Surgical Treatments for Parkinson's Disease

Surgical treatments for Parkinson's disease are generally considered when motor symptoms can no longer be adequately controlled with medication alone, particularly when patients experience significant motor fluctuations ("on-off" periods) or debilitating levodopa-induced dyskinesias. Surgery does not cure Parkinson's disease and does not slow its progression, but it can substantially improve motor symptoms and reduce the need for medication in carefully selected patients.

Deep Brain Stimulation (DBS)

Deep brain stimulation is the most widely performed surgical procedure for Parkinson's disease. It involves implanting thin electrodes into specific brain targets and connecting them to a pulse generator (similar to a cardiac pacemaker) placed under the skin near the collarbone. The device delivers continuous electrical impulses that modulate abnormal brain circuit activity.

How DBS Works

The exact mechanism of DBS is not fully understood, but it is believed to work by disrupting pathological neural oscillations in the basal ganglia circuits that are overactive in PD. The electrical stimulation effectively overrides the abnormal signaling patterns that cause motor symptoms. Stimulation parameters (frequency, amplitude, pulse width) can be adjusted after surgery to optimize benefit and minimize side effects.

Brain Targets

Two brain structures are the primary targets for DBS in Parkinson's disease:

• Subthalamic nucleus (STN). The most common target. STN-DBS can improve all cardinal motor features of PD and typically allows significant reduction in medication doses. A landmark 2006 randomized trial published in the New England Journal of Medicine demonstrated that STN-DBS significantly improved motor function and quality of life compared to best medical therapy alone.
• Globus pallidus internus (GPi). Particularly effective for reducing dyskinesias. A 2010 VA cooperative study (COMPARE trial) found that GPi-DBS and STN-DBS produced similar improvements in motor function at two years, though GPi-DBS may have fewer cognitive and behavioral side effects.

Who Is a Candidate

Ideal DBS candidates typically meet the following criteria:

• Idiopathic Parkinson's disease (not atypical parkinsonism)
• Good response to levodopa (symptoms that respond to medication will generally respond to DBS)
• Motor fluctuations or dyskinesias that significantly impair daily life despite medication optimization
• No significant cognitive impairment or untreated psychiatric conditions
• Medically fit for surgery
• Realistic expectations about outcomes

DBS is typically considered after at least four to five years of disease duration, though recent research (the EARLY-STIM trial) has explored DBS in earlier disease stages with promising results.

Benefits

• Reduction in motor fluctuations and "off" time by 50-70%
• Significant reduction in levodopa-induced dyskinesias
• Improvement in tremor, rigidity, and bradykinesia during stimulation
• Reduction in total daily medication dose (typically 30-50% with STN-DBS)
• Improved quality of life and ability to perform daily activities

Long-term outcomes data are encouraging. A 2025 study published in JAMA Neurology reported sustained improvements at 5 years: maintained motor function benefits, continued dyskinesia suppression, improvement in activities of daily living, and reduced medication requirements. These findings confirm that DBS benefits are durable, though the underlying disease continues to progress. The EARLY-STIM trial (NEJM 2013) demonstrated that DBS in earlier disease stages (within 3 years of motor fluctuation onset) was superior to best medical therapy for quality of life, motor function, and daily activities.

Risks and Limitations

• Surgical risks. Intracranial hemorrhage (1-2%), infection at the surgical site (3-5%), lead migration or fracture (rare).
• Stimulation side effects. Speech difficulties (particularly with bilateral STN-DBS), balance problems, paresthesias, and mood changes. These can often be managed by adjusting stimulation settings.
• Limitations. DBS does not significantly improve symptoms that do not respond to levodopa (except tremor), does not improve gait freezing in most cases, and does not prevent disease progression. Cognitive decline, speech problems, and postural instability may continue to worsen despite DBS.

MRI-Guided Focused Ultrasound (MRgFUS)

Focused ultrasound is a newer, incisionless approach that uses converging ultrasound beams to create a precise thermal lesion in the brain. The procedure is performed inside an MRI scanner, which provides real-time imaging to guide targeting and monitor the lesion. No incision, no electrodes, and no implanted hardware are required.

Current Indications

MRI-guided focused ultrasound has received progressively broader FDA approvals for PD: unilateral thalamotomy for tremor-dominant PD (2018), expanded indications for mobility, rigidity, bradykinesia, and dyskinesia (2021), and most recently, bilateral staged treatment (2025) targeting the pallidothalamic tract — with two procedures spaced at least 6 months apart.

A randomized trial published in the New England Journal of Medicine demonstrated significant tremor reduction compared to a sham procedure. The bilateral staged approach is particularly significant because it addresses the previous limitation of unilateral-only treatment, though it requires two separate sessions.

Advantages

• No incision, no anesthesia (patient is awake during the procedure)
• Real-time MRI monitoring for precise targeting
• Immediate effect that can be assessed during the procedure
• Lower risk of infection compared to implanted devices
• No implanted hardware requiring maintenance or battery replacement
• Typically completed within 1-2 hours per session
• Bilateral staged treatment now FDA-approved (2025)

Limitations

• The lesion is permanent and cannot be adjusted like DBS settings
• Not all patients are eligible — skull density ratio must allow adequate ultrasound penetration (approximately 15-20% of candidates are excluded)
• Bilateral treatment requires two separate sessions at least 6 months apart
• Less long-term follow-up data compared to DBS (decades of experience)
• Some patients experience transient numbness, balance disturbance, or gait changes

Lesioning Procedures

Before DBS became widely available, ablative (lesioning) surgeries were the primary surgical treatment for PD. These procedures create a permanent, targeted lesion to disrupt abnormal brain circuit activity. While largely supplanted by DBS in developed countries, lesioning procedures remain relevant in settings where DBS is unavailable or impractical, and have been revitalized by focused ultrasound technology.

Types of Lesioning Procedures

• Pallidotomy. Creates a lesion in the globus pallidus internus. Particularly effective for reducing contralateral dyskinesias and improving motor function. Historically performed with radiofrequency probes, now increasingly performed with focused ultrasound.
• Thalamotomy. Creates a lesion in the ventral intermediate nucleus (VIM) of the thalamus. Highly effective for contralateral tremor control. Now commonly performed with MRI-guided focused ultrasound.
• Subthalamotomy. Creates a lesion in the subthalamic nucleus. Under investigation as a focused ultrasound procedure, with early results suggesting improvements in motor scores comparable to STN-DBS.

Considerations

• Lesions are permanent; effects (both benefits and side effects) cannot be adjusted
• Bilateral lesioning carries a higher risk of speech and cognitive side effects
• May be appropriate for patients who cannot undergo DBS (e.g., those who cannot manage device maintenance or follow-up programming)
• Focused ultrasound has reduced the risk profile compared to traditional radiofrequency lesioning

Choosing the Right Procedure

The decision about which surgical approach is best depends on multiple factors, including the patient's predominant symptoms, overall health, cognitive status, and personal preferences. Key considerations include:

• Symptom profile. Tremor-predominant PD may respond well to focused ultrasound thalamotomy. Patients with significant motor fluctuations and dyskinesias are typically better served by DBS.
• Bilateral versus unilateral symptoms. DBS can be performed bilaterally and adjusted over time. Focused ultrasound lesioning is currently limited to unilateral treatment.
• Long-term management. DBS requires ongoing programming, battery replacements (every 3-5 years for non-rechargeable devices), and regular follow-up. Patients must be willing and able to manage this commitment.
• Cognitive status. Patients with significant cognitive impairment are generally not candidates for any surgical procedure. Mild cognitive changes may influence the choice of DBS target (GPi may be preferred over STN).

A comprehensive evaluation by a movement disorder specialist and neurosurgeon experienced in these procedures is essential before making a surgical decision. Many centers offer multidisciplinary presurgical evaluations that include neurological examination, neuropsychological testing, brain imaging, and a detailed discussion of risks, benefits, and expectations.

Patient Selection: Who Is a Candidate for Surgery?

Comprehensive presurgical evaluation is critical for all surgical PD interventions. Published consensus referral recommendations (npj Parkinson's Disease, 2025) emphasize that patient selection is the single most important factor in surgical outcomes. A multidisciplinary evaluation typically includes:

• Comprehensive neurological exam with motor testing in both the on-medication and off-medication states to confirm levodopa responsiveness
• Neuropsychological testing to assess cognitive function, mood, and identify psychiatric contraindications
• Brain MRI to evaluate anatomy and rule out structural abnormalities
• Realistic expectations discussion — surgery improves symptoms that respond to levodopa (except tremor, which can improve even without levodopa response) but does not cure PD or halt progression
• Social support assessment — patients need support for postoperative recovery and ongoing programming visits

The general principle is that a good surgical candidate is someone with clear idiopathic PD, good cognitive function, and motor symptoms (particularly motor fluctuations and dyskinesia) that significantly impair quality of life despite optimized medication.

Emerging Surgical Approaches

Research into new surgical treatments for PD continues at an accelerating pace. Several approaches are in various stages of clinical investigation:

Adaptive (Closed-Loop) DBS

Conventional DBS delivers continuous stimulation at fixed settings, regardless of the patient's moment-to-moment state. Adaptive DBS (aDBS) represents a paradigm shift: implanted sensors detect neural biomarkers (typically beta oscillations in the subthalamic nucleus) in real time and automatically adjust stimulation intensity to match the patient's current needs. Early clinical trials suggest that aDBS can provide better control of motor symptoms than conventional DBS, with a patient's most bothersome symptom and gait among the areas showing the most consistent benefits. Adaptive systems may also extend battery life by delivering stimulation only when needed.

Gene Therapy

Clinical trials are investigating viral vector delivery of therapeutic genes directly into the brain. The most advanced program — AB-1005 (GDNF gene therapy) — has received FDA Regenerative Medicine Advanced Therapy designation and is in Phase 2 trials (REGENERATE-PD), which are still enrolling, with estimated primary completion in 2028. A dual-mechanism approach (VGN-R09b) combines AADC gene delivery (to convert levodopa to dopamine) with GDNF neuroprotection. The first trial to correct a genetic cause of PD in humans (GBA gene correction) has also begun.

Cell-Based Therapies

Transplantation of dopamine-producing cells into the brain aims to restore dopamine production directly. The field has advanced significantly from early fetal tissue transplant trials (mixed results in the 1990s-2000s) to modern stem cell approaches. BlueRock Therapeutics (Bayer) initiated the first large-scale global Phase 3 cell therapy trial for PD (exPDite-2) in September 2025, using dopamine neurons derived from human embryonic stem cells (bemdaneprocel). Autologous approaches — using the patient's own reprogrammed stem cells — are also advancing at Mass General Brigham and other centers.

These approaches remain investigational and are not yet standard of care. Patients interested in clinical trials can discuss options with their movement disorder specialist or search for trials at ClinicalTrials.gov or through the Michael J. Fox Foundation Fox Trial Finder.