Stepwise dual-target magnetic resonance-guided focused ultrasound in tremor-dominant Parkinson disease: One-year follow-up

Abstract

Background and purpose: Magnetic resonance-guided focused ultrasound (MRgFUS) is a nonsurgical treatment for Parkinson disease (PD). Some selected anatomical structures can be targeted by MRgFUS in PD. However, there is no uniform target yet. We have reported that stepwise dual-target MRgFUS was successfully applied to treat refractory tremors with akinetic-rigid features in PD. It generated two precise thermal ablations in the ventral intermediate nucleus (VIM) and pallidothalamic tract (PTT). Here, we report more PD patients to verify the safety and efficacy of stepwise dual-target MRgFUS.

Methods: Ten tremor-dominant PD patients (mean age = 66.7 ± 3.2 years, eight men) received the stepwise dual-target MRgFUS treatment with a series of primary and secondary outcome measures. The VIM and PTT were navigated based on brain magnetic resonance images. Outcome measures were categorized into primary and secondary assessments. The primary outcome measures consisted of resting tremor, action/kinetic tremor, rigidity, and bradykinesia. Secondary outcome measures encompassed non-motor symptoms scale of PD. Data collected at follow-up time points, including 1 day, 3 months, 6 months, and 1 year posttreatment, were compared with baseline data.

Results: The severity of tremor and motor deficits represented by Clinical Rating Scale for Tremor parts A and B during off-medication status and Unified Parkinson's Disease Rating Scale III on the treated side were significantly improved (p < 0.05 by paired t-test) at 1-year follow-up. At the 1-year follow-up, significant improvement was observed in the non-motor symptoms scale. Additionally, no severe adverse effects were reported, except temporary treatment-related discomfort during the procedure.

Conclusions: In conclusion, stepwise dual-target MRgFUS emerges as a safe and effective therapeutic modality for PD patients, particularly in addressing medication-refractory tremor and akinetic-rigid syndrome.

Keywords: MR‐guided focused ultrasound (MRgFUS); Parkinson disease; pallidothalamic tract; stepwise dual‐target MRgFUS; thalamotomy; tremor; ventral intermediate nucleus.

FIGURE 1

Posttreatment magnetic resonance imaging of the final patient on day 1. The upper row contains axial T2‐weighted images captured at the anterior commissure–posterior commissure (AC–PC) level. Conversely, the lower row displays images obtained 2 mm superior to the AC–PC level. Both the upper and lower right images emphasize the intricate structures surrounding the targeted areas. Notably, both pallidothalamic tract (PTT) and ventral intermediate nucleus (VIM) exhibit distinct bright ring‐shaped regions. A, anterior; GPe, globus pallidus externa; GPi, globus pallidus interna; IC, internal capsule; MTT, mammillothalamic tract; P, posterior; PuT, putamen.

FIGURE 2

Lesion analysis of stepwise dual‐target magnetic resonance‐guided focused ultrasound in Parkinson disease patients. The images are arranged with the upper row displaying the ventral intermediate nucleus targets, and the lower row showing the pallidothalamic tract in standard axial, coronal, and sagittal magnetic resonance images. A, anterior; GP, globus pallidus; GPe, GP externa; GPi, GP interna; IC, internal capsule; L, left; MTT, mammillothalamic tract; Put, putamen.

FIGURE 3

One‐year follow‐up of the clinical changes in 10 patients after magnetic resonance‐guided focused ultrasound. (a) Clinical Rating Scale for Tremor (CRST) parts A and B over the treatment side; (b) Unified Parkinson's Disease Rating Scale (UPDRS) III over the treatment side; (c) 39‐item Parkinson's Disease Questionnaire (PDQ‐39); (d) Non‐Motor Symptoms Scale (NMSS). *Significant difference (p < 0.05 by paired t‐tests); pre, pretreatment; p1d, 1 day posttreatment; p1m, 1 month posttreatment; p3m, 3 months posttreatment; p6m, 6 months posttreatment; p1y, 1 year posttreatment.

FIGURE 4

A description of the average clinical score changes during stepwise dual‐target magnetic resonance‐guided focused ultrasound. Five patients received pallidothalamic tract (PTT) first treatment, whereas the other five patients received ventral intermediate nucleus (VIM) first treatment. Clinical scores are shown for tremor, rigidity, and finger taps at the time points of baseline, post‐first target lesioning, and post‐second target lesion in PTT first (a), and VIM first (b) treatment. Tremor scores included resting tremor, posture tremor, and action tremor in Clinical Rating Scale for Tremor (max = 12), whereas rigidity scores included upper and lower limbs (max = 8) and finger taps (max = 4) in Unified Parkinson's Disease Rating Scale.