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Neuropediatrics 2016; 47(04): 245-252
DOI: 10.1055/s-0036-1583184
Original Article
Georg Thieme Verlag KG Stuttgart · New York

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

Salini Thulasirajah
1   Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
,
Daniela Pohl
1   Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
,
Jorge Davila-Acosta
1   Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
,
Sunita Venkateswaran
1   Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
› Author Affiliations
Further Information

Publication History

15 January 2016

07 March 2016

Publication Date:
29 April 2016 (online)

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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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 13 Willison HJ, Linington C. Antibodies to MOG in NMO: a seasoned veteran finds a new role. Neurology 2012; 79 (12) 1198-1199
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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;
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar