Association between serum GFAP, BDNF and NfL levels and clinical symptoms in restless legs syndrome: a case-control...

Restless legs syndrome (RLS) is a prevalent neurological condition marked by an uncontrollable urge to move the legs, which often disrupts sleep and impairs quality of life. Although neuroinflammatory and neurodegenerative processes have been implicated, the roles of serum glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and neurofilament light chain (NfL) in treatment-naïve RLS remain unclear.

In this case-control study, 108 treatment-naïve RLS patients and 90 age- and sex-matched healthy controls were enrolled. Serum levels of GFAP, BDNF, and NfL were quantified using enzyme-linked immunosorbent assays (ELISA). Symptom severity and quality of life were assessed using the International Restless Legs Syndrome Study Group Rating Scale (IRLS) and the RLS Quality of Life Questionnaire (QoL-RLS), respectively. Multivariate logistic regression was conducted to evaluate biomarker associations with disease risk. In addition, receiver operating characteristic (ROC) curve analyses were conducted to assess the discriminative ability of serum GFAP, BDNF, and NfL levels in differentiating RLS patients from controls. The area under the curve (AUC), sensitivity, and specificity were calculated to evaluate diagnostic performance.

Compared to controls, RLS patients had significantly higher serum levels of GFAP (148.27 ± 32.53 vs. 96.44 ± 27.81 pg/mL, p < 0.001) and NfL (15.35 ± 4.82 vs. 9.78 ± 3.59 pg/mL, p < 0.001), and lower levels of BDNF (18.71 ± 5.69 vs. 23.95 ± 6.12 pg/mL, p = 0.002). Multivariate analyses confirmed these markers as independent predictors of RLS (GFAP: OR = 1.592, BDNF: OR = 0.372, NfL: OR = 1.953, all p < 0.01). NfL was positively correlated with both IRLS (β = 0.531, p = 0.012) and QoL-RLS scores (β = 0.356, p = 0.007), while GFAP was associated with QoL impairment (β = 0.724, p < 0.001), and BDNF showed a negative association with symptom severity (β = -0.287, p = 0.003). ROC analyses showed strong discriminative power for GFAP (AUC = 0.919), NfL (AUC = 0.856), and BDNF (AUC = 0.797).

Serum GFAP, BDNF, and NfL are independently associated with RLS presence and severity, highlighting their potential as peripheral biomarkers of neuroglial and axonal dysfunction. These findings provide mechanistic insight and support their utility in the diagnosis and monitoring of RLS and may serve as peripheral indicators of neurobiological involvement and could have potential utility in future research related to disease monitoring or treatment response.