Reduced Insular Glutamine and N-Acetylaspartate in Systemic Lupus Erythematosus

Abstract

Rationale and Objectives To investigate for differences in metabolic concentrations and ratios between patients with systemic lupus erythematosus (SLE) without (group SLE) and those with neurological symptoms (group NPSLE) compared to a healthy control (group HC) in three normal-appearing brain regions: the frontal white matter, right insula (RI), and occipital gray matter and whether changes in any of the metabolites or metabolic ratios are correlated to disease activity and other clinical parameters. Materials and Methods Twenty patients with SLE (18 women and 2 men, age range 23.4–64.6 years, mean age 43.9 years), 23 NPSLE patients (23 women, age range 23.7–69.8 years, mean age 42.4 years), and 21 HC (19 women and 2 men, age range 21.0–65.7 years, mean age 43.4 years) were included. All subjects had conventional brain magnetic resonance imaging and 1H single-voxel spectroscopy, clinical assessment, and laboratory testing. Results NPSLE patients had significantly reduced N-acetylaspartate (NAA)/creatine compared to HC (P = .02) and SLE patients (P = .01) in the RI. Lower glutamine/creatine levels were also detected in RI in both patient groups and in frontal white matter in NPSLE patients compared to HC (P = .01, P = .02). NAA/Cr ratio in the RI was significantly negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (r = −0.41; P = .008), and patients with active SLE symptoms also had a trend toward lower NAA/creatine ratios (1.02 vs 1.12; P = .07). Conclusions The present data support previous findings of abnormal metabolic changes in normal-appearing regions in the brain of both SLE and NPSLE patients and raise the possibility that especially NAA, glutamine, and glutamate may be additional biomarkers for cerebral disease activity in SLE patients as these early metabolic changes occur in the brain of SLE patients before neurologic and imaging manifestations become apparent.

A neurometabolite study of chronic daily headache in patients with systemic lupus erythematosus using magnetic resonance spectroscopy: comparison with fibromyalgia patients and healthy controls

“…First, the test was conducted only in two areas locally: BG and PWM. In other SLE studies, a number of areas such as periventricular, occipital, and frontal regions of white matter as well as the insular area were studied [4,11,16,17]. It has been reported that there was no difference in metabolites in the white matter regions between normal subjects and FMS patients and the NAA level in the hippocampus was reduced according to the 1 H-MRS studies [18-20].…”

Serum neuron specific enolase – a novel indicator for neuropsychiatric systemic lupus erythematosus?

“…29 Cagnoli and coworkers also demonstrated decreased brain metabolism in NPSLE patients and, to a lesser extent, in non-NPSLE individuals, and these authors also showed a specific decline of brain metabolism in the right insula region that was proportional to the activity of SLE. 30 Our study has several limitations, which must be taken into account in the interpretation of our results. Most importantly, some rare NPSLE manifestations were not represented in our sample, or they included too few patients to enable comparative analyses.…”

Advanced and Conventional Magnetic Resonance Imaging in Neuropsychiatric Lupus

“…Glutamate, a non-essential amino acid, is the most important excitatory neurotransmitter, and prolonged neuron excitation by glutamate can be toxic to neurons. NAA and glutamine-glutamate changes were demonstrated in normal-appearing brain in SLE patients, before neurologic and imaging manifestations became apparent, which suggests that these markers might predict the early cerebral involvement of SLE 85 . Lower NAA ratios were also reported in both SLE and NPSLE patients 63 , and increased myo-inositol, a marker of gliosis, was suggested as a marker of poor prognosis in NPSLE 86 .…”