Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2016; 74(12): 1021-1030
DOI: 10.1590/0004-282X20160150
VIEW AND REVIEW

Neuropsychiatric Lupus in clinical practice

Lúpus neuropsiquiátrico na prática clínica
Helena Alessi
1   Universidade Federal de São Paulo, Divisão de Neurologia Geral, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brasil;
,
Lívia Almeida Dutra
1   Universidade Federal de São Paulo, Divisão de Neurologia Geral, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brasil;
,
Pedro Braga Neto
2   Universidade Estadual do Ceará, Centro de Ciências da Saúde, Fortaleza CE, Brasil
3   Universidade Federal do Ceará, Faculdade de Medicina, Departamento de Medicina Clínica, Divisão de Neurologia, Fortaleza CE, Brasil;
,
José Luiz Pedroso
1   Universidade Federal de São Paulo, Divisão de Neurologia Geral, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brasil;
,
Fabio F. Toso
1   Universidade Federal de São Paulo, Divisão de Neurologia Geral, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brasil;
,
Cristiane Kayser
4   Universidade Federal de São Paulo, Divisão de Reumatologia, São Paulo SP, Brasil.
,
Orlando G. P. Barsottini
1   Universidade Federal de São Paulo, Divisão de Neurologia Geral, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brasil;
› Author AffiliationsSupport: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and grant #2015/08833-7, São Paulo Research Foundation (FAPESP), supported this study.
› Further Information
Also available at
   Permissions and Reprints

ABSTRACT

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs, characterized by the production of autoantibodies and the development of tissue injury. The etiology of SLE is partially known, involving multiple genetic and environmental factors. As many as 50% of patients with SLE have neurological involvement during the course of their disease. Neurological manifestations are associated with impaired quality of life, and high morbidity and mortality rates. Nineteen neuropsychiatric syndromes have been identified associated with SLE, and can be divided into central and peripheral manifestations. This article reviews major neuropsychiatric manifestations in patients with SLE and discusses their clinical features, radiological findings and treatment options.

RESUMO

Lúpus eritematoso sistêmico (LES) é uma doença autoimune crçnica que envolve múltiplos órgãos e sistemas, caracterizada pela produção de auto anticorpos e lesão tecidual. A etiologia do LES é parcialmente conhecida e envolve interação entre fatores genéticos e ambientais. Até 50% dos pacientes com LES apresentam envolvimento neurológico no decorrer da doença. Manifestações neurológicas estão associadas a prejuízo na qualidade de vida e altas taxas de mortalidade e morbidade. Foram identificadas 19 síndromes neuropsiquiátricas em pacientes com LES, divididas entre manifestações do sistema nervoso central e periférico. O objetivo deste artigo é revisar as manifestações neuropsiquiátricas mais importantes. Serão abordadas as características clínicas, os aspectos radiológicos e opções de tratamento dos eventos neuropsiquiátricos.

systemic lupus erythematosus - lupus vasculitis, central nervous system - seizures - myelitis - autoimmune diseases
lúpus eritematoso sistêmico - vasculite associada ao lúpus, sistema nervoso central - convulsões - mielite - doenças autoimunes

Support:

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and grant #2015/08833-7, São Paulo Research Foundation (FAPESP), supported this study.




Publication History

Received: 26 April 2016

Accepted: 11 August 2016

Article published online:
06 September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Hahn B. Lúpus eritematoso sistêmico. In: Fauci AS, Braunwald E, Kasper DL et al., editors. Harrison medicina interna. 17a ed. Rio de Janeiro: McGraw-Hill Interamericana do Brasil; 2008. p. 2075-83.
  • 2 Rother N, Vlag J. Disturbed T cell signaling and altered th17 and regulatory T cell subsets in the pathogenesis of systemic lupus erythematosus. Front Immunol. 2015;6:610. doi:10.3389/fimmu.2015.00610
  • 3 Kozora E, Erkan D, West SG, Filley CM, Zhang L, Ramon G et al. Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE). Lupus. 2013;22(1):73-80. doi:10.1177/0961203312468963
  • 4 Pamfil C, Fanouriakis A, Damian L, Rinzis M, Sidiropoulos P, Tsivgoulis G et al. EULAR recommendations for neuropsychiatric systemic lupus erythematosus vs usual care: results from two European centres. Rheumatology (Oxford). 2015;54(7):1270-8. doi:10.1093/rheumatology/keu482
  • 5 Liang M, Corzillius M, Bae S, Lew RA, Fortin PR, Gordon C. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42(4):599-608. doi:10.1002/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-
  • 6 Hanly JG. Diagnosis and management of neuropsychiatric SLE. Nat Rev Rheumatol. 2014;10(6):338-347. doi:10.1038/nrrheum.2014.15
  • 7 Sciascia S, Bertolaccini ML, Roccatello D, Khamashta MA, Sanna G. Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review. J Neurol. 2014;261(9):1706-14. doi:10.1007/s00415-014-7406-8
  • 8 Bertsias G, Ioannidis J, Aringer M, Bollen E, Bombardieri S, Bruce IN 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):2074-82. doi:10.1136/ard.2010.130476
  • 9 Bonfa E, Golombek SJ, Kaufman LD, Skelly S, Weissbach H, Brot N et al. Association between lupus psychosis and antiribosomal P protein antibodies. N Engl J Med. 1987;317(5):265-71. doi:10.1056/NEJM198707303170503
  • 10 Hirohata S, Sakuma Y, Yanagida T, Yoshio T. Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus. Arthritis Res Ther. 2014;16(5):450. doi:10.1186/s13075-014-0450-z
  • 11 Mitsikostas DD, Sfikakis PP, Goadsby PJ. A meta-analysis for headache in systemic lupus erythematosus: the evidence and the myth. Brain. 2004;127(5):1200-9. doi:10.1093/brain/awh146
  • 12 Hanly J, Urowitz MB, O’Keeffe AG, Gordon C, Bae SC, Sanchez-Guerrero J et al. Headache in systemic lupus erythematosus: Results from a prospective, international inception cohort study. Arthritis Rheum. 2013;65(11):2887-97. doi:10.1002/art.38106
  • 13 Jeong HW, Her M, Bae JS, Kim SK, Lee SW, Kim HK et al. Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions. Rheumatol Int. 2015;35(5):861-9. doi:10.1007/s00296-014-3150-8
  • 14 Schwartz N, Mitnick HJ, Nowatzky J. Headaches related to rheumatologic disease. Curr Pain Headache Rep. 2013;17(12). doi:10.1007/s11916-013-0381-4
  • 15 Diener HC, Charles A, Goadsby PJ, Holle D. New therapeutic approaches for the prevention and treatment of migraine. Lancet Neurol. 2015;14(10):1010-2. doi:10.1016/S1474-4422(15)00198-2
  • 16 Mikdashi J, Esdaile J, Alarcón GS, Crofford L, Fessler BJ, Shanberg L et al. Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials. Lupus. 2007;16(6):418-25. doi:10.1177/0961203307079044
  • 17 Adhikari T, Piatti A, Luggen M. Cognitive dysfunction in SLE: development of a screening tool. Lupus. 2011;20(11):1142-6. doi:10.1177/0961203311405374
  • 18 Kozora E, Arciniegas D, Zhang L, West S. Neuropsychological patterns in systemic lupus erythematosus patients with depression. Arthritis Res Ther. 2007;9(3):R48. doi:10.1186/ar2203
  • 19 Kozora E, Hanly J, Lapteva L, Filley C. Cognitive dysfunction in systemic lupus erythematosus: past, present, and future. Arthritis Rheum. 2008;58(11):3286-98. doi:10.1002/art.23991
  • 20 Peretti CS, Peretti CR, Kozora E, Papathanassiou D, Chouinard VA, Chouinard G. Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography. Psychother Psychosom. 2012;81(5):276-85. doi:10.1159/000336555
  • 21 Faust T, Chang E, Kowal C, Berlin R, Gazaryan IG, Bertini E et al. Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci USA. 2010;107(43):18569-74. doi:10.1073/pnas.1006980107
  • 22 Lauvsnes MB, Beyer MK, Kvaloy JT, Greve OJ, Appenzeller S, Kvivik I et al. Hippocampal atrophy is associated with cerebrospinal fluid anti-NR2 antibodies in patients with systemic lupus erythematosus and primary Sjögren’s syndrome. Arthritis Rheum. 2014;66(12):3387-94. doi:10.1002/art.38852
  • 23 Petri M, Naqibuddin M, Sampedro M, Omdal R, Carson KA. Memantine in systemic lupus erythematosus: a randomized, double-blind placebo-controlled trial. Semin Arthritis Rheum. 2011;41(2):194-202. doi:10.1016/j.semarthrit.2011.02.005
  • 24 Appenzeller S, Cendes F, Costallat LTL. Epileptic seizures in systemic lupus erythematosus. Neurology. 2004;63(10):1808-12. doi:10.1212/01.WNL.0000144178.32208.4F
  • 25 Nabbout R. Autoimmune and inflammatory epilepsies. Epilepsia. 2012;53 Suppl 4:58–62. doi:10.1111/j.1528-1167.2012.03614.x
  • 26 Mikdashi J, Krumholz A, Handwerger B. Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus erythematosus. Neurology. 2005;64(12):2102-7. doi:10.1212/01.WNL.0000165959.98370.D5
  • 27 Merayo-Chalico J, Apodaca E, Barrera-Vargas A, Alcocer-Varela A, Colunga-Pedraza I, González-Patiño A et al. Clinical outcomes and risk factors for posterior reversible encephalopathy syndrome in systemic lupus erythematosus: a multicentric case-control study. J Neurol Neurosurg Psychiatry. 2015;87(3):587-94. doi:10.1136/jnnp-2014-310145
  • 28 Hirohata S, Arinuma Y, Yanagida T, Yoshio T. Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther. Arthritis Res Ther. 2014;16(2):R77. doi:10.1186/ar4518
  • 29 Nishimura K, Omori M, Horikawa N, Tanaka E, Furuya T, Harigai M. Risperidone in the treatment of acute confusional state (delirium) due to neuropsychiatric lupus erythematosus: case report. Int J Psychiatry Med]. 2003;33(3):299-303. doi:10.2190/P2T8-Y12E-ANKM-8MWF
  • 30 Palagini L, Mosca M, Tani C, Gemignani A, Mauri M, Bombardieri S. Depression and systemic lupus erythematosus: a systematic review. Lupus. 2013;22(5):409-16. doi:10.1177/0961203313477227
  • 31 Postal M, Lapa AT, Sinicato NA, Peliçari KO, Peres FA, Costallat LT, et al. Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus. J Neuroinflammation. 2016;13(5):5. doi:10.1186/s12974-015-0471-9
  • 32 Kivity S, Agmon-Levin N, Zandman-Goddard G, Chapman J, Shoenfeld Y. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med. 2015;13(1):43. doi:10.1186/s12916-015-0269-8
  • 33 Holmqvist M, Simard JF, Asplund K, Arkema EV. Stroke in systemic lupus erythematosus: a meta-analysis of population-based cohort studies. RMD Open. 2015;1:e000168. doi:10.1136/rmdopen-2015-000168
  • 34 Mikdashi J, Handwerger B, Langenberg P, Miller M, Kittner S. Baseline disease activity, hyperlipidemia, and hypertension are predictive factors for ischemic stroke and stroke severity in systemic lupus erythematosus. Stroke. 2007;38(2):281-5. doi:10.1161/01.STR.0000254476.05620.14
  • 35 Panichpisal K, Rozner E, Levine SR. The management of stroke in antiphospholipid syndrome. Curr Rheumatol Rep. 2012;14(1):99-106. doi:10.1007/s11926-011-0223-5
  • 36 Sciascia S, Sanna G, Khamashta MA, Cuadrado MJ, Erkan D, Andreoli L et al. The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis. 2015;74(11):2028-33. doi:10.1136/annrheumdis-2014-205663
  • 37 Urbanus RT, Siegerink B, Roest M, Rosendaal FR, Groot PG, Algra A. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 2009;8(11):998-1005. doi:10.1016/S1474-4422(09)70239-X
  • 38 Behrouz R. The risk of ischemic stroke in major rheumatic disorders. J Neuroimmunol. 2014;277(1-2):1-5. doi:10.1016/j.jneuroim.2014.09.009
  • 39 Baizabal-Carvallo JF, Bonnet C, Jankovic J. Movement disorders in systemic lupus erythematosus and the antiphospholipid syndrome. J Neural Transm. 2013;120(11):1579-89. doi:10.1007/s00702-013-1023-z
  • 40 Cardoso F. Movement disorders in childhood. Parkinsonism Relat Disord. 2014;20 Suppl 1:S13-16. doi:10.1016/S1353-8020(13)70006-3
  • 41 Barsottini OG, Ferraz HB, Seviliano MM, Barbieri A. Brain SPECT imaging in Sydenham’s chorea. Braz J Med Biol Res. 2002;35(4):431-6. doi:10.1590/S0100-879X2002000400004
  • 42 Martino D, Chew NK, Mir P, Edwards MJ, Quinn NP, Bhatia KP. Atypical movement disorders in antiphospholipid syndrome. Mov Disord. 2006;21(7):944-9. doi:10.1002/mds.20842
  • 43 Baizabal-Carvallo J, Delgadillo-Márquez G, Estañol B, García-Ramos G. Clinical characteristics and outcomes of the meningitides in systemic lupus erythematosus. Eur Neurol. 2009;61(3):143-8. doi:10.1159/000186504
  • 44 Schulz SW, Shenin M, Mehta A, Kebede A, Fluerant M, Derk CT. Initial presentation of acute transverse myelitis in systemic lupus erythematosus: demographics, diagnosis, management and comparison to idiopathic cases. Rheumatol Int. 2012;32:2623-7. doi:10.1007/s00296-011-2053-1
  • 45 Fangtham M, Petri M. 2013 update: hopkins lupus cohort. Curr Rheumatol Rep. 2013;15(9):360. doi:10.1007/s11926-013-0360-0
  • 46 Saison J, Costedoat-Chalumeau N, Maucort-Boulch D, Iwaz J, Marignier R, Cacoub P et al. Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients. Lupus. 2015;24(1):74-81. doi:10.1177/0961203314547795
  • 47 Lacomis D, Zivković SA. Approach to vasculitic neuropathies. J Clin Neuromuscul Dis. 2007;9(1):265-76. doi:10.1097/CND.0b013e31815202b3
  • 48 Moore PM, Fauci AS. Neurologic manifestations of systemic vasculitis. A retrospective and prospective study of the clinicopathologic features and responses to therapy in 25 patients. Am J Med. 1981;71(4):517-24. doi:10.1016/0002-9343(81)90194-7
  • 49 Oomatia A, Fang H, Petri M, Birnbaum J. Peripheral neuropathies in systemic lupus erythematosus: clinical features, disease associations, and immunologic characteristics evaluated over a twenty-five-year study period. Arthritis Rheumatol. 2014;66(4):1000-9. doi:10.1002/art.38302
  • 50 Khan S, Zhou L. Characterization of non-length-dependent small-fiber sensory neuropathy. Muscle Nerve. 2012;45(1):86-91. doi:10.1002/mus.22255
  • 51 Servioli L, Pérez C, Consani S, Suárez A, Sehabiaga G, Collazo C et al. Prevalence and characteristics of immunomediated neuropathies in a group of patients with autoimmune diseases. J Clin Neuromuscul Dis. 2007;9(2):285-90. doi:10.1097/CND.0b013e318157614b
  • 52 Florica B, Aghdassi E, Su J, Gladman DD, Urowitz MB, Fortin PR. Peripheral neuropathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum. 2011;41(2):203-11. doi:10.1016/j.semarthrit.2011.04.001
  • 53 Hantson P, Kevers L, Fabien N, Van Den Bergh P. Acute-onset chronic inflammatory demyelinating polyneuropathy with cranial nerve involvement, dysautonomia, respiratory failure, and autoantibodies. Muscle Nerve. 2010;41(3):423-6. doi:10.1002/mus.21543
  • 54 Hsu TY, Wang SH, Kuo CF, Chiu TF, Chang YC. Acute inflammatory demyelinating polyneuropathy as the initial presentation of lupus. Am J Emerg Med. 2009;27(7):900.e3-5. doi:10.1016/j.ajem.2008.11.006
  • 55 Gaber W, Ezzat Y, El Fayoumy NM, Helmy H, Mohey AM. Detection of asymptomatic cranial neuropathies in patients with systemic lupus erythematosus and their relation to antiribosomal P antibody levels and disease activity. Clin Rheumatol. 2014;33(10):1459-66. doi:10.1007/s10067-014-2679-y
  • 56 Roverano S, Cassano G, Paira S, Chiavarini J, Graf C, Rico L et al. Asymptomatic sensorineural hearing loss in patients with systemic lupus erythematosus. J Clin Rheumatol. 2006;12(5):217-20. doi:10.1097/01.rhu.0000242777.71604.6
  • 57 Magro Checa C, Cohen D, Bollen EL, Buchem MA, Huizinga TW, Steup-Beekman GM. Demyelinating disease in SLE: is it multiple sclerosis or lupus? Best Pract Res Clin Rheumatol. 2013;27(3):405-24. doi:10.1016/j.berh.2013.07.010
  • 58 Lin YC, Wang AG, Yen MY. Systemic lupus erythematosus-associated optic neuritis: clinical experience and literature review. Acta Ophthalmol. 2009;87(2):204-10. doi:10.1111/j.1755-3768.2008.01193.x
  • 59 Karatas E, Onat AM, Durucu C, Baglam T, Kanlikama M, Altunoren O et al. Audiovestibular disturbance in patients with systemic lupus erythematosus. Otolaryngol Head Neck Surg. 2007;136(1):82-6. doi:10.1016/j.otohns.2006.06.1255
  • 60 Batuecas-Caletrío A, Pino-Montes J, Cordero-Civantos C, Calle-Cabanillas MI, Lopez-Escamez JA. Hearing and vestibular disorders in patients with systemic lupus erythematosus. Lupus. 2013;22(5):437-42. doi:10.1177/0961203313477223
  • 61 Zirkzee EJ, Steup-Beekman GM, Mast RC, Bollen EL, Wee NJ, Baptist E et al. Prospective study of clinical phenotypes in neuropsychiatric systemic lupus erythematosus; multidisciplinary approach to diagnosis and therapy. J Rheumatol. 2012;39(11):2118-26. doi:10.3899/jrheum.120545