A MR spectroscopy study P. Wang, R. Harris, P. Cagnoli, D. Frechtling, D. Bekris, S. Gebarski, J. McCune, and P. Sundgren

University of Michigan (US) & Lund University (Sweden)

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

M  headache  stroke or stroke like symptoms  psychosis  seizures  cognitive dysfunction

M white matter changes

M Copied with permission from Appenzeller et al. Arthritis Rheum Sep 52 (9): cerebral and corpus callosum atrophy

M  gross and microinfarcts  cortical atrophy  hemorrhage  demyelination

M  confirm diagnosis of lupus  careful history and physical exam  targeted workup for symptoms

M largely uncontrolled trials and anecdotal experiences  immunosuppressive tx  anticoagulation/antiplatelet tx

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

M  use MR spectroscopy to investigate whether differences in metabolic ratios exist between patients with:  NPSLE  SLE  healthy controls

M  20 SLE patients with no neurological sx  18 F: 2 M (ages ; mean 40.7)  20 SLE patients with neurological sx  20 F (ages ; mean 41.5)  20 healthy controls  17 F: 3M (ages ; mean 40.7)

M clinical workup including:  laboratory testing  SLE Disease Activity Index score (SLEDAI)  mini-mental status examination  fatigue, depression, and pain questionnaire

M  3T MRI of the brain, which was evaluated for:  signal abnormalities  hemorrhage  ischemic events  focal lesions  atrophy

frontal white matter right insula occipital gray matter SVS (single-voxel spectroscopy) MR PRESS TR 2000 ms TE 30 ms 2x2x2 cm voxel size

M Cho Cr NAA

M Healthy Controls SLE NPSLE NAA Cho Cr Cho Cr NAA

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)

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 = (SLE & HC)

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)

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.

M  Bernatsky S, Clarke A, Gladman DD, Et al. Mortality related to cerebrovasscualr disease in systemic lupus erythematosus. Lupus 2006;15:  Harel L, Snadborg C, Lee T, von Scheven E. Neuropsychiatric manifestiation in pediatric systemic lupus erythematosus: Attribution and clinical significance. J Rheumatol. 2004; 31:  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:  Hanly JG. Neuropsychiatric lupus. Curr Rheumatol Rep. 2001; 3:  Hanly JG. Walsh NM, Sangalang V. Brain pathology in systemic lupus erythematosus. J Rheumatol. 1992; 19:  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:  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:  Sibbitt WL Jr, Sibbitt RR, Brooks WM. Neuroimaging in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 1999; 42:

M We do not know… theories include:  damage from anti-phospholipid antibody  microangiopathy  atherosclerosis  intrathecal production of proinflammatory cytokines

M

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