Long-term Cognitive Outcomes in Patients With Pediatric-Onset vs Adult-Onset Multiple Sclerosis

McKay, Kyla A.; Manouchehrinia, Ali; Berrigan, Lindsay; Fisk, John D.; Olsson, Tomas; Hillert, Jan

doi:10.1001/jamaneurol.2019.1546

Cited by 75 publications

(63 citation statements)

References 33 publications

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“…While cognitive impairment was seen early in the disease at initial evaluation, those patients who did not have an escalation of treatment had a higher degree of impairment at time of follow up in comparison to those who had an escalation of therapy [94]. Studies additionally have shown that those with pediatric MS are at a higher risk of cognitive disability than adult MS patients [95,96]. Cognitive impairment is more significant in the pediatric MS population, and findings show that those who have been escalated to a higher efficacy treatment to have a lower degree of cognitive impairment; thus, this argues towards an induction or "step-down" treatment approach to help protect from development or further cognitive decline, although larger studies are warranted to confirm this hypothesis.…”

Section: Cognitive Impairment Fatigue and Psychiatric Comorbiditiesmentioning

confidence: 99%

Current Advances in Pediatric Onset Multiple Sclerosis

et al. 2020

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Multiple sclerosis (MS) is an autoimmune inflammatory disease affecting the central nervous system leading to demyelination. MS in the pediatric population is rare, but has been shown to lead to significant disability over the duration of the disease. As we have learned more about pediatric MS, there has been a development of improved diagnostic criteria leading to earlier diagnosis, earlier initiation of disease-modifying therapies (DMT), and an increasing number of DMT used in the treatment of pediatric MS. Over time, treatment with DMT has trended towards the initiation of higher efficacy treatment at time of diagnosis to help prevent further disease progression and accrual of disability over time, and there is evidence in current literature that supports this change in treatment patterns. In this review, we discuss the current knowledge in diagnosis, treatment, and clinical outcomes in pediatric MS.

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Section: Cognitive Impairment Fatigue and Psychiatric Comorbiditiesmentioning

confidence: 99%

Current Advances in Pediatric Onset Multiple Sclerosis

et al. 2020

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“…Individuals with pediatric multiple sclerosis (MS) tend to have higher relapse rates, greater accumulation of new magnetic resonance imaging (MRI) lesions, earlier age of reaching disability milestones, and greater long‐term cognitive impairment compared with adult onset MS, necessitating optimal management. Treating pediatric MS is challenging given high disease activity and lack of safety and efficacy data for most disease‐modifying therapies (DMTs) in children.…”

Section: Introductionmentioning

confidence: 99%

Real‐World Effectiveness of Initial Disease‐Modifying Therapies in Pediatric Multiple Sclerosis

Krysko

Graves

Rensel

et al. 2020

Annals of Neurology

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Objective To assess real‐world effectiveness of initial treatment with newer compared to injectable disease‐modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). Methods This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon‐β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS‐quintile. Time to new/enlarging T2‐hyperintense and gadolinium‐enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS‐quintile. Results A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS‐quintile–adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29–0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14–0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person‐years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36–0.72, p < 0.001) and gadolinium‐enhancing lesions (HR = 0.38, 95% CI = 0.23–0.63, p < 0.001) than those on injectables. Interpretation Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long‐term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42–55

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“…In principle, clinicians, and researchers may choose to use discrete norms that are commercially available for the cognitive tests they employ, locally validated norms, or regression-based norms from other populations. For example, regression-based norms derived from a Canadian sample have been employed in Sweden, albeit modified to exclude educational level ( 36 ). A large multi-center trial of exercise and cognitive rehabilitation will be applying Dutch norms at the Denmark site ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Performance of Regression-Based Norms for Cognitive Functioning of Persons With Multiple Sclerosis in an Independent Sample

et al. 2021

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Background: Cognitive impairment is common in multiple sclerosis (MS). Interpretation of neuropsychological tests requires the use of normative data. Traditionally, normative data have been reported for discrete categories such as age. More recently continuous norms have been developed using multivariable regression equations that account for multiple demographic factors. Regression-based norms have been developed for use in the Canadian population for tests included in the MACFIMS and BICAMS test batteries. Establishing the generalizability of these norms is essential for application in clinical and research settings.Objectives: We aimed to (i) test the performance of previously published Canadian regression-based norms in an independently collected sample of Canadian healthy controls; (ii) compare the ability of Canadian and non-Canadian regression-based norms to discriminate between healthy controls and persons with MS; and (iii) develop regression-based norms for several cognitive tests drawn from batteries commonly used in MS that incorporated race/ethnicity in addition to age, education, and sex.Methods: We included 93 adults with MS and 96 healthy adults in this study, with a replication sample of 104 (MS) and 39 (healthy adults). Participants reported their sociodemographic characteristics, and each was administered the oral Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). From the healthy control data, we developed regression-based norms incorporating race, age, education and sex. We then applied existing discrete norms and regression-based norms for the cognitive tests to the healthy controls, and generated z-scores which were compared using Spearman rank and concordance coefficients. We also used receiver operating characteristic (ROC) curves to compare the ability of each set of norms to discriminate between participants with and without MS. Within the MS samples we compared the ability of each set of norms to discriminate between differing levels of disability and employment status using relative efficiency.Results: When we applied the published regression norms to our healthy sample, impairment classification rates often differed substantially from expectations (7%), even when the norms were derived from a Canadian (Ontario) population. Most, but not all of the Spearman correlations between z-scores based on different existing published norms for the same cognitive test exceeded 0.90. However, concordance coefficients were often lower. All of the norms for the SDMT reliably discriminated between the MS and healthy control groups. In contrast, none of the norms for the CVLT-II or BVMT-R discriminated between the MS and healthy control groups. Within the MS population, the norms varied in their ability to discriminate between disability levels or employment status; locally developed norms for the SDMT and CVLT-II had the highest relative efficiency.Conclusion: Our findings emphasize the value of local norms when interpreting the results of cognitive tests and demonstrate the need to consider and assess the performance of regression-based norms developed in other populations when applying them to local populations, even when they are from the same country. Our findings also strongly suggest that the development of regression-based norms should involve larger, more diverse samples to ensure broad generalizability.

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Long-term Cognitive Outcomes in Patients With Pediatric-Onset vs Adult-Onset Multiple Sclerosis

Cited by 75 publications

References 33 publications

Current Advances in Pediatric Onset Multiple Sclerosis

Current Advances in Pediatric Onset Multiple Sclerosis

Real‐World Effectiveness of Initial Disease‐Modifying Therapies in Pediatric Multiple Sclerosis

Performance of Regression-Based Norms for Cognitive Functioning of Persons With Multiple Sclerosis in an Independent Sample

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