MRgFUS Pallidothalamic Tractotomy for Chronic Therapy-Resistant Parkinson's Disease in 51 Consecutive Patients: Single Center Experience

Abstract

Background: There is a long history, beginning in the 1940s, of ablative neurosurgery on the pallidal efferent fibers to treat patients suffering from Parkinson's disease (PD). Since the early 1990s, we undertook a re-actualization of the approach to the subthalamic region, and proposed, on a histological basis, to target specifically the pallidothalamic tract at the level of Forel's field H1. This intervention, the pallidothalamic tractotomy (PTT), has been performed since 2011 using the MR-guided focused ultrasound (MRgFUS) technique. A reappraisal of the histology of the pallidothalamic tract was combined recently with an optimization of our lesioning strategy using thermal dose control. Objective: This study was aimed at demonstrating the efficacy and risk profile of MRgFUS PTT against chronic therapy-resistant PD. Methods: This consecutive case series reflects our current treatment routine and was collected between 2017 and 2018. Fifty-two interventions in 47 patients were included. Fifteen patients received bilateral PTT. The median follow-up was 12 months. Results: The Unified Parkinson's Disease Rating Scale (UPDRS) off-medication postoperative score was compared to the baseline on-medication score and revealed percentage reductions of the mean of 84% for tremor, 70% for rigidity, and 73% for distal hypobradykinesia, all values given for the treated side. Axial items (for voice, trunk and gait) were not significantly improved. PTT achieved 100% suppression of on-medication dyskinesias as well as reduction in pain (p < 0.001), dystonia (p < 0.001) and REM sleep disorders (p < 0.01). Reduction of the mean L-Dopa intake was 55%. Patients reported an 88% mean tremor relief and 82% mean global symptom relief on the operated side and 69% mean global symptom improvement for the whole body. There was no significant change of cognitive functions. The small group of bilateral PTTs at 1 year follow-up shows similar results as compared to unilateral PTTs but does not allow to draw firm conclusions at this point. Conclusion: MRgFUS PTT was shown to be a safe and effective intervention for PD patients, addressing all symptoms, with varying effectiveness. We discuss the need to integrate the preoperative state of the thalamocortical network as well as the psycho-emotional dimension.

Keywords: Parkinson's disease; functional stereotactic neurosurgery; high intensity MR-guided focused ultrasound; minimally invasive; pallidothalamic tractotomy.

Figure 1

(A) Intraoperative MR axial T2 scan with body coil after PTT lesion, cut through the intercommissural plane. (B) PTT at higher magnification taken intraoperatively with superimposed atlas maps 0.9 mm ventral to the intercommissural plane, modified from the Morel Atlas of the Human Thalamus and Basal Ganglia. AC, anterior commissure; al, ansa lenticularis; fct, fasciculus cerebello-thalamicus; fx, Fornix; GPe, globus pallidus, external segment; GPi, globus pallidus, internal segment; H1, H1 field of Forel; ic, internal capsule; mcl, midcommissural line; mtt, mammillothalamic tract; PC, posterior commissure; PuT, putamen.

Figure 2

Flow diagram showing follow-ups (FU) of this cross-sectional study. Telemedicine stands for video and phone conversation instead of regular neurological examinations for patients unable to travel long distances.

Figure 3

Total UPDRS III scores (higher values indicate stronger impairments) measured preoperatively (baseline) on-medication and 3 months and 1 year after PTT off-medication.

Figure 4

Partial UPDRS III scores for the operated side (UPDRS III items 20.1, 20.3, 21.1, 22.2, 22.4, 23.1, 24.1, 25.1, 26.1 or 20.2, 20.4, 21.2, 22.3, 22.5, 23.2, 24.2, 25.2, 26.2; max. 36 points, higher values indicate stronger impairments) preoperatively (baseline), at 3 months and 1 year in on- and off-medication state (for n values, see Table 2).

Figure 5

Comparison of the baseline UPDRS III for the operated side in on-medication state with the 1 year postoperative examination in off-medication state with its linear regression line, thus comparing medication vs. surgery alone. In red: bilaterally treated patients. In green: patient with subjective full recurrence.

Figure 6

Comparison of the axial items of the UPDRS III (items 18, 19, 22, 27, 28, 29, 30, 31, higher values indicating stronger impairments, max. 32 points) preoperatively (baseline) in on-medication state and 1 year after PTT in off-medication state with its linear regression line. In red: bilaterally treated patients. In green: patient with subjective full recurrence.