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April 19, 2022; 98 (16) Research Article

Long-term Cognitive Outcomes and Socioprofessional Attainment in People With Multiple Sclerosis With Childhood Onset

View ORCID ProfileEmilio Portaccio, View ORCID ProfileAngelo Bellinvia, Lorenzo Razzolini, Luisa Pastò, Benedetta Goretti, Claudia Niccolai, Mattia Fonderico, Mauro Zaffaroni, Lorena Pippolo, Lucia Moiola, Monica Falautano, Claudia Celico, Rossella Viterbo, Francesco Patti, View ORCID ProfileClara Chisari, Paolo Gallo, Alice Riccardi, Martina Borghi, View ORCID ProfileAntonio Bertolotto, Marta Simone, Carlo Pozzilli, Valentina Bianchi, Marco Roscio, Vittorio Martinelli, Giancarlo Comi, View ORCID ProfileMassimo Filippi, Maria Trojano, Angelo Ghezzi, Maria Pia Amato, MS Study Group of the Italian Neurological Society
First published April 18, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200115
Emilio Portaccio
From the University of Florence (E.P., A.B., L.R., L. Pastò, B.G., C.N., M. Fonderico, M.P.A.); IRCCS Fondazione Don Carlo Gnocchi (E.P., M.P.A.), Florence; Multiple Sclerosis Centre (M.Z., L. Pippolo, M.R.), Hospital of Gallarate, ASST Della Valle Olona; Neurology and Neurological Rehabilitation Unit (L.M., M. Falautano, C. Celico, V.M.), IRCCS San Raffaele Scientific Institute, Milan; University of Bari “Aldo Moro” (R.V.); Department of Medical and Surgical Sciences and Advanced Technologies (F.P., C. Chisari), GF Ingrassia, University of Catania; Department of Neurosciences (P.G., A.R.), Multiple Sclerosis Centre–Veneto Region (CeSMuV), University Hospital of Padua; CRESM Regional Reference Centre for Multiple Sclerosis (M.B., A.B.), San Luigi Gonzaga Hospital, Turin; Department of Biomedical Sciences and Human Oncology (M.S., M.T.), University of Bari Aldo Moro; Department of Human Neuroscience (C.P.), Sapienza University; Azienda Ospedaliera Sant’Andrea (V.B.), Sapienza University, Rome; Vita Salute San Raffaele University (G.C.), Multiple Sclerosis Centre ASST Valle Olona–Gallarate Hospital; San Raffaele Scientific Institute (M. Filippi), Vita-Salute San Raffaele University; Neurology Unit and MS Center (M. Filippi), IRCCS San Raffaele Scientific Institute, Neuroimaging Research Unit, Division of Neuroscience, Neurorehabilitation Unit and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan; and Department of Health Sciences (A.G.), University of Piemonte Orientale, Novara, Italy.
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Angelo Bellinvia
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Lorenzo Razzolini
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Luisa Pastò
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Benedetta Goretti
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Claudia Niccolai
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Mattia Fonderico
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Mauro Zaffaroni
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Lorena Pippolo
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Lucia Moiola
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Monica Falautano
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Claudia Celico
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Rossella Viterbo
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Francesco Patti
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Clara Chisari
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Paolo Gallo
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Alice Riccardi
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Martina Borghi
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Antonio Bertolotto
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Marta Simone
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Carlo Pozzilli
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Valentina Bianchi
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Marco Roscio
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Vittorio Martinelli
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Giancarlo Comi
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Massimo Filippi
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Maria Trojano
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Angelo Ghezzi
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Maria Pia Amato
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Long-term Cognitive Outcomes and Socioprofessional Attainment in People With Multiple Sclerosis With Childhood Onset
Emilio Portaccio, Angelo Bellinvia, Lorenzo Razzolini, Luisa Pastò, Benedetta Goretti, Claudia Niccolai, Mattia Fonderico, Mauro Zaffaroni, Lorena Pippolo, Lucia Moiola, Monica Falautano, Claudia Celico, Rossella Viterbo, Francesco Patti, Clara Chisari, Paolo Gallo, Alice Riccardi, Martina Borghi, Antonio Bertolotto, Marta Simone, Carlo Pozzilli, Valentina Bianchi, Marco Roscio, Vittorio Martinelli, Giancarlo Comi, Massimo Filippi, Maria Trojano, Angelo Ghezzi, Maria Pia Amato, MS Study Group of the Italian Neurological Society
Neurology Apr 2022, 98 (16) e1626-e1636; DOI: 10.1212/WNL.0000000000200115

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Abstract

Background and Objectives Patients with pediatric-onset multiple sclerosis (MS) can be especially vulnerable to cognitive impairment (CI) due to the onset of MS during a critical period for CNS development and maturation. The objective of this longitudinal study was to assess long-term cognitive functioning and socioprofessional attainment in the Italian pediatric MS cohort, previously assessed at baseline and 2 and 5 years.

Methods The 48 patients evaluated at the 5-year assessment were screened for inclusion. All participants were assessed with a cognitive test battery exploring 4 different cognitive abilities. Depression, fatigue, and socioprofessional attainment were also assessed. Mean cognitive z scores were calculated for the whole cohort, and their evolution over time was analyzed with an analysis of variance for repeated measurements test. Predictors of cognitive worsening or improvement were assessed with a linear mixed-model analysis.

Results Thirty-three participants were included (mean follow-up 12.8 ± 0.8 years). The global cognitive performance worsened at year 2 and improved at year 5, although the z score remained significantly lower than at baseline (−0.9 ± 1.2 vs −0.3 ± 0.9, p = 0.002). There was no significant variation between years 5 and 12 (−0.7 ± 1.1, p = 0.452). Higher IQ (>90) at baseline (effect 0.3, 95% CI 0.1–0.5, p = 0.017) and lower number of relapses in the 2 years before baseline (effect −0.1, 95% CI −0.1 to 0.1, p = 0.025) predicted better cognitive performances. Eighteen (54.5%) patients failed at least 2 tests compared with healthy controls and were defined as cognitively impaired. The presence of CI predicted worse socioprofessional attainment (β = 4.8, 95% CI 1.4–8.2, p = 0.008).

Discussion The longitudinal cognitive trajectory in pediatric-onset MS has a heterogeneous course over time, with a decline in the first years followed by a partial recovery over the long term. However, at the last follow-up evaluation, the proportion of impaired patients was more than double compared with baseline, with a negative impact on the individual’s socioprofessional attainment in adulthood. This study underscores how cognitive reserve may partially mitigate the negative effects of brain damage, highlighting the critical importance of intellectual enrichment early during the disease course.

Glossary

BRB-N=
Brief Repeatable Battery of Neuropsychological Tests;
CI=
cognitive impairment;
CR=
cognitive reserve;
DMT=
disease-modifying therapy;
EDSS=
Expanded Disability Status Scale;
FSS=
Fatigue Severity Scale;
HC=
healthy control;
IPS=
information processing speed;
MADRS=
Montgomery and Asberg Depression Rating Scale;
MS=
multiple sclerosis;
POMS=
pediatric-onset MS;
PwMS=
people with MS;
SPART=
Spatial Recall Test;
SRT=
Selective Reminding Test;
WSAS=
Work and Social Adjustment Scale

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally as first authors

  • ↵† These authors contributed equally as senior authors.

  • Received August 25, 2021.
  • Accepted in final form January 11, 2022.
  • © 2022 American Academy of Neurology
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