Study Of The Relationship Between Clinical Characteristics And Brain Iron Content In Patients With Restless Legs Syndrome

Objective:To analyze the correlation between brain iron and clinical features such as disease severity,polysomnographic parameters and peripheral iron metabolism parameters in patients with Restless Legs Syndrome(RLS)using Quantitative Susceptibility Mapping(QSM),and to investigate the feasibility of using QSM to diagnose RLS.Methods:Patients who were first diagnosed with RLS at the outpatient clinic of the Department of Neurology,our hospital from July 2021 to November 2022 were recruited,42 patients were screened according to the inclusion and exclusion criteria,and 30 cases were finally included as the RLS patient group,and patients with scores of 1-20 on the International Restless Legs Syndrome Study Group severity scale(IRLS)were included as the mild to moderate RLS patient group,and patients with scores of 21-40 were included as the severe-very severe RLS patients.15 sex-and age-matched healthy controls were also recruited from the Physical Examination Centre of our hospital.General clinical information was collected from all patients,and the severity of all patients was assessed by applying the International Restless Legs Severity Scale and polysomnography.All subjects underwent blood routine tests and iron metabolism including iron,ferritin and total iron binding capacity.MRI sequences including TIWI,T2 WI,FLAIR,DWI+ADC and QSM were performed on all subjects.QSM data were post-processed using meditoobox software on the Matlab platform to obtain QSM maps,and ITK-SNAP software was used to obtain the susceptibility values of the region of interest(ROI),including bilateral red nucleus,substantia nigra,putamen,globus pallidus,caudate nucleus and dentate nucleus.All data obtained were statistically calculated with SPSS 27.0.Results:1.The mean susceptibility values of each ROI were significantly lower in RLS patients than in healthy controls,and the susceptibility value of the dentate nucleus was significantly lower in RLS patients than in healthy controls(P=0.004)).2.When comparing the susceptibility values of each ROI among mild to moderate RLS patients group,severe to very severe RLS patients group and healthy controls,differences were found in the susceptibility values of the dentate nucleus(P=0.008)and substantia nigra(P=0.001).Further pairwise comparisons showed that severe to very severe RLS patients had a lower susceptibility values of the substantia nigra than mild to moderate RLS patients(P<0.001)and healthy controls(P=0.006);mild to moderate RLS patients(P=0.046)and severe to very severe RLS patients(P=0.002)had a significantly reduced susceptibility values of the dentate nucleus compared to healthy controls.3.Correlation analysis of arousal index,sleep efficiency,sleep latency,wake time after sleep onset and susceptibility values of each ROI in RLS patients showed that periodical limb movement index was negatively correlated with susceptibility values of the dentate nucleus(rs=-0.551,P=0.010)and the substantia nigra(rs=-0.490,P=0.024);wake time after sleep onset was negatively correlated with susceptibility values of the putamen(rs=-0.447,P=0.025),but no significant correlation was found for the other factors.4.Correlations between susceptibility values of each ROI and indicators of peripheral iron metabolism were performed.Positive correlations were found between serum ferritin and susceptibility values of the dentate nucleus(rs=0.434,P=0.019),red nucleus(rs=0.498,P=0.006)and caudate nucleus(rs=0.455,P=0.013).There was a negative correlation between total iron binding capacity and susceptibility values of the dentate nucleus(r=-0.462,P=0.012)and red nucleus(r=-0.494,P=0.006),while no significant correlation was found between serum iron and transferrin saturation and susceptibility values of the ROIs.5.ROC curve analysis of the sensitivity values in each ROI was done using clinical confirmation of RLS as a positive status variable,and the area under the curve of the dentate nuclei was 0.795,whereas P = 0.002,95% CI was 0.652 to 0.939.The cut point of the dentate nuclei sensitivity values was 106.7364 ppm,at which point the sensitivity was 71.40% and the specificity was 86.70%,the Youden’s index was 0.581.Conclusion:1.Dentate nucleus iron levels were significantly reduced in RLS patients compared to healthy controls.2.Compared with mild to moderate RLS patients and healthy controls,iron levels in the substantia nigra were significantly lower in severe to very severe RLS patients.3.The lower the dentate nucleus or substantia nigra iron content of RLS patients,the higher the periodical limb movement index;the lower the putamen iron content,the longer the wake time after sleep onset.4.Peripheral iron metabolism in RLS patients may reflect their brain iron content to some extent.5.Using QSM to detect iron levels of the dentate nucleus has some diagnostic value for RLS.The sensitivity is 71.40% and the specificity is 86.70%.