Hippocampal Atrophy in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations

Wen

et al. 2021

Genes

Neuropsychiatric manifestations of systemic lupus erythematosus (SLE), specifically cognitive dysfunction and mood disorders, are widely prevalent in SLE patients, and yet poorly understood. TNF-like weak inducer of apoptosis (TWEAK) has previously been implicated in the pathogenesis of neuropsychiatric lupus (NPSLE), and we have recently shown its effects on the transcriptome of the cortex of the lupus-prone mice model MRL/lpr. As the hippocampus is thought to be an important focus of NPSLE processes, we explored the TWEAK-induced transcriptional changes that occur in the hippocampus, and isolated several genes (Dnajc28, Syne2, transthyretin) and pathways (PI3K-AKT, as well as chemokine-signaling and neurotransmission pathways) that are most differentially affected by TWEAK activation. While the functional roles of these genes and pathways within NPSLE need to be further investigated, an interesting link between neuroinflammation and neurodegeneration appears to emerge, which may prove to be a promising novel direction in NPSLE research.

Section: Phenotype-dependent Cortex-hippocampus Synchronous Expression Of Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model

Wen

et al. 2021

Genes

“…These volumetric differences are consistent with previously reported findings from individual studies and indicate both white matter and gray matter involvement. [26, 29, 33] When comparing patients with NPSLE to controls there was no significant difference in total gray matter volume.…”

Section: Discussionmentioning

confidence: 92%

A meta-analysis of structural MRI studies of the brain in systemic lupus erythematosus (SLE)

Cox

Groot

Cole

et al. 2022

Preprint

ObjectiveA comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases – Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Ulcerative Colitis (UC) with the intention of performing a meta-analysis of published data. Due to lack of data in RA and UC the reported meta-analysis was limited to SLE.MethodsThe MEDLINE database was searched for studies from 1988 through March 2022. A total of 175 papers met the initial inclusion criteria and 16 were included in a random effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions.ResultsA significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum and total gray matter volume measurements as compared to age and sex matched controls. There were not enough studies to perform a meta-analysis for RA and UC; instead we include a summary of published volumetric studies.ConclusionsThe meta-analyses revealed structural brain abnormalities in patients with SLE suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvement in SLE and suggest there may be both localised and global reductions in brain volume.KEY MESSAGESWhat’s already known on this topicCentral nervous system effects of lupus are common, however, agreement on principally affected neuroanatomical regions is lacking.What this study addsThis study combines the volumetric neuroimaging data from previously published SLE literature in a meta-analysis. The hippocampus, corpus callosum and total gray matter volume in patients with SLE is smaller than in age and sex matched controls. Additionally, a summary of published data in RA and UC is provided.How this study might affect research, practice or policyThis is the first meta-analysis on neuroimaging studies of volume differences in SLE. The regions identified can inform further research on disease progression and therapy evaluation targeted at brain volumetric changes in SLE.These results provide specific regions of interest to further explore in the central treatment and management of SLE. While these regions are shown to be directly affected, additional brain regions may be implicated. Further research to understand the potential link between these volumetric measurements and behavioural/cognitive changes observed in patients with lupus is warranted.

“…Some observational studies have found an association between brain MRI abnormalities in NPSLE and low serum levels of C3 and C4 [ 14 - 15 ]. Liu et al explored the effect of brain atrophy on NPSLE and found a relationship between hippocampal atrophy and the development of neuropsychiatric manifestations and lupus-related organ damage [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Association Between Hypocomplementemia (C3 and C4) and MRI Findings in Different Neuropsychiatric Lupus Syndromes in a Tertiary Hospital

Bawazir

Bahlas

Jali

et al. 2021

Cureus

Objective The aim of this study was to describe the magnetic resonance imaging (MRI) findings and correlate them with the complements level. Methodology This is a retrospective chart review study involving 187 lupus patients attending the rheumatology clinic during the period between 2010 and 2020. Out of the 187 patients, only 49 patients were diagnosed to have neuropsychiatric lupus manifestation and underwent MRI study. Results We included 49 neuropsychiatric systemic lupus erythematosus patients with a mean age of 35.33 years; most of them were Saudi (51%), with disease duration between -six and nine years (40.8%). In regard to MRI brain findings, 51% had abnormal findings, most commonly white matter changes in 42.9% followed by contrast enhancement in 36.7% and mild volume loss in 16.3%. Regarding the complement level, 21 (42.9%) patients had a low C3 level and 35 (71.4%) had a low C4 level. Lastly, following the main objective, C3 and C4 do not have a statistically significant relationship with white matter lesion given the sample of this data (p = 0.589 and p = 0.657, respectively). Conclusion MRI provides a significant clinical information to evaluate neuropsychiatric lupus manifestations. These clinical data can be correlated with immunological findings, which can help in the early diagnosis and management of this disease.