Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson’s disease: a meta-analysis of randomized controlled trials

Figures & data

Table 1 Characteristics of included randomized controlled trials comparing GPi DBS with STN DBS for advanced Parkinson’s disease

Study	Country	Target	Surgical modus	Subject size, n	Male/female, n	Age (years), mean ± SD	Disease duration (years), mean ± SD	Outcome measure	Assessment time points
Odekerken et al^Citation16	The Netherlands	GPi	Bilateral	58	40/18	59.2±7.7	10.9±4.0	Neurocognitive status	Baseline, 12 months
		STN		56	42/14	60.3±7.4	12.3±5.5
Rothlind et al^Citation15	USA	GPi	Bilateral	80	NA	61.3±8.9	11.0±4.7	Neurocognitive status	Baseline, 6 months, 12 months, 24 months
		STN		64		61.3±8.5	11.0±5.0
Okun et al^Citation17	USA	GPi	Bilateral	14	6/8	60.1±5.5	11.5±3.3	UPDRS-III, LED, BDI-II	Baseline, 2 months, 4 months, 6 months, 12 months
		STN		16	3/13	58.0±10.7	12.1±4.5
Odekerken et al^Citation6	The Netherlands	GPi	Bilateral	65	44/21	59.1±7.8	10.8±4.2	UPDRS-III, LED	Baseline, 12 months
		STN		63	44/19	60.9±7.6	12.0±5.3
Weaver et al^Citation7	USA	GPi	Bilateral	89	77/12	60.4±8.3	11.4±4.9	UPDRS-III, LED, PDQ-39	Baseline, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months
		STN		70	56/14	60.7±8.9	11.3±4.7
Rocchi et al^Citation8	Italy and USA	GPi	Bilateral	14	13/1	61.1±8.4	12.9±10.7	UPDRS-III, LED	Baseline, 6 months
		STN		15	11/4	61.4±5.5	11.9±4.8
Follett et al^Citation9	USA	GPi	Bilateral	152	133/19	61.8±8.7	NA	UPDRS-III, LED, BDI-II	Baseline, 6 months, 24 months
		STN		174	116/31	61.9±8.7		Neurocognitive status, PDQ-39
Zahodne et al^Citation10	USA	GPi	Unilateral	22	16/6	61.3±5.5	12.4±3.6	UPDRS-III, LED, BDI-II	Baseline, 6 months
		STN		20	14/6	61.3±9.0	13.6±3.9	PDQ-39
Rothlind et al^Citation11	USA	GPi	Bilateral	23	18/5	60.2±8.83	13.3±6.4	UPDRS-III, BDI-II, LED	Baseline, 6 months, 21 months
		STN		19	15/4	61.4±10.11	12.9±4.3	Neurocognitive status
Anderson et al^Citation13	Switzerland	GPi	Bilateral	10	NA	54±12	10.3±2	UPDRS-III	Baseline, 12 months
		STN		10		61±9	15.6±5

Abbreviations: GPi, globus pallidus interna; STN, subthalamic nucleus; DBS, deep brain stimulation; NA, not available; UPDRS-III, unified Parkinson’s disease rating scale III; LED, levodopa equivalent doses; BDI-II, Beck Depression Inventory II; PDQ-39, Parkinson’s Disease Questionnaire-39; SD, standard deviation.

Figure 1 Flow diagram of selection of RCTs.

Abbreviations: RCTs, randomized controlled trials; DBS, deep brain stimulation.

Figure 2 Risk of bias graph.

Notes: (A) Each risk of bias item for each included study. (B) The overall risk of bias is relatively low. “+” indicates yes; “?” indicates not clear.

Figure 3 Forest plot of mean difference of UPDRS-III score in the off-medication/on-stimulation state, stratified by follow-up length.

Abbreviations: UPDRS-III, unified Parkinson’s disease rating scale III; GPi, globus pallidus interna; STN, subthalamic nucleus; IV, inverse variance; CI, confidence interval.

Figure 4 Forest plot of mean difference of UPDRS-III score in the on-medication/on-stimulation state, stratified by follow-up length.

Abbreviations: UPDRS-III, unified Parkinson’s disease rating scale III; GPi, globus pallidus interna; STN, subthalamic nucleus; IV, inverse variance; CI, confidence interval.

Figure 5 Forest plot of standardized mean difference of levodopa equivalent doses.

Abbreviations: GPi, globus pallidus interna; STN, subthalamic nucleus; IV, inverse variance; CI, confidence interval; Std, standardized.

Figure 6 Forest plot of standardized mean difference of Beck Depression Inventory II.

Abbreviations: GPi, globus pallidus interna; STN, subthalamic nucleus; IV, inverse variance; CI, confidence interval; Std, standardized.

Table 2 Entire results of neurocognitive status comparison between GPi DBS and STN DBS

Measure	Included study number	SMD, IV, fixed, 95% CI	Test for heterogeneity		Test for overall effect
			I^2 (%)	P-value	Z	P-value
Verbal fluency
Semantic fluency	3	0.21 (0.03 to 0.40)	0	0.68	2.25	0.02
Phonemic fluency	3	0.19 (0.00 to 0.38)	0	0.79	1.97	0.05
Processing speed
Stroop word reading	3	0.33 (0.10 to 0.56)	41	0.16	2.83	0.005
Stroop color naming	3	0.19 (−0.29 to 0.67)	42	0.15	0.78	0.44
Trail making test A	3	0.05 (−0.18 to 0.27)	27	0.26	0.39	0.69
Language
Boston naming test	3	0.11 (−0.05 to 0.27)	0	0.86	1.41	0.16
Executive function
Trail making test B	3	0.10 (−0.27 to 0.47)	41	0.16	0.55	0.58
Stroop color–word interference	3	0.14 (−0.09 to 0.37)	0	0.84	1.21	0.23
Dementia
MDRS	2	0.14 (−0.05 to 0.33)	0	0.95	1.44	0.15

Abbreviations: GPi, globus pallidus interna; STN, subthalamic nucleus; DBS, deep brain stimulation; SMD, standardized mean difference; IV, inverse variance; CI, confidence interval; MDRS, Mattis dementia rating scale.

Figure 7 Forest plot of standardized mean difference of semantic fluency test.

Abbreviations: GPi, globus pallidus interna; STN, subthalamic nucleus; IV, inverse variance; CI, confidence interval; Std, standardized.

Table 3 Entire results of quality of life comparison between the two targets

PDQ-39	SMD, IV, fixed, 95% CI	Test for heterogeneity		Test for overall effect
		I^2 (%)	P-value	Z	P-value
Mobility	−0.35 (−0.53 to −0.17)	0	0.74	3.88	0.0001
Activities of daily living	−0.50 (−0.68 to −0.32)	0	0.57	5.44	<0.00001
Emotional well-being	−0.26 (−0.44 to −0.09)	0	0.38	2.90	0.004
Stigma	−0.13 (−0.30 to 0.05)	0	0.89	1.39	0.16
Social support	−0.21 (−0.39 to −0.04)	0	0.65	2.34	0.02
Cognition	−0.26 (−0.43 to −0.08)	0	0.95	2.85	0.004
Communication	−0.37 (−0.71 to −0.03)a	64	0.06	2.11	0.04
Bodily discomfort	−0.21 (−0.39 to −0.04)	0	0.46	2.38	0.02
Single index	−0.33 (−0.51 to −0.15)	0	0.91	3.63	0.0003

Note:

a The random-effects model was used because of significant heterogeneity (I²=64%, P=0.06).

Abbreviations: SMD, standardized mean difference; IV, inverse variance; CI, confidence interval.

Figure 8 Forest plot of standardized mean difference of the subscale “communication”.

Notes: (A) GPi had lower score and the difference was significant. But the heterogeneity between studies was substantial. (B) The heterogeneity reduced greatly (I²=0%, P=0.06) when the study “Weaver et al⁷” was excluded.
Abbreviations: GPi, globus pallidus interna; STN, subthalamic nucleus; IV, inverse variance; CI, confidence interval; Std, standardized.

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