Active contact proximity to the cerebellothalamic tract predicts initial therapeutic current requirement with DBS for ET: an application of 7T MRI

Abstract

Objective: To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET).

Background: DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely.

Methods: A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores.

Results: The therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R² = 0.458, p = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R² = -0.073, p = 0.58).

Conclusion: Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.

Keywords: 7-T MRI; cerebellothalamic tract; deep brain stimulation; diffusion tractography imaging; essential tremor; stimulation amplitude.

Figure 1

(A) The CTT centerline, denoted in blue, was reconstructed from 7T MRI-derived tractography. The Euclidean distance between the center of the active electrode contact (yellow) and the CTT centerline was then calculated (red). An example is shown from a single subject. (B) Therapeutic current at initial post-op programming as well as at 1-year and 2-year follow ups across implants, with errors bars displaying the standard error.

Figure 2

(A–C) Active contact proximity to the CTT was associated with lower therapeutic current at the time of initial programming; however, this association was not found at the 1-year and 2-year follow ups. (D) Distance to CTT did not predict 𝚫 stimulation amplitude, defined as the difference between therapeutic current at initial and 2-year follow up. Data points demarcated in red symbolize the use of a directional (segmented) electrode.

Figure 3

Improvement in FTM hemi-score with VIM DBS for ET. Baseline FTM hemi-score was 14.8 (±4.4), with post-operative score of 3.3 (±2.6) at mean follow up of 22.2 (±18.9) months. Mean OFF-stim score was 15.8 (±6.0) at mean follow up of 26.1 (1.7) months. FTM hemi-score values are represented as means, error bars as standard errors.

Figure 4

(A) Scatter plot with improvement in the FTM hemi-score after surgery (mean time to collection 22.2 months) in the Y axis and the stimulation applied in the X axis. Improvement in FTM score is defined as the difference between the baseline FTM hemi-score and post-operative FTM hemi-score. Subjects with lower stimulation amplitudes at the initial programming had better post-operative tremor control (R² = 0.459, p = 0.013). (B) Scatter plot with post-operative FTM hemi-score displayed as a percentage improvement from baseline FTM hemi-score. In this context, the finding was not statistically significant (R² = 0.139, p = 0.30).