White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE).
Objective
The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients.
Method
A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load.
Results
MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores (p < 0.05). Higher WMHI Scheltens scores in both DWMHI and PVH were associated with presence of cerebral infarct but higher PVH lesion load was significantly associated with active SLE disease.
Conclusion
Presence of WMHI lesions in SLE was significantly associated with cerebral infarcts, aPL and high general SLE activity, suggesting both inflammation and ischaemia as the underlying pathology of these lesions.
RovarisMVitiBCiboddoGet al.Brain involvement in systemic immune mediated diseases: Magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry2000; 68: 170–177.
2.
FilleyCMKozoraEBrownMSet al.White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus. Cogn Behav Neurol2009; 22: 38–44.
3.
JennekensFGKaterL. The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic mechanisms of clinical syndromes: A literature investigation. Rheumatology (Oxford)2002; 41: 619–630.
4.
DeCarliCFletcherERameyVHarveyDJagustWJ. Anatomical mapping of white matter hyperintensities (WMH): Exploring the relationships between periventricular WMH, deep WMH, and total WMH burden. Stroke2005; 36: 50–55.
5.
FazekasFKleinertROffenbacherHet al.Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology1993; 43: 1683–1689.
6.
JicklingGSalamAMohammadAet al.Circulating endothelial progenitor cells and age-related white matter changes. Stroke2009; 40: 3191–3196.
7.
PomperMGMillerTJStoneJHTidmoreWCHellmannDB. CNS vasculitis in autoimmune disease: MR imaging findings and correlation with angiography. AJNR Am J Neuroradiol1999; 20: 75–85.
8.
SibbittWLJrBrooksWMKornfeldMHartBLBankhurstADRoldanCA. Magnetic resonance imaging and brain histopathology in neuropsychiatric systemic lupus erythematosus. Semin Arthritis Rheum2010; 40: 32–52.
9.
KimKWMacFallJRPayneME. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol Psychiatry2008; 64: 273–280.
10.
ScarpelliMSalvoliniUDiamantiLMontironiRChiaromoniLMaricottiM. MRI and pathological examination of post-mortem brains: The problem of white matter high signal areas. Neuroradiology1994; 36: 393–398.
11.
FazekasFKleinertROffenbacherHet al.The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am J Neuroradiol1991; 12: 915–921.
12.
HarboeEGreveOJBeyerMet al.Fatigue is associated with cerebral white matter hyperintensities in patients with systemic lupus erythematosus. J Neurol Neurosurg Psychiatry2008; 79: 199–201.
13.
AppenzellerSVasconcelos FariaALiLMCostallatLTCendesF. Quantitative magnetic resonance imaging analyses and clinical significance of hyperintense white matter lesions in systemic lupus erythematosus patients. Ann Neurol2008; 64: 635–643.
14.
CsépányTBereczkiDKollárJSikulaJKissECsibaL. MRI findings in central nervous system systemic lupus erythematosus are associated with immunoserological parameters and hypertension. J Neurol2003; 250: 1348–1354.
15.
SannaGPigaMTerryberryJWet al.Central nervous system involvement in systemic lupus erythematosus: Cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations. Lupus2000; 9: 573–583.
KaichiYKakedaSMoriyaJet al.Brain MR findings in patients with systemic lupus erythematosus with and without antiphospholipid antibody syndrome. AJNR Am J Neuroradiol2014; 35: 100–105.
18.
LuyendijkJSteensSCOuwendijkWJet al.Neuropsychiatric systemic lupus erythematosus: Lessons learned from magnetic resonance imaging. Arthritis Rheum2011; 63: 722–732.
19.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725–1725.
20.
SpiltAGoekoopRWestendorpRGBlauwGJde CraenAJvan BuchemMA. Not all age-related white matter hyperintensities are the same: A magnetization transfer imaging study. AJNR Am J Neuroradiol2006; 27: 1964–1968.
21.
WardlawJMSmithEEBiesselsGJet al.Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol2013; 12: 822–838.
22.
SchaeferPWGrantPEGonzalezRG. Diffusion-weighted MR imaging of the brain. Radiology2000; 217: 331–345.
23.
ChowdhuryDWardlawJMDennisMS. Are multiple acute small subcortical infarctions caused by embolic mechanisms?J Neurol Neurosurg Psychiatry2004; 75: 1416–1420.
24.
ScheltensPBarkhofFLeysDet al.A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci1993; 114: 7–12.
25.
FazekasFChawlukJBAlaviAHurtigHIZimmermanRA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol1987; 149: 351–356.
26.
ScheltensPBarkhofFLeysDWoltersECRavidRKamphorstW. Histopathologic correlates of white matter changes on MRI in Alzheimer’s disease and normal aging. Neurology1995; 45: 883–888.
27.
KapellerPBarberRVermeulenRJet al.Visual rating of age-related white matter changes on magnetic resonance imaging: Scale comparison, interrater agreement, and correlations with quantitative measurements. Stroke2003; 34: 441–445.
28.
The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42: 599–608.
29.
BombardierCGladmanDDUrowitzMBCaronDChangCH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum1992; 35: 630–640.
30.
HawkerGGabrielSBombardierCGoldsmithCCaronDGladmanD. A reliability study of SLEDAI: A disease activity index for systemic lupus erythematosus. J Rheumatol1993; 20: 657–660.
31.
PetriMHellmannDHochbergM. Validity and reliability of lupus activity measures in the routine clinic setting. J Rheumatol1992; 19: 53–59.
32.
WardMMMarxASBarryNN. Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus. J Rheumatol2000; 27: 664–670.
33.
YeeCSFarewellVTIsenbergDAet al.The use of Systemic Lupus Erythematosus Disease Activity Index-2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients. Rheumatology (Oxford)2011; 50: 982–988.
34.
GladmanDGinzlerEGoldsmithCet al.The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum1996; 39: 363–369.
35.
BaumKAHopfUNehrigCStöverMSchörnerW. Systemic lupus erythematosus: Neuropsychiatric signs and symptoms related to cerebral MRI findings. Clin Neurol Neurosurg1993; 95: 29–34.
36.
FriedmanSDStidleyCABrooksWMHartBLSibbittWLJr. Brain injury and neurometabolic abnormalities in systemic lupus erythematosus. Radiology1998; 209: 79–84.
37.
HachullaEMichon-PasturelULeysDet al.Cerebral magnetic resonance imaging in patients with or without antiphospholipid antibodies. Lupus1998; 7: 124–131.
YlikoskiAErkinjunttiTRaininkoRSarnaSSulkavaRTilvisR. White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. Stroke1995; 26: 1171–1177.
40.
LaunerLJBergerKBretelerMMet al.Regional variability in the prevalence of cerebral white matter lesions: An MRI study in 9 European countries (CASCADE). Neuroepidemiology2006; 26: 23–29.
41.
LiaoDCooperLCaiJet al.The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: The ARIC Study. Neuroepidemiology1997; 16: 149–162.
42.
Gonzalez-CrespoMRBlancoFJRamosAet al.Magnetic resonance imaging of the brain in systemic lupus erythematosus. Br J Rheumatol1995; 34: 1055–1060.
43.
CastellinoGPadovanMBortoluzziAet al.Single photon emission computed tomography and magnetic resonance imaging evaluation in SLE patients with and without neuropsychiatric involvement. Rheumatology (Oxford)2008; 47: 319–323.
44.
SailerMBurchertWEhrenheimCet al.Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus. J Neurol1997; 244: 186–193.
45.
PietteJCFrancesCPapoTKarmochkineM. Vasculopathy and antiphospholipid antibodies in systemic lupus. J Clin Pathol1993; 46: 781–782.
46.
PantoniLGarciaJH. Pathogenesis of leukoaraiosis. A review. Stroke1997; 28: 652–659.
47.
MunozDGHastakSMHarperBLeeDHachinskiVC. Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging. Arch Neurol1993; 50: 492–497.
48.
O’RourkeMFSafarME. Relationship between aortic stiffening and microvascular disease in brain and kidney: Cause and logic of therapy. Hypertension2005; 46: 200–204.
49.
KnopmanDSMosleyTHJrBaileyKRJackCRJrSchwartzGLTurnerST. Associations of microalbuminuria with brain atrophy and white matter hyperintensities in hypertensive sibships. J Neurol Sci2008; 271: 53–60.
