Deep Brain Stimulation Target Selection Research Articles

Quality of Life after Deep Brain Stimulation in Parkinson's Disease: Does the Target Matter?

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is an accepted therapy for Parkinson's disease (PD) with disabling motor complications. For elderly patients with poorer cognition and postural instability, GPi has been proposed as the preferable DBS target based on expert opinion, arguing GPi-DBS may be less complicated by depression, apathy, worsened verbal fluency, and executive dysfunction, resulting in greater improvement in quality of life (QoL). However, data supporting such patient-tailored approach are lacking. The aims were to analyze whether the DBS target influences QoL in a PD cohort and a matched subgroup of frail patients with poor cognitive status and reduced postural stability, and whether other factors affect the QoL outcomes. In this retrospective study, we analyzed a single-center cohort of 138 PD patients who received bilateral STN-DBS (117) or GPi-DBS (21) using the mentioned approach for target selection. All patients underwent standardized clinical evaluations of motor- and nonmotor signs as well as QoL before and 1 year after surgery. DBS of both targets improved motor signs, dyskinesias, and pain. QoL improved without significant difference between the targets, but with a trend for greater improvement across all QoL domains in favor of the STN, even in an STN subgroup matched to the GPi group. Our results contradict the prevailing belief that GPi-DBS is superior in frail PD patients with cognitive decline and postural instability, questioning the proposed patient-tailored approach of DBS target selection. Further studies are needed for a data-driven approach.

Globus pallidus internus versus subthalamic nucleus deep brain stimulation for isolated dystonia: A 3-year follow-up.

Bilateral deep brain stimulation (DBS) surgery targeting the globus pallidus internus (GPi) or the subthalamic nucleus (STN) is widely used in medication-refractory dystonia. However, evidence regarding target selection considering various symptoms remains limited. This study aimed to compare the effectiveness of these two targets in patients with isolated dystonia. This retrospective study evaluated 71 consecutive patients (GPi-DBS group, n = 32; STN-DBS group, n = 39) with isolated dystonia. Burke-Fahn-Marsden Dystonia Rating Scale scores and quality of life were evaluated preoperatively and at 1, 6, 12, and 36 months postoperatively. Cognition and mental status were assessed preoperatively and at 36 months postoperatively. Targeting the STN (STN-DBS) yielded effects within 1 month (65% vs. 44%; p = 0.0076) and was superior at 1 year (70% vs. 51%; p = 0.0112) and 3 years (74% vs. 59%; p = 0.0138). For individual symptoms, STN-DBS was preferable for eye involvement (81% vs. 56%; p = 0.0255), whereas targeting the GPi (GPi-DBS) was better for axis symptoms, especially for the trunk (82% vs. 94%; p = 0.015). STN-DBS was also favorable for generalized dystonia at 36-month follow-up (p = 0.04) and required less electrical energy (p < 0.0001). Disability, quality of life, and depression and anxiety measures were also improved. Neither target influenced cognition. We demonstrated that the GPi and STN are safe and effective targets for isolated dystonia. The STN has the benefits of fast action and low battery consumption, and is superior for ocular dystonia and generalized dystonia, while the GPi is better for trunk involvement. These findings may offer guidance for future DBS target selection for different types of dystonia.

Patterns of neural activity and clinical outcomes in a juvenile Huntington's Disease patient undergoing Deep Brain Stimulation of the subthalamic nucleus

BackgroundHuntington's disease (HD) is a hereditary neurodegenerative disease leading to cognitive and motor impairment. HD depends on basal ganglia dysfunctions, but the role of subthalamic nucleus (STN) neurons is not completely known. Drug-resistant motor symptoms of HD can be alleviated by neuromodulation of the basal ganglia through Deep Brain Stimulation (DBS) of STN. DBS target selection is supported by intra-operative microelectrode recordings (MER). MER have been previously used to characterize neural dynamics of STN in several movement disorders and can provide information on firing patterns underlying HD. MethodsWe analyzed MER data acquired during bilateral DBS of STN in a juvenile HD female patient with hypokinetic motor symptoms (generalized dystonia, stiffness, and severe gait impairment). Firing patterns of STN in HD were characterized by isolating single neuron activities (n = 23) and measuring their regularity, bursting, and oscillatory behavior. Multi-unit activity recordings spectrum was used to estimate the presence of network oscillations. ResultsSTN neurons displayed irregular dynamics and intense and sparse bursting. Only 3/23 neurons presented oscillatory activity. However, network oscillations were detected, in particular in the beta (12–30 Hz) band. After bilateral STN-DBS surgery, the Unified Huntington's Disease Rating Scale decreased from 60 to 54. ConclusionsThe most salient difference between HD and other movement disorders in STN activity is the presence of a weakly synchronized oscillatory mode, in which oscillations are evident at the network level but not at the single neuron level.

Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy.

Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15 years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment-resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high-resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above-mean and below-mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient-specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426-443.

Deep Brain Stimulation Management of Essential Tremor with Dystonic Features

<strong>Clinical Vignette:</strong> A 64-year-old female with essential tremor (ET) presents for evaluation of deep brain stimulation (DBS) candidacy. Examination revealed subtle dystonic features as well as a disabling postural-action tremor. <strong>Clinical Dilemma:</strong> Can dystonia occur in the setting of the diagnosis of ET and can its presence alter DBS target selection? <strong>Clinical Solution:</strong> Unilateral DBS implantation of the ventralis intermedius (Vim) led to improvement in both tremor and dystonic posturing. <strong>Gap in Knowledge:</strong> Case reports of DBS in dystonic tremor suggest Vim, globus pallidus internus (GPi), and subthalamic targets may all be effective, to varying degrees, in improving both tremor and dystonia. More rigorous studies are needed to identify the optimal target(s). <strong>Expert Commentary:</strong> This case underscores the limited evidence available to guide a clinician’s choice of DBS targets in patients with ET and dystonia. The severity of the dystonia and the presence of more generalized dystonia may alter the thinking about optimal targeting. Vim, GPi, and subthalamic targets appear potentially acceptable options, though Vim is usually the first target attempted when postural-action tremor is the chief complaint. Occasionally, a second rescue DBS lead may be necessary.

Before and after the veterans affairs cooperative program 468 study: Deep brain stimulator target selection for treatment of Parkinson's disease

IntroductionThe Veterans Affairs Cooperative Study Program 468 study (CSP 468) produced significant findings regarding deep brain stimulation (DBS) target selection for Parkinson's Disease (PD) treatment, yet its impact on clinical practices has not been described. Here we assess how CSP 468 influenced target selection at a high-volume movement disorders treatment center. MethodsWe compared DBS target site selection between 4-year periods that immediately preceded and followed CSP 468 publication. Additionally, we examined how baseline clinical features influenced target selection following CSP 468. ResultsThe STN was the predominant site of DBS implantation before and after CSP 468 publication (93.2% of cases, and 60.4%, respectively), but GPi targeting increased significantly following CSP 468 publication (from 5.3% to 37.4%; p < .001). Patients who underwent GPi stimulation following CSP 468 exhibited worse indices of depression (p < .001), less responsiveness to medications (p < .05), and a trend towards worse pre-operative cognitive performance (p = .06). In multi-variate analysis, advanced patient age and depression were independent predictors of GPi targeting (p < .01). ConclusionsKey findings of CSP 468 were reflected in our target selection of DBS for Parkinson's Disease. Following CSP 468, GPi targeting increased, and it was selected for patients with poorer cognitive and mood indices.

Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression.

Clinical VignetteA 67-year-old female with advanced Parkinson’s disease (PD), medically refractory tremor, and a history of significant depression presented for evaluation of deep brain stimulation (DBS) candidacy.Clinical DilemmaTraditionally, the subthalamic nucleus (STN) has been preferred over the globus pallidus interna (GPi) as a DBS target for PD patients with levodopa-responsive fluctuations in rigidity and akinesia, for whom tremor is also a significant source of impairment. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.Clinical SolutionBilateral DBS of the GPi led to significant short-term improvement in PD motor symptoms, including significant tremor reduction.Gap in KnowledgeThere is insufficient evidence to support or refute clinicians’ traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

Deep Brain Stimulation Target Selection in an Advanced Parkinson’s Disease Patient with Significant Tremor and Comorbid Depression

Deep Brain Stimulation Target Selection in an Advanced Parkinson’s Disease Patient with Significant Tremor and Comorbid Depression

Deep Brain Stimulation Target Selection for Parkinson's Disease.

During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to discuss three main questions on target selection for deep brain stimulation (DBS) of patients with Parkinson's disease (PD). First, is the subthalamic nucleus (STN) or the globus pallidus internus (GPi) the ideal target? In summary, both targets are equally effective in improving the motor symptoms of PD. STN allows a greater medications reduction, while GPi exerts a direct antidyskinetic effect. Second, are there further potential targets? Ventral intermediate nucleus DBS has significant long-term benefit for tremor control but insufficiently addresses other motor features of PD. DBS in the posterior subthalamic area also reduces tremor. The pedunculopontine nucleus remains an investigational target. Third, should DBS for PD be performed unilaterally, bilaterally or staged? Unilateral STN DBS can be proposed to asymmetric patients. There is no evidence that a staged bilateral approach reduces the incidence of DBS-related adverse events.

Site of deep brain stimulation and jaw velocity in Parkinson disease

While deep brain stimulation (DBS) has proven to be an effective treatment for many symptoms of Parkinson disease (PD), a deterioration of axial symptoms frequently occurs, particularly for speech and swallowing. These unfavorable effects of DBS may depend on the site of stimulation. The authors made quantitative measures of jaw velocity to compare the relative effectiveness of DBS in the globus pallidus internus (GPi) or the subthalamic nucleus (STN). This was a randomized, double-blind, and longitudinal study, with matched healthy controls. The peak velocities of self-scaled and externally scaled jaw movements were studied in 27 patients with PD before and after 6 months of bilateral DBS in the GPi or the STN. A mixed-effects model was used to identify differences in jaw velocity before DBS surgery (baseline) while off and on levodopa therapy, and after 6 months of DBS (postoperative) during 4 treatment conditions (off- and on-levodopa states with and without DBS). Self-scaled jaw velocity was impaired by the DBS procedure in the STN; velocity was significantly decreased across all postoperative conditions compared with either the off- or on-levodopa baseline conditions. In contrast, the postoperative velocity in the GPi group was generally faster than the baseline off-levodopa state. Turning the DBS off and on had no effect on jaw velocity in either group. Unlike baseline, levodopa therapy postoperatively no longer increased jaw velocity in either group, and this lack of effect was not related to postoperative changes in dose. The externally scaled jaw velocity was little affected by PD, but DBS still slightly affected performance, with the STN group significantly slower than the GPi group for most conditions. The authors' results suggest that either the electrode implant in STN or the subsequent period of continuous STN stimulation negatively affected voluntary jaw velocity, including the loss of the preoperative levodopa-induced improvement. While the GPi group showed some improvement in voluntary jaw velocity postoperatively, their performance during the combination of DBS and levodopa was not different from their best medical management presurgery. The results have implications for DBS target selection, particularly for those patients with oromotor dysfunctions.