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Year : 2022  |  Volume : 11  |  Issue : 3  |  Page : 159-164

Focused ultrasound and deep brain stimulation for Parkinsonism – Review of literature to investigate tradeoff between safety and efficacy

1 College of Medicine, Taibah University, Madinah, Saudi Arabia
2 Department of Pediatric Hematology/Oncology, King Faisal Special Hospital and Research Center, Riyadh, Saudi Arabia
3 Department of Mechanical and Mechatronics, University of Waterloo, Ontario, Canada
4 Department of Family and Community Medicine, College of Medicine, Taibah University, Madinah, Saudi Arabia

Date of Submission08-Aug-2022
Date of Acceptance08-Nov-2022
Date of Web Publication30-Nov-2022

Correspondence Address:
Uthman Alshenqiti
College of Medicine, Taibah University, Madinah
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjhs.sjhs_86_22

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Parkinsonism is a movement disorder, mostly caused by the neurodegenerative Parkinson's disease (PD), the second most common movement disorder. Its symptoms include rigidity, slow movement, tremor, and disruption of balance. First treatment line is dopamine replacement drugs, and surgery is due when medication fails. Surgery options include deep brain stimulation (DBS), which revolves around implanting impulse generator in the target structure, and magnetic resonance-guided focused ultrasound (MRgFUS), where transcranial sonication ablates certain structures to counter the excitotoxic circuitopathy. This review aims to compare results described in peer-reviewed publications describing DBS and MRgFUS in Parkinsonism in terms of improvement in symptoms and side effects. This study was carried out by searching prominent computerized biomedical databases (PubMed, Web of Science, Cochrane, and EMBASE) to assess and compare the safety and efficacy of MRgFUS and DBS procedures done for the treatment of PD. Most of the published results for each of the two operations are comparable, in tremor and Unified Parkinson's Disease Rating Scale scores, though minimal superiority is shown in the DBS results. The neurological adverse effects are similar between the two types, including mild-to-moderate transient instances of dysarthria and gait disturbances, which are the most common two adverse events, among others. However, DBS has a more severe or significant adverse event profile that includes hemorrhage and infection. Long-term improvement is observed more with DBS which can sustain improvement for up to 5 years. DBS, therefore, tends to better improve Parkinsonism prognosis at the cost of safety. Postoperative complications are less severe in MRgFUS, which can be a safe, efficient alternative procedure for medication-refractory Parkinsonism.

Keywords: Deep brain stimulation, high-intensity focused ultrasound ablation, Parkinson's disease, Parkinsonian disorders, Tremor

How to cite this article:
Alshenqiti U, Alzalabani Y, Siddiqui K, Alfaisal S, Albadrani M. Focused ultrasound and deep brain stimulation for Parkinsonism – Review of literature to investigate tradeoff between safety and efficacy. Saudi J Health Sci 2022;11:159-64

How to cite this URL:
Alshenqiti U, Alzalabani Y, Siddiqui K, Alfaisal S, Albadrani M. Focused ultrasound and deep brain stimulation for Parkinsonism – Review of literature to investigate tradeoff between safety and efficacy. Saudi J Health Sci [serial online] 2022 [cited 2023 Jan 28];11:159-64. Available from: https://www.saudijhealthsci.org/text.asp?2022/11/3/159/362380

  Introduction Top

Parkinsonism is a movement disorder, mostly caused by the neurodegenerative disease known as Parkinson's disease (PD). There is no evidence to directly identify a particular cause for the disease, but environmental factors and lifestyle are thought to be part of its etiology.[1] PD is the second most common movement disorder,[2],[3] affecting over 6 million people in the world,[4],[5] and this number may double by 2030. The incidence of the disease for people over 65 in developing countries is 160 in 100,000[6] and 27 in 100,000 in Saudi Arabia.[7] The pathogenesis of PD is characterized by degeneration of neurons in substantia nigra pars compacta of the midbrain, though it later involves other regions in the brain.[8],[9] The symptoms include rigidity, slow movement, tremor, and disruption of balance, to which the cardinal treatment regimen is the administration of dopamine replacement drugs.[6] Such drugs, e.g., levodopa, do not comprise a cure for the disorder, but rather counter the manifestation of symptoms, with the degeneration process ongoing. While the medication treatment is efficient, some cases fail to continue with the regimen. Such cases are optimally referred to surgical treatment. Operations used in PD include deep brain stimulation (DBS) and magnetic resonance-guided focused ultrasound (MRgFUS). DBS is a well-established neurosurgical procedure first applied for PD in 1948, where an impulse generator is implanted to the target area using a frame for stereotaxis, while computed tomography or magnetic resonance imaging (MRI) is used for guidance to the target area. One suggested mechanism with which DBS functions is that it stimulates targets in the brain by the implantable pulse generator.[8] MRgFUS, on the other hand, was first applied in 1947 in the USA, and it functions by transcranial lesioning of certain structures in the brain without requiring a cranial window. It achieves its function by blocking nerve conduction which raises the temperature locally, and at high frequencies, it can cause tissue ablation. The location of sonication can be tracked by several ways, including live MRI.[10] Radiosurgery can also be used to treat PD. Despite being efficiently used for resistant and late cases of PD, surgical operations should not be expected to be curative.[7] The aim of this review was to explore and compare the therapeutic and prognostic profiles of the DBS and MRgFUS used for Parkinsonism, such as improvement in symptoms, rates of relapse, and complications.

  Methodology Top

This review was carried out following the guidelines of PRISMA statement.[11] The primary aim of the review was to assess and compare the safety and efficacy of MRgFUS and DBS procedures done for the treatment of PD. We also wanted to search the parameters related to treatment outcome and any side effect reported in the literature.

Literature search strategy

We searched prominent computerized biomedical databases (PubMed, Web of Science, Cochrane, and EMBASE) for Medical Subject Headings terms and text words “Parkinson's Disease,” “Deep brain stimulation,” and “Magnetic Resonance-guided Focused Ultrasound.”

Screening of the studies

After searching the biomedical databases, the resulting studies were screened by the authors according to the inclusion criteria defined as: studies reporting the safety and/or efficacy of DBS and MRgFUS for the treatment of PD and published in English language. Nonhuman studies and conference abstracts were excluded. After removing the duplicates from the searched studies, we screened the studies by title and abstract. For studies reporting duplicated data, we kept only those with the most recent and complete reports. Screening process was carried out based on consensus among the authors in the face of any discrepancy.

Data extraction, quality assessment, and analysis

Data on study characteristics including authors, year of publication, study design, number of patients, age and gender, PD duration, type, and follow-up were extracted along with motor and nonmotor symptoms, quality of life, and adverse symptoms after the procedure were collected. Quality of each study was assessed by the authors using MINORS guidelines.[12] A descriptive analysis of the data thus collected was performed.

  Results Top

Of all the collected literature, 18 studies on MRgFUS were finally included in the review. Three of the studies were randomized clinical trials, four prospective studies, two reporting meta-analyses, three systematic reviews, four reviews, and the remaining two were pilot studies. Published studies which are the focus of this review are listed in [Table 1].
Table 1: List of studies reviewed

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Magnetic resonance-guided focused ultrasound

Improvement after magnetic resonance-guided focused ultrasound

Martínez-Fernández et al. in their study published in 2020 reported an improvement of 50.1% in scores from baseline to 4 months in the treatment group following focused ultrasound subthalamotomy in a randomized clinical trial in two groups of patients, measuring motor functions (using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (UPDRS), whereas in comparison, three other studies (Park et al., Chang et al., and Halpern et al.) used the Clinical Rating Scale for Tremor (CRST)[13],[14],[15]). The study with the least score found a 22% improvement, although the same study recorded a higher improvement from a lesser but relatively close baseline. Thirty-one percent (31%) improvement in UPDRS II is the second least in the reviewed literature reported by Park et al. in 2019.[13]

In a pilot study by the aforementioned Martínez-Fernández done in 2018, improvement of 53% is observed in off-medication UPDRS III and 47% in on-medication UPDRS III. This result was limited to 6 months following subthalamotomy in 8 out of 10 patients,[16] In the follow-up study, the off-medication UPDRS III score dropped from 19.9 to 9.8 which amounts to 52.6% improvement, with 8.1 score points between the treated group and the control group (95% confidence interval [CI], 6.0–10.3; P < 0.001) and the on-medication score improved by 46.4%.[17] In a similar study by Jung et al. in 2018, it was found that at 6 months after pallidotomy, all average scores improved: 31% for UPDRS II, 32.2% for “medication-off” UPDRS III (P = 0.018) and 39.1% after 1 year (P = 0.046), 12.9% for “medication-on” part III, and 57.4% for UPDRS IV.[18] Following thalamotomy, Park et al. in 2019 reported a 56% improvement in tremor (P = 0.013), 70% in maintenance of posture (P = 0.017), and 63% in both disability (P = 0.007) and action score (P = 0.006).[13]

In another study, hand tremor observations recorded at 6 months, 1 year, and 2 years improved by 55%, 53%, and 56%, respectively (95% CI, 7.6–10.0; P < 0.001). Furthermore, the study measured the disability after 6 months, 1 year, and 2 years at 56%, sustained for most subjects (P < 0.001).[14] This is similar to the finding of Bond et al. in 2020, which recorded a 62% improvement from a baseline tremor score of 17, though from a higher score of 23, only 22% improvement was recorded (P = 0.04).[19]

Another study reported improvement from baseline to 3 years ranging between 38% and 50% in hand tremor, between 50% and 75% in postural tremor, and between 43% and 56% in disability (all P < 0.0001),[15] and another reported a 45.2% improvement from a baseline score of 20 at 1 year (P < 0.0001).[20] In a systematic review, an average improvement of 55.6% in tremor and 60.1% in quality of life was recorded by Giordano et al.[21] A 2021 meta-analysis reported a UPDRS improvement of 47.0% ± 5.2% and 35.8% ± 4.5% following bilateral subthalamotomy and bilateral pallidotomy, respectively, and a lesser improvement of 24.8% ± 3.0% and 32.2% ± 5.5% following unilateral subthalamotomy and pallidotomy, respectively.[22] Moreover, CRST scores have been reported in a trial of thalamotomy to have dropped from 40.7 ± 11.6 to 8.2 ± 5.0 at 6 months (P < 0.001).[23] Another meta-analysis on MRgFUS thalamotomy and cerebellothalamic tract lesioning reported that the CRST Total, CRST Part A, and CRST Part C scores all improved by 62.2%, 62.4%, and 69.1%, respectively,[24] while in a different systematic review, a significant 96% initial improvement in CRST A and B is reported, though at 30 months, it dropped to 53.8%.[25] Improvement in mean tremor score of 47% at 3 months and 40% at 1 year is reported by Dallapiazza et al. in their study.[26]

Adverse events of magnetic resonance-guided focused ultrasound

The adverse effect of these operations is almost completely regarded as mild or moderate. The most severe reported adverse effects were pain related to sonication in two subjects and nausea and vomiting in one.[27] The most reported adverse event is dysarthria,[16],[17],[18],[20],[21],[22] reported in six studies, and described as mild and transient. An adverse event reported as frequently is ataxic gait, or gait disturbance, also reported in six studies.[14],[17],[21],[22],[23],[25] Among the six studies, this effect resolved by 3 months in one,[17] and by 4 in another,[23] while it persisted in another two but did not worsen.[14],[25] Other less common adverse events include hemiparesis[18],[19] and paresthesia,[19],[23] which are listed by Mohammed et al. in 2018 and Dallapiazza et al. in 2019 as the most common persistent adverse events,[24],[26] and due to the heat of sonication, scalp pain or burning sensation was experienced.[20],[23] These adverse events might be due to the heat energy of sonication, by affecting “off-target” structures, such as pyramidal tracts, or by the size of the lesion, as reported by Krishna in a systemic review published in 2018.[10]

Deep brain stimulation

Improvement after deep brain stimulation

A 2009 review has found that in advanced PD patients, bilateral subthalamic nucleus stimulation (STN-DBS) or globus pallidus internus stimulation (GPi-DBS) has been shown to enhance motor function in many trials, STN-DBS resulted in a 60% decrease in off-symptoms, and in most cases, dopaminergic therapy can be steadily decreased, resulting in a 60% reduction in severe dyskinesias. It also states that after treatment, the UPDRS motor score improved by 37% following GPi-DBS and 49% following STN-DBS, and the percentage of time spent with good movement and no disabling dyskinesias improved by double. These findings conform with other studies, and they were eventually validated in a broad prospective, randomized, multicenter trial that revealed a 41% increase in motor functions 6 months after surgery.[28] Other studies, trials, and reviews arrived at similar conclusions. Barbe et al. in their publication in 2018 reported a 64% improvement of tremor following posterior subthalamic area stimulation (PSA-DBS) (P = 0.002), and 50% following ventral intermediate nucleus stimulation (VIM-DBS) (P = 0.008).[29] Another study showed a 60% tremor improvement at 6 months (P < 0.001),[30] and a similar result of 60.1% on average was reported in the review by Giordano et al. in 2020 following bilateral treatment, though unilateral treatment yielded a lesser average of 56%.[21] Following bilateral VIM-DBS tremor has been reported to improve by a ranging percentage of 66%–78%, which marks the greatest percentage in the reviewed literature.[26] A trial by Weaver published in 2012, recorded a drop in UPDRS score from 41.1 to 27.1, which means an improvement of 34% following GPi-DBS (P < 0.001), whereas an improvement of 30% from a baseline of 42.5 is recorded after STN-DBS (P < 0.001).[27] Comparable results of 32.9% ± 3.2% UPDRS improvement after unilateral STN-DBS were reported, although bilateral stimulation of the nucleus resulted in 46.1% ± 3.1% improvement. The same study reported a 22.3% ± 2.8% and 38.5% ± 4.1% improvement after unilateral GPi-DBS and bilateral GPi-DBS, respectively.[22]

Adverse events of deep brain stimulation

DBS can cause serious adverse events. Speech deterioration has been observed,[26],[29],[30],[31] and some researchers documented changes in various areas of oral control and voice, while some patients' speech activity was unchanged by DBS of the nucleus subthalamus (STN).[31] Another commonly reported adverse event is gait disturbance.[26],[29],[30] More serious adverse events include hemorrhage and wound infection.[26],[30] In the systemic review by Dallapiazza in 2019, hemorrhage and infection are reported to have occurred in 0.5%–1.5% and 1.7%–5.4% of reviewed cases.[26] The neurological adverse events listed above can be ascribed to current-to-adjacent tracts, same as in MRgFUS, seeing as speech disturbance occurs at high stimulation amplitudes.[31]

  Discussion Top

Both procedures provided noticeable and favorable results. The MRgFUS procedures counter the excitotoxic nature of the disease by direct noninvasive lesioning,[1] which provides a major advantage for people ineligible for craniotomy. This method helps circumvent the nonneurological complications observed with DBS such as hemorrhage and infection, which are reported to be severe or significant.[26],[30] As for the neurological adverse events, both procedures have a similar profile. The findings of studies on each procedure show the common occurrence of dysarthria, gait abnormalities, and less commonly found effects of hemiparesis and paresthesia which are transient and not qualified as severe. In terms of beneficial effects, although MRgFUS promises favorable results, the UPDRS and other score improvement is more superior in DBS. This superiority is mild, however, and the results of both procedures are comparable regarding the primary outcome of this review which is the improvement of motor symptoms. Specifically, and disregarding the target area in the brain, tremor scores are close between the procedures, a recorded improvement in tremor is recorded as up to 75% improvement in postural tremor, and 78% in total tremor score for MRgFUS and DBS respectively. Although comparable, the highest aforementioned tremor improvement for MRgFUS is reported in a trial, while that of DBS is of better evidence in a systematic review. Therefore, in cases of tremor, DBS has a higher “best” score and reliability. It must be emphasized that this only alludes to the capacity each procedure can reach, although the majority of the results for tremor are more comparable. As for UPDRS motor scores, DBS also possesses the highest score reported in a trial study. DBS has the additional advantage of being more relevant for psychiatric symptoms accompanying the motor ones, such as frontal cognitive function defects and anxiety in PD.[32] In the long run, DBS is more sustainable, possibly due to the continuous impulse provided by the electrode, while MRgFUS studies report variant cases of fluctuation. DBS has been shown to have beneficial effects for up to 5 years in some studies,[26] which is not reported in the reviewed literature on MRgFUS.

From an economic perspective, both procedures have been deemed cost-effective. One review specified that the cost-effectiveness of MRgFUS was achieved with simultaneous medical therapy, more so than DBS, but also describes this advantage over DBS as “less substantial.”[33] Another study, however, describes DBS as the most cost-effective procedure for PD, though the advantageous status of MRgFUS has been more affirmed in the findings of two other reviews which conclude that MRgFUS is “significantly less” costly,[34],[35] and one describing it as more effective.[34] This somewhat evident economic advantage, along with the noninvasive nature of the procedure, stands as a further proof that MRgFUS is the more patient-favorite choice. However, these claims are disputed by a 2019 review, which states that data in the literature are too minimal to arrive at a conclusion.[36] It must also be mentioned that the costs of procedures and of medication differ from one country or state to another.

  Conclusion Top

The prognosis of Parkinsonism is promising with both DBS and MRgFUS, and the DBS procedure appears to be slightly more effective and more sustainable on the expense of safety. MRgFUS, on the other hand, offers the more patient-favorite option due to minimal invasion, and it should be the optimal choice for patients unable to undergo invasive surgery, though it can be the first choice operation to any medication refractive Parkinsonism due to its safety and a therapeutic profile relatively close to that of DBS, although more research on the subject is still needed.

Ethical approval

This study is a literature review and does not involve any patient-specific data. Therefore, it was not submitted to any regulatory body for ethical approval.

Submission declaration and verification

The work described in this article has not been published previously (except in the form of an abstract, a published lecture, or academic thesis), and is not under consideration for publication elsewhere. Its publication is approved by all authors and is explicitly approved by the responsible authorities where the work was carried out. If the work gets published in Saudi journal for health sciences, it will not be published elsewhere in the same form, in English, or in any other language, including electronically without the written consent of the copyright holder.

Data statement

The data used in this work can be shared publically upon reasonable request from the corresponding author.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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