Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis
Objective This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. Methods Prospectively collected clinical information from Italian Multiple Scl...
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Veröffentlicht in: | Annals of neurology 2022-04, Vol.91 (4), p.483-495 |
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creator | De Meo, Ermelinda Filippi, Massimo Trojano, Maria Comi, Giancarlo Patti, Francasco Brescia Morra, Vincenzo Salemi, Giuseppe Onofrj, Marco Lus, Giacomo Cocco, Eleonora Fonderico, Mattia Torri Clerici, Valentina Maniscalco, Giorgia Teresa Valentino, Paola Bertolotto, Antonio Lugaresi, Alessandra Bergamaschi, Roberto Rovaris, Marco Sola, Patrizia Tedeschi, Gioacchino Pesci, Ilaria Aguglia, Umberto Cavalla, Paola Maimone, Davide Granella, Franco Vianello, Marika Simone, Marta Portaccio, Emilio Amato, Maria Pia |
description | Objective
This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis.
Methods
Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease‐modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated.
Results
A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease‐modifying treatment exposure were independent predictors for long‐term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long‐term disability.
Interpretation
These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022;91:483–495 |
doi_str_mv | 10.1002/ana.26322 |
format | Article |
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This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis.
Methods
Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease‐modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated.
Results
A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease‐modifying treatment exposure were independent predictors for long‐term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long‐term disability.
Interpretation
These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022;91:483–495</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.26322</identifier><identifier>PMID: 35150168</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Autoimmune diseases ; Brain stem ; Child ; Demyelination ; Disabled Persons ; Disease Progression ; Humans ; Male ; Medical prognosis ; Multiple sclerosis ; Multiple Sclerosis - diagnosis ; Multiple Sclerosis - epidemiology ; Multiple Sclerosis - therapy ; Neuritis ; Optic neuritis ; Patients ; Pediatrics ; Phenotypes ; Prognosis ; Recurrence ; Risk assessment ; Signs and symptoms</subject><ispartof>Annals of neurology, 2022-04, Vol.91 (4), p.483-495</ispartof><rights>2022 American Neurological Association.</rights><rights>2022 American Neurological Association</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-914f905267ac2283767da1c1aab8aaadb40fc6c0ec777693c6fd2a8cd0b7c8c23</citedby><cites>FETCH-LOGICAL-c3532-914f905267ac2283767da1c1aab8aaadb40fc6c0ec777693c6fd2a8cd0b7c8c23</cites><orcidid>0000-0001-5531-1111 ; 0000-0002-6923-0846 ; 0000-0002-6989-1054 ; 0000-0002-5485-0479 ; 0000-0002-9662-1762</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.26322$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.26322$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35150168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Meo, Ermelinda</creatorcontrib><creatorcontrib>Filippi, Massimo</creatorcontrib><creatorcontrib>Trojano, Maria</creatorcontrib><creatorcontrib>Comi, Giancarlo</creatorcontrib><creatorcontrib>Patti, Francasco</creatorcontrib><creatorcontrib>Brescia Morra, Vincenzo</creatorcontrib><creatorcontrib>Salemi, Giuseppe</creatorcontrib><creatorcontrib>Onofrj, Marco</creatorcontrib><creatorcontrib>Lus, Giacomo</creatorcontrib><creatorcontrib>Cocco, Eleonora</creatorcontrib><creatorcontrib>Fonderico, Mattia</creatorcontrib><creatorcontrib>Torri Clerici, Valentina</creatorcontrib><creatorcontrib>Maniscalco, Giorgia Teresa</creatorcontrib><creatorcontrib>Valentino, Paola</creatorcontrib><creatorcontrib>Bertolotto, Antonio</creatorcontrib><creatorcontrib>Lugaresi, Alessandra</creatorcontrib><creatorcontrib>Bergamaschi, Roberto</creatorcontrib><creatorcontrib>Rovaris, Marco</creatorcontrib><creatorcontrib>Sola, Patrizia</creatorcontrib><creatorcontrib>Tedeschi, Gioacchino</creatorcontrib><creatorcontrib>Pesci, Ilaria</creatorcontrib><creatorcontrib>Aguglia, Umberto</creatorcontrib><creatorcontrib>Cavalla, Paola</creatorcontrib><creatorcontrib>Maimone, Davide</creatorcontrib><creatorcontrib>Granella, Franco</creatorcontrib><creatorcontrib>Vianello, Marika</creatorcontrib><creatorcontrib>Simone, Marta</creatorcontrib><creatorcontrib>Portaccio, Emilio</creatorcontrib><creatorcontrib>Amato, Maria Pia</creatorcontrib><title>Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis.
Methods
Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease‐modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated.
Results
A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease‐modifying treatment exposure were independent predictors for long‐term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long‐term disability.
Interpretation
These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022;91:483–495</description><subject>Autoimmune diseases</subject><subject>Brain stem</subject><subject>Child</subject><subject>Demyelination</subject><subject>Disabled Persons</subject><subject>Disease Progression</subject><subject>Humans</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - diagnosis</subject><subject>Multiple Sclerosis - epidemiology</subject><subject>Multiple Sclerosis - therapy</subject><subject>Neuritis</subject><subject>Optic neuritis</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Recurrence</subject><subject>Risk assessment</subject><subject>Signs and symptoms</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10EFLwzAYxvEgipvTg19AAl700O1N0qbtcYzphLkJ6rm8S1PJyNqZtMi-vdFND4KnXH78efMQcslgyAD4CGsccik4PyJ9lggWZTzOj0kfhIyjhIm4R868XwNALhmckp5IWAJMZn2ymDSbLTpTv9EFtp1DS2fGt43b0aaiU3R2R7Eu6RxbTZe11y190qXB1hlFHzvbmq3V9FlZ7Rpv_Dk5qdB6fXF4B-T1bvoymUXz5f3DZDyPlEgEj3IWVzkkXKaoOM9EKtMSmWKIqwwRy1UMlZIKtErTVOZCyarkmKkSVqnKFBcDcrPvbl3z3mnfFhvjlbYWa910vuAyVAHiRAZ6_Yeum87V4bqgYsjSDPI8qNu9UuEf3umq2DqzQbcrGBRfIxdh5OJ75GCvDsVutdHlr_xZNYDRHnwYq3f_l4rxYrxPfgL8CYS_</recordid><startdate>202204</startdate><enddate>202204</enddate><creator>De Meo, Ermelinda</creator><creator>Filippi, Massimo</creator><creator>Trojano, Maria</creator><creator>Comi, Giancarlo</creator><creator>Patti, Francasco</creator><creator>Brescia Morra, Vincenzo</creator><creator>Salemi, Giuseppe</creator><creator>Onofrj, Marco</creator><creator>Lus, Giacomo</creator><creator>Cocco, Eleonora</creator><creator>Fonderico, Mattia</creator><creator>Torri Clerici, Valentina</creator><creator>Maniscalco, Giorgia Teresa</creator><creator>Valentino, Paola</creator><creator>Bertolotto, Antonio</creator><creator>Lugaresi, Alessandra</creator><creator>Bergamaschi, Roberto</creator><creator>Rovaris, Marco</creator><creator>Sola, Patrizia</creator><creator>Tedeschi, Gioacchino</creator><creator>Pesci, Ilaria</creator><creator>Aguglia, Umberto</creator><creator>Cavalla, Paola</creator><creator>Maimone, Davide</creator><creator>Granella, Franco</creator><creator>Vianello, Marika</creator><creator>Simone, Marta</creator><creator>Portaccio, Emilio</creator><creator>Amato, Maria Pia</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5531-1111</orcidid><orcidid>https://orcid.org/0000-0002-6923-0846</orcidid><orcidid>https://orcid.org/0000-0002-6989-1054</orcidid><orcidid>https://orcid.org/0000-0002-5485-0479</orcidid><orcidid>https://orcid.org/0000-0002-9662-1762</orcidid></search><sort><creationdate>202204</creationdate><title>Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis</title><author>De Meo, Ermelinda ; Filippi, Massimo ; Trojano, Maria ; Comi, Giancarlo ; Patti, Francasco ; Brescia Morra, Vincenzo ; Salemi, Giuseppe ; Onofrj, Marco ; Lus, Giacomo ; Cocco, Eleonora ; Fonderico, Mattia ; Torri Clerici, Valentina ; Maniscalco, Giorgia Teresa ; Valentino, Paola ; Bertolotto, Antonio ; Lugaresi, Alessandra ; Bergamaschi, Roberto ; Rovaris, Marco ; Sola, Patrizia ; Tedeschi, Gioacchino ; Pesci, Ilaria ; Aguglia, Umberto ; Cavalla, Paola ; Maimone, Davide ; Granella, Franco ; Vianello, Marika ; Simone, Marta ; Portaccio, Emilio ; Amato, Maria Pia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-914f905267ac2283767da1c1aab8aaadb40fc6c0ec777693c6fd2a8cd0b7c8c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Autoimmune diseases</topic><topic>Brain stem</topic><topic>Child</topic><topic>Demyelination</topic><topic>Disabled Persons</topic><topic>Disease Progression</topic><topic>Humans</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - diagnosis</topic><topic>Multiple Sclerosis - epidemiology</topic><topic>Multiple Sclerosis - therapy</topic><topic>Neuritis</topic><topic>Optic neuritis</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Recurrence</topic><topic>Risk assessment</topic><topic>Signs and symptoms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Meo, Ermelinda</creatorcontrib><creatorcontrib>Filippi, Massimo</creatorcontrib><creatorcontrib>Trojano, Maria</creatorcontrib><creatorcontrib>Comi, Giancarlo</creatorcontrib><creatorcontrib>Patti, Francasco</creatorcontrib><creatorcontrib>Brescia Morra, Vincenzo</creatorcontrib><creatorcontrib>Salemi, Giuseppe</creatorcontrib><creatorcontrib>Onofrj, Marco</creatorcontrib><creatorcontrib>Lus, Giacomo</creatorcontrib><creatorcontrib>Cocco, Eleonora</creatorcontrib><creatorcontrib>Fonderico, Mattia</creatorcontrib><creatorcontrib>Torri Clerici, Valentina</creatorcontrib><creatorcontrib>Maniscalco, Giorgia Teresa</creatorcontrib><creatorcontrib>Valentino, Paola</creatorcontrib><creatorcontrib>Bertolotto, Antonio</creatorcontrib><creatorcontrib>Lugaresi, Alessandra</creatorcontrib><creatorcontrib>Bergamaschi, Roberto</creatorcontrib><creatorcontrib>Rovaris, Marco</creatorcontrib><creatorcontrib>Sola, Patrizia</creatorcontrib><creatorcontrib>Tedeschi, Gioacchino</creatorcontrib><creatorcontrib>Pesci, Ilaria</creatorcontrib><creatorcontrib>Aguglia, Umberto</creatorcontrib><creatorcontrib>Cavalla, Paola</creatorcontrib><creatorcontrib>Maimone, Davide</creatorcontrib><creatorcontrib>Granella, Franco</creatorcontrib><creatorcontrib>Vianello, Marika</creatorcontrib><creatorcontrib>Simone, Marta</creatorcontrib><creatorcontrib>Portaccio, Emilio</creatorcontrib><creatorcontrib>Amato, Maria Pia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Meo, Ermelinda</au><au>Filippi, Massimo</au><au>Trojano, Maria</au><au>Comi, Giancarlo</au><au>Patti, Francasco</au><au>Brescia Morra, Vincenzo</au><au>Salemi, Giuseppe</au><au>Onofrj, Marco</au><au>Lus, Giacomo</au><au>Cocco, Eleonora</au><au>Fonderico, Mattia</au><au>Torri Clerici, Valentina</au><au>Maniscalco, Giorgia Teresa</au><au>Valentino, Paola</au><au>Bertolotto, Antonio</au><au>Lugaresi, Alessandra</au><au>Bergamaschi, Roberto</au><au>Rovaris, Marco</au><au>Sola, Patrizia</au><au>Tedeschi, Gioacchino</au><au>Pesci, Ilaria</au><au>Aguglia, Umberto</au><au>Cavalla, Paola</au><au>Maimone, Davide</au><au>Granella, Franco</au><au>Vianello, Marika</au><au>Simone, Marta</au><au>Portaccio, Emilio</au><au>Amato, Maria Pia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2022-04</date><risdate>2022</risdate><volume>91</volume><issue>4</issue><spage>483</spage><epage>495</epage><pages>483-495</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis.
Methods
Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease‐modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated.
Results
A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease‐modifying treatment exposure were independent predictors for long‐term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long‐term disability.
Interpretation
These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022;91:483–495</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>35150168</pmid><doi>10.1002/ana.26322</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5531-1111</orcidid><orcidid>https://orcid.org/0000-0002-6923-0846</orcidid><orcidid>https://orcid.org/0000-0002-6989-1054</orcidid><orcidid>https://orcid.org/0000-0002-5485-0479</orcidid><orcidid>https://orcid.org/0000-0002-9662-1762</orcidid></addata></record> |
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subjects | Autoimmune diseases Brain stem Child Demyelination Disabled Persons Disease Progression Humans Male Medical prognosis Multiple sclerosis Multiple Sclerosis - diagnosis Multiple Sclerosis - epidemiology Multiple Sclerosis - therapy Neuritis Optic neuritis Patients Pediatrics Phenotypes Prognosis Recurrence Risk assessment Signs and symptoms |
title | Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis |
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