title: Revisiting the molecular mechanism of neurological manifestations in antiphospholipid syndrome: beyond vascular damage.
abstract: Antiphospholipid syndrome (APS) is a multiorgan disease often affecting the central nervous system (CNS). Typically, neurological manifestations of APS include thrombosis of cerebral vessels leading to stroke and requiring prompt initiation of treatment with antiplatelet drugs or anticoagulant therapy. In these cases, alterations of the coagulation system at various levels caused by multiple effects of antiphospholipid antibodies (aPL) have been postulated to explain the vascular damage to the CNS in APS. However, several nonvascular neurological manifestations of APS have progressively emerged over the past years. Nonthrombotic, immune-mediated mechanisms altering physiological basal ganglia function have been recently suggested to play a central role in the pathogenesis of these manifestations that include, among others, movement disorders such as chorea and behavioral and cognitive alterations. Similar clinical manifestations have been described in other autoimmune CNS diseases such as anti-NMDAR and anti-VGCK encephalitis, suggesting that the spectrum of immune-mediated basal ganglia disorders is expanding, possibly sharing some pathophysiological mechanisms. In this review, we will focus on thrombotic and nonthrombotic neurological manifestations of APS with particular attention to immune-mediated actions of aPL on the vascular system and the basal ganglia.
authors.affiliation: Section of Neurology, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Carecchio
authors.affiliation: Section of Neurology, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cantello
authors.affiliation: Section of Neurology, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy ; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Comi
mesh_terms: D016736:Antiphospholipid Syndrome / Q000150:complications / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology
references.citation: Ann Rheum Dis. 2010 Dec;69(12):2074-82
references.pmid: 20724309
references.citation: Am J Neurodegener Dis. 2013 Jun 21;2(2):89-107
references.pmid: 23844334
references.citation: Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii46-50
references.pmid: 12379621
references.citation: Neurosci Lett. 1998 Nov 27;257(2):116-8
references.pmid: 9865941
references.citation: Arthritis Care Res (Hoboken). 2013 Nov;65(11):1869-73
references.pmid: 23861221
references.citation: J Thromb Haemost. 2007 Jul;5(7):1538-44
references.pmid: 17470198
references.citation: Neurology. 1997 Aug;49(2):639-40
references.pmid: 9270624
references.citation: J Biol Chem. 2005 Nov 4;280(44):36729-36
references.pmid: 16091370
references.citation: Clin Dev Immunol. 2012;2012:981519
references.pmid: 22489254
references.citation: Blood. 2012 Jul 12;120(2):266-74
references.pmid: 22553312
references.citation: Blood. 2005 Feb 15;105(4):1540-5
references.pmid: 15507529
references.citation: Nat Med. 2003 Jul;9(7):914-20
references.pmid: 12819778
references.citation: Autoimmun Rev. 2012 Aug;11(10):717-22
references.pmid: 22269862
references.citation: Rheum Dis Clin North Am. 2006 Aug;32(3):465-90
references.pmid: 16880079
references.citation: Pediatr Med Chir. 2002 Sep-Oct;24(5):392-3
references.pmid: 12494544
references.citation: Mov Disord. 2004 Apr;19(4):406-15
references.pmid: 15077238
references.citation: Neuropediatrics. 1996 Jun;27(3):149-53
references.pmid: 8837075
references.citation: AJR Am J Roentgenol. 1996 Dec;167(6):1573-8
references.pmid: 8956600
references.citation: J Neural Transm (Vienna). 2013 Nov;120(11):1579-89
references.pmid: 23580159
references.citation: Stroke. 1996 Oct;27(10):1724-30
references.pmid: 8841318
references.citation: Clin Exp Rheumatol. 1992 Sep-Oct;10(5):455-60
references.pmid: 1458697
references.citation: Rheumatology (Oxford). 2003 Feb;42(2):200-13
references.pmid: 12595612
references.citation: J Neurol Sci. 2009 Jun 15;281(1-2):101-3
references.pmid: 19344915
references.citation: Clin Neurol Neurosurg. 2006 Feb;108(2):135-42
references.pmid: 16412834
references.citation: Ann Neurol. 2009 Nov;66(5):704-9
references.pmid: 19938173
references.citation: Rheumatology (Oxford). 2008 Nov;47(11):1628-34
references.pmid: 18782854
references.citation: J Thromb Haemost. 2006 Feb;4(2):295-306
references.pmid: 16420554
references.citation: Clin Rheumatol. 2007 Dec;26(12):2145-2147
references.pmid: 17487450
references.citation: Ann Neurol. 1995 Jul;38(1):119-24
references.pmid: 7611714
references.citation: Dev Med Child Neurol. 2011 Jun;53(6):522-8
references.pmid: 21574989
references.citation: Medicine (Baltimore). 1997 May;76(3):203-12
references.pmid: 9193455
references.citation: Ann Neurol. 2009 Jul;66(1):11-8
references.pmid: 19670433
references.citation: Lupus. 2003;12(6):436-42
references.pmid: 12873044
references.citation: Lupus. 2002;11(11):736-43
references.pmid: 12475004
references.citation: J Neuroimmunol. 2003 Mar;136(1-2):149-53
references.pmid: 12620654
references.citation: J Alzheimers Dis. 2010;19(4):1143-8
references.pmid: 20308780
references.citation: Lupus. 2003;12(12):908-15
references.pmid: 14714910
references.citation: Thromb Res. 1994 Jun 1;74(5):495-504
references.pmid: 8085250
references.citation: Arch Intern Med. 1997 Oct 13;157(18):2101-8
references.pmid: 9382667
references.citation: Arthritis Rheum. 2002 Apr;46(4):1019-27
references.pmid: 11953980
references.citation: Stroke. 1997 Dec;28(12):2363-9
references.pmid: 9412615
references.citation: Lupus. 2001;10(7):496-9
references.pmid: 11480848
references.citation: Eur J Clin Invest. 2010 Apr;40(4):350-9
references.pmid: 20192975
references.citation: Neurology. 2005 Dec 13;65(11):1701-7
references.pmid: 16207842
references.citation: Nat Clin Pract Rheumatol. 2008 Apr;4(4):192-9
references.pmid: 18285765
references.citation: Autoimmune Dis. 2012;2012:404815
references.pmid: 22454760
references.citation: Ann Hematol. 2004 Nov;83(11):704-11
references.pmid: 15300407
references.citation: Blood. 2008 Sep 1;112(5):1687-95
references.pmid: 18577708
references.citation: Blood. 2007 Feb 15;109(4):1490-4
references.pmid: 17053060
references.citation: Biol Psychiatry. 1994 Apr 1;35(7):495-8
references.pmid: 8018803
references.citation: Ann Neurol. 2007 Jan;61(1):25-36
references.pmid: 17262855
references.citation: J Rheumatol. 1998 Mar;25(3):589-92
references.pmid: 9517786
references.citation: Arch Dis Child. 2004 Jul;89(7):611-4
references.pmid: 15210488
references.citation: Lancet Neurol. 2010 Aug;9(8):776-85
references.pmid: 20580615
references.citation: Parkinsonism Relat Disord. 2001 Apr;7(2):139-141
references.pmid: 11248596
references.citation: Blood. 2007 Jan 15;109(2):422-30
references.pmid: 16985176
references.citation: AJNR Am J Neuroradiol. 1998 Apr;19(4):611-6
references.pmid: 9576644
references.citation: Mov Disord. 1999 May;14(3):530-2
references.pmid: 10348488
references.citation: Lupus. 2012 Dec;21(14):1497-505
references.pmid: 22933620
references.citation: Autoimmun Rev. 2013 May;12(7):752-7
references.pmid: 23282546
references.citation: J Thromb Haemost. 2007 Feb;5(2):369-77
references.pmid: 17096706
references.citation: Am J Psychiatry. 1998 Feb;155(2):264-71
references.pmid: 9464208
references.citation: Neurobiol Dis. 2008 Apr;30(1):56-64
references.pmid: 18308578
references.citation: Br Med J (Clin Res Ed). 1983 Oct 15;287(6399):1088-9
references.pmid: 6414579
references.citation: Ann Rheum Dis. 1987 Aug;46(8):605-11
references.pmid: 3116954
references.citation: J Rheumatol. 2003 May;30(5):985-92
references.pmid: 12734893
references.citation: J Clin Invest. 1997 Aug 1;100(3):613-9
references.pmid: 9239409
references.citation: Pediatr Neurol. 1996 Sep;15(2):108-13
references.pmid: 8888043
references.citation: Clin Exp Immunol. 1992 Nov;90(2):266-70
references.pmid: 1424285
references.citation: J Thromb Haemost. 2008 Aug;6(8):1405-12
references.pmid: 18485085
references.citation: Arthritis Rheum. 2013 Feb;65(2):464-71
references.pmid: 23124321
references.citation: Mov Disord. 2011 Oct;26(12):2176
references.pmid: 22319790
references.citation: Neurology. 2011 Jul 12;77(2):179-89
references.pmid: 21747075
references.citation: Mov Disord. 2012 Jul;27(8):935-46
references.pmid: 22555904
references.citation: Arthritis Rheum. 1999 Apr;42(4):728-34
references.pmid: 10211887
references.citation: Neurology. 2002 Jul 23;59(2):227-31
references.pmid: 12136062
references.citation: J Rheumatol. 2002 Jul;29(7):1574-5
references.pmid: 12136923
references.citation: Brain. 2010 Sep;133(9):2734-48
references.pmid: 20663977
references.citation: J Neuroimmunol. 2006 Oct;179(1-2):173-9
references.pmid: 16875742
references.citation: Neurobiol Aging. 2011 Feb;32(2):272-9
references.pmid: 19282067
references.citation: Mov Disord. 2009 Jul 15;24(9):1267-79
references.pmid: 19353683
references.citation: Semin Arthritis Rheum. 2011 Feb;40(4):349-57
references.pmid: 20701956
references.citation: J Neurol Neurosurg Psychiatry. 2012 Jun;83(6):638-45
references.pmid: 22448032
references.citation: Dement Geriatr Cogn Disord. 2000 Jan-Feb;11(1):36-8
references.pmid: 10629360
references.citation: Brain. 2012 Nov;135(Pt 11):3453-68
references.pmid: 23065479
references.citation: J Rheumatol. 2004 Jul;31(7):1344-8
references.pmid: 15229954
references.citation: Pediatrics. 2008 Nov;122(5):e1100-7
references.pmid: 18955411
references.citation: Lupus. 1999;8(2):127-33
references.pmid: 10192507
references.citation: J Neurol Sci. 1998 Apr 1;156(2):211-9
references.pmid: 9588860
references.citation: Mov Disord. 2005 Jan;20(1):111-3
references.pmid: 15390045
references.citation: Mov Disord. 2006 Jul;21(7):944-9
references.pmid: 16538618
references.citation: Ann N Y Acad Sci. 2009 Sep;1173:805-13
references.pmid: 19758232
references.citation: J Child Neurol. 2012 Nov;27(11):1470-81
references.pmid: 22832771
references.citation: J Rheumatol. 1988 Feb;15(2):377-9
references.pmid: 3361549