Localization of cerebral functional deficits in patients with non‐neuropsychiatric systemic lupus erythematosus

Abstract

Neuropsychiatric systemic lupus erythematosus (NP-SLE) is a common complication of systemic lupus erythematosus (SLE), and clinical interventions are of only limited efficacy despite relatively high prevalence. Such complications have been studied extensively, but the pathoetiology of NP-SLE has not yet been elucidated. Diagnosis of NP-SLE focuses primarily on psychological manifestations, and the underlying mechanisms leading to neuropsychiatric complications remain unknown. To address potential changes in brain function before NP-SLE development, we used resting-state functional magnetic resonance imaging (MRI) to compare regional brain activity in SLE patients versus matched controls. We report that regional activity in cerebellum and in areas of the default mode network are attenuated in patients with SLE, and moreover individual alterations in cerebellar activity correlated positively with the disease activity index. These findings provide direct evidence that significant alteration of brain function, resembling that observed in patients with NP-SLE, is already present in SLE patients without neuropsychiatric complications, highlighting the need for early evaluation and intervention in SLE patients. Furthermore, the disease activity rating correlated with regional functional alterations in the cerebellum, suggesting that the cerebellum could play a role in the pathogenesis of NP-SLE.

Alterations of white matter structural networks in patients with non-neuropsychiatric systemic lupus erythematosus identified by probabilistic tractography and connectivity-based analyses

“…Thus, the altered structural connectivity in these subnetwork components can confer a particular risk of dysfunction. As expected, Lin et al demonstrated that the ReHo values of several DMN regions were significantly altered in non-NPSLE patients (Lin et al, 2011). The decreased and increased probabilistic connections among the identified subnetworks in the current study might be the structural foundation of the ReHo alterations.…”

Altered functional neuronal activity in neuropsychiatric lupus: A systematic review of the fMRI investigations

“…Lin et al (15) reported a significant attenuation of regional brain activity in the bilateral Mackay et al (14) indicated lack of correlation between regional brain activation patterns by fMRI in SLE patients stratified by disease duration and SDI. Such findings suggest that SDI is not a surrogate marker of neurologic damage in SLE.…”

“…Disease activity and SLE damage index were obtained using SLE disease activity index (SLEDAI) (23), and systemic lupus international collaborating clinic damage index (SDI) (24) respectively. Disease activity was assessed in relation to functional alteration of different regions of the brain in three studies (13,15,20); whereas disease activity was stable in most of the other studies.…”

“…A summary of the studies (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) is depicted in Table 1. The largest original study contained 31 participants with SLE, whilst the smallest included 9 patients.…”

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus

“…This may imply that these patients are recruiting brain areas within the DMN during cognitive tasks to try to maintain cognitive performance. 15,[41][42][43] These three forms of compensatory mechanisms (increased BOLD response in task-related regions, recruitment of additional regions to maintain task performance and decreased task-switching from default mode) are seen in other diseases as well as in the few SLE fMRI papers. It may be that the findings from other diseases, where fMRI is a wellestablished method of investigation, can help to direct future fMRI research in SLE.…”