Sophie Duignan1, Sukhvir Wright2, Tom Rossor3, John Cazabon4, Kimberly Gilmour5, Olga Ciccarelli6,7, Evangeline Wassmer2, Ming Lim3,8, Cheryl Hemingway1, Yael Hacohen1,6. 1. Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, UK. 2. Department of Paediatric Neurology, Birmingham Children's Hospital, Birmingham, UK. 3. Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK. 4. Immunology Department, King's College Hospital, London, UK. 5. Immunology Department, Great Ormond Street Hospital for Children, London, UK. 6. Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, UK. 7. National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre (BRC), London, UK. 8. Faculty of Life Sciences and Medicine, Kings College, London, UK.
Abstract
AIM: Our objectives were to evaluate the utility of measuring myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in clinical practice and describe their associated neurological phenotypes in children. METHOD: Between 2012 and 2017, 371 children with suspected acquired demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG-Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and demographic data compiled. Clinical phenotyping was performed blinded to the antibody results. RESULTS: After review, 237 of the 371 were diagnosed with ADS. Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%) were AQP4-Ab positive. None were positive for both autoantibodies. All 134 patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75 (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6 were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab remained positive during the disease course compared to 35 out of 43 MOG-Ab (13/16 monophasic and 22/27 relapsing). INTERPRETATION: Myelin oligodendrocyte glycoprotein antibodies were identified in a third of children with ADS. Almost half of the MOG-Ab positive children relapsed and the majority of them remained antibody positive over 4-years follow-up. WHAT THIS PAPER ADDS: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are not identified in children with peripheral demyelination or genetic leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients relapse, higher than previously thought. Seroconversion to MOG-Ab negative status is infrequent; patients may test MOG-Ab positive at follow-up sampling even when asymptomatic. Myelin oligodendrocyte glycoprotein antibodies status should only be used in conjunction with the clinical information to guide maintenance therapy.
AIM: Our objectives were to evaluate the utility of measuring myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in clinical practice and describe their associated neurological phenotypes in children. METHOD: Between 2012 and 2017, 371 children with suspected acquired demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG-Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and demographic data compiled. Clinical phenotyping was performed blinded to the antibody results. RESULTS: After review, 237 of the 371 were diagnosed with ADS. Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%) were AQP4-Ab positive. None were positive for both autoantibodies. All 134 patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75 (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6 were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab remained positive during the disease course compared to 35 out of 43 MOG-Ab (13/16 monophasic and 22/27 relapsing). INTERPRETATION:Myelin oligodendrocyte glycoprotein antibodies were identified in a third of children with ADS. Almost half of the MOG-Ab positive children relapsed and the majority of them remained antibody positive over 4-years follow-up. WHAT THIS PAPER ADDS: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are not identified in children with peripheral demyelination or genetic leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients relapse, higher than previously thought. Seroconversion to MOG-Ab negative status is infrequent; patients may test MOG-Ab positive at follow-up sampling even when asymptomatic. Myelin oligodendrocyte glycoprotein antibodies status should only be used in conjunction with the clinical information to guide maintenance therapy.
Authors: D H Whittam; V Karthikeayan; E Gibbons; R Kneen; S Chandratre; O Ciccarelli; Y Hacohen; J de Seze; K Deiva; R Q Hintzen; B Wildemann; S Jarius; I Kleiter; K Rostasy; P Huppke; B Hemmer; F Paul; O Aktas; A K Pröbstel; G Arrambide; M Tintore; M P Amato; M Nosadini; M M Mancardi; M Capobianco; Z Illes; A Siva; A Altintas; G Akman-Demir; L Pandit; M Apiwattankul; J Y Hor; S Viswanathan; W Qiu; H J Kim; I Nakashima; K Fujihara; S Ramanathan; R C Dale; M Boggild; S Broadley; M A Lana-Peixoto; D K Sato; S Tenembaum; P Cabre; D M Wingerchuk; B G Weinshenker; B Greenberg; M Matiello; E C Klawiter; J L Bennett; A I Wallach; I Kister; B L Banwell; A Traboulsee; D Pohl; J Palace; M I Leite; M Levy; R Marignier; T Solomon; M Lim; S Huda; A Jacob Journal: J Neurol Date: 2020-07-04 Impact factor: 4.849
Authors: C L de Mol; Y Y M Wong; E D van Pelt; I A Ketelslegers; D P Bakker; M Boon; K P J Braun; K G J van Dijk; M J Eikelenboom; M Engelen; K Geleijns; C A Haaxma; J M F Niermeijer; E H Niks; E A J Peeters; C M P C D Peeters-Scholte; B T Poll-The; R P Portier; J F de Rijk-van Andel; J P A Samijn; H M Schippers; I N Snoeck; H Stroink; R J Vermeulen; A Verrips; F Visscher; J S H Vles; M A A P Willemsen; C E Catsman-Berrevoets; R Q Hintzen; R F Neuteboom Journal: J Neurol Date: 2018-03-22 Impact factor: 4.849