Skip to main content

Neurological presentations of the antiphospholipid syndrome: three illustrative cases

Abstract

The antiphospholipid syndrome (APS) is defined by the association of high titers of antiphospholipid antibodies (aPLs) with thrombotic events and/or obstetrical problems. APS can be isolated or associated with immune system diseases. Several central nervous system (CNS) manifestations have been reported in APS, but are still not included in the international diagnostic criteria. We present here three cases of APS revealed by CNS manifestations. The first patient had a primary APS with stroke, dementia, epilepsy and the “so-called” Liebman–Sacks disease, a subacute thrombotic non-bacterial valvulopathy. The second one developed a primary APS with a Sneddon syndrome, while the third case is a neurolupus-associated APS with subacute encephalopathy, chorea, stroke, and epilepsy. The pathogenesis of the APS is related to both prothrombotic and immunologic effects of the aPLs. Long-term anticoagulation by low-weight heparin or warfarin is currently recommended in APS. We propose to search the presence of aPLs in any case of young adults’ stroke, unexplained dementia, and acquired chorea.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. Hughes G, Harris NN, Gharavi AE (1986) The anticardiolipin syndrome. J Rheumatol 13(3):486–489

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  3. Urbanus RT, Siegerink B, Roest M et al (2009) Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case–control study. Lancet Neurol 8(11):998–1005

    CAS  PubMed  Article  Google Scholar 

  4. Bodiguel E (1992) Antiphospholipid antibodies and the central nervous system. Rev Neurol 148(11):655–662

    CAS  PubMed  Google Scholar 

  5. Morrissette N, Gorman T (2010) Antiphospholipid syndrome and homozygous factor V Leiden mutation in a young patient with Libeman–sacks endocarditis and stroke. Am J Med 123(9):e3–e4

    Article  Google Scholar 

  6. Giannakopoulos B, Krilis SA (2013) The pathogenesis of the antiphospholipid syndrome. N Engl J Med 368(11):1033–1044

    CAS  PubMed  Article  Google Scholar 

  7. Cervera R, Bucciarelli S, Plasín MA et al (2009) Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the “CAPS Registry”. J Autoimmun 32(3–4):240–245

    CAS  PubMed  Article  Google Scholar 

  8. Asherson RA, Khamashta MA, Gil A et al (1989) Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome. Am J Med 86:391–399

    CAS  PubMed  Article  Google Scholar 

  9. Briley DP, Coull BM, Goodnight SH Jr (1989) Neurological disease associated with antiphospholipid syndrome. Ann Neurol 25:221–227

    CAS  PubMed  Article  Google Scholar 

  10. Krause I, Lev S, Fraser A et al (2005) Close association between valvar heart disease and central nervous system manifestations in the antiphospholipid syndrome. Ann Rheum Dis 64(10):1490–1493

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  11. Brey R (2005) Antiphospholipid syndrome in young adults with stroke. J Thromb Thrombolysis 20(2):105–112

    CAS  PubMed  Article  Google Scholar 

  12. Muscal E, Brey RL (2010) Antiphospholipid syndrome and the brain in pediatric and adult patients. Lupus 19(4):406–411

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  13. Ferro JM, Canhão P, Stam J et al (2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke 35:664–670

    PubMed  Article  Google Scholar 

  14. Cervera R, Piette JC, Font J et al (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum 46(4):1019–1027

    PubMed  Article  Google Scholar 

  15. Gomez-Puerta JA, Cervera R, Calvo LM et al (2005) Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics of 30 patients. Rheumatology 44:95–99

    CAS  PubMed  Article  Google Scholar 

  16. Marinho JL, Piovesan EJ, Pereira Leite Neto M et al (2007) Clinical, neurovascular and neuropathological features in Sneddon’s syndrome. Arq Neuropsiquiatr 65(2B):390–395

    PubMed  Article  Google Scholar 

  17. Montané de la Roque P, Michard JF, Pinganaud-Shrestha C et al (2006) Syndrome démentiel révélant un syndrome de Sneddon. Rev Med Interne 27:156–164

    Article  Google Scholar 

  18. Uthman IW, Khamashta MA (2006) Livedo racemosa: a striking dermatological sign for the antiphospholipid syndrome. J Rheumatol 33:12

    Google Scholar 

  19. Maamar M, Rahmani M, Aidi S et al (2007) Sneddon’s syndrome: 15 cases with cerebral angiography. Revue Neurologique 163(8–9):809–816

    CAS  PubMed  Article  Google Scholar 

  20. Dutra L, Braga-Neto P, Pedroso JL et al (2012) Sneddon’s syndrome: case report and review of its relationship with antiphospholipid syndrome. Einstein 10(2):230–232

    PubMed  Article  Google Scholar 

  21. El Benaye J, Hsaini Y, Zoobo T et al (2013) Le syndrome de Sneddon. Presse Med 42:138–144

    PubMed  Article  Google Scholar 

  22. Stockhammer G, Stephan R, Felber R et al (1993) Sneddon’s syndrome. Diagnostic by skin biopsy and RMI in 17 patients. Stroke 24:685–690

    CAS  PubMed  Article  Google Scholar 

  23. Francès C, Papo T, Wechsler B et al (1999) Sneddon syndrome with or without antiphospholipid antibodies. A comparative study in 46 patients. Medicine (Baltimore) 78(4):209–219

    Article  Google Scholar 

  24. Brey RL, Holliday SL, Saklad AR et al (2002) Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 58(8):1214–1220

    CAS  PubMed  Article  Google Scholar 

  25. Joseph FG, Lammie GA, Scolding NJ et al (2007) CNS lupus: a study of 41 patients. Neurology 69:644–654

    PubMed  Article  Google Scholar 

  26. Spinosa MJ, Bandeira M, Liberalesso PB et al (2007) Clinical, laboratory and neuroimage findings in juvenile systemic lupus erythematosus presenting involvement of the nervous system. Arq Neuropsiquiatr 65(2B):433–439

    PubMed  Article  Google Scholar 

  27. Asherson RA, Derksen RH, Harris EN et al (1987) Chorea in systemic lupus erythematosus and “lupus-like” disease: association with antiphospholipid antibodies. Semin Arthritis Rheum 16(4):253–259

    CAS  PubMed  Article  Google Scholar 

  28. Baizabal-Carvallo J, Alonso-Juarez M, Koslowski M (2011) Chorea in systemic lupus erythematosus. J Clin Rheumatol 17(2):69–72

    PubMed  Article  Google Scholar 

  29. Cervera R, Asherson RA, Font J et al (1997) Chorea in the antiphospholipid syndrome. Clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature. Medicine (Baltimore) 76(3):203–212

    CAS  Article  Google Scholar 

  30. de la Fuente-Fernández R (1997) Lupus anticoagulant and chorea. Neurology 49(2):639–640

    PubMed  Article  Google Scholar 

  31. Avcin T, Benseler SM, Tyrrell PN et al (2008) A follow-up study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus. Arthritis Rheum 59(2):206–213

    PubMed  Article  Google Scholar 

  32. Erkan D, Harrison MJ, Levy R et al (2007) Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum 56(7):2382–2391

    CAS  PubMed  Article  Google Scholar 

  33. Cervera R, Khamashta MA, Shoenfeld Y et al (2009) Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 68(9):1428–1432

    CAS  PubMed  Article  Google Scholar 

  34. Giannakopoulos B, Krilis SA (2013) The pathogenesis of the antiphospholipid syndrome. N Engl J Med 368(11):1033–1044

    CAS  PubMed  Article  Google Scholar 

  35. Lim W, Crowther MA, Eikelboom JW (2006) Management of antiphospholipid antibody syndrome: a systematic review. JAMA 295(9):1050–1057

    CAS  PubMed  Article  Google Scholar 

  36. Crowther MA, Ginsberg JS, Julian J et al (2003) A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. NEJM 349:1133–1138

    CAS  PubMed  Article  Google Scholar 

  37. Finazzi G, Marchioli R, Brancaccio V et al (2005) A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J Thromb Haemost 3:848–853

    CAS  PubMed  Article  Google Scholar 

  38. Saadoun D, Piette J-C, Wahl D et al (2012) Management of antiphospholipid syndrome. Rev Med Interne 33(4):217–222

    CAS  PubMed  Article  Google Scholar 

  39. Asherson RA, Cervera R, Piette JC et al (2001) Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 80:355–376

    CAS  Article  Google Scholar 

  40. Erkan D, Cervera R, Asherson RA (2003) Catastrophic antiphospholipid syndrome: where do we stand? Arthritis Rheum 48(12):3320–3327

    PubMed  Article  Google Scholar 

  41. Statkute L, Traynor A, Oyama Y et al (2005) Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation. Blood 106(8):2700–2709

    CAS  PubMed  Article  Google Scholar 

  42. Erkan D, Vega J, Ramón G et al (2013) A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum 65(2):464–471

    CAS  PubMed  Article  Google Scholar 

  43. Arachchillage DJ, Cohen H (2013) Use of new oral anticoagulants in antiphospholipid syndrome. Curr Rheumatol Rep 15(6):331

    PubMed  Article  Google Scholar 

  44. Comarmond C, Cacoub P (2013) Antiphospholipid syndrome: from pathogenesis to novel immunomodulatory therapies. Autoimmun Rev 12(7):752–757

    Google Scholar 

  45. Lopez-Pedrera C, Ruiz-Limon P, Aguirre MA et al (2012) Potential use of statins in the treatment of antiphospholipid syndrome. Curr Rheumatol Rep 14(1):87–94

    CAS  PubMed  Article  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Gille.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

De Maeseneire, C., Duray, M.C., Rutgers, M.P. et al. Neurological presentations of the antiphospholipid syndrome: three illustrative cases. Acta Neurol Belg 114, 117–123 (2014). https://doi.org/10.1007/s13760-013-0275-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-013-0275-6

Keywords

  • Antiphospholipid syndrome
  • Stroke
  • Dementia
  • Sneddon syndrome
  • Chorea