Clarifying Order and Carry-Over Considerations in Dual-Target MRgFUS for Parkinson's Disease - Letter to the Editor

Sep 30, 2026

Uploaded by Cipher

Letter to the editor clarifies the rationale behind intraoperative target sequencing and possible post-lesion carry-over in a dual-target MR-guided focused ultrasound strategy for Parkinson’s disease. The authors describe a deliberate first ablation of VIM followed by PTT within the same session, with immediate pre/post evaluations to limit sequence bias. They address transient edema or conduction effects by using VIM scoring timed before effective PTT sonication and confirm lesion confinement by post-op MRI. They argue observed tremor versus rigidity responses support target-specific physiology and outline planned randomized, multi-center validation including a VIM-only control arm.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Order Effect

Carry-Over and Microlesional Effects

Future Directions

Conclusion

European Journal of Neurology LETTER TO THE EDITOR OPEN ACCESS Clarifying Order and Carry-Over Considerations in Dual-Target MRgFUS for Parkinson's Disease Jui-Cheng Chen | Ming-Kuei Lu | Chon-Haw Tsai Division of Parkinson's Disease and Movement Disorders, China Medical University Hospital, Taichung, Taiwan Correspondence: Jui-Cheng Chen ([013132@tool.caaumed.org.tw](013132@tool.caaumed.org.tw)) Received: 14 November 2025 | Revised: 14 November 2025 | Accepted: 27 November 2025 To the Editor, We appreciate the thoughtful comments regarding our recent article, “Immediate Motor Control Enhancement via Pallidothalamic Tract (PTT) Circuit Ablation: A Dual-Target MR-Guided Focused Ultrasound Approach for TremorDominant Parkinson's Disease” [1] . We welcome this opportunity to address concerns regarding the possible influence of order effects and carry-over phenomena in our intraoperative design. 1 | Order Effect All participants underwent ventral intermediate nucleus (VIM) ablation first, followed by PTT ablation within the same MRgFUS session. This sequence was deliberately selected based on safety and anatomical hierarchy. The VIM is a well-validated and relatively superficial target for tremor control, whereas the PTT lies deeper, adjacent to eloquent structures such asthe Mammillothalamic tract (MTT) and subthalamic nucleus (STN) . Performing VIM first ensured procedural safety, patient tolerance, and adequate acoustic transmission before proceeding to the deeper lesion. To mitigate potential sequence bias, clinical evaluations were performed immediately before and after each step (VIM evaluation → PTT evaluation), allowing within-subject comparison. Distinct temporal and domain-specific effects were observed: all tremor subtypes improved primarily after VIM, while rigidity improved most prominently after PTT. These differential response patterns argue against a non-specific additive or orderdriven gain. 2 | Carry-Over and Microlesional Effects We concur that transient edema or temperature-dependent conduction block may transiently influence immediate post-lesion testing. To minimize such effects, the VIM score used for analysis was obtained immediately before the first effective PTT sonication, with a latency of less than 10 min. Lesion overlap was also evaluated by post-op MRI, confirming confinement to the intended PTT zone. While our study design cannot fully exclude microlesional carry-over, the parameter-specific dissociation (rigidity versus tremor) and the consistency across subjects support targetspecific physiological effects rather than generalized intraoperative augmentation. 3 | Future Directions We fully agree that randomized or counterbalanced target order, standardized lesion metrics, and objective blinded kinematic assessments are essential to confirm causality. These refinementshave already been incorporated into our upcoming multi-center trial, which will include a VIM-only intraoperative control arm to rigorously evaluate the incremental contribution of PTTlesioning. 4 | Conclusion Our present study was intended as a physiological feasibility investigation, not as a definitive randomized comparison. In This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2026 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. European Journal of Neurology, 2026; 33:e70467 1 of 2 [https://doi.org/10.1111/ene.70467](https://doi.org/10.1111/ene.70467) clinical practice, patients with Parkinson's disease frequently present with a mixed motor phenotype in which disabling tremor coexists with varying degrees of rigidity and bradykinesia. For such individuals, our standard treatment algorithm prioritizes VIM ab

FAQs

Why did the study perform VIM ablation before PTT in the same MRgFUS session?

The sequence was chosen based on safety and anatomical hierarchy, with VIM being a validated, relatively superficial target and PTT located deeper near eloquent structures. Performing VIM first aimed to ensure procedural safety, patient tolerance, and adequate acoustic transmission before the deeper lesion.

How did the authors reduce the influence of sequence bias and carry-over on assessments?

Clinical evaluations were conducted immediately before and after each step (VIM then PTT) to enable within-subject comparison. For carry-over, VIM scoring used for analysis was obtained immediately before the first effective PTT sonication, with latency under 10 minutes, and lesion overlap was checked with post-op MRI.

What do the differential outcomes for tremor versus rigidity suggest?

Tremor subtypes improved primarily after VIM, while rigidity improved most prominently after PTT. The authors interpret this parameter-specific dissociation as evidence against a non-specific additive or order-driven effect and as support for target-specific physiological effects.

Sep 30, 2026

Uploaded by Cipher