Magnetic resonance guided focused ultrasound thalamotomy for essential tremor [Neurosurgery Wiki]

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====== Magnetic resonance guided focused ultrasound thalamotomy for essential tremor ======

//J.Sales-Llopis//

//Neurosurgery Department, University General Hospital of Alicante, Spain//

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1-ohVP9Y35P5jK4Qp4RkUxnkipLzc7IYMc5hbXmFN4fa1O-kBE/?limit=15&utm_campaign=pubmed-2&fc=20240116171259}}
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Focused ultrasound as an evolving therapy for
Parkinson's disease
((Fishman P, Lipsman N. Focused ultrasound as an evolving therapy for
Parkinson's disease. Mov Disord. 2019 Sep;34(9):1241-1242. doi:
10.1002/mds.27809. PubMed PMID: 31539464.)).


Focused ultrasound enables non-invasive MRI-guided formation of small destruction foci in the relevant targets, providing therapeutic neuromodulating effects in patients with [[Parkinson's disease]], [[essential tremor]], [[pain]] syndromes, [[obsessive-compulsive disorder]]s, and other diseases. So far, this treatment was carried out on more than 300 patients. Several cases of ultrasound thermal destruction of intracranial neoplasms were published. There are attempts to perform [[third ventriculostomy]] using ultrasound in animals. 

see [[Magnetic resonance guided focused ultrasound thalamotomy]].

Transcranial [[Magnetic resonance guided focused ultrasound]] (TcMRgFUS) is a noninvasive alternative to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors
((Ghanouni P, Pauly KB, Elias WJ, Henderson J, Sheehan J, Monteith S, Wintermark
M. Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and
Neurologic Applications. AJR Am J Roentgenol. 2015 Jul;205(1):150-9. doi:
10.2214/AJR.14.13632. Review. PubMed PMID: 26102394; PubMed Central PMCID:
PMC4687492.
)).

===Parkinson tremor===
Thirteen consecutive patients suffering from chronic (mean disease duration 9.7 years) and therapy-resistant PD were treated unilaterally with an MRgFUS PTT. Primary relief assessment indicators were the score reduction of the Unified Parkinson Disease Rating Scale (UPDRS) and the patient estimation of global symptom relief (GSR) taken at 3 months follow-up. Final temperatures at target were between 52°C and 59°C. The MR examinations were performed before the treatment, 2 days and 3 months after it. The accuracy of the targeting was calculated on 2 days post-treatment MR pictures for each PTT lesion.

The first four patients received a PTT using the lesional parameters applied for thalamotomies. They experienced clear-cut recurrences at 3 months (mean UPDRS relief 7.6%, mean GSR 22.5%), and their MR showed no sign of thermal lesion in T2-weighted (T2w) images. As a consequence, the treatment protocol was adapted for the following nine patients by applying repetition of the final temperatures 4 to 5 times. That produced thermocoagulations of larger volumes (172 mm3 against 83 mm3 for the first four patients), which remained visible at 3 months on T2w images. These nine patients enjoyed a mean UPDRS reduction of 60.9% and a GSR of 56.7%, very close to the results obtained with radiofrequency lesioning. The targeting accuracy for the whole patient group was 0.5, 0.5, and 0.6 mm for the anteroposterior (AP), mediolateral (ML), and dorsoventral (DV) dimensions, respectively.

This study demonstrated the feasibility, safety, and accuracy of the MRgFUS PTT. To obtain similar results as the ones of RF PTT, it was necessary to integrate the fact that white matter, in this case, the pallidothalamic tract, requires repeated thermal exposition to achieve full lesioning and thus full therapeutic effect
((Magara A, hler RB, Moser D, Kowalski M, Pourtehrani P, Jeanmonod D. First experience with MR-guided focused ultrasound in the treatment of Parkinson's disease. 2014 May 31;2(1):1–8.)).
----


[[Magnetic resonance guided focused ultrasound]] is a minimally invasive surgical procedure for symptomatic treatment of [[Parkinson's disease]]. With this technology, the [[ventral intermediate nucleus]], [[STN]], and [[internal globus pallidus]] have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures. 

In a pilot study published in 2013, [[essential tremor]] improved in 15 patients treated with [[magnetic resonance guided focused ultrasound thalamotomy]]. 
((Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC,
Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. 
A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J
Med. 2013 Aug 15;369(7):640-8. doi: 10.1056/NEJMoa1300962. PubMed PMID: 23944301.
)).

Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant [[Parkinson's disease]] (TDPD) is unknown.

It might change the way that patients with essential tremor and potentially other disorders are treated
((Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, Hynynen K, Lozano
AM. MR-guided focused ultrasound thalamotomy for essential tremor: a
proof-of-concept study. Lancet Neurol. 2013 May;12(5):462-8. doi:
10.1016/S1474-4422(13)70048-6. Epub 2013 Mar 21. PubMed PMID: 23523144.
)).

====Effectiveness====
The post-treatment effectiveness was evaluated using the [[tremor&#rating_scales|clinical rating scale for tremors]]. Thalamic MRgHIFU had substantial therapeutic effects on patients, based on MRgHIFU-mediated improvements in movement control and significant changes in brain [[mu rhythm]]s. Ultrasonic [[thalamotomy]] may reduce hyper-excitable activity in the [[motor cortex]], resulting in normalized behavioral activity after sonication treatment. Thus, non-invasive and spatially accurate MRgHIFU technology can serve as a potent therapeutic tool with broad clinical applications
((Chang JW, Min BK, Kim BS, Chang WS, Lee YH. Neurophysiologic correlates of
sonication treatment in patients with essential tremor. Ultrasound Med Biol. 2015
Jan;41(1):124-31. doi: 10.1016/j.ultrasmedbio.2014.08.008. Epub 2014 Oct 22.
PubMed PMID: 25438838.
)).

====Safety====
[[Magnetic resonance guided focused ultrasound]] (MRgFUS) for [[thalamotomy]] is a safe, effective and less-invasive surgical method for treating medication-refractory [[essential tremor]] (ET). However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment
((Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW.
Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential
tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg
Psychiatry. 2015 Mar;86(3):257-64. doi: 10.1136/jnnp-2014-307642. Epub 2014 May
29. PubMed PMID: 24876191.
)).

Jung et al. found different [[MRI]] pattern evolution after MRgFUS for [[white matter]] and [[gray matter]]. Their results suggest that skull characteristics, such as low skull density, should be evaluated prior to MRgFUS to successfully achieve thermal rise
((Jung HH, Chang WS, Rachmilevitch I, Tlusty T, Zadicario E, Chang JW. Different
magnetic resonance imaging patterns after transcranial magnetic resonance-guided 
focused ultrasound of the ventral intermediate nucleus of the thalamus and
anterior limb of the internal capsule in patients with essential tremor or
obsessive-compulsive disorder. J Neurosurg. 2015 Jan;122(1):162-8. doi:
10.3171/2014.8.JNS132603. PubMed PMID: 25343176.
)).

====Nursing management====
In a large academic medical center in the mid-Atlantic region, the Department of Neurosurgery conducted a continued access study, recently approved by the Food and Drug Administration, to evaluate the effectiveness of transcranial FUS thalamotomy for the treatment of medication-refractory ET.

One patient's experience will be introduced, including discussion of evidence-based treatment options for ET and information on the nursing management of the patient undergoing FUS thalamotomy
((Shaw KD, Johnston AS, Rush-Evans S, Prather S, Maynard K. Nursing Management
of the Patient Undergoing Focused Ultrasound: A New Treatment Option for
Essential Tremor. J Neurosci Nurs. 2017 Aug 16. doi:
10.1097/JNN.0000000000000301. [Epub ahead of print] PubMed PMID: 28817495.
)).

===== Meta-analysis =====
A PubMed search was performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses ([[PRISMA]]) guidelines. Studies were included if hand [[tremor scores]] (HTS), total Clinical Rating Scale for Tremor (CRST) scores, or [[Quality of Life in Essential Tremor Questionnaire]] (QUEST) scores at regular intervals following [[MRgFUS]] treatment for [[essential tremor]] were documented. Data analyses included a random effects model of meta-analysis and mixed-effects model of meta-regression. Twenty-one articles reporting HTS for 395 patients were included. Mean pre-operative HTS was 19.2 ± 5.0. Mean HTS at 3 months post-treatment was 7.4 ± 5.0 (61.5% improvement, p < 0.001). Treatment effect was mildly decreased at 36 months at 9.1 ± 5.4 (8.8% reduction). Meta-regression of time since treatment as a modifier of HTS revealed a downward trend in effect size, though this was not statistically significant (p = 0.208). Only 4 studies included follow-up ≥ 24 months. Thirteen included articles reported total CRST scores with standardized follow-up for 250 patients. Mean pre-operative total CRST score decreased by 46.2% at 3 months post-treatment (p < 0.001). Additionally, mean QUEST scores at 3 months post-treatment significantly improved compared to baseline (p < 0.001). HTS is significantly improved from baseline ≥ 24 months post-treatment and possibly ≥ 48 months post-treatment. There is a current paucity of long-term CRST and QUEST score reporting in the literature
((Miller WK, Becker KN, Caras AJ, Mansour TR, Mays MT, Rashid M, Schwalb J. Magnetic resonance-guided focused ultrasound treatment for essential tremor shows sustained efficacy: a meta-analysis. Neurosurg Rev. 2021 May 12. doi: 10.1007/s10143-021-01562-w. Epub ahead of print. PMID: 33978922.)).

===== Prospective randomized clinical trials =====

In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions
((Moosa S, Martínez-Fernández R, Elias WJ, Del Alamo M, Eisenberg HM, Fishman
PS. The role of high-intensity focused ultrasound as a symptomatic treatment for 
Parkinson's disease. Mov Disord. 2019 Jul 10. doi: 10.1002/mds.27779. [Epub ahead
of print] Review. PubMed PMID: 31291491.
)).

===== Case series =====

see [[Magnetic resonance guided focused ultrasound thalamotomy for essential tremor case series]].

===== Case reports =====

A 55-yr-old man with a history of right frontal [[craniotomy]] for resection of a [[colloid cyst]] underwent a left ventrointermedius nucleus thalamotomy through MRgFUS. The prior craniotomy flap was not excluded in the treatment plan; however, all bony defects and hardware were marked as "no-pass" regions. Clinical outcomes were collected at the 6-mo follow-up.

Transducer elements whose acoustic paths would have been altered by the craniotomy defect were turned off. Sonications reaching lesional temperatures of up to 56°C were successfully delivered. The procedure was well-tolerated, without any persistent intra-ablation or post-ablation adverse effects. The presence of a lesion was confirmed on MRI, which was associated with a significant reduction in the patient's tremor that was sustained at the 6-mo follow-up.

This case demonstrates the safety and efficacy of MRgFUS thalamotomy in a patient with prior craniotomies and highlights our strategy for acoustic lesioning in this setting
((Wathen C, Yang AI, Hitti FL, Henry L, Chaibainou H, Baltuch GH. Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy. Oper Neurosurg (Hagerstown). 2022 Feb 1;22(2):61-65. doi: 10.1227/ONS.0000000000000012. PMID: 35007218.))
((Yamamoto K, Lozano AM, Fasano A. Commentary: Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy. Oper Neurosurg (Hagerstown). 2022 Jan 14. doi: 10.1227/ONS.0000000000000087. Epub ahead of print. PMID: 35030144.)).
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De Vloo et al. reported on an ET patient who underwent an [[Magnetic resonance guided focused ultrasound thalamotomy]]  but experienced [[tremor]] recurrence. They expanded the MRgFUS-induced thalamic cavity using [[radiofrequency]] (RF), with good effect on the tremor but transient sensorimotor deficits and permanent [[ataxia]]. This is the first report of a patient undergoing RF thalamotomy after an unsuccessful MRgFUS thalamotomy. As they used [[microelectrode recording]] to guide the RF thalamotomy, they could also study for the first time the electrophysiological properties of previously sonicated thalamic neurons bordering the MRgFUS-induced cavity. These [[neuron]]s displayed electrophysiological characteristics identical to those recorded from nonsonicated thalamic cells in ET patients. Hence, this findings support the widespread assumption that [[sonication]] below the necrotic threshold does not permanently alter neuronal function
((De Vloo P, Milosevic L, Gramer RM, et al. Microelectrode Recording and Radiofrequency Thalamotomy following Focused Ultrasound Thalamotomy [published online ahead of print, 2020 Sep 16]. Stereotact Funct Neurosurg. 2020;1-4. doi:10.1159/000510109)).
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===== References =====