Treatment Of Advanced Parkinson's Disease Research Articles

Application of multimodal deep learning and multi-instance learning fusion techniques in predicting STN-DBS outcomes for Parkinson's disease patients

Parkinson's Disease (PD) is a progressive neurodegenerative disorder with substantial impact on patients' quality of life. Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced PD, but patient responses vary, necessitating predictive models for personalized care. Recent advancements in medical imaging and machine learning offer opportunities to enhance predictive accuracy, particularly through deep learning and multi-instance learning (MIL) techniques. This retrospective study included 127 PD patients undergoing STN-DBS. Medical records and imaging data were collected, and patients were categorized based on treatment outcomes. Advanced segmentation models were trained for automated region of interest (ROI) delineation. A novel 2.5D deep learning approach incorporating multi-slice representation was developed to extract detailed ROI features. Multi-instance learning fusion techniques integrated predictions across multiple slices, combining radiomics and deep learning features to enhance model performance. Various machine learning algorithms were evaluated, and model robustness was assessed using cross-validation and hyperparameter optimization. The MIL model achieved an area under the curve (AUC) of 0.846 for predicting STN-DBS outcomes, surpassing the radiomics model's AUC of 0.825. Integration of MIL and radiomics features in the DLRad model further improved discriminative ability to an AUC of 0.871. Calibration tests showed good model reliability, and decision curve analysis demonstrated clinical utility, affirming the model's predictive advantage. This study demonstrates the efficacy of integrating MIL, radiomics, and deep learning techniques to predict STN-DBS outcomes in PD patients. The multimodal fusion approach enhances predictive accuracy, supporting personalized treatment planning and advancing patient care.

The effect of subthalamic nucleus deep brain stimulation on speech performance: a prospective clinical and tractography study.

Speech changes significantly impact the quality of life for Parkinson's disease (PD) patients. Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) is a standard treatment for advanced PD, but its effects on speech remain unclear. This study aimed to investigate the relationship between STN-DBS and speech changes in PD patients using comprehensive clinical assessments and tractography. Forty-seven PD patients underwent STN-DBS, with preoperative and 3-month postoperative assessments. Speech analyses included acoustic measurements, auditory-perceptual evaluations, and fluency-intelligibility tests. On the other hand, structures within the volume tissue activated (VTA) were identified using MRI and DTI. The clinical and demographic data and structures associated with VTA (Corticospinal tract, Internal capsule, Dentato-rubro-thalamic tract, Medial forebrain bundle, Medial lemniscus, Substantia nigra, Red nucleus) were compared with speech analyses. The majority of patients (36.2-55.4% good, 29.7-53.1% same) exhibited either improved or unchanged speech quality following STN-DBS. Only a small percentage (8.5-14.9%) experienced deterioration. Older patients and those with worsened motor symptoms postoperatively were more likely to experience negative speech changes (p < 0.05). Interestingly, stimulation of the right Substantia Nigra correlated with improved speech quality (p < 0.05). No significant relationship was found between other structures affected by VTA and speech changes. This study suggests that STN-DBS does not predominantly negatively impact speech in PD patients, with potential benefits observed, especially in younger patients. These findings underscore the importance of individualized treatment approaches and highlight the need for further long-term studies to optimize therapeutic outcomes and better understand the effects of STN-DBS on speech.

Polyneuropathy monitoring in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel.

ObjectivesLevodopa‐carbidopa‐intestinal‐gel (LCIG) infusion is an effective treatment for advanced PD with motor fluctuations. Polyneuropathy occurs as a complication in 10–15% of patients. We wanted to assess the frequency of polyneuropathy in Finnish advanced Parkinson's disease (PD) patients with continuous LCIG infusion, and the value of different clinical monitoring parameters during follow‐up.Materials and methodsPatient records of PD patients started on LCIG infusion at Helsinki University Hospital who received nerve conduction studies at baseline and 6 months after treatment initiation were reviewed for epidemiological information, mini mental state examination, baseline and 6 months’ UPRDS‐III, weight, body mass index, levodopa dose (LD), plasma homocysteine levels, folate, vitamin B6 and B12.ResultsOut of 19 patients (n = 6 on B‐vitamin substitution), two (10.5%) developed new‐onset polyneuropathy after initiation of LCIG therapy (n = 0 with vitamin substitution). Neuropathy was associated with significant weight loss (BMI reduction > 1.5), but not with other monitoring parameters. Homocysteine rose significantly in patients not substituted with B‐vitamin complex, but not in patients with B‐vitamin substitution. Homocysteine changes correlated with LD changes in the absence of vitamin B substitution. After oral B‐vitamin substitution, both patients’ polyneuropathy remained electrophysiologically and clinically stable.ConclusionsRates of polyneuropathy in Finnish PD patients with LCIG treatment are comparable to previous studies. Patients’ weight should be included in regular follow up monitoring and can be used for patient self‐monitoring. Vitamin B substitution appears to reduce coupling between levodopa dose and homocysteine and may be useful to prevent polyneuropathy related to LCIG.

Effectiveness of Deep Brain Stimulation in Iraqi Patients with Parkinson Disease

Background: Surgical treatment for advanced Parkinson disease (PD) is considered when medical therapyfails to control the symptoms.Objective: Assessment of effectiveness of deep brain stimulation (DBS) in controlling motor manifestationsof advanced PD.Patients and Method: Twenty patients (14 male and 6 female) whom fulfill the requirements for DBSsurgery, were included in this study. All patients were on Levodopa (L-dopa), procyclidine, pramipexol, andamantadine medications. The study conducted between March 2017 and March 2018 in the neurosurgicalteaching hospital and neuroscience hospitalin Baghdad/Iraq. Unified Parkinson’s Disease RatingScale(UPDRS) was used before and after surgery.Results: There was a statistically significant improvement in the tremor, rigidity, and bradykinesia.Conclusion: Most disabling axial symptoms of gait and postural instability, that failed to respond to medicaltherapy, will show effective response to the bilateral STN stimulation in advanced PD cases.

Deep Brain Stimulation Effects on Gait Pattern in Advanced Parkinson's Disease Patients.

BackgroundGait disturbance accompanies many neurodegenerative diseases; it is characteristic for Parkinson’s disease (PD). Treatment of advanced PD often includes deep brain stimulation (DBS) of the subthalamic nucleus. Regarding gait, previous studies have reported non-significant or conflicting results, possibly related to methodological limitations.ObjectiveThe objective of this prospective study was to assess the effects of DBS on biomechanical parameters of gait in patients with PD.MethodsTwenty-one patients with advanced PD participated in this prospective study. Gait was examined in all patients using the Zebris FDM-T pressure-sensitive treadmill (Isny, Germany) before DBS implantation and after surgery immediately, further immediately after the start of neurostimulation, and 3 months after neurostimulator activation. We assessed spontaneous gait on a moving treadmill at different speeds. Step length, stance phase of both lower limbs, double-stance phase, and cadence were evaluated.ResultsIn this study, step length increased, allowing the cadence to decrease. Double-stance phase duration, that is, the most sensitive parameter of gait quality and unsteadiness, was reduced, in gait at a speed of 4.5 km/h and in the narrow-based gaits at 1 km/h (tandem gait), which demonstrates improvement.ConclusionThis study suggests positive effects of DBS treatment on gait in PD patients. Improvement was observed in several biomechanical parameters of gait.

Indicación de estimulación cerebral profunda en casos complejos de enfermedad de Parkinson. Experiencia en el Hospital Clínico Universidad de Chile

Introduction: Deep brain stimulation (DBS) is a standard surgical procedure for the treatment of advanced Parkinson Disease (PD) with motor complications that cannot be adequately managed by medical treatment. Currently available literature can guide physicians on basic aspects of patients’ selection and indications for DBS. However, there is a range of real-world clinical settings where the indications of DBS for Parkinson disease are debatable. Objective: to present the experience on PD patients with complex clinical manifestations treated with DBS in our hospital. Method: Report of four PD cases treated with DBS. Case 1: 63-year old woman with advanced PD and severe motor complications; Case 2: 60-year old man with 5 years of disease duration and mild motor complications; Case 3: 67-year old man with severe ventriculomegaly that may have precluded direct electrode passage to the surgical target; Case 4: 67- year-old woman with putative severe axial disability. Results: After one year of follow-up, all patients showed improvement on motor symptoms as well as quality of life. Discussion: We provide a brief rationale for the patient selection in each case to support the decision-making in the management of PD patients with complex clinical cases.

Asymmetric STN DBS for FOG in Parkinson's disease: A pilot trial

BackgroundIn Parkinson's disease (PD), freezing of gait (FOG) is a highly disabling gait disorder. Though deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient treatment for advanced PD, the management of STN DBS refractory FOG remains challenging. ObjectiveTo evaluate the long-term impact on FOG of unilateral stimulation reduction in PD treated with bilateral STN DBS. MethodsPatients with bilateral STN DBS for at least one year and refractory FOG were included in a randomized, double blind, cross-over clinical trial. They were randomized to chronic (CHR) vs. experimental (EXP) stimulation (30% amplitude reduction contralateral to the least affected body side), each condition for 4 weeks. Gait and FOG were assessed both in the OFF and ON medication conditions. Primary outcome was the difference in the FOG percentage during gait assessment and in a composite gait score in CHR vs. EXP stimulation. ResultsThe study was stopped early for futility. Of the 12 patients included, eight dropped out because of re-emerging of PD symptoms. In the four patients who sustained the experimental condition, the FOG percentage did not improve, whether in the OFF (CHR: 13.4% vs. EXP: 16.8%) or in the ON (CHR: 19.5% vs. EXP: 19.8%) medication condition. There was no change in the composite gait score (CHR: 5.5 ± 1.3 vs. EXP: 6.3 ± 3.3). ConclusionsMost patients did not tolerate the unilateral amplitude reduction of STN DBS in the long-term. Moreover, this strategy failed to improve FOG in patients who could sustain the procedure. Clinicaltrial.gov identifierNCT02704195.

An Update on Surgical Treatment of Parkinson Disease

Over the last several decades, surgery became an integral part of comprehensive treatment of advanced Parkinson disease (PD). Better understanding of disease mechanisms and advancement of technological innovations resulted in universal acceptance of deep brain stimulation (DBS) as an important part of the PD treatment algorithm. Based on experience with thousands of operated patients, the criteria for patient selection, preoperative evaluation, procedural details, and nuances of post-operative management are now well established. As a matter of fact, surgery in general and DBS in particular are now included in every guideline of PD management making it an option to consider when disease progresses and medical side effects occur.

Patient Evaluation and Selection for Movement Disorders Surgery: The Changing Spectrum of Indications.

This report summarizes the state-of-the-art and controversies around patient selection for deep brain stimulation (DBS) for various conditions. Parkinson's disease (PD): several class I studies have shown superiority of DBS over best medical treatment for advanced PD with fluctuations and further inclusion criteria. One class I study suggests that PD patients with early motor complications might gain more quality of life if operated within 3 years after the onset of fluctuations. The subthalamic nucleus (STN) is still the standard target. STN DBS has an impact on impulse control disorders though the exact mechanism is unclear. Tremor: essential tremor (ET) patients found to be eligible for DBS surgery should first be treated with primidone, propranolol, and with a combined therapy preoperatively. Second-line drugs (i.e., topiramate and gabapentin) may be useful. No class I studies exist for DBS treatment of ET. The optimal target of DBS in ET might be the posterior subthalamic area. Dystonia: there is class I evidence for primary generalized and segmental dystonia and for some botulinum-resistant focal dystonias. The impact of age, symptom duration, and DYT-mutation status in primary dystonia on the outcome of DBS surgery clearly demands more studies. DBS has a role in SCGE-mutation positive myoclonus dystonia and tardive dystonia. Finally, neurostimulation in secondary dystonia might be considered in selected patients based on an individual patient's approach.

Patient Preferences for Device-Aided Treatments Indicated for Advanced Parkinson Disease

BackgroundEffective treatment for advanced Parkinson disease (PD) uncontrolled with oral medication includes device-aided therapies such as deep brain stimulation (DBS) and continuous levodopa-carbidopa infusion to the duodenum via a portable pump. ObjectiveOur objective was to quantify patient preferences for attributes of these device-aided treatments. MethodsWe administered a Web-enabled survey to 401 patients in the United States. A discrete-choice experiment (DCE) was used to evaluate patients’ willingness to accept tradeoffs among efficacy, tolerability, and convenience of alternative treatments. DCE data were analyzed using random-parameters logit. Best-worst scaling (BWS) was used to elicit the relative importance of device-specific attributes. Conditional logit was used to analyze the BWS data. We tested for differences in preferences among subgroups of patients. ResultsImproving ability to think clearly was twice as important as a 6-hour-per-day improvement in control of movement symptoms. After controlling for efficacy, treatment delivered via portable infusion pump was preferred over DBS, and both devices were preferred to oral therapy with poor symptom control. Patients were most concerned about device attributes relating to risk of stroke, difficulty thinking, and neurosurgery. Avoiding surgery to insert a wire in the brain was more important than avoiding surgery to insert a tube into the small intestine. Some differences in preferences among subgroups were statistically, but not qualitatively, significant. ConclusionsThis study clarifies the patient perspective in therapeutic choices for advanced PD. These findings may help improve communication between patients and providers and also provide evidence on patient preferences to inform regulatory and access decisions.

New development of diagnosis and treatment for Parkinson's disease.

New methods for the diagnosis and new treatments for Parkinson's disease (PD) were explained. As imaging tools, neuromelanin imaging using brain MRI, meta-iodobenzylguanidine (MIBG) cardiac scintigraphy, dopamine transporter scintigraphy, and transcranial sonography were introduced. Olfactory dysfunction and REM sleep behavior disorders (RBD), which are important non-motor symptoms, and the new Clinical Criteria for PD launched by Movement Disorder Society (MDS) were also described. Investigative new medications and new anti-PD medications, which recently became available in Japan, were introduced. I explained the rationale of early treatment, strategy of initial treatment, the significance of continuous dopaminergic stimulation, strategy of treatment for advanced PD, and deep brain stimulation as a surgical treatment together with promising new treatments including gene therapy and cell transplantation.

Benefits of subthalamic stimulation for elderly parkinsonian patients aged 70 years or older

ObjectivesDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson disease (PD). However, there is general reluctance in considering this therapy for PD patients over age 70 years with limited supporting evidence. Present study investigates age impacts in STN-DBS outcomes, focusing particularly on the elderly patients. Patients and methodsSeventy-two consecutive patients were divided into younger and elderly (n=16, cutoff age=70years) groups. Both groups were comparable in preoperative clinical severity, except the elderly exhibited a levodopa (LD) response (P<0.05) inferior to that of the younger. Improvements in drug-off/DBS-on Unified PD Rating Scale (UPDRS) scores and reduction in daily LD-equivalent dose (LED) after 6 months were evaluated relative to the presurgical drug-off baseline. Preoperative factors predictive of favorable surgical outcomes were analyzed using a multivariate linear regression model. ResultsAfter DBS therapy, elderly patients exhibited clinical improvements particularly in the tremor (56%) and LD-induced dyskinesia (78%). Improvement of axial dysfunction (24%) and reduction of daily LED (24%) showed no intergroup difference. Adverse events, particularly dysarthria, occurred frequently in elderly group. The overall improvements in UPDRS scores were suboptimal in elderly group, correlating with their preoperative inferior LD responses. Elderly patients who presented predominantly with akinesia before surgery achieved superior surgical outcomes (adjusted R2=0.657, P<0.001). ConclusionSTN-DBS therapy is beneficial to some elderly PD patients aged 70 years or older. Tremor, axial dysfunctions and drug-induced dyskinesia are the main indications for the elderly; however, their clinical benefits are inferior to those of younger patients.

One-year Outcome of Bilateral Subthalamic Stimulation in Parkinson Disease: An Eastern Experience

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely accepted as a treatment for advanced Parkinson disease (PD). However, published studies were conducted mainly in Western centers and recruited small numbers of patients. This study presents 1-year outcomes in Taiwanese patients with PD. Sixty-two consecutive patients underwent STN-DBS surgery during a 7-year period. Their median drug-off Hoehn and Yahr stage was 3 and mean illness history was 8 years. Clinical outcomes were evaluated by the change in drug-off/DBS-on Unified Parkinson Disease Rating Scale (UPDRS) scores relative to presurgical drug-off baseline and change in daily levodopa-equivalent dose (LED). After 1 year of DBS therapy, patients showed significant improvements with a clinically high effect size in cardinal signs, particularly in tremor (63%). Posture instability was also improved, whereas speech dysfunction was hardly corrected. The LED need was significantly reduced, therefore preoperative drug-induced complications were prominently (51%) ameliorated after surgery and drug-induced dyskinesia was remarkably (63%) diminished. No serious adverse effects were encountered after surgery. Overall, motor functions declined by 15% within 1 year in drug-off state. Bilateral STN-DBS therapy provided effective and sustained benefits to Eastern patients with PD over a 1-year period.

Comprehensive, Multidisciplinary Deep Brain Stimulation Screening for Parkinson Patients: No Room for "Short Cuts".

Careful, often cumbersome, screening is a fundamental part of DBS evaluation in Parkinson's disease (PD). It often involves a brain MRI, neuropsychological testing, neurological, surgical, and psychiatric evaluation, and "ON/OFF" motor testing. Given that DBS has now been a standard treatment for advanced PD, with clinicians' improved comfort and confidence in screening and referring patients for DBS, we wondered whether we can now streamline our lengthy evaluation process. We reviewed all PD patients evaluated for DBS at our center between 2006 and 2011 and analyzed the reasons for exclusion and for dropping out despite passing the screening process. A total of 223 PD patients who underwent DBS evaluation had complete charting. Only 131 (58.7%) patients were successfully implanted. Sixty-one (27.3%) patients were excluded after screening because of significant cognitive decline (32.7%), early disease with room for medication adjustment (29.5%), behavioral dysfunction (21.3%), suspected secondary parkinsonism or atypical parkinsonism syndrome (13.1%), PD, but with poor levodopa response (11.4%), unrealistic goals (9.8%), PD with predominant axial symptoms (6.5%), significant comorbidities (6.5%), or abnormal brain imaging (3.2%). In addition, 31 (13.9%) patients were cleared for surgery, but either chose not have it (18 patients), were lost to follow-up (12 patients), or were denied by medical insurance (1 patient). Through careful screening, a significant percentage of surgical candidates continue to be identified as less suitable because of a variety of reasons. This underscores the continued need for a comprehensive, multidisciplinary screening process.

Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease.

Deep brain stimulation (DBS) is a well-established modality for the treatment of advanced Parkinson disease (PD). Recent studies have found DBS plus best medical therapy to be superior to best medical therapy alone for patients with PD and early motor complications. Although no specific age cutoff has been defined, most clinical studies have excluded patients older than 75 years of age. We hypothesize that increasing age would be associated with an increased number of postoperative complications. To evaluate the stepwise effect of increasing age (in 5-year epochs) on short-term complications following DBS surgery. A large, retrospective cohort study was performed using the Thomson Reuters MarketScan national database that examined 1757 patients who underwent DBS for PD during the period from 2000 to 2009. Primary measures examined included hospital length of stay and aggregate and individual complications within 90 days following surgery. Multivariate logistic regression analysis was used to calculate complication-related odds ratios (ORs) for each 5-year age epoch after controlling for covariates. Overall, 132 of 1757 patients (7.5%) experienced at least 1 complication within 90 days, including wound infections (3.6%), pneumonia (2.3%), hemorrhage or hematoma (1.4%), or pulmonary embolism (0.6%). After adjusting for covariates, we found that increasing age (ranging from <50 to 90 years of age) did not significantly affect overall 90-day complication rates (OR, 1.10 per 5-year increase [95% CI, 0.96-1.25]; P = .17). The 2 most common procedure-related complications, hemorrhage (OR, 0.82 [95% CI, 0.63-1.07]; P = .14) and infection (OR, 1.04 [95% CI, 0.87-1.24]; P = .69), did not significantly increase with age. Older patients with PD (>75 years) who were selected to undergo DBS surgery showed a similar 90-day complication risk (including postoperative hemorrhage or infection) compared with younger counterparts. Our findings suggest that age alone should not be a primary exclusion factor for determining candidacy for DBS. Instead, a clear focus on patients with medication-refractory and difficult to control on-off fluctuations with preserved cognition, regardless of age, may allow for an expansion of the traditional therapeutic window.

Cost-Effectiveness of Subthalmic Nucleus Deep Brain Stimulation for the Treatment of Advanced Parkinson Disease in Hong Kong: A Prospective Study

Deep brain stimulation (DBS) is an effective but costly treatment for patients with advanced Parkinson disease (PD). This study examined the cost-effectiveness of DBS in relation to its improved effectiveness to help funding decision makers decide whether the treatment should be adopted. The incremental cost-effective ratio (ICER) per quality-adjusted life year has been benchmarked as being between US$50,000 and US$100,000 by US agencies, whereas it is less than €30,000 per quality-adjusted life year in Europe. To provide cost-effectiveness information of subthalamic nucleus DBS for patients with advanced PD. Direct medical expenses during the year before the DBS treatment were used to measure the baseline cost. Cost-effectiveness was measured by the ICER for the Unified Parkinson's Disease Rating Scale Part III and the ICER for the EuroQol Group's Health-Related Quality of Life measurement. Thirteen patients with advanced PD were recruited between January 2009 and January 2011. A 1-point improvement in the Unified Parkinson's Disease Rating Scale Part III score was associated with an ICER of US$926 in the first year and US$421 in the second year. A 1-point improvement on the EuroQol Group's Health-Related Quality of Life measurement was associated with an ICER of US$123,110 in the first year and US$62,846 in the second year. Cost-effectiveness of subthalamic nucleus DBS for treatment of advanced PD is greater during a 2-year period than 1 year only. These results can be used as a reference for the use of DBS for PD in a region with public health financing.

PND26 - Cost Effectiveness of Apomorphine in the Treatment of Advanced Parkinson Disease in the UK and Germany: Results from a Multicounty Decision Analytic Model

CONTACT: Dr. Evelyn Walter IPF Institute for Pharmaeconomic Research Wolfengasse 4/7 1010 Vienna, Austria Tel +43-1-5132007-13 Fax +43-1-5132007-15 Email: e.walter@ipf-ac.at Web: www.ipf-ac.at Objectives Parkinson Disease (PD) is the second commonest cause of neurological disability. Approximately, 5.2 million men and women are affected worldwide. Continuous subcutaneous apomorphine (CSAI) represents an alternative treatment option of advanced PD with motor fluctuation. The purpose of this analysis was to estimate the cost-effectiveness of CSAI compared with Levodopa/carbidopa intestinal gel (LCIG), Deep-Brain-Stimulation (DBS) and Standard-of-care (SOC).

Elevated potassium provides an ionic mechanism for deep brain stimulation in the hemiparkinsonian rat

The mechanism of high-frequency stimulation used in deep brain stimulation (DBS) for Parkinson's disease (PD) has not been completely elucidated. Previously, high-frequency stimulation of the rat entopeduncular nucleus, a basal ganglia output nucleus, elicited an increase in [K(+)](e) to 18 mm, in vitro. In this study, we assessed whether elevated K(+) can elicit DBS-like therapeutic effects in hemiparkinsonian rats by employing the limb-use asymmetry test and the self-adjusting stepping test. We then identified how these effects were meditated with in-vivo and in-vitro electrophysiology. Forelimb akinesia improved in hemiparkinsonian rats undergoing both tests after 20 mm KCl injection into the substantia nigra pars reticulata (SNr) or the subthalamic nucleus. In the SNr, neuronal spiking activity decreased from 38.2 ± 1.2 to 14.6 ± 1.6 Hz and attenuated SNr beta-frequency (12-30 Hz) oscillations after K(+) treatment. These oscillations are commonly associated with akinesia/bradykinesia in patients with PD and animal models of PD. Pressure ejection of 20 mm KCl onto SNr neurons in vitro caused a depolarisation block and sustained quiescence of SNr activity. In conclusion, our data showed that elevated K(+) injection into the hemiparkinsonian rat SNr improved forelimb akinesia, which coincided with a decrease in SNr neuronal spiking activity and desynchronised activity in SNr beta frequency, and subsequently an overall increase in ventral medial thalamic neuronal activity. Moreover, these findings also suggest that elevated K(+) may provide an ionic mechanism that can contribute to the therapeutic effects of DBS for the motor treatment of advanced PD.

Turning tables

Half a decade ago, a provocative editorial envisioned a “rematch” between globus pallidus pars interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of advanced Parkinson disease (PD).1 The idea of a boxing bout between the 2 most common DBS targets for the treatment of PD summarized a decade-long controversy. While GPi had been the preferred target of ablative procedures for the treatment of advanced PD in the 1990s, the advent of DBS coincided with an overwhelming preference for the STN. Such instantaneous supremacy was originally supported by a theoretical rationale, namely the central role of the STN in the pathophysiology of PD,2 but for over a decade it remained fundamentally based on preference more than evidence.

Treating PD axial signs with DBS

Axial signs are among the most incapacitating problems of advanced Parkinson disease (PD), leading to falls and social isolation. While widely accepted as an effective treatment of advanced PD, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has relatively poor efficacy on axial signs1 and does not prevent worsening over time. A meta-regression of the long-term effects of DBS confirmed that high-frequency STN DBS alone does not offer the same improvement to gait and balance as it does to the cardinal symptoms of PD, particularly “on” medications.2 Alternative approaches have been proposed to circumvent the relative failure of STN DBS to improve postural and gait difficulty in PD, including new targets and stimulation settings. Stimulation of the globus pallidum pars interna (GPi) in combination with levodopa seems to preserve gait and balance better than STN DBS over time,2 but the experience with GPi DBS is still limited. Due to its relevant role in gait initiation,3 modulation of the pedunculopontine nucleus (PPN) activity by DBS has received substantial attention over the past few …