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Original research
MR T2-relaxation time as an indirect measure of brain water content and disease activity in NMOSD
  1. Laura Cacciaguerra1,2,3,
  2. Elisabetta Pagani1,
  3. Marta Radaelli2,
  4. Sarlota Mesaros4,
  5. Vittorio Martinelli2,
  6. Jovana Ivanovic4,
  7. Jelena Drulovic4,
  8. Massimo Filippi1,2,3,5,6,
  9. Maria A Rocca1,2,3
  1. 1 Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy
  2. 2 Neurology Unit, IRCCS Ospedale San Raffaele, Milano, Italy
  3. 3 Vita-Salute San Raffaele University, Milano, Italy
  4. 4 Clinic of Neurology, Faculty of Medicine, University of Belgrade, Beograd, Serbia
  5. 5 Nerorehabilitation Unit, IRCCS Ospedale San Raffaele, Milano, Italy
  6. 6 Neurophysiology Service, IRCCS Ospedale San Raffaele, Milano, Italy
  1. Correspondence to Maria A Rocca, Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy; rocca.mara{at}


Objective Since astrocytes at the blood–brain barrier are targeted by neuromyelitis optica spectrum disorder (NMOSD), this study aims to assess whether patients with NMOSD have a subclinical accumulation of brain water and if it differs according to disease activity.

Methods Seventy-seven aquaporin-4-positive patients with NMOSD and 105 healthy controls were enrolled at two European centres. Brain dual-echo turbo spin-echo MR images were evaluated and maps of T2 relaxation time (T2rt) in the normal-appearing white matter (NAWM), grey matter and basal ganglia were obtained. Patients with a clinical relapse within 1 month before or after MRI acquisition were defined ‘active’. Differences between patients and controls were assessed using z-scores of T2rt obtained with age-adjusted and sex-adjusted linear models from each site. A stepwise binary logistic regression was run on clinical and MRI variables to identify independent predictors of disease activity.

Results Patients had increased T2rt in both white and grey matter structures (p range: 0.014 to <0.0001). Twenty patients with NMOSD were defined active. Despite similar clinical and MRI features, active patients had a significantly increased T2rt in the NAWM and grey matter compared with those clinically stable (p range: 0.010–0.002). The stepwise binary logistic regression selected the NAWM as independently associated with disease activity (beta=2.06, SE=0.58, Nagelkerke R2=0.46, p<0.001).

Conclusions In line with the research hypothesis, patients with NMOSD have increased brain T2rt. The magnitude of this alteration might be useful for identifying those patients with active disease.

  • neuromyelitis optica spectrum disorders
  • MRI
  • water channel
  • astrocytopathy

Data availability statement

Data are available on reasonable request. The dataset used and analysed during the current study are available from the corresponding author on reasonable request.

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Data availability statement

Data are available on reasonable request. The dataset used and analysed during the current study are available from the corresponding author on reasonable request.

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  • Contributors LC, EP: Study concept, data analysis, statistical analysis, drafting/revising the manuscript. MR, VM, SM, JI and JD: Patient recruitment, clinical assessment, drafting/revising the manuscript. MF, MAR: Study concept, drafting/revising the manuscript. All authors have approved the final version of the manuscript. MAR acts as guarantor and accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests LC received speaker and consultant honoraria from ACCMED, Roche, BMS Celgene, and Sanofi. EP received speaker honoraria from Biogen Idec. MR reports no disclosures. SM has received grants or contracts from the Ministry of Education and Science, Republic of Serbia (Project 175031); and payment or honoraria for lectures, presentations, manuscript writing, or educational events from Merck Serono and Novartis; and support for attending meetings from Bayer, Genzyme Sanofi, Medis, Merck, and Schering. VM received honoraria for consulting services or speaking activity from Biogen, Merck, Novartis, TEVA, Almirall, and Sanofi. JI has nothing to report. JD has received travel support and/or research grants and/or lecture fees and/or advisory services from Novartis, Bayer, Merck, Sanofi Genzyme, Roche, Teva, Medis, Hemofarm, and Medtronic. MF is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). MAR received speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche and Teva, and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

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

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