A Systematic Clinico-Serologic Study of Recurrent Longitudinally Extensive Transverse Myelitis (rTM) and Comparison with NMO (P02.141)

OBJECTIVE: 1) Investigate in rTM patients the AQP4-IgG detection rate in recombinant antigen-based assays for sera scored negative by 1st generation tissue-based indirect-immunofluorescence assay (IIF); 2) Compare clinical characteristics of seropositive rTM and NMO. BACKGROUND: Seropositive rTM is classified as an NMO-spectrum disorder. Evolving serological assay sensitivity has precluded comparison of the clinical characteristics of rTM and NMO. DESIGN/METHODS: From 2005-2011, 5349 samples from Mayo Clinic patients were tested by IIF assay. Clinical records revealed 48 patients had rTM (pediatric onset in 3). Of those, 36 (75%) were IIF-positive and 12 (25%) IIF-negative; 11 of the 12 scored negative were available for testing by ELISA (RSR/Kronus) and AQP4-transfected cell-binding assays (CBA slides [EUROIMMUN] and in-house fluorescence-activated-cell-sorting [FACS]). Clinical characteristics were compared based on finally assigned serostatus. 138 AQP4-IgG-positive NMO patients served as control cases. RESULTS: Overall, the AQP4-IgG detection rate improved to 91% by FACS, 85% by CBA, and 83% by ELISA. Only 4 cases remained seronegative: 2 boys (onset ages 3 and 6) and 2 adults (1 male, 1 female). Among 42 seropositive adult rTM cases (excluding single female with onset age 15) the female:male ratio = 5:1. rTM cases required a cane sooner (median 19.5 months) than NMO cases (48 months; p=0.04).Two findings suggest seropositive rTM may progress to NMO: 1) rTM cases had a shorter median disease duration (first attack to last follow-up, 61 months) than control NMO cases (106 months); 2) For the NMO subgroup with initial rTM course, time from onset to 1st optic neuritis (54 months) was similar to rTM cases9 median disease duration. CONCLUSIONS: Adult rTM is rarely AQP4-IgG-seronegative. NMO evolution can be anticipated in seropositive cases. The 2 seronegative boys may have MS because ∼ 14% of pediatric MS cases have longitudinally-extensive lesions [Banwell et al, Neurology, 2008]; adult MS cases do not. Supported by: Mayo Clinic Foundation, Guthy-Jackson Charitable Foundation (VL, CL, SP, BW, DW) and NIH (R01-NS65829, SP). Disclosure: Dr. Jiao has nothing to disclose. Dr. Fryer has nothing to disclose. Dr. Lennon stands to receive royalties for commercial assays to detect of aquaporin 4-specific autoan. Dr. McKeon has nothing to disclose. Ms. Smith has received research support from Abbott Laboratories. Dr. Jenkins has nothing to disclose. Dr. Iorio has nothing to disclose. Dr. Costanzi has nothing to disclose. Dr. Quek has nothing to disclose. Dr. Weinshenker has received personal compensation for activities with Novartis, Biogen Idec, Elan Corporation, GlaxoSmithKline Inc., Asahi Kasei Kuraray Medical Company as a consultant and/or participant on a data safety monitoring board. Dr. Weinshenker has received (royalty or license fee or contractual rights) payments from Mayo Medical Ventures. Dr. Wingerchuk has received research support from Genentech, Genzyme, Alexion, TerumoBCT and the Guthy-Jackson Charitable Foundation. Dr. Shuster has nothing to disclose. Dr. Lucchinetti stands to receive royalties for commercial assays to detect aquaporin 4-specific autoantibody. Dr. Pittock and Mayo Clinic have a financial interest in the technology entitled "Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia." This technology has been licensed to a commercial entity but no royalties have been received. Dr Sean Pittock has received research support from Alexion Pharmaceuticals, Inc.