Difference in the effectiveness of subthalamic nucleus and globus pallidus deep brain stimulation in Parkinson’s disease | Azari | Aging Pathobiology and Therapeutics

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Difference in the effectiveness of subthalamic nucleus and globus pallidus deep brain stimulation in Parkinson’s disease


Hushyar Azaria, *

a Faculty of Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia 571478334, Iran.

* Corresponding author: Hushyar Azari, MD.
Mailing address: Faculty of Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia 571478334, Iran.
Email: hushyarazari@hotmail.com

Received: 20 April 2022 / Revised: 17 May 2022 / Accepted: 23 May 2022 / Published: 30 June 2022

DOI: 10.31491/APT.2022.06.082

Abstract

Deep brain stimulation (DBS) is regarded as a feasible Parkinson’s disease (PD) treatment option. The subthalamic nucleus (STN) and globus pallidus (GPi) are the two most common sites for DBS. The following criteria were used to select studies that examined the Unified PD Rating Scale (UPDRS) III: (1) had at least three months of follow-up; (2) compared both GPi and STN-DBS; (3) each group included at least five individuals; (4) were conducted after 2010. The majority of studies found no statistically significant difference in UPDRS score improvements between groups. Although there were some encouraging findings in terms of action tremor, rigidity, and urinary symptoms, indicating that STN-DBS would be a better alternative, GPi appeared to be better in terms of side effects; nonetheless, it cannot be said that it is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are required to determine which target is more effective for stimulation and has fewer negative side effects on patients.

Keywords

Deep brain stimulation, globus pallidus, Parkinson’s disease, subthalamic nucleus, UPDRS


Parkinson’s disease (PD) is the most common mobility condition, as well as the second most common progressive, debilitating, and neurodegenerative disease, with 12.9 million cases projected by 2040 [1-4]. Slow motions, rigidity, and low amplitude movements without antecedent automaticity characterize PD. In 1911, the dopamine precursor levodopa was developed for the first time [5]. It has been used as an effective PD treatment for more than 50 years, although its efficacy has been demonstrated to decrease as the disease advances [6, 7]. The deep brain stimulation (DBS) technique was first used in 1987 to treat movement disorders by targeting the ventral intermediate nucleus of the thalamus [8, 9]. DBS is a frequent and effective surgical treatment for motor symptom relief. It was first used roughly three decades ago and is now used on a variety of new brain targets, including the subthalamic nucleus (STN) and globus pallidus (GPi) [10-12]. According to studies, the efficacy of these two targets is varied. It has been suggested that in PD, there is chronic betaband oscillation coordination, and short-term bursts of these oscillations demonstrate normal sensory and motor processing. In PD, DBS can shorten bursts and enhance movement [13].
Embase, Cochrane Library, and PubMed databases were searched for potentially relevant English-language papers published between 2010 and 2021. We looked for studies that included both the targets (GPi and STN) as well as their associated characteristics. DBS [MeSH term] or a combination of the following keywords: controlled clinical trial [Publication Category], randomized controlled trial [Publication Category], globus pallidus internus [MeSH term], globus pallidus [MeSH term], GPi [MeSH term], STN [MeSH term], and PD [MeSH term].
We included clinical studies that (1) evaluated the unified PD rating scale (UPDRS) III before and after DBS; (2) compared GPi-DBS and STN-DBS for PD; (3) recruited more than five subjects in the GPi and STN groups; (4) had a description of adverse events; (5) had a follow-up period of more than three months; (6) were available in English full text. The main characteristics of the studies are shown in Table 1.

Table 1
Main characteristics of studies.

Reference Target Age Sample size UPDRS on-periodbaseline UPDRS off-periodbaseline Follow up period Location
Odekerken [14] GPi
STN
59.10 ± 7.80
60.90 ± 7.60
62
63
16.00 ± 8.00
17.00 ± 9.90
43.80 ± 13.50
44.40±15.50
12 Europe
Troche [15] GPi
STN
64.26 ± 8.79
66.50 ± 7.02
19
14
23.13 ± 6.73
23.43 ± 10.64
39.89 ± 11.06
35.93 ± 8.98
6 Asia
Odekerken [16] GPi
STN
59.10 ± 7.80
60.90 ± 7.60
43
47
N/A 43.00
41.00
36 Europe
Gong [17] GPi
STN
63.20 ± 9.10
62.30 ± 10.40
28
36
26.20 ± 7.50
29.00 ± 10.00
N/A 4 Asia
Fan [18] GPi
STN
60.43 ± 8.44
59.65 ± 9.11
23
20
N/A 50.68 ± 15.36
47.85 ± 14.95
12 Asia
Celiker [20] GPi
STN
54.00 ± 4.51
56.16 ± 9.60
6
6
22.50 ± 6.65
22.16 ± 6.55
49.00 ± 13.57
47.00 ± 14.01
24 Asia
Okun [21] GPi
STN
60.10 ± 5.50
58.00 ± 10.70
14
16
20.80 ± 8.68
21.30 ± 7.56
40.50 ± 11.20
41.20 ± 9.32
12 USA
Wong [19] GPi
STN
63.00 ± 8.12
61.00 ± 10.33
31
57
N/A 47.32 ± 11.79
44.12 ± 10.45
12 USA

Note: Data presented as mean ± SD.

Odekerken et al. found that the GPi group had a lower change in UPDRS score during the off-drug phase than the STN group, and the GPi group had less dyskinesia during the on-drug period than the STN group. The reduction in time was similar in both phases, however, it was only significant in the off-phase (P = 0.02) [14]. Troche et al. found that both groups’ UPDRS scores improved significantly in the off-medication state before and after surgery (P < 0.001) [15]. Odekerken et al. found that the STN group showed larger improvements in the off-drug phase UPDRS-ME score after three years (P = 0.04), whereas there were no between-group differences in the on-drug phase [16]. Gong et al. found that four months after DBS, all patients experienced improvement (≥ 30% ) in UPDRS score in off-period, and pain symptoms improvement rate was 79% ± 27% and 75% ± 27% in STN and GPi groups, respectively [17]. In the drug off-phase, Fan et al. found that the mean improvement of UPDRS in the STN and GPi groups was 41.50% and 43.56%, respectively, with no significant difference between the groups (P = 0.609). GPi-DBS also demonstrated anti-dyskinesia effects directly [18]. When compared to GPi-DBS, Wong et al. found that STN-DBS was associated with a statistically significant decrease in bradykinesia and rigidity at six months (P < 0.001 and P = 0.025, respectively). In terms of tremor results, however, there was no significant difference between groups [19]. Celiker et al. found that on-phase UPDRS motor scores decreased considerably in both the STN and GPi groups (P < 0.05) and that STNDBS improved bladder symptoms better. Furthermore, both groups experienced reduced sleep issues following surgery [20]. Okun and colleagues looked at the effects of unilateral and staged bilateral STN and GPi-DBS. They discovered that off-phase UPDRS motor scores improved considerably after four and twelve months of follow-up in both unilateral and staged bilateral modes [20].
In terms of adverse events, Odekerken et al. found no statistically significant difference between groups (P > 0.05) [14]. According to Troche et al., mean penetrationaspiration (PA) scores did not change substantially for participants who got GPi surgery (P = 0.857) but significantly worsened for those who received STN-DBS (P = 0.007), indicating that STN-DBS has a negative influence on swallowing performance. In contrast, unilateral GPiDBS does not have this negative effect [15]. In the study by Fan et al., 50% of patients in the STN group showed dyskinesia caused by stimulation. In ten of these patients, the direct anti-dyskinesia effect of STN-DBS was also noticed [18]. Okun et al. found relatively minor effects on mood and apathy that were not significant [21]. Odekerken et al. revealed no significant differences in adverse events between the two groups in another trial, only mild incidents were noted [16]. The most prevalent adverse events, according to Wong et al., were difficulties with DBS lead hardware and bleeding, both of which were small and controlled easily [22]. The results of this study should be viewed with caution. Both STN-DBS and GPiDBS are potential stimulation sites, but this has not been confirmed. STN, on the other hand, had better results in terms of urinary symptoms, discomfort, dyskinesia, and action tremor.

Declarations

Acknowledgments

The author would like to express his gratitude to Urmia University of Medical Sciences, for English editing, especially Dr. Nazila Farrokh Eslamloo.

Authors’ contributions

The author contributed solely to the article.

Availability of data and materials

Not applicable.

Financial support and sponsorship

None.

Conflicts of interest

The author declared that there are no conflicts of interest.

Ethical approval and consent to participate

Not applicable.

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