Objective: Evaluate the relationship between baseline iron levels in the subthalamic nucleus (STN) and their impact on motor function and dopaminergic medication needs after deep brain stimulation (DBS).

Background: DBS is an effective treatment option for Parkinson’s disease (PD). It improves motor symptoms and decreases the need for dopaminergic medication in PD patients. However, the degree of motor improvement and the reduction in medication dosage after DBS varies among individuals. The iron content in the deep grey nuclei, including the STN, may reflect the pathophysiological changes associated with PD and could be related to outcomes of DBS.

Method: Ten DBS candidates with PD consented pre-DBS. Preoperative MRI (T1-weighted [T1w], T2-weighted [T2w, and multi-gradient-echo) was obtained 2 to 4 weeks before DBS. During the screening visit, assessments included the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and the levodopa equivalent dosage (LEED) calculation. These evaluations were repeated 6 months after DBS surgery. An atlas-based segmentation technique, followed by manual correction, was employed to extract STN regions from T1w and T2w images. The iron content in the STN was measured using quantitative susceptibility values obtained through the MEDI-0 approach. Regression analyses were performed to evaluate whether STN iron content could predict motor improvement and LEED reduction.

Results: We included six participants (target: 4 STN, 2 GPi) with pre- and post-DBS clinical outcome data for preliminary analysis. At baseline, a higher iron content in the STN was associated with improved motor function (r = 0.87, p = 0.024, uncorrected) and a decrease in levodopa equivalent dosage (r = 0.88, p = 0.020, uncorrected).

Conclusion: The findings indicate that iron content in the STN may be a valuable imaging biomarker for predicting motor outcomes and dosage reductions following DBS. The observed positive correlation between STN iron content and improved clinical response suggests that this iron content may represent the functional reserve capacity for neuromodulation. These preliminary findings warrant validation in a larger cohort to establish STN iron content as a clinically useful predictor of DBS efficacy.

References: 1. Brown G, Du G, Farace E, Lewis MM, Eslinger PJ, McInerney J, Kong L, Li R, Huang X, De Jesus S. Subcortical Iron Accumulation Pattern May Predict Neuropsychological Outcomes After Subthalamic Nucleus Deep Brain Stimulation: A Pilot Study. J Parkinsons Dis. 2022;12(3):851-863. doi: 10.3233/JPD-212833. PMID: 34974437; PMCID: PMC9181238.

2. Zhao W, Yang C, Tong R, Chen L, Chen M, Gillen KM, Li G, Ma C, Wang Y, Wu X, Li J. Relationship Between Iron Distribution in Deep Gray Matter Nuclei Measured by Quantitative Susceptibility Mapping and Motor Outcome After Deep Brain Stimulation in Patients With Parkinson’s Disease. J Magn Reson Imaging. 2023 Aug;58(2):581-590. doi: 10.1002/jmri.28574. Epub 2023 Jan 3. PMID: 36594513.

3. Huang W, Ogbuji R, Zhou L, Guo L, Wang Y, Kopell BH. Motoric impairment versus iron deposition gradient in the subthalamic nucleus in Parkinson’s disease. J Neurosurg. 2020 Aug 7;135(1):284-290. doi: 10.3171/2020.5.JNS201163. PMID: 32764171.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/stn-iron-content-correlates-with-dbs-efficacy-in-parkinsons-patients-a-preliminary-study/