Contributions
Abstract: P668
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Paediatric MS
Antibodies against myelin oligodendrocyte glycoprotein (MOGabs) are detected in a subgroup of children with inflammatory demyelinating disease, some of whom have a relapsing disease course meeting the international diagnostic criteria for multiple sclerosis (MS).
Aim: To compare the baseline and serial clinical and MRI features of MOGabs+ and MOGabs- children diagnosed with MS.
Methods: MS was diagnosed based on clinical relapses or new MRI lesions according to international diagnostic criteria. The presence of MOGabs was assessed on serial serum samples of 66 children with a diagnosis of MS prospectively followed for a median of 5 years from first clinical episode. Serial MRI scans were analyzed with a standardized scoring tool, blinded to MOGabs status. T2 lesion volume was quantified by validated methods.
Results: At clinical onset, 11 MS patients were MOGabs+, 54 were MOGabs-, and one had a borderline result. MOGabs+ patients were younger (p< 0.0001), and all presented at age less than 11 years. The presenting phenotype was optic neuritis (ON) and/or transverse myelitis (TM) for 80% MOGabs+ versus 41% of the MOGabs- patients. Brain MRI scans at onset were available for 8/11 MOGabs+ and 41/54 MOGabs- patients. MRI brain at onset was atypical for MS in 7 MOGabs+ (88%) and 2 MOGabs- patients (5%, p = < 0.0001). In particular, 3 MOGabs+ patients had no brain lesions within 30 days from onset, 3 showed a diffuse bilateral pattern and 1 had only minimal lesions. Oligoclonal bands (OCBs) were detected in 2 of 8 (25%) MOGabs+ and in 30 of 36 MOGabs- patients (83%, p = 0.0027). At baseline, 5 MOGabs+ patients met 2010 and 2017 McDonald criteria for dissemination in space, while none met 2010 dissemination in time (DIT) due to absence of lesion enhancement. McDonald 2017 DIT was met at baseline by 2 MOGabs+ patients due to the presence of OCBs. Of 11 MOG+ patients, 10 developed new brain lesions over time, one developed new spinal cord lesions, and seven experienced clinical relapses, in almost all cases ON or TM. New lesions in MOG+ were significantly smaller than the ones in the MOGabs- group (p = 0.0004). Of 11 MOG+ patients, 3 were persistently seropositive over time and experienced clinical relapses, 6 became seronegative (3 of whom had clinical relapses), 2 developed borderline results (1 with clinical relapses).
Conclusion: MOGabs+ children have clinical relapses largely restricted to the optic nerve and spinal cord and MRI features atypical for MS.
Disclosure: G. Fadda has no disclosure related to this work. 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. R. A. Brown has received personal compensation for consulting services from Biogen Idec and NeuroRx Research. M. Woodhall has no disclosure related to this work. S.R. Irani is P. Waters coapplicant and receive royalties on patent application WO/2010/046716 entitled ´Neurological Autoimmune Disorders´. 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: P668
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Paediatric MS
Antibodies against myelin oligodendrocyte glycoprotein (MOGabs) are detected in a subgroup of children with inflammatory demyelinating disease, some of whom have a relapsing disease course meeting the international diagnostic criteria for multiple sclerosis (MS).
Aim: To compare the baseline and serial clinical and MRI features of MOGabs+ and MOGabs- children diagnosed with MS.
Methods: MS was diagnosed based on clinical relapses or new MRI lesions according to international diagnostic criteria. The presence of MOGabs was assessed on serial serum samples of 66 children with a diagnosis of MS prospectively followed for a median of 5 years from first clinical episode. Serial MRI scans were analyzed with a standardized scoring tool, blinded to MOGabs status. T2 lesion volume was quantified by validated methods.
Results: At clinical onset, 11 MS patients were MOGabs+, 54 were MOGabs-, and one had a borderline result. MOGabs+ patients were younger (p< 0.0001), and all presented at age less than 11 years. The presenting phenotype was optic neuritis (ON) and/or transverse myelitis (TM) for 80% MOGabs+ versus 41% of the MOGabs- patients. Brain MRI scans at onset were available for 8/11 MOGabs+ and 41/54 MOGabs- patients. MRI brain at onset was atypical for MS in 7 MOGabs+ (88%) and 2 MOGabs- patients (5%, p = < 0.0001). In particular, 3 MOGabs+ patients had no brain lesions within 30 days from onset, 3 showed a diffuse bilateral pattern and 1 had only minimal lesions. Oligoclonal bands (OCBs) were detected in 2 of 8 (25%) MOGabs+ and in 30 of 36 MOGabs- patients (83%, p = 0.0027). At baseline, 5 MOGabs+ patients met 2010 and 2017 McDonald criteria for dissemination in space, while none met 2010 dissemination in time (DIT) due to absence of lesion enhancement. McDonald 2017 DIT was met at baseline by 2 MOGabs+ patients due to the presence of OCBs. Of 11 MOG+ patients, 10 developed new brain lesions over time, one developed new spinal cord lesions, and seven experienced clinical relapses, in almost all cases ON or TM. New lesions in MOG+ were significantly smaller than the ones in the MOGabs- group (p = 0.0004). Of 11 MOG+ patients, 3 were persistently seropositive over time and experienced clinical relapses, 6 became seronegative (3 of whom had clinical relapses), 2 developed borderline results (1 with clinical relapses).
Conclusion: MOGabs+ children have clinical relapses largely restricted to the optic nerve and spinal cord and MRI features atypical for MS.
Disclosure: G. Fadda has no disclosure related to this work. 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. R. A. Brown has received personal compensation for consulting services from Biogen Idec and NeuroRx Research. M. Woodhall has no disclosure related to this work. S.R. Irani is P. Waters coapplicant and receive royalties on patent application WO/2010/046716 entitled ´Neurological Autoimmune Disorders´. 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.