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Published on: August 21, 2017
Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With
Rosa Cortese1, Ferran Prados Carrasco1, Carmen Tur1
1From the Department of Neuroinflammation (R.C., F.P.C., C.T., A.B., W.B., F.D.A., I.D.L.P., F.G., L.H., L.M., A.T., M.Y., A.T.T., Y.H.R.C.P.C.H., F.B., O.C.), Queen Square MS Centre, UCL Queen Square Institute of Neurology, Faculty of Brain Science, University College of London; Department of Medicine (R.C.), Surgery and Neuroscience, University of Siena, Italy; Department of Medical Physics and Biomedical Engineering (F.P.C., B.K., F.B.), Centre for Medical Imaging Computing, University College of London; Universitat Oberta de Catalunya (F.P.C.), Barcelona, Spain; MS Centre of Catalonia (Cemcat) (C.T.), Vall d'Hebron Institute of Research, Spain; Radiomics Group (F.G.), Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Barcelona, Spain; Department of Biomedical Imaging and Image Guided Therapy (L.H.), Medical University of Vienna, Austria; NMO Clinical Service at the Walton Centre (A.J.), Liverpool, United Kingdom; Division of Multiple Sclerosis and Autoimmune Neurology (A.J.), Neurological Institute, Cleveland Clinic Abu Dhabi, United Arab Emirates; Division of Brain Sciences (R.S.N.), Department of Medicine, Imperial College London; National Institute for Health Research (NIHR) (A.T., F.B., O.C.), University College London Hospitals (UCLH), Biomedical Research Centre; and Department of Radiology and Nuclear Medicine (F.B.), Amsterdam University Medical Centre, the Netherlands.
Background And Objectives:
Relapsing-remitting multiple sclerosis (RRMS), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may have overlapping clinical features. There is an unmet need for imaging markers that differentiate between them when serologic testing is unavailable or ambiguous. We assessed whether imaging characteristics typical of MS discriminate RRMS from AQP4-NMOSD and MOGAD, alone and in combination.
Methods:
Adult, nonacute patients with RRMS, APQ4-NMOSD, and MOGAD and healthy controls were prospectively recruited at the National Hospital for Neurology and Neurosurgery (London, United Kingdom) and the Walton Centre (Liverpool, United Kingdom) between 2014 and 2019. They underwent conventional and advanced brain, cord, and optic nerve MRI and optical coherence tomography (OCT).
Results:
A total of 91 consecutive patients (31 RRMS, 30 APQ4-NMOSD, and 30 MOGAD) and 34 healthy controls were recruited. The most accurate measures differentiating RRMS from AQP4-NMOSD were the proportion of lesions with the central vein sign (CVS) (84% vs 33%, accuracy/specificity/sensitivity: 91/88/93%, p < 0.001), followed by cortical lesions (median: 2 [range: 1-14] vs 1 [0-1], accuracy/specificity/sensitivity: 84/90/77%, p = 0.002) and white matter lesions (mean: 39.07 [±25.8] vs 9.5 [±14], accuracy/specificity/sensitivity: 78/84/73%, p = 0.001). The combination of higher proportion of CVS, cortical lesions, and optic nerve magnetization transfer ratio reached the highest accuracy in distinguishing RRMS from AQP4-NMOSD (accuracy/specificity/sensitivity: 95/92/97%, p < 0.001). The most accurate measures favoring RRMS over MOGAD were white matter lesions (39.07 [±25.8] vs 1 [±2.3], accuracy/specificity/sensitivity: 94/94/93%, p = 0.006), followed by cortical lesions (2 [1-14] vs 1 [0-1], accuracy/specificity/sensitivity: 84/97/71%, p = 0.004), and retinal nerve fiber layer thickness (RNFL) (mean: 87.54 [±13.83] vs 75.54 [±20.33], accuracy/specificity/sensitivity: 80/79/81%, p = 0.009). Higher cortical lesion number combined with higher RNFL thickness best differentiated RRMS from MOGAD (accuracy/specificity/sensitivity: 84/92/77%, p < 0.001).
Discussion:
Cortical lesions, CVS, and optic nerve markers achieve a high accuracy in distinguishing RRMS from APQ4-NMOSD and MOGAD. This information may be useful in clinical practice, especially outside the acute phase and when serologic testing is ambiguous or not promptly available.
Classification Of Evidence:
This study provides Class II evidence that selected conventional and advanced brain, cord, and optic nerve MRI and OCT markers distinguish adult patients with RRMS from AQP4-NMOSD and MOGAD.
