Transcranial Sonographic Characteristics of Substantia Nigra in End-Stage Renal Disease Patients with Restless Legs Syndrome - A Diagnostic Marker Study

Sep 30, 2026

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Restless legs syndrome (RLS) is a frequent neurological complication in end-stage renal disease (ESRD). This study evaluates transcranial sonography (TCS) characteristics of the substantia nigra (SN) and brainstem raphe (BR) in ESRD patients with and without RLS, and tests whether SN echogenicity can serve as a diagnostic marker for ESRD-related RLS. Among 65 ESRD participants and 30 matched controls, bilateral SN echogenic area and BR semiquantitative echogenicity were assessed, and ROC analysis determined the optimal SN echogenic area cutoff.

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Article Transcranial Sonographic Characteristics of Substantia Nigra in End-Stage Renal Disease Patients with Restless Legs Syndrome: A Diagnostic Marker Study Caishan Wang 1, Zhoubing Zhan 2, Changwei Ding 1, Yingchun Zhang 1 and Weifeng Luo 3, * Academic Editor: Kenji Tsuji Received: 17 November 2025 Revised: 14 December 2025 Accepted: 20 December 2025 Published: 22 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; [wcs9422@suda.edu.cn](wcs9422@suda.edu.cn) (C.W.); [dd15755386072@163.com](dd15755386072@163.com) (C.D.); [richer777@126.com](richer777@126.com) (Y.Z.) 2 Department of Nephrology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; [zhanzhoubing@foxmail.com](zhanzhoubing@foxmail.com) 3 Department of Neurology and Clinical Research Centre of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China * Correspondence: [lwfwxx@126.com](lwfwxx@126.com) Abstract Objective: Restless legs syndrome (RLS) is a highly prevalent neurological complication in end-stage renal disease (ESRD) patients. This study aimed to explore the transcranial sonography (TCS) characteristics of the substantia nigra (SN) and brainstem raphe (BR) in ESRD patients with and without RLS and to evaluate the diagnostic value of SN echogenicity for ESRD-related RLS. Methods: A total of 65 ESRD patients (45 with RLS [ESRD + RLS] and 20 without RLS [ESRD − RLS]) from the dialysis center and 30 age-and gender-matched healthy controls (NC) from the health management center were enrolled between January 2017 and December 2022 . All participants underwent TCS to measure the bilateral SN echogenic area, and the total SN echogenic area (SNsA) was calculated. BR echogenicity was assessed using a semiquantitative scale. Receiver operating characteristic (ROC) curves were plotted to determine the optimal SNsA cutoff for diagnosing ESRD + RLS. Results: The SNsA in the ESRD + RLS group [0.15 (0.13–0.22) cm2 ] was significantly smaller than that in the ESRD − RLS group [0.27 (0.23–0.31) cm2 ] and the NC group [0.27 (0.22–0.30) cm2 ](both p < 0.001) . ROC curve analysis showed that SNsA had the highest diagnostic efficacy for ESRD + RLS, with an area under the curve (AUROC) of 0.823 (95% confidence interval [CI]: 0.722–0.924) . At a cutoff of 0.22 cm2, SNsA yielded a sensitivity of 85.0%, specificity of 73.3%, accuracy of 76.92%, positive predictive value (PPV) of 58.6%, and negative predictive value (NPV) of 91.7% . The prevalence of BR hypoechogenicity was significantly higher in ESRD + RLS (33.33%) and ESRD − RLS (35.00%) groups than in the NC group (10.00%) (both p < 0.05), but no difference was observed between the two ESRD subgroups (p > 0.05) . No significant differences in third ventricle (TV) width or bilateral middle cerebral artery peak systolic velocity (MCA-PSV) were found among the three groups (all p > 0.05) . Conclusions: ESRD + RLS patients exhibit significant SN hypoechogenicity compared with ESRD − RLS patients and healthy controls. SNsA with a cutoff of 0.22 cm2 serves as a reliable imaging biomarker for diagnosing ESRD + RLS, and TCS is a valuable noninvasive tool to assist clinical decision-making in this population. Keywords: end-stage renal disease; transcranial sonography; restless legs syndrome; substantia nigra; diagnostic marker 1. Introduction Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an irresistible urge to move the lower limbs, often accompanied by uncomfortable paresthesias [1] . Clinically, RLS is classified into primary (idiopathic) and secondary subtypes, with ESRD-related RLS (ESRD + RLS) being one of the most common second

FAQs

What was the main objective of the study?

To explore TCS characteristics of the substantia nigra and brainstem raphe in ESRD patients with and without RLS, and to evaluate the diagnostic value of substantia nigra echogenicity for ESRD-related RLS.

How were the participants grouped and how many were included?

The study enrolled 65 ESRD patients (45 with RLS and 20 without RLS) and 30 age- and gender-matched healthy controls.

What did ROC analysis show for diagnosing ESRD + RLS?

The total substantia nigra echogenic area (SNsA) showed the highest diagnostic efficacy, with an AUROC of 0.823. At a cutoff of 0.22 cm², sensitivity was 85.0% and specificity was 73.3%.

Sep 30, 2026

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