Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

August 30, 2016; 87 (9 Supplement 2) Article

Consensus definitions for pediatric MS and other demyelinating disorders in childhood

Marc Tardieu, Brenda Banwell, Jerry S. Wolinsky, Daniela Pohl, Lauren B. Krupp
First published August 29, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002877
Marc Tardieu
From the National Reference Center for Inflammatory Diseases of the Brain (M.T.), Hôpitaux Universitaires Paris-Sud, University Paris-Sud, France; Perelman School of Medicine (B.B.), The Children's Hospital of Philadelphia, University of Pennsylvania; University of Texas Health Science Center at Houston (J.W.); Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Canada; and Lourie Center for Pediatric MS (L.B.K.), Stony Brook Children's, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brenda Banwell
From the National Reference Center for Inflammatory Diseases of the Brain (M.T.), Hôpitaux Universitaires Paris-Sud, University Paris-Sud, France; Perelman School of Medicine (B.B.), The Children's Hospital of Philadelphia, University of Pennsylvania; University of Texas Health Science Center at Houston (J.W.); Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Canada; and Lourie Center for Pediatric MS (L.B.K.), Stony Brook Children's, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jerry S. Wolinsky
From the National Reference Center for Inflammatory Diseases of the Brain (M.T.), Hôpitaux Universitaires Paris-Sud, University Paris-Sud, France; Perelman School of Medicine (B.B.), The Children's Hospital of Philadelphia, University of Pennsylvania; University of Texas Health Science Center at Houston (J.W.); Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Canada; and Lourie Center for Pediatric MS (L.B.K.), Stony Brook Children's, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniela Pohl
From the National Reference Center for Inflammatory Diseases of the Brain (M.T.), Hôpitaux Universitaires Paris-Sud, University Paris-Sud, France; Perelman School of Medicine (B.B.), The Children's Hospital of Philadelphia, University of Pennsylvania; University of Texas Health Science Center at Houston (J.W.); Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Canada; and Lourie Center for Pediatric MS (L.B.K.), Stony Brook Children's, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lauren B. Krupp
From the National Reference Center for Inflammatory Diseases of the Brain (M.T.), Hôpitaux Universitaires Paris-Sud, University Paris-Sud, France; Perelman School of Medicine (B.B.), The Children's Hospital of Philadelphia, University of Pennsylvania; University of Texas Health Science Center at Houston (J.W.); Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Canada; and Lourie Center for Pediatric MS (L.B.K.), Stony Brook Children's, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Consensus definitions for pediatric MS and other demyelinating disorders in childhood
Marc Tardieu, Brenda Banwell, Jerry S. Wolinsky, Daniela Pohl, Lauren B. Krupp
Neurology Aug 2016, 87 (9 Supplement 2) S8-S11; DOI: 10.1212/WNL.0000000000002877

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
4307

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

In light of the published 2012 International Pediatric Multiple Sclerosis Group definitions for pediatric multiple sclerosis (MS) and related disorders and given that pediatric-onset MS is now formally included in the 2010 McDonald criteria for MS, we sought to review these criteria and summarize their application in children with acquired CNS demyelination. In addition, proposals are made for definitions of no evidence of disease activity and inadequate treatment response that are important because of new therapeutic options and trials.

GLOSSARY

ADEM=
acute disseminated encephalomyelitis;
ARR=
annualized relapse rate;
CIS=
clinically isolated syndrome;
DIS=
dissemination of inflammatory lesions in space;
DIT=
dissemination of inflammatory lesions in time;
EDSS=
Expanded Disability Status Scale;
IPMSSG=
International Pediatric Multiple Sclerosis Study Group;
MOG=
myelin oligodendroglial glycoprotein;
MS=
multiple sclerosis;
NEDA=
no evidence of disease activity;
NMO=
neuromyelitis optica;
RIS=
radiologically isolated syndrome

The International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed definitions for pediatric multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and clinically isolated syndromes (CIS) to facilitate research providing consistency in terminology.1 In 2012, these definitions were revised to incorporate advances in research and to include components of the 2010 revision of the McDonald criteria.1,2 The cornerstone of a diagnosis of MS, both in adults and children, is the demonstration of dissemination of inflammatory lesions in space (DIS) and in time (DIT) in association with clinical symptoms consistent with acquired CNS demyelination and after the careful exclusion of numerous differential diagnoses. Incorporation of the 2010 McDonald criteria (that in addition to confirming relapsing-remitting MS diagnosis on the basis of new clinical or MRI disease activity over time, also permit MS diagnosis at the time of a first clinical MS attack if the MRI fulfils specific DIS and DIT criteria) to the revised IPMSSG definitions facilitated earlier diagnosis of pediatric MS and provided inclusion criteria for new therapeutic trials (table).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table

Summary of 2012 International Pediatric Multiple Sclerosis Study Group definitions for pediatric multiple sclerosis (MS) and immune-mediated CNS demyelinating disorders1

Our aim is to review application of the 2012 IPMSSG definitions in pediatric cohorts with acute demyelinating syndromes, discuss clinical scenarios that do not conform to the current definitions, suggest concepts regarding definition of adequate and inadequate treatment responses, and consider future research directions.

EVALUATIONS OF 2012 IPMSSG AND 2010 MCDONALD CRITERIA TO DIAGNOSE MS IN CHILDREN

Clinically isolated syndromes.

Five reports evaluated the accuracy of the 2010 McDonald criteria to diagnose MS in children, with similar results despite methodologic differences.3,–,7 At time of first CIS, after application of the 2010 McDonald criteria to the initial brain MRI, the diagnosis of MS was met in 53%–63% of the children who subsequently developed a clinical relapse. DIT was less frequently present at initial brain MRI than DIS, which was observed in more than 80% of children. Interestingly, the inclusion of spinal cord imaging did not increase accuracy of MS diagnosis.4,6 A follow-up MRI performed at 3 months, demonstrating new lesions, increased the identification of MS to 84%–100% of children who later had clinical relapse.4,6

Three points are discussed:

  1. The 2012 IPMSSG criteria (but not the Mc Donald 2010 criteria) required an age of 12 years or older for applying DIS and DIT criteria to diagnose MS at the time of the initial CIS.1 However, subsequent studies3,–,6 found that MS diagnostic criteria at CIS are applicable in younger children, provided that clinicians are aware that 2010 McDonald criteria have a lower positive predictive power and a higher false-positive rate.5 Documentation of new lesions on serial images or evidence of clinical relapses is strongly supportive of an MS diagnosis in all patients.

  2. The fulfilment of DIS and DIT: DIS criteria are not specific for MS, nor sufficient for MS diagnosis in absence of a clinically relevant history, even in patients who accrue new lesions on serial MRI scans. The diagnosis of MS should also not be made, even if lesions are numerous on the baseline scan, in absence of radiologic signs of DIT (enhancing and nonenhancing clinically silent lesions at baseline or a single new T2 lesion or enhancing lesion on a scan performed more than 30 days from baseline).2 In daily clinical practice, it has not yet been established when it is best to repeat an MRI after a first CIS for clinically stable patients. Two studies on follow-up MRI performed at 3 months3,6 suggest that this time interval is both efficient (most patients will be recognized) and safe (treatment will not be excessively delayed). As such, we recommend a repeat MRI 3 months after a diagnosis of pediatric CIS.

  3. Other diagnosis such as vasculitis might fulfil DIS and DIT criteria: a clinically relevant history is mandatory to diagnose MS.

Acute disseminated encephalomyelitis.

In children presenting with ADEM (in whom the presence of multiple lesions is likely to meet DIS and the presence of enhancing and nonenhancing lesions would also meet DIT), the criteria for a MS diagnosis using baseline DIT and DIS imaging criteria are not appropriate.5 As an ADEM-like attack is the first MS event in only 5%–15% of children,1 the diagnosis of MS in such children requires a second non-ADEM attack as well as either further MRI findings of clinically silent new lesions or a third attack also not meeting criteria for ADEM.

Radiologically isolated syndrome (RIS).

RIS refers to individuals with incidental MS-typical MRI findings in whom clinical history or signs of MS are lacking. The following adult criteria8 are believed to be appropriate for pediatric RIS but should be validated:

  1. MRI showing ovoid, well-circumscribed, and homogenous T2 hyperintensities fulfilling at least 3 Barkhof criteria (at least 1 gadolinium-enhancing lesion or 9 T2-hyperintense lesions; at least 1 infratentorial lesion; at least 1 juxtacortical lesion; at least 3 periventricular lesions).

  2. No historical account of remitting symptoms of neurologic dysfunction indicating MS.

  3. MRI findings do not account for symptoms for which the individual was imaged.

  4. MRI findings are not better explained by another disease process.

In adults, male sex and an MRI lesion in the spinal cord increase the likelihood that RIS will be associated with a subsequent clinical attack9 but data are lacking for children. Published experience of pediatric RIS is limited to 5 cases (2–13 years): none developed a clinical event during 5–15 years of follow-up.10 The prevalence of cognitive deficits in children with RIS is unknown but worthy of investigation as adults with RIS have a cognitive profile similar to those with remitting-relapsing MS.11

CNS-directed antibodies as potential biomarkers for distinct demyelinating disease phenotypes.

The identification of anti-aquaporin 4 antibodies as a relevant biomarker for neuromyelitis optica spectrum disorders emphasizes the potential for antibodies to aid in the diagnosis of CNS inflammatory disorders. Key considerations for antibodies as biomarkers include (1) fidelity with clinical features (see chapter 9); (2) persistent detection if such persistence distinguishes a specific disorder from transient immune recognition of multiple CNS antigens; and (3) pathogenicity of the antibodies within the CNS (required if the antibodies are thought to contribute to the disease directly). The assays used to measure antibodies must also be carefully validated (the increased sensitivity of cell-based assays now used for detection of aquaporin-4 antibodies emphasizes this point).

Anti–myelin oligodendroglial glycoprotein (MOG) antibodies have been detected in 18%–35% of children with a first acute episode of inflammatory demyelination12,–,14 (see “Immunopathophysiology of pediatric CNS inflammatory demyelinating disease” on page S12). The transient detection of anti-MOG antibodies is more frequent in children at onset of ADEM, optic neuritis, and relapsing optic neuritis, and anti-MOG positivity predicts a non-MS disease course.13,–,16 MOG-positive children have clinical and radiologic features typical for ADEM and elevated lymphocyte counts in CSF, suggesting a high degree of inflammation.16,17 Persistence of anti-MOG antibodies has been associated with MS, although fewer than 25% of pediatric patients with MS have detectable anti-MOG antibodies.12 Demonstrating the pathogenicity of anti-MOG antibodies and following larger cohorts of pediatric patients who have been tested for them are needed for the presence of MOG antibodies to serve as a disease-specific biomarker and to guide patient care.

DEFINITION OF NO EVIDENCE OF DISEASE ACTIVITY (NEDA) IN PEDIATRIC MS

With multiple effective MS therapies, NEDA has become an MS treatment goal.18,19 Whether the definition of inactive disease should focus solely on inflammatory disease activity or also include brain volume changes, cognition, or other measures remains unresolved.20,–,22 Defining the more global aspects of MS effect, such as the effect on brain growth, is even more challenging for pediatric than adult MS, since estimations of pathologic brain volume changes during development will require complex algorithms that incorporate expected physiologic brain growth.23,24 Incorporating the effects of MS on cognitive development is also difficult.25 Although specific pediatric NEDA criteria are still under development, the authors agree that the following elements are critical—absence of new, enlarging, or enhancing lesions on MRI; clinical relapses; and confirmed disability progression—and suggest that consideration be given to preservation of age-expected global and regional brain growth and to age-expected cognitive maturation and function.

DEFINITION OF TREATMENT RESPONSE

Clinical relapse remains the gold standard metric for relapsing-remitting MS disease activity, and is a required primary endpoint for Food and Drug Administration–supported clinical trials in MS. Treatment-naive pediatric patients with MS have an annualized relapse rate of 0.9–3.2 in the first 2 years following the first attack and of 0.5–0.8 in the next 3–5 years.26,27 Assuming that first-line disease-modifying therapies in children should provide a reduction in relapses similar to the 30%–40% observed in adults, a treatment goal would be to initially achieve an annualized relapse rate (ARR) lower than 0.6 relapses per year (or roughly 1 relapse over the first 2 years of disease) and ≤0.35 between years 2–5 post disease onset.26,27 Treatment benefit in adult MS trials often includes absence of sustained Expanded Disability Status Scale (EDSS) increase. This metric is less appropriate in pediatric-onset MS as EDSS rarely worsens during the first 10 years following disease onset.28 Reduction in new T2-bright or gadolinium-enhancing T1-dark lesions on MRI is another possible measure of treatment benefit that can be used in children since a serial MRI study of pediatric patients with MS showed a mean of 9 new lesions 6 months following the first attack.29

A proposed definition for an inadequate treatment response (in a fully compliant patient) is an increase or lack of reduction in ARR, 2 or more gadolinium-enhancing lesions on MRI or accrual of more than 2 new lesions when compared to the pretreatment period, and 2 or more confirmed relapses within a 12-month period or less.30

Cognitive impairment, fatigue, and emotional health are important MS symptoms that should be considered when deciding to start or change MS treatment.

PERSPECTIVES

We propose to incorporate in IPMSSG criteria the 2010 McDonald criteria for MS for children of all ages when MRI-defined DIT and DIS requirements for MS are present at the first attack provided the sentinel event is consistent with acute demyelination and the attack does not conform to the criteria of ADEM. All other definitions are unchanged, except for the NMO spectrum disorders (See “Neuromyelitis optica sectrum disorders in children and adolescent” on page S59). Future goals are to better define reliable prognostic markers to define subgroups of patients and better understand and measure the degenerative component of MS in children, particularly in reference to cognitive functioning, age-expected brain growth, and diffuse neural networks.

AUTHOR CONTRIBUTIONS

All authors contributed to the elaboration of the content and revised the manuscript equally.

STUDY FUNDING

This supplement is made possible by funding from the MS Cure Fund, Danish MS Society, German MS Society, Italian MS Association, MS International Federation, MS Research Foundation (Netherlands), National MS Society (USA) and Swiss MS Society.

DISCLOSURE

M. Tardieu received honoraria or consultation fees from Novartis, Sanofi, Teva, and Biogen. B. Banwell serves as a central MRI reviewer for a clinical trial for Novartis. J. Wolinsky and D. Pohl report no disclosures relevant to the manuscript. L. Krupp received honoraria or consultation fees from Biogen, Novartis, Teva Neurosciences, Pfizer, Projects in Knowledge, Providence Health Services, and Multicell; royalty payments from Avanir Pharmaceuticals, Abbvie Inc., Osmotica Pharmaceutical Corp., and Demos Medical Publishing; and received research funding from Novartis, Teva Neurosciences, Biogen Idec, Genentech, National Multiple Sclerosis Society, Department of Defense, National Institutes of Health, and the Lourie Foundation. Go to Neurology.org for full disclosures.

Footnotes

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

  • Received August 19, 2015.
  • Accepted in final form March 1, 2016.
  • © 2016 American Academy of Neurology

REFERENCES

  1. 1.↵
    1. Krupp LB,
    2. Tardieu M,
    3. Amato MP, et al.
    International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 2013;19:1261–1267.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Poman CH,
    2. Reingold SC,
    3. Banwell B, et al.
    Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292–302.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Sedani S,
    2. Lim MJ,
    3. Hemingway C,
    4. Wassmer E,
    5. Absoud M
    . Paediatric multiple sclerosis: examining utility of the McDonald 2010 criteria. Mult Scler 2012;18:679–682.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Kornek B,
    2. Schmitl B,
    3. Vass K, et al.
    Evaluation of the 2010 McDonald multiple sclerosis criteria in children with a clinically isolated syndrome. Mult Scler 2012;18:1768–1774.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Sadaka Y,
    2. Verhey LH,
    3. Shroff MM, et al.
    2010 McDonald criteria for diagnosing pediatric multiple sclerosis. Ann Neurol 2012;72:211–223.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Hummel H-M,
    2. Brück W,
    3. Dreha-Kulaczewski S,
    4. Gärtner J,
    5. Wuerfel J
    . Pediatric onset multiple sclerosis: McDonald criteria 2010 and the contribution of spinal cord MRI. Mult Scler 2013;19:1330–1335.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Williams MT,
    2. Tapos DO,
    3. Juhasz C
    . Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly Black cohort. Pediatr Neurol 2014;51:826–830.
    OpenUrlPubMed
  8. 8.↵
    1. Okuda DT,
    2. Mowry EM,
    3. Beheshtian A, et al.
    Incidental MRI anomalies suggestive of multiple sclerosis: radiologically isolated syndrome. Neurology 2009;72:800–805.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Okuda DT,
    2. Siva A,
    3. Kantarci O, et al.
    Radiologically isolated syndrome: 5-year risk for an initial clinical event. PloS One 2014;9:e90509.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Eraksoy M,
    2. Yapici Z,
    3. Tekturk P,
    4. Kurtuncu M,
    5. Ozcan H
    . Radiologically isolated syndrome in children: report of 5 children with long-term follow-up. Neurology 2014;82(suppl):P2.243.
    OpenUrl
  11. 11.↵
    1. Lebrun C,
    2. Blanc F,
    3. Brassat D, et al.
    On behalf of CFSEP cognitive function in radiologically isolated syndrome. Mult Scler 2010;16:919–925.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Pröbstel AK,
    2. Dormair K,
    3. Bittner R, et al.
    Antibodies to MOG are transient in childhood ADEM. Neurology 2011;77:580–588.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Hacohen Y,
    2. Absoud M,
    3. Deiva K, et al.
    Myelin oligodendrocytes glycoprotein antibodies predict a non-MS demyelination course in children. Neurol Neuroimmunol Neuroinflamm 2015;2:e81.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Ketelslegers IA,
    2. VanPelt DE,
    3. Bryde S, et al.
    Anti-MOG antibodies plead against MS diagnosis in an acquired demyelinating syndromes cohort. Mult Scler 2015;12:1513–1520.
    OpenUrl
  15. 15.↵
    1. Reindl M,
    2. Rostasy K
    . MOG antibody-associated diseases. Neurol Neuroimmunol Neuroinflamm 2015;2:e60.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Fernandez-Carbonell C,
    2. Vargas-Lowy D,
    3. Masallam A, et al.
    Clinical and MRI phenotype of children with MOG. Mult Scler 2016;22:2174–2184.
    OpenUrl
  17. 17.↵
    1. Baumann M,
    2. Sahin K,
    3. Lechner C, et al.
    Clinical and neuroradiological differences of paediatric acute dissemination encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry 2015;86:265–272.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Bevan CJ,
    2. Cree BA
    . Disease activity free status: a new end point for a new era in multiple sclerosis clinical research? JAMA Neurol 2014;71:269–270.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Stangel M,
    2. Penner IK,
    3. Kallmann BA,
    4. Lukas C,
    5. Kieseier BC
    . Towards the Implementation of “no evidence of disease activity” in multiple sclerosis treatment: the multiple sclerosis decision model. Ther Adv Neurol Disord 2015;8:3–13.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Havrdova E,
    2. Galetta S,
    3. Stefoski D,
    4. Comi G
    . Freedom from disease activity in multiple sclerosis. Neurology 2010;74(suppl 3):S3–S7.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Lublin F
    . Disease activity free Status in MS. Mult Scler Relat Dis 2012;1:6–7.
    OpenUrlCrossRef
  22. 22.↵
    1. Rotstein D,
    2. Healy BC,
    3. Malik MT,
    4. Chitnis T,
    5. Weiner HL
    . Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol 2015;72:152–158.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Aubert-Broche B,
    2. Fonov V,
    3. Narayanan S, et al.
    Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth. Neurology 2014;83:2140–2146.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Mesaros S,
    2. Rocca MA,
    3. Absinta M, et al.
    Evidence of thalamic gray matter loss in pediatric multiple sclerosis. Neurology 2008;70:1107–1112.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Amato MP,
    2. Goretti B,
    3. Ghezzi A, et al.
    Neuropsychological features in childhood and juvenile multiple sclerosis: five-year follow-up. Neurology 2014;83:1432–1438.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Chitnis T,
    2. Tardieu M,
    3. Amato MP, et al.
    International Pediatric MS Study Group clinical trials summit. Neurology 2013;80:1161–1168.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Banwell B,
    2. Bar-Or A,
    3. Giovannoni G, et al.
    Therapies for multiple sclerosis: considerations in the pediatric patient. Nat Rev Neurol 2011;7:109–122.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Renoux C,
    2. Vukusic S,
    3. Mikaeloff Y, et al.
    Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007;356:2603–2613.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Verhey LH,
    2. Branson HM,
    3. Shroff MM, et al.
    MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study. Lancet Neurol 2011;10:1065–1073.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Chitnis T,
    2. Tenembaum S,
    3. Banwell B, et al.
    Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler 2012;18:116–127.
    OpenUrlAbstract/FREE Full Text

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • GLOSSARY
    • EVALUATIONS OF 2012 IPMSSG AND 2010 MCDONALD CRITERIA TO DIAGNOSE MS IN CHILDREN
    • DEFINITION OF NO EVIDENCE OF DISEASE ACTIVITY (NEDA) IN PEDIATRIC MS
    • DEFINITION OF TREATMENT RESPONSE
    • PERSPECTIVES
    • AUTHOR CONTRIBUTIONS
    • STUDY FUNDING
    • DISCLOSURE
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Disclosures
Advertisement

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials

Dr. Nicole Sur and Dr. Mausaminben Hathidara

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Multiple sclerosis
  • Acute disseminated encephalomyelitis

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Article
    MRI in the evaluation of pediatric multiple sclerosis
    Brenda Banwell, Douglas L. Arnold, Jan-Mendelt Tillema et al.
    Neurology, August 29, 2016
  • Article
    International Pediatric MS Study Group Global Members Symposium report
    Evangeline Wassmer, Tanuja Chitnis, Daniela Pohl et al.
    Neurology, August 29, 2016
  • Introduction
    Pediatric demyelinating disorders
    Global updates, controversies, and future directions
    Tanuja Chitnis, Daniela Pohl et al.
    Neurology, August 29, 2016
  • Articles
    Challenges in the classification of pediatric multiple sclerosis and future directions
    Anita L. Belman, Tanuja Chitnis, Christel Renoux et al.
    Neurology, April 16, 2007
Neurology: 100 (22)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise