Clinical features and high-risk indicators of central nervous system involvement in primary Sjögren's syndrome

Evidence for central nervous system involvement in primary Sjögren's syndrome (pSS) patients is controversial and extremely limited. We aimed to describe the clinical profiles and high-risk indicators of primary Sjögren's syndrome (pSS) patients with central nervous system (CNS) involvement (pSS-CNS).

A total of 412 participants with pSS from a hospital in China from January 2012 to December 2019 were enrolled in the retrospective study. 42 pSS-CNS patients were compared with 370 pSS patients without CNS involvement. The clinical features, laboratory examinations, imaging characteristics, and treatment of the pSS-CNS cases were systematically analyzed. Potential risk factors related to pSS-CNS patients were identified by multivariate logistic regression analysis.

The prevalence of central nervous system involvement in the studied pSS patients was 10.2% (42/412), with 31.3% (14/42) of pSS patients having neurological manifestations as the initial symptom. The manifestations of hemiparesis (35.7%, 15/42), paraparesis (28.6%, 12/42), dysphonia (31.0%, 13/42), blurred vision (21.4%, 9/42), and dysfunctional proprioception (23.8%, 10/42) were more common in the pSS-CNS patients. Cerebral infarction (57.1%, 24/42), demyelination (31.0%, 13/42), myelitis (23.8%, 11/42), and angiostenosis (21.4%, 9/42) were most often found on MRI or CT scan imaging in the pSS-CNS patients. Intrathecal IgG level and total protein of cerebrospinal fluid were increased in 50% (8/16) of the pSS-CNS group. In comparison with patients without CNS involvement, the pSS-CNS patients were found to also have kidney and lung involvement, hematologic abnormalities, positive ANA and anti-SSA antibody tests, and reduced complement 3 (C3) and complement 4 (C4) levels (all p < 0.05). The prevalence of lung involvement, immune thrombocytopenia, and high-titer ANA (1:1000) were significantly higher in pSS-CNS disease activity compared to those in the moderately active group. Multivariate analysis identified lung involvement, anti-SSA positivity, and low C3 levels as prognostic factors for pSS-CNS. After high-dose glucocorticoids and immunosuppressive therapy, 60.5% (26/38) of pSS-CNS patients improved, 36.8% (14/38) were unresponsive to treatment, and 2.6% (1/38) died.

Clinical features are diverse in pSS-CNS patients, and the morbidity rate is low. CNS involvement was the initial presentation in state percentage here pSS patients. Pulmonary involvement, a positive anti-SSA antibody test, and reduced C3 levels are potential risk factors for CNS involvement in pSS. Treatment with high-dose glucocorticoids and immunosuppressive therapy appeared effective in 60% of pSS-CNS patients. Key Points • The CNS manifestations of pSS are diverse, and CNS imaging and CSF analysis are important for the diagnosis. • Pulmonary involvement, positive anti-SSA, and reduced C3 levels are potential risk factors of pSS-CNS. • About 60% of pSS-CNS patients were responsive to high-dose glucocorticoid administration and immunosuppressive therapy.