NMO-Spektrum-Erkrankungen

Zusammenfassung

Neuromyelitis optica-Spektrum-Erkrankungen (NMOSD) stellen eine seltene Subgruppe chronisch-entzündlicher ZNS-Erkrankungen dar. Trotz heterogener Verläufe im Hinblick auf die Krankheitsaktivität ist die Behinderungsakkumulation häufig aufgrund der Schwere einzelner Schubereignisse sehr stark ausgeprägt. Nach Revision der Diagnosekriterien 2015 wurde der Begriff der NMO verlassen und stattdessen der Begriff NMOSD für alle Entitäten vorgeschlagen. Klinisch leiden die Patienten am häufigsten unter Optikusneuritiden und transversen Myelitiden, jedoch sind Manifestationen an verschiedenen Lokalisationen des zentralen Nervensystems möglich (z. B. auch in Hirnstamm oder Hypothalamus). Neben Formen mit und ohne Nachweis von Aquaporin 4-Antikörpern wird seit einiger Zeit auch diskutiert, ob Erkrankungen mit Vorkommen von Antikörpern gegen Myelin-Oligodendrozyten-Glykoprotein (MOG) dem Spektrum der NMOSD zuzurechnen sind oder eine eigene Entität darstellen. Aufgrund der hohen Krankheitsaktivität dieser Erkrankungen ist eine konsequente Therapie indiziert. In Ermangelung zugelassener Therapien werden hierzu konventielle Immunsuppressiva oder monoklonale Antikörper mit antiinflammatorischen Effekten eingesetzt. Seit einiger Zeit sind 4 Substanzen in der fortgeschrittenen klinischen Erprobung.

Abstract

Neuromyelitis optica spectrum disorders (NMOSD) represent a rare subset of chronic-inflammatory diseases of the central nervous system. Despite heterogeneities in disease activity, NMOSD patients have worse disability accumulation compared to MS patients. Revised diagnostic criteria comprise recommendations to abandon the term NMO and to summarize these conditions as NMOSD. Clinical presentation of NMOSD patients in most cases is optic neuritis and transverse myelitis; nevertheless, NMOSD can affect most parts of the central nervous system (e. g. brainstem and hypothalamus). Originally characterised as AQP4-antibody-dependent disease, recently the question was raised whether conditions with the presence of antibodies against myelin-oligodendrocyte glycoprotein (MOG) belong to the family of NMOSD. Due to the severity of the disease with often devastating relapses, systematic therapy is necessary. Usually, immunosuppressants or monoclonal antibodies with anti-inflammatory properties are used. Recently, 4 substances entered clinical testing for treatment of NMOSD.

Schlüsselwörter

NMOSD - Aquaporin-4 - Myelin-Oligodendrozyten-Glykoprotein - Neuromyelitis optica-Spektrum-Erkrankung - Neuroimmunologie

Keywords

neuroimmunology - neuromyelitis optica-spectrum disorder - NMOSD - myelin-oligodendrocyte-glykoprotein - MOG - Aquaporin

• Literatur

• 1 Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation 2013; 10: 8
• 2 Wingerchuk DM, Hogancamp WF, O’Brien PC. et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999; 53: 1107-1114
• 3 Lennon VA, Wingerchuk DM, Kryzer TJ. et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364: 2106-2112
• 4 Lennon VA, Kryzer TJ, Pittock SJ. et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Ep Med 2005; 202: 473-477
• 5 Wingerchuk DM, Lennon VA, Pittock SJ. et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66: 1485-1489
• 6 Wingerchuk DM, Banwell B, Bennett JL. et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85: 177-189
• 7 Flanagan EP, Cabre P, Weinshenker BG et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol 2016, doi: 10.1002/ana.24617
• 8 Asgari N, Lillevang ST, Skejoe HP. et al. A population-based study of neuromyelitis optica in Caucasians. Neurology 2011; 76: 1589-1595
• 9 Bizzoco E, Lolli F, Repice AM. et al. Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution. J Neurol 2009; 256: 1891-1898
• 10 Kira J, Kanai T, Nishimura Y. et al. Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders. Ann Neurol 1996; 40: 569-574
• 11 Tanaka K, Tani T, Tanaka M. et al. Anti-aquaporin 4 antibody in selected Japanese multiple sclerosis patients with long spinal cord lesions. Mult Scler 2007; 13: 850-855
• 12 Tanaka M, Tanaka K, Komori M. et al. Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody. J Neurol Neurosurg Psychiatry 2007; 78: 990-992
• 13 Kira J. Multiple sclerosis in the Japanese population. Lancet Neurol 2003; 2: 117-127
• 14 Jarius S, Ruprecht K, Wildemann B. et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation 2012; 9: 14
• 15 Sato DK, Callegaro D, Lana-Peixoto MA. et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82: 474-481
• 16 McKeon A, Lennon VA, Jacob A. et al. Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica. Muscle Nerve 2009; 39: 87-90
• 17 Nagaishi A, Takagi M, Umemura A. et al. Clinical features of neuromyelitis optica in a large Japanese cohort: comparison between phenotypes. J Neurol Neurosurg Psychiatry 2011; 82: 1360-1364
• 18 Wingerchuk DM, Weinshenker BG. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Mult Scler 2012; 18: 5-10
• 19 Spillane J, Christofi G, Sidle KC. et al. Myasthenia gravis and neuromyelitis opica: A causal link. Mult Scler Relat Disord 2013; 2: 233-237
• 20 Wingerchuk DM, Lennon VA, Lucchinetti CF. et al. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6: 805-815
• 21 Pittock SJ, Weinshenker BG, Lucchinetti CF. et al. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 2006; 63: 964-968
• 22 Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 2010; 6: 383-392
• 23 Marignier R, Nicolle A, Watrin C. et al. Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain 2010; 133: 2578-2591
• 24 Hinson SR, Roemer SF, Lucchinetti CF. et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med 2008; 205: 2473-2481
• 25 Ciccarelli O, Thomas DL, De Vita E. et al. Low myo-inositol indicating astrocytic damage in a case series of neuromyelitis optica. Ann Neurol 2013; 74: 301-305
• 26 Matthews L, Kolind S, Brazier A. et al. Imaging surrogates of disease activity in neuromyelitis optica allow distinction from multiple sclerosis. PLoS One 2015; 10: e0137715
• 27 Uzawa A, Mori M, Arai K. et al. Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. Mult Scler 2010; 16: 1443-1452
• 28 Jarius S, Paul F, Franciotta D. et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci 2011; 306: 82-90
• 29 Schneider-Hohendorf T, Rossaint J, Mohan H. et al. VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells. J Exp Med 2014; 211: 1833-1846
• 30 Barnett MH, Prineas JW, Buckland ME. et al. Massive astrocyte destruction in neuromyelitis optica despite natalizumab therapy. Mult Scler 2012; 18: 108-112
• 31 Jarius S, Aboul-Enein F, Waters P. et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 2008; 131: 3072-3080
• 32 Nour MM, Nakashima I, Coutinho E. et al. Pregnancy outcomes in aquaporin-4-positive neuromyelitis optica spectrum disorder. Neurology 2016; 86: 79-87
• 33 Piccolo L, Woodhall M, Tackley G. et al. Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up. J Neurol 2016; 263: 370-379
• 34 Kim HJ, Paul F, Lana-Peixoto MA. et al. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology 2015; 84: 1165-1173
• 35 Petzold A, Plant GT. Chronic relapsing inflammatory optic neuropathy: a systematic review of 122 cases reported. J Neurol 2014; 261: 17-26
• 36 Trebst C, Raab P, Voss EV. et al. Longitudinal extensive transverse myelitis – it’s not all neuromyelitis optica. Nat Rev Neurol 2011; 7: 688-698
• 37 Flanagan EP, Weinshenker BG, Krecke KN. et al. Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders. JAMA Neurol 2015; 72: 81-87
• 38 Kim SH, Huh SY, Hyun JW. et al. A longitudinal brain magnetic resonance imaging study of neuromyelitis optica spectrum disorder. PLoS One 2014; 9: e108320
• 39 Weinshenker BG, Wingerchuk DM, Vukusic S. et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol 2006; 59: 566-569
• 40 Jiao Y, Fryer JP, Lennon VA. et al. Aquaporin 4 IgG serostatus and outcome in recurrent longitudinally extensive transverse myelitis. JAMA Neurol 2014; 71: 48-54
• 41 Popescu BF, Lennon VA, Parisi JE. et al. Neuromyelitis optica unique area postrema lesions: nausea, vomiting, and pathogenic implications. Neurology 2011; 76: 1229-1237
• 42 Takahashi T, Miyazawa I, Misu T. et al. Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations. J Neurol Neurosurg Psychiatry 2008; 79: 1075-1078
• 43 Chan KH, Tse CT, Chung CP. et al. Brain involvement in neuromyelitis optica spectrum disorders. Arch Neurol 2011; 68: 1432-1439
• 44 Kume K, Deguchi K, Ikeda K. et al. Neuromyelitis optica spectrum disorder presenting with repeated hypersomnia due to involvement of the hypothalamus and hypothalamus-amygdala linkage. Mult Scler 2015; 21: 960-962
• 45 Poppe AY, Lapierre Y, Melancon D. et al. Neuromyelitis optica with hypothalamic involvement. Mult Scler 2005; 11: 617-621
• 46 Pittock SJ, Lennon VA, Krecke K. et al. Brain abnormalities in neuromyelitis optica. Arch Neurol 2006; 63: 390-396
• 47 Matthews L, Marasco R, Jenkinson M. et al. Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution. Neurology 2013; 80: 1330-1337
• 48 Newey CR, Bermel RA. Fulminant cerebral demyelination in neuromyelitis optica. Neurology 2011; 77: 193
• 49 Waters PJ, Pittock SJ, Bennett JL. et al. Evaluation of aquaporin-4 antibody assays. Clin Exp Neuroimmunol 2014; 5: 290-303
• 50 Kitley J, Woodhall M, Waters P. et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012; 79: 1273-1277
• 51 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: 276-283
• 52 Jarius S, Ruprecht K, Kleiter I. 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 outcome. J Neuroinflammation 2016; 13: 280
• 53 Pache F, Zimmermann H, Mikolajczak J. 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; 13: 282
• 54 Jarius S, Kleiter I, Ruprecht K. 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; 13: 281
• 55 Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 2003; 60: 848-853
• 56 Jarius S, Franciotta D, Bergamaschi R. et al. Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry 2008; 79: 1134-1136
• 57 Takano R, Misu T, Takahashi T. et al. Astrocytic damage is far more severe than demyelination in NMO: a clinical CSF biomarker study. Neurology 2010; 75: 208-216
• 58 Chang KH, Ro LS, Lyu RK. et al. Biomarkers for neuromyelitis optica. Clin Chim Acta 2015; 440: 64-71
• 59 Jiao Y, Fryer JP, Lennon VA. et al. Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica. Neurology 2013; 81: 1197-1204
• 60 Sato DK, Callegaro D, de Haidar Jorge FM. et al. Cerebrospinal fluid aquaporin-4 antibody levels in neuromyelitis optica attacks. Ann Neurol 2014; 76: 305-309
• 61 Flanagan EP, Kaufmann TJ, Krecke KN. et al. Discriminating long myelitis of neuromyelitis optica from sarcoidosis. Ann Neurol 2016; 79: 437-447
• 62 Pittock SJ, Lennon VA, de Seze J. et al. Neuromyelitis optica and non organ-specific autoimmunity. Arch Neurol 2008; 65: 78-83
• 63 Adawi M, Bisharat B, Bowirrat A. Systemic Lupus Erythematosus (SLE) Complicated by Neuromyelitis Optica (NMO – Devic’s Disease): Clinic-Pathological Report and Review of the Literature. Clin Med Insights Case Rep 2014; 7: 41-47
• 64 Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol 2008; 10: 55-66
• 65 Kleiter I, Gahlen A, Borisow N. et al. Neuromyelitis optica: Evaluation of 871 attacks and 1153 treatment courses. Ann Neurol 2016; 79: 206-216
• 66 Bonnan M, Valentino R, Olindo S. et al. Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder. Mult Scler 2009; 15: 487-492
• 67 Watanabe S, Nakashima I, Misu T. et al. Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult Scler 2007; 13: 128-132
• 68 Abboud H, Petrak A, Mealy M. et al. Treatment of acute relapses in neuromyelitis optica: Steroids alone versus steroids plus plasma exchange. Mult Scler 2016; 22: 185-192
• 69 Absoud M, Gadian J, Hellier J. et al. Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE). BMJ Open 2015; 5: e008312
• 70 Elsone L, Panicker J, Mutch K. et al. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler 2014; 20: 501-504
• 71 Viswanathan S, Wong AH, Quek AM. et al. Intravenous immunoglobulin may reduce relapse frequency in neuromyelitis optica. J Neuroimmunol 2015; 282: 92-96
• 72 Cree BA, Bennett JL, Sheehan M. et al. Placebo-controlled study in neuromyelitis optica-Ethical and design considerations. Mult Scler 2016; 22: 862-872
• 73 Kleiter I, Gold R. Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders. Neurotherapeutics 2016; 13: 70-83
• 74 Elsone L, Kitley J, Luppe S. et al. Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler 2014; 20: 1533-1540
• 75 Costanzi C, Matiello M, Lucchinetti CF. et al. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology 2011; 77: 659-666
• 76 Mandler RN, Ahmed W, Dencoff JE. Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 1998; 51: 1219-1220
• 77 Huh SY, Kim SH, Hyun JW. et al. Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder. JAMA Neurol 2014; 71: 1372-1378
• 78 Kim SH, Huh SY, Lee SJ. et al. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 2013; 70: 1110-1117
• 79 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: 989-995
• 80 Trebst C, Jarius S, Berthele A. et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 2014; 261: 1-16
• 81 Ayzenberg I, Kleiter I, Schroder A. et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 2013; 70: 394-397
• 82 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: 756-763
• 83 Pittock SJ, Lennon VA, McKeon A. et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol 2013; 12: 554-562
• 84 Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol 2014; 10: 493-506