Autoimmune Encephalitis in Children

Abstract

Autoimmune encephalitis (AIE) can produce a very wide range of neuropsychiatric symptoms. A major challenge in diagnosis is that different symptoms may appear at different times and different levels of intensity, so the disease may mimic many other disorders. Pathogenesis is likely to be mediated by antibodies (Abs) to CNS proteins. This article focuses on recent clinical advances, newly characterized Abs, and treatment approaches to these disorders.

Keywords

autoimmune encephalitis - antibodies - childhood

Note

Laura Papetti is participating in a PhD program in biotechnology at the Sapienza University of Rome.

• References

• 1 Pillai SC, Hacohen Y, Tantsis E. , et al. Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome. Pediatrics 2015; 135 (04) e974-e984
• 2 Ramanathan S, Mohammad SS, Brilot F, Dale RC. Autoimmune encephalitis: recent updates and emerging challenges. J Clin Neurosci 2014; 21 (05) 722-730
• 3 Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol 2014; 27 (03) 361-368
• 4 Erol I. Autoimmune encephalitis in children. Minerva Pediatr 2013; 65 (03) 295-305
• 5 Graus F, Delattre JY, Antoine JC. , et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75 (08) 1135-1140
• 6 Vincent A, Buckley C, Schott JM. , et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127 (Pt 3): 701-712
• 7 Suleiman J, Dale RC. The recognition and treatment of autoimmune epilepsy in children. Dev Med Child Neurol 2015; 57 (05) 431-440
• 8 Irani SR, Vincent A. NMDA receptor antibody encephalitis. Curr Neurol Neurosci Rep 2011; 11 (03) 298-304
• 9 Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmau J. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol 2005; 58 (04) 594-604
• 10 Vincent A, Bien CG. Anti-NMDA-receptor encephalitis: a cause of psychiatric, seizure, and movement disorders in young adults. Lancet Neurol 2008; 7 (12) 1074-1075
• 11 Florance NR, Davis RL, Lam C. , et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66 (01) 11-18
• 12 Gable MS, Gavali S, Radner A. , et al. Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 2009; 28 (12) 1421-1429
• 13 Lim M. Childhood N-methyl-D-aspartic acid receptor (NMDAR) antibody mediated encephalitis. Neuropediatrics 2011; 42 (05) 177-178
• 14 Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011; 10 (01) 63-74
• 15 Irani SR, Bera K, Waters P. , et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 2010; 133 (Pt 6): 1655-1667
• 16 Granerod J, Ambrose HE, Davies NW. , et al; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10 (12) 835-844
• 17 Titulaer MJ, McCracken L, Gabilondo I. , et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013; 12 (02) 157-165
• 18 Dalmau J, Gleichman AJ, Hughes EG. , et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7 (12) 1091-1098
• 19 Miya K, Takahashi Y, Mori H. Anti-NMDAR autoimmune encephalitis. Brain Dev 2014; 36 (08) 645-652
• 20 Tsutsui K, Kanbayashi T, Tanaka K. , et al. Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features. BMC Psychiatry 2012; 12: 37 . https://doi.org/10.1186/1471-244X-12-37
• 21 Steiner J, Walter M, Glanz W. , et al. Increased prevalence of diverse N-methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis. JAMA Psychiatry 2013; 70 (03) 271-278
• 22 Barry H, Hardiman O, Healy DG. , et al. Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis. Br J Psychiatry 2011; 199 (06) 508-509
• 23 Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol 2014; 27 (03) 361-368
• 24 Gastaldi M, Thouin A, Vincent A. Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics 2016; 13 (01) 147-162
• 25 Hart IK, Waters C, Vincent A. , et al. Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Ann Neurol 1997; 41 (02) 238-246
• 26 Vincent A. Autoimmune channelopathies: John Newsom-Davis's work and legacy. A summary of the Newsom-Davis Memorial Lecture 2008. J Neuroimmunol 2008; 201–202: 245-249
• 27 Buckley C, Oger J, Clover L. , et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol 2001; 50 (01) 73-78
• 28 Pozo-Rosich P, Clover L, Saiz A, Vincent A, Graus F. Voltage-gated potassium channel antibodies in limbic encephalitis. Ann Neurol 2003; 54 (04) 530-533
• 29 Tofaris GK, Irani SR, Cheeran BJ, Baker IW, Cader ZM, Vincent A. Immunotherapy-responsive chorea as the presenting feature of LGI1-antibody encephalitis. Neurology 2012; 79 (02) 195-196
• 30 Klein CJ, Lennon VA, Aston PA, McKeon A, Pittock SJ. Chronic pain as a manifestation of potassium channel-complex autoimmunity. Neurology 2012; 79 (11) 1136-1144
• 31 Majoie HJ, de Baets M, Renier W, Lang B, Vincent A. Antibodies to voltage-gated potassium and calcium channels in epilepsy. Epilepsy Res 2006; 71 (2-3): 135-141
• 32 Suleiman J, Brenner T, Gill D. , et al. VGKC antibodies in pediatric encephalitis presenting with status epilepticus. Neurology 2011; 76 (14) 1252-1255
• 33 Kruer MC, Hoeftberger R, Lim KY. , et al. Aggressive course in encephalitis with opsoclonus, ataxia, chorea, and seizures: the first pediatric case of γ-aminobutyric acid type B receptor autoimmunity. JAMA Neurol 2014; 71 (05) 620-623
• 34 Petit-Pedrol M, Armangue T, Peng X. , et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol 2014; 13 (03) 276-286
• 35 Damásio J, Leite MI, Coutinho E. , et al. Progressive encephalomyelitis with rigidity and myoclonus: the first pediatric case with glycine receptor antibodies. JAMA Neurol 2013; 70 (04) 498-501
• 36 Hacohen Y, Wright S, Waters P. , et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013; 84 (07) 748-755
• 37 Wuerfel E, Bien CG, Vincent A, Woodhall M, Brockmann K. Glycine receptor antibodies in a boy with focal epilepsy and episodic behavioral disorder. J Neurol Sci 2014; 343 (1–2): 180-182
• 38 Saiz A, Blanco Y, Sabater L. , et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008; 131 (Pt 10): 2553-2563
• 39 Mishra N, Rodan LH, Nita DA, Gresa-Arribas N, Kobayashi J, Benseler SM. Anti-glutamic Acid decarboxylase antibody associated limbic encephalitis in a child: expanding the spectrum of pediatric inflammatory brain diseases. J Child Neurol 2014; 29 (05) 677-683
• 40 Baumann M, Hennes EM, Schanda K. , et al. Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): Extending the spectrum of MOG antibody positive diseases. Mult Scler 2016; 22 (14) 1821-1829
• 41 Tenembaum SN. Acute disseminated encephalomyelitis. Handb Clin Neurol 2013; 112: 1253-1262
• 42 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
• 43 Banwell B, Tenembaum S, Lennon VA. , et al. Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology 2008; 70 (05) 344-352
• 44 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 (07) 941-946
• 45 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 (02) e81 . doi: 10.1212/NXI.0000000000000081
• 46 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
• 47 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 (03) 265-272
• 48 Brain L, Jellinek EH, Ball K. Hashimoto's disease and encephalopathy. Lancet 1966; 2 (7462): 512-514
• 49 Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopathy: syndrome or myth?. Arch Neurol 2003; 60 (02) 164-171
• 50 Mocellin R, Walterfang M, Velakoulis D. Hashimoto's encephalopathy : epidemiology, pathogenesis and management. CNS Drugs 2007; 21 (10) 799-811
• 51 Hoffmann F, Reiter K, Kluger G. , et al. Seizures, psychosis and coma: severe course of hashimoto encephalopathy in a six-year-old girl. Neuropediatrics 2007; 38 (04) 197-199
• 52 Yu HJ, Lee J, Seo DW, Lee M. Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy. J Child Neurol 2014; 29 (07) 938-942
• 53 Alink J, de Vries TW. Unexplained seizures, confusion or hallucinations: think Hashimoto encephalopathy. Acta Paediatr 2008; 97 (04) 451-453
• 54 Payer J, Petrovic T, Baqi L, Lisy L, Langer P. Hashimoto's encephalopathy and rare cases of hyperthyroidism (review and case report). Endocr Regul 2009; 43 (04) 169-178
• 55 Watemberg N, Greenstein D, Levine A. Encephalopathy associated with Hashimoto thyroiditis: pediatric perspective. J Child Neurol 2006; 21 (01) 1-5
• 56 Schäuble B, Castillo PR, Boeve BF, Westmoreland BF. EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis. Clin Neurophysiol 2003; 114 (01) 32-37
• 57 Pozo-Rosich P, Villoslada P, Canton A, Simo R, Rovira A, Montalban X. Reversible white matter alterations in encephalopathy associated with autoimmune thyroid disease. J Neurol 2002; 249 (08) 1063-1065
• 58 Schiess N, Pardo CA. Hashimoto's encephalopathy. Ann N Y Acad Sci 2008; 1142: 254-265
• 59 Ferracci F, Carnevale A. The neurological disorder associated with thyroid autoimmunity. J Neurol 2006; 253 (08) 975-984