Early effective treatment may protect from cognitive decline in paediatric multiple sclerosis

Johnen, Andreas; Elpers, Christiane; Riepl, Ester; Landmeyer, Nils C.; Krämer, Julia; Polzer, Philipp; Lohmann, Hubertus; Omran, Heymut; Wiendl, Heinz; Göbel, Kerstin; Meuth, Sven G.

doi:10.1016/j.ejpn.2019.08.007

Cited by 25 publications

(19 citation statements)

References 37 publications

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“…Cognitive subdomains such as worse visual memory, as measured by 10/36 Spatial Recall Test, and information processing speed and executive functions, as measured by Symbol Digit Modalities Test, have been associated with relapses and possibly predictive of increased motor disability in pediatric and young (<25 years of age) patients with MS (47). Treating pediatric patients with effective DMTs early in the disease appears to reduce disease progression and may protect against or slow cognitive decline (48,49).…”

Section: Discussionmentioning

confidence: 99%

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Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Alroughani

Huppke

Mazurkiewicz‐Bełdzińska³

et al. 2021

Front. Neurol.

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Background: Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS.Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13–17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR).Results: Twenty participants [median (range) age, 17 (14–18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16–24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0–6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.

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Section: Discussionmentioning

confidence: 99%

“…Participants then completed a safety follow-up visit up to 4 weeks after the last dose of study treatment. During the treatment period, clinic visits were conducted on day 1 and weeks 12,16,24,36,48,60,64,72,84,96, and a safety follow-up visit. Follow-up brain MRIs occurred at weeks 16, 24, 64, and 72.…”

Section: Study Design and Participantsmentioning

confidence: 99%

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Alroughani

Huppke

Mazurkiewicz‐Bełdzińska³

et al. 2021

Front. Neurol.

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“…Six patients were escalated to a higher efficacy treatment (three to natalizumab and three fingolimod), and the remainder did not require escalation of treatment (10 on interferon beta-1a, two on glatiramer acetate, and one on dimethyl fumarate). 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].…”

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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“…Cognitive issues in pediatric MS have become a research priority in this field, and more studies surrounding cognitive evaluation for these patients were published over the past decade. Although routine cognitive screening is recommended for pediatric MS [ 26 ], and cognition has been incorporated into disease activity measure and treatment consideration [ 5 , 27 , 28 ], the best assessment tools for pediatric MS remain to be determined. Findings yielded by commonly used tools were sometimes discrepant across studies.…”

Section: Discussionmentioning

confidence: 99%

“…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 , 3 , 4 , 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 , 5 , 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Cognitive Assessment and Rehabilitation for Pediatric-Onset Multiple Sclerosis: A Scoping Review

Lin

Hsu

2020

Children

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Cognitive impairment is increasingly recognized as an important clinical issue in pediatric multiple sclerosis (MS). However, variations regarding its assessment and remediation are noted in clinical arena. This scoping review aims to collate available evidence concerning cognitive assessment tool and cognitive rehabilitation for pediatric MS. We performed a systematic search of electronic databases (MEDLINE, PubMed, CINAHL Plus, and Web of Science) from inception to February 2020. Reference lists of included articles and trial registers were also searched. We included original studies published in English that addressed cognitive assessment tools or cognitive rehabilitation for pediatric-onset MS. Fourteen studies fulfilled our inclusion criteria. Among them, 11 studies evaluated the psychometric aspects of various cognitive assessment tools in the context of pediatric MS, and different neuro-cognitive domains were emphasized across studies. There were only three pilot studies reporting cognitive rehabilitation for pediatric-onset MS, all of which used home-based computerized programs targeting working memory and attention, respectively. Overall, more systematic research on cognitive assessment tools and rehabilitation for pediatric MS is needed to inform evidence-based practice. Computer-assisted cognitive assessment and rehabilitation appear feasible and deserve further studies.

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Early effective treatment may protect from cognitive decline in paediatric multiple sclerosis

Cited by 25 publications

References 37 publications

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Current Advances in Pediatric Onset Multiple Sclerosis

Cognitive Assessment and Rehabilitation for Pediatric-Onset Multiple Sclerosis: A Scoping Review

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