Bilateral Subthalamic Nucleus Stimulation Research Articles

Enhancing Attentional Performance in Parkinson's Disease: The Impact of Combined Deep Brain Stimulation of the Substantia Nigra Pars Reticulata and the Subthalamic Nucleus

ObjectiveThe concomitant stimulation of the subthalamic nucleus and the substantia nigra pars reticulata is a promising approach to improve treatment of refractory axial symptoms in Parkinson's disease. While dual stimulation of the subthalamic nucleus and the substantia nigra pars reticulata has previously shown beneficial effects on gait, the role of the substantia nigra, a crucial component of the basal ganglia circuitry, in cognitive functions such as attention and executive control remains underexplored. This study aimed to investigate the impact of selective substantia nigra pars reticulata stimulation on attentional performance in patients receiving standard deep brain stimulation of the subthalamic nucleus. MethodsTwelve patients with bilateral subthalamic nucleus stimulation underwent computerized assessment of attention using a simple reaction time task. Reaction times were assessed under standard stimulation of the subthalamic nucleus versus simultaneous stimulation of the subthalamic nucleus and the substantia nigra pars reticulata. ResultsThe results revealed a significant improvement in reaction times during the simple reaction time task when patients received dual stimulation compared to standard stimulation. ConclusionsOur findings provide further evidence for the pivotal role of the substantia nigra pars reticulata in cognitive functions such as attention. Despite the limitations of the study, including a small sample size, our results suggest potential benefits of simultaneous deep brain stimulation of the subthalamic nucleus and the substantia nigra pars reticulata on attentional performance in patients with Parkinson's disease. Further research with larger cohorts is warranted to confirm these findings and better understand the underlying mechanisms.

Apathy in Parkinson's Disease: Clinical Patterns and Neurobiological Basis.

Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson's disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.

Effects of the combined treatment of bilateral subthalamic nucleus stimulation and levodopa on balance and mobility in Parkinson's disease.

<p>Background and purpose &ndash; To evaluate the efficacy of the combined therapy of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and dopaminergic medication on balance and mobility in patients with Parkinson&rsquo;s disease (PD).</p>. <p>Eighteen PD patients under bilateral STN-DBS stimulation therapy, were enrolled in this study. Unified Parkinson&rsquo;s Disease Rating Scale (UPDRS) was applied to assess the patients&rsquo; clinical characteristics. UPDRS part III postural instability/gait disorder (PIGD) scores (sum of items 3.9-3.13) and UPDRS part III postural stability item (item 3.12) were calculated separately. Patients were evaluated with Berg Balance Scale (BBS), Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go (TUG) test, dual-task TUG test, and Forward Functional Reach (FFR) Test in two conditions: Stimulation-ON (stim-ON)/Medication-ON (Med-ON) and Stimulation-OFF (Stim-OFF)/Med-ON.</p>. <p>The mean age of patients was 59.5&plusmn;9.1 (R: 41-71) years. The UPDRS part III total score and PIGD subsection score significantly improved after stimulation (p=0.001), but the postural instability item of the UPDRS part III did not change significantly (p=0.1). There were no significant differences between the Stim-ON/Med-ON and Stim-OFF/Med-ON conditions, in terms of total Mini-BESTest total scores, total BBS score, FFR test score (p&gt;0.05 for all of them). TUG test was significantly improved in the Stim-ON/Med-ON condition compared to Stim-OFF/Med-ON condition (p=0.03), but DT-TUG test did not change (p=0.1).&nbsp;</p>. <p>Combined bilateral STN-DBS and dopaminergic medication therapy had an additional improvement on motor symptoms and mobility performance, but not on balance and dual-task mobility.&nbsp;</p>.

Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus Internus in Parkinson's Disease: A Meta-Analysis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder typically manifested by its motor symptoms. In addition, PD patients also suffer from many nonmotor symptoms (NMSs), such as apathy. Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus internus (GPi) are recommended as therapeutic interventions for PD, given their pronounced benefit in reducing troublesome dyskinesia. Apathy, a mood disorder recognized as a NMS of PD, has a negative impact on the prognosis of PD patients. However, the effect of STN-DBS and GPi-DBS on apathy is controversial. In the current meta-analysis, we analyzed apathy following bilateral STN-DBS and GPi-DBS in PD patients. Relevant literature was retrieved from public databases, including PubMed, Cochrane Library, and Embase. Studies were included in our analysis based on the following criterion: such studies should report apathy scores presurgery and postsurgery determined by using the Starkstein Apathy Scale or Apathy Evaluation Scale in patients receiving STN or GPi-DBS with at least three months of follow-up. Upon applying this strict criterion, a total of 13 out of 302 studies were included in our study. A mean difference (MD) and 95% confidence interval (CI) were calculated to show the change in apathy scores. We found a statistically significant difference between the presurgery and postsurgery scores in patients receiving STN-DBS (MD = 2.59, 95% CI = 2.23–2.96, P < 0.00001), but not in patients receiving GPi-DBS (MD = 0.32, 95% CI = −2.78–3.41, P=0.84). STN-DBS may worsen the condition of apathy, which may result from the reduction of dopaminergic medication. In conclusion, STN-DBS seems to relatively worsen the condition of apathy compared to GPi-DBS. Further studies should focus on the mechanisms of postoperatively apathy and the degree of apathy in STN-DBS versus GPi-DBS.

Effects of Bilateral Subthalamic Nucleus Stimulation on Depressive Symptoms and Cerebral Glucose Metabolism in Parkinson's Disease: A 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography Study.

Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor symptoms in Parkinson’s disease (PD), as well as potentially improving otherwise intractable comorbid depressive symptoms. To address the latter issue, we evaluated the severity of depressive symptoms along with the severity of motor symptoms in 18 PD patients (mean age, 58.4 ± 5.4 years; 9 males, 9 females; mean PD duration, 9.4 ± 4.4 years) with treatment-resistant depression (TRD) before and after approximately 1 year of STN-DBS treatment. Moreover, to gain more insight into the brain mechanism mediating the therapeutic action of STN-DBS, we utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess cerebral regional glucose metabolism in the patients at baseline and 1-year follow-up. Additionally, the baseline PET data from patients were compared with PET data from an age- and sex-matched control group of 16 healthy volunteers. Among them, 12 PD patients underwent post-operative follow-up PET scans. Results showed that the severity of both motor and depressive symptoms in patients with PD-TRD was reduced significantly at 1-year follow-up. Also, patients used significantly less antiparkinsonian medications and antidepressants at 1-year follow-up, as well as experiencing improved daily functioning and a better quality of life. Moreover, relative to the PET data from healthy controls, PD-TRD patients displayed widespread abnormalities in cerebral regional glucose metabolism before STN-DBS treatment, which were partially recovered at 1-year follow-up. Additionally, significant correlations were observed between the patients’ improvements in depressive symptoms following STN-DBS and post-operative changes in glucose metabolism in brain regions implicated in emotion regulation. These results support the view that STN-DBS provides a promising treatment option for managing both motor and depressive symptoms in patients who suffer from PD with TRD. However, the results should be interpreted with caution due to the observational nature of the study, small sample size, and relatively short follow-up.

Differential Effects of Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation on Motor Subtypes in Parkinson's Disease

To investigate differences in motor symptom change outcomes following bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in well-defined motor subtypes of Parkinson's disease (PD) to improve clinical decision making. We included 114 patients undergoing STN-DBS and 65 patients undergoing GPi-DBS. The patients were classified as akinetic-rigid type (ART), tremor-dominant type (TD), and mixed type (MT) based on the preoperative the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part-Ⅲ (MDS-UPDRS-III) scores in the medication-off state. Outcome measures included the med-off MDS-UPDRS-III and its subscores changes at the last follow-up after surgery. Outcomes were compared among different motor subtypes and between STN-DBS and GPi-DBS. At the last follow-up (14.92 ± 8.35 months), TD patients had greater median overall motor improvement in med-off MDS-UPDRS-III scores compared with ART patients (62.90% vs 46.67%, P < 0.001), regardless of stimulation target. ART patients showed greater improvement after STN-DBS compared with GPi-DBS (54.44% vs 37.21%, P < 0.001), with improvement in rigidity, akinesia, and posture and gait disorders accounting for this difference. Our results suggest that the different PD motor subtypes show differential responses to STN-DBS and GPi-DBS, that TD patients have greater improvement than ART patients, and STN-DBS has a better effect in ART patients than GPi-DBS. Besides, different motor symptoms among different motor subtypes may respond differently to STN-DBS vs GPi-DBS. All above may reflect the heterogeneity of PD. Longer-term outcomes across different motor subtypes and stimulation targets should be further studied.

Bilateral stimulation of the subthalamic nucleus under local and general anaesthesia

Introduction. Bilateral stimulation of the subthalamic nucleus (STN) is successfully used to treat advanced stages of Parkinson's disease. The standard surgical technique includes microelectrode recording and intraoperative stimulation. The introduction of 3T MRI into clinical practice and new impulse sequences have led to the question of whether the surgery can be performed under general anaesthesia.&#x0D; Aim of the study: to compare the efficacy and safety of bilateral stimulation of STN in patients with Parkinson's disease, using 3T MRI under local and general anaesthesia.&#x0D; Materials and methods. This prospective, randomized controlled study included 40 patients, who underwent electrode implantation using 3T MRI. The patients in the main group (n = 20) had electrodes implanted under general anaesthesia, while the control group (n = 20) had local anaesthesia, intraoperative stimulation and microelectrode recording. The patients motor status, quality of life, cognitive function and required levodopa dose were evaluated after 6 months.&#x0D; Results. The results of 6 months of stimulation were obtained from 30 patients (15 from the main group and 15 from the control group). Reduced motor impairment was observed in both groups as measured on the UPDRS III scale during the 'off' time, with a reduction of 68.7% in the main group and 74.7% in the control group. Improved quality of life, reduced drug-induced motor complications and a reduction in the levodopa dose were also comparable in both groups. No intraoperative haemorrhagic complications were recorded during the study.&#x0D; Conclusions. Preliminary analysis of the data showed that with high-quality visualization of the STN, electrode implantation under anaesthesia is equally effective to awake surgery.

Cognitive effects of theta frequency bilateral subthalamic nucleus stimulation in Parkinson’s disease: A pilot study

BackgroundThere is significant evidence for cognitive decline following deep brain stimulation (DBS). Current stimulation paradigms utilize gamma frequency stimulation for optimal motor benefits; however, little has been done to optimize stimulation parameters for cognition. Recent evidence implicates subthalamic nucleus (STN) theta oscillations in executive function, and theta oscillations are well-known to relate to episodic memory, suggesting that theta frequency stimulation could potentially improve cognition in Parkinson’s disease (PD). ObjectiveTo evaluate the acute effects of theta frequency bilateral STN stimulation on executive function in PD versus gamma frequency and off, as well as investigate the differential effects on episodic versus nonepisodic verbal fluency. MethodsTwelve patients (all males, mean age 60.8) with bilateral STN DBS for PD underwent a double-blinded, randomized cognitive testing during stimulation at (1) 130–135 Hz (gamma), (2) 10 Hz (theta) and (3) off. Executive functions and processing speed were evaluated using verbal fluency tasks (letter, episodic category, nonepisodic category, and category switching), color-word interference task, and random number generation task. Performance at each stimulation frequency was compared within subjects. ResultsTheta frequency significantly improved episodic category fluency compared to gamma, but not compared to off. There were no significant differences between stimulation frequencies in other tests. ConclusionIn this pilot trial, our results corroborate the role of theta oscillations in episodic retrieval, although it is unclear whether this reflects direct modulation of the medial temporal lobe and whether similar effects can be found with more canonical memory paradigms. Further work is necessary to corroborate our findings and investigate the possibility of interleaving theta and gamma frequency stimulation for concomitant motor and cognitive effects.

Deep brain stimulation of the subthalamic nucleus for parkinson's disease: awake vs asleep

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to be an effective and safe neurosurgical procedure for Parkinson's disease (PD). Traditionally, awake implantation of stimulation system is carried out using microelectrode registration and intraoperative stimulation. Development of neuroimaging technologies enables direct STN imaging. Therefore, asleep surgery without additional intraoperative verification is possible. This approach reduces surgery time and can potentially decrease the incidence of hemorrhagic and infectious complications. The advantages of one method or another are being discussed. To assess the benefits and limitations of various methods for DBS system implantation for bilateral STN stimulation, to study the issues of stereotaxic accuracy, efficiency and safety of asleep and awake electrode implantation into STN. We reviewed the articles published in the PubMed database. Searching algorithm included the following keywords: «asleep DBS», «Parkinson's disease», «subthalamic nucleus», «3T MRI», «SWI», «SWAN». There were 31 articles devoted to asleep DBS of STN including 4 meta-analyses, 3 prospective controlled studies, 13 retrospective controlled studies and 11 studies without a control group. Asleep implantation of electrodes for DBS of STN can be performed only after a clear imaging of STN boundaries with high-quality MRI.

The probable REM sleep behavior disorder negatively affects health-related quality of life in Parkinson's disease with bilateral subthalamic nucleus stimulation

ObjectiveThe aim of this study was to compare the short- and long-term outcomes of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients with and without probable REM sleep behavior disorder (RBD). MethodsWe retrospectively reviewed 127 patients who underwent bilateral STN-DBS for PD with probable RBD from September 2011 to November 2018. Motor performance, physical and mental health-related quality of life (HRQoL), cognitive function, and depressive severity were compared between with or without probable RBD at the baseline and at the 1-, 3- or 5-year follow-up. ResultsOne hundred three PD patients (55 with RBD; 48 without RBD) were evaluated at the baseline and at the 1-year follow-up and 33 (17 with RBD, 16 without RBD) of them were examined at the 5-year follow-up. Motor performances were significantly improved in the non-RBD group compared to the RBD group at the 1-year follow-up, and there was a trend toward a greater difference in the physical HRQoL compared with the 1-year follow-up. There were also marked improvements of axial symptom and physical HRQoL in the non-RBD group compared with the RBD group from baseline to 5 years after STN-DBS. ConclusionOur study showed that RBD negatively affected the short- and long-term outcomes on motor performances, especially axial symptom and HRQoL after STN-DBS in PD patients.

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson’s Disease and Essential Tremor Patients

Newer generation deep brain stimulation (DBS) systems have recently become available in the United States. Data on real-life experience are limited. We present our initial experience incorporating newer generation DBS with Parkinson's disease (PD) and essential tremor (ET) patients. Newer systems allow for smart energy delivery and more intuitive programming and hardware modifications including constant current and directional segmented contacts. We compared six-month outcomes between 42 newer generation and legacy leads implanted in 28 patients. Two cohorts each included 7 PD patients with bilateral subthalamic nucleus (STN) stimulation and 7 ET patients with unilateral ventral intermediate nucleus (VIM) stimulation of the thalamus. All directional leads included 6172 Infinity 8-Channel Directional leads and Infinity internal pulse generators (Abbott Neuromodulation, Plano, TX, USA) and nondirectional leads included lead 3389 with Activa SC for VIM and PC for STN (Medtronic, Minneapolis, MN, USA). Six-month outcomes for medication reduction and motor score improvements between new and legacy DBS systems in PD and ET patients were similar. Directionality was employed in 1/3 of patients. Therapeutic window (difference between amplitude when initial symptom relief was obtained and when intolerable side effects appeared with the contact being used) was significantly greater in new DBS systems in both PD (p = 0.005) and ET (p = 0.035) patients. The windows for new and legacy systems were 3.60 V ± 0.42 and 2.00 V ± 0.32 for STN and 3.06 V ± 0.44 and 1.85 V ± 0.28 for VIM, respectively. The therapeutic window of newer systems, whether or not directionality was used, was significantly greater than that of the legacy system, which suggests increased benefit and programming options. Improvements in hardware and programming interfaces in the newer systems may also contribute to wider therapeutic windows. We expect that as we alter workflow associated with newer technology, more patients will use directionality, and amplitudes will become lower.

Exploring the effects of deep brain stimulation and vision on tremor in Parkinson\u2019s disease - benefits from objective methods

BackgroundTremor is a cardinal symptom of Parkinson’s disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision.MethodsWe studied 10 patients with idiopathic PD, who were responsive to L-Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design.ResultsTremor was detected with the Unified Parkinson’s Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON.ConclusionsTechnical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.

Three-Year Gait and Axial Outcomes of Bilateral STN and GPi Parkinson's Disease Deep Brain Stimulation.

Objective: To examine the short- and long-term clinical outcomes of the bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on gait and axial symptoms in Parkinson’s disease (PD) patients. Available data have been inconsistent and mostly short-term regarding the effect of both brain targets on gait and axial symptoms. We aimed to identify potential target specific differences at 3-year follow-up from a large single-center experience.Methods: We retrospectively reviewed short-term (6-month follow-up) and long-term (36-month follow-up) changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and III total scores of 72 PD patients (53 with bilateral STN-DBS and 19 with bilateral GPi-DBS). An interdisciplinary team made target-specific decisions for each DBS patient. We analyzed changes in gait and axial subscores derived from UPDRS II and III.Results: In both the STN- and GPi-DBS cohorts, we observed no significant differences in gait and axial UPDRS derived subscores in the off-med/on stimulation state at long-term follow-up when compared to baseline. On-med axial scores remained similar in the short-term but worsened in both groups (STN, 2.23 ± 3.43, p < 0.001; GPi, 2.53 ± 2.37, p < 0.01) in the long-term possibly due to disease progression. At long-term follow-up, the UPDRS III off-med/on stimulation scores worsened but were persistently improved from baseline in both groups (−9.07 ± 13.9, p < 0.001).Conclusions: The study showed that long-term both STN- and GPi-DBS had a similar effect on gait and axial symptoms in UPDRS derived subscores at 36-month follow-up despite potential baseline differences in criteria for selection of each target. More sophisticated measures of gait and balance beyond the categorical UPDRS score will be needed for future studies.

Visualization of volume of tissue activated modeling in a clinical planning system for deep brain stimulation.

Pathway activating models try to describe stimulation spread in deep brain stimulation (DBS). Volume of tissue activated (VTA) models are simplified model variants allowing faster and easier computation. Our study aimed to investigate, how VTA visualization can be integrated into a clinical workflow applying directional electrodes using a standard clinical DBS planning system. Twelve patients underwent DBS, using directional electrodes for bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease. Preoperative 3T magnetic resonance imaging was used for automatic visualization of the STN outline, as well as for fiber tractography. Intraoperative computed tomography was used for automatic lead detection. The Guide XT software, closely integrated into the DBS planning software environment, was used for VTA calculation and visualization. VTA visualization was possible in all cases. The percentage of VTA covering the STN volume ranged from 25% to 100% (mean: 60±25%) on the left side and from 0% to 98% (51±30%) on the right side. The mean coordinate of all VTA centers was: 12.6±1.2 mm lateral, 2.1±1.2 mm posterior, and 2.3±1.4 mm inferior in relation to the midcommissural point. Stimulation effects can be compared to the VTA visualization in relation to surrounding structures, potentially facilitating programming, which might be especially beneficial in case of suboptimal lead placement. VTA visualization in a clinical planning system allows an intuitive adjustment of the stimulation parameters, supports programming, and enhances understanding of effects and side effects of DBS.

Long-term effects of bilateral subthalamic nucleus stimulation on sleep in patients with Parkinson's disease.

ObjectivesDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been reported to have a positive effect on sleep-wake disturbance in Parkinson's disease (PD). We aimed to investigate the long-term effects of STN DBS on sleep in patients with PD.MethodsSixty-one patients with PD who had undergone bilateral STN DBS were followed for 3 years with assessments including the Parkinson’s disease sleep scale (PDSS), Epworth sleepiness scale (ESS), total sleep hours per day, Unified PD Rating Scale part I-III, Hoehn & Yahr stage, levodopa equivalent dose, quality of life measure, and depression scale measured preoperatively and at 6 months after postoperatively, and annually thereafter.ResultsAmong the 61 patients at baseline, 46 patients completed the last follow-up assessment. The total PDSS score significantly improved after STN DBS from baseline up to 3 years after STN DBS (79.0±30, 100.0±23.3, 98.8±23.0, 97.1±29.6, and 93.3±28.0 at baseline, 6, 12, 24, and 36 months, respectively, p = 0.006 for the change over time). Among the eight PDSS domains, the domains for overall quality of a night’s sleep, sleep onset and maintenance insomnia, and nocturnal motor symptoms showed significant improvement after STN DBS (p = 0.036, 0.029, and < 0.001, respectively, for the change over time). The total sleep hours per day were increased, but the total ESS score did not show significant change after STN DBS (p = 0.001 and 0.055, respectively, for the change over time). Changes in the total PDSS were associated with changes in the depression and motivation items in the Unified PD Rating Scale part I, depression scale, and quality of life measure, but those variables at baseline were not predictive of changes in the total PDSS after STN DBS.ConclusionIn the largest systematic long-term follow-up study, the improvement in subjective sleep quality after bilateral STN DBS was sustained in PD patients. Improved nocturnal sleep and nocturnal motor symptoms were correlated with an improved mood and quality of life. However, STN DBS did not reduce excessive daytime sleepiness despite reductions in antiparkinsonian medications.

Determinants of Functional Independence or Its Loss following Subthalamic Nucleus Stimulation in Parkinson’s Disease

Objective: This study aimed to describe the change in functional status following bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson’s disease (PD) and to identify predictors of postoperative functional dependence. Methods: We included PD patients with bilateral STN-DBS who had complete Schwab & England Activities of Daily Living (S&E ADL) Scale data at baseline and 6 months after surgery from our prospective registry. Functional dependence was defined as an S&E ADL score of less than 80%. All data were collected from the on-medication state and on-stimulation state (after surgery). Logistic regression analyses were performed to determine the factors predictive of functional dependence after surgery. Results: A total of 196 patients were included. At baseline, 41 patients were functionally dependent and the other 155 were functionally independent. Among the patients with preoperative dependence, 32 (78%) became functionally independent after surgery, and this conversion was associated with a lower baseline axial score (p = 0.012). Among the patients with preoperative independence, 21 (14%) developed postoperative dependence, and this conversion was associated with a higher baseline axial score (p = 0.013) and its smaller improvement (p < 0.001). Female sex (odds ratio [OR] 3.214; 95% confidence interval [CI] 1.210–8.542; p = 0.019) and a higher baseline axial score (OR 1.184; 95% CI 1.056–1.327; p = 0.004) significantly predicted the risk of postoperative functional dependence. Conclusions: We found that functional status following bilateral STN-DBS is closely related to preoperative axial symptoms. When loss of independence is a potential target for STN-DBS, clinicians should take into consideration the severity of axial impairment before surgery.

Initial Results of Bilateral Subthalamic Nucleus Stimulation for Parkinson Disease in a Newly Established Center in a Developing Country: Shiraz, Southern Iran

To report the establishment of a new center for deep brain stimulation (DBS) as a surgical treatment for Parkinson disease and the surgical outcomes, from 2014 to 2017 in Shiraz, Southern Iran. A new treatment program was established in Shiraz through a multidisciplinary team in 2014. Thirty-four patients underwent implantation of subthalamic nucleus (STN) electrodes during the last 3 years. Twenty-five patients fulfilled the minimum 6-month follow-up criteria. The baseline Unified Parkinson Disease Rating Scale (UPDRS) was assessed 1 month before surgery in both off-medication and on-medication states by a movement disorder neurologist. To evaluate the outcomes, subscores of the UPDRS were assessed in all patients before surgery and at least 6 months after the operation. All 25 patients had advanced Parkinson disease categorized as stage 3 or 4 using the Hoehn and Yahr scale. STN DBS resulted in a dramatic improvement in motor function of most patients. A reduction in dopaminergic medication dosage (average 60% reduction) was observed. The mean improvement was 40% in UPDRS II and 67% in UPDRS III. No surgical or hardware complications were observed. Stimulation-related adverse effects, including increased falling and worsening of speech, occurred in a few patients after surgery. Most of the patients experienced weight gain after surgery. Bilateral STN DBS is a satisfactory and safe treatment for carefully selected patients with advanced Parkinson disease. According to the results, the procedure can be performed safely and with comparable results in developing countries around the world.

Battery Longevity Comparison of Two Commonly Available Dual Channel Implantable Pulse Generators Used for Subthalamic Nucleus Stimulation in Parkinson’s Disease

Objectives: Deep brain stimulation for Parkinson’s disease (PD) utilises an implantable pulse generator (IPG) whose finite lifespan in non-rechargeable systems necessitates their periodic replacement. We wish to determine if there is any significant difference in longevity of 2 commonly used IPG systems; the Medtronic Kinetra, and the Medtronic Activa Primary Cell (PC), which has come to replace it. Methods: All patients with bilateral Subthalamic Nucleus stimulators for PD performed in our centre were included. Battery life was then assessed using a Kaplan-Meier approach and comparisons between the Kinetra and Activa PC batteries were performed using log-rank tests. Results: Complete data was available for 183 patients. There was a significant difference in the average battery duration with an estimated median battery life in the Kinetra cohort of 6.6 years (95% CI 6.4–6.7), compared to 4.5 years (95% CI 4.4–4.5) in the Activa PC cohort (p < 0.001). Conclusion: The Activa PC IPG demonstrates a significantly reduced battery life of 2.1 years, with a median battery life of 4.5 years in comparison to 6.6 years in the Kinetra IPG. Future technology developments should therefore be focused on improving the battery life of the newer IPG systems.

Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis.

Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS) has proven effective in improving motor symptoms in Parkinson's disease (PD) patients. However, psychiatric changes after surgery are controversial. In this study, we specifically analyzed apathy following bilateral STN-DBS in PD patients using a meta-analysis. Relevant articles utilized for this study were obtained through literature search on PubMed, ScienceDirect, and Embase databases. The articles included were those contained both pre- and postsurgery apathy data acquired using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow-up of at least three months. A total of 9 out of 86 articles were included in our study through this strict screening process. Standardized mean difference (SMD), that is, Cohen's d, with a 95% confidence interval (CI) was calculated to show the change. We found a significant difference between the presurgery stage and the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17∼0.52, P < 0.001). STN-DBS seems to relatively worsen the condition of apathy, which may result from both the surgery target (subthalamic nucleus) and the reduction of dopaminergic medication. Further studies should focus on the exact mechanisms of possible postoperative apathy in the future.

The Dominant-Subthalamic Nucleus Phenomenon in Bilateral Deep Brain Stimulation for Parkinson's Disease: Evidence from a Gait Analysis Study.

It has been suggested that parkinsonian [Parkinson's disease (PD)] patients might have a "dominant" (DOM) subthalamic nucleus (STN), whose unilateral electrical stimulation [deep brain stimulation (DBS)] could lead to an improvement in PD symptoms similar to bilateral STN-DBS. Since disability in PD patients is often related to gait problems, in this study, we wanted to investigate in a group of patients bilaterally implanted for STN-DBS: (1) if it was possible to identify a subgroup of subjects with a dominant STN; (2) in the case, if the unilateral stimulation of the dominant STN was capable to improve gait abnormalities, as assessed by instrumented multifactorial gait analysis, similarly to what observed with bilateral stimulation. We studied 10 PD patients with bilateral STN-DBS. A clinical evaluation and a kinematic, kinetic, and electromyographic (EMG) analysis of overground walking were performed-off medication-in four conditions: without stimulation, with bilateral stimulation, with unilateral right or left STN-DBS. Through a hierarchical agglomerative cluster analysis based on motor Unified Parkinson's Disease Rating Scale scores, it was possible to separate patients into two groups, based on the presence (six patients, DOM group) or absence (four patients, NDOM group) of a dominant STN. In the DOM group, both bilateral and unilateral stimulation of the dominant STN significantly increased gait speed, stride length, range of motion of lower limb joints, and peaks of moment and power at the ankle joint; moreover, the EMG activation pattern of distal leg muscles was improved. The unilateral stimulation of the non-dominant STN did not produce any significant effect. In the NDOM group, only bilateral stimulation determined a significant improvement of gait parameters. In the DOM group, the effect of unilateral stimulation of the dominant STN determined an improvement of gait parameters similar to bilateral stimulation. The pre-surgical identification of these patients, if possible, could allow to reduce the surgical risks and side effects of DBS adopting a unilateral approach.