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Neuropsychiatric Manifestations of Antiphospholipid Syndrome

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Antiphospholipid Syndrome

Abstract

Neurologic manifestations are challenging in the antiphospholipid syndrome (APS) due to their partially understood etiopathogenesis and potential severity. Stroke, cognitive dysfunction, migraine, seizure, chorea, myelitis, and multiple sclerosis-like disease are reported in antiphospholipid antibody (aPL)-positive patients; however a strong association has only been reported between aPL and cerebral ischemia/infarction. Clinical studies are mostly underpowered. Small sample size and/or retrospective design limits the ability to conclude on the potential associations between nonischemic neurological manifestations and aPL. Although some evidence of a direct immune effect of aPL on the brain is supported by animal studies and human research, further clinical studies of patients enrolled based on internationally accepted APS/aPL definitions, and neuroimaging studies are needed to better evaluate the impact of these manifestations in APS.

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References

  1. Hughes GR. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J Clin Res Ed. 1983;15(287):1088–9.

    Article  Google Scholar 

  2. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost JTH. 2006;4:295–306.

    Article  CAS  PubMed  Google Scholar 

  3. Hess DC, Krauss J, Adams RJ, Nichols FT, Zhang D, Rountree HA. Anticardiolipin antibodies: a study of frequency in TIA and stroke. Neurology. 1991;41:525–8.

    Article  CAS  PubMed  Google Scholar 

  4. Ginsburg KS, Liang MH, Newcomer L, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992;15:997–1002.

    Google Scholar 

  5. Cervera R, Piette J-C, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019–27.

    Article  PubMed  Google Scholar 

  6. Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res. 2013;65:1869–73.

    Article  CAS  Google Scholar 

  7. Urbanus RT, Siegerink B, Roest M, Rosendaal FR, de 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;8:998–1005.

    Article  CAS  PubMed  Google Scholar 

  8. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;1:1827–32.

    Google Scholar 

  9. Sciascia S, Sanna G, Khamashta MA, et al. The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis. 2015;74:2028–33.

    Article  CAS  PubMed  Google Scholar 

  10. Zuily S, Regnault V, Selton-Suty C, et al. Increased risk for heart valve disease associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: meta-analysis of echocardiographic studies. Circulation. 2011;12:215–24.

    Google Scholar 

  11. Pezzini A, Grassi M, Lodigiani C, et al. Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults. Circulation. 2014;22:1668–76.

    Google Scholar 

  12. Brey RL, Escalante A. Neurological manifestations of antiphospholipid antibody syndrome. Lupus. 1998;7(Suppl 2):S67–74.

    Article  PubMed  Google Scholar 

  13. Erkan D, Kozora E, Lockshin MD. Cognitive dysfunction and white matter abnormalities in antiphospholipid syndrome. Pathophysiol Off J Int Soc Pathophysiol ISP. 2011;18:93–102.

    CAS  Google Scholar 

  14. Hachulla E, Michon-Pasturel U, Leys D, et al. Cerebral magnetic resonance imaging in patients with or without antiphospholipid antibodies. Lupus. 1998;7:124–31.

    Article  CAS  PubMed  Google Scholar 

  15. Pierangeli SS, Colden-Stanfield M, Liu X, Barker JH, Anderson GL, Harris EN. Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation. 1999;20:1997–2002.

    Google Scholar 

  16. Pierangeli SS, Espinola RG, Liu X, Harris EN. Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and P-selectin. Circ Res. 2001;2(88):245–50.

    Google Scholar 

  17. Arad A, Proulle V, Furie RA, Furie BC, Furie B. 2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model. Blood. 2011;18:3453–9.

    Google Scholar 

  18. Urbanus RT, Derksen RHWM, de Groot PG. Platelets and the antiphospholipid syndrome. Lupus. 2008;17:888–94.

    Article  CAS  PubMed  Google Scholar 

  19. Brandt KJ, Kruithof EKO, de Moerloose P. Receptors involved in cell activation by antiphospholipid antibodies. Thromb Res. 2013;132:408–13.

    Article  CAS  PubMed  Google Scholar 

  20. Lambert M, Boullier A, Hachulla E, et al. Paraoxonase activity is dramatically decreased in patients positive for anticardiolipin antibodies. Lupus. 2000;9:299–300.

    Article  CAS  PubMed  Google Scholar 

  21. Charakida M, Besler C, Batuca JR, et al. Vascular abnormalities, paraoxonase activity, and dysfunctional HDL in primary antiphospholipid syndrome. JAMA J Am Med Assoc. 2009;16:1210–7.

    Google Scholar 

  22. Kobayashi K, Kishi M, Atsumi T, et al. Circulating oxidized LDL forms complexes with beta2-glycoprotein I: implication as an atherogenic autoantigen. J Lipid Res. 2003;44:716–26.

    Article  CAS  PubMed  Google Scholar 

  23. Vaarala O. Atherosclerosis in SLE and Hughes syndrome. Lupus. 1997;6:489–90.

    Article  CAS  PubMed  Google Scholar 

  24. Harats D, George J, Levy Y, Khamashta MA, Hughes GR, Shoenfeld Y. Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus. QJM Mon J Assoc Physicians. 1999;92:57–9.

    Article  CAS  Google Scholar 

  25. Jacobson MW, Rapport LJ, Keenan PA, Coleman RD, Tietjen GE. Neuropsychological deficits associated with antiphospholipid antibodies. J Clin Exp Neuropsychol. 1999;21:251–64.

    Article  CAS  PubMed  Google Scholar 

  26. Erkan D, Barbhaiya M, George D, Sammaritano L, Lockshin M. Moderate versus high-titer persistently anticardiolipin antibody positive patients: are they clinically different and does high-titer anti-beta 2-glycoprotein-I antibody positivity offer additional predictive information? Lupus. 2010;19:613–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kozora E, Erkan D, Zhang L, et al. Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients. Clin Exp Rheumatol. 2014;32:34–40.

    PubMed  Google Scholar 

  28. Tektonidou MG, Varsou N, Kotoulas G, Antoniou A, Moutsopoulos HM. Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med. 2006;13:2278–84.

    Google Scholar 

  29. Coín MA, Vilar-López R, Peralta-Ramírez I, et al. The role of antiphospholipid autoantibodies in the cognitive deficits of patients with systemic lupus erythematosus. Lupus. 2015;24:875–9.

    Article  PubMed  Google Scholar 

  30. Arvanitakis Z, Brey RL, Rand JH, et al. Antiphospholipid antibodies, brain infarcts, and cognitive and motor decline in aging (ABICMA): design of a community-based, longitudinal, clinical-pathological study. Neuroepidemiology. 2013;40:73–84.

    Article  PubMed  Google Scholar 

  31. Juby A, Davis P, Genge T, McElhaney J. Anticardiolipin antibodies in two elderly subpopulations. Lupus. 1995;4:482–5.

    Article  CAS  PubMed  Google Scholar 

  32. Mosek A, Yust I, Treves TA, Vardinon N, Korczyn AD, Chapman J. Dementia and antiphospholipid antibodies. Dement Geriatr Cogn Disord. 2000;11:36–8.

    Article  CAS  PubMed  Google Scholar 

  33. Chapman J, Abu-Katash M, Inzelberg R, et al. Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants. J Neurol Sci. 2002;15:81–4.

    Google Scholar 

  34. Gómez-Puerta JA, Cervera R, Calvo LM, et al. Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics of 30 patients. Rheumatology (Oxford). 2005;44:95–9.

    Article  Google Scholar 

  35. Schmidt R, Auer-Grumbach P, Fazekas F, Offenbacher H, Kapeller P. Anticardiolipin antibodies in normal subjects. Neuropsychological correlates and MRI findings. Stroke J Cereb Circ. 1995;26:749–54.

    Article  CAS  Google Scholar 

  36. Zhu D-S, Fu J, Zhang Y, et al. Neurological antiphospholipid syndrome: clinical, neuroimaging, and pathological characteristics. J Neurol Sci. 2014;15:138–44.

    Google Scholar 

  37. Kozora E, Uluğ AM, Erkan D, et al. Functional magnetic resonance imaging of working memory and executive dysfunction in systemic lupus erythematosus and antiphospholipid antibody-positive patients. Arthritis Care Res. 2016;68:1655–63.

    Article  CAS  Google Scholar 

  38. Tomietto P, Annese V, D’agostini S, et al. General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum. 2007;15:1461–72.

    Google Scholar 

  39. Murray SG, Yazdany J, Kaiser R, et al. Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus. Arthritis Care Res. 2012;64:1328–33.

    Article  Google Scholar 

  40. Afeltra A, Garzia P, Mitterhofer AP, et al. Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies. Neurology. 2003;8:108–10.

    Google Scholar 

  41. Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort. Rheumatol Oxf Engl. 2004;43:1555–60.

    Article  CAS  Google Scholar 

  42. McLaurin EY, Holliday SL, Williams P, Brey RL. Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology. 2005;25:297–303.

    Google Scholar 

  43. Menon S, Jameson-Shortall E, Newman SP, Hall-Craggs MR, Chinn R, Isenberg DA. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum. 1999;42:735–41.

    Article  CAS  PubMed  Google Scholar 

  44. Hanly JG, McCurdy G, Fougere L, Douglas J-A, Thompson K. Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J Rheumatol. 2004;31:2156–62.

    PubMed  Google Scholar 

  45. Conti F, Alessandri C, Perricone C, Scrivo R, Rezai S, Ceccarelli F, et al. Neurocognitive dysfunction in systemic lupus erythematosus: association with antiphospholipid antibodies, disease activity and chronic damage. PLoS One. 2012;7:e33824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hanly JG, Hong C, Smith S, Fisk JD. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum. 1999;42:728–34.

    Article  CAS  PubMed  Google Scholar 

  47. Borowoy AM, Pope JE, Silverman E, et al. Neuropsychiatric lupus: the prevalence and autoantibody associations depend on the definition: results from the 1000 faces of lupus cohort. Semin Arthritis Rheum. 2012;42:179–85.

    Article  PubMed  Google Scholar 

  48. Sanna G, Bertolaccini ML, Cuadrado MJ, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003;30:985–92.

    PubMed  Google Scholar 

  49. Katzav A, Pick CG, Korczyn AD, et al. Hyperactivity in a mouse model of the antiphospholipid syndrome. Lupus. 2001;10:496–9.

    Article  CAS  PubMed  Google Scholar 

  50. Appenzeller S, Lapa AT, Guirau CR, de Carvalho JF, Shoenfeld Y. Cognitive impairment in antiphospholipid syndrome: evidence from animal models. Clin Rheumatol. 2012;31:403–6.

    Article  PubMed  Google Scholar 

  51. Girardi G, Fraser J, Lennen R, Vontell R, Jansen M, Hutchison G. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) – conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development. Mol Psychiatry. 2015;20:1017–26.

    Article  CAS  PubMed  Google Scholar 

  52. Ziporen L, Shoenfeld Y, Levy Y, Korczyn AD. Neurological dysfunction and hyperactive behavior associated with antiphospholipid antibodies. A mouse model. J Clin Invest. 1997;1:613–9.

    Google Scholar 

  53. Frauenknecht K, Katzav A, Weiss Lavi R, Sabag A, Otten S, Chapman J, et al. Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones. Neuropathol Appl Neurobiol. 2015;41:657–71.

    Article  CAS  PubMed  Google Scholar 

  54. Katzav A, Faust-Socher A, Kvapil F, et al. Antiphospholipid syndrome induction exacerbates a transgenic Alzheimer disease model on a female background. Neurobiol Aging. 2011;32:272–9.

    Article  CAS  PubMed  Google Scholar 

  55. Mekinian A, Lachassinne E, Nicaise-Roland P, et al. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis. 2013;72:217–22.

    Article  PubMed  Google Scholar 

  56. Marder W, Romero VC, Ganser MA, et al. Increased usage of special educational services by children born to mothers with systemic lupus erythematosus and antiphospholipid antibodies. Lupus Sci Med. 2014;1:e000034.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Hughes GRV. Migraine, memory loss, and “multiple sclerosis ”. Neurological features of the antiphospholipid (Hughes’) syndrome. Postgrad Med J. 2003;79:81–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Iñiguez C, Pascual C, Pardo A, Martinez-Castrillo JC, Alvarez-Cermeño JC. Antiphospholipid antibodies in migraine. Headache. 1991;31:666–8.

    Article  PubMed  Google Scholar 

  59. Cavestro C, Micca G, Molinari F, et al. Migraineurs show a high prevalence of antiphospholipid antibodies. J Thromb Haemost JTH. 2011;9:1350–4.

    Article  CAS  PubMed  Google Scholar 

  60. Tsakiris DA, Kappos L, Reber G, et al. Lack of association between antiphospholipid antibodies and migraine. Thromb Haemost. 1993;3:415–7.

    Google Scholar 

  61. Tietjen GE, Day M, Norris L, et al. Role of anticardiolipin antibodies in young persons with migraine and transient focal neurologic events: a prospective study. Neurology. 1998;50:1433–40.

    Article  CAS  PubMed  Google Scholar 

  62. Intiso D, Crociani P, Fogli D, et al. Occurrence of factor V Leiden mutation (Arg506Gln) and anticardiolipin antibodies in migraine patients. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2002;22:455–8.

    CAS  Google Scholar 

  63. Williams FMK, Cherkas LF, Bertolaccini ML, et al. Migraine and antiphospholipid antibodies: no association found in migraine-discordant monozygotic twins. Cephalalgia Int J Headache. 2008;28:1048–52.

    Article  CAS  Google Scholar 

  64. Rajan R, Ahluwalia J, Lal V. Prothrombotic states in migraine. Clin Appl Thromb Hemost. 2014;20:851–6.

    Google Scholar 

  65. Abreu MM, Danowski A, Wahl DG, et al. The relevance of “non-criteria” clinical manifestations of antiphospholipid syndrome: 14th International Congress on Antiphospholipid Antibodies Technical Task Force Report on Antiphospholipid Syndrome Clinical Features. Autoimmun Rev. 2015;14:401–14.

    Article  PubMed  Google Scholar 

  66. Cuadrado MJ, Khamashta MA, Hughes GR. Migraine and stroke in young women. QJM Mon J Assoc Physicians. 2000;93:317–8.

    Article  CAS  Google Scholar 

  67. Stojanovich L, Kontic M, Smiljanic D, Djokovic A, Stamenkovic B, Marisavljevic D. Association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipid syndrome. Clin Exp Rheumatol. 2013;31:756–60.

    PubMed  Google Scholar 

  68. Pardos-Gea J, Ordi-Ros J, Avegliano G, et al. Echocardiography at diagnosis of antiphospholipid syndrome provides prognostic information on valvular disease evolution and identifies two subtypes of patients. Lupus. 2010;19:575–82.

    Article  CAS  PubMed  Google Scholar 

  69. Krause I, Lev S, Fraser A, et al. Close association between valvar heart disease and central nervous system manifestations in the antiphospholipid syndrome. Ann Rheum Dis. 2005;64:1490–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Krause I, Leibovici L, Blank M, Shoenfeld Y. Clusters of disease manifestations in patients with antiphospholipid syndrome demonstrated by factor analysis. Lupus. 2007;16:176–80.

    Article  CAS  PubMed  Google Scholar 

  71. Islam MA, Alam F, Hoque MR, et al. Risk of migraine and antiphospholipid antibodies in European Cohort: a systematic review and meta-analysis. Lupus. 2016;25:72.

    Google Scholar 

  72. Intiso D, Di Rienzo F, Rinaldi G, et al. Brain MRI white matter lesions in migraine patients: is there a relationship with antiphospholipid antibodies and coagulation parameters? Eur J Neurol. 2006;13:1364–9.

    Article  CAS  PubMed  Google Scholar 

  73. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988;8(Suppl 7):1–96.

    Google Scholar 

  74. Montalbán J, Cervera R, Font J, et al. Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus. Neurology. 1992;42:681–2.

    Article  PubMed  Google Scholar 

  75. Appenzeller S, Costallat LTL. Clinical implications of migraine in systemic lupus erythematosus: relation to cumulative organ damage. Cephalalgia Int J Headache. 2004;24:1024–30.

    Article  CAS  Google Scholar 

  76. Hawro T, Bogucki A, Krupińska-Kun M, Maurer M, Woźniacka A. Intractable headaches, ischemic stroke, and seizures are linked to the presence of anti-β2GPI antibodies in patients with systemic lupus erythematosus. PLoS One. 2015;10:e0119911.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Hanly JG, Urowitz MB, O’Keeffe AG, et al. Headache in systemic lupus erythematosus: results from a prospective, international inception cohort study. Arthritis Rheum. 2013;65:2887–97.

    Article  PubMed  Google Scholar 

  78. de Carvalho JF, Pasoto SG, Appenzeller S. Seizures in primary antiphospholipid syndrome: the relevance of smoking to stroke. Clin Dev Immunol. 2012;2012:981519.

    PubMed  PubMed Central  Google Scholar 

  79. Cervera R, Serrano R, Pons-Estel GJ, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74:1011–8.

    Article  CAS  PubMed  Google Scholar 

  80. Shoenfeld Y, Lev S, Blatt I, et al. Features associated with epilepsy in the antiphospholipid syndrome. J Rheumatol. 2004;31:1344–8.

    PubMed  Google Scholar 

  81. Noureldine MHA, Harifi G, Berjawi A, et al. Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies? Lupus. 2016;25:1397–411.

    Google Scholar 

  82. Liimatainen S, Peltola M, Fallah M, Kharazmi E, Haapala A-M, Peltola J. The high prevalence of antiphospholipid antibodies in refractory focal epilepsy is related to recurrent seizures. Eur J Neurol Off J Eur Fed Neurol Soc. 2009;16:134–41.

    CAS  Google Scholar 

  83. Ong M-S, Kohane IS, Cai T, Gorman MP, Mandl KD. Population-level evidence for an autoimmune etiology of epilepsy. JAMA Neurol. 2014;71:569–74.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Ranua J, Luoma K, Peltola J, et al. Anticardiolipin and antinuclear antibodies in epilepsy – a population-based cross-sectional study. Epilepsy Res. 2004;58:13–8.

    Article  CAS  PubMed  Google Scholar 

  85. Debourdeau P, Gérome P, Zammit C, et al. Frequency of anticardiolipin, antinuclear and anti beta2GP1 antibodies is not increased in unselected epileptic patients: a case-control study. Seizure. 2004;13:205–7.

    Article  PubMed  Google Scholar 

  86. Krause I, Blank M, Fraser A, et al. The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome. Immunobiology. 2005;210:749–54.

    Article  CAS  PubMed  Google Scholar 

  87. Alam F, Islam MA, Hoque MR, et al. Comorbidity risk of epilepsy and antiphospholipid antibodies in European cohort: a systematic review and meta-analysis. Lupus. 2016;25:4–100 (abstract).

    Google Scholar 

  88. Herranz MT, Rivier G, Khamashta MA, Blaser KU, Hughes GR. Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus. Arthritis Rheum. 1994;37:568–71.

    Article  CAS  PubMed  Google Scholar 

  89. Shrivastava A, Dwivedi S, Aggarwal A, Misra R. Anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures. Lupus. 2001;10:45–50.

    Article  CAS  PubMed  Google Scholar 

  90. Hanly JG, Urowitz MB, Siannis F, et al. Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum. 2008;58:843–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Liou HH, Wang CR, Chen CJ, et al. Elevated levels of anticardiolipin antibodies and epilepsy in lupus patients. Lupus. 1996;5:307–12.

    Article  CAS  PubMed  Google Scholar 

  92. Angelini L, Granata T, Zibordi F, Binelli S, Zorzi G, Besana C. Partial seizures associated with antiphospholipid antibodies in childhood. Neuropediatrics. 1998;29:249–53.

    Article  CAS  PubMed  Google Scholar 

  93. Cimaz R, Meroni PL, Shoenfeld Y. Epilepsy as part of systemic lupus erythematosus and systemic antiphospholipid syndrome (Hughes syndrome). Lupus. 2006;15:191–7.

    Article  CAS  PubMed  Google Scholar 

  94. Liou HH, Wang CR, Chou HC, et al. Anticardiolipin antisera from lupus patients with seizures reduce a GABA receptor-mediated chloride current in snail neurons. Life Sci. 1994;54:1119–25.

    Article  CAS  PubMed  Google Scholar 

  95. Liedorp M, Sanchez E, van Hoogstraten IMW, et al. No evidence of misdiagnosis in patients with multiple sclerosis and repeated positive anticardiolipin antibody testing based on magnetic resonance imaging and long term follow-up. J Neurol Neurosurg Psychiatry. 2007;78:1146–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Karussis D, Leker RR, Ashkenazi A, Abramsky O. A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? Ann Neurol. 1998;44:629–34.

    Article  CAS  PubMed  Google Scholar 

  97. Tourbah A, Clapin A, Gout O, et al. Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study. Arch Neurol. 1998;55:517–21.

    Article  CAS  PubMed  Google Scholar 

  98. Heinzlef O, Weill B, Johanet C, et al. Anticardiolipin antibodies in patients with multiple sclerosis do not represent a subgroup of patients according to clinical, familial, and biological characteristics. J Neurol Neurosurg Psychiatry. 2002;72:647–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bidot CJ, Horstman LL, Jy W, et al. Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study. BMC Neurol. 2007;7:36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Sastre-Garriga J, Reverter JC, Font J, Tintoré M, Espinosa G, Montalban X. Anticardiolipin antibodies are not a useful screening tool in a nonselected large group of patients with multiple sclerosis. Ann Neurol. 2001;49:408–11.

    Article  CAS  PubMed  Google Scholar 

  101. Roussel V, Yi F, Jauberteau MO, et al. Prevalence and clinical significance of anti-phospholipid antibodies in multiple sclerosis: a study of 89 patients. J Autoimmun. 2000;14:259–65.

    Article  CAS  PubMed  Google Scholar 

  102. Sugiyama Y, Yamamoto T. Characterization of serum anti-phospholipid antibodies in patients with multiple sclerosis. Tohoku J Exp Med. 1996;178:203–15.

    Article  CAS  PubMed  Google Scholar 

  103. Fukazawa T, Moriwaka F, Mukai M, Hamada T, Koike T, Tashiro K. Anticardiolipin antibodies in Japanese patients with multiple sclerosis. Acta Neurol Scand. 1993;88:184–9.

    Article  CAS  PubMed  Google Scholar 

  104. Vilisaar J, Wilson M, Niepel G, Blumhardt LD, Constantinescu CS. A comparative audit of anticardiolipin antibodies in oligoclonal band negative and positive multiple sclerosis. Mult Scler Houndmills Basingstoke Engl. 2005;11:378–80.

    Article  CAS  Google Scholar 

  105. Etemadifar M, Dehghani L, Tahani S, Toghianifar N, Rahaimi M, Eskandari N. Neurological manifestations in patients with antiphospholipid syndrome. Iran J Neurol. 2013;12:172–5.

    PubMed  PubMed Central  Google Scholar 

  106. Sherer Y, Hassin S, Shoenfeld Y, et al. Transverse myelitis in patients with antiphospholipid antibodies – the importance of early diagnosis and treatment. Clin Rheumatol. 2002;21:207–10.

    Article  CAS  PubMed  Google Scholar 

  107. Mok CC, Lau CS, Wong RW. Neuropsychiatric manifestations and their clinical associations in southern Chinese patients with systemic lupus erythematosus. J Rheumatol. 2001;28:766–71.

    CAS  PubMed  Google Scholar 

  108. Costallat BL, Ferreira DM, Costallat LTL, Appenzeller S. Myelopathy in systemic lupus erythematosus: clinical, laboratory, radiological and progression findings in a cohort of 1,193 patients. Rev Bras Reumatol. 2016;56:240–51.

    Article  Google Scholar 

  109. Cuadrado MJ, Wakefield K, Sanna G, Khamashta MA, Hughes GRV. Multiple sclerosis and the antiphospholipid (Hughes) syndrome: a common differential diagnosis? Clin Exp Rheumatol. 2004;22:652–3.

    CAS  PubMed  Google Scholar 

  110. Kovacs B, Lafferty TL, Brent LH, DeHoratius RJ. Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature. Ann Rheum Dis. 2000;59:120–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Carter D, Olchovsky D, Yonath H, Langevitz P, Ezra D. Simultaneous deep vein thrombosis and transverse myelitis with negative serology as a first sign of antiphospholipid syndrome: a case report and review of the literature. Clin Rheumatol. 2006;25:756–8.

    Article  PubMed  Google Scholar 

  112. Appenzeller S, Yeh S, Maruyama M, Barros SM, de Carvalho JF. Chorea in primary antiphospholipid syndrome is associated with rheumatic fever. Rheumatol Int. 2012;32:2857–61.

    Article  PubMed  Google Scholar 

  113. Huang Y-C, Lyu R-K, Chen S-T, Chu Y-C, Wu Y-R. Parkinsonism in a patient with antiphospholipid syndrome – case report and literature review. J Neurol Sci. 2008;15:166–9.

    Google Scholar 

  114. Carecchio M, Comi C, Varrasi C, et al. Complex movement disorders in primary antiphospholipid syndrome: a case report. J Neurol Sci. 2009;15:101–3.

    Google Scholar 

  115. Chen W-H, Chen C-H, Chui C, Lui C-C, Chen C-J, Yin H-L. Antiphospholipid antibodies and cerebellar ataxia: a clinical analysis and literature review. Neuroimmunomodulation. 2014;21:283–90.

    Article  CAS  PubMed  Google Scholar 

  116. Ishikawa N, Kobayashi M. Recurrent acute cerebellar ataxia associated with anti-cardiolipin antibodies. Brain and Development. 2010;32:588–91.

    Article  PubMed  Google Scholar 

  117. Reiner P, Galanaud D, Leroux G, et al. Long-term outcome of 32 patients with chorea and systemic lupus erythematosus or antiphospholipid antibodies. Mov Disord Off 2011;26:2422–7.

    Google Scholar 

  118. Cervera R, Khamashta MA, Font J, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore). 1993;72:113–24.

    Article  CAS  Google Scholar 

  119. Orzechowski NM, Wolanskyj AP, Ahlskog JE, Kumar N, Moder KG. Antiphospholipid antibody-associated chorea. J Rheumatol. 2008;35:2165–70.

    Article  PubMed  Google Scholar 

  120. Wu SW, Graham B, Gelfand MJ, Gruppo RE, Dinopolous A, Gilbert DL. Clinical and positron emission tomography findings of chorea associated with primary antiphospholipid antibody syndrome. Mov Disord Off J Mov Disord Soc. 2007;15:1813–5.

    Google Scholar 

  121. Raza H, Epstein SA, Pao M, Rosenstein DL. Mania: psychiatric manifestations of the antiphospholipid syndrome. Psychosomatics. 2008;49:438–41.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Avari JN, Young RC. A patient with bipolar disorder and antiphospholipid syndrome. J Geriatr Psychiatry Neurol. 2012;25:26–8.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Schwartz M, Rochas M, Weller B, et al. High association of anticardiolipin antibodies with psychosis. J Clin Psychiatry. 1998;59:20–3.

    Article  CAS  PubMed  Google Scholar 

  124. Sokol DK, O’Brien RS, Wagenknecht DR, Rao T, McIntyre JA. Antiphospholipid antibodies in blood and cerebrospinal fluids of patients with psychosis. J Neuroimmunol. 2007;190:151–6.

    Article  CAS  PubMed  Google Scholar 

  125. Strous RD, Shoenfeld Y. Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. J Autoimmun. 2006;27:71–80.

    Article  CAS  PubMed  Google Scholar 

  126. Chengappa KN, Carpenter AB, Keshavan MS, et al. Elevated IGG and IGM anticardiolipin antibodies in a subgroup of medicated and unmedicated schizophrenic patients. Biol Psychiatry. 1991;1(30):731–5.

    Article  Google Scholar 

  127. Schwartz M, Silver H. Lymphocytes, autoantibodies and psychosis – coincidence versus etiological factor: an update. Isr J Psychiatry Relat Sci. 2000;37:32–6.

    CAS  PubMed  Google Scholar 

  128. Toubi E, Khamashta MA, Panarra A, Hughes GR. Association of antiphospholipid antibodies with central nervous system disease in systemic lupus erythematosus. Am J Med. 1995;99:397–401.

    Article  CAS  PubMed  Google Scholar 

  129. Appenzeller S, Cendes F, Costallat LTL. Acute psychosis in systemic lupus erythematosus. Rheumatol Int. 2008;28:237–43.

    Article  PubMed  Google Scholar 

  130. Montalbán J, Arboix A, Staub H, et al. Transient global amnesia and antiphospholipid antibodies. Clin Exp Rheumatol. 1989;7:85–7.

    PubMed  Google Scholar 

  131. Ortego-Centeno N, Callejas-Rubio JL, Fernández MG, Camello MG. Transient global amnesia in a patient with high and persistent levels of antiphospholipid antibodies. Clin Rheumatol. 2006;25:407–8.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Rare Disease Reference Center, Chef de Clinique Universitaire-Assistant des Hopitaux, Claude Huriez, Centre Hospitalier et Universitaire de Lille, Lille, France

    Cécile M. Yelnik

  2. Faculty of Medical Science, Rheumatology Unit Faculty of Medical Science, State University of Campinas, Campinas, SP, Brazil

    Simone Appenzeller

  3. Guy’s and St Thomas’ NHS Foundation Trust, Louise Coote Lupus Unit, Rheumatology Department, Guy’s Hospital, London, UK

    Giovanni Sanna

  4. National Jewish Health, University of Colorado School of Medicine, Department of Medicine, Denver, CO, USA

    Elizabeth Kozora

  5. Academic Department of Vascular Surgery, Cardiovascular Division, King’s College London, St Thomas’ Hospital, London, UK

    Maria Laura Bertolaccini

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  1. Cécile M. Yelnik
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  2. Simone Appenzeller
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  3. Giovanni Sanna
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  4. Elizabeth Kozora
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  5. Maria Laura Bertolaccini
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Correspondence to Cécile M. Yelnik .

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  1. The Barbara Volcker Center for Women and Rheumatic Diseases, Associate Attending Physician, Hospital for Special Surgery, Associate Professor of Medicine, Weill Cornell Medicine, New York, New York, USA

    Doruk Erkan

  2. The Barbara Volcker Center for Women and Rheumatic Diseases, Attending Physician, Hospital for Special Surgery, Professor of Medicine and Obstetrics-Gynecology, Weill Cornell Medicine, New York, New York, USA

    Michael D. Lockshin

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Yelnik, C.M., Appenzeller, S., Sanna, G., Kozora, E., Bertolaccini, M.L. (2017). Neuropsychiatric Manifestations of Antiphospholipid Syndrome. In: Erkan, D., Lockshin, M. (eds) Antiphospholipid Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-55442-6_10

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