Contributions
Abstract: 65
Type: Scientific Session
Abstract Category: Clinical aspects of MS - Paediatric MS
Background: The presence of serum anti-MOG antibodies identifies a subgroup of children with acquired demyelinating syndromes (ADS).
Aim: To describe the clinical features and outcomes of a large and well characterized cohort of children with ADS tested for the presence of anti-MOG antibodies.
Methods: MOG-abs were assessed at the time of incident ADS, blinded to clinical detail, in 297 children with ADS recruited as part of the Canadian Demyelinating Disease Study (CPDDS). Serial serum samples, collected over a median of 3.85 years, were evaluated in a subgroup of 265 participants. Baseline and serial brain MRI were examined with a standardized scoring tool.
Results: MOG-abs were detected in 85/297 (29%) children at onset. There was no gender bias, but children testing positive were younger than their seronegative counterparts (7.3 v 12.3 years old; p< 0.0001). A presenting phenotype of optic neuritis, transverse myelitis or both accounted for almost 3/4 of the MOG-abs cases (~50% with brain lesions), with the remainder predominantly presenting with acute disseminated encephalomyelitis (ADEM). Presenting MRI features of MOG-ab children largely consisted of ill-defined, diencephalic and thalamic lesions, with 21/45 patients who had brain lesions at baseline (47%; 11 with ADEM) demonstrating complete lesion resolution after a median time from onset of 4 months, range 2-62. The analysis of serial serum samples revealed an unexpected, high rate of conversion to a seronegative status, with only 36/85 (42%) patients who were positive at onset remaining positive at three months, 26 (31%) at one year, and 17 (20%) at two years. Twenty of the 85 children who were MOG-abs positive at incident ADS were found in follow-up to have a relapsing disease; 9 were diagnosed as relapsing non-MS phenotypically, while 11 children met criteria for MS but with atypical clinical features (relapses largely restricted to optic nerves or spinal cord, MRI features at baseline and/or changes over time inconsistent with typical MS). Only 50% of the relapsing patients remained seropositive for the whole length of observation (median 4.7, range 1.7-12.1 years). Three (4%) of the MOG positive and 10 (5%) of the negative children had seizures.
Conclusion: The presence of MOGabs at the time of clinical onset, identifies a subgroup of children with clinical and MRI features distinct from MS.
Disclosure: P. Waters is a named inventor on patents for antibody assays and has received royalties. He has received consulting or speaking fees from Biogen Idec, Euroimmun AG, and Mereo Biopharma and travel grants from the Guthy-Jackson Charitable Foundation.G. Fadda has no disclosure related to this work. SR Irani is P. Waters coapplicant and receive royalties on patent application WO/2010/046716 entitled ´Neurological Autoimmune Disorders´. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. M. Woodall has no disclosure related to this work. R. A. Brown has received personal compensation for consulting services from Biogen Idec and NeuroRx Research.J. O´Mahony has no disclosure related to this work. Dr. Castro has nothing to disclose. G. Longoni receives training and research support from the National Multiple Sclerosis Society. R. A. Marrie: receives research funding from Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, National Multiple Sclerosis Society, Rx & D Health Research Foundation, the Waugh Family Chair in Multiple Sclerosis, Crohn´s and Colitis Canada, and has conducted clinical trials funded by Sanofi- Aventis. E. A. Yeh has received funds from NMSS, CIHI, CIHR, OIRM, MS Society of Canada, Mario Battaglia Foundation, SickKids Foundation, CBMH Innovation Fund, CMSC, Rare Diseases Foundation and Guthy Jackson Foundation. She serves as a relapse adjudicator for ACI. She has served on a scientific advisory panel for Juno Therapeutics and has received a speaker´s honorarium from Novartis. D. Arnold has served on advisory boards, received speaker honoraria, served as a consultant, or received research support from Adelphi, Biogen, Celgene, Genentech, Genzyme, Medday, NeuroRx Research, Novartis, Pfizer, Receptos, Roche, Sanofi, the Canadian Institutes of Health Research, and the Multiple Sclerosis Society of Canada; and holds stock in NeuroRx Research. B. Banwell serves as a central MRI reviewer for Novartis in the context of a clinical trial, and as a non-remunerated advisor on clinical trial design to Sanofi-Aventis, Novartis, Biogen-IDEC, and Teva Neuroscience. Dr. Banwell has received grant support as listed above, as well as from the MS Society of Canada, CIHR, NIH, and NMSS. A. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Biogen Idec, Diogenix, Roche/Genentech, Sanofi-Genzyme, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Teva Neuroscience, Celgene/Receptos Inc, and Merck/EMD Serono.
Abstract: 65
Type: Scientific Session
Abstract Category: Clinical aspects of MS - Paediatric MS
Background: The presence of serum anti-MOG antibodies identifies a subgroup of children with acquired demyelinating syndromes (ADS).
Aim: To describe the clinical features and outcomes of a large and well characterized cohort of children with ADS tested for the presence of anti-MOG antibodies.
Methods: MOG-abs were assessed at the time of incident ADS, blinded to clinical detail, in 297 children with ADS recruited as part of the Canadian Demyelinating Disease Study (CPDDS). Serial serum samples, collected over a median of 3.85 years, were evaluated in a subgroup of 265 participants. Baseline and serial brain MRI were examined with a standardized scoring tool.
Results: MOG-abs were detected in 85/297 (29%) children at onset. There was no gender bias, but children testing positive were younger than their seronegative counterparts (7.3 v 12.3 years old; p< 0.0001). A presenting phenotype of optic neuritis, transverse myelitis or both accounted for almost 3/4 of the MOG-abs cases (~50% with brain lesions), with the remainder predominantly presenting with acute disseminated encephalomyelitis (ADEM). Presenting MRI features of MOG-ab children largely consisted of ill-defined, diencephalic and thalamic lesions, with 21/45 patients who had brain lesions at baseline (47%; 11 with ADEM) demonstrating complete lesion resolution after a median time from onset of 4 months, range 2-62. The analysis of serial serum samples revealed an unexpected, high rate of conversion to a seronegative status, with only 36/85 (42%) patients who were positive at onset remaining positive at three months, 26 (31%) at one year, and 17 (20%) at two years. Twenty of the 85 children who were MOG-abs positive at incident ADS were found in follow-up to have a relapsing disease; 9 were diagnosed as relapsing non-MS phenotypically, while 11 children met criteria for MS but with atypical clinical features (relapses largely restricted to optic nerves or spinal cord, MRI features at baseline and/or changes over time inconsistent with typical MS). Only 50% of the relapsing patients remained seropositive for the whole length of observation (median 4.7, range 1.7-12.1 years). Three (4%) of the MOG positive and 10 (5%) of the negative children had seizures.
Conclusion: The presence of MOGabs at the time of clinical onset, identifies a subgroup of children with clinical and MRI features distinct from MS.
Disclosure: P. Waters is a named inventor on patents for antibody assays and has received royalties. He has received consulting or speaking fees from Biogen Idec, Euroimmun AG, and Mereo Biopharma and travel grants from the Guthy-Jackson Charitable Foundation.G. Fadda has no disclosure related to this work. SR Irani is P. Waters coapplicant and receive royalties on patent application WO/2010/046716 entitled ´Neurological Autoimmune Disorders´. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. M. Woodall has no disclosure related to this work. R. A. Brown has received personal compensation for consulting services from Biogen Idec and NeuroRx Research.J. O´Mahony has no disclosure related to this work. Dr. Castro has nothing to disclose. G. Longoni receives training and research support from the National Multiple Sclerosis Society. R. A. Marrie: receives research funding from Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, National Multiple Sclerosis Society, Rx & D Health Research Foundation, the Waugh Family Chair in Multiple Sclerosis, Crohn´s and Colitis Canada, and has conducted clinical trials funded by Sanofi- Aventis. E. A. Yeh has received funds from NMSS, CIHI, CIHR, OIRM, MS Society of Canada, Mario Battaglia Foundation, SickKids Foundation, CBMH Innovation Fund, CMSC, Rare Diseases Foundation and Guthy Jackson Foundation. She serves as a relapse adjudicator for ACI. She has served on a scientific advisory panel for Juno Therapeutics and has received a speaker´s honorarium from Novartis. D. Arnold has served on advisory boards, received speaker honoraria, served as a consultant, or received research support from Adelphi, Biogen, Celgene, Genentech, Genzyme, Medday, NeuroRx Research, Novartis, Pfizer, Receptos, Roche, Sanofi, the Canadian Institutes of Health Research, and the Multiple Sclerosis Society of Canada; and holds stock in NeuroRx Research. B. Banwell serves as a central MRI reviewer for Novartis in the context of a clinical trial, and as a non-remunerated advisor on clinical trial design to Sanofi-Aventis, Novartis, Biogen-IDEC, and Teva Neuroscience. Dr. Banwell has received grant support as listed above, as well as from the MS Society of Canada, CIHR, NIH, and NMSS. A. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Biogen Idec, Diogenix, Roche/Genentech, Sanofi-Genzyme, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Teva Neuroscience, Celgene/Receptos Inc, and Merck/EMD Serono.