Neurological involvement in Sjögren's disease was infrequent (5.0%), with PNS involvement clustering with vasculitic and B-cell-driven features and worse outcomes, whereas CNS manifestations showed a distinct demographic profile characterised by younger age and male sex.
The overall prevalence of neurological involvement in Sjögren's disease was 5.0% in this large Portuguese registry cohort.
Patients with neurological manifestations had higher disease activity, more vasculitic features, and higher mortality compared to those without neurological involvement.
Cryoglobulinaemia and higher baseline ESSDAI (excluding neurological domains) were independently associated with overall neurological involvement.
PNS involvement was independently associated with older age at symptom onset, cryoglobulinaemia, lymphopenia, and higher ESSDAI.
CNS involvement was independently associated with male sex and younger age at diagnosis.
PNS and CNS neurological involvement in Sjögren's disease appear to represent pathophysiologically and demographically distinct entities.
The study population consisted of 1234 Sjögren's disease patients from a multicentre Portuguese registry (PORTRESS).
This research suggests that neurological complications in Sjögren's disease—an autoimmune condition that primarily causes dry eyes and dry mouth—are relatively uncommon, affecting about 1 in 20 patients (5%) in this large Portuguese patient registry of over 1,200 people. The most common type was peripheral nervous system (PNS) involvement, affecting nerves outside the brain and spinal cord (3.7%), while central nervous system (CNS) involvement affecting the brain and spinal cord was rarer (1.4%). Patients who developed any neurological complication tended to have more active disease overall, a higher rate of a blood abnormality called cryoglobulinaemia, more skin vasculitis (inflammation of blood vessels), and unfortunately higher mortality rates. The study also found that PNS and CNS neurological involvement appear to be quite different from each other. PNS complications were linked to immune system features suggesting blood vessel inflammation and overactive B-cells (a type of immune cell), including cryoglobulinaemia, low complement protein C4, skin vasculitis, and low lymphocyte counts. In contrast, CNS complications were more likely in men and in patients diagnosed at a younger age, without the same inflammatory blood markers. This suggests the two types may arise through different biological mechanisms. This research is important because it suggests that doctors caring for Sjögren's disease patients should evaluate peripheral and central neurological complications separately, as they have different risk profiles and potentially different underlying causes. The findings could help identify which patients need closer neurological monitoring. However, because the number of cases—especially CNS cases—was small, the authors caution that these results are exploratory and need to be confirmed in larger studies before firm clinical conclusions can be drawn.
Pereira da Costa R, Bandeira M, Silvério-António M, Lopes A, Cunha-Santos F, Pereira P, et al.. (2026). NeuroPORTRESS: prevalence, clinical spectrum, and factors associated with neurological involvement in Sjögren's disease.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1791369