Skip to main content

Advertisement

Log in

Neurologic manifestations of the antiphospholipid syndrome

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Neurologic disorders are among the most prominent clinical manifestations associated with the antiphospholipid syndrome. Such neurologic disorders are predominantly related to focal central nervous system thrombo-occlusive events. This review summarizes the latest data regarding the clinical aspects of stroke and other neurologic manifestations associated with antiphospholipid antibodies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Briley DP, Coull BM, Goodnight SHJr: Neurological disease associated with antiphospholipid antibodies. Ann Neurol 1989, 25:221–227.

    Article  PubMed  CAS  Google Scholar 

  4. Asherson, RA: The catastrophic antiphospholipid syndrome, 1998: a review of the clinical features, possible pathogenesis and treatment. Lupus 1998, 7:S55-S62.

    PubMed  Google Scholar 

  5. Caronti B, Calderaro C, Alessandri C, et al.: Serum anti-beta2-glycoprotein I antibodies from patients with antiphospholipid antibody syndrome bind central nervous system cells. J Autoimmun 1998, 11:425–429.

    Article  PubMed  CAS  Google Scholar 

  6. Kent MN, Alvarez FJ, Ng AK, et al.: Ultrastructural localization of monoclonal antiphospholipid antibody binding to rat brain. Exp Neurol 2000, 163:173–179.

    Article  PubMed  CAS  Google Scholar 

  7. Tanne D, Levine SR, Kittner SJ: Epidemiology of antiphospholipid antibodies and vascular disease. In Clinical Approach to Antiphospholipid Antibodies. Edited by Levine SR and Brey R. Woburn, MA: Butterworth-Heinemann; 2000:1–18.

    Google Scholar 

  8. Rosove MH, Brewer PM: Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992, 117:303–308.

    PubMed  CAS  Google Scholar 

  9. Finazzi G, Brancaccio V, Moia M, et al.: Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a 4-year prospective study from the Italian registry. Am J Med 1996, 100:530–536. In this multicenter Italian prospective study, 360 patients with antiphospholipid antibodies were observed for 4 years. Previous thrombosis and aCL > 40 GPL were found to be independent predictors of future thrombosis.

    Article  PubMed  CAS  Google Scholar 

  10. Levine SR, Salowich-Palm L, Sawaya KL, et al.: IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death: a prospective cohort study. Stroke 1997, 28:1660–1665.

    PubMed  CAS  Google Scholar 

  11. Ginsburg KS, Liang MH, Newcomer L, et al.: Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992, 117:997–1002.

    PubMed  CAS  Google Scholar 

  12. Tuhrim S, Rand JH, Wu XX, et al.: Elevated anticardiolipin antibody titer is a stroke risk factor in a multiethnic population independent of isotype or degree of positivity. Stroke 1999, 30:1561–1565. This is the largest case-control study to date, demonstrating that aCL constitutes an independent stroke risk factor, conferring a fourfold increased risk of ischemic stroke. IgG and IgM aCL were shown to be associated with increased stroke risk.

    PubMed  CAS  Google Scholar 

  13. Tuhrim S, Rand JH, Wu X, et al.: Antiphosphatidyl serine antibodies are independently associated with ischemic stroke. Neurology 1999, 53:1523–1527.

    PubMed  CAS  Google Scholar 

  14. Toschi V, Motta A, Castelli C, et al.: High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause. Stroke 1998, 29:1759–1764.

    PubMed  CAS  Google Scholar 

  15. Fiallo P, Tomasina C, Clapasson A, et al.: Antibodies to beta(2)-glycoprotein I in ischemic stroke. Cerebrovasc Dis 2000, 10:293–297.

    Article  PubMed  CAS  Google Scholar 

  16. Tanne D, Triplett DA, Levine SR: Antiphospholipid-protein antibodies and ischemic stroke: not just cardiolipin any more. Stroke 1998, 29:1755–1758.

    PubMed  CAS  Google Scholar 

  17. deVeber G, Monagle P, Chan A, et al.: Prothrombotic disorders in infants and children with cerebral thromboembolism. Arch Neurol 1998, 55:1539–1543.

    Article  PubMed  CAS  Google Scholar 

  18. Kenet G, Sadetzki S, Murad H, et al.: Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children. Stroke 2000, 31:1283–1288.

    PubMed  CAS  Google Scholar 

  19. Chakravarty KK, Byron MA, Webley M, et al.: Antibodies to cardiolipin in stroke: association with mortality and functional recovery in patients without systemic lupus erythematosus. Q J Med 1991, 79:397–405.

    PubMed  CAS  Google Scholar 

  20. Montalban J, Codina A, Ordi J, et al.: Antiphospholipid antibodies in cerebral ischemia. Stroke 1991, 22:750–753.

    PubMed  CAS  Google Scholar 

  21. Camerlingo M, Casto L, Censori B, et al.: Anticardiolipin antibodies in acute non-hemorrhagic stroke seen within six hours after onset. Acta Neurol Scand 1995, 92:69–71.

    Article  PubMed  CAS  Google Scholar 

  22. The Antiphospholipid Antibodies in Stroke Study (APASS) Group: Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. Neurology 1993, 43:2069–2073. In this multicenter, case-control study, positive aCL levels were present in 9.7% of stroke patients and 4.3% of controls. The odds ratio for stroke status, given aCL positivity, was 2.31 after adjusting for conventional vascular risk factors, suggesting that aCL appears to be an independent risk factor for stroke in these patients.

    Google Scholar 

  23. Zielinska J, Ryglewicz D, Wierzchowska E, et al.: Anticardiolipin antibodies are an independent risk factor for ischemic stroke. Neurol Res 1999, 21:653–657.

    PubMed  CAS  Google Scholar 

  24. Muir KW, Squire IB, Alwan W, et al.: Anticardiolipin antibodies in an unselected stroke population. Lancet 1994, 344:452–456.

    Article  PubMed  CAS  Google Scholar 

  25. Metz LM, Edworthy S, Mydlarski R, et al.: The frequency of phospholipid antibodies in an unselected stroke population. Can J Neurol Sci 1998, 25:64–69.

    PubMed  CAS  Google Scholar 

  26. Ahmed E, Stegmayr B, Trifunovic J, et al.: Anticardiolipin antibodies are not an independent risk factor for stroke: an incident case-referent study nested within the MONICA and Vasterbotten cohort project. Stroke 2000, 31:1289–1293.

    PubMed  CAS  Google Scholar 

  27. Tanne D, D’Olhaberriague L, Trivedi AM, et al.: Anticardiolipin antibodies and mortality in patients with ischemic stroke: a prospective follow-up study. 2001, Submitted for publication.

  28. The Antiphospholipid Antibodies and Stroke Study Group: Anticardiolipin antibodies and the risk of recurrent thrombo-occlusive events and death. Neurology 1997, 48:91–94.

    Google Scholar 

  29. Levine SR, Brey RL, Sawaya KL, et al.: Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome. Ann Neurol 1995, 38:119–124.

    Article  PubMed  CAS  Google Scholar 

  30. WARSS, APASS, PICSS, and HAS Study Groups: The feasibility of a collaborative double-blind study using an anticoagulant: the Warfarin-Aspirin Recurrent Stroke Study (WARSS), the Antiphospholipid Antibodies and Stroke Study (APASS), the Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), and the Hemostatic System Activation Study (HAS). Cerebrovasc Dis 1997, 7:100–112.

    Google Scholar 

  31. Levine SR, Deegan MJ, Futrell N, et al.: Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases. Neurology 1990, 40:1181–1189.

    PubMed  CAS  Google Scholar 

  32. Castanon C, Amigo MC, Banales JL, et al.: Ocular vasoocclusive disease in primary antiphospholipid syndrome. Ophthalmology 1995, 102:256–262.

    PubMed  CAS  Google Scholar 

  33. Demirci FY, Kucukkaya R, Akarcay K, et al.: Ocular involvement in primary antiphospholipid syndrome. Int Ophthalmol 1998, 22:323–329.

    Article  PubMed  CAS  Google Scholar 

  34. Verro P, Levine SR, Tietjen GE: Cerebrovascular ischemic events with high positive anticardiolipin antibodies. Stroke 1998, 29:2245–2253.

    PubMed  CAS  Google Scholar 

  35. Hojnik M, George J, Ziporen L, et al.: Heart valve involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation 1996, 93:1579–1587.

    PubMed  CAS  Google Scholar 

  36. Espinola-Zavaleta N, Vargas-Barron J, Colmenares-Galvis T, et al.: Echocardiographic evaluation of patients with primary antiphospholipid syndrome. Am Heart J 1999, 137:973–978.

    Article  PubMed  CAS  Google Scholar 

  37. Chaturvedi S: Coagulation abnormalities in adults with cryptogenic stroke and patent foramen ovale. J Neurol Sci 1998, 160:158–160.

    Article  PubMed  CAS  Google Scholar 

  38. George J, Harats D, Gilburd B, et al.: Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression. Circulation 1999, 99:2227–2230.

    PubMed  CAS  Google Scholar 

  39. Harats D, George J, Levy Y, et al.: Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus. QJM 1999, 92:57–59.

    Article  PubMed  CAS  Google Scholar 

  40. Tanne D, D’Olhaberriague L, Schultz LR, et al.: Anticardiolipin antibodies and their associations with cerebrovascular risk factors. Neurology 1999, 52:1368–1373. A study demonstrating that the presence of multiple cerebrovascular risk factors is associated with substantially higher rates of positive IgG isotype aCL and with higher immunoreactivity. These findings caution against overdiagnosis of the antiphospholipid syndrome, and consequent changes in management among patients with multiple cerebrovascular risk factors.

    PubMed  CAS  Google Scholar 

  41. Deschiens MA, Conard J, Horellou MH, et al.: Coagulation studies, factor V Leiden, and anticardiolipin antibodies in 40 cases of cerebral venous thrombosis. Stroke 1996, 27:1724–1730.

    PubMed  CAS  Google Scholar 

  42. Carhuapoma JR, Mitsias P, Levine SR: Cerebral venous thrombosis and anticardiolipin antibodies. Stroke 1997, 28:2363–2369.

    PubMed  CAS  Google Scholar 

  43. Christopher R, Nagaraja D, Dixit NS, et al.: Anticardiolipin antibodies: a study in cerebral venous thrombosis. Acta Neurol Scand 1999, 99:121–124.

    PubMed  CAS  Google Scholar 

  44. Mokri B, Jack CRJ, Petty GW: Pseudotumor syndrome associated with cerebral venous sinus occlusion and antiphospholipid antibodies. Stroke 1993, 24:469–472.

    PubMed  CAS  Google Scholar 

  45. Leker RR, Steiner I: Anticardiolipin antibodies are frequently present in patients with idiopathic intracranial hypertension. Arch Neurol 1998, 55:817–820.

    Article  PubMed  CAS  Google Scholar 

  46. Erkinjuntti T, Bowler JV, DeCarli CS, et al.: Imaging of static brain lesions in vascular dementia: implications for clinical trials. Alzheimer Dis Assoc Disord 1999, 13:S81-S90.

    Article  PubMed  Google Scholar 

  47. Mosek A, Yust I, Treves TA, et al.: Dementia and antiphospholipid antibodies. Dement Geriatr Cogn Disord 2000, 11:36–38.

    Article  PubMed  CAS  Google Scholar 

  48. Van Horn G, Arnett FC, Dimachkie MM: Reversible dementia and chorea in a young woman with the lupus anticoagulant. Neurology 1996, 46:1599–1603.

    PubMed  Google Scholar 

  49. Frances C, Papo T, Wechsler B, et al.: Sneddon syndrome with or without antiphospholipid antibodies: a comparative study in 46 patients. Medicine 1999, 78:209–219.

    Article  PubMed  CAS  Google Scholar 

  50. Fetoni V, Grisoli M, Salmaggi A, et al.: Clinical and neuroradiological aspects of Sneddon’s syndrome and primary antiphospholipid antibody syndrome: a follow-up study. Neurolog Sci 2000, 21:157–164.

    Article  CAS  Google Scholar 

  51. Schmidt R, Auer-Grumbach P, Fazekas F, et al.: Anticardiolipin antibodies in normal subjects: neuropsychological correlates and MRI findings. Stroke 1995, 26:749–754.

    PubMed  CAS  Google Scholar 

  52. Jacobson, MW, Rapport, LJ, Keenan, PA, et al.: Neuropsychological deficits associated with antiphospholipid antibodies. J Clin Exp Neuropsychol 1999, 21:251–264.

    Article  PubMed  CAS  Google Scholar 

  53. Kao CH, Lan JL, Hsieh JF, et al.: Evaluation of regional cerebral blood flow with 99mTc-HMPAO in primary antiphospholipid antibody syndrome. J Nucl Med 1999, 40:1446–1450.

    PubMed  CAS  Google Scholar 

  54. Lavalle C, Pizarro S, Drenkard C, et al.: Transverse myelitis: a manifestation of systemic lupus erythematosus strongly associated with antiphospholipid antibodies. J Rheumatol 1990, 17:34–37.

    PubMed  CAS  Google Scholar 

  55. Kovacs B, Lafferty TL, Brent LH, et al.: Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature. Ann Rheum Dis 2000, 59:120–124.

    Article  PubMed  CAS  Google Scholar 

  56. Campi A, Filippi M, Comi G, et al.: Recurrent acute transverse myelopathy associated with anticardiolipin antibodies. AJNR Am J Neuroradiol 1998, 19:781–786.

    PubMed  CAS  Google Scholar 

  57. Aziz A, Conway MD, Robertson HJ, et al.: Acute optic neuropathy and transverse myelopathy in patients with antiphospholipid antibody syndrome: favorable outcome after treatment with anticoagulants and glucocorticoids. Lupus 2000, 9:307–310.

    Article  PubMed  CAS  Google Scholar 

  58. Masala C, Morino S, Zangari P, et al.: Chorea in primary antiphospholipid syndrome. Clin Neurol Neurosurg 1996, 98:247–248.

    Article  PubMed  CAS  Google Scholar 

  59. Kiechl-Kohlendorfer U, Ellemunter H, Kiechl S: Chorea as the presenting clinical feature of primary antiphospholipid syndrome in childhood. Neuropediatrics 1999, 30:96–98.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  61. Verrotti A, Cieri F, Pelliccia P, et al.: Lack of association between antiphospholipid antibodies and migraine in children. Int J Clin Lab Res 2000, 30:109–111.

    Article  PubMed  CAS  Google Scholar 

  62. 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, 50:1433–1440. This is a large case-control study in which aCL positivity was assessed for 645 patients with transient focal neurologic events, 518 patients with transient focal neurologic events with migraine with aura, 497 patients with migraine without aura, and 366 controls. aCL positivity did not differ significantly between the groups, demonstrating that aCL is not associated with migraine.

    PubMed  CAS  Google Scholar 

  63. Silvestrini M, Matteis M, Troisi E, et al.: Migrainous stroke and the antiphospholipid antibodies. Eur Neurol 1994, 34:316–319.

    PubMed  CAS  Google Scholar 

  64. Schwartz M, Rochas M, Weller B, et al.: High association of anticardiolipin antibodies with psychosis. J Clin Psychiatry 1998, 59:20–23.

    PubMed  CAS  Google Scholar 

  65. Herranz MT, Rivier G, Khamashta MA, et al.: Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus. Arthritis Rheum 1994, 37:568–571.

    Article  PubMed  CAS  Google Scholar 

  66. Angelini L, Granata T, Zibordi F, et al.: Partial seizures associated with antiphospholipid antibodies in childhood. Neuropediatrics 1998, 29:249–253.

    Article  PubMed  CAS  Google Scholar 

  67. Inzelberg R, Korczyn AD: Lupus anticoagulant and late onset seizures. Acta Neurol Scand 1989, 79:114–118.

    Article  PubMed  CAS  Google Scholar 

  68. Karussis D, Leker RR, Ashkenazi A, et al.: A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? Ann Neurol 1998, 44:629–634. The authors isolated a subgroup of 20 patients from a cohort of 100 patients with MS who are consistently positive for aCL and characterized them clinically and by ancillary laboratory test results. These patients showed a slower progression and had some atypical features for MS, such as persistent headaches and absence of oligoclonal bands in the cerebrospinal fluid, suggesting involvement of other pathogenetic mechanisms.

    Article  PubMed  CAS  Google Scholar 

  69. Cuadrado MJ, Khamashta MA, Ballesteros A, et al.: Can neurologic manifestations of Hughes (antiphospholipid) syndrome be distinguished from multiple sclerosis? Analysis of 27 patients and review of the literature. Medicine 2000, 79:57–68.

    Article  PubMed  CAS  Google Scholar 

  70. Montalban J, Arboix A, Staub H, et al.: Transient global amnesia and antiphospholipid antibodies. Clin Exp Rheumatol 1989, 7:85–87.

    PubMed  CAS  Google Scholar 

  71. Sherer Y, Livneh A, Levy Y, et al.: Dermatomyositis and polymyositis associated with the antiphospholipid syndrome: a novel overlap syndrome. Lupus 2000, 9:42–46.

    Article  PubMed  CAS  Google Scholar 

  72. Gilburd B, Stein M, Tomer Y, et al.: Autoantibodies to phospholipids and brain extract in patients with the Guillain-Barré syndrome: cross-reactive or pathogenic? Autoimmunity 1993, 16:23–27.

    PubMed  CAS  Google Scholar 

  73. Marchiori PE, Dos Reis M, Quevedo ME, et al.: Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barré syndrome and systemic lupus erythematosus. Arq Neuropsiquiatr 1990, 48:465–468.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanne, D., Hassin-Baer, S. Neurologic manifestations of the antiphospholipid syndrome. Curr Rheumatol Rep 3, 286–292 (2001). https://doi.org/10.1007/s11926-001-0032-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-001-0032-3

Keywords

Navigation