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Letters to the Editor 4. Etemadifar M and Abtahi SH. Multiple sclerosis in Isfahan, Iran: Past, present and future. Int J Prev Med 2012; 3: 301–302. 5. Etemadifar M, Sajjadi S, Nasr Z, et al. Epidemiology of multiple sclerosis in Iran: A systematic review. Eur Neurol 2013; 70: 356–363.

Masoud Etemadifar1,2, Seyed-Hossein Abtahi2,3, Mojtaba Akbari4, Richard T Murray2, Sreeram V Ramagopalan5, and Mahboobeh Fereidan-Esfahani2,3 1Department of Neurology, Isfahan University of Medical Sciences, Iran 2Isfahan Research Committee of Multiple Sclerosis (IRCOMS), Isfahan University of Medical Sciences, Iran 3Medical Student’s Research Center, Isfahan University of Medical Sciences, Iran 4Department of Epidemiology, School of Health and Nutrition, Shiraz University of Medical Science, Iran. 5Department of Physiology, Anatomy and Genetics, University of Oxford, UK Corresponding author: Mahboobeh Fereidan-Esfahani, Isfahan MS Society, No.2, Behesht Building, Bozorgmehr Ave, Isfahan, Iran. Email: [email protected]

Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders

Kim and colleagues investigated the utility of aquaporin-4 antibodies (AQP4-Ab) in patients with neuromyelitis optica (NMO) spectrum disorders (NMOSD).1 We agree that the discovery of autoantibodies targeting the water channel protein AQP4 on astrocytes has revolutionized the understanding of NMO.2 We now know that some limited forms of NMO or atypical lesions are associated with AQP4-Ab. However, the definition of NMOSD has seemingly been misinterpreted by the authors and we would like to argue against the so-called AQP4-Ab-negative NMOSD. Although still controversial, it is more commonly accepted that NMOSD is defined by AQP4-Ab-seropositivity.3 The term NMOSD refers to cases in which patients have been seropositive for AQP4-Ab but have not fully met clinical criteria for NMO.4 NMOSD encompasses definitive NMO, as well as limited forms, such as AQP4-Ab-positive, longitudinally extensive, transverse myelitis, or recurrent or bilateral AQP4-Ab-positive optic neuritis. A possibility is that present assays are not sensitive enough to detect AQP4-Ab. With improvements in assay sensitivity, serum AQP4-Ab has been detected in an increasing number of patients with apparently

AQP4-Ab-negative disease.5 If NMOSD can be diagnosed without seropositivity of APQ4-Ab, another newly identified clinical entity, namely paraneoplastic neurological syndrome that may involve optic nerves and spinal cord while without APQ4-Ab can also be categorized into NMOSD.6 However, this ambiguous classification does not seem to contribute to the elucidation of NMOSD. In Reference 5 of the article, the authors did not propose diagnostic criteria for NMOSD.7 Instead, Wingerchuk and colleagues7 claimed that AQP4-Ab is detected in the serum of patients with disorders related to NMO, including Asian optic-spinal multiple sclerosis, recurrent myelitis associated with longitudinally extensive spinal cord lesions, recurrent isolated optic neuritis, and optic neuritis or myelitis in the context of certain organ-specific and non-organ-specific autoimmune diseases. Conflict of interest None declared.

Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References 1. Kim SM, Waters P, Woodhall M, et al. Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders. Mult Scler 2013; 19: 1060–1067. 2. Lennon VA, Kryzer TJ, Pittock SJ, et al. IgG marker of opticspinal multiple sclerosis binds to the aquaporin 4 water channel. J Exp Med 2005; 202: 473–477. 3. Papadopoulos MC and Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol 2012; 11: 535–544. 4. Weinshenker BG. Neuromyelitis optica is distinct from multiple sclerosis. Arch Neurol 2007; 64: 899–901. 5. Waters PJ, McKeon A, Leite MI, et al. Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays. Neurology 2012; 78: 665–671. 6. Jarius S, Wandinger KP, Borowski K, et al. Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: Case report and review of the literature. Clin Neurol Neurosurg 2012; 114: 331–335. 7. Wingerchuk DM, Lennon VA, Lucchinetti CF, et al. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6: 810–815.

Chunkui Zhou, Yi Yang and Hongliang Zhang Department of Neurology, The First Hospital of Jilin University, Changchun, China Corresponding author: Hongliang Zhang, Department of Neurology, The First Hospital of Jilin University, Jilin University, Xinmin Street 71#, 130021, Changchun, China Email: [email protected]

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Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders.

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