Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, often presenting with neuropsychiatric manifestations. Reports on the frequency and patterns of these manifestations vary substantially and remain incompletely understood. We examined neuropsychiatric manifestations in the prospective nationwide cohort of Swiss SLE (SSCS) patients and conducted a systematic literature review to contextualise our findings.

Methods We reviewed all patients included in the SSCS from 2007–2019 and classified severe neuropsychiatric manifestations. Searches were performed in relevant electronic databases from 1.1999–1.2020 and by checking reference lists of the pertinent literature. Authors of important papers were contacted to obtain further (unpublished) studies. We included prospective or cross-sectional studies focussing on neuropsychiatric manifestations in SLE, defined according the ACR criteria of 1999. Study selection and data extraction was made in duplicate. We secured salient study characteristics, composition of cohorts, the definitions and the frequencies of neuropsychiatric manifestations. We assessed heterogeneity across reports and investigated sources of variation using meta-regression models.

Results The frequencies of severe manifestations found in the SSLE were 7.1% (49/688) for cerebrovascular events, 5.3% (37/688) for seizures and 6.5% (45/688) for psychosis. The time-to-event analysis showed a linear relationship between duration of SLE and cumulative incidence of severe neuropsychiatric manifestations. Searches identified 530 studies and authors’ contact yielded another unpublished report. We included 28 studies. The mean rates of the most commonly reported severe neuropsychiatric manifestations ranged in the magnitude of 50 percent points. Study characteristics and composition of cohorts could not explain heterogeneity of reported manifestation rates.

Conclusions The spectrum of neuropsychiatric manifestations in SLE is widely dispersed. The diagnostic work-up and the reporting of manifestations varied substantially across studies which may explain inconsistencies to some extent. We call for concerted efforts and a broad consensus regarding stringent definitions of neuropsychiatric SLE manifestations that allow targeted detection, particularly with view to timely intervention and patient outcomes.