Changes in White Matter Microstructure Suggest an Inflammatory Origin of Neuropsychiatric Systemic Lupus Erythematosus

Abstract

Objective. To assess white matter (WM) and gray matter (GM) magnetization transfer ratio histogram peak heights (MTR-HPHs) in different subsets of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) who have unremarkable findings on 3T magnetic resonance imaging of the brain and to evaluate whether these values could be used to highlight different clinically suspected underlying pathogenic processes or identify the clinical NPSLE status or whether they could be associated with a specific NPSLE syndrome.Methods. Sixty-four SLE patients with neuropsychiatric symptoms were included. The initial NPSLE diagnosis and suspected underlying pathogenic process were established by multidisciplinary evaluation. The final diagnosis was made after also considering the disease course 6-18 months later. Thirty-three patients with central nervous system (CNS) NPSLE and 31 SLE patients with neuropsychiatric symptoms unrelated to SLE (non-SLE-related NP) were included. Twenty SLE patients without neuropsychiatric symptoms and 36 healthy control subjects were included for comparison. Differences in the WM and GM mean MTR-HPHs and between the different NPSLE subgroups (CNS NPSLE diagnosis, NPSLE phenotype [inflammatory or ischemic], and clinical changes after treatment) and the relationship to NPSLE syndromes were evaluated.Results. Patients with inflammatory NPSLE had significantly lower WM MTR-HPHs than did the healthy controls, the SLE patients, and the non-SLErelated NP patients. Cognitive disorder, mood disorder, and psychosis were related to lower WM MTR-HPH values and cerebrovascular symptoms to higher values. Furthermore, the mean MTR-HPHs in the WM increased when the clinical status of the NPSLE patients improved.Conclusion. Measurement of MTR-HPH of the WM has the potential to identify inflammatory NPSLE with CNS involvement. This finding underscores the usefulness of this technique for the detection of cerebral changes in NPSLE patients and for the assessment of clinical changes after treatment.

Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions

“…A decrease in bound molecules (e.g., due to demyelination) or an increase in unbound molecules (e.g., due to edema) can diminish the energy transfer or MTR. Decreased whole‐brain MTR, even in the absence of other structural MRI changes, has been reported in SLE . It is reversible and most likely reflects parenchymal edema .…”

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort

“…Evaluations included in the multidisciplinary assessment and MRI-scanning protocol are described elsewhere. 2,16 The multidisciplinary team met every two weeks to discuss the patients and evaluate the complementary assessments. The following aspects were taken into account: (a) objective confirmation of symptoms assessed to standard of care of the appropriate medical specialty; (b) attribution to SLE or other aetiology.…”

Laboratory and Neuroimaging Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: Where Do We Stand, Where To Go?

“…They are, however, sensitive to diffuse, global effects, and successive studies have shown the sensitivity of MTR histograms to a variety of disease related clinical factors (69–73), including to the presence of specific antibodies. It was recently shown that white matter MTR histogram peak heights (HPH) were significantly lower in inflammatory NP-SLE patients than in NP-SLE patients diagnosed as ischemic, as well as than SLE patients with no NP complaints and healthy controls (74). The mechanism by which the MTR is decreased in NP-SLE is not clear, but its reversibility upon successful treatment suggests intracellular edema and gliosis as the associated pathomechanisms (75).…”