Acute and Chronic Therapies in Pediatric Inflammatory Central Nervous System Diseases

Abstract

Recognition of pediatric neuroinflammatory disorders has increased in recent years, together with an increased knowledge of the immune mechanisms underlying these disorders. These insights have led to paying greater attention to the classification of these disorders, and importantly, increasing information on therapeutic interventions that may improve outcomes. Furthermore, this has occurred in the wake of the development of multiple targeted immune therapies, thus creating a complex treatment landscape. This review aims to summarize the available literature regarding acute and chronic therapies for pediatric inflammatory central nervous system (CNS) disorders. A standardized approach to the initial management of these diseases is presented.

Keywords

neuroinflammatory disorders - autoimmune disorders - immune therapy

• References

• 1 Byrne S, Walsh C, Hacohen Y. , et al. Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome. Neurol Neuroimmunol Neuroinflamm 2015; 2 (04) e130
• 2 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
• 3 Mitchell WG, Wooten AA, O'Neil SH, Rodriguez JG, Cruz RE, Wittern R. Effect of increased immunosuppression on developmental outcome of opsoclonus myoclonus syndrome (OMS). J Child Neurol 2015; 30 (08) 976-982
• 4 Longoni G, Levy DM, Yeh EA. The changing landscape of childhood inflammatory central nervous system disorders. J Pediatr 2016; 179: 24-32.e2
• 5 Milligan NM, Newcombe R, Compston DA. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects. J Neurol Neurosurg Psychiatry 1987; 50 (05) 511-516
• 6 Beck RW, Cleary PA, Anderson Jr MM. , et al; The Optic Neuritis Study Group. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992; 326 (09) 581-588
• 7 Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 1999; 53 (05) 1107-1114
• 8 Zekeridou A, Karantoni E, Viaccoz A. , et al. Treatment and outcome of children and adolescents with N-methyl-D-aspartate receptor encephalitis. J Neurol 2015; 262 (08) 1859-1866
• 9 Hutchinson C, Elbers J, Halliday W. , et al. Treatment of small vessel primary CNS vasculitis in children: an open-label cohort study. Lancet Neurol 2010; 9 (11) 1078-1084
• 10 Sébire G, Hollenberg H, Meyer L, Huault G, Landrieu P, Tardieu M. High dose methylprednisolone in severe acute transverse myelopathy. Arch Dis Child 1997; 76 (02) 167-168
• 11 Kalra V, Sharma S, Sahu J. , et al. Childhood acute transverse myelitis: clinical profile, outcome, and association with antiganglioside antibodies. J Child Neurol 2009; 24 (04) 466-471
• 12 Waldman AT, Gorman MP, Rensel MR, Austin TE, Hertz DP, Kuntz NL. ; Network of Pediatric Multiple Sclerosis Centers of Excellence of National Multiple Sclerosis Society. Management of pediatric central nervous system demyelinating disorders: consensus of United States neurologists. J Child Neurol 2011; 26 (06) 675-682
• 13 Le Page E, Veillard D, Laplaud DA. , et al; COPOUSEP investigators; West Network for Excellence in Neuroscience. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet 2015; 386 (9997): 974-981
• 14 La Mantia L, Eoli M, Milanese C, Salmaggi A, Dufour A, Torri V. Double-blind trial of dexamethasone versus methylprednisolone in multiple sclerosis acute relapses. Eur Neurol 1994; 34 (04) 199-203
• 15 Zwanikken CM, Zorgdrager A, Oenema D, Boon M. ; De Keyser J. Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone: a pilot study. J Clin Neurosci 1999; 6 (05) 382-384
• 16 Perumal JS, Caon C, Hreha S. , et al. Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis. Eur J Neurol 2008; 15 (07) 677-680
• 17 Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville BG. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 2000; 123 (Pt 12): 2407-2422
• 18 Anlar B, Basaran C, Kose G. , et al. Acute disseminated encephalomyelitis in children: outcome and prognosis. Neuropediatrics 2003; 34 (04) 194-199
• 19 Watanabe S, Misu T, Miyazawa I. , et al. Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis. Mult Scler 2007; 13 (08) 968-974
• 20 Jarius S, Ruprecht K, Kleiter I. , et al; in cooperation with the Neuromyelitis Optica Study Group (NEMOS). MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation 2016; 13 (01) 279
• 21 Larkins N, Kim S, Craig J, Hodson E. Steroid-sensitive nephrotic syndrome: an evidence-based update of immunosuppressive treatment in children. Arch Dis Child 2016; 101 (04) 404-408
• 22 Brucato A, Imazio M, Gattorno M. , et al. Effect of anakinra on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence: The AIRTRIP randomized clinical trial. JAMA 2016; 316 (18) 1906-1912
• 23 Nosadini M, Mohammad SS, Suppiej A, Sartori S, Dale RC. ; IVIG in Neurology Study Group. Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long-term outcome. Dev Med Child Neurol 2016; 58 (11) 1180-1192
• 24 Elovaara I, Apostolski S, van Doorn P. , et al; EFNS. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol 2008; 15 (09) 893-908
• 25 Feasby T, Banwell B, Benstead T. , et al. Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev 2007; 21 (02) (Suppl. 01) S57-S107
• 26 Sorensen PS, Haas J, Sellebjerg F, Olsson T, Ravnborg M. ; TARIMS Study Group. IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS. Neurology 2004; 63 (11) 2028-2033
• 27 Visser LH, Beekman R, Tijssen CC. , et al. A randomized, double-blind, placebo-controlled pilot study of i.v. immune globulins in combination with i.v. methylprednisolone in the treatment of relapses in patients with MS. Mult Scler 2004; 10 (01) 89-91
• 28 Nishikawa M, Ichiyama T, Hayashi T, Ouchi K, Furukawa S. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol 1999; 21 (02) 583-586
• 29 Marchioni E, Marinou-Aktipi K, Uggetti C. , et al. Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis. J Neurol 2002; 249 (01) 100-104
• 30 DeSena A, Graves D, Morriss MC, Greenberg BM. Transverse myelitis plus syndrome and acute disseminated encephalomyelitis plus syndrome: a case series of 5 children. JAMA Neurol 2014; 71 (05) 624-629
• 31 Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler 2014; 20 (04) 501-504
• 32 Shin YW, Lee ST, Shin JW. , et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol 2013; 265 (1–2): 75-81
• 33 Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011; 76 (03) 294-300
• 34 Schwartz J, Padmanabhan A, Aqui N. , et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. Shaz B, ed. J Clin Apher 2016; 31 (03) 149-162
• 35 Abboud H, Petrak A, Mealy M, Sasidharan S, Siddique L, Levy M. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler 2016; 22 (02) 185-192
• 36 DeSena AD, Noland DK, Matevosyan K. , et al. Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-D-aspartate receptor antibody encephalitis: a retrospective review. J Clin Apher 2015; 30 (04) 212-216
• 37 Armstrong MB, Robertson PL, Castle VP. Delayed, recurrent opsoclonus-myoclonus syndrome responding to plasmapheresis. Pediatr Neurol 2005; 33 (05) 365-367
• 38 Weinshenker BG, O'Brien PC, Petterson TM. , et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999; 46 (06) 878-886
• 39 Bigi S, Banwell B, Yeh EA. Outcomes after early administration of plasma exchange in pediatric central nervous system inflammatory demyelination. J Child Neurol 2015; 30 (07) 874-880
• 40 Magaña SM, Keegan BM, Weinshenker BG. , et al. Beneficial plasma exchange response in central nervous system inflammatory demyelination. Arch Neurol 2011; 68 (07) 870-878
• 41 Borras-Novell C, García Rey E, Perez Baena LF, Jordan Garcia I, Catella Cahiz D, Cambra F. Therapeutic plasma exchange in acute disseminated encephalomyelitis in children. J Clin Apher 2015; 30 (06) 335-339
• 42 Banwell B, Kennedy J, Sadovnick D. , et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology 2009; 72 (03) 232-239
• 43 Banwell B, Bar-Or A, Arnold DL. , et al. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol 2011; 10 (05) 436-445
• 44 Kappos L, Polman CH, Freedman MS. , et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006; 67 (07) 1242-1249
• 45 Comi G, Martinelli V, Rodegher M. , et al; PreCISe study group. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009; 374 (9700): 1503-1511
• 46 Miller AE, Wolinsky JS, Kappos L. , et al; TOPIC Study Group. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13 (10) 977-986
• 47 Iaffaldano P, Simone M, Lucisano G. , et al; Italian iMedWeb Registry and the MSBase Registry. Prognostic indicators in pediatric clinically isolated syndrome. Ann Neurol 2017; 81 (05) 729-739
• 48 Tardieu M, Banwell B, Wolinsky JS, Pohl D, Krupp LB. Consensus definitions for pediatric MS and other demyelinating disorders in childhood. Neurology 2016; 87 (09) (Suppl. 02) S8-S11
• 49 Matta AP, Nascimento OJ, Ferreira AC. , et al. No evidence of disease activity in multiple sclerosis patients. Expert Rev Neurother 2016; 16 (11) 1279-1284
• 50 Giovannoni G. Multiple sclerosis should be treated using a step-down strategy rather than a step-up strategy-YES. Mult Scler 2016; 22 (11) 1397-1400
• 51 Naismith RT. Multiple sclerosis should be treated using a step-down strategy rather than a step-up strategy-NO. Mult Scler 2016; 22 (11) 1400-1402
• 52 Yeh EA, Waubant E, Krupp LB. , et al; National Network of Pediatric MS Centers of Excellence. Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis. Arch Neurol 2011; 68 (04) 437-444
• 53 Chitnis T, Tenembaum S, Banwell B. , et al; International Pediatric Multiple Sclerosis Study Group. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler 2012; 18 (01) 116-127
• 54 The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 1995; 45 (07) 1277-1285
• 55 Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998; 352 (9139): 1498-1504
• 56 Jacobs LD, Cookfair DL, Rudick RA. , et al; The Multiple Sclerosis Collaborative Research Group (MSCRG). Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39 (03) 285-294
• 57 Calabresi PA, Kieseier BC, Arnold DL. , et al; ADVANCE Study Investigators. Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol 2014; 13 (07) 657-665
• 58 Kieseier BC, Arnold DL, Balcer LJ. , et al. Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Mult Scler 2015; 21 (08) 1025-1035
• 59 Pakdaman H, Fallah A, Sahraian MA, Pakdaman R, Meysamie A. Treatment of early onset multiple sclerosis with suboptimal dose of interferon beta-1a. Neuropediatrics 2006; 37 (04) 257-260
• 60 Pohl D, Rostásy K, Gärtner J, Hanefeld F. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology 2005; 64 (05) 888-890
• 61 Ghezzi A, Amato MP, Annovazzi P. , et al; ITEMS (Immunomodulatory Treatment of Early-onset MS) Group. Long-term results of immunomodulatory treatment in children and adolescents with multiple sclerosis: the Italian experience. Neurol Sci 2009; 30 (03) 193-199
• 62 Tenembaum SN, Banwell B, Pohl D. , et al; REPLAY Study Group. Subcutaneous interferon Beta-1a in pediatric multiple sclerosis: a retrospective study. J Child Neurol 2013; 28 (07) 849-856
• 63 Johnson KP, Brooks BR, Cohen JA. , et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45 (07) 1268-1276
• 64 Comi G, Filippi M, Wolinsky JS. ; European/Canadian Glatiramer Acetate Study Group. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging--measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol 2001; 49 (03) 290-297
• 65 Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R. ; GALA Study Group. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol 2013; 73 (06) 705-713
• 66 Wolinsky JS, Borresen TE, Dietrich DW. , et al; GLACIER Study Group. GLACIER: an open-label, randomized, multicenter study to assess the safety and tolerability of glatiramer acetate 40 mg three-times weekly versus 20 mg daily in patients with relapsing-remitting multiple sclerosis. Mult Scler Relat Disord 2015; 4 (04) 370-376
• 67 O'Connor P, Filippi M, Arnason B. , et al; BEYOND Study Group. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol 2009; 8 (10) 889-897
• 68 Mikol DD, Barkhof F, Chang P. , et al; REGARD study group. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol 2008; 7 (10) 903-914
• 69 Kornek B, Bernert G, Balassy C, Geldner J, Prayer D, Feucht M. Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis. Neuropediatrics 2003; 34 (03) 120-126
• 70 Kappos L, Wiendl H, Selmaj K. , et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med 2015; 373 (15) 1418-1428
• 71 Gorman MP, Tillema JM, Ciliax AM, Guttmann CRG, Chitnis T. Daclizumab use in patients with pediatric multiple sclerosis. Arch Neurol 2012; 69 (01) 78-81
• 72 Zynbryta [FDA label]. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761029Orig1s000Lbl.pdf . Accessed April 29, 2017
• 73 Kappos L, Radue EW, O'Connor P. , et al; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362 (05) 387-401
• 74 Cohen JA, Barkhof F, Comi G. , et al; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362 (05) 402-415
• 75 Calabresi PA, Radue EW, Goodin D. , et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13 (06) 545-556
• 76 Fragoso YD, Alves-Leon SV, Barreira AA. , et al. Fingolimod prescribed for the treatment of multiple sclerosis in patients younger than age 18 years. Pediatr Neurol 2015; 53 (02) 166-168
• 77 Gold R, Kappos L, Arnold DL. , et al; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367 (12) 1098-1107
• 78 Fox RJ, Miller DH, Phillips JT. , et al; CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367 (12) 1087-1097
• 79 Makhani N, Schreiner T. Oral dimethyl fumarate in children with multiple sclerosis: a dual-center study. Pediatr Neurol 2016; 57: 101-104
• 80 O'Connor P, Wolinsky JS, Confavreux C. , et al; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365 (14) 1293-1303
• 81 Vermersch P, Czlonkowska A, Grimaldi LME. , et al; TENERE Trial Group. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler 2014; 20 (06) 705-716
• 82 Polman CH, O'Connor PW, Havrdova E. , et al; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354 (09) 899-910
• 83 Rudick RA, Stuart WH, Calabresi PA. , et al; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354 (09) 911-923
• 84 Ghezzi A, Moiola L, Pozzilli C. , et al; MS Study Group-Italian Society of Neurology. Natalizumab in the pediatric MS population: results of the Italian registry. BMC Neurol 2015; 15 (01) 174
• 85 Hauser SL, Waubant E, Arnold DL. , et al; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358 (07) 676-688
• 86 Beres SJ, Graves J, Waubant E. Rituximab use in pediatric central demyelinating disease. Pediatr Neurol 2014; 51 (01) 114-118
• 87 Salzer J, Lycke J, Wickström R, Naver H, Piehl F, Svenningsson A. Rituximab in paediatric onset multiple sclerosis: a case series. J Neurol 2016; 263 (02) 322-326
• 88 Hauser SL, Bar-Or A, Comi G. , et al; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus interferon Beta-1a in relapsing multiple sclerosis. N Engl J Med 2017; 376 (03) 221-234
• 89 Coles AJ, Twyman CL, Arnold DL. , et al; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012; 380 (9856): 1829-1839
• 90 Cohen JA, Coles AJ, Arnold DL. , et al; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012; 380 (9856): 1819-1828
• 91 Edan G, Miller D, Clanet M. , et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 1997; 62 (02) 112-118
• 92 Hartung HP, Gonsette R, König N. , et al; Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360 (9350): 2018-2025
• 93 Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M. ; French–Italian Mitoxantrone Interferon-beta-1b Trial Group. Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial. J Neurol Neurosurg Psychiatry 2011; 82 (12) 1344-1350
• 94 Kornek B, Bernert G, Rostasy K. , et al. Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis. Neuropediatrics 2011; 42 (01) 7-12
• 95 Weiner HL, Cohen JA. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Mult Scler 2002; 8 (02) 142-154
• 96 Gladstone DE, Zamkoff KW, Krupp L. , et al. High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis. Arch Neurol 2006; 63 (10) 1388-1393
• 97 Patti F, Reggio E, Palermo F. , et al. Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta. J Neurol 2004; 251 (12) 1502-1506
• 98 Smith DR, Weinstock-Guttman B, Cohen JA. , et al. A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult Scler 2005; 11 (05) 573-582
• 99 Makhani N, Gorman MP, Branson HM, Stazzone L, Banwell BL, Chitnis T. Cyclophosphamide therapy in pediatric multiple sclerosis. Neurology 2009; 72 (24) 2076-2082
• 100 Wingerchuk DM, Banwell B, Bennett JL. , et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85 (02) 177-189
• 101 Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol 2015; 27 (06) 489-495
• 102 Graus F, Titulaer MJ, Balu R. , et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404
• 103 Pranzatelli MR, Travelstead AL, Tate ED, Allison TJ, Verhulst SJ. CSF B-cell expansion in opsoclonus-myoclonus syndrome: a biomarker of disease activity. Mov Disord 2004; 19 (07) 770-777
• 104 Panzer JA, Anand R, Dalmau J, Lynch DR. Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia syndrome. J Neuroimmunol 2015; 286: 86-92
• 105 Waters PJ, McKeon A, Leite MI. , et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology 2012; 78 (09) 665-671 ; discussion 669
• 106 Rostásy K, Mader S, Hennes EM. , et al. Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica. Mult Scler 2013; 19 (08) 1052-1059
• 107 Banwell B, Tenembaum S, Lennon VA. , et al. Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology 2008; 70 (05) 344-352
• 108 Fragoso YD, Ferreira MLB, Oliveira EML. , et al. Neuromyelitis optica with onset in childhood and adolescence. Pediatr Neurol 2014; 50 (01) 66-68
• 109 Collongues N, Marignier R, Zéphir H. , et al. Long-term follow-up of neuromyelitis optica with a pediatric onset. Neurology 2010; 75 (12) 1084-1088
• 110 Longoni G, Banwell B, Filippi M, Yeh EA. Rituximab as a first-line preventive treatment in pediatric NMOSDs: preliminary results in 5 children. Neurol Neuroimmunol Neuroinflamm 2014; 1 (04) e46
• 111 Kim SH, Jeong IH, Hyun JW. , et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol 2015; 72 (09) 989-995
• 112 Nosadini M, Alper G, Riney CJ. , et al. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm 2016; 3 (01) e188
• 113 Costanzi C, Matiello M, Lucchinetti CF. , et al. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology 2011; 77 (07) 659-666
• 114 Chen H, Qiu W, Zhang Q. , et al. Comparisons of the efficacy and tolerability of mycophenolate mofetil and azathioprine as treatments for neuromyelitis optica and neuromyelitis optica spectrum disorder. Eur J Neurol 2017; 24 (01) 219-226
• 115 Jeong IH, Park B, Kim SH, Hyun JW, Joo J, Kim HJ. Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder using multifaceted endpoints. Mult Scler 2016; 22 (03) 329-339
• 116 Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M. Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol 2014; 71 (03) 324-330
• 117 Araki M, Matsuoka T, Miyamoto K. , et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology 2014; 82 (15) 1302-1306
• 118 Ayzenberg I, Kleiter I, Schröder A. , et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 2013; 70 (03) 394-397
• 119 Ringelstein M, Ayzenberg I, Harmel J. , et al. Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol 2015; 72 (07) 756-763
• 120 Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 2013; 70 (09) 1110-1117
• 121 Brunklaus A, Pohl K, Zuberi SM, de Sousa C. Outcome and prognostic features in opsoclonus-myoclonus syndrome from infancy to adult life. Pediatrics 2011; 128 (02) e388-e394
• 122 Tate ED, Pranzatelli MR, Verhulst SJ. , et al. Active comparator-controlled, rater-blinded study of corticotropin-based immunotherapies for opsoclonus-myoclonus syndrome. J Child Neurol 2012; 27 (07) 875-884
• 123 Wright S, Hacohen Y, Jacobson L. , et al. N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children. Arch Dis Child 2015; 100 (06) 521-526
• 124 Sommeling C, Santens P. Anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody encephalitis in a male adolescent with a large mediastinal teratoma. J Child Neurol 2014; 29 (05) 688-690
• 125 Lee WJ, Lee ST, Byun JI. , et al. Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology 2016; 86 (18) 1683-1691
• 126 Pranzatelli MR, Tate ED, Travelstead AL. , et al. Rituximab (anti-CD20) adjunctive therapy for opsoclonus-myoclonus syndrome. J Pediatr Hematol Oncol 2006; 28 (09) 585-593
• 127 Lee WJ, Lee ST, Moon J. , et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics 2016; 13 (04) 824-832
• 128 Benseler SM, deVeber G, Hawkins C. , et al. Angiography-negative primary central nervous system vasculitis in children: a newly recognized inflammatory central nervous system disease. Arthritis Rheum 2005; 52 (07) 2159-2167
• 129 Elbers J, Halliday W, Hawkins C, Hutchinson C, Benseler SM. Brain biopsy in children with primary small-vessel central nervous system vasculitis. Ann Neurol 2010; 68 (05) 602-610
• 130 de Boysson H, Parienti JJ, Arquizan C. , et al. Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system. Rheumatology (Oxford) 2017; 56 (10) 1684-1693
• 131 Sibbitt Jr WL, Brandt JR, Johnson CR. , et al. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J Rheumatol 2002; 29 (07) 1536-1542
• 132 Miller JJ, Venna N, Siva A. Neuro-Behçet disease and autoinflammatory disorders. Semin Neurol 2014; 34 (04) 437-443
• 133 Rossi CM, Di Comite G. The clinical spectrum of the neurological involvement in vasculitides. J Neurol Sci 2009; 285 (1–2): 13-21
• 134 Bertsias GK, Ioannidis JPA, Aringer M. , et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69 (12) 2074-2082
• 135 McGeoch L, Twilt M, Famorca L. , et al; Canadian Vasculitis Research Network. CanVasc recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitides. J Rheumatol 2016; 43 (01) 97-120
• 136 Rubin LG, Levin MJ, Ljungman P. , et al; Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58 (03) e44-e100
• 137 Ntatsaki E, Carruthers D, Chakravarty K. , et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford) 2014; 53 (12) 2306-2309
• 138 Saag KG, Teng GG, Patkar NM. , et al; American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59 (06) 762-784
• 139 Keith PJ, Wetter DA, Wilson JW, Lehman JS. Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses. Br J Dermatol 2014; 171 (06) 1307-1317
• 140 Bloomgren G, Richman S, Hotermans C. , et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366 (20) 1870-1880
• 141 D'Amico E, Zanghì A, Leone C, Tumani H, Patti F. Treatment-related progressive multifocal leukoencephalopathy in multiple sclerosis: a comprehensive review of current evidence and future needs. Drug Saf 2016; 39 (12) 1163-1174
• 142 EMA. Updated recommendations to minimise the risk of the rare brain infection PML with Tecfidera. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500196017&mid=WC0b01ac058009a3dc . Accessed February 19, 2017
• 143 Neff RT, Hurst FP, Falta EM. , et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008; 86 (10) 1474-1478
• 144 Schmedt N, Andersohn F, Garbe E. Signals of progressive multifocal leukoencephalopathy for immunosuppressants: a disproportionality analysis of spontaneous reports within the US Adverse Event Reporting System (AERS). Pharmacoepidemiol Drug Saf 2012; 21 (11) 1216-1220
• 145 Vermeer NS, Straus SMJM, Mantel-Teeuwisse AK. , et al. Drug-induced progressive multifocal leukoencephalopathy: lessons learned from contrasting natalizumab and rituximab. Clin Pharmacol Ther 2015; 98 (05) 542-550
• 146 Gutierrez-Dalmau A, Campistol JM. Immunosuppressive therapy and malignancy in organ transplant recipients: a systematic review. Drugs 2007; 67 (08) 1167-1198
• 147 Ognenovski VM, Marder W, Somers EC. , et al. Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide. J Rheumatol 2004; 31 (09) 1763-1767
• 148 Klumb EM, Araújo Jr ML, Jesus GR. , et al. Is higher prevalence of cervical intraepithelial neoplasia in women with lupus due to immunosuppression?. J Clin Rheumatol 2010; 16 (04) 153-157
• 149 Beaugerie L, Brousse N, Bouvier AM. , et al; CESAME Study Group. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009; 374 (9701): 1617-1625
• 150 Robson R, Cecka JM, Opelz G, Budde M, Sacks S. Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil. Am J Transplant 2005; 5 (12) 2954-2960
• 151 Yilmaz N, Emmungil H, Gucenmez S. , et al. Incidence of cyclophosphamide-induced urotoxicity and protective effect of mesna in rheumatic diseases. J Rheumatol 2015; 42 (09) 1661-1666
• 152 Huong DLT, Amoura Z, Duhaut P. , et al. Risk of ovarian failure and fertility after intravenous cyclophosphamide. a study in 84 patients. J Rheumatol 2002; 29 (12) 2571-2576
• 153 Harward LE, Mitchell K, Pieper C, Copland S, Criscione-Schreiber LG, Clowse MEB. The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease. Lupus 2013; 22 (01) 81-86
• 154 Alarfaj AS, Khalil N. Fertility, ovarian failure, and pregnancy outcome in SLE patients treated with intravenous cyclophosphamide in Saudi Arabia. Clin Rheumatol 2014; 33 (12) 1731-1736
• 155 Chemaitilly W, Li Z, Krasin MJ. , et al. Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude lifetime cohort. J Clin Endocrinol Metab 2017; 102 (07) 2242-2250
• 156 Loren AW, Mangu PB, Beck LN. , et al; American Society of Clinical Oncology. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31 (19) 2500-2510