Sensitivity of quantitative (1)H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus

Abstract

Objective: To quantify N-acetylaspartate (NAA), total creatines (tCr), total cholines (tCho), and myo-inositol (mI) levels in normal and abnormal appearing white matter of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in order to determine the specific changes in metabolite concentrations.

Methods: Axial proton density and T(2) weighted magnetic resonance images, and short echo time (TE 30 ms) (1)H spectra were acquired with a GE SIGNA 1.5 T magnetic resonance system. Concentrations of NAA, tCr, tCho, and mI were determined, using brain tissue water as a reference, from nine patients (seven female, mean age 40.3 years, range 16-65) with NPSLE and eight healthy women (mean age 43 years, range 31-65).

Results: A significant rise of tCho (12.4%, p<0.05) and mI (31.4%, p<0.005) and a significant reduction in NAA (-12%, p<0.05) was found in normal appearing white matter compared with controls. Analysis according to severity of the clinical NPSLE features (subgrouped as major or minor) showed that SLE major had reduced NAA compared with SLE minor (-18.4%, p<0.05) and controls (-20%, p<0.005). The SLE major group showed a significant rise of mI (32%, p<0.01) and the SLE minor group a significant increase in tCho (18.6%, p<0.05) compared with controls. Longitudinal analysis of brain metabolites in normal appearing white matter showed consistent abnormalities in NAA, tCho, and mI in a patient with stable clinical features and a constant rise of tCho, but transient rise of mI was seen during a flare of disease in another patient.

Conclusion: Quantitative (1)H magnetic resonance spectroscopy (MRS) suggests a particular course of neurometabolite changes that precedes irreversible reductions in NAA and permanent neuronal loss. Initially, in patients with SLE minor, there is a significant rise in tCho and a trend (reversible) for mI also to be raised. In patients with SLE major the NAA is significantly and permanently reduced and mI is significantly raised, whereas the tCho levels are near normal. Further investigations are needed to determine how specific MRS is as a clinical marker for brain disturbance in SLE.

Figure 1

T₂ weighted image showing several small foci of increased signal intensity in the white matter of both cerebral hemispheres. The largest of these is indicated by an arrow. The box represents a voxel from which ¹H spectra were obtained.

Figure 2

Magnetic resonance spectra from patient 6 at months 1 (A) and 18 (B) showing raised levels of tCho and mI at month 18 in comparison with month 1. (Note: the spectral changes observed above 4 ppm are not significant because this region of the spectrum is distorted by the techniques of water suppression and removal of residual water during data processing.)

Figure 3

Relation between N-acetylaspartate (NAA) and myo-inositol (mI) levels in patients with major and minor features of neuropsychiatric systemic lupus erythematosus and normal subjects.

Figure 4

Longitudinal analysis of brain metabolites from patient No 6. This patient developed a flare of disease between months 6 and 27. During this time myo-inositol (mI) levels became significantly abnormal and reduced to baseline after treatment with a course of intravenous immunoglobulin. NAA = N-acetylaspartate; Cr = creatines; Cho = cholines.