Grey Matter Volume Changes Following VIM-MRgFUS in Tremor-Dominant Parkinson’s Disease
Poster No:
58
Submission Type:
Abstract Submission
Authors:
Jonas Krauss1, Neeraj Upadhyay2, Vernonika Purrer1, Valeri Borger2, Hannah Weiland2, Marcel Daamen2, Angelika Maurer2, Carsten Schmeel2, Alexander Radbruch2, Wüllner Ullrich2, Henning Boecker3
Institutions:
1University Hospital Bonn, Bonn, Nordrhein-Westfahlen, 2University Hospital Bonn, Bonn, NRW, 3Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, NRW
First Author:
Co-Author(s):
Henning Boecker
Department of Diagnostic and Interventional Radiology, University Hospital Bonn
Bonn, NRW
Department of Diagnostic and Interventional Radiology, University Hospital Bonn
Bonn, NRW
Introduction:
Parkinson's Disease (PD) is one of the most common neurodegenerative disorders in the aging population. Tremor, particularly resting tremor, is a hallmark feature of PD, alongside bradykinesia and rigidity, and it often has the most severe impact on patients' quality of life and autonomy (Weiss et al., 2021; Heusinkveld et al., 2018). A significant number of patients fail to achieve adequate symptom control due to intolerable side effects or "wearing-off" phenomena associated with pharmacotherapy.
Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a novel treatment option for patients with tremor-dominant PD who are unresponsive to medication or ineligible for Deep Brain Stimulation (DBS). While the optimal ablation target remains a topic of debate-with the subthalamic nucleus, pallidothalamic tract, and globus pallidus all showing potential for tremor alleviation-thermoablation of the ventral intermediate nucleus (VIM) of the thalamus is currently the most widely performed MRgFUS procedure in PD (Schlesinger et al., 2017).
Despite the demonstrated clinical efficacy of MRgFUS, the underlying mechanisms driving tremor improvement remain poorly understood. Although limited work exists on structural changes in white matter following VIM ablation (e.g. Lin et al., 2021), Grey Matter Volume (GMV) changes were not yet investigated with a adequate sample size. Widespread GMV changes have been observed in essential tremor following VIM-MRgFUS (Krauß et al., 2024) and in other studies have been associated with tremor reduction (Tuleasca et al., 2017). Investigating adaptive processes in grey matter following VIM-MRgFUS in PD could provide crucial insights into the mechanisms of tremor improvement and the neuroplastic changes that accompany this intervention.
Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a novel treatment option for patients with tremor-dominant PD who are unresponsive to medication or ineligible for Deep Brain Stimulation (DBS). While the optimal ablation target remains a topic of debate-with the subthalamic nucleus, pallidothalamic tract, and globus pallidus all showing potential for tremor alleviation-thermoablation of the ventral intermediate nucleus (VIM) of the thalamus is currently the most widely performed MRgFUS procedure in PD (Schlesinger et al., 2017).
Despite the demonstrated clinical efficacy of MRgFUS, the underlying mechanisms driving tremor improvement remain poorly understood. Although limited work exists on structural changes in white matter following VIM ablation (e.g. Lin et al., 2021), Grey Matter Volume (GMV) changes were not yet investigated with a adequate sample size. Widespread GMV changes have been observed in essential tremor following VIM-MRgFUS (Krauß et al., 2024) and in other studies have been associated with tremor reduction (Tuleasca et al., 2017). Investigating adaptive processes in grey matter following VIM-MRgFUS in PD could provide crucial insights into the mechanisms of tremor improvement and the neuroplastic changes that accompany this intervention.
Methods:
Twenty-two patients (21m, 1f) underwent unilateral VIM-MRgFUS. Voxel-based morphometry (VBM) was applied to investigate GMV changes over a time span of 6 months in the whole brain. Clinical tremor assessments (FTM, UPDRS-III) were conducted at baseline and 6 months post treatment. Voxel-wise comparisons of segmented GMVs extracted from the T1w images were compared at whole-brain level with pairwise t-tests. The clusters were obtained at voxel-wise p<0.001 and further corrected for multiple comparisons using cluster-level family-wise-error correction (p<0.05 FWEc) according to Gaussian Random Field theory.
Results:
Clinically, tremor on the contralesional (treated) side significantly decreased by 52.2 % at 6 months following MRgFUS. In addition to local GMV decline in the thalamus, VBM revealed remote GMV decreases in the ipsilesional insula, anterior cingulate cortex (ACC) and the supplementary motor area (SMA) as well as the contralesional superior dorsolateral frontal gyrus (see Figure 1). No significant GMV increases were found.
·GMV decline 6-month post VIM-MRgFUS
Conclusions:
Our findings indicate that unilateral VIM-MRgFUS leads to structural changes beyond the targeted thalamic region. The insula, ACC, SMA as well as frontal areas exhibit structural connections to the ventrally located thalamic nuclei situated within or adjacent to the lesion center (Craig, 2014; Bertino et al., 2021; Barbas et al., 2014). Given those connections, structural losses likely reflect Wallerian degeneration of thalamic output neurons. This interpretation aligns with similar findings reported in VIM-MRgFUS-treated cohorts with Essential Tremor (Krauß et al., 2024).
Brain Stimulation:
Sonic/Ultrasound 1
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
Movement Disorder
STRUCTURAL MRI
Thalamus
ULTRASOUND
Other - MRgFUS
1|2Indicates the priority used for review
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Provide references using APA citation style.
Bertino, S., Basile, G. A., Bramanti, A., Ciurleo, R., Tisano, A., Anastasi, G. P., Milardi, D. & Cacciola, A. (2021). Ventral intermediate nucleus structural connectivity-derived segmentation: anatomical reliability and variability. NeuroImage, 243, 118519. https://doi.org/10.1016/j.neuroimage.2021.118519
Craig, A. (2013). Topographically organized projection to posterior insular cortex from the posterior portion of the ventral medial nucleus in the long‐tailed macaque monkey. The Journal Of Comparative Neurology, 522(1), 36–63. https://doi.org/10.1002/cne.23425
Heusinkveld, L. E., Hacker, M. L., Turchan, M., Davis, T. L. & Charles, D. (2018). Impact of Tremor on Patients With Early Stage Parkinson’s Disease. Frontiers in Neurology, 9. https://doi.org/10.3389/fneur.2018.00628
Lin, J., Kang, X., Xiong, Y., Zhang, D., Zong, R., Yu, X., Pan, L. & Lou, X. (2021). Convergent structural network and gene signatures for MRgFUS thalamotomy in patients with Parkinson’s disease. NeuroImage, 243, 118550. https://doi.org/10.1016/j.neuroimage.2021.118550
Krauß, J., Upadhyay, N., Purrer, V., Borger, V., Daamen, M., Maurer, A., Schmeel, C., Radbruch, A., Wüllner, U., & Boecker, H. Beyond the CTCT: Remote structural changes after VIM-MRgFUS in Essential Tremor. bioRxiv, 2024. https://doi.org/10.1101/2024.10.08.617157
Schlesinger, I., Sinai, A. & Zaaroor, M. (2017). MRI-Guided Focused Ultrasound in Parkinson’s Disease: a review. Parkinson S Disease, 2017, 1–5. https://doi.org/10.1155/2017/8124624
Tuleasca, C., Witjas, T., Najdenovska, E., Verger, A., Girard, N., Champoudry, J., Thiran, J., Van De Ville, D., Cuadra, M. B., Levivier, M., Guedj, E. & Régis, J. (2017). Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest! Acta Neurochirurgica, 159(11), 2139–2144. https://doi.org/10.1007/s00701-017-3317-7
Weiss, D., Volkmann, J., Fasano, A., Kühn, A., Krack, P. & Deuschl, G. (2021). Changing gears – DBS for dopaminergic desensitization in Parkinson’s Disease? Annals Of Neurology, 90(5), 699–710. https://doi.org/10.1002/ana.26164