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CSP 468

Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's Disease

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Year of Publication: 2010

Authors: Kenneth A. Follett, Frances M. Weaver, Matthew Stern, ..., Claudia Moy

Journal: New England Journal of Medicine

Citation: N Engl J Med 2010;362:2077-91

Link: https://doi.org/10.1056/NEJMoa0907083

Clinical Question

Is bilateral deep-brain stimulation of the globus pallidus interna (pallidal stimulation) superior to bilateral stimulation of the subthalamic nucleus (subthalamic stimulation) for improving motor function in patients with advanced Parkinson's disease?

Bottom Line

Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation at 24 months. Subthalamic stimulation allowed greater medication reduction but showed greater decline in visuomotor processing speed and worsening depression compared to pallidal stimulation.

        Major Points
        Mean changes in UPDRS-III motor scores did not differ significantly between groups (−11.8 points for GPi vs −10.7 points for STN, P=0.50)
Patients undergoing STN stimulation required lower doses of dopaminergic agents (reduction of 408 mg vs 243 mg levodopa equivalents, P=0.02)
Visuomotor processing speed declined more after STN stimulation than after GPi stimulation (P=0.03)
Depression scores worsened after STN stimulation but improved after GPi stimulation (P=0.02)
Serious adverse events occurred in 51% of GPi and 56% of STN patients with no significant difference
Quality of life measures showed no significant differences between groups

      

Design

Study Type: Randomized Controlled Trial

Randomization: 1

Blinding: Single-blind (evaluators blinded to surgical target assignment; patients unaware of surgical target)

Enrollment Period: Not explicitly stated

Follow-up Duration: 24 months

Centers: 13

Countries: United States

Sample Size: 299

Analysis: Intention-to-treat analysis with mixed-effects models

Inclusion Criteria

Idiopathic Parkinson's disease
At least 21 years of age
Hoehn and Yahr stage 2 or higher while off medication
Response to levodopa
Persistent and disabling symptoms (motor fluctuations and dyskinesia) despite optimal medical therapy
At least 3 hours per 24-hour period with poor motor function or symptom control
Receiving medical therapy with no changes in regimen for at least 1 month

Exclusion Criteria

Not explicitly detailed in the document

Arms

Field	Pallidal Stimulation (GPi)	Subthalamic Stimulation (STN)
Intervention	Bilateral deep-brain stimulation of the globus pallidus interna. Average stimulation: 3.95 V, 95.7 μsec, 168 Hz	Bilateral deep-brain stimulation of the subthalamic nucleus. Average stimulation: 3.16 V, 75.9 μsec, 165 Hz
Duration	24 months	24 months

Outcomes

Outcome	Type	Control	Intervention	P-value
Change in UPDRS-III motor score from baseline to 24 months with stimulation but without medication	Primary	GPi: −11.8 points (95% CI −14.1 to −9.5)	STN: −10.7 points (95% CI −12.9 to −8.5)	0.50
Levodopa equivalents reduction	Secondary	GPi: −243 mg	STN: −408 mg	0.02
Processing speed index (Wechsler Adult Intelligence Scales III)	Secondary	GPi: Change −3.0	STN: Change −5.9	0.03
Beck Depression Inventory II	Secondary	GPi: Change −0.6 (improvement)	STN: Change +1.3 (worsening)	0.02
PDQ-39 quality of life	Secondary	GPi: Improvement −4.8 points	STN: Improvement −4.2 points	0.69
Serious adverse events - GPi	Adverse	77 patients (50.7%)		0.35
Serious adverse events - STN	Adverse		83 patients (56.5%)
Implantation-site infection	Adverse	GPi: 12 (7.9%)	STN: 11 (7.5%)
Falls	Adverse	GPi: 5 (3.3%)	STN: 13 (8.8%)
Deaths	Adverse	GPi: 5	STN: 8

Subgroup Analysis

Results were consistent across subgroups. Patients originally assigned to medical therapy vs. those directly assigned to DBS showed similar results.

Criticisms

No formal correction for multiple comparisons in secondary outcomes
Single-blind design (evaluators blinded but surgeons and treating physicians aware of target)
13 deaths during follow-up with differential attrition between groups
Limited follow-up duration (24 months)
Predominantly male veteran population may limit generalizability

Funding

Veterans Affairs Cooperative Studies Program, NINDS, Medtronic

Based on: CSP 468 (New England Journal of Medicine, 2010)

Authors: Kenneth A. Follett, Frances M. Weaver, Matthew Stern, ..., Claudia Moy

Citation: N Engl J Med 2010;362:2077-91

Content summarized and formatted by NeuroTrials.ai.

CSP 468

(2010)

Objective

To compare 24-month outcomes for patients who underwent bilateral stimulation of the globus pallidus interna (pallidal/GPi) or subthalamic nucleus (STN) for advanced Parkinson's disease.

Study Summary

• No significant difference in motor function improvement between GPi and STN DBS (UPDRS-III reduction 11.8 vs 10.7 points, P=0.50)
• STN group required less dopaminergic medication (reduction of 408 mg vs 243 mg levodopa equivalents, P=0.02)
• Depression worsened after STN but improved after GPi (P=0.02); processing speed declined more with STN (P=0.03)

Intervention

Bilateral GPi DBS vs bilateral STN DBS with 24-month follow-up

Inclusion Criteria

Adults >=21 years with idiopathic PD, Hoehn and Yahr stage >=2 off medication, levodopa-responsive, persistent motor fluctuations/dyskinesia despite optimal medical therapy

Study Design

Arms: GPi (Pallidal) DBS, STN (Subthalamic) DBS

Patients per Arm: GPi: 152, STN: 147

Outcome

• Primary: UPDRS-III change at 24 months (on stim, off med): -11.8 (GPi) vs -10.7 (STN), P=0.50
• Serious adverse events: 51% GPi vs 56% STN (NS)
• Depression score: improved with GPi, worsened with STN (P=0.02)
• Processing speed: greater decline with STN (P=0.03)

Bottom Line

Major Points

Mean changes in UPDRS-III motor scores did not differ significantly between groups (−11.8 points for GPi vs −10.7 points for STN, P=0.50)
Patients undergoing STN stimulation required lower doses of dopaminergic agents (reduction of 408 mg vs 243 mg levodopa equivalents, P=0.02)
Visuomotor processing speed declined more after STN stimulation than after GPi stimulation (P=0.03)
Depression scores worsened after STN stimulation but improved after GPi stimulation (P=0.02)
Serious adverse events occurred in 51% of GPi and 56% of STN patients with no significant difference
Quality of life measures showed no significant differences between groups

Study Design

Study Type: Randomized Controlled Trial
Randomization: Yes
Blinding: Single-blind (evaluators blinded to surgical target assignment; patients unaware of surgical target)
Sample Size: 299
Follow-up: 24 months
Centers: 13
Countries: United States

Primary Outcome

Definition: Change in UPDRS-III motor score from baseline to 24 months with stimulation but without medication

Control	Intervention	HR/OR	P-value
GPi: −11.8 points (95% CI −14.1 to −9.5)	STN: −10.7 points (95% CI −12.9 to −8.5)	- (Difference −1.1 points (95% CI −4.3 to 2.1))	0.50

Limitations & Criticisms

No formal correction for multiple comparisons in secondary outcomes
Single-blind design (evaluators blinded but surgeons and treating physicians aware of target)
13 deaths during follow-up with differential attrition between groups
Limited follow-up duration (24 months)
Predominantly male veteran population may limit generalizability

Citation

N Engl J Med 2010;362:2077-91

View Original Publication →

CSP 468

Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's Disease

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

Ask about CSP 468