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Neurite orientation dispersion and density imaging discloses early changes in the normal-appearing white matter in paediatric multiple sclerosis
  1. Monica Margoni1,2,
  2. Umberto Villani2,3,
  3. Livio Finos2,4,
  4. Silvia Franciotta1,
  5. Martina Rubin1,
  6. Margherita Nosadini5,6,
  7. Stefano Sartori5,6,
  8. Maria Giulia Anglani7,
  9. Francesco Causin7,
  10. Paola Perini1,
  11. Francesca Rinaldi1,
  12. Alessandra Bertoldo2,3,
  13. Paolo Gallo1,8
  1. 1Multiple Sclerosis Centre of the Veneto Region (CeSMuV), University Hospital of Padua, Padua, Italy
  2. 2Padova Neuroscience Centre (PNC), University of Padua, Padua, Italy
  3. 3Department of Information Engineering, University of Padua, Padua, Italy
  4. 4Department of Developmental Psychology and Socialisation, University of Padua, Padua, Italy
  5. 5Department of Women's and Children's Health, Paediatric Neurology and Neurophysiology Unit, University Hospital of Padua, Padua, Italy
  6. 6Neuroimmunology Group, Paediatric Research Institute "Città della Speranza", Padua, Italy
  7. 7Neuroradiology Unit, University Hospital of Padua, Padua, Italy
  8. 8Department of Neurosciences, Medical School, University of Padua, Padua, Italy
  1. Correspondence to Monica Margoni, Department of Neurosciences, University of Padua, Padova, Veneto 35122, Italy; monicamargoni{at}hotmail.com

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Introduction

Paediatric multiple sclerosis (pedMS) brain is known to be impacted by heightened inflammation and axonal degeneration.1 Structural changes in the normal-appearing white matter (NAWM) of pedMS have been disclosed by diffusion tensor imaging, further emphasising that MRI visible white matter (WM) lesions do not capture the full extent of tissue damage in MS.2 Understanding of the complexity of early brain pathology in pedMS can help to better characterise the relationship between inflammation and neurodegeneration in MS.

Neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, is a clinically feasible method for better capturing brain microstructural complexity in vivo.3 Specifically, NODDI provides quantitative measures including the neurite density index (NDI), considered a measure of neurites (ie, axons and dendrites) volume and orientation dispersion index (ODI), reflecting neurite orientation variability.

In this exploratory study, we applied NODDI to investigate the presence of early microstructural damage in pedMS compared with a matched group of healthy controls (HC), and its correlation with physical disability and WM lesion volume (LV) within tracts. A list of the acronyms used throughout the manuscript is provided in online supplemental table 1).

Supplemental material

[jnnp-2021-326355supp001.pdf]

Materials and methods

Subjects

Nineteen relapsing-remitting pedMS patients (aged ≤17 years) were prospectively enrolled in a single MS Centre between January 2019 and April 2021. Eight patients were treatment naïve; the remaining patients were in stable treatment with natalizumab. The median number of infusions at the time of MRI scan was 12 (IQR, 6–20). Twelve HC, balanced by age and sex, with no previous history of neurological dysfunction and a normal neurological examination, were also evaluated (see the online Supplemental Methods for pedMS inclusion criteria). All subjects underwent a detailed neurological evaluation, including Expanded Disability Status Scale (EDSS) score, within 1 week from the MRI acquisition.

MRI

The following sequences were acquired during a 3T …

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Footnotes

  • Contributors MM: drafting/revising the manuscript, study concept, and acquisition, analysis and interpretation of the data. UV and LF: drafting/revising the manuscript, analysis and interpretation of the data. SF, MR, MN, SS, MAG, FC, PP and FR: drafting/revising the manuscript and acquisition of the data. AB: drafting/revising the manuscript, acquisition and interpretation of the data and study supervisor. PG: drafting/revising the manuscript, study concept, acquisition and interpretation of the data and study supervisor.

  • Funding We thank Biogen for their financial support (no award/grant number).

  • Competing interests Monica Margoni reports grants and personal fees from Sanofi Genzyme, Merck Serono, Novartis and Almirall. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. Umberto Villani, Livio Finos, Silvia Franciotta, Martina Rubin, Margherita Nosadini, Stefano Sartori, Maria Giulia Anglani, Francesco Causin, Alessandra Bertoldo have nothing to disclose. Francesca Rinaldi reports grants and personal fees from Sanofi Genzyme, Merck Serono, Biogen and Novartis. Paola Perini reports grants and personal fees from Merck Serono, Biogen, Sanofi Genzyme, Roche, Bayer Schering Pharma and Novartis. Paolo Gallo reports grants and personal fees from Merck Serono, Biogen, Sanofi Genzyme, Roche, Bayer Schering Pharma, Novartis, University of Padua, Department of Neurosciences DNS, Veneto Region of Italy, Italian Association for Multiple Sclerosis (AISM) and Italian Ministry of Public Health.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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