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

Journal of Neuroinflammation

Volumn 13, Issue 1, 2016, Pages

  Jarius, Sven ^a   Ruprecht, Klemens ^b   Kleiter, Ingo ^c   Borisow, Nadja ^b   Asgari, Nasrin ^d   Pitarokoili, Kalliopi ^c   Pache, Florence ^b   Stich, Oliver ^e   Beume, Lena Alexandra ^e   Hümmert, Martin W ^f   Trebst, Corinna ^f   Ringelstein, Marius ^g   Aktas, Orhan ^g   Winkelmann, Alexander ^h   Buttmann, Mathias ⁱ   Schwarz, Alexander ^a   Zimmermann, Hanna ^b   Brandt, Alexander U ^b   Franciotta, Diego ^j   Capobianco, Marco ^k   Kuchling, Joseph ^b   Haas, Jürgen ^a   Korporal Kuhnke, Mirjam ^a   Lillevang, Soeren Thue ^l   Fechner, Kai ^m   Schanda, Kathrin ⁿ   Paul, Friedemann ^b   Wildemann, Brigitte ^a   Reindl, Markus ⁿ   more..

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c RUHR UNIVERSITY BOCHUM   (Germany)

^d UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^e UNIVERSITY OF FREIBURG   (Germany)

^f HANNOVER MEDICAL SCHOOL   (Germany)

^g HEINRICH HEINE UNIVERSITY   (Germany)

^h UNIVERSITY OF ROSTOCK   (Germany)

ⁱ UNIVERSITY OF WÜRZBURG   (Germany)

^j C MONDINO NATIONAL NEUROLOGICAL INSTITUTE   (Italy)

^k SAN LUIGI GONZAGA UNIVERSITY HOSPITAL   (Italy)

^l ODENSE UNIVERSITY HOSPITAL   (Denmark)

^m Institute of Experimental Immunology   (Germany)

ⁿ INNSBRUCK MEDICAL UNIVERSITY   (Austria)

more..

Author keywords

Antibody index; Aquaporin 4 antibodies (AQP4 IgG); Autoantibodies; Cell based assays; Cerebrospinal fluid; Devic's syndrome; Longitudinally extensive transverse myelitis (LETM); Multiple sclerosis; Myelin oligodendrocyte glycoprotein antibodies (MOG IgG); Neuromyelitis optica (NMO); Neuromyelitis optica antibodies (NMO IgG); Neuromyelitis optica spectrum disorders (NMOSD); Optic neuritis; Transverse Myelitis

Indexed keywords

AQUAPORIN 4 ANTIBODY; AUTOANTIBODY; IMMUNOGLOBULIN G1 ANTIBODY; MYELIN OLIGODENDROCYTE GLYCOPROTEIN ANTIBODY; UNCLASSIFIED DRUG; AQUAPORIN 4; MYELIN OLIGODENDROCYTE GLYCOPROTEIN;

ADULT; ANTIBODY DETECTION; ANTIBODY TITER; ARTICLE; CAUCASIAN; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DISEASE ACTIVITY; DISEASE ASSOCIATION; DISEASE COURSE; FEMALE; HUMAN; MALE; MEDICAL HISTORY; MYELOOPTIC NEUROPATHY; OPTIC NEURITIS; PROTEIN CEREBROSPINAL FLUID LEVEL; REMISSION; TREATMENT OUTCOME; BLOOD; CEREBROSPINAL FLUID; CLINICAL TRIAL; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; IMMUNOLOGY; MULTICENTER STUDY; MYELITIS; PATHOPHYSIOLOGY; SEVERITY OF ILLNESS INDEX;

ADULT; AQUAPORIN 4; AUTOANTIBODIES; FEMALE; HEK293 CELLS; HUMANS; MALE; MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; MYELITIS; NEUROMYELITIS OPTICA; SEVERITY OF ILLNESS INDEX; TRANSFECTION;

EID: 84992524536     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-016-0717-1     Document Type: Article

References (70)

1. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202:473-7.
2. Jarius S, Paul F, Franciotta D, Waters P, Zipp F, Hohlfeld R, Vincent A, Wildemann B. Mechanisms of Disease: Aquaporin-4 antibodies in neuromyelitis optica. Nat Clin Pract Neurol. 2008;4:202-14.
3. Jarius S, Wildemann B, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin Exp Immunol. 2014;176:149-64.
4. Levy M, Wildemann B, Jarius S, Orellano B, Sasidharan S, Weber MS, Stuve O. Immunopathogenesis of neuromyelitis optica. Adv Immunol. 2014;121:213-42.
5. Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol. 2010;6:383-92.
6. Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation. 2013;10:8.
7. Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, Kleiter I, Kleinschnitz C, Berthele A, Brettschneider J, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
8. Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, Stoecker W, Wandinger KP. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci. 2010;291:52-6.
9. Jarius S, Wildemann B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol. 2013;23:661-83.
10. Jarius S, Franciotta D, Paul F, Bergamaschi R, Rommer PS, Ruprecht K, Ringelstein M, Aktas O, Kristoferitsch W, Wildemann B. Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity, and direct comparison with immunohistochemistry. J Neurol Sci. 2012;320:32-7.
11. Jarius S, Paul F, Fechner K, Ruprecht K, Kleiter I, Franciotta D, Ringelstein M, Pache F, Aktas O, Wildemann B. Aquaporin-4 antibody testing: direct comparison of M1-AQP4-DNA-transfected cells with leaky scanning versus M23-AQP4-DNA-transfected cells as antigenic substrate. J Neuroinflammation. 2014;11:129.
12. Reindl M, Di Pauli F, Rostasy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol. 2013;9:455-61.
13. Wingerchuk D, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, et al. International Consensus Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorders. Neurology. 2015;85:177-89.
14. O'Connor KC, McLaughlin KA, De Jager PL, Chitnis T, Bettelli E, Xu C, Robinson WH, Cherry SV, Bar-Or A, Banwell B, et al. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med. 2007;13:211-7.
15. Brilot F, Dale RC, Selter RC, Grummel V, Kalluri SR, Aslam M, Busch V, Zhou D, Cepok S, Hemmer B. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol. 2009;66:833-42.
16. McLaughlin KA, Chitnis T, Newcombe J, Franz B, Kennedy J, McArdel S, Kuhle J, Kappos L, Rostasy K, Pohl D, et al. Age-dependent B cell autoimmunity to a myelin surface antigen in pediatric multiple sclerosis. J Immunol. 2009;183:4067-76.
17. Mader S, Gredler V, Schanda K, Rostasy K, Dujmovic I, Pfaller K, Lutterotti A, Jarius S, Di Pauli F, Kuenz B, et al. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation. 2011;8:184.
18. Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, Palace J, Vincent A. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology. 2012;79:1273-7.
19. Kitley J, Waters P, Woodhall M, Leite MI, Murchison A, George J, Kuker W, Chandratre S, Vincent A, Palace J. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol. 2014;71:276-83.
20. Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, Nakashima I, Apostolos-Pereira SL, Talim N, Simm RF, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014;82:474-81.
21. Probstel AK, Rudolf G, Dornmair K, Collongues N, Chanson JB, Sanderson NS, Lindberg RL, Kappos L, de Seze J, Derfuss T. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. J Neuroinflammation. 2015;12:46.
22. Nakajima H, Motomura M, Tanaka K, Fujikawa A, Nakata R, Maeda Y, Shima T, Mukaino A, Yoshimura S, Miyazaki T, et al. Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis. BMJ Open. 2015;5, e007766.
23. Waters P, Woodhall M, O'Connor KC, Reindl M, Lang B, Sato DK, Jurynczyk M, Tackley G, Rocha J, Takahashi T, et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm. 2015;2, e89.
24. van Pelt ED, Wong YY, Ketelslegers IA, Hamann D, Hintzen RQ. Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands. Eur J Neurol. 2015.
25. Hoftberger R, Sepulveda M, Armangue T, Blanco Y, Rostasy K, Cobo Calvo A, Olascoaga J, Ramio-Torrenta L, Reindl M, Benito-Leon J, et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler. 2015;21:866-74.
26. Rostasy K, Mader S, Hennes E, Schanda K, Gredler V, Guenther A, Blaschek A, Korenke C, Pritsch M, Pohl D, et al. Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica. Mult Scler. 2013;19:1052-9.
27. Ramanathan S, Reddel SW, Henderson A, Parratt JD, Barnett M, Gatt PN, Merheb V, Kumaran RY, Pathmanandavel K, Sinmaz N, et al. Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis. Neurol Neuroimmunol Neuroinflamm. 2014;1, e40.
28. Probstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S, Villalobos A, Breithaupt C, Weissert R, Jacob U, et al. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology. 2011;77:580-8.
29. 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;2:35.
30. Konig FB, Wildemann B, Nessler S, Zhou D, Hemmer B, Metz I, Hartung HP, Kieseier BC, Bruck W. Persistence of immunopathological and radiological traits in multiple sclerosis. Arch Neurol. 2008;65:1527-32.
31. Jarius S, Metz I, König F, Ruprecht K, Reindl M, Paul F, Brück W, Wildemann B. Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case. Mult Scler. 2015. doi: 10.1177/1352458515622986.
32. Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, Breithaupt C, Hogen T, Straube A, Giese A, et al. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol. 2015;2:295-301.
33. Di Pauli F, Hoftberger R, Reindl M, Beer R, Rhomberg P, Schanda K, Sato D, Fujihara K, Lassmann H, Schmutzhard E, Berger T. Fulminant demyelinating encephalomyelitis: Insights from antibody studies and neuropathology. Neurol Neuroimmunol Neuroinflamm. 2015;2, e175.
34. Yoshimura S, Isobe N, Matsushita T, Yonekawa T, Masaki K, Sato S, Kawano Y, Kira J. Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin 4 antibody status. J Neurol Neurosurg Psychiatry. 2013;84:29-34.
35. Yan Y, Li Y, Fu Y, Yang L, Su L, Shi K, Li M, Liu Q, Borazanci A, Liu Y, et al. Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD. Sci China Life Sci. 2016. doi: 10.1007/s11427-015-4997-y.
36. Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume L, Hümmert MW, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term prognosis. J Neuroinflammation. 2016. doi: 10.1186/s12974-016-0718-0.
37. Jarius S, Kleiter I, Ruprecht K, Asgari N, Pitarokoili K, Borisow N, Hümmert M, Trebst C, Pache F, Winkelmann A, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome. J Neuroinflammation. 2016. doi: 10.1186/s12974-016-0719-z.
38. Pache F, Zimmermann H, Mikolajczak J, Schumacher S, Lacheta A, Oertel FC, Bellmann-Strobl J, Jarius S, Wildemann B, Reindl M, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflammation. 2016. doi: 10.1186/s12974-016-0720-6.
39. Jarius S, Jacobi C, de Seze J, Zephir H, Paul F, Franciotta D, Rommer P, Mader S, Kleiter I, Reindl M, et al. Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders. Mult Scler. 2011;17:1067-73.
40. Reiber H. Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases. Mult Scler. 1998;4:99-107.
41. Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4:111-7.
42. Jarius S, Franciotta D, Paul F, Ruprecht K, Bergamaschi R, Rommer PS, Reuss R, Probst C, Kristoferitsch W, Wandinger KP, Wildemann B. Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance. J Neuroinflammation. 2010;7:52.
43. Jarius S, Eichhorn P, Wildemann B, Wick M. Usefulness of antibody index assessment in cerebrospinal fluid from patients negative for total-IgG oligoclonal bands. Fluids Barriers CNS. 2012;9:14.
44. Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem. 1991;37:1153-60.
45. Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001;184:101-22.
46. Martinez-Hernandez E, Sepulveda M, Rostasy K, Hoftberger R, Graus F, Harvey RJ, Saiz A, Dalmau J: Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor alpha1 subunit in patients with isolated optic neuritis. JAMA Neurol. 2015;72:187-93.
47. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85:177-89.
48. Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain. 2008;131:3072-80.
49. Dale RC, Tantsis EM, Merheb V, Kumaran RY, Sinmaz N, Pathmanandavel K, Ramanathan S, Booth DR, Wienholt LA, Prelog K, et al. Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton. Neurol Neuroimmunol Neuroinflamm. 2014;1, e12.
50. Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, Rommer P, Kleiter I, Stich O, Reuss R, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci. 2011;306:82-90.
51. Kalluri SR, Illes Z, Srivastava R, Cree B, Menge T, Bennett JL, Berthele A, Hemmer B. Quantification and functional characterization of antibodies to native aquaporin 4 in neuromyelitis optica. Arch Neurol. 2010;67:1201-8.
52. Suzuki C, Nakashima I, Takahashi T, Bar-Or A, Itoyama Y, Fujihara K. Anti-Aquaporin-4 Antibody Production from Peripheral B cells in neuromyelitis Optica. Neurology. 2009;72:A281.
53. Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, Geraldes R, Vale T, Jacob A, Palace J, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol. 2008;65:913-9.
54. Jarius S, Jacob S, Leite MI, Waters P, Vincent A. NMO-IgG/Aqp4-Ab belongs to the IgG1 subclass and activates complement in vitro. Mult Scler. 2007;13:P533.
55. Lechner C, Baumann M, Hennes EM, Schanda K, Marquard K, Karenfort M, Leiz S, Pohl D, Venkateswaran S, Pritsch M, et al. Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J Neurol Neurosurg Psychiatry. 2015;87:897-905.
56. Rostasy K, Mader S, Schanda K, Huppke P, Gartner J, Kraus V, Karenfort M, Tibussek D, Blaschek A, Bajer-Kornek B, et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol. 2012;69:752-6.
57. Mader S, Lutterotti A, Di Pauli F, Kuenz B, Schanda K, Aboul-Enein F, Khalil M, Storch MK, Jarius S, Kristoferitsch W, et al. Patterns of antibody binding to aquaporin-4 isoforms in neuromyelitis optica. PLoS One. 2010;5, e10455.
58. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106-12.
59. Jarius S, Franciotta D, Bergamaschi R, Wright H, Littleton E, Palace J, Hohlfeld R, Vincent A. NMO-IgG in the diagnosis of neuromyelitis optica. Neurology. 2007;68:1076-7.
60. Paul F, Jarius S, Aktas O, Bluthner M, Bauer O, Appelhans H, Franciotta D, Bergamaschi R, Littleton E, Palace J, et al. Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med. 2007;4, e133.
61. Titulaer MJ, Hoftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, Benson LA, Shu H, Irioka T, Hirano M, et al. Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;75:411-28.
62. Wildemann B, Jarius S. The expanding range of autoimmune disorders of the nervous system. Lancet Neurol. 2013;12:22-4.
63. Baron R, Ferriero DM, Frisoni GB, Bettegowda C, Gokaslan ZL, Kessler JA, Vezzani A, Waxman SG, Jarius S, Wildemann B, Weller M. Neurology-the next 10 years. Nat Rev Neurol. 2015;11:658-64.
64. Jarius S, Wildemann B. 'Medusa-head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII. J Neuroinflammation. 2015;12:166.
65. Jarius S, Wildemann B. 'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC. J Neuroinflammation. 2015;12:167.
66. Jarius S, Wildemann B. 'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook. J Neuroinflammation. 2015;12:168.
67. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292-302.
68. Spadaro M, Gerdes LA, Krumbholz M, Ertl-Wagner B, Thaler FS, Schuh E, Metz I, Blaschek A, Dick A, Bruck W, et al. Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016;3, e257.
69. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005;58:840-6.
70. Tumani H, Deisenhammer F, Giovannoni G, Gold R, Hartung HP, Hemmer B, Hohlfeld R, Otto M, Stangel M, Wildemann B, Zettl UK. Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis. Ann Neurol. 2011;70:520. author reply 521.