Systemic lupus erythematosus (SLE) is an auto-immune disease characterized by multi-organ involvement. Although uncommon, central nervous system involvement in SLE, termed neuropsychiatric SLE ... Show moreSystemic lupus erythematosus (SLE) is an auto-immune disease characterized by multi-organ involvement. Although uncommon, central nervous system involvement in SLE, termed neuropsychiatric SLE (NPSLE), is not an exception. Current knowledge on underlying pathogenic mechanisms is incomplete, however, neuroinflammation is thought to play a critical role. Evidence from neurodegenerative diseases and multiple sclerosis suggests that neuroinflammation is correlated with brain iron accumulation, making quantitative susceptibility mapping (QSM) a potential hallmark for neuroinflammation in vivo. This study assessed susceptibility values of the thalamus and basal ganglia in (NP)SLE patients and further investigated the in vivo findings with histological analyses of postmortem brain tissue derived from SLE patients. We used a 3T MRI scanner to acquire single-echo T2*-weighted images of 44 SLE patients and 20 age-matched healthy controls. Of the 44 patients with SLE, all had neuropsychiatric complaints, of which 29 were classified as non-NPSLE and 15 as NPSLE (seven as inflammatory NPSLE and eight as ischemic NPSLE). Mean susceptibility values of the thalamus, caudate nucleus, putamen, and globus pallidus were calculated. Formalin-fixed paraffin-embedded post-mortem brain tissue including the putamen and globus pallidus of three additional SLE patients was obtained and stained for iron, microglia and astrocytes. Susceptibility values of SLE patients and age-matched controls showed that iron levels in the thalamus and basal ganglia were not changed due to the disease. No subgroup of SLE showed higher susceptibility values. No correlation was found with disease activity or damage due to SLE. Histological examination of the post-mortem brain showed no increased iron accumulation. Our results suggest that neuroinflammation in NPSLE does not necessarily go hand in hand with iron accumulation, and that the inflammatory pathomechanism in SLE may differ from the one observed in neurodegenerative diseases and in multiple sclerosis. Show less
Introduction: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic... Show moreIntroduction: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE).Methods: A systematic search on PubMed was conducted. English studies with full text availability that investigated the correlation between blood-brain barrier (BBB) dysfunction, intrathecal synthesis of antibodies, antibodies, cytokines, chemokines, metalloproteinases, complement and psychiatric NPSLE manifestations in adults were included.Results: Both transient BBB-dysfunction with consequent access of antibodies to the cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies could occur in psychiatric NPSLE. Anti-phospholipid antibodies, anti-NMDA antibodies and anti-ribosomal protein p antibodies seem to mediate concentration dependent neuronal dysfunction. Interferon-a may induce microglial engulfment of neurons, direct neuronal damage and production of cytokines and chemokines in psychiatric NPSLE. Several cytokines, chemokines and matrix metalloproteinase-9 may contribute to the pathophysiology of psychiatric NPSLE by attracting and activating Th1-cells and B-cells.Discussion: This potential pathophysiology may help understand NPSLE and may have implications for the diagnostic management and therapy of psychiatric NPSLE. However, the presented pathophysiological model is based on correlations between potential immunologic etiologies and psychiatric NPSLE that remain questionable. More research on this topic is necessary to further elucidate the pathophysiology of NPSLE. Show less
Magro Checa, C.; Beaart-van de Voorde, L.J.J.; Middelkoop, H.A.M.; Dane, M.L.; Wee, N.J. van der; Buchem, M.A. van; ... ; Steup-Beekman, G.M. 2017
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a rheumatologic disorder causing neurologic, psychiatric and/or psychologic symptoms. The most important clinical problems are the aspecific... Show moreNeuropsychiatric systemic lupus erythematosus (NPSLE) is a rheumatologic disorder causing neurologic, psychiatric and/or psychologic symptoms. The most important clinical problems are the aspecific nature of signs and symptoms, the limited knowledge on pathogenesis and the absence of a diagnostic gold standard. Magnetic resonance imaging (MRI) is considered the most important imaging modality of the brain in NPSLE patients. Abnormalities visible on conventional MRI appear anywhere in the brain, and may normalize, stabilize or increase with loss of brain parenchyma. Apart from conventional MRI sequences, in this thesis advanced MRI techniques such as magnetization transfer imaging (MTI) were also applied, which are more sensitive to microscopic brain damage invisible to the human eye. Microscopic brain damage in NPSLE appears mostly in the cortical gray matter and is associated with the presence of anticardiolipin antibodies. The final brain damage, as observed using different MRI techniques, consists of neuronal and axonal damage, atrophy, demyelination and gliosis. Changes in the total amount of microscopic brain damage as detected by MTI correlate with changes in clinical status. This thesis contributes to the knowledge on the pathogenesis of NPSLE, and illustrates that advanced and conventional radiological techniques can be helpful in making diagnostic and therapeutic decisions. Show less
