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Published online before print April 23, 2008, doi:10.1212/01.wnl.0000303817.82134.da)
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Volume 70, Number 23, June 3, 2008
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NEUROLOGY 2008;70:2197-2200
© 2008 American Academy of Neurology

NMO-IgG predicts the outcome of recurrent optic neuritis

M. Matiello, MD, V. A. Lennon, MD, PhD, A. Jacob, MD, S. J. Pittock, MD, C. F. Lucchinetti, MD, D. M. Wingerchuk, MD and B. G. Weinshenker, MD

From the Departments of Neurology (M.M., V.A.L., A.J., S.J.P., C.F.L., B.G.W.) and Laboratory Medicine and Pathology (V.A.L., S.J.P.), Mayo Clinic College of Medicine, Rochester, MN; and Department of Neurology (D.M.W.), Mayo Clinic College of Medicine, Scottsdale, AZ.

Address correspondence and reprint requests to Dr. Brian Weinshenker, Department of Neurology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905 weinb{at}mayo.edu

Objective: To determine the prognostic value of neuromyelitis optica (NMO)–immunoglobulin G (IgG) in patients with recurrent optic neuritis (ON). The aquaporin-4-specific serum autoantibody, NMO-IgG, is a biomarker for NMO and relapsing transverse myelitis. Recurrent ON may herald multiple sclerosis (MS) or NMO, or it may occur as an isolated syndrome. The prognosis and response to therapy differs in each of these contexts.

Methods: We evaluated 34 patients who were tested for NMO-IgG between 2000 and 2007 and who had two or more episodes of ON without satisfying a diagnosis of MS or NMO prior to serologic testing. Clinical data were available for 25 Mayo Clinic patients (5 NMO-IgG positive and 20 NMO-IgG negative) and for an additional 9 seropositive patients whose serum was referred to the Mayo Clinic Neuroimmunology laboratory for testing.

Results: Twenty percent of the patients with recurrent ON seen at Mayo Clinic were seropositive. All NMO-IgG-positive patients (vs 65% NMO-IgG-negative patients) had at least one attack with visual acuity in the affected eye worse than 20/200 (p = 0.05). In seropositive patients for whom long-term follow-up was possible (median 8.9 years after the initial ON), 6 of 12 (50%) experienced an episode of myelitis and fulfilled criteria for NMO. In contrast, 1 of 15 seronegative patients (6.7%) fulfilled McDonald criteria for MS (p = 0.03). Seropositive patients had a final visual score which was worse than that of seronegative patients (p = 0.02).

Conclusions: Neuromyelitis optica (NMO)–immunoglobulin G seropositivity predicts poor visual outcome and development of NMO. Seropositive recurrent optic neuritis is a limited form of NMO.

Abbreviations: IgG = immunoglobulin G; LETM = longitudinally extensive transverse myelitis; MS = multiple sclerosis; NMO = neuromyelitis optica; ON = optic neuritis; RON = recurrent ON; TM = transverse myelitis; VA = visual acuity.


Editorial, page 2192

e-Pub ahead of print on April 23, 2008, at www.neurology.org.

Dr. Matiello is supported by a du Pré fellowship grant provided by the Multiple Sclerosis International Federation (www.msif.org). This research is sponsored in part by a grant to Dr. Weinshenker from the Olson Foundation.

Disclosure: Drs. Marcelo Matiello, Anu Jacob, and Sean Pittock have nothing to disclose. Drs. Brian Weinshenker, Vanda Lennon, and Claudia Lucchinetti have intellectual property associated with the discovery of NMO-IgG, which has been licensed to a commercial entity. The NMO-IgG test is offered on a service basis by Mayo Collaborative Service Inc., an agency of Mayo Foundation. Dean Wingerchuk and Brian Weinshenker have served as consultants for Genentech for development of a clinical trial for neuromyelitis optica. Dr. Wingerchuk has consulted for Teva pharmaceuticals. Drs. Weinshenker and Wingerchuk have also been investigators in clinical trials for MS.

Received August 2, 2007. Accepted in final form October 18, 2007.




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