Selective gray matter damage in neuropsychiatric lupus

Abstract

Objective. Damage of brain parenchyma in patients with primary diffuse neuropsychiatric systemic lupus erythematosus (NPSLE) has been indicated by magnetization transfer imaging (MTI). However, the location of MTI abnormalities is unknown. This study was undertaken to assess the distribution of MTI abnormalities over gray matter (GM) and white matter (WM) in SLE patients with a history of NP symptoms without explanatory magnetic resonance imaging (MRI) evidence of focal disease.Methods. MTI was performed in 24 female SLE patients with a history of diffuse NP symptoms and 24 healthy female controls. Magnetization transfer ratio (MTR) maps were calculated for GM and WM separately, and GM and WM MTR histograms were generated. Univariate and multivariate analyses with age as an additional covariate were performed on the histogram parameters peak location (PL), peak height (PH), and mean MTR.Results. Compared with controls, significantly reduced PH (mean ؎ SD 136 ؎ 22 arbitrary units versus 151 ؎ 13 arbitrary units) and mean MTR (33.3 ؎ 1.0 percent units versus 33.6 ؎ 0.5 percent units) were found in the GM of NPSLE patients (P ‫؍‬ 0.002 and P ‫؍‬ 0.033, respectively, in multivariate analyses). No significant differences were observed for WM MTR parameters.Conclusion. This is the first study to demonstrate, using MTI, that in SLE patients with a history of NP symptoms and without explanatory focal abnormalities on MRI, the GM is particularly affected. These findings support the hypothesis that neuronal injury may underlie central nervous system manifestations in NPSLE.Up to 75% of patients with systemic lupus erythematosus (SLE) experience neuropsychiatric symptoms indicative of central nervous system (CNS) involvement. In primary neuropsychiatric SLE (NPSLE), these NP manifestations are attributed to the SLE disease process itself, rather than to secondary factors such as infections or metabolic disorders (1). Focal neurologic NP syndromes are often associated with antiphospholipid antibodies; however, the cause of diffuse neurologic and psychiatric symptoms is largely unknown (2). Findings of conventional magnetic resonance imaging (MRI) of the brain are frequently unremarkable, and abnormalities are nonspecific (3,4). However, quantitative MRI techniques, such as magnetization transfer imaging (MTI), diffusion-weighted imaging, and MR spectroscopy (MRS), are now being assessed for their diagnostic value (4).Using MTI, a quantitative MRI technique that is sensitive to both macroscopic and microscopic CNS damage (4), abnormalities that had been invisible by conventional MRI were demonstrated in the brain parenchyma of NPSLE patients (5). Significant associations with parameters of neurologic, psychiatric, and neuropsychological function demonstrated the clinical relevance of these findings (6). Although the underlying pathogenesis of diffuse brain damage in NPSLE is largely unknown, recent findings of neuronal and astrocytic degradation products in the cerebrospinal fluid (CSF) of SLE patients have focused attention...

Cortical damage in brains of patients with adult-form of myotonic dystrophy type 1 and no or minimal MRI abnormalities

“…Low MTr indicates a reduced capacity of the protons in the brain tissue matrix to exchange magnetization with the surrounding water protons, which seems to be strongly associated with the degree of tissue (matrix) damage [17,30]. Several recent studies have demonstrated marked MTr reductions in lesional and normalappearing tissues of a number of neurological disorders [5,20,21,30,36]. As these reductions have been interpreted as the expression of subtle microscopic pathology possibly occurring in both myelin and axons [32], the low cortical-MTr found in our patients is likely to reflect a diffuse underlying structural pathology occurring in the cortex of DM1 brains.…”

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

“…Autoantibodies in the CSF and immunocompetent cells in the choroid plexus of mice (Sakic et al, 2000b;Vogelweid et al, 1991) and the NP-SLE patient are further evidence that the blood-brain barrier in SLE becomes permeable to circulating factors (Abbott et al, 2003). Previous clinical studies had engendered the hypothesis that various brain-reactive antibodies (Denburg et al, 1993), cytokines, and toxic metabolites (Svenungsson et al, 2001;Trysberg et al, 2000) play principal roles in induction of SLEinduced brain damage in general, and gray matter in particular (Steens et al, 2004). With respect to the origin of autoantibodies, one of the important issues is whether they passively diffuse through the damaged blood-brain barrier or are synthesized intrathecally (i.e., within the brain).…”

Sources of variation in multi-centre brain MTR histogram studies: body-coil transmission eliminates inter-centre differences

“…For given subjects, the volume of each segmented compartment (in ml) is a convenient way of comparing segmentation methods. The segmentation method crucially affects the peak height estimate, which can be a sensitive measure of clinical status [10] (see Fig. 8).…”

“…The histogram is just a frequency distribution showing how many voxels there are at each value of a tissue parameter; it is usually normalised so that the total area under the curve is fixed (this reduces the effect of differing brain sizes). Extremely small changes can be detected, for example between different subgroups in multiple sclerosis (MS) [7,8] and systemic lupus erythematosus [9,10], and in serial studies of MS [11][12][13][14][15][16].…”