Cognitive impacts of unilateral MR-guided focused ultrasound thalamotomy: a meta-analysis and a call for systematic neuropsychological assessment

J Neurosurg 142:1271–1279, 2025

A meta-analysis of unilateral MR-guided focused ultrasound thalamotomy for pharmacoresistant tremors shows no significant cognitive or emotional decline post-procedure. However, the limited studies and short-term assessments necessitate further research, especially on long-term effects and bilateral procedures.

Objective: Evaluate cognitive and emotional effects of unilateral MR-guided focused ultrasound (MRgFUS) thalamotomy in patients with pharmacoresistant tremors.

Methods: Conducted a meta-analysis following PRISMA guidelines, focusing on cognitive functions pre- and post-procedure.

Results: No significant deterioration in cognitive domains or emotional states post-procedure.

Sample: Included 112 patients, mostly with essential tremor and some with Parkinson’s disease.

Findings: MRgFUS thalamotomy is safe concerning cognitive and emotional outcomes, but more research is needed for long-term effects.

Limitations: Small number of studies, short-term assessments, and potential publication bias.

Conclusion: Encouraging findings on safety, but further comprehensive investigations are necessary.

Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study

J Neurosurg 140:1799–1809, 2024

Medial thalamotomy has been shown to benefit patients with neuropathic pain, but widespread adoption of this procedure has been limited by reporting of clinical outcomes in studies without a control group. This study aimed to minimize confounders associated with medial thalamotomy for treating chronic pain by using modern MRI-guided stereotactic lesioning and a rigorous clinical design.

METHODS This prospective, double-blinded, randomized controlled trial in 10 patients with trigeminal neuropathic pain used sham procedures as controls. Participants underwent assessments by a pain psychologist and pain management clinician, including use of the following measures: the Numeric Pain Rating Scale (NPRS); patient-reported outcome measures; and patient’s impression of improvement at baseline, 1 day, 1 week, 1 month, and 3 months postprocedure. Patients in the treated group underwent bilateral focused ultrasound (FUS) medial thalamotomy targeting the central lateral nucleus. Patients in the control group underwent sham procedures with energy output disabled. The primary efficacy outcome measure was between-group differences in pain intensity (using the NPRS) at baseline and at 3 months postprocedure. Adverse events were measured for safety and included MRI analysis. Exploratory measures of connectivity and metabolism were analyzed using diffusion tensor imaging, functional MRI, and PET, respectively.

RESULTS There were no serious complications from the FUS procedures. MRI confirmed bilateral medial thalamic ablations. There was no significant improvement in pain intensity from baseline to 3 months, either for patients undergoing FUS medial thalamotomy or for sham controls; and the between-group change in NPRS score as the primary efficacy outcome measure was not significantly different. Patient-reported outcome assessments demonstrated improvement (i.e., a decrease) only in pain interference with enjoyment of life at 3 months. There was a perception of benefit at 1 week, but only for patients treated with FUS and not for the sham cohort. Advanced neuroimaging showed that these medial thalamic lesions altered structural connectivity with the postcentral gyrus and demonstrated a trend toward hypometabolism in the insula and amygdala.

CONCLUSIONS This randomized controlled trial of bilateral FUS medial thalamotomy did not reduce the intensity of trigeminal neuropathic pain, although it should be noted that the ability to estimate the magnitude of treatment effects is limited by the small cohort.

Clinical trial registration no.: NCT03309813 (ClinicalTrials.gov)

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson’s Disease

Neurosurgery 93:884–891, 2023

Magnetic resonance–guided focused ultrasound (MRgFUS) has emerged as a precise, incisionless approach to cerebral lesioning and an alternative to neuromodulation in movement disorders. Despite rigorous clinical trials, long-term patient-centered outcome data after MRgFUS for tremor-predominant Parkinson’s Disease (TPPD) are relatively lacking.

OBJECTIVE: To report long-term data on patient satisfaction and quality of life after MRgFUS thalamotomy for TPPD.

METHODS: In a retrospective study of patients who underwent MRgFUS thalamotomy for TPPD at our institution between 2015 and 2022, a patient survey was administered to collect self-reported measures of tremor improvement, recurrence, Patients’ Global Impression of Change (PGIC), and side effects. Patient demographics, FUS parameters, and lesion characteristics were analyzed.

RESULTS: A total of 29 patients were included with a median follow-up of 16 months. Immediate tremor improvement was achieved in 96% of patients. Sustained improvement was achieved in 63% of patients at last follow-up. Complete tremor recurrence to baseline occurred for 17% of patients. Life quality improvement denoted by a PGIC of 1 to 2 was reported by 69% of patients. Long-term side effects were reported by 38% of patients and were mostly mild. Performing a secondary anteromedial lesion to target the ventralis oralis anterior/posterior nucleus was associated with higher rates of speech-related side effects (56% vs 12%), without significant improvement in tremor outcomes.

CONCLUSION: Patient satisfaction with FUS thalamotomy for tremor-predominant PD was very high, even at longer term. Extended lesioning to target the motor thalamus did not improve tremor control and may contribute to greater frequency of postoperative motor- and speech-related side effects.

Initial experience with magnetic resonance–guided focused ultrasound stereotactic surgery for central brain lesions in young adults

J Neurosurg 137:760–767, 2022

Magnetic resonance–guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown.

METHODS The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children’s Hospital in Miami, Florida, are presented. Patients 15–22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA).

RESULTS In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort.

CONCLUSIONS This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms. Clinical trial registration no.: NCT03028246

 

Ultrasound Ablation in Neurosurgery: Current Clinical Applications and Future Perspectives

Neurosurgery 87:1–10, 2020

The concept of focusing high-intensity ultrasound beams for the purpose of cerebral ablation has interested neurosurgeons for more than 70 yr. However, the need for a craniectomy or a cranial acoustic window hindered the clinical diffusion of this technique.

Recent technological advances, including the development of phased-array transducers and magnetic resonance imaging technology, have rekindled the interest in ultrasound for ablative brain surgery and have led to the development of the transcranial magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation procedure. In the last decade, this method has become increasingly popular, and its clinical applications are broadening.

Despite the demonstrated efficacy of MRgFUS, transcranial thermal ablation using ultrasound is limited in that it can target exclusively the central region of the brain where the multiple acoustic beams are most optimally focused. On the contrary, lesioning of the cortex, the superficial subcortical areas, and regions close to the skull base is not possible with the limited treatment envelope of current phased-array transducers.

Therefore, new ultrasound ablative techniques, which are not based on thermal mechanisms, have been developed and tested in experimental settings. This review describes the mechanisms by which these novel, nonthermal ablative techniques are based and also presents the current clinical applications of MRgFUS thermal ablation.