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)
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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
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worse prognosis
increased morbidity and mortality
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headache
stroke or stroke like symptoms
psychosis
seizures
cognitive dysfunction
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white matter changes
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cerebral and corpus callosum atrophy
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Copied with permission from Appenzeller et al. Arthritis Rheum. 2005 Sep 52 (9):2783-9.
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gross and microinfarcts
cortical atrophy
hemorrhage
demyelination
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confirm diagnosis of lupus
careful history and physical exam
targeted workup for symptoms
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largely uncontrolled trials and anecdotal
experiences
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immunosuppressive tx
anticoagulation/antiplatelet tx
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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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use MR spectroscopy to investigate whether
differences in metabolic ratios exist between
patients with:
 NPSLE
 SLE
 healthy controls
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20 SLE patients with no neurological sx
 18 F: 2 M (ages 21.0-61.0; mean 40.7)
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20 SLE patients with neurological sx
 20 F (ages 25.2-67.3; mean 41.5)
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20 healthy controls
 17 F: 3M (ages 18.8-61.0; mean 40.7)
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clinical workup including:
 laboratory testing
 SLE Disease Activity Index score (SLEDAI)
 mini-mental status examination
 fatigue, depression, and pain questionnaire
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3T MRI of the brain, which was evaluated for:
 signal abnormalities
 hemorrhage
 ischemic events
 focal lesions
 atrophy
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SVS (single-voxel spectroscopy) MR
PRESS
TR 2000 ms
TE 30 ms
2x2x2 cm voxel size
frontal white matter
right insula
occipital gray matter
NAA
Cr
Cho
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NAA
Cho
Cr
NAA
Cho
Cr
Healthy Controls
NAA
Cho
Cho Cr
NAA
SLE
Cr
NPSLE
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frontal white matter Cho/Cr ratio:
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SLE: 0.22 mean [0.13 SD]
NPSLE: 0.30 mean [0.09 SD]
HC: 0.31 mean [0.09 SD]
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p = 0.04 (NPSLE) and 0.02 (HC)
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right insular NAA/Cr ratio:
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SLE: 1.12 mean [0.17 SD]
NPSLE: 0.98 mean [0.12 SD]
HC: 1.12 mean [0.078 SD]
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p = 0.002 (SLE & HC)
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high neurobiologic involvement
 NAA/Cr ratios = 0.98 mean [0.04 SD]
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no neurobiologic involvement
 NAA/Cr ratios = 1.10 mean [0.17 SD]
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NAA/Cr was significantly negatively
correlated with the SLEDAI score (r= -0.45; p
= 0.005)
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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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We do not know… theories include:
 damage from anti-phospholipid antibody
 microangiopathy
 atherosclerosis
 intrathecal production of proinflammatory
cytokines
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Active SLE sx
 NAA/Cr ratio = 0.99 mean [0.15 SD]
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No SLE sx
 NAA/Cr ratio = 1.12 mean [0.15 SD]
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p = 0.01
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