contribute to disease progression, but also how brain plasticity may counterbalance structural damage accumulation. Although rare, POMS is a severe disease, characterized by a prominent clinical and radiological activity at disease onset and by the accumulation of physical and cognitive disability at a younger age compared to the adult counterpart, with significant detrimental consequences at long-term. Early and accurate diagnosis, together with early treatment, is highly warranted.

KEYWORDS:

• Pediatric multiple sclerosis
• MRI
• diagnostic criteria
• prognostic factors

Article highlights

• Pediatric-onset (PO) multiple sclerosis (MS) is typically characterized by a higher inflammatory activity but better recovery from acute relapses possibly due to more efficient reparative mechanisms compared to adult-onset MS.

• Although irreversible clinical disability takes a longer time to become clinically evident in POMS compared to adult-onset MS thanks to better reparative mechanisms, it occurs at a younger age and is associated with a faster deterioration in cognitive efficiency.

• The 2017 revisions of the McDonald criteria have a high specificity in the diagnosis of POMS and similar sensitivity to adult-onset MS, supporting their application in clinical practice also for pediatric patients.

• Similarly to adult-onset MS, female sex, older age at onset, multifocal onset, optic nerve involvement, presence of oligoclonal bands, and higher neurofilament light chain levels are predictors of the occurrence of a second clinical attack in pediatric patients with a clinically isolated syndrome.

• Similarly to adult-onset MS, older age at onset, multifocal onset and/or with spinal cord/brainstem/cerebellar involvement, higher relapse rate, incomplete recovery from relapse, sustained disability accumulation in the first years, higher lesion burden and accumulation of lesions are predictors of disability progression in pediatric MS patients.

Abbreviations

GM = gray matter;

MS = multiple sclerosis;

NAWM = normal-appearing white matter;

WM = white matter

Disclosure statement

M. Margoni reports grants and personal fees from Almiral. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020.

P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.

M.A. Rocca received speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva, and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

M. Filippi is Editor-in-Chief of the Journal of Neurology and Associate Editor of Radiology, Human Brain Mapping and Neurological Sciences, received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries, and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi, Almiral, Eli Lilly, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article..