Sjögren’s syndrome with and without neurological involvement

Abstract

Objective Neurological manifestations of Sjögren’s syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of primary Sjögren’s syndrome and find clinical features allowing sufficient identification of affected patients (pSSN) among those with Sjögren’s syndrome without neurological involvement (pSS). Methods Para-/clinical features of patients with primary Sjögren’s syndrome (2016 ACR/EULAR classification criteria) were compared between pSSN and pSS. At our university-based center, patients with suggestive neurological symptoms undergo screening for Sjögren’s syndrome, and newly diagnosed pSS patients are thoroughly evaluated for neurologic involvement. pSSN disease activity was rated by the Neurological Involvement of Sjögren’s Syndrome Disease Activity Score (NISSDAI). Results 512 patients treated for pSS/pSSN at our site between 04/2018 and 07/2022 were included (238 pSSN patients [46%] vs. 274 pSS patients [54%], cross-sectional design). Independent predictors of neurological involvement in Sjögren’s syndrome were male sex [p < 0.001], older age at disease onset [p < 0.0001], hospitalization at first presentation [p < 0.001], lower IgG levels [p = 0.04] and higher eosinophil values (treatment-naïve) [p = 0.02]. Univariate regression additionally showed older age at diagnosis [p < 0.001], lower prevalence of rheumatoid factor [p = 0.001], SSA(Ro)/SSB(La) antibodies [p = 0.03; p < 0.001], higher white blood cell count [p = 0.02] and CK levels [p = 0.02] (treatment-naïve) in pSSN. Interpretation Patients with pSSN had different clinical characteristics than patients with pSS and represented a large proportion of the cohort. Our data suggest that neurological involvement in Sjögren’s syndrome has been underestimated. Intensified screening for neurologic involvement should be included in the diagnostic algorithm for Sjögren’s syndrome, especially in males of older age and with severe disease course requiring hospitalization.

Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing

“…Furthermore, the therapeutic effects of immunosuppressants on SjS-associated neuropathies are limited in some cases [35]. These findings suggest that neuropathies, at least in part, result from a genetic predisposition rather than secondary injury to glandular autoimmunity [31,33]. One of the putative etiologies underlying the hypothesis of shared genetic…”

“…An increasing number of studies have shown that neurological involvement in SjS has been previously underestimated or under-diagnosed [31][32][33]. More recently, Seeliger et al demonstrated that nearly half of patients with SjS suffered from neurological involvement, including muscular, central, and peripheral nervous system, and this subset of patients have a different clinical phenotype from that of patients without neurological involvement [31]. These findings support our hypothesis that a subset of SjS and neuropathies share a similar genetic predisposition and suggest that a specific phenotype could be shaped by this underlying genetic predisposition.…”

Sjogren's syndrome: a neurological perspective

“…3 Furthermore, patients with SS and neurologic involvement may present with different clinical features and prognoses when compared with patients with SS without neurologic involvement. 2,4 This review aims to describe and highlight the main neurological manifestations of SS, its treatment, and prognosis.…”

“…A wide spectrum of clinical manifestations with multi-systemic involvement, including the nervous system, has been described. 2 Notably, SS could affect both the peripheral and central nervous system (CNS) with variable prevalence and clinical manifestations. 3 Furthermore, patients with SS and neurologic involvement may present with different clinical features and prognoses when compared with patients with SS without neurologic involvement.…”

“…3 Furthermore, patients with SS and neurologic involvement may present with different clinical features and prognoses when compared with patients with SS without neurologic involvement. 2 4…”