Intraoperative lesion characterization after focused ultrasound thalamotomy

OBJECTIVE Outcomes after focused ultrasound ablation (FUSA) for essential tremor remain heterogeneous, despite therapeutic promise. Clinical outcomes are directly related to the volume and location of the therapeutic lesions, consistent with CNS ablative therapies. Recent data demonstrate that postoperative diffusion MRI, specifically the quantification of intracellular diffusion by restricted diffusion imaging (RDI), can accurately characterize focused ultrasound lesions. However, it is unclear whether RDI can reliably detect focused ultrasound lesions intraoperatively (i.e., within a few minutes of lesioning) and whether the intraoperative lesions predict delayed clinical outcomes. METHODS An intraoperative imaging protocol was implemented that included RDI and T2-weighted imaging in addition to intraoperative MR thermography. Lesion characteristics were defined with each sequence and then compared. An imaging-outcomes analysis was performed to determine lesion characteristics associated with delayed clinical outcomes. RESULTS Intraoperative RDI accurately identified the volume and location of focused ultrasound lesions. Intraoperative T2-weighted imaging underestimated the lesion volume but accurately identified the location. Intraoperative RDI revealed that lesions of the ventral border of the ventral intermediate nucleus were significantly associated with postoperative tremor improvement. In contrast, the lesions extending into the inferolateral white matter were associated with postoperative ataxia. CONCLUSIONS These data support the acquisition of intraoperative RDI to characterize focused ultrasound lesions. Future research should test the histological correlates of intraoperative RDI and test whether it can be developed as feedback to optimize the current technique of FUSA.

Targeting for stereotactic radiosurgical thalamotomy based on tremor treatment response

OBJECTIVE Stereotactic radiosurgery (SRS) treats severe, medically refractory essential tremor and tremor-dominant Parkinson disease. However, the optimal target for SRS treatment within the thalamic ventral intermediate nucleus (VIM) is not clearly defined. This work evaluates the precision of the physician-selected VIM target, and determines the optimal SRS target within the VIM by correlation between early responders and nonresponders. METHODS Early responders and nonresponders were assessed retrospectively by Elements Basal Ganglia Atlas autocontouring of the VIM on the pre–SRS-treatment 1-mm slice thickness T1-weighted MRI and correlating the center of the post–SRS-treatment lesion. Using pre- and posttreatment diffusion tensor imaging, the fiber tracking package in the Elements software generated tremor-related tracts from autosegmented motor cortex, thalamus, red nucleus, and dentate nucleus. Autocontouring of the VIM was successful for all patients. RESULTS Among 23 patients, physician-directed SRS targets had a medial–lateral target range from +2.5 mm to −2.0 mm from the VIM center. Relative to the VIM center, the SRS isocenter target was 0.7–0.9 mm lateral for 6 early responders and 0.9–1.1 mm medial for 4 nonresponders (p = 0.019), and without differences in the other dimensions: 0.2 mm posterior and 0.6 mm superior. Dose–volume histogram analyses for the VIM had no significant differences between responders and nonresponders between 20 Gy and 140 Gy, mean or maximum dose, and dose to small volumes. Tractography data was obtained for 4 patients. CONCLUSIONS For tremor control in early responders, the Elements Basal Ganglia Atlas autocontour for the VIM provides the optimal SRS target location that is 0.7–0.9 mm lateral to the VIM center.

Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.

Reducing Ataxic Side Effects from Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation Implantation in Essential Tremor: Potential Advantages of Directional Stimulation

<b><i>Objective:</i></b> The aim of the study was to retrospectively evaluate the effect of directional deep brain stimulation (DBS) on ataxia in an essential tremor patient population. <b><i>Materials and Methods:</i></b> A retrospective chart review of documented Scale for Assessment and Rating of Ataxia (SARA) scores were analyzed using a case-control design. All subjects we evaluated were treated at a single, tertiary care academic center. We reviewed 14 patients who underwent bilateral ventral intermediate nucleus of the thalamus (VIM) implantation with microelectrode recording, with electrodeposition and segmented contact orientation confirmed via postoperative computed tomography. The main outcome was to determine change in ataxia scores between directional versus monopolar circumferential stimulation. <b><i>Results:</i></b> Fourteen patients (9 males, median age at implantation 69 [range 63–82]) underwent surgery between October 2017 and July 2020 at the UNC Movement Disorders Center. SARA scores between directional stimulation and monopolar circumferential stimulation demonstrated a significant reduction in total scores with best possible segmented stimulation (<i>n</i> = 13, <i>p</i> &#x3c; 0.0001, 95% confidence interval [CI] −3.496 to −6.789). This difference remained statistically significant even after removing the SARA tremor subscore (<i>n</i> = 13, <i>p</i> &#x3c; 0.0001, 95% CI −3.155 to −6.274). In line with prior reports, SARA score changes from the preoperative state were generally worsened when applying monopolar circumferential stimulation bilaterally (<i>n</i> = 13, <i>p</i> = 0.655; 95% CI −2.836 to 4.359), but improved with directional stimulation (<i>n</i> = 13, <i>p</i> = 0.010; 95% CI −1.216 to −7.547). <b><i>Conclusion:</i></b> This retrospective analysis appears to show evidence for improved outcomes through directional stimulation in bilateral VIM DBS implantation with reduction of ataxic side effects that have traditionally plagued postoperative results, all while providing optimized tremor reduction via stimulation.

Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort

OBJECTIVE The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density–weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting. METHODS Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author’s institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure–posterior commissure line). RESULTS Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention. CONCLUSIONS Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.

Impact of deep brain stimulation surgery on speech and swallowing in patients with essential tremor

Purpose: The ventral intermediate nucleus (VIM) of the thalamus is the typical target of deep brain stimulation (DBS) for controlling tremor in essential tremor (ET). It remains unclear whether the outcomes are significantly different on speech and/or swallowing functions. This study was to compare speech and swallowing outcomes in patients with ET without VIM DBS, and those with unilateral/bilateral VIM DBS.Methods: We conducted a retrospective review of 133 patients with the diagnosis of ET. We analyzed the clinical speech and swallowing evaluations, and compared outcomes across four ‘DBS disposition’ groupings: no DBS, left, right, or bilateral VIM DBS.Results: Speech function was worse in bilateral group versus no DBS and unilateral groups. Orofacial (p=0.000), rate (p=0.001), and prosody (p=0.003) were significantly different between groups. No DBS and unilateral groups demonstrated either no dysarthria or mild hyperkinetic dysarthria versus exhibiting higher rates of dysarthria including an ataxic component in bilateral group. Bilateral group showed more impaired swallowing severity versus no DBS and unilateral groups, however, these differences were not statistically significant.Conclusions: The results demonstrated speech and swallowing changes in the ET patient population after VIM DBS. This data provides support for further study in order to better understand the speech and/or swallowing changes that may occur with VIM DBS.

Deep Brain Stimulation for Tremor: Update on Long-Term Outcomes, Target Considerations and Future Directions

Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus is one of the main advanced neurosurgical treatments for drug-resistant tremor. However, not every patient may be eligible for this procedure. Nowadays, various other functional neurosurgical procedures are available. In particular cases, radiofrequency thalamotomy, focused ultrasound and radiosurgery are proven alternatives to DBS. Besides, other DBS targets, such as the posterior subthalamic area (PSA) or the dentato-rubro-thalamic tract (DRT), may be appraised as well. In this review, the clinical characteristics and pathophysiology of tremor syndromes, as well as long-term outcomes of DBS in different targets, will be summarized. The effectiveness and safety of lesioning procedures will be discussed, and an evidence-based clinical treatment approach for patients with drug-resistant tremor will be presented. Lastly, the future directions in the treatment of severe tremor syndromes will be elaborated.

Single-orientation Quantitative Susceptibility Mapping identifies the Ventral Intermediate Nucleus of the Thalamus

Introduction: The ventral intermediate nucleus (VIM) represents the primary target in the treatment of tremor. Accurate localization is extremely important given its proximity to other thalamic nuclei. We utilized single orientation quantitative susceptibility mapping (QSM) at 3T to directly visualize the VIM. Methods: Four adult volunteers, one adult cadaver, and an essential tremor patient were scanned on a 3T MRI using a multi-echo gradient echo sequence. QSM images were generated using the improved sparse linear equation and least-squares (iLSQR) algorithm. Two adult subjects underwent multiple head orientation imaging for multi-orientation QSM reconstruction. The VIM was prospectively identified with direct visualization as well as indirect landmark-based localization. Results: The bilateral VIM was consistently identified as a hypointense structure within the lateral thalamus, appearing similar on multi-orientation and single-orientation QSM, corresponding to the myelinated dentatorubrothalamic tract (DRTT). The indirect method resulted in a comparatively inferomedial localization, at times missing the VIM and DRTT. Conclusion: Single-orientation QSM offers a clinically feasible, non-invasive imaging-based approach to directly localize the VIM.