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Neuroradiologie Scan 2021; 11(02): 111-126
DOI: 10.1055/a-1372-9203
CME-Fortbildung

Neuromyelitis-optica-Spektrum-Erkrankungen – alte und neue Entwicklungen

Lisa Lohmann
,
Luisa Klotz
,
Heinz Wiendl
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Die Entwicklung der letzten 15 Jahre hat die Diagnostik und Therapie der Neuromyelitis-optica-Spektrum-Erkrankungen (NMOSD) maßgeblich geprägt – von der Entdeckung der Aquaporin-4-Antikörper über die Differenzierung der diagnostischen Kriterien bis zur kürzlichen Zulassung von Eculizumab als erste verlaufsmodifizierende Therapie. Dieser Artikel soll einen Überblick über die bisherigen Erkenntnisse und zukünftigen Therapiemöglichkeiten vermitteln.

Kernaussagen

  • Neuromyelitis-optica-Spektrum-Erkrankungen (NMOSD) stellen eine seltene, heterogene Gruppe schubförmig oder monophasisch verlaufender chronisch-entzündlicher ZNS Erkrankungen dar.

  • Die Diagnosestellung ist abhängig vom Aquaporin-4 (AQP4)-Ak-Serostatus. Die 6 Kardinalsymptome sind: Neuritis n. optici, akute Myelitis, Area-postrema-Syndrom, akutes Hirnstammsyndrom, akutes Zwischenhirnsyndrom, symptomatisches zerebrales Syndrom.

  • AQP4-Ak-positive NMOSD sind Astrozytopathien, Myelin-Oligodendrozyten-Glykoprotein (MOG)-Ak-positive NMOSD sind primär demyelinisierende Erkrankungen.

  • Die differenzialdiagnostische Abgrenzung zur Multiplen Sklerose (MS) ist essenziell, da MS-Therapeutika zu einer Exazerbation der Krankheitsaktivität einer NMOSD führen können.

  • NMOSD können mit weiteren Antikörper-vermittelten Erkrankungen assoziiert sein.

  • Die Therapie gliedert sich in Schubtherapie und Schubprophylaxe.

  • Ein früher Therapiebeginn und die konsequente Eskalation der Schubtherapie sind entscheidend.

  • Azathioprin, Mycophenolat Mofetil (MMF) und Rituximab sind etablierte Off-Label-Therapien mit positiven Langzeitdaten.

  • Eculizumab ist das erste zugelassene Medikament für die verlaufsmodifizierende Therapie. Satralizumab und Inebilizumab werden folgen.



Publication History

Article published online:
17 May 2021

© 2021. Thieme. All rights reserved.

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  • Literatur

  • 1 Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation 2013; 10: 8
    CrossrefPubMedSearch in Google Scholar
  • 2 Wingerchuk DM, Hogancamp WF, O'Brien PC. et al. The clinical course of neuromyelitis optica (Devicʼs syndrome). Neurology 1999; 53: 1107-1114
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 4 Lennon VA, Kryzer TJ, Pittock SJ. et al. IgG marker of opticspinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202: 473-477
    CrossrefPubMedSearch in Google Scholar
  • 5 Wingerchuk DM, Lennon VA, Pittock SJ. et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66: 1485-1489
    CrossrefPubMedSearch in Google Scholar
  • 6 Popescu BFG, Lennon VA, Parisi JE. et al. Neuromyelitis optica unique area postrema lesions. Nausea, vomiting, and pathogenic implications. Neurology 2011; 76: 1229-1237
    CrossrefPubMedSearch in Google Scholar
  • 7 Kitley J, Woodhall M, Waters P. et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012; 79: 1273-1277
    CrossrefPubMedSearch in Google Scholar
  • 8 Wingerchuk DM, Banwell B, Bennett JL. et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85: 177-189
    CrossrefPubMedSearch in Google Scholar
  • 9 Mori M, Kuwabara S, Paul F. Worldwide prevalence of neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiat 2018; 89: 555-556
    CrossrefPubMedSearch in Google Scholar
  • 10 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 Psychiat 2007; 78: 990-992
    CrossrefPubMedSearch in Google Scholar
  • 11 Kira J-I. Multiple sclerosis in the Japanese population. Lancet Neurol 2003; 2: 117-127
    CrossrefPubMedSearch in Google Scholar
  • 12 Flanagan EP, Cabre P, Weinshenker BG. et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol 2016; 79: 775-783
    CrossrefPubMedSearch in Google Scholar
  • 13 Kim S-H, Mealy MA, Levy M. et al. Racial differences in neuromyelitis optica spectrum disorder. Neurology 2018; 91: e2089-e2099
    CrossrefPubMedSearch in Google Scholar
  • 14 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
    CrossrefPubMedSearch in Google Scholar
  • 15 Wingerchuk DM, Weinshenker BG. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Mult Scler 2012; 18: 5-10
    CrossrefPubMedSearch in Google Scholar
  • 16 Zoccarato M, Saddi MV, Serra G. et al. Aquaporin-4 antibody neuromyelitis optica following anti-NMDA receptor encephalitis. J Neurol 2013; 260: 3185-3187
    CrossrefPubMedSearch in Google Scholar
  • 17 Spillane J, Christofi G, Sidle KC. et al. Myasthenia gravis and neuromyelitis opica. A causal link. Mult Scler Relat Disord 2013; 2: 233-237
    CrossrefPubMedSearch in Google Scholar
  • 18 Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies. A decade later. Ann NY Acad Sci USA 2016; 1366: 20-39
    CrossrefPubMedSearch in Google Scholar
  • 19 Lucchinetti CF, Mandler RN, McGavern D. et al. A role for humoral mechanisms in the pathogenesis of Devicʼs neuromyelitis optica. Brain 2002; 125: 1450-1461
    CrossrefPubMedSearch in Google Scholar
  • 20 Uzawa A, Mori M, Kuwabara S. Role of interleukin-6 in the pathogenesis of neuromyelitis optica. Clin Exp Neuroimmunol 2013; 4: 167-172
    CrossrefSearch in Google Scholar
  • 21 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: 187-193
    CrossrefPubMedSearch in Google Scholar
  • 22 Papais-Alvarenga RM, Carellos SC, Alvarenga MP. et al. Clinical course of optic neuritis in patients with relapsing neuromyelitis optica. Arch Ophthalmol 2008; 126: 12-16
    CrossrefPubMedSearch in Google Scholar
  • 23 Pekcevik Y, Mitchell CH, Mealy MA. et al. Differentiating neuromyelitis optica from other causes of longitudinally extensive transverse myelitis on spinal magnetic resonance imaging. Mult Scler 2016; 22: 302-311
    CrossrefPubMedSearch in Google Scholar
  • 24 Apiwattanakul M, Popescu BF, Matiello M. et al. Intractable vomiting as the initial presentation of neuromyelitis optica. Ann Neurol 2010; 68: 757-761
    CrossrefPubMedSearch in Google Scholar
  • 25 Cheng C, Jiang Y, Lu X. et al. The role of anti-aquaporin 4 antibody in the conversion of acute brainstem syndrome to neuromyelitis optica. BMC Neurol 2016; 16: 203
    CrossrefPubMedSearch in Google Scholar
  • 26 Kanbayashi T, Shimohata T, Nakashima I. et al. Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis. New neurochemical and immunological implications. Arch Neurol 2009; 66: 1563-1566
    CrossrefPubMedSearch in Google Scholar
  • 27 Suzuki K, Nakamura T, Hashimoto K. et al. Hypothermia, hypotension, hypersomnia, and obesity associated with hypothalamic lesions in a patient positive for the anti-aquaporin 4 antibody. A case report and literature review. Arch Neurol 2012; 69: 1355-1359
    CrossrefPubMedSearch in Google Scholar
  • 28 Newey CR, Bermel RA. Fulminant cerebral demyelination in neuromyelitis optica. Neurology 2011; 77: 193
    CrossrefPubMedSearch in Google Scholar
  • 29 Ogawa R, Nakashima I, Takahashi T. et al. MOG antibodypositive, benign, unilateral, cerebral cortical encephalitis with epilepsy. Neurol Neuroimmunol Neuroinflamm 2017; 4: e322
    CrossrefPubMedSearch in Google Scholar
  • 30 Guo Y, Lennon VA, Popescu BFG. et al. Autoimmune aquaporin-4 myopathy in neuromyelitis optica spectrum. JAMA Neurol 2014; 71: 1025-1029
    CrossrefPubMedSearch in Google Scholar
  • 31 Qian P, Lancia S, Alvarez E. et al. Association of neuromyelitis optica with severe and intractable pain. Arch Neurol 2012; 69: 1482-1487
    CrossrefPubMedSearch in Google Scholar
  • 32 Chavarro VS, Mealy MA, Simpson A. et al. Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm 2016; 3: e286
    CrossrefPubMedSearch in Google Scholar
  • 33 Hyun J-W, Kim S-H, Jeong IH. et al. Bright spotty lesions on the spinal cord. An additional MRI indicator of neuromyelitis optica spectrum disorder?. J Neurol Neurosurg Psychiatry 2015; 86: 1280-1282
    CrossrefPubMedSearch in Google Scholar
  • 34 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
    CrossrefPubMedSearch in Google Scholar
  • 35 Waters P, Reindl M, Saiz A. et al. Multicentre comparison of a diagnostic assay. Aquaporin-4 antibodies in neuromyelitis optica. J Neurol Neurosurg Psychiat 2016; 87: 1005-1015
    CrossrefPubMedSearch in Google Scholar
  • 36 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
    CrossrefPubMedSearch in Google Scholar
  • 37 Wingerchuk DM, Lennon VA, Lucchinetti CF. et al. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6: 805-815
    CrossrefPubMedSearch in Google Scholar
  • 38 Jarius S, Eichhorn P, Franciotta D. et al. The MRZ reaction as a highly specific marker of multiple sclerosis. Re-evaluation and structured review of the literature. J Neurol 2017; 264: 453-466
    CrossrefPubMedSearch in Google Scholar
  • 39 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
    CrossrefPubMedSearch in Google Scholar
  • 40 Kira J-i. Unexpected exacerbations following initiation of disease-modifying drugs in neuromyelitis optica spectrum disorder. Which factor is responsible, anti-aquaporin 4 antibodies, B cells, Th1 cells, Th2 cells, Th17 cells, or others?. Mult Scler 2017; 23: 1300-1302
    CrossrefPubMedSearch in Google Scholar
  • 41 Kitley JL, Leite MI, George JS. et al. The differential diagnosis of longitudinally extensive transverse myelitis. Mult Scler 2012; 18: 271-285
    CrossrefPubMedSearch in Google Scholar
  • 42 Kleiter I, Gahlen A, Borisow N. et al. Apheresis therapies for NMOSD attacks. A retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm 2018; 5: e504
    CrossrefPubMedSearch in Google Scholar
  • 43 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
    CrossrefPubMedSearch in Google Scholar
  • 44 Bonnan M, Valentino R, Debeugny S. et al. Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiat 2018; 89: 346-351
    CrossrefPubMedSearch in Google Scholar
  • 45 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
    CrossrefPubMedSearch in Google Scholar
  • 46 Nikoo Z, Badihian S, Shaygannejad V. et al. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder. A randomized clinical trial. J Neurol 2017; 264: 2003-2009
    CrossrefPubMedSearch in Google Scholar
  • 47 Evangelopoulos ME, Andreadou E, Koutsis G. et al. Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A sixyear follow-up. J Neurol Sci 2017; 372: 92-96
    CrossrefPubMedSearch in Google Scholar
  • 48 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
    CrossrefPubMedSearch in Google Scholar
  • 49 Pittock SJ, Berthele A, Fujihara K. et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med 2019; 381: 614-625
    CrossrefPubMedSearch in Google Scholar
  • 50 Cree BAC, Bennett JL, Kim HJ. et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (NMOmentum). A double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 2019;
    CrossrefPubMedSearch in Google Scholar
  • 51 Yamamura T, Kleiter I, Fujihara K. et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med 2019; 381: 2114-2124
    CrossrefPubMedSearch in Google Scholar