Pallidal Deep Brain Stimulation for Parkinson’s Disease
Pallidal Deep Brain Stimulation (DBS) is a well-established neuromodulation therapy for Parkinson’s disease (PD), particularly targeting the globus pallidus internus (GPi).
Mechanism of Action
DBS involves delivering continuous electrical stimulation to the GPi via implanted electrodes, modulating abnormal neuronal activity. This helps in:
- Reducing excessive oscillatory activity in the basal ganglia.
- Restoring more physiological motor function.
- Modulating neurotransmitter release (dopamine, GABA, glutamate).
Indications
GPi-DBS is mainly used in: - Levodopa-responsive Parkinson’s disease with motor fluctuations or dyskinesias.
- Medication-resistant dystonia or disabling dyskinesias.
- Patients with prominent bradykinesia and rigidity who may not be ideal candidates for subthalamic nucleus (STN) DBS.
### GPi vs. STN DBS
- GPi-DBS is preferred in patients with significant dyskinesias as it has a direct antidyskinetic effect.
- STN-DBS often allows for greater medication reduction but may have a higher risk of worsening mood and cognitive symptoms.
- GPi-DBS generally has a lower risk of neuropsychiatric side effects compared to STN-DBS.
Clinical Outcomes
Studies have shown that GPi-DBS:
- Improves motor function (UPDRS-III scores).
- Reduces dyskinesias without worsening bradykinesia.
- Provides long-term symptom control, with sustained benefits beyond 5-10 years.
- Has less impact on cognition and speech compared to STN-DBS.
Limitations and Risks
- Requires surgical expertise and precise targeting. - Potential for hardware-related complications (infection, lead migration). - May not significantly reduce the need for dopaminergic medications as much as STN-DBS. - Limited effect on non-motor symptoms of PD (e.g., cognitive decline, autonomic dysfunction).
Future Directions
- Adaptive DBS (aDBS): Uses real-time feedback from local field potentials (LFPs) to optimize stimulation.
- Closed-loop DBS: Aims to fine-tune stimulation based on patient activity and symptoms.
- Gene therapy & neurostimulation synergy: Exploring combined approaches to modify disease progression.
Pallidal Deep Brain Stimulation (GPi-DBS) and Subthalamic Deep Brain Stimulation (STN-DBS) for Parkinson’s disease (PD) are not the same. They target different brain structures and have distinct effects.
Key Differences
Targeted Brain Structure:
GPi-DBS: Targets the Globus Pallidus internus (GPi).
STN-DBS: Targets the Subthalamic Nucleus (STN).
Effects on Symptoms
GPi-DBS: Effective for dyskinesias, rigidity, and motor fluctuations but does not allow for as much medication reduction.
STN-DBS: More potent for tremor, bradykinesia, and rigidity, and allows for greater reduction of dopaminergic medications, which can reduce medication-induced side effects.
Cognitive and Psychiatric Considerations
GPi-DBS: Considered safer for cognition and behavior, making it preferable for patients with cognitive decline or psychiatric issues.
STN-DBS: Has a higher risk of cognitive and mood side effects, such as depression, apathy, and impulsivity.
Medication Reduction
GPi-DBS: Less reduction in levodopa is typically achieved.
STN-DBS: Can lead to significant medication reduction, which may be beneficial for patients with motor fluctuations.
Patient Selection
GPi-DBS: Often preferred for older patients or those with dyskinesias and minimal tremor.
STN-DBS: Preferred for younger patients with significant tremor and those who want to reduce medication burden.
Which One is Better?
There is no universally “better” option; it depends on the patient’s symptoms and overall profile.
If tremor is dominant → STN-DBS is often preferred.
If dyskinesias are a major issue or cognitive preservation is a priority → GPi-DBS may be better.
Subthalamic deep brain stimulation for Parkinson's disease
Clinical research studies
The magnitude and factors associated with levodopa equivalent daily dose (LEDD) reduction in deep brain stimulation (DBS) of the Globus pallidus internus (GPi) for Parkinson's Disease (PD) remain unclear.
A consecutive cohort of 74 patients who had undergone GPi DBS was analyzed. Regression and probabilistic efficacy mapping were performed to evaluate factors predicting LEDD reduction.
32.4% of GPi individuals experienced significant LEDD reduction (>30%). Anteromedial GPi stimulation was associated with higher LEDD reduction.
Anteromedial stimulation of the GPi appears to be associated with medication reduction, challenging the idea that GPi DBS is ineffective at reducing LEDD. Further prospective study will be needed to validate these findings 1).
The study by Di Luca et al. provides compelling evidence that GPi DBS, particularly targeting the anteromedial region, can lead to significant LEDD reduction in a subset of patients. This challenges the conventional notion that GPi DBS is ineffective for medication reduction. However, several limitations—including heterogeneity in patient profiles, lack of direct STN comparisons, and absence of long-term follow-up—necessitate caution in interpreting these findings.
Future studies should:
Conduct direct comparative analyses between GPi and STN DBS in similar patient populations. Investigate the functional impact of LEDD reduction beyond a numerical threshold. Incorporate advanced imaging techniques to refine target localization. Extend follow-up to assess durability of medication reduction over time. In summary, while the study presents an important shift in our understanding of GPi DBS, its conclusions should be validated in larger, prospective, and comparative trials before influencing clinical practice.