Myelin Oligodendrocyte Glycoprotein-Associated Pediatric Central Nervous System Demyelination: Clinical Course, Neuroimaging Findings, and Response to Therapy

Abstract

Under the umbrella of pediatric-acquired demyelinating syndromes, there is a multitude of disorders, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), and neuromyelitis optica spectrum disorders (NMOSD). Due to overlapping clinical and magnetic resonance imaging (MRI) features, it can be challenging to provide an accurate diagnosis. In view of therapeutic and prognostic implications, an early and reliable diagnosis is however of utmost importance. Recent studies of myelin oligodendrocyte glycoprotein (MOG) identify MOG, as a promising target for antibody-mediated demyelination and a biomarker for a relatively benign and non-MS disease course. We describe the clinical and MRI presentation of five children presenting with an acute, severe central nervous system inflammatory disease involving the brain and spinal cord, all of whom were positive for MOG-IgG antibody. Encephalopathy was uncommon at presentation and all had quick resolution of symptoms with intravenous steroid and intravenous immunoglobulin (IVIG) treatment. All patients recovered well, and have been treated with IVIG to potentially prevent relapses.

Keywords

demyelination - MOG - multiple sclerosis - optic neuritis - transverse myelitis

• References

• 1 Mayer MC, Meinl E. Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more. Ther Adv Neurol Disord 2012; 5 (3) 147-159
• 2 Lennon VA, Wingerchuk DM, Kryzer TJ , et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364 (9451) 2106-2112
• 3 Pröbstel A-K, Rudolf G, Dornmair K , et al. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. J Neuroinflammation 2015; 12 (1) 46
• 4 Martinez-Hernandez E, Sepulveda M, Rostásy K , et al. Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor α1 subunit in patients with isolated optic neuritis. JAMA Neurol 2015; 72 (2) 187-193
• 5 Ramanathan S, Reddel SW, Henderson A , et al. Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis. Neurol Neuroimmunol Neuroinflamm 2014; 1 (4) e40-e40
• 6 Hacohen Y, Absoud M, Deiva K , et al. Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol Neuroimmunol Neuroinflamm 2015; 2 (2) e81
• 7 Saadoun S, Waters P, Owens GP, Bennett JL, Vincent A, Papadopoulos MC. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol Commun 2014; 2 (1) 35
• 8 Gao J, Pan W, Zhang H. Features of neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies. JAMA Neurol 2014; 71 (7) 923-924
• 9 Cobo-Calvo Á, Sepúlveda M, Bernard-Valnet R , et al. Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody seronegative longitudinally extensive transverse myelitis: Clinical and prognostic implications. Mult Scler 2016; 22 (3) 312-319
• 10 Tanaka M, Tanaka K. Anti-MOG antibodies in adult patients with demyelinating disorders of the central nervous system. J Neuroimmunol 2014; 270 (1–2) 98-99
• 11 Waters P, Woodhall M, O'Connor KC , et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm 2015; 2 (3) e89-e89
• 12 Aktas O. Collateral benefit: the comeback of MOG antibodies as a biomarker in neurological practice. J Neurol Neurosurg Psychiatry 2015; 86 (3) 243-243
• 13 Willison HJ, Linington C. Antibodies to MOG in NMO: a seasoned veteran finds a new role. Neurology 2012; 79 (12) 1198-1199
• 14 Höftberger R, Sepulveda M, Armangue T , et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler 2015; 21 (7) 866-874
• 15 Reindl M, Di Pauli F, Rostásy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013; 9 (8) 455-461
• 16 Rostasy K, Mader S, Schanda K , et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol 2012; 69 (6) 752-756
• 17 Pröbstel AK, Dornmair K, Bittner R , et al. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 2011; 77 (6) 580-588
• 18 Brilot F, Dale RC, Selter RC , et al. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol 2009; 66 (6) 833-842
• 19 Ketelslegers IA, Van Pelt DE, Bryde S , et al. Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort. Mult Scler 2015; 21 (12) 1513-1520
• 20 Di Pauli F, Mader S, Rostasy K , et al. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin Immunol 2011; 138 (3) 247-254
• 21 Kitley J, Waters P, Woodhall M , et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol 2014; 71 (3) 276-283
• 22 Mader S, Gredler V, Schanda K , et al. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation 2011; 8: 184
• 23 Huppke P, Rostasy K, Karenfort M , et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler 2013; 19 (7) 941-946
• 24 Kitley J, Woodhall M, Waters P , et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012; 79 (12) 1273-1277
• 25 Lechner C, Baumann M, Hennes E-M , et al. Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J Neurol Neurosurg Psychiatry 2015;
• 26 Baumann M, Sahin K, Lechner C , et al. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry 2015; 86 (3) 265-272
• 27 Krupp LB, Tardieu M, Amato MP , et al; International Pediatric Multiple Sclerosis Study Group. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 2013; 19 (10) 1261-1267
• 28 Tsuburaya RS, Miki N, Tanaka K , et al. Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in a Japanese boy with recurrent optic neuritis. Brain Dev 2015; 37 (1) 145-148
• 29 Sato DK, Callegaro D, Lana-Peixoto MA , et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82 (6) 474-481
• 30 Hacohen Y, Absoud M, Woodhall M , et al; UK & Ireland Childhood CNS Inflammatory Demyelination Working Group. Autoantibody biomarkers in childhood-acquired demyelinating syndromes: results from a national surveillance cohort. J Neurol Neurosurg Psychiatry 2014; 85 (4) 456-461
• 31 Spadaro M, Gerdes LA, Mayer MC , et al. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol 2015; 2 (3) 295-301
• 32 Di Pauli F, Höftberger R, Reindl M , et al. Fulminant demyelinating encephalomyelitis: Insights from antibody studies and neuropathology. Neurol Neuroimmunol Neuroinflamm 2015; 2 (6) e175