Yan Fang, Cheng Yanwei, Feng Shuman
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
Sleep Med. 2025 Jul 17;134:106694. doi: 10.1016/j.sleep.2025.106694.
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.
不宁腿综合征（RLS）是一种常见的神经系统疾病，其特征是无法控制的腿部移动冲动，这常常扰乱睡眠并损害生活质量。尽管神经炎症和神经退行性变过程与之相关，但血清胶质纤维酸性蛋白（GFAP）、脑源性神经营养因子（BDNF）和神经丝轻链（NfL）在未经治疗的RLS中的作用仍不清楚。
在这项病例对照研究中，纳入了108例未经治疗的RLS患者和90例年龄及性别匹配的健康对照。使用酶联免疫吸附测定（ELISA）对血清GFAP、BDNF和NfL水平进行定量。分别使用国际不宁腿综合征研究组评分量表（IRLS）和RLS生活质量问卷（QoL-RLS）评估症状严重程度和生活质量。进行多变量逻辑回归以评估生物标志物与疾病风险的关联。此外，进行了受试者工作特征（ROC）曲线分析，以评估血清GFAP、BDNF和NfL水平在区分RLS患者与对照方面的鉴别能力。计算曲线下面积（AUC）、敏感性和特异性以评估诊断性能。
与对照组相比，RLS患者的血清GFAP水平显著更高（148.27±32.53对96.44±27.81 pg/mL，p<0.001），NfL水平也显著更高（15.35±4.82对9.78±3.59 pg/mL，p<0.001），而BDNF水平更低（18.71±5.69对23.95±6.12 pg/mL，p=0.002）。多变量分析证实这些标志物是RLS的独立预测因子（GFAP：OR=1.592，BDNF：OR=0.372，NfL：OR=1.953，均p<0.01）。NfL与IRLS（β=0.531，p=0.012）和QoL-RLS评分均呈正相关（β=0.356，p=0.007），而GFAP与生活质量受损相关（β=0.724，p<0.001），BDNF与症状严重程度呈负相关（β=-0.287，p=0.003）。ROC分析显示GFAP（AUC=0.919）、NfL（AUC=0.856）和BDNF（AUC=0.797）具有较强的鉴别能力。
血清GFAP、BDNF和NfL与RLS的存在和严重程度独立相关，突出了它们作为神经胶质和轴突功能障碍外周生物标志物的潜力。这些发现提供了机制性见解，并支持它们在RLS诊断和监测中的实用性，可能作为神经生物学参与的外周指标，并在未来与疾病监测或治疗反应相关的研究中具有潜在用途。
