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

## TL;DR

This study finds that transcranial sonography can detect brain changes in kidney disease patients with restless legs syndrome, offering a noninvasive diagnostic tool.

## Contribution

The study identifies SN echogenic area as a novel noninvasive biomarker for diagnosing RLS in ESRD patients using transcranial sonography.

## Key findings

- ESRD patients with RLS had significantly smaller substantia nigra echogenic areas compared to those without RLS and healthy controls.
- A SN echogenic area cutoff of 0.22 cm² achieved high sensitivity and specificity for diagnosing ESRD + RLS.
- Brainstem raphe hypoechogenicity was more common in ESRD patients than in healthy controls but not different between ESRD subgroups.

## 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.