NeuroPORTRESS: prevalence, clinical spectrum, and factors associated with neurological involvement in Sjögren’s disease

Objectives Neurological involvement is a heterogeneous complication of Sjögren’s disease (SjD). We aimed to describe its prevalence and spectrum, and identify factors associated with peripheral (PNS) and central nervous system (CNS) involvement. Methods We conducted a cross-sectional, multicentre study based on PORTRESS, the Portuguese SjD registry. Demographic and clinical data were compared between groups. Independent associations of overall neurological, PNS, and CNS involvement were identified through logistic regression models using complete-case analysis. Results Among 1234 patients, 62 (5.0%) had neurological involvement: 46 (3.7%) PNS, 17 (1.4%) CNS, with one patient having both. Patients with neurological manifestations had higher ESSDAI, more cryoglobulinaemia, purpura/cutaneous vasculitis and monoclonal gammopathy, and higher mortality. Cryoglobulinaemia and higher baseline ESSDAI (excluding neurological domains) were independently associated with neurological involvement. PNS involvement was associated with older age at symptom onset, cryoglobulinaemia, lymphopenia and higher ESSDAI. A sensitivity analysis revealed low C4, persistent salivary gland swelling and purpura/cutaneous vasculitis also as independently associated with PNS involvement. CNS involvement was associated with male sex and younger age at diagnosis. Conclusion Neurological involvement in SjD was infrequent. PNS involvement clustered with vasculitic and B-cell-driven features and worse outcomes, whereas CNS manifestations appeared to show a distinct demographic profile, characterised by younger age and male sex. These findings support separate evaluation of PNS and CNS involvement and may help identify patients requiring neurological surveillance. Given the limited number of cases, particularly of CNS involvement, these findings remain exploratory and require confirmation in larger cohorts.