Unilateral Subthalamic Nucleus Research Articles

Unilateral Magnetic Resonance-Guided Focused Ultrasound Lesion of the Subthalamic Nucleus in Parkinson's Disease: A Prospective Study.

Unilateral subthalamic nucleus (STN) ablation using magnetic resonance-guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD). The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions. This prospective, single-center, open-label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6-month follow-up. We also evaluated cognitive-neuropsychological changes, self-assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes. On the treated side, the MDS-UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow-up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive-neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS-UPDRS III and contralateral tremor scores (P < 0.05). Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Unilateral globus pallidus internus combined contralateral subthalamic nucleus deep brain stimulation in the treatment of cervical dystonia: a case report and literature review

Background: Deep brain stimulation (DBS) is an effective treatment modality for medication-refractory cervical dystonia (CD). In recent years, the asymmetric targets for lead implantation of DBS have become a more valued topic. Objectives: To explore the efficacy of the asymmetric targets for lead implantation of DBS. Methods: A patient with CD underwent unilateral globus pallidus internus (GPi) combined contralateral subthalamic nucleus (STN) deep brain stimulation. Results: Although neither unilateral GPi nor STN stimulation relieved the patient’s clinical symptoms during temporary testing after surgery, the positive effect of bilateral stimulation was substantial. At the 12-month postoperative evaluation, the patient’s clinical symptoms improved remarkably, with an improvement rate of 78% compared with the preoperative assessment. Conclusions: Combined with the previous kinds of literature we reviewed in this article, we propose that in addition to conventional lead implantation, the option of using asymmetric targets for lead implantation can be considered when physicians encounter special conditions and can also be effective in relieving clinical symptoms in patients with CD.

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 &lt; 0.0001; bilateral: p &lt; 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.

Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

A multicenter double-blind randomized crossover study comparing the impact of dorsal subthalamic nucleus deep brain stimulation versus standard care on apathy in Parkinson’s disease: a study protocol

BackgroundNeuroimaging studies suggest an association between apathy after deep brain stimulation (DBS) and stimulation of the ventral part of the subthalamic nucleus (STN) due to the associative fibers connected to the non-motor limbic circuits that are involved in emotion regulation and motivation. We have previously described three patients with severe apathy that could be fully treated after switching stimulation from a ventral electrode contact point to a more dorsal contact point.ObjectivesTo determine whether more dorsal stimulation of the STN decreases apathy compared to standard care in a multicenter randomized controlled trial with a crossover design.MethodsWe will include 26 patients with a Starkstein Apathy Scale (SAS) score of 14 or more after subthalamic nucleus (STN) deep brain stimulation (DBS) for refractory Parkinson’s disease. This is a multicenter trial conducted in two teaching hospitals and one university medical center in the Netherlands after at least 3 months of STN DBS. Our intervention will consist of 1 month of unilateral dorsal STN stimulation compared to treatment as usual. The primary outcome is a change in SAS score following 1 month of DBS on the original contact compared to the SAS score following 1 month of DBS on the more dorsal contact. Secondary outcomes are symptom changes on the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale motor part III, Montgomery-Åsberg Depression Rating Scale, 39-item Parkinson’s disease questionnaire, Parkinson’s disease impulsive-compulsive disorders questionnaire, changes in levodopa-equivalent daily dosage, apathy rated by the caregiver, and burden and quality of life of the caregiver.Trial registrationClinicalTrials.gov NL8279. Registered on January 10, 2020.

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.

Successful Treatment of Biphasic and Peak-dose Dyskinesia With Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation.

Successful Treatment of Biphasic and Peak-dose Dyskinesia With Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation.

Local anatomy, stimulation site, and time alter directional deep brain stimulation impedances.

Directional deep brain stimulation (DBS) contacts provide greater spatial flexibility for therapy than traditional ring-shaped electrodes, but little is known about longitudinal changes of impedance and orientation. We measured monopolar and bipolar impedance of DBS contacts in 31 patients who underwent unilateral subthalamic nucleus deep brain stimulation as part of a randomized study (SUNDIAL, NCT03353688). At different follow-up visits, patients were assigned new stimulation configurations and impedance was measured. Additionally, we measured the orientation of the directional lead during surgery, immediately after surgery, and 1 year later. Here we contrast impedances in directional versus ring contacts with respect to local anatomy, active stimulation contact(s), and over time. Directional contacts display larger impedances than ring contacts. Impedances generally increase slightly over the first year of therapy, save for a transient decrease immediately post-surgery under general anesthesia during pulse generator placement. Local impedances decrease at active stimulation sites, and contacts in closest proximity to internal capsule display higher impedances than other anatomic sites. DBS leads rotate slightly in the immediate postoperative period (typically less than the angle of a single contact) but otherwise remain stable over the following year. These data provide useful information for setting clinical stimulation parameters over time.

Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation for Treatment of Parkinson Disease: A Pilot Study of Symptom-Tailored Stimulation

Zhang, Chencheng MD, PhD; Wang, Linbin MSc; Hu, Wei MD; Wang, Tao MD; Zhao, Yijie PhD; Pan, Yixin MD; Almeida, Leonardo MD; Ramirez-Zamora, Adolfo MD, PhD; Sun, Bomin MD, PhD; Li, Dianyou MD, PhD Author Information

Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapeutic principle in Parkinson's disease, but the underlying mechanisms, particularly mediating non-motor actions, remain largely enigmatic. Objective/hypothesisThe delayed onset of neuropsychiatric actions in conjunction with first experimental evidence that STN-DBS causes disease-modifying effects prompted our investigation on how cellular plasticity in midbrain dopaminergic systems is affected by STN-DBS. MethodsWe applied unilateral or bilateral STN-DBS in two independent cohorts of 6-hydroxydopamine hemiparkinsonian rats four to eight weeks after dopaminergic lesioning to allow for the development of a stable dopaminergic dysfunction prior to DBS electrode implantation. ResultsAfter 5 weeks of STN-DBS, stimulated animals had significantly more TH+ dopaminergic neurons and fibres in both the nigrostriatal and the mesolimbic systems compared to sham controls with large effect sizes of gHedges = 1.9–3.4. DBS of the entopeduncular nucleus as the homologue of the human Globus pallidus internus did not alter the dopaminergic systems. STN-DBS effects on mesolimbic dopaminergic neurons were largely confirmed in an independent animal cohort with unilateral STN stimulation for 6 weeks or for 3 weeks followed by a 3 weeks washout period. The latter subgroup even demonstrated persistent mesolimbic dopaminergic plasticity after washout. Pilot behavioural testing showed that augmentative dopaminergic effects on the mesolimbic system by STN-DBS might translate into improvement of sensorimotor neglect. ConclusionsOur data support sustained neurorestorative effects of STN-DBS not only in the nigrostriatal but also in the mesolimbic system as a potential factor mediating long-latency neuropsychiatric effects of STN-DBS in Parkinson's disease.

Walking Speed Reliably Measures Clinically Significant Changes in Gait by Directional Deep Brain Stimulation.

Introduction: Although deep brain stimulation (DBS) often improves levodopa-responsive gait symptoms, robust therapies for gait dysfunction from Parkinson's disease (PD) remain a major unmet need. Walking speed could represent a simple, integrated tool to assess DBS efficacy but is often not examined systematically or quantitatively during DBS programming. Here we investigate the reliability and functional significance of changes in gait by directional DBS in the subthalamic nucleus.Methods: Nineteen patients underwent unilateral subthalamic nucleus DBS surgery with an eight-contact directional lead (1-3-3-1 configuration) in the most severely affected hemisphere. They arrived off dopaminergic medications >12 h preoperatively and for device activation 1 month after surgery. We measured a comfortable walking speed using an instrumented walkway with DBS off and at each of 10 stimulation configurations (six directional contacts, two virtual rings, and two circular rings) at the midpoint of the therapeutic window. Repeated measures of ANOVA contrasted preoperative vs. maximum and minimum walking speeds across DBS configurations during device activation. Intraclass correlation coefficients examined walking speed reliability across the four trials within each DBS configuration. We also investigated whether changes in walking speed related to modification of step length vs. cadence with a one-sample t-test.Results: Mean comfortable walking speed improved significantly with DBS on vs. both DBS off and minimum speeds with DBS on (p < 0.001, respectively). Pairwise comparisons showed no significant difference between DBS off and minimum comfortable walking speed with DBS on (p = 1.000). Intraclass correlations were ≥0.949 within each condition. Changes in comfortable walk speed were conferred primarily by changes in step length (p < 0.004).Conclusion: Acute assessment of walking speed is a reliable, clinically meaningful measure of gait function during DBS activation. Directional and circular unilateral subthalamic DBS in appropriate configurations elicit acute and clinically significant improvements in gait dysfunction related to PD. Next-generation directional DBS technologies have significant potential to enhance gait by individually tailoring stimulation parameters to optimize efficacy.

Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation for Treatment of Parkinson Disease: A Pilot Study of Symptom-Tailored Stimulation.

BACKGROUNDSubthalamic nucleus (STN) and globus pallidus interna (GPi) are the most effective targets in deep brain stimulation (DBS) treatment for Parkinson disease (PD). However, the individualized selection of targets remains a clinical challenge.OBJECTIVETo combine unilateral STN and contralateral GPi stimulation (STN DBS in one brain hemisphere and GPi DBS in the other) to maximize the clinical advantages of each target while inducing fewer adverse side effects in selected patients with PD because each target has its own clinical effects and risk profiles.METHODSWe reviewed the clinical outcomes of 8 patients with idiopathic PD treated with combined unilateral STN and contralateral GPi DBS. Clinical outcome assessments, focusing on motor and nonmotor symptoms, were performed at baseline and 6-mo and 12-mo follow-up. We performed the assessments under the following conditions: medication on and off (bilateral stimulation on and off and unilateral STN stimulation on).RESULTSPatients showed a significant improvement in motor symptoms, as assessed by the Unified Parkinson Disease Rating Scale III (UPDRS-III) and Timed Up-and-Go Test (TUG), in the off-medication/on-stimulation state at 6-mo and 12-mo follow-up. Also, patients reported a better quality of life, and their intake of levodopa was reduced at 12-mo follow-up. In the on-medication condition, bilateral stimulation was associated with an improvement in axial symptoms, with a 64% improvement in measures of gait and falls at 12-mo follow-up. No irreversible adverse side effects were observed.CONCLUSIONOur findings suggest that combined unilateral STN and contralateral GPi DBS could offer an effective and well-tolerated DBS treatment for certain PD patients.

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

Long-term Parkinson\u2019s disease quality of life after staged DBS: STN vs GPi and first vs second lead

Deep brain stimulation (DBS) for Parkinson’s disease (PD) improves quality of life (QoL), but longitudinal follow-up data are scarce. We sought to quantify long-term benefits of subthalamic nucleus (STN) vs globus pallidus internus (GPi), and unilateral vs staged bilateral PD-DBS on postoperative QoL. This is a retrospective, longitudinal, non-randomized study using the PD QoL questionnaire (PDQ)-39 in patients with STN- or GPi-DBS, and with unilateral (N = 191) or staged bilateral (an additional contralateral lead implant) surgery (N = 127 and 156 for the first and second lead, respectively). Changes in PDQ-39 summary index (PDQ-39SI) and subscores throughout 60 months of follow-up were used as the primary analysis. We applied mixed models that included levodopa and covariates that differed at baseline across groups. For unilateral implantation, we observed an initial improvement in PDQ-39SI of 15.55 ± 3.29% (µ ± SE) across both brain targets at 4 months postoperatively. Unilateral STN patients demonstrated greater improvement in PDQ-39SI than GPi patients at 4 and 18 months postoperatively. Analysis of patients with staged bilateral leads revealed an initial 25.34 ± 2.74% (µ ± SE) improvement in PDQ-39SI at 4 months after the first lead with further improvement until 18 months, with no difference across targets. Scores did not improve after the second lead with gradual worsening starting at 18 months postoperatively. STN-DBS provided greater short-term QoL improvement than GPi-DBS for unilateral surgery. For staged bilateral DBS, overall QoL improvement was explained primarily by the first lead. Decision-making for patients considering DBS should include a discussion surrounding the potential risks and benefits from a second DBS lead.

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.

Subthalamic Gamma Knife Radiosurgery in Parkinson’s Disease: A Cautionary Tale

Introduction: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has been shown to reliably improve several symptoms of Parkinson’s disease (PD) in appropriately selected patients. Various factors may preclude patients from undergoing DBS and for them, non-invasive lesion-based therapies such as focused ultrasound and Gamma Knife (GK) radiosurgery may present a safer alternative. Materials and Methods: Based on preliminary positive reports of STN GK for PD, we conducted a prospective, open-label, single-center, pilot study in PD patients deemed potential candidates for unilateral DBS based on their disease characteristics, but contraindicated due to age >74, an irreversible bleeding diathesis, or significant comorbid medical disease. Stereotactic MRI-guided GK radiosurgery was performed using a single 110- or 120-Gy dose targeting the STN contralateral to the more symptomatic extremity. Clinical follow-up and imaging assessed the safety and efficacy of the procedure over a 12-month period. Results: Four PD patients with medication-refractory tremors and disabling dyskinesias underwent unilateral STN GK radiosurgery. Contraindications to DBS included high-risk comorbid cardiovas­cular disease in 3 patients and an irreversible bleeding diathesis in 1. There were no immediate post-procedural adverse events. One patient who underwent left STN GK radiosurgery developed right hemiparesis and dysarthria 7 months post-procedure followed by hospitalization at 9 months for bacterial endocarditis and liver failure from which he died. The remaining 3 patients were free of adverse events up to 12 months post-procedure and experienced a reduction in contralateral rigidity, bradykinesia, and tremor. Upon extended follow-up, 2 patients developed subacute worsening of gait. One died at 16 months due to complications of a fall whereas the other saw no change in gait up to 42 months post-procedure. All 3 patients with adverse events demonstrated a hyper-response in the targeted area on follow-up neuroimaging. Discussion/Conclusion: Despite the potential for clinical improvement, our results suggest that unilateral STN GK radiosurgery should be approached cautiously in medically frail PD patients who may be at higher risk of GK hyper-response and neurologic complications.

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.

A systematic review of deep brain stimulation for the treatment of drug-resistant epilepsy in childhood.

OBJECTIVE Drug-resistant epilepsy (DRE) presents a therapeutic challenge in children, necessitating the consideration of multiple treatment options. Although deep brain stimulation (DBS) has been studied in adults with DRE, little evidence is available to guide clinicians regarding the application of this potentially valuable tool in children. Here, the authors present the first systematic review aimed at understanding the safety and efficacy of DBS for DRE in pediatric populations, emphasizing patient selection, device placement and programming, and seizure outcomes. METHODS The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations. Relevant articles were identified from 3 electronic databases (MEDLINE, Embase, and Cochrane CENTRAL) from their inception to November 17, 2017. Inclusion criteria of individual studies were 1) diagnosis of DRE; 2) treatment with DBS; 3) inclusion of at least 1 pediatric patient (age ≤ 18 years); and 4) patient-specific data. Exclusion criteria for the systematic review included 1) missing data for age, DBS target, or seizure freedom; 2) nonhuman subjects; and 3) editorials, abstracts, review articles, and dissertations. RESULTS This review identified 21 studies and 40 unique pediatric patients (ages 4–18 years) who received DBS treatment for epilepsy. There were 18 patients with electrodes placed in the bilateral or unilateral centromedian nucleus of the thalamus (CM) electrodes, 8 patients with bilateral anterior thalamic nucleus (ATN) electrodes, 5 patients with bilateral and unilateral hippocampal electrodes, 3 patients with bilateral subthalamic nucleus (STN) and 1 patient with unilateral STN electrodes, 2 patients with bilateral posteromedial hypothalamus electrodes, 2 patients with unilateral mammillothalamic tract electrodes, and 1 patient with caudal zona incerta electrode placement. Overall, 5 of the 40 (12.5%) patients had an International League Against Epilepsy class I (i.e., seizure-free) outcome, and 34 of the 40 (85%) patients had seizure reduction with DBS stimulation. CONCLUSIONS DBS is an alternative or adjuvant treatment for children with DRE. Prospective registries and future clinical trials are needed to identify the optimal DBS target, although favorable outcomes are reported with both CM and ATN in children. ABBREVIATIONS ATN = anterior thalamic nucleus; CM = centromedian nucleus of the thalamus; DBS = deep brain stimulation; DRE = drug-resistant epilepsy; RNS = responsive neurostimulation; STN = subthalamic nucleus; VNS = vagus nerve stimulation.

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.