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N- Acetylaspertate (NAA) as a biomarker for disease in neuropsychiatric lupus (NPSLE) patients

A MR spectroscopy study. N- Acetylaspertate (NAA) as a biomarker for disease in neuropsychiatric lupus (NPSLE) patients. P. Wang, R. Harris, P. Cagnoli, D. Frechtling, D. Bekris, S. Gebarski, J. McCune, and P. Sundgren . University of Michigan (US) & Lund University (Sweden).

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N- Acetylaspertate (NAA) as a biomarker for disease in neuropsychiatric lupus (NPSLE) patients

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  1. A MR spectroscopy study N-Acetylaspertate (NAA) as a biomarker for disease in neuropsychiatric lupus (NPSLE) patients P. Wang, R. Harris, P. Cagnoli, D. Frechtling, D. Bekris, S. Gebarski, J. McCune, and P. Sundgren

  2. University of Michigan (US) & Lund University(Sweden) no disclosures

  3. introduction • 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

  4. NPSLE presents clinically with: • headache • stroke or stroke like symptoms • psychosis • seizures • cognitive dysfunction

  5. NPSLE presents anatomically with: white matter changes

  6. NPSLE presents anatomically with: cerebral and corpus callosum atrophy Copied with permission from Appenzeller et al. Arthritis Rheum. 2005 Sep 52 (9):2783-9.

  7. NPSLE histopathologic features • gross and microinfarcts • cortical atrophy • hemorrhage • demyelination

  8. NPSLE diagnosis • confirm diagnosis of lupus • careful history and physical exam • targeted workup for symptoms

  9. NPSLE treatment largely uncontrolled trials and anecdotal experiences • immunosuppressive tx • anticoagulation/antiplatelettx

  10. who cares? • 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

  11. aim • use MR spectroscopy to investigate whether differences in metabolic ratios exist between patients with: • NPSLE • SLE • healthy controls

  12. methods • 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)

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

  14. methods • 3T MRI of the brain, which was evaluated for: • signal abnormalities • hemorrhage • ischemic events • focal lesions • atrophy

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

  16. LC model NAA Cr Cho

  17. results NAA Cho Cr NAA Cr Cho Healthy Controls NAA Cho Cr NAA Cho SLE Cr NPSLE

  18. results – frontal white matter 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)

  19. results – right insula 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)

  20. results – SLEDAI scores • 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)

  21. conclusion 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.

  22. Thank you

  23. Referenences • 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

  24. why do pts develop NPSLE? We do not know… theories include: • damage from anti-phospholipid antibody • microangiopathy • atherosclerosis • intrathecal production of proinflammatory cytokines

  25. results – active SLE symptoms • 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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