Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (po = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (po = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
Conflicts of interest
Dr. Jurynczyk received research fellowship from the Polish Ministry of Science and Higher Education programme Mobliność Plus (1070/MOB/2013/0). Dr. Weinshenker is a member of data safety monitoring boards: Novartis, Biogen Idec and Mitsubishi; Adjudication panel member: MedImmune. Consultant: Elan, GlaxoSmithKline, Ono, CHORD Therapeutics, and Chugai. Editorial board membership: Neurology, the Canadian Journal of Neurological Sciences, and the Turkish Journal ofNeurology. Research support: Guthy-Jackson Charitable Foundation. Royalties and patent: RSR Ltd. and Oxford University for a patent regarding AQP4-associated antibodies for diagnosis of neuromyelitis optica. Dr. Akman-Demir reports no disclosures. Dr Asgari reports no disclosures. Dr. Barnes reports no disclosures. Dr. Boggild reports no disclosures. Dr Chaudhuri received travel grants, sponsorship for attending medical congresses, speaker fees and honoraria from: Novartis, Biogen Idec, Bayer-Schering, UCB, Eisai, Terumo BCT and Genzyme. Dr. D’hooghe reports no disclosures. Dr. Evangelou reports no disclosures. Dr. Geraldes reports no disclosures. Dr. Illes reports no disclosures. Dr. Jacob reports no disclosures. Dr. Kim reports no disclosures. Dr. Kleiter reports no disclosures. Dr. Levy reports no disclosures. Dr Marignier was supported by the European research project on rare diseases ERA-Net E-RARE-2 in the frame of the Eugene Devic European Network (EDEN) and Association pour la Recherche contre la Sclerose en Plaques(ARSEP) Foundation. Dr McGuigan has received research funding from Biogen Idec, Novartis, Bayer and Genzyme and honoraria for advisory boards from Biogen Idec, Novartis and Genzyme. Dr. Murray reports no disclosures. Dr. Nakashima reports no disclosures. Dr. Pandit reports no disclosures. Dr Paul was supported by the German Research Foundation (DFG Exc 257), the German Ministry for Education and Research (KKNMS Competence Network Multiple Sclerosis) and the Guthy-Jackson Charitable Foundation. Dr. Pittock reports no disclosures. Dr. Selmaj reports no disclosures. Dr. de Sèze reports no disclosures. Dr. Siva reports no disclosures. Dr. Tanasescu reports no disclosures. Dr. Vukusic reports no disclosures. Dr. Wingerchuk reports no disclosures. Dr. Wren reports no disclosures. Dr. Leite reports no disclosures. Dr. Palace reports no disclosures.
This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
All patients gave their informed consent to include their anonymised clinical data in the manuscript.
Min J-H, Kim BJ, Lee KH (2012) Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder. Mult Scler J 18:113–115. doi:10.1177/1352458511431973CrossRefGoogle Scholar
Kitley J, Waters P, Woodhall M et al (2014) Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol. doi:10.1001/jamaneurol.2013.5857Google Scholar
Paty DW, Oger JJ, Kastrukoff LF et al (1988) MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 38:180–185CrossRefPubMedGoogle Scholar
Peabody JW, Luck J, Glassman P et al (2004) Measuring the quality of physician practice by using clinical vignettes: a prospective validation study. Ann Intern Med 141:771–780CrossRefPubMedGoogle Scholar
Waters P, Woodhall M, O’Connor KC et al (2015) MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflam 2:e89CrossRefGoogle Scholar