Association of global brain damage and clinical functioning in neuropsychiatric systemic lupus erythematosus

Abstract

Objective. To investigate the relationship between quantitative estimates of global brain damage based on magnetization transfer imaging (MTI) and cerebral functioning, as measured by neurologic, psychiatric, and cognitive assessments, as well as disease duration in patients with a history of neuropsychiatric systemic lupus erythematosus (NPSLE).Methods. In patients with systemic lupus erythematosus (SLE), neurologic, psychiatric, and psychological symptoms often occur. The frequency of nervous system involvement has been reported to range from 11% to 60% (1). Infection, drug side effects, hypertension, or metabolic derangements, as well as an intrinsic brain manifestation of SLE (i.e., neuropsychiatric SLE [NPSLE]), can cause such symptoms. The uncertain pathogenesis and the wide variety of manifestations of NPSLE complicate the development of a uniform diagnostic decision-making protocol and a uniform method of monitoring a patient with this type of SLE. Findings of routine brain imaging studies are often unremarkable in patients with NPSLE, or the studies reveal abnormalities, such as cerebral atrophy and white matter hyperintensities (on magnetic resonance imaging [MRI]), that can also be found in SLE patients without neuropsychiatric symptoms. Furthermore, no correlation has thus far been demonstrated between quantitative measures of such nonspecific abnormalities and measures of brain function (2-5).Recently, magnetization transfer ratio (MTR) histogram analysis, a quantitative MRI technique based on magnetization transfer imaging (MTI), was applied in patients with primary NPSLE but without abnormalities on MRI that could account for the clinical picture. With this technique, cerebral abnormalities were identified in these patients (6,7). Such abnormalities were found in SLE patients who had had episodes of neuropsychiatric symptoms in the past (chronic NPSLE) as well as in patients who were experiencing an active phase of neuropsychiatric symptoms (active NPSLE) (6,7). The

Selective gray matter damage in neuropsychiatric lupus

“…Patients were included only if MRI revealed no abnormalities that could possibly explain a history of NP symptoms. Patient characteristics, specific NP manifestations, and abnormalities on conventional MRI are described in a previous report on the same patient group (6).…”

“…Conventional T1-weighted spin-echo, fluid-attenuated inversion recovery and dual (proton density and T2-weighted) images (6) were acquired in all patients and interpreted by an experienced neuroradiologist (MAvB). For MTI, a 3-dimensional gradientecho pulse sequence with an echo time/repetition time of 6/106 msec and a flip angle of 12°was chosen, resulting in proton density contrast in the absence of MT saturation pulses (6). A 256 ϫ 256 matrix with 50% acquisition and 220-mm field of view was used for 28 contiguous 5-mm slices.…”

“…From these MTR maps, histograms were generated and the corresponding peak location (PL), peak height (PH), and mean MTR were derived for GM and WM separately. Since the PH is dependent on both lesion load and the physiologic variation in volumes of the different compartments, a volume correction was performed by dividing the number of voxels for each MTR value by the total number of voxels for that tissue type (6). Univariate analyses and multivariate linear regression analyses with age as an additional covariate were performed to test for significant differences in GM and WM MTR parameters between healthy controls and NPSLE patients.…”

“…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 on the role of neuronal damage (7).…”

Detection of change in CNS involvement in neuropsychiatric SLE: A magnetization transfer study

“…MTR histograms, normalized for tissue volume, were generated for the whole brain and for normal-appearing brain tissue. From these MTR histograms the peak height was calculated (12,16,17). The peak height of these histograms was used as a measure of cerebral lesion load (17).…”