Multiple Sclerosis | Neurologic Manifestations of the Antiphospholipid Syndrome — an Update

1.

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. 2006;4(2):295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.x.CrossRefPubMed

2.

Shoenfeld Y, Twig G, Katz U, Sherer Y. Autoantibody explosion in antiphospholipid syndrome. J Autoimmun. 2008;30(1-2):74–83. https://doi.org/10.1016/j.jaut.2007.11.011.CrossRefPubMed

3.

Cervera R. Antiphospholipid syndrome. Thromb Res. 2017;151(Suppl):S43–7. https://doi.org/10.1016/S0049-3848(17)30066-X.CrossRefPubMed

4.

Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, et al. Antiphospholipid syndrome. Nat Rev Dis Prim. 2018;4:17103. https://doi.org/10.1038/nrdp.2017.103.CrossRefPubMed

5.

Ginsburg KS, Liang MH, Newcomer L, Goldhaber SZ, Schur PH, Hennekens CH, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992;117(12):997–1002. https://doi.org/10.7326/0003-4819-117-12-997.CrossRefPubMed

6.

Cervera R, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Kiss E, et al. Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2009;68(9):1428–32. https://doi.org/10.1136/ard.2008.093179.CrossRefPubMed

7.

Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramón E, 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(6):1011–8. https://doi.org/10.1136/annrheumdis-2013-204838.CrossRefPubMed

8.

Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. 2002;346(10):752–63. https://doi.org/10.1056/NEJMra002974.CrossRefPubMed

9.

Ünlü O, Zuily S, Erkan D. The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Eur J Rheumatol. 2016;3(2):75–84. https://doi.org/10.5152/eurjrheum.2015.0085.CrossRefPubMed

10.

Sène D, Piette J-C, Cacoub P. Antiphospholipid antibodies, antiphospholipid syndrome and infections. Autoimmun Rev. 2008;7(4):272–7. https://doi.org/10.1016/j.autrev.2007.10.001.CrossRefPubMed

11.

Gharavi AE, Sammaritano LR, Wen J, Miyawaki N, Morse JH, Zarrabi MH, et al. Characteristics of human immunodeficiency virus and chlorpromazine induced antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to phospholipid. J Rheumatol. 1994;21(1):94–9.PubMed

12.

Dlott JS, Roubey RAS. Drug-induced lupus anticoagulants and antiphospholipid antibodies. Curr Rheumatol Rep. 2012;14(1):71–8. https://doi.org/10.1007/s11926-011-0227-1.CrossRefPubMed

13.

Aggarwal R, Ringold S, Khanna D, Neogi T, Johnson SR, Miller A, et al. Distinctions between diagnostic and classification criteria? Arthritis Care Res. 2015;67(7):891–7. https://doi.org/10.1002/acr.CrossRef

14.

Cervera R, Rodríguez-Pintó I, Colafrancesco S, Conti F, Valesini G, Rosário C, et al. 14th International Congress on Antiphospholipid Antibodies Task Force report on catastrophic antiphospholipid syndrome. Autoimmun Rev. 2014;13(7):699–707. https://doi.org/10.1016/j.autrev.2014.03.002.CrossRefPubMed

15.

Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet (London, England). 2010;376(9751):1498–509. https://doi.org/10.1016/S0140-6736(10)60709-X.CrossRef

16.

Barbhaiya M, Zuily S, Ahmadzadeh Y, et al. Development of new international antiphospholipid syndrome classification criteria phase I/II report: generation and reduction of candidate criteria.; 2020. doi:10.1002/acr.24520

17.

Mekinian A, Bourrienne M-C, Carbillon L, Benbara A, Noémie A, Chollet-Martin S, et al. Non-conventional antiphospholipid antibodies in patients with clinical obstetrical APS: prevalence and treatment efficacy in pregnancies. Semin Arthritis Rheum. 2016;46(2):232–7. https://doi.org/10.1016/j.semarthrit.2016.05.006.CrossRefPubMed

18.

Shi H, Zheng H, Yin Y-F, Hu QY, Teng JL, Sun Y, et al. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome. Clin Chem Lab Med. 2018;56(4):614–24. https://doi.org/10.1515/cclm-2017-0502.CrossRefPubMed

19.

de Laat B, Mertens K, de Groot PG. Mechanisms of disease: antiphospholipid antibodies-from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol. 2008;4(4):192–9. https://doi.org/10.1038/ncprheum0740.CrossRefPubMed

20.

de Laat B, Pengo V, Pabinger I, et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost. 2009;7(11):1767–73. https://doi.org/10.1111/j.1538-7836.2009.03588.x.CrossRefPubMed

21.

•• Volkov I, Seguro L, Leon EP, et al. Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome. Auto- Immun highlights. 2020;11(1):8. https://doi.org/10.1186/s13317-020-00131-3Recent study mainly on non-criteria aPLs. First study to correlate CNS manifestations to a specific aPL profile, with simultaneous positivity for IgG antibodies against prothrombin, phosphatidylglycerol, phosphatidylinositol, and annexin-5.CrossRefPubMedPubMedCentral

22.

Zhang S, Wu Z, Li J, Li P, Chen S, Wen X, et al. Clinical performance of antibodies to prothrombin and thrombin in Chinese patients with antiphospholipid syndrome: potential interest in discriminating patients with thrombotic events and non-thrombotic events. Rheumatol Int. 2017;37(4):579–84. https://doi.org/10.1007/s00296-016-3594-0.CrossRefPubMed

23.

Cervera R, Conti F, Doria A, Iaccarino L, Valesini G. Does seronegative antiphospholipid syndrome really exist? Autoimmun Rev. 2012;11(8):581–4. https://doi.org/10.1016/j.autrev.2011.10.017.CrossRefPubMed

24.

Orzechowski NM, Wolanskyj AP, Ahlskog JE, Kumar N, Moder KG. Antiphospholipid antibody-associated chorea. J Rheumatol. 2008;35(11):2165–70. https://doi.org/10.3899/jrheum.080268.CrossRefPubMed

25.

Reine P, Galanaud D, Leroux G, et al. Long-term outcome of 32 patients with chorea and systemic lupus erythematosus or antiphospholipid antibodies. Mov Disord. 2011;26(13):2422–7. https://doi.org/10.1002/mds.23851.CrossRef

26.

Pignatelli P, Ettorre E, Menichelli D, Pani A, Violi F, Pastori D. Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management. Haematologica. 2020;105(3):562–72. https://doi.org/10.3324/haematol.2019.221945.CrossRefPubMedPubMedCentral

27.

Tebo AE. Laboratory Evaluation of antiphospholipid syndrome: an update on autoantibody testing. Clin Lab Med. 2019;39(4):553–65. https://doi.org/10.1016/j.cll.2019.07.004.CrossRefPubMed

28.

Hoxha A, Mattia E, Tonello M, Grava C, Pengo V, Ruffatti A. Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome. Clin Chem Lab Med. 2017;55(6):890–8. https://doi.org/10.1515/cclm-2016-0638.CrossRefPubMed

29.

Rand JH, Wu X-X, Quinn AS, Taatjes DJ. The annexin A5-mediated pathogenic mechanism in the antiphospholipid syndrome: role in pregnancy losses and thrombosis. Lupus. 2010;19(4):460–9. https://doi.org/10.1177/0961203310361485.CrossRefPubMed

30.

Amoroso A, Mitterhofer AP, Del Porto F, et al. Antibodies to anionic phospholipids and anti-beta2-GPI: association with thrombosis and thrombocytopenia in systemic lupus erythematosus. Hum Immunol. 2003;64(2):265–73. https://doi.org/10.1016/s0198-8859(02)00789-9.CrossRefPubMed

31.

Atsumi T, Ieko M, Bertolaccini ML, Ichikawa K, Tsutsumi A, Matsuura E, et al. Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant. Arthritis Rheum. 2000;43(9):1982–93. https://doi.org/10.1002/1529-0131(200009)43:9<1982::AID-ANR9>3.0.CO;2-2.CrossRefPubMed

32.

Tonello M, Mattia E, Favaro M, del Ross T, Calligaro A, Salvan E, et al. IgG phosphatidylserine/prothrombin antibodies as a risk factor of thrombosis in antiphospholipid antibody carriers. Thromb Res. 2019;177:157–60. https://doi.org/10.1016/j.thromres.2019.03.006.CrossRefPubMed

33.

Nakamura H, Oku K, Amengual O, Ohmura K, Fujieda Y, Kato M, et al. First-line, non-criterial antiphospholipid antibody testing for the diagnosis of antiphospholipid syndrome in clinical practice: a combination of anti-β(2) -glycoprotein I domain I and anti-phosphatidylserine/prothrombin complex antibodies tests. Arthritis Care Res. 2018;70(4):627–34. https://doi.org/10.1002/acr.23310.CrossRef

34.

Žigon P, Podovšovnik A, Ambrožič A, Tomšič M, Hočevar A, Gašperšič N, et al. Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements. Clin Rheumatol. 2019;38(2):371–8. https://doi.org/10.1007/s10067-018-4251-7.CrossRefPubMed

35.

Núñez-Álvarez CA, Hernández-Molina G, Bermúdez-Bermejo P, Zamora-Legoff V, Hernández-Ramírez DF, Olivares-Martínez E, et al. Prevalence and associations of anti-phosphatidylserine/prothrombin antibodies with clinical phenotypes in patients with primary antiphospholipid syndrome: aPS/PT antibodies in primary antiphospholipid syndrome. Thromb Res. 2019;174:141–7. https://doi.org/10.1016/j.thromres.2018.12.023.CrossRefPubMed

36.

Canti V, Del Rosso S, Tonello M, et al. Antiphosphatidylserine/prothrombin antibodies in antiphospholipid syndrome with intrauterine growth restriction and preeclampsia. J Rheumatol. 2018;45(9):1263–72. https://doi.org/10.3899/jrheum.170751.CrossRefPubMed

37.

Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. GAPSS: the Global Anti-Phospholipid Syndrome Score. Rheumatology (Oxford). 2013;52(8):1397–403. https://doi.org/10.1093/rheumatology/kes388.CrossRef

38.

• Cervera R, Boffa MC, Khamashta MA, Hughes GRV. The Euro-Phospholipid project: epidemiology of the antiphospholipid syndrome in Europe. Lupus. 2009;18(10):889–93. https://doi.org/10.1177/0961203309106832The Euro-Phospholipid cohort includes 1000 primary and secondary APS patients and detailed prevalence of different clinical manifestations, including neurological and other non-criteria manifestations.CrossRefPubMed

39.

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;166(20):2278–84. https://doi.org/10.1001/archinte.166.20.2278.CrossRefPubMed

40.

Trysberg E, Nylen K, Rosengren LE, Tarkowski A. Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum. 2003;48(10):2881–7. https://doi.org/10.1002/art.11279.CrossRefPubMed

41.

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(5):613–9. https://doi.org/10.1177/0961203309355300.CrossRefPubMed

42.

Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019–27. https://doi.org/10.1002/art.10187.CrossRefPubMed

43.

Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, De Jesus GR, 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(11):1869–73. https://doi.org/10.1002/acr.22066.CrossRef

44.

Gašperšič N, Zaletel M, Kobal J, Žigon P, Čučnik S, Šemrl SS, et al. Stroke and antiphospholipid syndrome—antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event. Clin Rheumatol. 2019;38(2):379–84. https://doi.org/10.1007/s10067-018-4247-3.CrossRefPubMed

45.

Babikian VL, Brey RL, Coull BM, et al. Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia. Stroke. 1990;21(9):1268–73. https://doi.org/10.1161/01.STR.21.9.1268.CrossRef

46.

Fleetwood T, Cantello R, Comi C. Antiphospholipid syndrome and the neurologist: from pathogenesis to therapy. Front Neurol. 2018;9(NOV). doi:https://doi.org/10.3389/fneur.2018.01001

47.

Hughes GRV. Migraine, memory loss, and “multiple sclerosis”. Neurological features of the antiphospholipid (Hughes’) syndrome. Postgrad Med J. 2003;79(928):81–3. https://doi.org/10.1136/pmj.79.928.81.CrossRefPubMedPubMedCentral

48.

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. https://doi.org/10.1136/annrheumdis-2014-205663.CrossRefPubMed

49.

Roldan JF, Brey RL. Neurologic Manifestations of the antiphospholipid syndrome. Curr Rheumatol Rep. 2007;9:109–15.CrossRef

50.

Brey RL. Management of the neurological manifestations of APS - what do the trials tell us? Thromb Res. 2004;114(5-6 SPEC. ISS.):489-499. doi:https://doi.org/10.1016/j.thromres.2004.06.018

51.

Provenzale JM, Barboriak DP, Allen NB, Ortel TL. Antiphospholipid antibodies: findings at arteriography. Am J Neuroradiol. 1998;19(4):611–6.PubMed

52.

Ricarte IF, Dutra LA, Abrantes FF, Toso FF, Barsottini OGP, Silva GS, et al. Neurologic manifestations of antiphospholipid syndrome. Lupus. 2018;27(9):1404–14. https://doi.org/10.1177/0961203318776110.CrossRefPubMed

53.

De Amorim LCD, Maia FM, Rodrigues CEM. Stroke in systemic lupus erythematosus and antiphospholipid syndrome: risk factors, clinical manifestations, neuroimaging, and treatment. Lupus. 2017;26(5):529–36. https://doi.org/10.1177/0961203316688784.CrossRefPubMed

54.

Erdogan D, Goren MT, Diz-Kucukkaya R, Inanc M. Assessment of cardiac structure and left atrial appendage functions in primary antiphospholipid syndrome: a transesophageal echocardiographic study. Stroke. 2005;36(3):592–6. https://doi.org/10.1161/01.STR.0000154858.27353.df.CrossRefPubMed

55.

Koniari I, Siminelakis SN, Baikoussis NG, Papadopoulos G, Goudevenos J, Apostolakis E. Antiphospholipid syndrome; its implication in cardiovascular diseases: a review. J Cardiothorac Surg. 2010;5(1):101. https://doi.org/10.1186/1749-8090-5-101.CrossRefPubMedPubMedCentral

56.

Panichpisal K, Rozner E, Levine SR. The management of stroke in antiphospholipid syndrome. Curr Rheumatol Rep. 2012;14(1):99–106. https://doi.org/10.1007/s11926-011-0223-5.CrossRefPubMed

57.

Provenzale JM, Barboriak DP, Alen NB, Ortel TL. Patients with antiphospholipid antibodies: CT and MR findings of the brain. AJR. 1996;167:1573–8.CrossRef

58.

Silvis SM, De Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol. 2017;13(9):555–65. https://doi.org/10.1038/nrneurol.2017.104.CrossRefPubMed

59.

Martinelli I, Battaglioli T, Pedotti P, Cattaneo M, Mannucci PM. Hyperhomocysteinemia in cerebral vein thrombosis. Blood. 2003;102(4):1363–6. https://doi.org/10.1182/blood-2003-02-0443.CrossRefPubMed

60.

Christopher R, Nagaraja D, Dixit NS, Narayanan CP. Anticardiolipin antibodies: a study in cerebral venous thrombosis. Acta Neurol Scand. 1999;99(2):121–4. https://doi.org/10.1111/j.1600-0404.1999.tb00669.x.CrossRefPubMed

61.

Tsai CL, Hueng DY, Tsao WL, Lin JC. Cerebral venous sinus thrombosis as an initial manifestation of primary antiphospholipid syndrome. Am J Emerg Med. 2013;31(5):888.e1–3. https://doi.org/10.1016/j.ajem.2012.12.020.CrossRef

62.

Ferro JM, Bousser MG, Canhão P, Coutinho JM, Crassard I, Dentali F, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – endorsed by the European Academy of Neurology. Eur J Neurol. 2017;24(10):1203–13. https://doi.org/10.1111/ene.13381.CrossRefPubMed

63.

Samanta D, Cobb S, Arya K. Sneddon syndrome: a comprehensive overview. J Stroke Cerebrovasc Dis. 2019;28(8):2098–108. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.05.013.CrossRefPubMed

64.

Francès C, Papo T, Wechsler B, Laporte J-L, Biousse V, Piette J-C. Sneddon syndrome with or without antiphospholipid antibodies: a comparative study in 46 patients. Medicine (Baltimore). 1999;78(4):209–19.CrossRef

65.

Wu S, Xu Z, Liang H. Sneddon’s syndrome: a comprehensive review of the literature. Orphanet J Rare Dis. 2014;9:215. https://doi.org/10.1186/s13023-014-0215-4.CrossRefPubMedPubMedCentral

66.

Gupta S, Zivadinov R, Ramasamy D, Ambrus JL. Reversible cerebral vasoconstriction syndrome (RCVS) in antiphospholipid antibody syndrome (APLA): the role of centrally acting vasodilators. Case series and review of literature. Clin Rheumatol. 2014;33(12):1829–33. https://doi.org/10.1007/s10067-013-2434-9.CrossRefPubMed

67.

Wang Z, Fu Z, Wang J, Cui H, Zhang Z, Zhang B. Moyamoya syndrome with antiphospholipid antibodies: a case report and literature review. Lupus. 2014;23(11):1204–6. https://doi.org/10.1177/0961203314540761.CrossRefPubMed

68.

Krause I, Leibovici L, Blank M, Shoenfeld Y. Clusters of disease manifestations in patients with antiphospholipid syndrome demonstrated by factor analysis. Lupus. 2007;16(3):176–80. https://doi.org/10.1177/0961203306075977.CrossRefPubMed

69.

Shoenfeld Y, Lev S, Blatt I, Blank M, Font J, von Landenberg P, et al. Features associated with epilepsy in the antiphospholipid syndrome. J Rheumatol. 2004;31(7):1344–8.PubMed

70.

Arnson Y, Shoenfeld Y, Alon E, Amital H. The antiphospholipid syndrome as a neurological disease. Semin Arthritis Rheum. 2010;40(2):97–108. https://doi.org/10.1016/j.semarthrit.2009.05.001.CrossRefPubMed

71.

De Carvalho JF, Pasoto SG, Appenzeller S. Seizures in primary antiphospholipid syndrome: the relevance of smoking to stroke. Clin Dev Immunol. 2012;2012:1–7. https://doi.org/10.1155/2012/981519.CrossRef

72.

• Noureldine MHA, Harifi G, Berjawi A, et al. Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies? Lupus. 2016;25(13):1397–411. https://doi.org/10.1177/0961203316651747An up-to-date and comprehensive review on the relationship between APS, aPL, and seizures/epilepsy.CrossRefPubMed

73.

Yelnik CM, Kozora E, Appenzeller S. Non-stroke central neurologic manifestations in antiphospholipid syndrome. Curr Rheumatol Rep. 2016;18(2):1–9. https://doi.org/10.1007/s11926-016-0568-x.CrossRef

74.

Jacobson MW, Rapport LJ, Keenan PA, Coleman RD, Tietjen GE. Neuropsychological deficits associated with antiphospholipid antibodies. J Clin Exp Neuropsychol. 1999;21(2):251–64. https://doi.org/10.1076/jcen.21.2.251.931.CrossRefPubMed

75.

Coín MA, Vilar-López R, Peralta-Ramírez I, Hidalgo-Ruzzante N, Callejas-Rubio JL, Ortego-Centeno N, et al. The role of antiphospholipid autoantibodies in the cognitive deficits of patients with systemic lupus erythematosus. Lupus. 2015;24(8):875–9. https://doi.org/10.1177/0961203315572717.CrossRefPubMed

76.

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- β2-glycoprotein-I antibody positivity offer additional predictive information? Lupus. 2010;19(5):613–9. https://doi.org/10.1177/0961203309355300.CrossRefPubMed

77.

Gómez-Puerta JA, Cervera R, Calvo LM, Gómez-Ansón B, Espinosa G, Claver G, et al. Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics of 30 patients. Rheumatology. 2005;44(1):95–9. https://doi.org/10.1093/rheumatology/keh408.CrossRefPubMed

78.

Sanna G, Bertolaccini ML, Cuadrado MJ, Khamashta MA, Hughes GRV. Central nervous system involvement in the antiphospholipid (Hughes) syndrome. Rheumatology. 2003;42(2):200–13. https://doi.org/10.1093/rheumatology/keg080.CrossRefPubMed

79.

Erkan D, Vega J, Ramón G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum. 2013;65(2):464–71. https://doi.org/10.1002/art.37759.CrossRefPubMed

80.

Maes M, Meltzer H, Jacobs J, Suy E, Calabrese J, Minner B, et al. Autoimmunity in depression: increased antiphospholipid autoantibodies. Acta Psychiatr Scand. 1993;87(3):160–6. https://doi.org/10.1111/j.1600-0447.1993.tb03349.x.CrossRefPubMed

81.

Raza H, Epstein SA, Pao M, Rosenstein DL. Mania: psychiatric manifestations of the antiphospholipid syndrome. Psychosomatics. 2008;49(5):438–41. https://doi.org/10.1176/appi.psy.49.5.438.Mania.CrossRefPubMedPubMedCentral

82.

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(1-2):151–6. https://doi.org/10.1016/j.jneuroim.2007.08.002.CrossRefPubMed

83.

Graf J. Central nervous system manifestations of antiphospholipid syndrome. Rheum Dis Clin N Am. 2017;43(4):547–60. https://doi.org/10.1016/j.rdc.2017.06.004.CrossRef

84.

Gris JC, Cyprien F, Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, Mercier E, et al. Antiphospholipid antibodies are associated with positive screening for common mental disorders in women with previous pregnancy loss. The NOHA-PSY observational study. World J Biol Psychiatry. 2019;20(1):51–63. https://doi.org/10.1080/15622975.2017.1333146.CrossRefPubMed

85.

Briley DP, Coull BM, Goodnight SH. Neurological disease associated with antiphospholipid antibodies. Ann Neurol. 1989;25(3):221–7. https://doi.org/10.1002/ana.410250303.CrossRefPubMed

86.

Cavestro C, Micca G, Molinari F, et al. Migraineurs show a high prevalence of antiphospholipid antibodies. J Thromb Haemost. 2011;9(7):1350–4. https://doi.org/10.1111/j.1538-7836.2011.04348.x.CrossRefPubMed

87.

Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339(7728):1015. https://doi.org/10.1136/bmj.b3914.CrossRef

88.

Islam MA, Alam F, Wong KK. Comorbid association of antiphospholipid antibodies and migraine: a systematic review and meta-analysis. Autoimmun Rev. 2017;16(5):512–22. https://doi.org/10.1016/j.autrev.2017.03.005.CrossRefPubMed

89.

Silvestrini M, Cupini LM, Matteis M, De Simone R, Bernardi G. Migraine in patients with stroke and antiphospholipid antibodies. Headache J Head Face Pain. 1993;33(8):421–6. https://doi.org/10.1111/j.1526-4610.1993.hed3308421.x.CrossRef

90.

Pezzini A, Grassi M, Lodigiani C, Patella R, Gandolfo C, Zini A, 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;129(16):1668–76. https://doi.org/10.1161/CIRCULATIONAHA.113.005663.CrossRefPubMed

91.

• Cavestro C, Degan D, Micca G, et al. Thrombophilic alterations, migraine, and vascular disease: results from a case-control study. Neurol Sci. 2021. https://doi.org/10.1007/s10072-020-05006-zA recent case-control study on the association between migraine, thrombophilic conditions, and vascular events.

92.

Mawet J, Kurth T, Ayata C. Migraine and stroke: in search of shared mechanisms. Cephalalgia. 2015;35(2):165–81. https://doi.org/10.1177/0333102414550106.CrossRefPubMed

93.

• Schofield JR, Hughes HN, Birlea M, Hassell KL. A trial of antithrombotic therapy in patients with refractory migraine and antiphospholipid antibodies: a retrospective study of 75 patients. Lupus. 2021. https://doi.org/10.1177/0961203320983913A retrospective study of 75 patients with refractory migraine and aPL who were given a 2–4-week trial of antiplatelets or anticoagulation showed a high rate of symptomatic response to antithrombotic therapy and a low bleeding risk on long-term follow-up.

94.

•• D’Angelo C, Franch O, Fernández-Paredes L, et al. Antiphospholipid antibodies overlapping in isolated neurological syndrome and multiple sclerosis: neurobiological insights and diagnostic challenges. Front Cell Neurosci. 2019;13. https://doi.org/10.3389/fncel.2019.00107An insightfully written review on the pathophysiological mechanisms of neuroimmune disorders associated with APS, with a particular focus on multiple sclerosis.

95.

Ijdo JW, Conti-Kelly AM, Greco P, et al. Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS? Lupus. 1999;8:109–15 http://www.stockton-press.co.uk/lup.CrossRef

96.

Cuadrado MJ, Khamashta MA, Ballesteros A, Godfrey T, Simon MJ, Hughes G. Can Neurologic manifestations of Hughes (antiphospholipid) syndrome be distinguished from multiple sclerosis. Medicine (Baltimore). 2000;79:57–68.CrossRef

97.

Uthman I, Noureldine MHA, Berjawi A, Skaf M, Haydar AA, Merashli M, et al. Hughes syndrome and multiple sclerosis. Lupus. 2015;24(2):115–21. https://doi.org/10.1177/0961203314555539.CrossRefPubMed

98.

Renaud M, Aupy J, Uring-Lambert B, Chanson JB, Collongues N, Blanc F, et al. Isolated anti-β2-glycoprotein I antibodies in neurology: a frontier syndrome between multiple sclerosis and antiphospholipid syndrome? Eur J Neurol. 2014;21(6):901–6. https://doi.org/10.1111/ene.12408.CrossRefPubMed

99.

Bidot CJ, Horstman LL, Jy W, Jimenez JJ, Bidot C Jr, Ahn YS, et al. Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study. BMC Neurol. 2007;7. https://doi.org/10.1186/1471-2377-7-36.

100.

Garg N, Zivadinov R, Ramanathan M, Vasiliu I, Locke J, Watts K, et al. Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients. J Neuroimmunol. 2007;187(1-2):159–65. https://doi.org/10.1016/j.jneuroim.2007.04.008.CrossRefPubMed

101.

Filippidou N, Krashias G, Pericleous C, Rahman A, Ioannou Y, Giles I, et al. The association between IgG and IgM antibodies against cardiolipin, β2-glycoprotein I and domain I of β2-glycoprotein I with disease profile in patients with multiple sclerosis. Mol Immunol. 2016;75:161–7. https://doi.org/10.1016/j.molimm.2016.05.022.CrossRefPubMed

102.

Collard RC, Koehler RP, Mattson DH. Frequency and significance of antinuclear antibodies in multiple sclerosis.; 1997.

103.

Tourbah A, Clapin A, Gout O, et al. Systemic autoimmune features and multiple sclerosis a 5-year follow-up study. http://archneur.jamanetwork.com/.

104.

Filippidou N, Krashias G, Christodoulou C, Pantzaris M, Lambrianides A. Mechanisms of activation induced by antiphospholipid antibodies in multiple sclerosis: Potential biomarkers of disease? J Immunol Methods. 2019;474:112663. https://doi.org/10.1016/j.jim.2019.112663.CrossRefPubMed

105.

Stosic M, Ambrus J, Garg N, Weinstock-Guttman B, Ramanathan M, Kalman B, et al. MRI characteristics of patients with antiphospholipid syndrome and multiple sclerosis. J Neurol. 2010;257(1):63–71. https://doi.org/10.1007/s00415-009-5264-6.CrossRefPubMed

106.

Rovaris M, Viti B, Ciboddo G, Gerevini S, Capra R, Iannucci G, et al. Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry. 2000;68:170–7.CrossRef

107.

Ferreira S, D’Cruz DP, Hughes GRV. Multiple sclerosis, neuropsychiatric lupus and antiphospholipid syndrome: Where do we stand? Rheumatology. 2005;44(4):434–42. https://doi.org/10.1093/rheumatology/keh532.CrossRefPubMed

108.

Sastre-Garriga J, Reverter J c, 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.CrossRef

109.

Kavaliunas A, Manouchehrinia A, Stawiarz L, Ramanujam R, Agholme J, Hedström AK, et al. Importance of early treatment initiation in the clinical course of multiple sclerosis. Mult Scler. 2017;23(9):1233–40. https://doi.org/10.1177/1352458516675039.CrossRefPubMed

110.

Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Prim. 2020;6(1). https://doi.org/10.1038/s41572-020-0214-9.

111.

Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177–89.CrossRef

112.

Iyer A, Elsone L, Appleton R, Jacob A. A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica. Autoimmunity. 2014;47(3):154–61. https://doi.org/10.3109/08916934.2014.883501.CrossRefPubMed

113.

Wingerchuk DM, Weinshenker BG. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Mult Scler J. 2012;18(1):5–10. https://doi.org/10.1177/1352458511431077.CrossRef

114.

Lee EJ, Lim YM, Kim SY, Lee JK, Kim H, Jin JY, et al. The clinical and prognostic value of antinuclear antibodies in NMO-IgG seropositive neuromyelitis optica spectrum disorder. J Neuroimmunol. 2019;328:1–4. https://doi.org/10.1016/j.jneuroim.2018.11.012.CrossRefPubMed

115.

Long Y, He Y, Zheng Y, Chen M, Zhang B, Gao C. Serum anticardiolipin antibodies in patients with neuromyelitis optica spectrum disorder. J Neurol. 2013;260(12):3150–7. https://doi.org/10.1007/s00415-013-7128-3.CrossRefPubMed

116.

Guerra H, Pittock SJ, Moder KG, Froehling DA, Flanagan EP. Neuromyelitis optica spectrum initially diagnosed as antiphospholipid antibody myelitis. J Neurol Sci. 2016;361:204–5. https://doi.org/10.1016/j.jns.2016.01.003.CrossRefPubMed

117.

Margoni M, Carotenuto A. Very late-onset recurrent myelitis in a patient diagnosed with antiphospholipid syndrome: a puzzle of autoimmunity. J Neuroimmunol. 2019;337:577051. https://doi.org/10.1016/j.jneuroim.2019.577051.CrossRefPubMed

118.

Sherer Y, Hassin S, Shoenfeld Y, et al. Transverse myelitis in patients with antiphospholipid antibodies-the importance of early diagnosis and treatment.

119.

Rodrigues CEM, de Carvalho JF. Clinical, radiologic, and therapeutic analysis of 14 patients with transverse myelitis associated with antiphospholipid syndrome: report of 4 cases and review of the literature. Semin Arthritis Rheum. 2011;40(4):349–57. https://doi.org/10.1016/j.semarthrit.2010.05.004.CrossRefPubMed

120.

Peluso S, Antenora A, De Rosa A, et al. Antiphospholipid-related chorea. Front Neurol. 2012:1–8. https://doi.org/10.3389/fneur.2012.00150.

121.

Cervera R, Asherson RA, Font J, Tikly M, Pallarés L, Chamorro A, et al. Chorea in the antiphospholipid syndrome: clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature. Med. 1997;76(3):203–12.CrossRef

122.

Safarpour D, Buckingham S, Jabbari B. Chorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome. Tremor and Other Hyperkinetic Movements. 2015;5(0):294. https://doi.org/10.5334/tohm.250.CrossRefPubMedPubMedCentral

123.

Zhang L, Pereira AC. Oromandibular chorea in antiphospholipid syndrome. Pract Neurol. 2018;18(2):132–3. https://doi.org/10.1136/practneurol-2017-001824.CrossRefPubMed

124.

Huang YC, Lyu RK, Chen ST, Chu YC, Wu YR. Parkinsonism in a patient with antiphospholipid syndrome - case report and literature review. J Neurol Sci. 2008;267(1-2):166–9. https://doi.org/10.1016/j.jns.2007.10.003.CrossRefPubMed

125.

Carecchio M, Comi C, Varrasi C, Stecco A, Sainaghi PP, Bhatia K, et al. Complex movement disorders in primary antiphospholipid syndrome: a case report. J Neurol Sci. 2009;281(1-2):101–3. https://doi.org/10.1016/j.jns.2009.03.011.CrossRefPubMed

126.

Chen WH, Chen CH, Chui C, Lui CC, Chen CJ, Yin HL. Antiphospholipid antibodies and cerebellar ataxia: a clinical analysis and literature review. Neuroimmunomodulation. 2014;21(6):283–90. https://doi.org/10.1159/000354614.CrossRefPubMed

127.

Ishikawa N, Kobayashi M. Recurrent acute cerebellar ataxia associated with anti-cardiolipin antibodies. Brain and Development. 2010;32(7):588–91. https://doi.org/10.1016/j.braindev.2009.07.009.CrossRefPubMed

128.

Jeruc J. Multiple mononeuropathy due to vasculitis associated with anticardiolipin antibodies: a case report. Vol 44.; 2006.

129.

Nakos G, Tziakou E, Maneta-Peyret L, Nassis C, Lekka ME. Anti-phospholipid antibodies in serum from patients with Guillain-Barré syndrome. Intensive Care Med. 2005;31(10):1401–8. https://doi.org/10.1007/s00134-005-2736-8.CrossRefPubMed

130.

Gilburd B, Stein M, Tomer Y, Tanne D, Abramski O, Chapman Y, et al. Autoantibodies to phospholipids and brain extract in patients with the guillain-barre syndrome: cross-reactive or pathogenic? Autoimmunity. 1993;16:23–44.CrossRef

131.

• Santos MSF, De Carvalho JF, Brotto M, Bonfa E, Rocha FAC. Peripheral neuropathy in patients with primary antiphospholipid (Hughes) syndrome. Lupus. 2010;19(5):583–90. https://doi.org/10.1177/0961203309354541A cohort of 26 consecutive patients with primary APS with clinical and electrophysiologic characterization of peripheral nerve involvement.CrossRefPubMed

132.

Schofield JR. Autonomic neuropathy—in its many guises—as the initial manifestation of the antiphospholipid syndrome. Immunol Res. 2017;65(2):532–42. https://doi.org/10.1007/s12026-016-8889-4.CrossRefPubMed

133.

Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019;78(10):1296–304. https://doi.org/10.1136/annrheumdis-2019-215213.CrossRefPubMed

134.

Arnaud L, Mathian A, Ruffatti A, Erkan D, Tektonidou M, Cervera R, et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis. Autoimmun Rev. 2014;13(3):281–91. https://doi.org/10.1016/j.autrev.2013.10.014.CrossRefPubMed

135.

•• Cohen H, Hunt BJ, Efthymiou M, et al. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol. 2016;3(9):e426–36. https://doi.org/10.1016/S2352-3026(16)30079-5A randomized, controlled, open-label, non-inferiority trial that failed to show non-inferiority of rivaroxaban compared to warfarin.CrossRefPubMedPubMedCentral

136.

• Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132(13):1365–71. https://doi.org/10.1182/blood-2018-04-848333A trial that associated the use of rivaroxaban in high-risk patients with antiphospholipid syndrome with an increased rate of events compared with warfarin, thus showing no benefit and excess risk.CrossRefPubMed

137.

Bala MM, Celinska-Lowenhoff M, Szot W, et al. Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome. Cochrane Database Syst Rev. 2020;2020(10). https://doi.org/10.1002/14651858.CD012169.pub3.

138.

Pengo V, Denas G, Zoppellaro G, Jose SP, Hoxha A, Ruffatti A, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132(13):1365–71. https://doi.org/10.1182/blood-2018-04-848333.CrossRefPubMed

139.

• Woller SC, Stevens SM, Kaplan DA, et al. Apixaban for the secondary prevention of thrombosis among patients with antiphospholipid syndrome: study rationale and design (ASTRO-APS). Clin Appl Thromb Off J Int Acad Clin Appl Thromb. 2016;22(3):239–47. https://doi.org/10.1177/1076029615615960Ongoing trial on apixaban for secondary prevention of thrombosis in APS.CrossRef

140.

Woller S, Stevens S, Kaplan D, Rondina M. Protocol modification of apixaban for the secondary prevention of thrombosis among patients with antiphospholipid syndrome study. Clin Appl Thromb. 2017;24:107602961772921. https://doi.org/10.1177/1076029617729214.CrossRef

141.

Fazili M, Stevens SM, Woller SC. Direct oral anticoagulants in antiphospholipid syndrome with venous thromboembolism: Impact of the European Medicines Agency guidance. Res Pract Thromb Haemost. 2020;4(1):9–12. https://doi.org/10.1002/rth2.12287.CrossRefPubMed

142.

Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017;76(3):476–85. https://doi.org/10.1136/annrheumdis-2016-209770.CrossRefPubMed

143.

Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. 2020 American College of Rheumatology Guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Care Res. 2020;72(4):461–88. https://doi.org/10.1002/acr.24130.CrossRef

144.

Legault K, Schunemann H, Hillis C, Yeung C, Akl EA, Carrier M, et al. McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome. J Thromb Haemost. June 2018;16:1656–64. https://doi.org/10.1111/jth.14192.CrossRef

145.

Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089–98. https://doi.org/10.1007/s00134-020-06062-x.CrossRef

146.

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan. China JAMA Neurol. 2020;77(6):683–90. https://doi.org/10.1001/jamaneurol.2020.1127.CrossRefPubMed

147.

Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020;91(8):889–91. https://doi.org/10.1136/jnnp-2020-323586.CrossRefPubMed

148.

Baldini T, Asioli G, Romoli M, et al. Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: a systematic review and meta-analysis. Eur J Neurol. 2021. https://doi.org/10.1111/ene.14727.

149.

Harzallah I, Debliquis A, Drénou B. Lupus anticoagulant is frequent in patients with Covid-19. J Thromb Haemost. 2020;18(8):2064–5. https://doi.org/10.1111/jth.14867.CrossRefPubMed

150.

• Siguret V, Voicu S, Neuwirth M, et al. Are antiphospholipid antibodies associated with thrombotic complications in critically ill COVID-19 patients? Thromb Res. 2020;195:74–6. https://doi.org/10.1016/j.thromres.2020.07.016A single-center observational study establishing a very high prevalence of LA in critically ill COVID-19 patients not associated with thrombotic complications.CrossRefPubMedPubMedCentral

151.

Abdel-Wahab N, Talathi S, Lopez-Olivo MA, Suarez-Almazor ME. Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis. Lupus. 2018;27(4):572–83. https://doi.org/10.1177/0961203317731532.CrossRefPubMed

152.

Schouwers SME, Delanghe JR, Devreese KMJ. Lupus Anticoagulant (LAC) testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results? Thromb Res. 2010;125(1):102–4. https://doi.org/10.1016/j.thromres.2009.09.001.CrossRefPubMed

153.

Olsen NJ, Schleich MA, Karp DR. Multifaceted effects of hydroxychloroquine in human disease. Semin Arthritis Rheum. 2013;43(2):264–72. https://doi.org/10.1016/j.semarthrit.2013.01.001.CrossRefPubMed

154.

Borghi MO, Beltagy A, Garrafa E, Curreli D, Cecchini G, Bodio C, et al. Anti-phospholipid antibodies in COVID-19 are different from those detectable in the anti-phospholipid syndrome. Front Immunol. 2020;11:584241. https://doi.org/10.3389/fimmu.2020.584241.CrossRefPubMedPubMedCentral

155.

Gatto M, Perricone C, Tonello M, Bistoni O, Cattelan AM, Bursi R, et al. Frequency and clinical correlates of antiphospholipid antibodies arising in patients with SARS-CoV-2 infection: findings from a multicentre study on 122 cases. Clin Exp Rheumatol. 2020;38(4):754–9.PubMed

At a glance: The STEP trials

Springer Medicine

Neurologic Manifestations of the Antiphospholipid Syndrome — an Update

Abstract

Purpose of Review

Recent Findings

Summary

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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