A Scoping Review and Meta-Analysis of Proportions of Central Nervous System Manifestations Reported in Patients with...

The objective of this scoping review was to synthesize evidence on the proportion of individuals living with Sjögren's disease who experience central nervous system (CNS) manifestations.

We searched MEDLINE (via PubMed) and Embase from 1980 through January 29, 2026, and the ECRI Guidelines Trust from 2020 through January 29, 2026. Title and abstract screening, followed by full-text review, were performed in duplicate using prespecified inclusion and exclusion criteria. One reviewer extracted data, with an independent audit completed by one of the project coleads. Meta-analyses of proportions were conducted. Sensitivity analyses were planned a priori to evaluate the influence of statistical outliers.

We identified 22,857 citations, of which 108 met the inclusion criteria. Pooled proportion estimates were generated for 23 CNS manifestations. Several manifestations occurred at frequencies exceeding those reported in the general population, including depression, migraine, insomnia, cognitive dysfunction, psychosis, movement disorders, aseptic meningoencephalitis, neuromyelitis optica spectrum disorder, optic neuritis, multiple sclerosis, cerebral vasculitis, cerebellar syndrome, spinal cord involvement, and non-localizing somatosensory complaints. The degree of increased frequency differed substantially across manifestations, and several estimates were highly influenced by individual studies, as indicated by sensitivity analyses.

The spectrum of CNS involvement in Sjögren's disease is broad and heterogeneous. Attributing CNS manifestations to direct Sjögren's disease involvement or coexisting conditions remains unclear and cannot be assumed to be causally linked. Our findings underscore the complexity of CNS manifestations in Sjögren's disease and highlight the need for evidence-informed guidance to support accurate diagnosis, attribution, and management of neurologic manifestations.