**1. Introduction**

Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by inflammatory demyelination and neurodegeneration, and around 3–5% of patients have their disease onset prior to adulthood. Although physical disability is rarely seen in the first decade of disease course in pediatric-onset MS (POMS) [1], cognitive impairment is fairly common in this patient population. Findings across studies showed that around one-third of pediatric MS patients suffer from some degree of cognitive impairment, and it could be detected as early as nearing disease onset in a subset of patients [2–5]. Multiple cognitive domains have been reported to be affected in pediatric MS, including information processing speed, attention, working memory (WM), verbal and visuospatial memory, executive function, visuo-motor integration, and aspects of language function [4–10]. While reports of cognitive profiles of POMS have been accumulating, direct comparisons between these studies are often hampered by differences in patient characteristics and assessment tools. Indeed, it was noted that the results of cognitive evaluation might vary with the instruments used. For instance, Wuerfel et al. used several tests to tap WM and found that only more cognitively demanding tasks revealed group-level difference in WM performance between POMS and controls [6]. This exemplifies the

importance to clarify the applicability and performance of various cognitive assessment tools in this patient population.

Despite growing awareness of cognitive issues in pediatric MS in recent years, there has been limited information to date concerning ways of cognitive remediation for these patients. Rehabilitative strategies for POMS are often extrapolated from those for adult MS in the real-world situations, but this approach needs validation. To obtain a panorama of this emerging field, we here seek to collate existing evidence on cognitive assessment tools and cognitive rehabilitation for POMS, which may serve as the basis for future directions of research and clinical practice.

### **2. Materials and Methods**

We followed the methodological framework developed by Arksey and O'Malley [11], and this scoping review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR, Supplementary File S1) [12]. This study was retrospectively registered at Open Science Framework database (https://osf.io/uyd2q/) on 12 April 2020, and the review protocol is presented in Supplementary File S2.

### *2.1. Literature Search, Screening, and Selection*

We conducted systematic literature searches in the following databases: PubMed, MEDLINE, CINAHL Plus, and Web of Science. Date of publication was not restricted (from inception to February 2020). The terms used in the searches were: "multiple sclerosis" AND ("pediatric" or "paediatric") AND ("cognitive" or "cognition"). The most recent search was executed on 21 March 2020. The titles and abstracts of retrieved articles were then screened for relevance to cognitive evaluation and/or cognitive rehabilitation. The inclusion criteria were: (a) peer-reviewed original studies published in English; (b) studies that specifically addressed either cognitive assessment tools or cognitive rehabilitation for POMS. The exclusion criteria were: (a) articles that were either not peer-reviewed (e.g., book chapter) or not reporting original studies (e.g., review paper); (b) studies that aimed to characterize the cognitive profile of POMS, rather than to examine the performance and applicability of cognitive assessment tools or the e ffects of cognitive rehabilitation in this patient population. Every e ffort was made to obtain the full text of all potentially relevant articles, which were examined to determine the eligibility. We also screened the reference lists of relevant articles. The above process was independently carried out by two of the authors (W.-S.L. and S.-J.L.), and discrepancies were resolved by discussion with the senior author (T.-R.H.) and consensus among the authors.

On the other hand, we also searched ClinicalTrials.gov, European Union Clinical Trials Register, and Open Science Framework database for trials or projects pertinent to the themes of our review.

### *2.2. Data Charting*

The included articles were read by two of the authors (W.-S.L. and S.-J.L.), and relevant data were charted and tabulated. For studies evaluating cognitive assessment tools, we extracted the year of publication, the tests (and subtests, if applicable) of interest and their targeted cognitive domains, the characteristics of study participants (such as sample size of disease and control groups, demographic and disease-related features), and main findings (particularly in relation to psychometric performance). For studies evaluating cognitive rehabilitation, we extracted the mode of intervention (including its frequency and duration, requirement of supervision, and targeted cognitive domains), study design, the characteristics of study participants, e ffects of intervention (including e ffects on targeted and non-targeted domains, and sustainability of e ffect), and factors associated with outcomes.

For relevant clinical trials identified from trial registers, the principal investigator, the aim and the design of the trial, and other relevant information were collected.
