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A MR spectroscopy study P. Wang, R. Harris, P. Cagnoli, D. Frechtling, D. Bekris, S. Gebarski, J. McCune, and P. Sundgren
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University of Michigan (US) & Lund University (Sweden)
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M SLE is an autoimmune disorder neuropsychiatric systemic lupus erythematosus or NPSLE 30-40% of lupus patients at the time of diagnosis or 2 years thereafter worse prognosis increased morbidity and mortality
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M headache stroke or stroke like symptoms psychosis seizures cognitive dysfunction
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M white matter changes
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M Copied with permission from Appenzeller et al. Arthritis Rheum. 2005 Sep 52 (9):2783-9. cerebral and corpus callosum atrophy
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M gross and microinfarcts cortical atrophy hemorrhage demyelination
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M confirm diagnosis of lupus careful history and physical exam targeted workup for symptoms
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M largely uncontrolled trials and anecdotal experiences immunosuppressive tx anticoagulation/antiplatelet tx
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M some patients have no serologic or systemic signs detect early metabolic changes help narrow the differential diagnosis monitor therapy run outcome trials to validate treatment
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M use MR spectroscopy to investigate whether differences in metabolic ratios exist between patients with: NPSLE SLE healthy controls
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M 20 SLE patients with no neurological sx 18 F: 2 M (ages 21.0-61.0; mean 40.7) 20 SLE patients with neurological sx 20 F (ages 25.2-67.3; mean 41.5) 20 healthy controls 17 F: 3M (ages 18.8-61.0; mean 40.7)
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M clinical workup including: laboratory testing SLE Disease Activity Index score (SLEDAI) mini-mental status examination fatigue, depression, and pain questionnaire
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M 3T MRI of the brain, which was evaluated for: signal abnormalities hemorrhage ischemic events focal lesions atrophy
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frontal white matter right insula occipital gray matter SVS (single-voxel spectroscopy) MR PRESS TR 2000 ms TE 30 ms 2x2x2 cm voxel size
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M Cho Cr NAA
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M Healthy Controls SLE NPSLE NAA Cho Cr Cho Cr NAA
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M frontal white matter Cho/Cr ratio: SLE: 0.22 mean [0.13 SD] NPSLE: 0.30 mean [0.09 SD] HC: 0.31 mean [0.09 SD] p = 0.04 (NPSLE) and 0.02 (HC)
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M right insular NAA/Cr ratio: SLE: 1.12 mean [0.17 SD] NPSLE: 0.98 mean [0.12 SD] HC: 1.12 mean [0.078 SD] p = 0.002 (SLE & HC)
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M high neurobiologic involvement NAA/Cr ratios = 0.98 mean [0.04 SD] no neurobiologic involvement NAA/Cr ratios = 1.10 mean [0.17 SD] NAA/Cr was significantly negatively correlated with the SLEDAI score (r= -0.45; p = 0.005)
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M NPSLE patients have decreased NAA/Cr in the insular region indicating: neuronal injury/loss and demyelination Therefore, NAA may be an helpful biomarker for the diagnosis of NPSLE.
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M Bernatsky S, Clarke A, Gladman DD, Et al. Mortality related to cerebrovasscualr disease in systemic lupus erythematosus. Lupus 2006;15:835-9. Harel L, Snadborg C, Lee T, von Scheven E. Neuropsychiatric manifestiation in pediatric systemic lupus erythematosus: Attribution and clinical significance. J Rheumatol. 2004; 31:2156-62 Hanley JG, Urowitz MB, Sanchez-Guerrero J. et al. Neuropsychiatric evens at the time of diagnosis of systemic lupus ertheymatosus: An international inception cohort study. Arthritis and Rheumatism 2007;56:265-73. Hanly JG. Neuropsychiatric lupus. Curr Rheumatol Rep. 2001; 3:205-212. Hanly JG. Walsh NM, Sangalang V. Brain pathology in systemic lupus erythematosus. J Rheumatol. 1992; 19:732-41. Jimenez S, Cervera R, Font J, Ingelmo M. The epidemiology of systemic lupus erythematosis. Clin Rev Allergy Immunology 2003; 25:3-12 Kovacs J, Urowitz M, Gladman D. Dilemmas in neuropsychiatric lupus. Rheum Dis Clin North Am 1993; 19:795-819 Rivest C, Lew RA, Welsing PM et al. Association between clinical factors, socioeconomic status, and organ damage in recent onset systemic lupus erythematosus. J Rheumatol. 2000; 27:680-4 Shimojima Y, Matsuda M, GonoT et al relationship between clinical factors and neuropsychiatric manifestations in sytemic lupus erythematosus. Clin Rheumatol. 2005; 24:469-75. Sibbitt WL Jr, Sibbitt RR, Brooks WM. Neuroimaging in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 1999; 42:2026-38
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M We do not know… theories include: damage from anti-phospholipid antibody microangiopathy atherosclerosis intrathecal production of proinflammatory cytokines
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M
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M Active SLE sx NAA/Cr ratio = 0.99 mean [0.15 SD] No SLE sx NAA/Cr ratio = 1.12 mean [0.15 SD] p = 0.01
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