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Neuroradiologie Scan 2024; 14(02): 141-163
DOI: 10.1055/a-2165-1856
CME-Fortbildung

Systemischer Lupus erythematodes des zentralen Nervensystems

Pathophysiologische, klinische und bildgebende Merkmale
Yoshiaki Ota
,
Ashok Srinivasan
,
Aristides A. Capizzano
,
Jayapalli R. Bapuraj
,
John Kim
,
Ryo Kurokawa
,
Akira Baba
,
Toshio Moritani
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Der systemische Lupus erythematodes wird mit einer hohen Mortalitätsrate in Verbindung gebracht. Umso wichtiger ist die Kenntnis der zugrunde liegenden Pathomechanismen, der neuroimmunen Schnittstellen und der Komplikationen dieser Erkrankung für die adäquate Diagnostik und Behandlung.
Kernaussagen

  • Die klinischen Erscheinungsformen des NPSLE reichen von Kopfschmerzen und leichten kognitiven Störungen bis hin zu akuter Verwirrtheit, Psychosen und Krampfanfällen. Basierend auf der Nomenklatur des American College of Rheumatology wurden Falldefinitionen für 12 zentrale und 7 periphere NPSLE-Erscheinungsformen entwickelt.

  • Das Gehirn ist immunprivilegiert, da es mehrere neuroimmune Schnittstellen wie die Blut-Hirn-Schranke, die Blut-Liquor-Schranke, die meningeale Barriere und das glymphatische System aufweist. Diese regulieren den Eintritt von Immunzellen und Antikörpern.

  • Die SLE-Vaskulopathie betrifft insbesondere Arteriolen und Kapillaren, sodass dies zu vermehrten Gefäßwindungen, vaskulärer Hyalinisierung, endothelialer Proliferation und perivaskulärer Entzündung oder Gliose führt.

  • Ein klinisch isoliertes Syndrom ist definiert als das erste klinische demyelinisierende Ereignis, das mindestens 24 h andauert und in der Bildgebung diskrete Läsionen des klinisch isolierten Syndroms erkennen lässt.

  • Es existieren bekannte, das zentrale Nervensystem betreffende Komplikationen im Zusammenhang mit SLE, darunter PRES, PML, durch Immunsuppressiva induzierte lymphoproliferative Störungen und die toxische Leukoenzephalopathie.

Schlüsselwörter

systemischer Lupus erythematodes - zentrales Nervensystem - Pathomechanismen - Bildgebung


Publication History

Article published online:
02 April 2024

© 2022. The Radiological Society of North America. All rights reserved. Originally published in English in RadioGraphics 2022; 42: 212–232. Online published in 10.1148/rg.210045. Translated and reprinted with permission of RSNA. RSNA is not responsible for any inaccuracy or error arising from the translation from English to German.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 The American College of Rheumatology. Nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42: 599-608
    CrossrefPubMedSearch in Google Scholar
  • 2 Magro-Checa C, Zirkzee EJ, Huizinga TW. et al. Management of neuropsychiatric systemic lupus erythematosus: current approaches and future perspectives. Drugs 2016; 76: 459-483
    CrossrefPubMedSearch in Google Scholar
  • 3 Schwartz N, Stock AD, Putterman C. Neuropsychiatric lupus: new mechanistic insights and future treatment directions. Nat Rev Rheumatol 2019; 15: 137-152
    CrossrefPubMedSearch in Google Scholar
  • 4 Unterman A, Nolte JE, Boaz M. et al. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 5 Hanly JG, Urowitz MB, Su L. et al. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann Rheum Dis 2010; 69: 529-535
    CrossrefPubMedSearch in Google Scholar
  • 6 Kivity S, Agmon-Levin N, Zandman-Goddard G. et al. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 2015; 13: 43
    CrossrefPubMedSearch in Google Scholar
  • 7 Zhang L, Fu T, Yin R. et al. Prevalence of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis. BMC Psychiatry 2017; 17: 70
    CrossrefPubMedSearch in Google Scholar
  • 8 Marín JD, Posso-Osorio I, Vargas S. et al. Antibodies associated with neuropsychiatric lupus: pathophysiological role, prevalence and diagnostic usefulness. Rev Colomb Reumatol (Engl Ed) 2019; 26 (02) 111-117
    Search in Google Scholar
  • 9 Narshi CB, Giles IP, Rahman A. The endothelium: an interface between autoimmunity and atherosclerosis in systemic lupus erythematosus?. Lupus 2011; 20: 5-13
    CrossrefPubMedSearch in Google Scholar
  • 10 Cieslik P, Hrycek A, Klucinski P. Vasculopathy and vasculitis in systemic lupus erythematosus. Pol Arch Med Wewn 2008; 118: 57-63
    CrossrefPubMedSearch in Google Scholar
  • 11 Cohen D, Rijnink EC, Nabuurs RJ. et al. Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement. Rheumatology (Oxford) 2017; 56: 77-86
    CrossrefPubMedSearch in Google Scholar
  • 12 Govoni M, Bortoluzzi A, Padovan M. et al. The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J Autoimmun 2016; 74: 41-72
    CrossrefPubMedSearch in Google Scholar
  • 13 Schreiber K, Sciascia S, de Groot PG. et al. Antiphospholipid syndrome. Nat Rev Dis Primers 2018; 4 (1): 17103; published correction in Nat Rev Dis Primers 2018; 4: 18005
    CrossrefPubMedSearch in Google Scholar
  • 14 Ho RC, Thiaghu C, Ong H. et al. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmun Rev 2016; 15: 124-138
    CrossrefPubMedSearch in Google Scholar
  • 15 Zhang EN, Jorgensen T. Neuropsychiatric SLE: from immune mechanisms to clinical management. In: Lionaki S, ed. Lupus: new advances and challenges. London, England: IntechOpen; 2020
    Search in Google Scholar
  • 16 Faria R, Gonçalves J, Dias R. Neuropsychiatric systemic lupus erythematosus involvement: towards a tailored approach to our patients?. Rambam Maimonides Med J 2017; 8: e0001
    CrossrefPubMedSearch in Google Scholar
  • 17 Titulaer MJ, Dalmau J. Antibodies to NMDA receptor, blood-brain barrier disruption and schizophrenia: a theory with unproven links. Mol Psychiatry 2014; 19: 1054
    CrossrefPubMedSearch in Google Scholar
  • 18 Lauvsnes MB, Omdal R. Systemic lupus erythematosus, the brain, and anti-NR2 antibodies. J Neurol 2012; 259: 622-629
    CrossrefPubMedSearch in Google Scholar
  • 19 Gerosa M, Poletti B, Pregnolato F. et al. Antiglutamate receptor antibodies and cognitive impairment in primary antiphospholipid syndrome and systemic lupus erythematosus. Front Immunol 2016; 7: 5
    CrossrefPubMedSearch in Google Scholar
  • 20 Eber T, Chapman J, Shoenfeld Y. Anti-ribosomal P-protein and its role in psychiatric manifestations of systemic lupus erythematosus: myth or reality?. Lupus 2005; 14: 571-575
    CrossrefPubMedSearch in Google Scholar
  • 21 Segovia-Miranda F, Serrano F, Dyrda A. et al. Pathogenicity of lupus anti-ribosomal P antibodies: role of cross-reacting neuronal surface P antigen in glutamatergic transmission and plasticity in a mouse model. Arthritis Rheumatol 2015; 67: 1598-1610
    CrossrefPubMedSearch in Google Scholar
  • 22 Katzav A, Solodeev I, Brodsky O. et al. Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system. Arthritis Rheum 2007; 56: 938-948
    CrossrefPubMedSearch in Google Scholar
  • 23 Jeltsch-David H, Muller S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol 2014; 10: 579-596
    CrossrefPubMedSearch in Google Scholar
  • 24 Alexopoulos H, Kampylafka EI, Fouka P. et al. Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease. J Neuroimmunol 2015; 289: 8-11
    CrossrefPubMedSearch in Google Scholar
  • 25 Mader S, Jeganathan V, Arinuma Y. et al. Understanding the antibody repertoire in neuropsychiatric systemic lupus erythematosus and neuromyelitis optica spectrum disorder: Do they share common targets?. Arthritis Rheumatol 2018; 70: 277-286
    CrossrefPubMedSearch in Google Scholar
  • 26 Lucchinetti CF, Guo Y, Popescu BF. et al. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol 2014; 24: 83-97
    CrossrefPubMedSearch in Google Scholar
  • 27 Ichinose K, Ohyama K, Furukawa K. et al. Novel anti-suprabasin antibodies may contribute to the pathogenesis of neuropsychiatric systemic lupus erythematosus. Clin Immunol 2018; 193: 123-130
    CrossrefPubMedSearch in Google Scholar
  • 28 Williams Jr RC, Sugiura K, Tan EM. Antibodies to microtubule-associated protein 2 in patients with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2004; 50: 1239-1247
    CrossrefPubMedSearch in Google Scholar
  • 29 Sato T, Fujii T, Yokoyama T. et al. Anti-U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease. Arthritis Rheum 2010; 62: 3730-3740
    CrossrefPubMedSearch in Google Scholar
  • 30 Tsuchiya H, Haga S, Takahashi Y. et al. Identification of novel autoantibodies to GABA(B) receptors in patients with neuropsychiatric systemic lupus erythematosus. Rheumatology (Oxford) 2014; 53: 1219-1228
    CrossrefPubMedSearch in Google Scholar
  • 31 Ota Y, Capizzano AA, Moritani T. et al. Comprehensive review of Wernicke encephalopathy: pathophysiology, clinical symptoms and imaging findings. Jpn J Radiol 2020; 38: 809-820
    CrossrefPubMedSearch in Google Scholar
  • 32 Reboldi A, Coisne C, Baumjohann D. et al. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 2009; 10: 514-523
    CrossrefPubMedSearch in Google Scholar
  • 33 Gelb S, Stock AD, Anzi S. et al. Mechanisms of neuropsychiatric lupus: the relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier. J Autoimmun 2018; 91: 34-44
    CrossrefPubMedSearch in Google Scholar
  • 34 Stock AD, Gelb S, Pasternak O. et al. The blood brain barrier and neuropsychiatric lupus: new perspectives in light of advances in understanding the neuroimmune interface. Autoimmun Rev 2017; 16: 612-619
    CrossrefPubMedSearch in Google Scholar
  • 35 Plog BA, Nedergaard M. The glymphatic system in central nervous system health and disease: past, present, and future. Annu Rev Pathol 2018; 13: 379-394
    CrossrefPubMedSearch in Google Scholar
  • 36 Hanly JG, Kozora E, Beyea SD. et al. Review: nervous system disease in systemic lupus erythematosus: current status and future directions. Arthritis Rheumatol 2019; 71: 33-42
    CrossrefPubMedSearch in Google Scholar
  • 37 Jung RE, Caprihan A, Chavez RS. et al. Diffusion tensor imaging in neuropsychiatric systemic lupus erythematosus. BMC Neurol 2010; 10: 65
    CrossrefPubMedSearch in Google Scholar
  • 38 Belmont HM, Abramson SB, Lie JT. Pathology and pathogenesis of vascular injury in systemic lupus erythematosus: interactions of inflammatory cells and activated endothelium. Arthritis Rheum 1996; 39 (01) 9-22
    CrossrefPubMedSearch in Google Scholar
  • 39 Sarbu N, Alobeidi F, Toledano P. et al. Brain abnormalities in newly diagnosed neuropsychiatric lupus: systematic MRI approach and correlation with clinical and laboratory data in a large multicenter cohort. Autoimmun Rev 2015; 14: 153-159
    CrossrefPubMedSearch in Google Scholar
  • 40 Postal M, Lapa AT, Reis F. et al. Magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus: current state of the art and novel approaches. Lupus 2017; 26 (05) 517-521
    CrossrefPubMedSearch in Google Scholar
  • 41 Appenzeller S, Vasconcelos Faria A, Li LM. et al. Quantitative magnetic resonance imaging analyses and clinical significance of hyperintense white matter lesions in systemic lupus erythematosus patients. Ann Neurol 2008; 64: 635-643
    CrossrefPubMedSearch in Google Scholar
  • 42 Raymond AA, Zariah AA, Samad SA. et al. Brain calcification in patients with cerebral lupus. Lupus 1996; 5: 123-128
    CrossrefPubMedSearch in Google Scholar
  • 43 Moritani T, Shrier DA, Numaguchi Y. et al. Diffusion-weighted echo-planar MR imaging of CNS involvement in systemic lupus erythematosus. Acad Radiol 2001; 8: 741-753
    CrossrefPubMedSearch in Google Scholar
  • 44 Luyendijk J, Steens SC, Ouwendijk WJ. et al. Neuropsychiatric systemic lupus erythematosus: lessons learned from magnetic resonance imaging. Arthritis Rheum 2011; 63: 722-732
    CrossrefPubMedSearch in Google Scholar
  • 45 Ainiala H, Dastidar P, Loukkola J. et al. Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol 2005; 34: 376-382
    CrossrefPubMedSearch in Google Scholar
  • 46 Zivadinov R, Shucard JL, Hussein S. et al. Multimodal imaging in systemic lupus erythematosus patients with diffuse neuropsychiatric involvement. Lupus 2013; 22: 675-683
    CrossrefPubMedSearch in Google Scholar
  • 47 Sarbu N, Bargalló N, Cervera R. Advanced and conventional magnetic resonance imaging in neuropsychiatric lupus. F1000 Res 2015; 4: 162
    CrossrefPubMedSearch in Google Scholar
  • 48 Kaichi Y, Kakeda S, Moriya J. et al. Brain MR findings in patients with systemic lupus erythematosus with and without antiphospholipid antibody syndrome. AJNR Am J Neuroradiol 2014; 35: 100-105
    CrossrefPubMedSearch in Google Scholar
  • 49 Gao N, Wang ZL, Li MT. et al. Clinical characteristics and risk factors of intracranial hemorrhage in systemic lupus erythematosus. Lupus 2013; 22: 453-460
    CrossrefPubMedSearch in Google Scholar
  • 50 Wu Y, Chen T. An up-to-date review on cerebral microbleeds. J Stroke Cerebrovasc Dis 2016; 25: 1301-1306
    CrossrefPubMedSearch in Google Scholar
  • 51 Chang YS, Liu CJ, Chen WS. et al. Increased risk of subarachnoid hemorrhage in patients with systemic lupus erythematosus: a nationwide population-based study. Arthritis Care Res (Hoboken) 2013; 65: 601-606
    CrossrefPubMedSearch in Google Scholar
  • 52 Mitchell P, Wilkinson ID, Hoggard N. et al. Detection of subarachnoid haemorrhage with magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2001; 70: 205-211
    CrossrefPubMedSearch in Google Scholar
  • 53 Howard BM, Hu R, Barrow JW. et al. Comprehensive review of imaging of intracranial aneurysms and angiographically negative subarachnoid hemorrhage. Neurosurg Focus 2019; 47: E20
    CrossrefPubMedSearch in Google Scholar
  • 54 Torné R, Rodríguez-Hernández A, Bernard T. et al. Subarachnoid hemorrhage in systemic lupus erythematosus: systematic review and report of three cases. Clin Neurol Neurosurg 2015; 128: 17-24
    CrossrefPubMedSearch in Google Scholar
  • 55 Mimori A, Suzuki T, Hashimoto M. et al. Subarachnoid hemorrhage and systemic lupus erythematosus. Lupus 2000; 9: 521-526
    CrossrefPubMedSearch in Google Scholar
  • 56 Bukhari W, Barnett MH, Prain K. et al. Molecular pathogenesis of neuromyelitis optica. Int J Mol Sci 2012; 13: 12970-12993
    CrossrefPubMedSearch in Google Scholar
  • 57 Yadav SK, Mindur JE, Ito K. et al. Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurol 2015; 28: 206-219
    CrossrefPubMedSearch in Google Scholar
  • 58 Piga M, Chessa E, Peltz MT. et al. Demyelinating syndrome in SLE encompasses different subtypes: Do we need new classification criteria? Pooled results from systematic literature review and monocentric cohort analysis. Autoimmun Rev 2017; 16: 244-252
    CrossrefPubMedSearch in Google Scholar
  • 59 Chessa E, Piga M, Floris A. et al. Demyelinating syndrome in SLE: review of different disease subtypes and report of a case series. Reumatismo 2017; 69: 175-183
    CrossrefPubMedSearch in Google Scholar
  • 60 Khanna S, Sharma A, Huecker J. et al. Magnetic resonance imaging of optic neuritis in patients with neuromyelitis optica versus multiple sclerosis. J Neuroophthalmol 2012; 32: 216-220
    CrossrefPubMedSearch in Google Scholar
  • 61 Costallat BL, Ferreira DM, Costallat LT. et al. Myelopathy in systemic lupus erythematosus: clinical, laboratory, radiological and progression findings in a cohort of 1.193 patients. Rev Bras Reumatol Engl Ed 2016; 56 (03) 240-251
    PubMedSearch in Google Scholar
  • 62 Polman CH, Reingold SC, Banwell B. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302
    CrossrefPubMedSearch in Google Scholar
  • 63 Kelley BP, Corrigan JJ, Patel SC. et al. Neuropsychiatric lupus with antibody-mediated striatal encephalitis. AJNR Am J Neuroradiol 2018; 39: 2263-2269
    CrossrefPubMedSearch in Google Scholar
  • 64 Angst DBM, de Figueiredo NSV, Passarelli V. et al. Autoimmune limbic encephalitis: a manifestation of systemic lupus erythematosus in the central nervous system. Dement Neuropsychol 2015; 9: 189-195
    CrossrefPubMedSearch in Google Scholar
  • 65 Zhang T, Duan Y, Ye J. et al. Brain MRI characteristics of patients with anti-N-methyl-D-aspartate receptor encephalitis and their associations with 2-year clinical outcome. AJNR Am J Neuroradiol 2018; 39: 824-829
    CrossrefPubMedSearch in Google Scholar
  • 66 Liu B, Zhang X, Zhang FC. et al. Posterior reversible encephalopathy syndrome could be an underestimated variant of “reversible neurological deficits” in systemic lupus erythematosus. BMC Neurol 2012; 12: 152
    CrossrefPubMedSearch in Google Scholar
  • 67 Bertsias GK, Ioannidis JP, 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: 2074-2082
    CrossrefPubMedSearch in Google Scholar
  • 68 Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14: 914-925
    CrossrefPubMedSearch in Google Scholar
  • 69 Tsang HH, Trendell-Smith NJ, Wu AK. et al. Diffuse large B-cell lymphoma of the central nervous system in mycophenolate mofetil-treated patients with systemic lupus erythematosus. Lupus 2010; 19: 330-333
    CrossrefPubMedSearch in Google Scholar
  • 70 Kvarta MD, Sharma D, Castellani RJ. et al. Demyelination as a harbinger of lymphoma: a case report and review of primary central nervous system lymphoma preceded by multifocal sentinel demyelination. BMC Neurol 2016; 16: 72
    CrossrefPubMedSearch in Google Scholar
  • 71 Chiavazza C, Pellerino A, Ferrio F. et al. Primary CNS lymphomas: challenges in diagnosis and monitoring. BioMed Res Int 2018; 2018: 3606970
    CrossrefPubMedSearch in Google Scholar
  • 72 Haldorsen IS, Espeland A, Larsson EM. Central nervous system lymphoma: characteristic findings on traditional and advanced imaging. AJNR Am J Neuroradiol 2011; 32: 984-992
    CrossrefPubMedSearch in Google Scholar
  • 73 Rimkus CM, Andrade CS, Leite CC. et al. Toxic leukoencephalopathies, including drug, medication, environmental, and radiation-induced encephalopathic syndromes. Semin Ultrasound CT MR 2014; 35: 97-117
    CrossrefPubMedSearch in Google Scholar
  • 74 Koksel Y, Ozutemiz C, Rykken J. et al. “CHOICES”: an acronym to aid in delineating potential causes of non-metabolic, non-infectious acute toxic leukoencephalopathy. Eur J Radiol Open 2019; 6: 243-257
    CrossrefPubMedSearch in Google Scholar
  • 75 Barile-Fabris L, Ariza-Andraca R, Olguín-Ortega L. et al. Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 620-625
    CrossrefPubMedSearch in Google Scholar