Leksell Gamma Knife® radiosurgery for essential tremor

Case: Essential tremor

Contributors: Geert-Jan Rutten MD, PhD, Liselotte Lamers, MD and Patrick Hanssens, MD.

Institution: Department of Neurosurgery, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands.

Overview

Essential tremor (ET) is a neurological movement disorder characterized by an involuntary tremor in certain parts of the body. Treatments for ET include medications, deep brain stimulation (DBS), radiofrequency lesioning and radiosurgery.

An 86-year-old female with a 30-year history of essential tremor was increasingly invalided by a limb tremor, in particular of her right arm, which was unresponsive to medication. As a consequence, the patient had become completely dependent on others for her daily care. Given her age, she was not considered a suitable candidate for surgical treatment (DBS or radiofrequency lesioning) and so she was referred for Gamma Knife radiosurgery.

Gamma Knife radiosurgery is a non-invasive treatment option for medically refractory essential tremor [1]. As the ventralis intermedius nucleus (VIM) is not directly visible by MRI, it was indirectly targeted on a T1 weighted MRI image using coordinates relating to the AC-PC line, the distance from the lateral border of the third ventricle (typically 11 mm) and the border of thalamus (see first Gamma Knife procedure below). More recently, newer imaging modalities–Fast Grey Matter Acquisition T1 Inversion Recovery (FGATIR) MRI [2] and diffusion MRI tractography [3]–allow better visualization of thalamus contours and the rubrothalamic connections that are hypothesized to play a critical role in tremor control [4], respectively (see second Gamma Knife procedure below).

First Gamma Knife procedure

June 2021

Following immobilization of the patient using the Leksell stereotactic frame, a T1 MRI scan was obtained for planning purposes. A dose of 130 Gy was delivered to the region of the left VIM via a single 4 mm shot (with 65 Gy on the 50% isodose line). Since the VIM was not directly visible by MRI, it was indirectly targeted via coordinates related to the AC-PC line, and by visual inspection of T1-weighted MR images to assure that the 50% isodose line fell within the contours of the thalamus (figure 1).

Figure 1
Figure 1. T1-weighted MRI scan showing 50% isodose line (yellow) in the VIM region of the thalamus.

The patient tolerated the procedure well. Unfortunately, however, there was no effect on her tremor

Adoption of new imaging modalities

More recently new imaging modalities were added to our DBS and lesioning procedures, including FGATIR MRI. [2] This sequence provides excellent delineation of grey and white matter, allowing better visualization of the thalamus contours and the rubro-thalamic connections. [4] Note that during these invasive procedures, the awake patient is monitored to maximize tremor control and minimize unwanted side effects. In our experience, in concordance with the literature, these new landmarks are beneficial in determining the optimal target for tremor control (figure 2).

Figure 1
Figure 2. Intraoperative screenshots from the surgical guidance system, showing the planned trajectory for radiofrequency lesioning of the VIM in a patient with essential tremor (awake surgical procedure). The initial surgical plan was guided by 3T FGATIR MRI, with diffusion MRI tractographic information of the corticospinal tract (green) and of the dentato-rubro-thalamic tract (DRT) (orange). Excellent and persistent tremor control was obtained after the RF lesion in this case.

Second Gamma Knife procedure

January 2023

Following these new imaging developments, it was decided to review the essential tremor case first treated in January 2021. 3T FGATIR MRI images were obtained, which allowed visualization of the nucleus ruber and rubral wing (figure 3). The latter is a hypointense white matter tract in the thalamus that contains the dentato-rubro-thalamic tract (DRT), which is considered a potential target in DBS for the treatment of tremor [2].

Figure 3
Figure 3. Coronal slice of FGATIR scan showing the nucleus ruber (dotted circle) and rubral wing (the triangular convergence indicated with the white lines). Colored circles indicate the first (blue) and second (yellow) Gamma Knife treatment.

Coregistration of the frameless 3T FGATIR MRI scan to the frame-based stereotactic 1.5 T planning MRI scan in GammaPlan revealed that the initial shot was located slightly above the DRT (figure 3). It was decided to perform a second Gamma Knife procedure, with the new 4 mm shot located more inferiorly and medially to better target the DRT. The patient was immobilized as before.

The treatment was planned in Leksell GammaPlan® version 11.3.2 and was delivered using Gamma Knife® Icon™. A dose of 32.5 Gy was prescribed on the 50% isodose line (see Figure 3). The distance between both isocenters was 2.6 mm. The prescription dose was lowered to limit dose in the region that overlapped the original treatment.

Ten days after the second Gamma Knife treatment the tremor had almost completely disappeared and the patient’s right hand was fully functional again. A recent follow-up confirmed that tremor control has now persisted for eight months.

Conclusions

A second Gamma Knife treatment resulted in almost complete and persistent tremor control in this elderly patient.

Retrospective analysis of the gamma knife treatments for essential tremor at Elisabeth Tweesteden hospital, using current target (as in the first treatment) (n=89) shows that this method is effective in up to 60% of cases. This is lower than the invasive procedures, however Gamma Knife radiosurgery offers virtually no risks or complications. As a result, it is possible to treat older and more fragile patients (average age was 78 years in this series) or patients with high co-morbidity who are seriously invalided by a tremor but are not suitable for surgery.

New imaging modalities, such as FGATIR MRI, and new insights into essential tremor networks present the possibility of improved and more personalized target identification.

References

  1. Stereotactic radiosurgery for tremor: systematic review. J Neurosurg. 2018 Feb 1:1-12. Martinez-Moreno NE et al. doi: 10.3171/2017.8.JNS17749
  2. The Fast Gray Matter Acquisition T1 Inversion Recovery Sequence in Deep Brain Stimulation: Introducing the Rubral Wing for Dentato-Rubro-Thalamic Tract Depiction and Tremor Control. Neuromodulation 2022 Jan 15:S1094- 7159(21)06948-8. Bot M, Pauwels R, van den Munckhof P, et al. PMID: 35088745.doi: 10.1016/j.neurom.2021.11.015.
  3. Advancements in Diffusion MRI Tractography for Neurosurgery. Investigative Radiology. 2032 Sept 15. Kamagata, K et al. doi: 10.1097/ RLI.0000000000001015
  4. The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series. Acta Neurochir (Wien) 2020 May;162(5):1053-1066. Coenen VA, Sajonz B, Prokop T, et al. PMID: 31997069 doi: 10.1007/s00701-020-04248-2.