Epidemiology of Pediatric-Onset Multiple Sclerosis: A Systematic Review of the Literature

Multiple sclerosis onset in youth is increasingly recognized. A systematic review was conducted to assess incidence and prevalence of pediatric-onset multiple sclerosis, focusing on occurrence by age subgroups and disease course. A literature search for the period 1965-2018 was carried out, selecting population-based studies of multiple sclerosis in individuals aged 19 years and younger. Nineteen studies met inclusion criteria. One pediatric neurologist extracted the data. Overall incidence ranged from 0.05 (95% confidence interval 0.03-0.08) to 2.85 (95% confidence interval 2.83-2.86) per 100 000 children and overall prevalence from 0.69 (95% confidence interval 0.58-0.80) to 26.92 (95% confidence interval 26.61-27.23) per 100 000 children. Incidence increased with age. The female-male ratio increased from 1.2:1 in children <12 years old to 2.8:1 in children ≥12 years old. Ten studies (n=521 children) reported disease course. Seven studies found only relapsing-remitting disease and 3 studies found primary-progressive disease in 3.0% to 6.7%. Two secondary-progressive disease cases were identified. Epidemiologic data aid in understanding the magnitude of multiple sclerosis and its clinical phenotypes, for planning for new disease-modifying therapies in the pediatric population.

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Epilepsy in multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000004740 ◽

2017 ◽

Vol 89 (24) ◽

pp. 2462-2468 ◽

Cited By ~ 22

Author(s):

Joachim Burman ◽

Johan Zelano

Keyword(s):

Multiple Sclerosis ◽

Clinical Features ◽

Cumulative Incidence ◽

Progressive Disease ◽

Disease Duration ◽

Population Based ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Relapsing Remitting ◽

Edss Score

Objective:To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.Methods:All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.Results:The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).Conclusions:Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

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Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511417479 ◽

2011 ◽

Vol 18 (1) ◽

pp. 45-54 ◽

Cited By ~ 52

Author(s):

M Cossburn ◽

G Ingram ◽

C Hirst ◽

Y Ben-Shlomo ◽

TP Pickersgill ◽

...

Keyword(s):

Multiple Sclerosis ◽

Late Onset ◽

Age At Onset ◽

Disease Onset ◽

Complete Recovery ◽

Population Based ◽

Disease Course ◽

Index Event ◽

Relapsing Remitting ◽

Age Dependent

Background: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. Objectives: To determine the nature of age-specific presentations of relapsing–remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. Methods: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Results: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest ( p = 0.009). Conclusions: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

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Prevalence of radiologically isolated syndrome in a pediatric population-based cohort: A longitudinal description of a rare diagnosis

Multiple Sclerosis Journal ◽

10.1177/1352458521989220 ◽

2021 ◽

pp. 135245852198922

Author(s):

CL de Mol ◽

AL Bruijstens ◽

PR Jansen ◽

MHG Dremmen ◽

YYM Wong ◽

...

Keyword(s):

Multiple Sclerosis ◽

General Population ◽

Confidence Interval ◽

Pediatric Population ◽

Population Based ◽

Radiologically Isolated Syndrome ◽

Demyelinating Lesions ◽

Rare Diagnosis

Background: Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown. Objective: The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children. Methods: We used data from the Generation R study to identify the childhood RIS prevalence. Results: In 5238 participants, only one RIS case was identified (prevalence: 0.02%; 95% confidence interval (CI): 0.00–0.11). During a 62-month follow-up, imaging examinations showed accrual of new focal demyelinating lesions; however, no clinical MS symptoms occurred. Conclusions: This study shows that the occurrence of RIS in children from the general population is rare.

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Faculty Opinions recommendation of Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1058900.510836 ◽

2007 ◽

Author(s):

Myla Goldman

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Demographic Predictors ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

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Machine Learning Use for Prognostic Purposes in Multiple Sclerosis

Life ◽

10.3390/life11020122 ◽

2021 ◽

Vol 11 (2) ◽

pp. 122

Author(s):

Ruggiero Seccia ◽

Silvia Romano ◽

Marco Salvetti ◽

Andrea Crisanti ◽

Laura Palagi ◽

...

Keyword(s):

Machine Learning ◽

Multiple Sclerosis ◽

High Impact ◽

Prognostic Models ◽

Early Prediction ◽

Disease Course ◽

Slow Progression ◽

Relapsing Remitting ◽

Long Time ◽

Effective Drugs

The course of multiple sclerosis begins with a relapsing-remitting phase, which evolves into a secondarily progressive form over an extremely variable period, depending on many factors, each with a subtle influence. To date, no prognostic factors or risk score have been validated to predict disease course in single individuals. This is increasingly frustrating, since several treatments can prevent relapses and slow progression, even for a long time, although the possible adverse effects are relevant, in particular for the more effective drugs. An early prediction of disease course would allow differentiation of the treatment based on the expected aggressiveness of the disease, reserving high-impact therapies for patients at greater risk. To increase prognostic capacity, approaches based on machine learning (ML) algorithms are being attempted, given the failure of other approaches. Here we review recent studies that have used clinical data, alone or with other types of data, to derive prognostic models. Several algorithms that have been used and compared are described. Although no study has proposed a clinically usable model, knowledge is building up and in the future strong tools are likely to emerge.

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A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry

Multiple Sclerosis Journal ◽

10.1177/13524585211019649 ◽

2021 ◽

pp. 135245852110196

Author(s):

Jan Hillert ◽

Jon A Tsai ◽

Mona Nouhi ◽

Anna Glaser ◽

Tim Spelman

Keyword(s):

Multiple Sclerosis ◽

Real World ◽

Clinical Effectiveness ◽

Dimethyl Fumarate ◽

Population Based ◽

Life Outcomes ◽

Treatment Persistence ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis

Background: Teriflunomide and dimethyl fumarate (DMF) are first-line disease-modifying treatments for multiple sclerosis with similar labels that are used in comparable populations. Objectives: The objective of this study was to compare the effectiveness and persistence of teriflunomide and DMF in a Swedish real-world setting. Methods: All relapsing-remitting multiple sclerosis (RRMS) patients in the Swedish MS registry initiating teriflunomide or DMF were included in the analysis. The primary endpoint was treatment persistence. Propensity score matching was used to adjust comparisons for baseline confounders. Results: A total of 353 teriflunomide patients were successfully matched to 353 DMF. There was no difference in the rate of overall treatment discontinuation by treatment group across the entire observation period (hazard ratio (HR) = 1.12; 95% confidence interval (CI) = 0.91–1.39; p = 0.277; reference = teriflunomide). Annualised relapse rate (ARR) was comparable ( p = 0.237) between DMF (0.07; 95% CI = 0.05–0.10) and teriflunomide (0.09; 95% CI = 0.07–0.12). There was no difference in time to first on-treatment relapse (HR = 0.78; 95% CI = 0.50–1.21), disability progression (HR = 0.55; 95% CI = 0.27–1.12) or confirmed improvement (HR = 1.17; 95% CI = 0.57–2.36). Conclusion: This population-based real-world study reports similarities in treatment persistence, clinical effectiveness and quality of life outcomes between teriflunomide and dimethyl fumarate.

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Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

Brain Sciences ◽

10.3390/brainsci11111444 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1444

Author(s):

Mattia Fonderico ◽

Emilio Portaccio ◽

Lorenzo Razzolini ◽

Luisa Pastò ◽

Angelo Bellinvia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Clinical Course ◽

Meta Analysis ◽

Clinically Isolated Syndrome ◽

Relapsing Remitting ◽

Oligoclonal Igg ◽

Almost All ◽

Present Systematic Review ◽

Oligoclonal Igg Bands

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

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