Abstract
Antiphospholipid syndrome is an important cause of neurologic morbidity. The clinical criteria for antiphospholipid syndrome include only cerebrovascular arterial and venous thrombosis, but many other neurologic manifestations have been associated with antiphospholipid antibodies (aPL). This review discusses the role of aPL in cerebrovascular manifestations and in some of the other neurologic manifestations commonly associated with these antibodies, as well as data pertaining to the pathophysiology of aPL-associated neurologic manifestations and treatment issues.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References and Recommended Reading
Miyakis S, Lockshin M, Atsumi T, et al.: International consensus statement on an updated classification criteria for definite antiphospholipid syndrome. J Thromb Haemos 2006, 4:295–306.
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, 46:1019–1027.
Campbell AL, Pierangeli SS, Wellhausen S, Harris EN: Comparison of the effects of anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome and with syphilis on platelet activation and aggregation. Thromb Haemost 1995, 73:529–534.
Ziporen L, Shoenfeld Y: Antiphospholipid syndrome: from patient’s bedside to experimental animal models and back to the patient’s bedside. Hematol Cell Ther 1998, 40:175–182.
Gharavi EE, Chaimovich H, Cucurull E, et al.: Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides. Lupus 1999, 8:449–455.
Pierangeli SS, Harris EN: Antiphospholipid antibodies in an in vivo thrombosis model in mice. Lupus 1994, 3:247–251.
Pierangeli SS, Vega-Ostertag M, Harris EN: Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: a pathway to targeted therapies. Thromb Res 2004, 114:467–476.
Chen Q, Stone PR, Woon ST, et al.: Antiphospholipid antibodies bind to activated but not resting endothelial cells: is an independent triggering even required to induce antiphospholipid antibody-mediated disease? Thromb Res 2004, 114:101–111.
Tenedios F, Erkan D, Lockshin MD: Cardiac manifestations in the antiphospholipid syndrome. Rheum Dis Clin North Am 2006, 32:491–507.
Brey RL: Antiphospholipid antibodies in young adults with stroke. J Thromb Thrombolysis 2005, 20:105–112.
Brey RL: Management of the neurological manifestations of APS-what do the trials tell us? Thromb Res 2004, 114:489–499.
Nencini P, Baruffi MC, Abbate R, et al.: Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia. Stroke 1992, 23:189–193.
van Goor MP, Alblas CL, Leebeek FW, et al.: Do antiphospholipid antibodies increase the long-term risk of thrombotic complications in young patients with a recent TIA or ischemic stroke? Acta Neurol Scand 2004, 109:410–415.
Lanthier S, Kirkham FJ, Mitchell LG, et al.: Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children. Neurology 2004, 62:194–200.
Strater R, Becker S, von Eckardstein A: Prospective assessment of risk factors for recurrent stroke during childhood—a 5-year follow-up study. Lancet 2002, 360:1540–1545.
Cervera R, Khamashta MA, Font J, et al.: Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003, 82:299–308.
Cervera R, Khamashta MA, Font J, et al.: Morbidity and mortality in Systemic Lupus Erythematosus during a 5-year period: a multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 1999, 78:167–175.
Cesbron JY, Amouyel P, Masy E: Anticardiolipin antibodies and physical disability in the elderly. Ann Intern Med 1997, 126:1003.
de Moerloose P, Boehlen F, Reber G: Prevalence of anticardiolipin and antinuclear antibodies in an elderly hospitalized population and mortality after a 6-year follow-up. Age Ageing 1997, 26:319–320.
Mosek A, Yust I, Treves TA, et al.: Dementia and antiphospholipid antibodies. Dement Geriatr Cogn Disord 2000, 11:36–38.
Schmidt R, Auer-Grumbach P, Fazekas F, et al.: Anticardiolipin antibodies in normal subjects. Neuropsychological correlates and MRI findings. Stroke 1995, 26:749–754.
Jacobson MW, Rapport LJ, Keenan PA, et al.: Neuropsychological deficits associated with antiphospholipid antibodies. J Clin Exp Neuropsychol 1999, 21:251–264.
Denburg SD, Carbotte RM, Ginsberg JS, Denburg J: The relationship of antiphospholipid antibodies to cognitive function in patients with systemic lupus erythematosus. J Int Neuropsychol Soc 1997, 3:377–386.
Hanly JG, Hong C, Smith S, Fisk JD: A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 1999, 42:728–734.
Leritz E, Brandt J, Minor M, et al.: Neuropsychological functioning and its relationship to antiphospholipid antibodies in patients with systemic lupus erythematosus. J Clin Exp Neuropsychol 2002, 24:527–533.
Menon S, Jameson-Shortall E, Newman SP, et al.: A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum 1999, 42:735–741.
Mikdashi J, Handwerger B: Predictors of neuropsychiatric damage in systemic lupus erythematosus: Data from the maryland lupus cohort. Rheumatology (Oxford) 2004, 43:1555–1560.
McLaurin EY, Holliday SL, Williams P, Brey RL: Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 2005, 64:297–303.
Sanna G, Bertolaccini ML, Hughes GR: Hughes syndrome, the antiphospholipid syndrome: a new chapter in neurology. Ann N Y Acad Sci 2005, 1051:465–486.
Sanna G, Bertolaccini ML, Cuadrado MJ, et al.: Neuropsychiatric manifestations in SLE: Prevelence and association with antiphospholipid antibodies. J Rheumatol 2003, 30:985–992.
Tietjen GE, Day M, Norris L, et al.: Role of anticardiolipin antibodies in young persons with migraine and transient focal neurologic events. Neurology 1998, 50:1433–1440.
Montalban J, Cervera R, Font J, et al.: Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus. Neurology 1992, 42(3 Pt 1):681–682.
Tourbah A, Clapin A, Gout O, et al.: Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study. Arch Neurol 1998, 55:517–521.
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, 72:647–649.
Sastre-Garriga J, Reverter JC, Font J, et al.: Anticardiolipin antibodies are not a useful screening tool in a nonselected large group of patients with multiple sclerosis. Ann Neurol 2001, 49:408–411.
Chapman J: The interface of multiple sclerosis and Antiphospholipid antibodies. Thromb Res 2004, 114:477–481.
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, 59:120–124.
Cimaz R, Meroni PL, Shoenfled Y: Epilepsy as part of systemic erythematosus and systemic antiphospholipid syndrome (Hughes syndrome). Lupus 2006, 15:191–197.
Appenzeller, S, Cendes F, Costallat LT: Epileptic seizures in systemic lupus erythematosus. Neurology 2004, 63:1808–1812.
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.
Sailer M, Burchert W, Ehrenheim C, et al.: Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus. J Neurol 1997, 244:186–193.
Hachulla E, Michon-Pasturel U, Leys D, et al.: Cerebral magnetic imaging in patients with or without antiphospholipid antibodies. Lupus 1998, 7:124–131.
Csepany T, Bereczki D, Kollar J, et al.: MRI findings in central nervous system systemic lupus erythematosus are associated with immunoserological parameters and hypertension. J Neurol 2003, 230:1348–1354.
Sun SS, Liu FY, Tsai JJ, et al.: Using 99mTc HMPAO brain SPECT to evaluate the effects of anticoagulant therapy on regional cerebral blood flow in primary antiphospholipid antibody syndrome patients with brain involvement — a preliminary report. Rheumatol Int 2003, 23:301–304.
Crowther MA, Ginsberg JS, Julian J, et al.: A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Eng J Med 2003, 349:1133–1138.
Khamashta MA, Cuadrado MJ, Mujic F, et al.: The management of thrombosis in the antiphospholipid antibody syndrome. N Eng J Med 1995, 332:993–997.
Rosove MH, Brewer PMC: Antiphospholipid thrombosis: Clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992, 117:303–308.
Levine SR, Brey RL, Tilley BC, et al.: Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004, 291:576–584.
Erkan D, Leibowitz E, Berman J, Lockshin MD: Perioperative medical management of antiphospholipid syndrome: Hospital for Special Surgery experience, review of literature, and recommendations. J Rheumatol 2002, 29:843–849.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Roldan, J.F., Brey, R.L. Neurologic manifestations of the antiphospholipid syndrome. Curr Rheumatol Rep 9, 109–115 (2007). https://doi.org/10.1007/s11926-007-0004-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11926-007-0004-3