Skip to main content
Top
Published in: Journal of Neurology 1/2010

01-01-2010 | Original Communication

MRI characteristics of patients with antiphospholipid syndrome and multiple sclerosis

Authors: Milena Stosic, Julian Ambrus, Neeta Garg, Bianca Weinstock-Guttman, Murali Ramanathan, Bernadette Kalman, Alireza Minagar, Frederick E. Munschauer, Timothy M. Galey, Sara Hussein, Rohit Bakshi, Robert Zivadinov

Published in: Journal of Neurology | Issue 1/2010

Login to get access

Abstract

MRI findings of primary anti-phospholipid antibody syndrome (PAPLS) are difficult to distinguish from those of multiple sclerosis (MS). Only a few previous studies have compared conventional and non-conventional MRI findings in MS and PAPLS patients. In addition, MRI differences between anti-phospholipid antibody (APLA) positive (+) and APLA negative (−) MS patients have not been reported. Therefore, the aim of this study was to investigate the differences in MRI measures among patients with PAPLS, MS and normal control (NC) subjects. We also explored non-conventional MRI measures in APLA+ and APLA− MS patients. Forty-nine (49) consecutive MS patients among whom 39 had relapsing-remitting (RR) and 10 secondary-progressive (SP) disease course, 30 patients with PAPLS and 49 NC were enrolled. Twenty-eight (28) MS patients were APLA+. MRI measures of T1- and T2-lesion volumes (LV) and brain atrophy, including fractions of whole brain (BPF), gray matter (GMF) and white matter (WMF), were evaluated. The magnetization transfer ratio (MTR) of T2- and T1-LVs and different normal-appearing brain tissue (NABT) compartments as well as diffusion-weighted imaging of whole brain mean parenchyma diffusivity (MPD) were obtained. MS patients differed significantly from NC in all MRI measures. PAPLS patients differed from NC in their T2-LV, in MTR measures and in MPD. When MS patients were compared to PAPLS patients, they showed significantly higher T2- and T1-LVs and T2-LV MTR, lower BPF and GMF and higher MPD. APLA+ RR and SPMS (all APLA+) patients showed significantly higher T2-LV, lower GMF, lower normal-appearing gray matter MTR and higher MPD when compared to APLA− patients. The results indicate that brain abnormalities can be detected in PAPLS patients with non-conventional MRI. MRI reveals more profound injury in patients with MS versus PAPLS. APLA mediates heterogeneous cerebral pathology that remains to be further investigated.
Literature
1.
go back to reference Abo SM, DeBari VA (2007) Laboratory evaluation of the antiphospholipid syndrome. Ann Clin Lab Sci 37:3–14PubMed Abo SM, DeBari VA (2007) Laboratory evaluation of the antiphospholipid syndrome. Ann Clin Lab Sci 37:3–14PubMed
2.
3.
go back to reference Atsumi T, Khamashta M, Haworth R, Brooks G, Amengual O, Ichikawa K, Koike T, Hughes GRV (1998) Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1. Arthritis Rheum 41:800–807CrossRefPubMed Atsumi T, Khamashta M, Haworth R, Brooks G, Amengual O, Ichikawa K, Koike T, Hughes GRV (1998) Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1. Arthritis Rheum 41:800–807CrossRefPubMed
4.
go back to reference Benedict RH, Bruce J, Dwyer MG, Weinstock-Guttman B, Tjoa C, Tavazzi E, Munschauer FE, Zivadinov R (2007) Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis. Mult Scler 13:722–730CrossRefPubMed Benedict RH, Bruce J, Dwyer MG, Weinstock-Guttman B, Tjoa C, Tavazzi E, Munschauer FE, Zivadinov R (2007) Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis. Mult Scler 13:722–730CrossRefPubMed
5.
go back to reference Bidot CJ, Horstman LL, Jy W, Jimenez JJ, Bidot C Jr, Ahn YS, Alexander JS, Gonzalez-Toledo E, Kelley RE, Minagar A (2007) Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study. BMC Neurol 7:36CrossRefPubMed Bidot CJ, Horstman LL, Jy W, Jimenez JJ, Bidot C Jr, Ahn YS, Alexander JS, Gonzalez-Toledo E, Kelley RE, Minagar A (2007) Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study. BMC Neurol 7:36CrossRefPubMed
6.
go back to reference Bink A, Schmitt M, Gaa J, Mugler JP, Lanfermann H, Zanella FE (2006) Detection of lesions in multiple sclerosis by 2D FLAIR and single-slab 3D FLAIR sequences at 3.0 T: initial results. Eur Radiol 16:1104–1110CrossRefPubMed Bink A, Schmitt M, Gaa J, Mugler JP, Lanfermann H, Zanella FE (2006) Detection of lesions in multiple sclerosis by 2D FLAIR and single-slab 3D FLAIR sequences at 3.0 T: initial results. Eur Radiol 16:1104–1110CrossRefPubMed
7.
go back to reference Carone DA, Benedict RH, Dwyer MG, Cookfair DL, Srinivasaraghavan B, Tjoa CW, Zivadinov R (2006) Semi-automatic brain region extraction (SABRE) reveals superior cortical and deep gray matter atrophy in MS. Neuroimage 29:505–514CrossRefPubMed Carone DA, Benedict RH, Dwyer MG, Cookfair DL, Srinivasaraghavan B, Tjoa CW, Zivadinov R (2006) Semi-automatic brain region extraction (SABRE) reveals superior cortical and deep gray matter atrophy in MS. Neuroimage 29:505–514CrossRefPubMed
8.
go back to reference Cuadrado MJ, Khamashta MA (2000) The anti-phospholipid antibody syndrome (Hughes syndrome): therapeutic aspects. Baillieres Best Pract Res Clin Rheumatol 14:151–163CrossRefPubMed Cuadrado MJ, Khamashta MA (2000) The anti-phospholipid antibody syndrome (Hughes syndrome): therapeutic aspects. Baillieres Best Pract Res Clin Rheumatol 14:151–163CrossRefPubMed
9.
go back to reference Dutta R, Trapp BD (2007) Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 68:S22–S31 discussion S43-54CrossRefPubMed Dutta R, Trapp BD (2007) Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 68:S22–S31 discussion S43-54CrossRefPubMed
10.
go back to reference Garg N, Zivadinov R, Ramanathan M, Vasiliu I, Locke J, Watts K, Lema J, Rajeswary J, Munschauer FE, Ambrus J Jr, Weinstock-Guttman B (2007) Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients. J Neuroimmunol 187:159–165CrossRefPubMed Garg N, Zivadinov R, Ramanathan M, Vasiliu I, Locke J, Watts K, Lema J, Rajeswary J, Munschauer FE, Ambrus J Jr, Weinstock-Guttman B (2007) Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients. J Neuroimmunol 187:159–165CrossRefPubMed
11.
go back to reference Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA (2005) Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236:254–260CrossRefPubMed Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA (2005) Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236:254–260CrossRefPubMed
12.
go back to reference Ghafourifar P, Mousavizadeh K, Parihar MS, Nazarewicz RR, Parihar A, Zenebe WJ (2008) Mitochondria in multiple sclerosis. Front Biosci 13:3116–3126CrossRefPubMed Ghafourifar P, Mousavizadeh K, Parihar MS, Nazarewicz RR, Parihar A, Zenebe WJ (2008) Mitochondria in multiple sclerosis. Front Biosci 13:3116–3126CrossRefPubMed
13.
go back to reference Grunewald T, Burmester GR, Schuler-Maue W, Hiepe F, Buttgereit F (1999) Anti-phospholipid antibodies and CD5+ B cells in HIV infection. Clin Exp Immunol 115:464–471CrossRefPubMed Grunewald T, Burmester GR, Schuler-Maue W, Hiepe F, Buttgereit F (1999) Anti-phospholipid antibodies and CD5+ B cells in HIV infection. Clin Exp Immunol 115:464–471CrossRefPubMed
14.
go back to reference Hachulla E, Michon-Pasturel U, Leys D, Pruvo JP, Queyrel V, Masy E, Arvieux J, Caron C, Brevet-Coupe F, Hatron PY, Devulder B (1998) Cerebral magnetic resonance imaging in patients with or without antiphospholipid antibodies. Lupus 7:124–131CrossRefPubMed Hachulla E, Michon-Pasturel U, Leys D, Pruvo JP, Queyrel V, Masy E, Arvieux J, Caron C, Brevet-Coupe F, Hatron PY, Devulder B (1998) Cerebral magnetic resonance imaging in patients with or without antiphospholipid antibodies. Lupus 7:124–131CrossRefPubMed
15.
go back to reference IJ JW, Conti-Kelly AM, Greco P, Abedi M, Amos M, Provenzale JM, Greco TP (1999) Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS? Lupus 8:109–115CrossRef IJ JW, Conti-Kelly AM, Greco P, Abedi M, Amos M, Provenzale JM, Greco TP (1999) Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS? Lupus 8:109–115CrossRef
16.
17.
go back to reference Karussis D, Leker RR, Ashkenazi A, Abramsky O (1998) A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? Ann Neurol 44:629–634CrossRefPubMed Karussis D, Leker RR, Ashkenazi A, Abramsky O (1998) A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? Ann Neurol 44:629–634CrossRefPubMed
18.
go back to reference Kim JH, Choi CG, Choi SJ, Lee HK, Suh DC (2000) Primary antiphospholipid antibody syndrome: neuroradiologic findings in 11 patients. Korean J Radiol 1:5–10CrossRefPubMed Kim JH, Choi CG, Choi SJ, Lee HK, Suh DC (2000) Primary antiphospholipid antibody syndrome: neuroradiologic findings in 11 patients. Korean J Radiol 1:5–10CrossRefPubMed
19.
go back to reference Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMed Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMed
20.
go back to reference Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911PubMed Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911PubMed
21.
go back to reference Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M, Reynolds R, Aloisi F (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130:1089–1104CrossRefPubMed Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M, Reynolds R, Aloisi F (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130:1089–1104CrossRefPubMed
22.
go back to reference McIntyre JA, Wagenknech DR, Waxman DW (2003) Frequency and specificities of antiphospholipid antibodies (aPL) in volunteer blood donors. Immunobiology 207:59–63CrossRefPubMed McIntyre JA, Wagenknech DR, Waxman DW (2003) Frequency and specificities of antiphospholipid antibodies (aPL) in volunteer blood donors. Immunobiology 207:59–63CrossRefPubMed
23.
go back to reference Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306 Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306
24.
go back to reference Molad Y, Sidi Y, Gornish M, Lerner M, Pinkhas J, Weinberger A (1992) Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions. J Rheumatol 19:556–561PubMed Molad Y, Sidi Y, Gornish M, Lerner M, Pinkhas J, Weinberger A (1992) Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions. J Rheumatol 19:556–561PubMed
25.
go back to reference Paran D, Chapman J, Korczyn AD, Elkayam O, Hilkevich O, Groozman GB, Levartovsky D, Litinsky I, Caspi D, Segev Y, Drory VE (2006) Evoked potential studies in the antiphospholipid syndrome: differential diagnosis from multiple sclerosis. Ann Rheum Dis 65:525–528CrossRefPubMed Paran D, Chapman J, Korczyn AD, Elkayam O, Hilkevich O, Groozman GB, Levartovsky D, Litinsky I, Caspi D, Segev Y, Drory VE (2006) Evoked potential studies in the antiphospholipid syndrome: differential diagnosis from multiple sclerosis. Ann Rheum Dis 65:525–528CrossRefPubMed
26.
go back to reference Pierangeli SS, Chen PP, Gonzalez EB (2006) Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Curr Opin Hematol 13:366–375PubMed Pierangeli SS, Chen PP, Gonzalez EB (2006) Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Curr Opin Hematol 13:366–375PubMed
27.
go back to reference Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMed Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMed
28.
go back to reference Rovaris M, Viti B, Ciboddo G, Gerevini S, Capra R, Iannucci G, Comi G, Filippi M (2000) Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry 68:170–177CrossRefPubMed Rovaris M, Viti B, Ciboddo G, Gerevini S, Capra R, Iannucci G, Comi G, Filippi M (2000) Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry 68:170–177CrossRefPubMed
29.
go back to reference Sanfilipo MP, Benedict RH, Zivadinov R, Bakshi R (2004) Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: the proportion vs. residual method. Neuroimage 22:1732–1743CrossRefPubMed Sanfilipo MP, Benedict RH, Zivadinov R, Bakshi R (2004) Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: the proportion vs. residual method. Neuroimage 22:1732–1743CrossRefPubMed
30.
go back to reference Schmidt R, Auer-Grumbach P, Fazekas F, Offenbacher H, Kapeller P (1995) Anticardiolipin antibodies in normal subjects. Neuropsychological correlates and MRI findings. Stroke 26:749–754PubMed Schmidt R, Auer-Grumbach P, Fazekas F, Offenbacher H, Kapeller P (1995) Anticardiolipin antibodies in normal subjects. Neuropsychological correlates and MRI findings. Stroke 26:749–754PubMed
31.
go back to reference Tarr T, Lakos G, Bhattoa HP, Szegedi G, Shoenfeld Y, Kiss E (2007) Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus. Lupus 16:324–328CrossRefPubMed Tarr T, Lakos G, Bhattoa HP, Szegedi G, Shoenfeld Y, Kiss E (2007) Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus. Lupus 16:324–328CrossRefPubMed
32.
go back to reference Tavazzi E, Dwyer MG, Weinstock-Guttman B, Lema J, Bastianello S, Bergamaschi R, Cosi V, Benedict RH, Munschauer FE 3rd, Zivadinov R (2007) Quantitative diffusion weighted imaging measures in patients with multiple sclerosis. Neuroimage 36:746–754CrossRefPubMed Tavazzi E, Dwyer MG, Weinstock-Guttman B, Lema J, Bastianello S, Bergamaschi R, Cosi V, Benedict RH, Munschauer FE 3rd, Zivadinov R (2007) Quantitative diffusion weighted imaging measures in patients with multiple sclerosis. Neuroimage 36:746–754CrossRefPubMed
33.
go back to reference Tourbah A, Clapin A, Gout O, Fontaine B, Liblau R, Batteux F, Stievenart JL, Weill B, Lubetzki C, Lyon-Caen O (1998) Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study. Arch Neurol 55:517–521CrossRefPubMed Tourbah A, Clapin A, Gout O, Fontaine B, Liblau R, Batteux F, Stievenart JL, Weill B, Lubetzki C, Lyon-Caen O (1998) Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study. Arch Neurol 55:517–521CrossRefPubMed
34.
go back to reference Weinstock-Guttman B, Zivadinov R, Tamano-Blanco M, Abdelrahman N, Badgett D, Durfee J, Hussein S, Feichter J, Patrick K, Benedict R, Ramanathan M (2007) Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis. J Neuroimmunol 188:167–174CrossRefPubMed Weinstock-Guttman B, Zivadinov R, Tamano-Blanco M, Abdelrahman N, Badgett D, Durfee J, Hussein S, Feichter J, Patrick K, Benedict R, Ramanathan M (2007) Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis. J Neuroimmunol 188:167–174CrossRefPubMed
35.
go back to reference Zivadinov R, Bergsland N, Stosic M, Sharma J, Nussenbaum F, Durfee J, Hani N, Abdelrahman N, Jaisani Z, Minagar A, Hoque R, Munschauer FE 3rd, Dwyer MG (2008) Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis. Neurol Res 30:816–826CrossRefPubMed Zivadinov R, Bergsland N, Stosic M, Sharma J, Nussenbaum F, Durfee J, Hani N, Abdelrahman N, Jaisani Z, Minagar A, Hoque R, Munschauer FE 3rd, Dwyer MG (2008) Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis. Neurol Res 30:816–826CrossRefPubMed
36.
go back to reference Zivadinov R, De Masi R, Nasuelli D, Bragadin LM, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M (2001) MRI techniques and cognitive impairment in the early phase of relapsing–remitting multiple sclerosis. Neuroradiology 43:272–278CrossRefPubMed Zivadinov R, De Masi R, Nasuelli D, Bragadin LM, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M (2001) MRI techniques and cognitive impairment in the early phase of relapsing–remitting multiple sclerosis. Neuroradiology 43:272–278CrossRefPubMed
37.
go back to reference Zivadinov R, Weinstock-Guttman B, Benedict R, Tamano-Blanco M, Hussein S, Abdelrahman N, Durfee J, Ramanathan M (2007) Preservation of Gray Matter Volume in Multiple Sclerosis Patients with the Met Allele of the rs6265 (Val66Met) SNP of Brain Derived Neurotrophic Factor (BDNF). Hum Mol Genet 16:2659–2668CrossRefPubMed Zivadinov R, Weinstock-Guttman B, Benedict R, Tamano-Blanco M, Hussein S, Abdelrahman N, Durfee J, Ramanathan M (2007) Preservation of Gray Matter Volume in Multiple Sclerosis Patients with the Met Allele of the rs6265 (Val66Met) SNP of Brain Derived Neurotrophic Factor (BDNF). Hum Mol Genet 16:2659–2668CrossRefPubMed
Metadata
Title
MRI characteristics of patients with antiphospholipid syndrome and multiple sclerosis
Authors
Milena Stosic
Julian Ambrus
Neeta Garg
Bianca Weinstock-Guttman
Murali Ramanathan
Bernadette Kalman
Alireza Minagar
Frederick E. Munschauer
Timothy M. Galey
Sara Hussein
Rohit Bakshi
Robert Zivadinov
Publication date
01-01-2010
Publisher
D. Steinkopff-Verlag
Published in
Journal of Neurology / Issue 1/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-009-5264-6

Other articles of this Issue 1/2010

Journal of Neurology 1/2010 Go to the issue