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Pediatric-onset MS may slow information processing in adulthood

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MS onset during brain development

The study by McKay et al. indicates that onset of multiple sclerosis (MS) during childhood or adolescence has long-term effects, Lauren B. Krupp, MD, and Leigh E. Charvet, PhD, wrote in an accompanying editorial.

In early adulthood, patients with pediatric-onset MS initially may perform better on the Symbol Digit Modalities Test, compared with patients with adult-onset MS. “However, the two groups diverged by the time the [pediatric-onset MS] patients reached 30 years of age, with slower performance in the [pediatric-onset MS] group relative to the [adult-onset MS] group, a difference that persisted over time,” Dr. Krupp and Dr. Charvet wrote. The findings remained even when the researchers adjusted for disease duration.

“Despite initial resiliency and age-based advantages, the study’s findings suggest greater deleterious long-term consequences from developing MS during a period of ongoing brain development,” they wrote.

The effect of slowed cognitive processing on quality of life is unclear, however. “The key question for future research is whether those with [pediatric-onset MS] attain their anticipated educational and occupational achievements in a manner comparable to those with [adult-onset MS],” Dr. Krupp and Dr. Charvet concluded.

Dr. Krupp and Dr. Charvet are affiliated with the Multiple Sclerosis Comprehensive Care Center at New York University. These comments are adapted from an editorial accompanying the article by McKay et al. ( JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546 ). Dr. Krupp reported receiving grants from the National Multiple Sclerosis Society; grants and personal fees from Biogen; and personal fees from Novartis, Sanofi Aventis, Sanofi Genzyme, Shire Pharmaceuticals, Roche, and RedHill Biopharma outside the submitted work. Dr. Charvet reported receiving grants and personal fees from Biogen, grants from the National Multiple Sclerosis Society, and research funding from Novartis and Biogen outside the submitted work.


 

FROM JAMA NEUROLOGY

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

A diagnosis form says multiple sclerosis. designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.

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