Neuromielitis

ORIGINAL CONTRIBUTION

Neuromyelitis Optica IgG Serostatus in Fulminant Central Nervous System Inflammatory Demyelinating Disease
Setty M. Magana, BS; Sean J. Pittock, MD; Vanda A. Lennon, MD, PhD; B. Mark Keegan, MD; ˜ Brian G. Weinshenker, MD; Claudia F. Lucchinetti, MD

Background: The aquaporin-4–specific serum autoantibody neuromyelitis optica (NMO) IgG is a validated biomarkerdistinguishing NMO spectrum disorders from multiple sclerosis (MS). Because fulminant attacks are more common in NMO spectrum disorders than in MS, some investigators suggest that NMO IgG may be a marker of destructive demyelination rather than a diseasespecific biomarker. To our knowledge, this study is the first to compare NMO IgG serostatus among patients with fulminant central nervous systeminflammatory demyelinating disease (CNS IDD). Objective: To determine whether NMO IgG distinguishes patients with NMO spectrum disorders from those with other fulminant corticosteroid-refractory CNS IDD. Design: Descriptive historical cohort. Setting: Neuroimmunology laboratory and neurology

Main Outcome Measures: Two blinded observers scored serum samples tested at 1:120 dilution. Clinical data wereobtained by medical record review. Results: Preplasmapheresis serum samples were available from 74 patients (ratio of women to men, 2:5); the mean interval between blood draw and plasmapheresis was 13 days. At the time of plasmapheresis, the mean age of patients was 46 years (age range, 7-80 years); the mean Expanded Disability Status Scale score was 7.0 (score range, 3.5-9.5 [10.0 is death]).Diagnoses included MS (18 patients with definite and 11 patients with probable), longitudinally extensive transverse myelitis involving at least 3 vertebral segments (20 patients), NMO (14 patients), transverse myelitis involving fewer than 3 vertebral segments (8 patients), optic neuritis (2 patients), and acute disseminated encephalomyelitis (1 patient). Neuromyelitis optica IgG was detected in 20patients (27%) (10 with longitudinally extensive transverse myelitis, 9 with NMO, and 1 with recurrent optic neuritis) and was not detected in any patient with MS, short transverse myelitis, monophasic optic neuritis, or acute disseminated encephalomyelitis. Conclusion: Neuromyelitis optica IgG is a specific biomarker for NMO spectrum disorders and is not simply a marker of destructive CNS IDD.practice, Mayo Clinic College of Medicine, Rochester, Minnesota.
Patients: Serum samples from 74 patients who under-

went plasmapheresis between February 24, 1993, and November 22, 2007, for a corticosteroid-refractory CNS IDD were tested for NMO IgG by indirect immunofluorescence assay.

Arch Neurol. 2009;66(8):964-966 ter, with necrosis, vascular hyalinization, eosinophilic and neutrophilicinflammatory infiltrates, and extensive vasculocentric deposits of immunoglobulins and complement.2 Early distinction of NMO from MS is prognostically and therapeutically important because their optimal treatments differ (immunosuppression for NMO and immunomodulation for MS).1 Although the aquaporin-4–specific autoantibody NMO IgG has been convincingly shown to be a biomarker that reliablydistinguishes NMO spectrum disorders from classic MS, to our knowledge, no previous study has investigated the specificity of NMO IgG expressly in the setting of fulmi-

Author Affiliations: Departments of Neurology (Ms Magana and Drs Pittock, ˜ Lennon, Keegan, Weinshenker, and Lucchinetti), Laboratory Medicine and Pathology (Drs Pittock and Lennon), and Immunology (Dr Lennon), Mayo Clinic College ofMedicine, Rochester, Minnesota.

(NMO) is a severe demyelinating disease of the central nervous system (CNS), conventionally recognized for its propensity to preferentially affect the optic nerves and spinal cord. Typically, NMO has a worse clinical outcome than multiple sclerosis (MS), with more frequent and earlier relapses.1 Prototypic MS is not usually fulminant in nature, and MS lesions...