MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis

Laura Clarke¹, Simon Arnett¹, Wajih Bukhari¹, Elham Khalilidehkordi¹, Sofia Jimenez Sanchez¹, Cullen O'Gorman¹, Jing Sun¹, Kerri M Prain², Mark Woodhall³, Roger Silvestrini⁴, Christine S Bundell⁵, David A Abernethy⁶, Sandeep Bhuta¹, Stefan Blum⁷, Mike Boggild⁸, Karyn Boundy⁹, Bruce J Brew¹⁰, Wallace Brownlee¹¹, Helmut Butzkueven¹², William M Carroll¹³, Cella Chen¹⁴, Alan Coulthard¹⁵, Russell C Dale¹⁶, Chandi Das¹⁷, Marzena J Fabis-Pedrini¹³, David Gillis¹⁵, Simon Hawke¹⁸, Robert Heard¹⁶, Andrew P D Henderson¹⁹, Saman Heshmat¹, Suzanne Hodgkinson²⁰, Trevor J Kilpatrick²¹, John King²², Christopher Kneebone²³, Andrew J Kornberg²⁴, Jeannette Lechner-Scott²⁵, Ming-Wei Lin¹⁸, Christopher Lynch²⁶, Richard A L Macdonell²⁷, Deborah F Mason²⁸, Pamela A McCombe²⁹, Jennifer Pereira²⁶, John D Pollard¹⁸, Sudarshini Ramanathan^{30

31}, Stephen W Reddel¹⁶, Cameron P Shaw³², Judith M Spies¹⁸, James Stankovich³³, Ian Sutton³⁴, Steve Vucic¹⁹, Michael Walsh⁷, Richard C Wong¹⁵, Eppie M Yiu²⁴, Michael H Barnett¹⁶, Allan G K Kermode¹³, Mark P Marriott¹², John D E Parratt¹⁸, Mark Slee⁹, Bruce V Taylor³³, Ernest Willoughby¹¹, Fabienne Brilot^{16

30}, Angela Vincent³, Patrick Waters³, Simon A Broadley^{1

35}

Affiliations

¹ Menzies Health Institute Queensland, Gold Coast, Griffith University, Southport, QLD, Australia.
² Department of Immunology, Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
³ Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
⁴ Department of Immunopathology, Westmead Hospital, Westmead, NSW, Australia.
⁵ School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia.
⁶ Department of Neurology, Wellington Hospital, Newtown, New Zealand.
⁷ Department of Neurology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
⁸ Department of Neurology, Townsville Hospital, Douglas, QLD, Australia.
⁹ Department of Neurology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.
¹⁰ Centre for Applied Medical Research, St. Vincent's Hospital, University of New South Wales, Darlinghurst, NSW, Australia.
¹¹ Department of Neurology, Auckland City Hospital, Grafton, New Zealand.
¹² Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
¹³ Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre, Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia.
¹⁴ Department of Ophthalmology, Flinders Medical Centre, Flinders University, Bedford Park, SA, Australia.
¹⁵ School of Medicine, Royal Brisbane and Women's Hospital, University of Queensland, Herston, QLD, Australia.
¹⁶ Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
¹⁷ Department of Neurology, Canberra Hospital, Garran, ACT, Australia.
¹⁸ Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, NSW, Australia.
¹⁹ Department of Neurology, Westmead Hospital, Westmead, NSW, Australia.
²⁰ South Western Sydney Medical School, Liverpool Hospital, University of New South Wales, Liverpool, NSW, Australia.
²¹ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
²² Department of Neurology, Royal Melbourne Hospital, Parkville, VIC, Australia.
²³ Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia.
²⁴ School of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, VIC, Australia.
²⁵ Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, Australia.
²⁶ School of Medicine, University of Auckland, Grafton, New Zealand.
²⁷ Department of Neurology, Austin Health, Heidelberg, VIC, Australia.
²⁸ Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
²⁹ Centre for Clinical Research, Royal Brisbane and Women's Hospital, University of Queensland, Herston, QLD, Australia.
³⁰ Neuroimmunology Group, Kids Neurosciences Centre, Children's Hospital at Westmead, University of Sydney, Westmead, NSW, Australia.
³¹ Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, Australia.
³² School of Medicine, Deakin University, Waurn Ponds, VIC, Australia.
³³ Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia.
³⁴ Department of Neurology, St. Vincent's Hospital, Darlinghurst, NSW, Australia.
³⁵ Department of Neurology, Gold Coast University Hospital, Southport, QLD, Australia.

PMID: 34566866
PMCID: PMC8458658
DOI: 10.3389/fneur.2021.722237

MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis

Laura Clarke et al. Front Neurol. 2021.

. 2021 Sep 9:12:722237.

doi: 10.3389/fneur.2021.722237. eCollection 2021.

Authors

Affiliations

¹ Menzies Health Institute Queensland, Gold Coast, Griffith University, Southport, QLD, Australia.
² Department of Immunology, Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
³ Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
⁴ Department of Immunopathology, Westmead Hospital, Westmead, NSW, Australia.
⁵ School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia.
⁶ Department of Neurology, Wellington Hospital, Newtown, New Zealand.
⁷ Department of Neurology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
⁸ Department of Neurology, Townsville Hospital, Douglas, QLD, Australia.
⁹ Department of Neurology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.
¹⁰ Centre for Applied Medical Research, St. Vincent's Hospital, University of New South Wales, Darlinghurst, NSW, Australia.
¹¹ Department of Neurology, Auckland City Hospital, Grafton, New Zealand.
¹² Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
¹³ Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre, Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, WA, Australia.
¹⁴ Department of Ophthalmology, Flinders Medical Centre, Flinders University, Bedford Park, SA, Australia.
¹⁵ School of Medicine, Royal Brisbane and Women's Hospital, University of Queensland, Herston, QLD, Australia.
¹⁶ Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
¹⁷ Department of Neurology, Canberra Hospital, Garran, ACT, Australia.
¹⁸ Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, NSW, Australia.
¹⁹ Department of Neurology, Westmead Hospital, Westmead, NSW, Australia.
²⁰ South Western Sydney Medical School, Liverpool Hospital, University of New South Wales, Liverpool, NSW, Australia.
²¹ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
²² Department of Neurology, Royal Melbourne Hospital, Parkville, VIC, Australia.
²³ Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia.
²⁴ School of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, VIC, Australia.
²⁵ Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, Australia.
²⁶ School of Medicine, University of Auckland, Grafton, New Zealand.
²⁷ Department of Neurology, Austin Health, Heidelberg, VIC, Australia.
²⁸ Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
²⁹ Centre for Clinical Research, Royal Brisbane and Women's Hospital, University of Queensland, Herston, QLD, Australia.
³⁰ Neuroimmunology Group, Kids Neurosciences Centre, Children's Hospital at Westmead, University of Sydney, Westmead, NSW, Australia.
³¹ Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, Australia.
³² School of Medicine, Deakin University, Waurn Ponds, VIC, Australia.
³³ Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia.
³⁴ Department of Neurology, St. Vincent's Hospital, Darlinghurst, NSW, Australia.
³⁵ Department of Neurology, Gold Coast University Hospital, Southport, QLD, Australia.

PMID: 34566866
PMCID: PMC8458658
DOI: 10.3389/fneur.2021.722237

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), "bright spotty" (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS.

Keywords: NMOSD; diagnosis; magnetic resonance imaging; multiple sclerosis; neuromyelitis optica.

Copyright © 2021 Clarke, Arnett, Bukhari, Khalilidehkordi, Jimenez Sanchez, O'Gorman, Sun, Prain, Woodhall, Silvestrini, Bundell, Abernethy, Bhuta, Blum, Boggild, Boundy, Brew, Brownlee, Butzkueven, Carroll, Chen, Coulthard, Dale, Das, Fabis-Pedrini, Gillis, Hawke, Heard, Henderson, Heshmat, Hodgkinson, Kilpatrick, King, Kneebone, Kornberg, Lechner-Scott, Lin, Lynch, Macdonell, Mason, McCombe, Pereira, Pollard, Ramanathan, Reddel, Shaw, Spies, Stankovich, Sutton, Vucic, Walsh, Wong, Yiu, Barnett, Kermode, Marriott, Parratt, Slee, Taylor, Willoughby, Brilot, Vincent, Waters and Broadley.

PubMed Disclaimer

Conflict of interest statement

MHB has received research support, speaking engagement honoraria, advisory board honoraria and travel sponsorship from Biogen Idec, Merck, Novartis, Roche and Sanofi-Genzyme, and is a consulting neurologist for RxMx and is Research Director of the Sydney Neuroimaging Analysis Centre. MB has received travel sponsorship and honoraria from Sanofi-Genzyme, Teva, Novartis, Biogen Idec and Roche. BB has received honoraria as a board member for GlaxoSmithKline, Biogen Idec, ViiV Healthcare and Merck Serono, has received speaker honoraria from ViiV Healthcare, Boehringer Ingelheim, Abbott, Abbvie, and Biogen Idec; has received travel sponsorship from Abbott and ViiV Healthcare, and has received research support funding from EI Lilly, GlaxoSmithKline, ViiV Healthcare and Merck Serono. FB has received speaker's honoraria from Biogen-Idec and EMD Serono. SAB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis, and Sanofi-Genzyme, has received speakers honoraria from Biogen-Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen Idec, Novartis and Genzyme, and was the recipient of an unencumbered research grant from Biogen-Idec. HB has received honoraria for serving on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Genzyme, has received conference travel sponsorship from Novartis and Biogen Idec, has received honoraria for speaking and acting as Chair at educational events organised by Novartis, Biogen Idec, Medscape and Merck Serono, serves on steering committees for trials conducted by Biogen Idec and Novartis, is chair (honorary) of the MSBase Foundation, which has received research support from Merck Serono, Novartis, Biogen Idec, Genzyme Sanofi and CSL Biopharma and has received research support form Merck Serono. WC has been the recipient of travel sponsorship from, and provided advice to, Bayer Schering Pharma, Biogen-Idec, Novartis, Genzyme, Sanofi-Aventis, BioCSL and Merck-Serono. RD has received research funding from the National Health and Medical Research Council, MS Research Australia, Star Scientific Foundation, Pfizer Neuroscience, Tourette Syndrome Association, University of Sydney, and the Petre Foundation and has received honoraria from Biogen-Idec and Bristol-Myers Squibb as an invited speaker. MF-P has received travel sponsorship from Biogen Australia and New Zealand. RH has received honoraria, educational support and clinic funding from Novartis, Biogen Idec, Genzyme and BioCSL. AGKK has received scientific consulting fees and/or lecture honoraria from Bayer, BioCSL, Biogen-Idec, Genzyme, Lgpharma, Merck, Mitsubishi Tanabe Pharma, NeuroScientific Biopharmaceuticals, Novartis, Roche, Sanofi-Aventis, and Teva. TK has received travel sponsorship from Novartis, BioCSL, Novartis, Merck Serono and Biogen Idec, has received speaker honoraria from Biogen Idec, BioCSL, Merck Serono, Teva, Genzyme and Novartis, has received research support from Biogen Idec, Genzyme, GlaxoSmithKline, Bayer-Schering and Merck Serono, and has received scientific consulting fees from GlaxoSmithKline China, Biogen-Idec and Novartis. JK has received remuneration for advisory board activities and presentations from Bayer Healthcare, Biogen Idec, BioCSL, Genzyme and Novartis. CK has received travel support, honoraria and advisory board payments from Biogen Idec, Bayer, Genzyme, Novartis and Serono. JL-S has received unencumbered funding as well as honoraria for presentations and membership on advisory boards from Sanofi Aventis, Biogen Idec, Bayer Health Care, CSL, Genzyme, Merck Serono, Novartis Australia and Teva. RM has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, CSL, Merck-Serono, Novartis, and Sanofi-Genzyme. MM has received travel sponsorship, honoraria, trial payments, research and clinical support from Bayer Schering, Biogen Idec, BioCSL, Genzyme, Novartis, and Sanofi Aventis Genzyme. DM has received honoraria for attendance at advisory boards from Biogen-Idec and Novartis, and travel sponsorship from Bayer-Schering, Biogen-Idec, and Sanofi-Genzyme. PM has received honoraria or travel sponsorship from Novartis, Sanofi-Aventis and Biogen Idec. JP has received travel sponsorship, honoraria for presentations and membership on advisory boards from Biogen Idec and Novartis and Sanofi Aventis. JDP has received honoraria for seminars or advisory boards from Teva, Biogen, Sanofi-Genzyme, Novartis, Merck, Bayer and research grants or fellowships from Merck, Novartis, Bayer, Biogen, Sanofi-Genzyme, and Teva. SR has received honoraria for advisory consultancy from UCB and speaker's honoraria from Biogen Idec. SWR has received travel sponsorship, honoraria, trial payments, research and clinical support from Aspreva, Baxter, Bayer Schering, Biogen Idec, BioCSL, Genzyme, Novartis, Sanofi Aventis Genzyme and Servier, and is a director of Medical Safety Systems Pty Ltd. CPS has received travel sponsorship from Biogen Idec, Novartis and Bayer-Schering. IS has received remuneration for Advisory Board activities from Biogen, CSL, and Bayer Schering and educational activities with Biogen, CSL and travel sponsorship from Biogen, Novartis and Bayer Schering. JMS has received honoraria for lectures and participation in advisory boards, and travel sponsorship from Novartis, BioCSL, Genzyme, and Biogen Idec. BT has received travel sponsorship from Novartis and Bayer Schering. AV and the University of Oxford hold patents and receive royalties for antibody testing. PW and the University of Oxford hold patents for antibody assays and have received royalties, has received honoraria from Alexion, Biogen Idec F. Hoffmann-La Roche, Retrogenix, UBC and Euroimmun AG, and travel grants from the Guthy-Jackson Charitable Foundation. EW has received honoraria for participation in advisory boards from Biogen-Idec and Novartis, travel sponsorship from Biogen-Idec, Bayer-Schering and Teva and is an investigator in clinical trials funded by Biogen-Idec and Teva. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**Figure 1**
Representative axial section of left frontal cortex with cortex in light grey and lateral ventricle in dark grey **(A)**. White matter lesions are shown in red. TMF, tumefactive lesion—note size >3 cm and extension from ventricular surface to juxtacortical zone; PV, periventricular—note lesions abutting or immediately adjacent to lateral ventricle; CT, cortical—lesion wholly or predominantly located with the cortex; JC, juxtacortical—subcortical white matter lesion following the contour of the cortex but sparing the U-fibre layer; SC, subcortical—any other lesion predominantly located superficial to an imaginary line drawn half-way between the lateral ventricular surface and the cortex. Diagrammatic representation of axial section of spinal cord showing quadrantic segmentation of central and peripheral zones used to define lesions, showing **(B)** a central spinal cord lesion occupying at least a part of all central quadrants and **(C)** a partial spinal cord lesion occupying part of only three central regions.

**Figure 2**
Flow chart of results of literature search used to identify MRI lesions and features associated with NMOSD and MS.

**Figure 3**
Venn diagram summarising availability of MRI of brain, orbits and spine in **(A)** NMOSD cases and **(B)** multiple sclerosis cases. Surface area of circles is proportional to the total number of MRI of each type. MRI brain in blue, orbits in green and spine in red. Numbers indicate numbers of patients with at least one MRI of specified type within each category or overlapping group.

**Figure 4**
Forest plot of odds ratios for lesion occurrence in NMOSD and multiple sclerosis. OR >1 favour NMOSD and OR <1 favour multiple sclerosis. Error bars indicate 95% confidence intervals. Lesions significantly associated with NMOSD are highlighted in blue and those associated with multiple sclerosis are highlighted in red.

**Figure 5**
Lesions of the spinal cord, brain and optic nerve associated with or exclusively seen in NMOSD. Spinal cord lesions: longitudinally extensive spinal cord lesion (arrows) seen on T2 sagittal image of the cervical cord **(A)**, peripheral Gd-enhancing lesion (arrows) seen on T1 sagittal image of the same lesion **(B)**, central cord lesion (arrow) on T2 axial image at the level of C4 from the same lesion **(C)** and central Gd-enhancement (arrow) on T1 axial image in the same region **(D)**; swelling (arrow) of a high signal lesion on T2 sagittal image of the cervical region **(E)**; bright spotty cord lesions (arrows) on axialT2 image of the cervical region **(F)**; spinal cord atrophy with myelomalacia (arrow) on sagittal T2 image of the cervico-thoracic region **(G)**; Brainstem lesions: bilateral nucleus tractus solitarius high signal lesions (arrows) on axial FLAIR image through the pons **(H)**; periaqueductal high signal lesion (arrow) on axial FLAIR image through the midbrain **(I)**; high signal FLAIR lesion involving the floor of the fourth ventricle on axial FLAIR imaging at the level of the pons **(J)**; central medullary lesion (arrow) on T2 axial image of the medulla **(K)** and sagittal T2 image of high cervical cord lesion showing extension into the medulla **(L)**. Leptomeningeal enhancement of the tent (arrows) on axial gadolinium enhanced T1 image at the level of the midbrain **(M)**. Brain FLAIR lesions: hypothalamic high signal lesion (arrows) on axial image **(N)** and midline sagittal image **(O)**; high signal lesion involving the walls of the third ventricle (arrows) on axial image **(P)**. Cloud-like Gd-enhancing lesions (arrows) shown on axial FLAIR image **(Q)** and Gd-enhanced T1 image **(R)**. Bilateral longitudinally extensive cortico-spinal tract lesions (arrows) seen on sequential axial DIR images through the basal ganglia and midbrain **(S–U)**. Optic nerve lesions: high signal lesion of the left optic nerve (arrow) on coronal T2 image of the orbits **(V)**; longitudinally extensive high signal lesion of the left optic nerve (arrows) on axial T2 image of the orbits **(W)**; bilaterally Gd-enhancing lesions of the optic nerves (arrows) on axial Gd-enhanced T1 image of the orbits **(X)**; optic chiasm lesion (arrow) on axial Flair image **(Y)** and Gd-enhanced T1 image **(Z)**.

**Figure 6**
Lesions and features on MRI of brain and spinal cord associated with multiple sclerosis: periventricular hyperintense T2 white matter lesions (arrows) on axial FLAIR image of the brain **(A)**; subcortical T2 white matter lesions (arrows) on axial FLAIR image of the brain **(B)**; juxtacortical hyperintense T2 white matter lesion (arrow) on axial proton density image of the brain **(C)**; cortical hyperintense T2 lesion (arrow) on sagittal FLAIR image of the brain **(D)**; cerebellar hyperintense T2 lesions (arrows) on sagittal FLAIR image of the brain **(E)**; ovoid hyperintense T2 periventricular lesion (arrow) on axial FLAIR image of the brain **(F)**; large supratentorial T2 lesion (arrow) on sagittal FLAIR image of the brain **(G)**; Dawson's finger lesions (arrows) on sagittal FLAIR image of the brain **(H)**; right cerebellar peduncle hyperintense T2 lesion (arrow) on axial T2 image of the brain **(I)**; pyramidal corpus callosum hyperintense T2 lesion (arrow) on sagittal FLAIR image of the brain **(J)**; splenium hyperintense T2 lesion (arrow) on axial **(K)** and sagittal **(L)** FLAIR images of the brain; Gd-enhancing T1 lesions of periventricular (arrow) **(M)**, juxtacortical (arrows) **(N)**, splenium (arrow) **(O)** regions on axial T1 images of the brain and ring-enhancing lesion (arrow) on coronal T1 image of the brain **(P)**; hypointense T1 (black hole) lesions (arrows) on axial T1 image of the brain **(Q)**; short segment C3 T2 lesion (arrow) on sagittal T2 image of the cervical spinal cord **(R)**; and hyperintense T2 partial cord lesion (arrow) on axial T2 image of the cervical spinal cord **(S)**.

**Figure 7**
Box and whisker plot of the number of T2 lesions seen in NMOSD and multiple sclerosis for the most numerous brain lesion types. Lesion counts were the highest number of unique lesions seen on an individual scan from all MRI per patient. Central bar indicates median, boxes show interquartile range and whiskers show range.

**Figure 8**
Lesions previously described in NMOSD that were seen with equal frequency in NMOSD (left panel) and multiple sclerosis (right panel): **(A)** linear periventricular periependymal T2 lesions; **(B)** “bridging” T2 lesion of the splenium; **(C)** heterogenous T2 lesion of the corpus callosum; **(D)** rounded corpus callosum lesion; **(E)** pencil-like corpus callosum lesion; **(F)** tumefactive white matter lesion; **(G)** cystic brain lesion; **(H)** periependymal brainstem T2 lesion; **(I)** cerebral peduncle lesion (here seen bilaterally in multiple sclerosis); **(J)** punctate white matter lesions; and **(K)** patch white matter lesions.

**Figure 9**
“Heat map” of lesion location in the spinal cord of individual cases with NMOSD and multiple sclerosis. Vertical columns indicate individual patients as numbered, horizontal rows indicate hemi-vertebral distances (i.e., two rows = one vertebral segment). Representation of lesions is for lesions appearing at any time during the disease course for an individual patient, hence consecutive short lesions spanning more than 3 vertebrae can be seen (i.e., multiple short lesions at different times). See text for definition of pseudo-long T2 lesion. Columns at far right of each group indicate a summary (S) of relative frequency of lesions for each level (any type of lesion). Dx, diagnosis; Pt, patient; C, cervical; T, thoracic; L, lumbar; NMOSD, neuromyelitis optica spectrum disorder; S, summary.

**Figure 10**
“Pseudo-longitudinally” extensive spinal cord lesion seen in multiple sclerosis. Sagittal T2 MRI of the cervical spine in a multiple sclerosis control showing longitudinally extensive high signal changes extending from C1 to C6. This lesion is confluent over at least 3 vertebral segments. Prior imaging confirmed that this lesion arose as a confluence of smaller lesions over time.

**Figure 11**
Machine learning decision tree to distinguish NMOSD from multiple sclerosis based binarised presence (Y) or absence (N) of specific lesion types and features as indicated in ovals. NMOSD, neuromyelitis optica spectrum disorder; MS, multiple sclerosis, Y, yes; N, no.

See this image and copyright information in PMC

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MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis

Affiliations

MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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