Pd surg trial

Technical challenges and incomplete understanding of potential biomarkers have hampered adoption into clinical practice. The ideal PD therapy would slow down or even reverse disease progression. Animal studies have suggested that electrical stimulation may have such effect [ , ]. This led to a pilot study in patients with very early PD in hopes that DBS would provide disease-modifying benefit rather than just symptomatic treatment as it is used today.

This study was primarily focused on safety and feasibility, but it showed potential slowing of rest tremor progression in patients with STN-DBS compared to medication therapy alone in a post hoc analysis. However, there was no significant difference in UPDRS motor scores and quality of life between the 2 groups. Also, the study has limitations including small sample size and open-label design; therefore, currently, there is insufficient evidence to support neuroprotective effect, and a larger clinical trial is planned [ ].

Lesioning or ablative surgeries LS involve selective destruction of a targeted brain tissue volume in order to interrupt maladaptive neural networks.

Although LS have been performed for several decades in selected patients with PD, their use decreased in the s after the introduction of levodopa and then again in the s because of DBS. SRS and HIFU are considered less invasive than radiofrequency lesioning because they do not require a burr hole or an intracranial probe. Despite the fact that most clinicians favor DBS over LS wherever the former is widely available, LS is still utilized in less developed countries because of lack of appropriate infrastructure and training, financial constraints, limited research, awareness and referrals to tertiary centers, and follow-up care for DBS [ ].

With advancement in imaging and localization approaches, LS remains an alternative therapeutic option for PD management. Criteria for LS candidacy are similar to those of DBS, and a multidisciplinary evaluation by a movement disorders neurologist, a neuropsychologist, and a neurosurgeon to determine the appropriateness of the therapy and target selection is recommended. Compared to DBS, successful LS is relatively cheaper and reduces postoperative care and hardware-related complications [ ]; however, LS is not reversible and postprocedure optimization is not possible without revision surgery.

Unilateral lesioning can be followed by contralateral DBS in patients who are appropriate candidates [ , ]. Due to concern of intractable hemiballismus with subthalamotomies, STN has been less studied for LS in PD, although recent studies have demonstrated significant improvement in motor symptoms with minimal development of hemiballismus [ , , , ].

Generally, thalamotomy is considered for tremor-predominant PD or ET, although in patients with PD, a pallidotomy might be a better choice as it can additionally improve bradykinesia and rigidity. Similar to DBS, this surgical method includes neuroimaging, a stereotactic headframe, and introduction of an electrode intracranially coupled to an RF generator.

Patients are awake during the procedure and a test stimulation is done to confirm the target. A thermally induced lesion is then achieved at the tip of the active electrode with alternating current. The electrode is retracted after lesioning is complete.

RF lesioning allows distinct lesion borders with immediate results, thus allowing intraoperative confirmation of symptom improvement. Adverse effects of pallidotomy include visual field deficits, paresis, and neuropsychological deficits, and they are mostly transient due to perilesional edema of variable duration [ , , , ]. The surgical risk associated with RF technique also includes hemorrhage and infection [ ]. SRS lesioning involves a single large dose of ionizing radiation delivered noninvasively to a limited intracranial target volume using computerized dosimetry planning and image-guided stereotaxy.

Drawbacks associated with SRS include lack of intraoperative feedback, variable lesion size, poorly defined lesion borders, exposure to ionizing radiation, and delayed effect [ ]. The median onset of benefit is around 2 months and benefits are sustained long term median 30 months [ , ].

SRS has also been shown to have a similar efficacy and safety profile to RF lesioning and DBS therapies for pallidal lesions [ , ]. FUS utilizes high-intensity focused ultrasound beams targeted to an intracranial region to perform thermal ablation. An array of transducers in a helmet is used to pass ultrasonic waves through the skull into a target in the brain. Advantages of this technique include lack of ionizing radiation, immediate results, ability to produce well-circumscribed lesions, and real-time MRI monitoring.

Limitations include MRI environment—related claustrophobia in patients and longer operative times [ , ]. Its use in pallidotomies and subthalamotomies is under investigation. In this study, there were a total of 38 adverse events over a 6-month follow-up period.

Of these, there were three events which were related to the STN lesioning directly: off-medication choreic dyskinesia, on-medication nondisabling dyskinesia, and subjective speech disturbance. The two patients with dyskinesia had near resolution of symptoms at 6 months after the medications were adjusted [ ]. Different surgical treatment options can be considered in selected PD patients to improve motor symptoms that are poorly controlled with oral medications.

Both DBS or lesioning surgeries have shown to reduce "off time" and dyskinesia, treat medication-resistant tremor, and improve quality of life. Deciding on a specific therapy requires a multidisciplinary team and is tailored towards the individual patient, based on their symptoms, expectations, risk—benefit ratio, and local expertise. In healthcare systems where DBS is readily available, it is generally preferred over lesioning procedures because stimulation effects are adjustable and DBS can be safely performed bilaterally.

Lesioning procedures may be appropriate for patients who may not tolerate DBS hardware e. A well-placed lesion can provide excellent motor benefit, but it is less forgiving if suboptimal. Bilateral lesions should not be performed because of a high risk of complications, especially for pallidal and thalamic targets.

The exact type of lesioning procedure offered will usually depend on local expertise. MRgFUS is increasingly attractive to patients because it does not require an incision, although access is still limited because of high equipment costs.

Radiotherapy is typically less favored given the less predictable lesion size and delayed onset of benefit, but it may be a good option for patients who are unable to undergo DBS or other lesioning procedures. Utilizing DBS in a patient who had a prior lesioning procedure can provide additional therapeutic benefit, and it may be considered in select cases. This assumes that the patient is able to undergo DBS procedure even though lesioning was preferred as the initial treatment.

For example, a patient may have initially chosen to undergo lesioning to avoid frequent clinic visits for programming and hardware maintenance, but eventually developed troublesome contralateral symptoms, or had unilateral surgical contraindication for DBS.

Utilizing DBS is expected to reduce the chance of adverse events such as speech and cognitive difficulties observed after bilateral lesioning surgeries. Additionally, DBS can be considered as a rescue therapy for patients who had previously undergone lesioning and had suboptimal benefit, recurrence of symptoms, or certain side effects.

For example, a lesion-induced dyskinesia from a subthalamotomy could be improved by pallidal DBS. Conversely, if there have been repeated infections with DBS hardware, a patient may benefit from lesioning procedure even utilizing the existing DBS lead to create a lesion.

Patients with significant cognitive impairment, those with unstable psychiatric symptoms including hallucinations , or those with significant medical comorbidities are not good surgical candidates for DBS or lesioning procedures. Some patients may opt against neurosurgical procedures based on personal beliefs and risk tolerance. For those patients, other advanced therapies including levodopa—carbidopa intestinal gel infusion LCIG or continuous subcutaneous apomorphine infusion CSAi options should be considered.

An in-depth discussion of infusion devices is beyond the scope of this review article, but a brief comparison of surgical procedures with other advanced therapies is presented in Table 3. Specific motor symptoms may respond to a different degree following DBS or lesioning procedure. Tremor, dyskinesias, and rigidity respond very well, followed by bradykinesia, then gait and other axial symptoms. Gait difficulty and freezing of gait will typically respond if they are levodopa responsive, but many patients either have or eventually develop nonresponsive features, whereas balance typically does not improve.

Given the unsatisfactory response of gait and balance to current treatments, more research is needed for experimental therapies such as motor cortex and spinal cord stimulation. Finally, as none of the therapies have clearly shown to be neuroprotective, further research is needed to understand their role in altering the disease course and the development of disease-modifying therapies.

In conclusion, there is a wide range of surgical therapy options for management of PD. Applying these techniques requires a skilled multidisciplinary team to help a patient choose the appropriate therapy, perform the intervention, and offer a long-term comprehensive follow-up.

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There was a small, significant gain in utility at 1 year but a statistically insignificant gain of 0. Conclusion: In this patient group, DBS is not cost-effective at 1 year. Extrapolation, however, reveals an increasing likelihood of cost-effectiveness up to 5 years and reducing cost-effectiveness between 5 and 10 years. These models are sensitive to assumptions about future costs and quality-adjusted life years gained.