Figure 1
A Decision Tree for the Treatment of Tremor. In patients with a limb tremor, unilateral procedure (either DBS or ablation) may sometimes be sufficient to reduce the disability. In the case of disabling bilateral limb, head, voice, or trunk tremors, a bilateral procedure is necessary. As bilateral thalamotomies carry a high risk of dysarthria, dysphagia or balance problems, mostly Vim-DBS is applied. Other less studied targets are the Zi, especially in its caudal part (Raprl), Vop and Voa nuclei of the thalamus (modified from ref. 75). BoNT, Botulinum Neurotoxin; DBS, Deep Brain Stimulation; EMG, Electromyogram; GA, General Anesthesia; GKRS, Gamma Knife Radiosurgery; M/C, Midline and/or Contralateral Tremor; MCS, Motor Cortex Stimulation; MRgFUS, MRI-guided Focused Ultrasound (of Vim); QoL, Quality of Life; Raprl, Prelemniscal Radiation; RF, Radiofrequency; rTMS, Repetitive Transcranial Magnetic Stimulation; Vim, Ventrointermedius Nucleus of the Thalamus; Voa, Ventral Oral Anterior of the Thalamus; Vop, Ventral Oral Posterior Nucleus of the Thalamus. *To be considered in patients with a severe bleeding risk (e.g., ongoing anticoagulation). **Medication reduction can contribute to the worsening of midline/contralateral tremor.
Table 1
The Features of the Neurosurgical Procedures Currently Used for Movement Disorders (listed chronologically).31,49,59
| Radiofrequency Lesioning | Deep Brain Stimulation | Gamma Knife Radio Surgery | MR-guided Focused Ultrasound | |
|---|---|---|---|---|
| Technique | A probe inserted into the brain is used to burn neurons in a selected area to create a focal lesion | One or more electrodes are inserted into the brain and are then connected to a implantable pulse generator providing constant electrical stimulation to modulate neuronal activity in the targeted brain region | Ionizing radiations are transmitted through the intact skull to generate a permanent lesion in a specific brain region | Ultrasound waves are transmitted through the intact skull to generate a permanent lesion in a specific brain region |
| Targeting | Neuroimaging, neuronal recording, intra-operative stimulation, intraoperative test lesions | Neuroimaging, neuronal recording, intra-operative stimulation, (real-time MRI guidance in selected centers) | Neuroimaging | Neuroimaging, thermic maps, real-time MRI guidance, intraoperative test lesions |
| Worldwide experience | Over 50 years | Over 30 years | Over 15 years | 4 years |
| Ablation (irreversible effects) | Yes | No | Yes | Yes |
| Use of general anesthesia | No | Yes | No | No |
| Invasive/incisions | Yes | Yes | No | No |
| Possibility of bilateral procedure | No | Yes | No | No |
| Device implantation | No | Yes | No | No |
| Benefit onset | Immediate | Delayed (when programming is completed, up to 6 months) | Delayed (up to 1 year) | Immediate |
Figure 2
Neuroimaging of Neurosurgical Procedures for Tremor. Brain MRI of a tremor patient 1 day and 6 months after MRgFUS-thalamotomy of the left hemisphere (right). CT scan of another tremor patient who underwent left RF-thalamotomy (arrow) followed by right Vim-DBS (left). DBS, Deep Brain Stimulation; DWI, Diffusion-weighted Imaging; MRgFUS, MRI-guided Focused Ultrasound (of Vim); RF, Radiofrequency; T2w, T2-weighted Imaging; Vim, Ventrointermedius Nucleus of the Thalamus.
Table 2
The Features of the Current Neurosurgical Approaches to Movement Disorders (listed chronologically).31,49,59
| Radiofrequency Lesioning | Deep Brain Stimulation | Gamma Knife Radio Surgery | MR-guided Focused Ultrasound | ||
|---|---|---|---|---|---|
| Possible target(s) | Vim | Yes | Yes | Yes | Yes |
| Vop | Yes | Yes | No | No | |
| GPi | Yes | Yes | (Yes)a | Yes | |
| STN | (Yes)a | Yes | No | No | |
| Zi | (Yes)a | Yes | No | No | |
| Effect on | Tremor | Effective | Effective (Vim>STN>GPi) | Effective but delayed | Effective but variable (Vim>GPi) |
| Bilateral/midline signs | No | Yes | No | No | |
| Other outcome attributes | Benefit onset | Immediate | Delayed (when programming is completed, up to 6 months) | Delayed (up to 1 year) | Immediate |
| Recurrence of symptoms/tolerance | Yes (disease progression) | Yes (disease progression) | Yes (disease progression) | Yes (disease progression and healing process) | |
| Log-term data | Yes | Yes | Yesa | Unknown | |
| Quality of the evidence | fair | good | poor | fair | |
| Risks | Brain bleedingc | Yes | Yes | No | No? |
| Infection | Yes | Yes | No | No | |
| Hardware malfunction | No | Yes | No | No | |
| Temporary side effectsd | Yes | Yes | No | Yes | |
| Permanent side effectsd | Yes | No | Yes | Yes | |
| Hyper-response of brain tissuee | No | No | Yes | Yes | |
| Radiation-related (delayed effects) | No | No | Yes | No | |
| Other features | Need of being monitored/multiple visits | No | Yes | No | No |
| Need of battery changes | No | Yes | No | No | |
| Adjustable over time | No | Yes | No | No | |
| Reversible | No | Yesb | No | No | |
| Possible in patients with MRI contraindications | Yes | Yesf | Yes | No | |
| “Ideal” candidate profile | Patients not able to be regularly seen (e.g., with psychiatric diseases), fragile subjects (old patients in whom general anesthesia is not possible) | Young patients needing long-term adjustments. Only possible option for patients requiring bilateral or midline tremor control | Patients with bleeding risk (e.g., on anticoagulant treatment), high infection risk or not able to be regularly seen (e.g., with psychiatric diseases) | Patients with high infection risk or not able to be regularly seen (e.g., with psychiatric diseases)Not possible in patients with high skull thickness, not possible in patients with previous brain surgery |
Abbreviations: DBS, Deep Brain Stimulation; GPi, Globus Pallidus Pars Interna; MRI, Magnetic Resonance Imaging; STN, Subthalamic Nucleus; Vim, Ventrointermedius Nucleus of the Thalamus; Vop, Ventro-oralis Posterior Nucleus of the Thalamus; Zi, Zona incerta.
d Paresthesia, sensory loss, weakness, ataxia, visual field defects, speech and swallowing difficulties NOT caused by an intraoperative complication (e.g., stroke).
Table 3
The Problems, Unknowns, and Possible Future Indications (based on experimental evidence) of FUS.
| Problems |
| Variable effects on symptoms control |
| Decay of tremor control in the short term |
| Relatively high number of persistent side effects |
| Unpredictable hyper-response of brain tissue |
| Not suitable to target both hemispheres |
| Not possible in patients with MRI contraindications |
| Not possible in patients with high skull thickness |
| Not possible in patients with previous brain surgery |
| Limited experience |
| Patients’ misperception of being non-surgical |
| Unknowns |
| Long-term effects |
| Re-operation of the same brain area (e.g., in case of tremor recurrence) |
| Efficacy of lesioning less centered brain targets (e.g., GPi) |
| Safety of bilateral procedures |
| Efficacy of DTI MRI to better target brain nuclei/fibersSafety of STN lesioning (risk of hemiballismus) |
| Bleeding risk in selected populations (e.g., patients on anticoagulants) |
| Impact of placebo effect in previous and future RCTs |
| Possible future applications |
| Opening the BBB using moderate-intensity pFUS to improve the delivery of therapeutic agents (growth factors and genes)60–68 |
| Improving the spread of nanoparticles combined with CED for the delivery of protein and gene therapy to the brain69 |
| Neuromodulation with a high degree of spatial resolution (either activation60,70 or suppression of neuronal activity71) using low-intensity pFUS |
| “Enhanced sonication” through inertial cavitation by microbubbles compressed and expanded by FUS72 |
| Sonothrombolysis of clotted blood in ICH, thereby facilitating minimally invasive evacuation of the clot via craniostomy and aspiration tube73 |