Unilateral Subthalamic Nucleus Deep Brain Stimulation Research Articles

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation

While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinson's disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using functional magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examination of cell-type specific STN feedforward neural activity. Unilateral optogenetic STN DBS elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, this modulation effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetic DBS induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS.

490 Unilateral Subthalamic Nucleus Deep Brain Stimulation Improves Motor Symptoms Without Neurocognitive Worsening in Parkinsons Disease

INTRODUCTION: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical intervention for patients with medically refractory Parkinson’s disease (PD). Numerous reports have described adverse nonmotor side effects, such as declines in verbal fluency and working memory, following bilateral implantation. Unilateral STN DBS is a possible alternative; however, it remains unclear whether unilateral implantation meaningfully reduces harmful effects on cognition. METHODS: This retrospective cohort study utilized chart review to collect pre- and postoperative Unified Parkinson’s Disease Rating Scale (UPDRS)-III, Levodopa Equivalent Daily Dosage (LEDD), imaging, and neurocognitive test results from 32 patients (unilateral, n = 12; bilateral, n = 20). For all statistical comparisons, p-values less than or equal to 0.05 were considered statistically significant. Student’s unpaired and paired T-tests were used to assess for differences between groups and within groups, respectively. RESULTS: There was no difference across 17 preoperative neurocognitive tests. Both unilateral and bilateral STN DBS resulted in significant decreases in postoperative UPDRS-III and LEDD (unilateral: p < 0.0001; bilateral: p < 0.0001) scores. There were no differences in the absolute decreases in UPDRS (p=0.055) and LEDD (p=0.120) scores between the groups. The bilateral STN DBS group had a significant deterioration in verbal fluency (COWAT FAS, p = 0.002; COWAT Animals, p = 0.014) and attention/executive function (Trails A, p=0.049 and Trails B, p = 0.011) compared to the unilateral group. CONCLUSIONS: Unilateral STN DBS is an effective and safe treatment option for patients with advanced PD. Particularly for patients with asymmetric motor symptoms, unilateral implantation provides a meaningful improvement in motor symptoms and reductions in dopaminergic medications without the risk of neurocognitive decline seen in bilateral implantation.

The Effects of Subthalamic Nucleus Deep Brain Stimulation and Retention Delay on Memory-Guided Reaching Performance in People with Parkinson's Disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) improves intensive aspects of movement (velocity) in people with Parkinson's disease (PD) but impairs the more cognitively demanding coordinative aspects of movement (error). We extended these findings by evaluating STN-DBS induced changes in intensive and coordinative aspects of movement during a memory-guided reaching task with varying retention delays. We evaluated the effect of STN-DBS on motor control during a memory-guided reaching task with short and long retention delays in participants with PD and compared performance to healthy controls (HC). Eleven participants with PD completed the motor section of the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) and performed a memory-guided reaching task under four different STN-DBS conditions (DBS-OFF, DBS-RIGHT, DBS-LEFT, and DBS-BOTH) and two retention delays (0.5 s and 5 s). An additional 13 HC completed the memory-guided reaching task. Unilateral and bilateral STN-DBS improved the MDS-UPDRS III scores. In the memory-guided reaching task, both unilateral and bilateral STN-DBS increased the intensive aspects of movement (amplitude and velocity) in the direction toward HC but impaired coordinative aspects of movement (error) away from the HC. Furthermore, movement time was decreased but reaction time was unaffected by STN-DBS. Shorter retention delays increased amplitude and velocity, decreased movement times, and decreased error, but increased reaction times in the participants with PD. There were no interactions between STN-DBS condition and retention delay. STN-DBS may affect cognitive-motor functioning by altering activity throughout cortico-basal ganglia networks and the oscillatory activity subserving them.

Evidence of Improved Verbal Fluency Following Unilateral Right Hemisphere Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease (S51.007)

<h3>Objective:</h3> To investigate verbal fluency following unilateral subthalamic nucleus deep brain stimulation (STN-DBS). <h3>Background:</h3> STN-DBS is safe and effective for motor symptoms, but a widely replicated cognitive outcome following bilateral STN-DBS is verbal fluency decline. Since non-motor symptoms, including mild cognitive impairment and dementia are a significant cause of disability in Parkinson’s disease (PD), reducing the risk of DBS-related cognitive decline is important. Compared to bilateral STN-DBS, little is known about unilateral STN-DBS effects on verbal fluency <h3>Design/Methods:</h3> We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL). Targets were based on treatment of the most symptomatic side (<i>n</i> = 17 left STN-DBS; 14 right STN-DBS). At 2-, 4-, and 6-months post-surgery, all participants completed a verbal fluency measure (FAS/CFL), and stimulation type (directional versus ring) was randomized. Welch’s two-sample t-test was used to compare verbal fluency baseline scores and the effects of hemisphere and stimulation on cognition were analyzed using linear mixed effects models. Covariates included age, education, and levodopa equivalents at each time point. <h3>Results:</h3> Left STN-DBS patients scored lower on a verbal fluency task than right STN-DBS patients (t(20.66) = −2.49, p = 0.02) at baseline. Following DBS surgery, we observed declines in verbal fluency over the study duration only in the left STN-DBS group (<i>p</i> = 0.02), while the right STN-DBS group improved (<i>p</i>&lt;.001). Stimulation type was not associated with verbal fluency performance. <h3>Conclusions:</h3> After adjusting for age, education, and levodopa equivalent dose, we found group-level verbal fluency declines following unilateral left STN-DBS and improved verbal fluency following unilateral right STN-DBS. In contrast with bilateral STN-DBS where verbal fluency declines are often reported, it is possible that selecting unilateral right STN-DBS to control left-sided symptoms may be a modifiable risk factor to potentially reduce the likelihood of verbal fluency declines in patients with PD. <b>Disclosure:</b> Dr. Del Bene has nothing to disclose. The institution of Roy C Martin, 4854 has received research support from NIH. Ms. Brinkerhoff has received research support from National Institute of Neurological Disorders and Stroke. Dr. Olson has nothing to disclose. The institution of Dr. Nelson has received research support from NIH. Dr. Marotta has nothing to disclose. Mr. Gonzalez has nothing to disclose. Dr. Mills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tilosia. The institution of Dr. Mills has received research support from NINDS. The institution of Dr. Mills has received research support from MJFF. The institution of Dr. Mills has received research support from GKC. The institution of Dr. Kamath has received research support from NIH. Dr. Bentley has nothing to disclose. Dr. Walker has nothing to disclose.

Letter: Evaluation and Surgical Treatment of Functional Neurosurgery Patients With Implanted Deep Brain Stimulation and Vagus Nerve Stimulation Pulse Generators During the COVID-19 Pandemic.

Author(s): Gross, Robert E; Buetefisch, Cathrin M; Miocinovic, Svjetlana; Bullinger, Katie L; Okun, Michael S; Ostrem, Jill L; Foote, Kelly D; Starr, Phillip A

The Effect of Unilateral Subthalamic Nucleus Deep Brain Stimulation on Contralateral Subthalamic Nucleus Local Field Potentials

Unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) improves ipsilateral symptoms, but how this occurs is not well understood. We investigated whether unilateral STN DBS suppresses contralateral STN beta activity in the local field potential (LFP), since previous research has shown that activity in the beta band can correlate with the severity of contralateral clinical symptoms and is modulated by DBS. We recorded STN LFPs from 14 patients who underwent bilateral STN DBS for PD. Following a baseline recording, unilateral STN stimulation was delivered at therapeutic parameters while LFPs were recorded from the contralateral (unstimulated) STN. Unilateral STN DBS suppressed contralateral beta power (p = 0.039, relative suppression = -5.7% ± [SD] 16% when averaging across the highest beta peak channels; p = 0.033, relative suppression = -5.2% ± 13% when averaging across all channels). Unilateral STN DBS produced a 17% ipsilateral (p = 0.016) and 29% contralateral (p = 0.002) improvement in upper limb hemi-body bradykinesia-rigidity (UPDRS-III, items 3.3-3.6). The ipsilateral clinical improvement and the change in contralateral beta power were not significantly correlated. Unilateral STN DBS suppresses contralateral STN beta LFP. This indicates that unilateral STN DBS modulates bilateral basal ganglia networks. It remains unclear whether this mechanism accounts for the ipsilateral motor improvements.

Asymmetric Deep Brain Stimulation Electrodes for Parkinson's Disease: A Pilot Study of Symptom-Tailored Stimulation

Abstract INTRODUCTION Bilateral subthalamic nucleus (STN) and globus pallidus interna (GPi) deep brain stimulation (DBS) are well established targets for the management of Parkinson's disease (PD). Each target has its own advantage, we presume the simultaneous unilateral STN and contralateral GPi DBS may compromise side effects of bilateral stimulation and keep each nucleus and its own efficacy on the motor and nonmotor symptoms. METHODS Eight patients with idiopathic PD with this kind of procedure were retrospectively reviewed. Motor, nonmotor symptoms, quality of life were measured before surgery, 6 mo, 1-yr post surgery under following conditions: medication on and off, bilateral stimulation on and off, unilateral STN stimulation on. Medication and stimulation parameters were noted. RESULTS Unilateral STN and contralateral GPi DBS significantly improved the UPDRS-? scores, with a 45% reduction at 6 mo and a 43% reduction at 1 yr. In total, 41% of levodopa equivalent daily dose was reduced at 1-yr follow-up. In the medication on condition, bilateral stimulation improved axial symptoms by 28.4% at 1-yr follow-up. In total, 3 m TUG (Time-Up Go test) improved by 41% at 6-mo follow-up compared to baseline, which lasts for 1 yr. In total, 64% reduction was found between baseline and 1-yr follow-up in gait and fall questionnaires. No deterioration was found in nonmotor measurements. No adverse events other than stimulation related were reported. CONCLUSION Our results provide the first evidence that supports unilateral STN and contralateral GPi DBS might be effective and safe in advanced PD patients. Future efforts are needed to explore the potential advantage in axial and cognitive symptoms in long term.

Effect of unilateral subthalamic deep brain stimulation in highly asymmetrical Parkinson's disease: 7-year follow-up.

For patients with highly asymmetrical Parkinson's disease (PD), unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) has been suggested as a reasonable treatment. However, the results of a previous 2-year follow-up study involving patients with prominently asymmetrical PD who had unilateral STN DBS suggested that simultaneous bilateral surgery should be performed. In the present study, the authors analyze 7-year follow-up data from the same patient group to examine changes in motor benefit from unilateral STN DBS over time and the interval between initial unilateral surgery and a second (contralateral) STN DBS surgery. Eight patients with highly asymmetrical parkinsonism who underwent unilateral STN DBS were evaluated. The factors measured were scores on the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III), Hoehn and Yahr (HY) stage, and levodopa equivalent daily dose (LEDD). Evaluations occurred at 3, 6, and 12 months after the initial surgery and annually thereafter. The mean follow-up period was 91.5 months (range 36-105 months). Three years after the initial unilateral surgery, motor benefits on the contralateral side continued; however, an aggravation of the ipsilateral parkinsonism attenuated the improvement in total UPDRS III scores, which reverted to baseline. Axial motor score, LEDD, and HY stage did not differ from the baseline. Seven of 8 patients (87.5%) were considered candidates for a second surgery to offer additional motor benefits. Of the 7 candidates, 4 patients (50% of total patients) underwent the second surgery at 58.5 ± 11.6 (mean ± SD) months after the initial surgery. Three patients were not able to have the second surgery: one patient died of gastric cancer, one patient was severely immobilized by an accident, and one patient could not afford the second surgery. One patient remained content with the initial unilateral surgery throughout the follow-up period. Seven of 8 patients with unilateral STN DBS became candidates for second surgery before battery replacement surgery of the first implanted device. Baseline asymmetry alone may not predict appropriate candidates for unilateral STN DBS. This study provides further evidence that, from a long-term perspective, initial simultaneous bilateral STN DBS should be considered for PD patients with prominently asymmetrical motor symptoms.

Anatomical Correlates of Uncontrollable Laughter With Unilateral Subthalamic Deep Brain Stimulation in Parkinson’s Disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for the management of motor complications in Parkinson's disease. Uncontrollable laughter has been reported as a rare side effect of STN stimulation. The precise mechanism responsible for this unique phenomenon remains unclear. We examined in detail the DBS electrode position and stimulation parameters in two patients with uncontrollable laughter during programming after STN-DBS surgery and illustrated the anatomical correlates of the acute mood changes with STN stimulation. Unilateral STN-DBS induced uncontrollable laughter with activation of the most ventral contacts in both patients. However, the location of the electrodes responsible for this adverse effect differed between the patients. In the first patient, the DBS lead was placed more inferiorly and medially within the STN. In the second patient, the DBS lead was implanted more anteriorly and inferiorly than initially planned at the level of the substantia nigra reticulata (SNr). Unilateral STN-DBS can induce acute uncontrollable laughter with activation of electrodes located more anterior, medial, and inferior in relationship with the standard stereotactic STN target. We suggest that simulation of ventral and medial STN, surrounding limbic structures or the SNr, is the most plausible anatomical substrate responsible for this acute mood and behavioral change. Our findings provide insight into the complex functional neuroanatomical relationship of the STN and adjacent structures important for mood and behavior. DBS programming with more dorsal and lateral contacts within the STN should be entertained to minimize the emotional side effects.

Theinfluence of the learning and memory ability after stimulation by subthalamic nucleus-deep brain stimulation in rats with Parkinson’s disease

Objective To investigate the changes of the learning and memory ability after being stimulated by subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s Disease (PD) rats. Methods 60 healthy male SD rats were randomly divided into normal control group (n=15), PD group (n=15), the rats in sham stimulation group(n=15) and stimulation group (n=15). Stimulation and sham stimulation groups were planted in unilateral STN-DBS. STN-DBS in stimulation group was powered on and was stimulated 7 consecutive days at the regular time, while the rats in Sham stimulation group complied with the same process except power on the STN-DBS. The apomorphine rotation was observed at pre-stimulation、stimulation and post-stimulation. The latency to find the platform, swimming speed, swimming distance and crossing times of rats were detected with Morris water maze. Results The symptoms of PD rats were improved significantly after stimulated by STN-DBS. Compared with PD model group and sham stimulation model group, not only escape latency of rats in the DBS stimulated model group was decreased (P=0.008, P=0.009), but also swimming speed (P=0.002, P=0.001) and swimming distance (P=0.091, P=0.001) were descend. The crossing times、the percentage swimming distance and the percentage swimming time in which the platform located of PD model group [respectively (1.380±1.193) times, (19.470±3.226)%, (18.766±5.486)%] and sham stimulation model group [respectively (1.730±1.009) times, (19.862±4.125)%, (21.846±4.234)%] were definitely lesser than stimulation model group [respectively (6.800±1.135) times, (28.010±4.113)%, (31.836±9.940)%]. In terms of the crossing times(P=0.003, P=0.022), the percentage swimming distance (P=0.011, P=0.014) and the percentage swimming time (P=0.016, P=0.021) in the platform, there were significant differences that stimulation model group compared with PD model group and sham stimulation model group. Conclusion STN-DBS stimulation can not only improve the ability of cognition, but also delay the condition worsen. Key words: Parkinson’s disease; Cognition; Morris water maze; Subthalamic nucleus-deep brain stimulation; Rats

The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson's disease.

Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study.

Gait dysfunction in Parkinson's disease (PD) does not always respond to bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Since right hemisphere motor networks may be dominant for gait control, identical stimulation of asymmetric circuits could account for gait dysfunction. We compared the effects of bilateral and unilateral STN-DBS on gait kinematics in PD patients who developed gait impairment after STN-DBS. Twenty-two PD patients with >50% improvement in motor scores, but dopamine-resistant gait dysfunction 6-12months after bilateral STN-DBS were blindly tested off dopaminergic effects in four randomly assigned DBS conditions: bilateral, right-sided, left-sided and off stimulation. Motor scores (MDS-UPDRS III), gait scores (MDS-UPRDS 2.11-2.13+3.9-3.13), turning time (seconds), stride length (meters) and velocity (meters/second) were measured 1h after DBS changes. Motor and gait scores significantly improved with bilateral versus unilateral STN-DBS. Stride length and velocity (0.95±0.06, 0.84±0.07) significantly improved with bilateral (1.09±0.04, 0.95±0.05), right-sided (1.06±0.04, 0.92±0.05) and left-sided stimulation (1.01±0.05, 0.90±0.05) (p<0.05). Stride length significantly improved with right-sided versus left-sided (0.05±0.02) and bilateral versus left-sided stimulation (0.07±0.02) (p<0.05). Turning time (4.89±0.6) tended to improve with bilateral (4.13±0.5) (p=0.15) and right-sided (4.27±0.6) (p=0.2) more than with left STN-DBS (4.69±0.5) (p=0.5). Bilateral STN-DBS yields greater improvement in motor and gait scores in PD patients. Yet, unilateral stimulation has similar effects on gait kinematics. Particularly, right-sided stimulation might produce slightly greater improvements. Although the clinical relevance of differential programming of right versus left-sided STN-DBS is unclear, this approach could be considered in the management of treatment-resistant gait dysfunction in PD.

Hyperhidrosis associated with subthalamic deep brain stimulation in Parkinson's disease: Insights into central autonomic functional anatomy

IntroductionThere is limited evidence regarding the precise location and connections of thermoregulatory centers in humans. We present two patients managed with subthalamic nucleus (STN) Deep Brain Stimulation (DBS) for motor fluctuations in PD that developed reproducible hyperhidrosis with high frequency DBS. ObjectiveTo describe the clinical features and analyze the location of the electrodes leading to autonomic activation in both patients. MethodsWe retrospectively assessed the anatomical localization, electrode programming settings and effects of unilateral STN DBS leading to hyperhidrosis. ResultsUnilateral stimulation of anterior and medially located contacts within the STN and zona incerta (Zi) caused bilateral, consistent, reproducible, and reversible sweating in our patients. Adequate control of motor symptoms without autonomic side effects was accomplished with alternative programming settings. ConclusionStimulation of the medial Zi and medial and anterior STN causes hyperhidrosis in a pattern similar to that described in primates and rats. We speculate that central autonomic fibers originating in the lateral hypothalamic area project laterally to the ventral/medial Zi and then to brainstem nuclei following an medial and posterior trajectory in relationship to STN.

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.

Functional anatomy of subthalamic nucleus stimulation in Parkinson disease.

We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3-dimensional brain region and to assign statistical significance after stringent type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS. Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site. Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive, and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory). Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, because movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive, and limbic information in STN.

Swallowing Outcomes Following Unilateral STN vs. GPi Surgery: A Retrospective Analysis

The adverse effects of deep brain stimulation (DBS) surgery on swallowing could potentially exacerbate the natural deterioration of airway protection associated with Parkinson's disease (PD) degeneration and increase the incidence of aspiration pneumonia and associated death. There are no studies that compare swallowing outcomes associated with subthalamic nucleus (STN) versus globus pallidus interna (GPi) DBS surgery; therefore, we completed a retrospective study comparing swallowing outcomes in a cohort of patients with PD who underwent unilateral DBS surgery in either the STN or GPi. A chart review was completed to identify all patients with a diagnosis of PD who received videofluoroscopic swallowing evaluations before DBS and after unilateral DBS in the STN or GPi. The retrospective search yielded 33 patients (STN=14, GPi=19) with idiopathic PD who met the inclusion criteria. Mean penetration-aspiration (PA) scores did not change significantly for participants who underwent GPi surgery (z=-.181, p=.857), but mean PA scores significantly worsened for participants who underwent STN DBS (z=-2.682, p=.007). There was a significant improvement in Unified PD Rating Scale (UPDRS) scores off medication before surgery, to off medication and on stimulation after surgery for both groups (F=23.667, p<.001). Despite the limitations of a retrospective analysis, this preliminary study suggests that unilateral STN DBS may have an adverse effect on swallowing function, while unilateral GPi DBS does not appear to have a similar deleterious effect. This study and other future studies should help to elucidate the mechanisms underpinning the effects of DBS on swallowing function.

The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease

While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (STN) DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However, little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and Part 3 scores were retained at the end of the 2-year follow-up period in both subsets of patients. Multivariate logistic regression analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

Subthalamic Deep Brain Stimulation With a New Device in Parkinson’s Disease: An Open-Label Trial

We aimed to evaluate the safety and efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) with a new stimulator (Beijing PINS Medical Co., Ltd, PNS 1101) in Parkinson's disease (PD). Forty patients received a PINS device implantation in the subthalamic nucleus. The effects of stimulation on motor score, activities of daily living, good-quality on-time, and the levodopa-equivalent dose were analyzed for all 40 patients with PD treated with bilateral or unilateral STN-DBS. The scores were collected at baseline in two conditions (on/off medication) and at 3, 6, 9, 12, and 24 months of follow-up with stimulation in the absence or presence of medication. The patients were followed up for two years. At 3, 6, 9, 12, and 24 months of follow-up, our results showed a significant increase from baseline in both activities of daily living and motor scores (p < 0.001) and good-quality on-time (p < 0.001); the daily levodopa-equivalent dose decreased compared with baseline (p < 0.01). No patient died during the study, and none of the adverse effects were classified as severe. All of the adverse events were resolved or improved by the end of the study. STN-DBS with the PINS device significantly improved the symptoms of PD when compared with baseline in this trial. This new device may be recommended for the treatment of patients with advanced PD; however, a randomized, double-blinding trial will be required.

Verbal Fluency in Patients Receiving Bilateral versus Left-Sided Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease

The purpose of this study was to investigate the relative effects of unilateral (left-sided) versus bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on verbal fluency. To do this, 10 Parkinson's disease patients with predominantly bilateral motor symptoms who received bilateral STN DBS were compared with 6 patients suffering from predominantly unilateral symptoms who received STN DBS on the left side only. The results suggest that unilateral STN DBS of the speech dominant hemisphere is associated with significantly less declines in measures of verbal fluency as compared to bilateral stimulation.

Effect of deep brain stimulation on speech in Parkinson's disease: From research lab to clinic

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN), an evidence-based, effective surgical treatment with increasing popularity, can help patients with advanced Parkinson's disease eliminate or lessen many of the motor symptoms they experience. However, one of its unfortunate adverse effects is that it may worsen existing speech impairment as well as causing new impairment. As a result, the patients may be unable to speak loudly or clearly, or simply unable to initiate speech. The problems often associate with active as well as chronic STN stimulation. Further, there does not seem to be a uniform effect on different speech subsystems of respiration, phonation, and articulation. In this presentation, we will first review studies which have shown differential effects on phonation, articulation, and prosody associated with unilateral vs. bilateral STN DBS. Next, we will discuss the preliminary outcomes of several potential treatment approaches and strategies including the Lee Silverman voice treatment, change of DBS settings, and the altered auditory feedback. Lastly, we will discuss our experience of using the approaches and strategies helping patients with their speech deficits associated with STN DBS in clinical settings. Both mechanisms and limitations will be explored.