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Abstract Background The efficacy of levodopa, the most crucial metric for Parkinson’s disease diagnosis and treatment, is traditionally gauged through the levodopa challenge test, which lacks a predictive model. This study aims to probe the predictive power of T1-weighted MRI, the most accessible modality for levodopa response. Methods This retrospective study used two datasets: from the Parkinson’s Progression Markers Initiative (219 records) and the external clinical dataset from Ruijin Hospital (217 records). A novel feature extraction method using MedicalNet, a pre-trained deep learning network, along with three previous approaches was applied. Three machine learning models were trained and tested on the PPMI dataset and included clinical features, imaging features, and their union set, using the area under the curve (AUC) as the metric. The most significant brain regions were visualized. The external clinical dataset was further evaluated using trained models. A paired one-tailed t-test was performed between the two sets; statistical significance was set at p

Abstract Background Postural abnormalities (PA) are common in the advanced stages of Parkinson’s disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. Methods T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. Results Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. Conclusions Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. Trial registration Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)–nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST–NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

BackgroundRemote programming (RP) is an emerging technology that enables the adjustment of implantable pulse generators (IPGs) via the Internet for people with Parkinson's disease (PwPD) who have undergone deep brain stimulation (DBS). Previous studies have not comprehensively explored the effectiveness of RP in managing motor symptoms, often omitting assessments such as the rigidity and retropulsion tests during the follow-up. This study evaluates the comprehensive improvements in motor performance and the potential cost benefits of RP for PwPD with DBS.MethodsA retrospective analysis was conducted on two groups of patients—those who received RP and those who received standard programming (SP). Clinical outcomes including motor improvement, quality of life, and daily levodopa dosage were compared between the groups during a 12 (± 3)-month in-clinic follow-up.ResultsA total of 44 patients were included in the study, with 18 in the RP group and 26 in the SP group. No significant differences were observed in the frequency of programming sessions or clinical outcomes between the groups (p > 0.05). However, the RP group experienced significantly lower costs per programming session than the SP group (p < 0.05), despite patients in the former group living further from our center (p < 0.05).ConclusionsOur findings suggest that RP could significantly reduce the costs of programming for PwPD with DBS, especially without compromising the effectiveness of treatment across all motor symptoms in the short term.

The characterization of neural signatures within the somatosensory pathway is essential for elucidating the pathogenic mechanisms of central post-stroke pain (CPSP) and developing more effective treatments such as deep brain stimulation (DBS). We explored the characteristics of thalamic neural oscillations in response to varying pain levels under multi-day local field potential (LFP) recordings and examined the influences of continuous DBS on these thalamic activities. We recorded LFPs from the left ventral posterolateral thalamus (VPL) of a patient with CPSP in the resting state under both off- and on-stimulation conditions. We observed significant differences in the power spectral density (PSD) of different pain levels in the delta, theta and gamma frequency bands of the left VPL; 75Hz DBS significantly increased the PSD of delta and decreased the PSD of low-beta, while 130Hz DBS significantly reduced the PSD of theta and low-beta. Thalamic stimulation modulated the neural oscillations related to pain, and the changes in neural activities in response to stimulation could serve as quantitative indicators for pain relief.

Introduction: Deep brain stimulation (DBS) of subthalamic nucleus (STN) has been well-established and increasingly applied in patients with isolated dystonia. Nevertheless, the surgical efficacy varies among patients. This study aims to explore the factors affecting clinical outcomes of STN-DBS on isolated dystonia and establish a well-performed prediction model. Methods: In this prospective study, thirty-two dystonia patients were recruited and received bilateral STN-DBS at our center. Their baseline characteristics and up to one-year follow-up outcomes were assessed. Implanted electrodes of each subject were reconstructed with their contact coordinates and activated volumes calculated. We explored correlations between distinct clinical characteristics and surgical efficacy. Those features were then trained for the model in outcome prediction via support vector regression (SVR) algorithm and testified through cross-validation. Results: Patients demonstrated an average clinical improvement of 56 ± 25 % after STN-DBS, significantly affected by distinct symptom forms and activated volumes. The optimal targets and activated volumes were concentratedly located at the dorsal posterior region to STN. Most patients had a rapid response to STN-DBS, and their motor score improvement within one week was highly associated with long-term outcomes. The trained SVR model, contributed by distinct weights of features, could reach a maximum prediction accuracy with mean errors of 11 ± 7 %. Conclusion: STN-DBS demonstrated significant and rapid therapeutic effects in patients with isolated dystonia, by possibly affecting the pallidofugal fibers. Early improvement highly indicates the ultimate outcomes. SVR proves valid in outcome prediction. Patients with predominant phasic and generalized symptoms, shorter disease duration, and younger onset age may be more favorable to STN-DBS in the long run.

BackgroundPatients suffering from refractory obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS) surgery require repeated in-person programming visits. These sessions could be labor-intensive and may not always be feasible, particularly when in-person hospital visits are restricted. Telemedicine is emerging as a potential supplementary tool for post-operative care. However, its reliability and feasibility still require further validation due to the unconventional methods of interaction.MethodsA study was conducted on three patients with refractory OCD who had undergone DBS. Most of their programming sessions were completed via a remote programming system. These patients were recruited and monitored for a year. Changes in their clinical symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale–Second Edition (Y-BOCS-II), the Hamilton Anxiety Scale-14 (HAMA), the Hamilton Depression Scale-17 (HAMD), and the Short Form 36 Health Survey Questionnaire (SF-36). The scores from these assessments were reported.ResultsAt the last follow-up, two out of three patients were identified as responders, with their Y-BOCS-II scores improving by more than 35% (P1: 51%, P3: 42%). These patients also experienced some mood benefits. All patients observed a decrease in travel expenses during the study period. No severe adverse events were reported throughout the study.ConclusionThe group of patients showed improvement in their OCD symptoms within a 1-year follow-up period after DBS surgery, without compromising safety or benefits. This suggests that telemedicine could be a valuable supplementary tool when in-person visits are limited.

Background: Psychiatric comorbidities are common in Parkinson's disease (PD) and may change with high-frequency stimulation targeting the subthalamic nucleus. Numerous accounts indicate subthalamic alpha-frequency oscillation is implicated in emotional processing. While intermittent alpha-frequency (10Hz) stimulation induces positive emotional effects, with more ventromedial contacts inducing larger effects, little is known about the subacute effect of ventral 10Hz subthalamic stimulation on emotional processing. Objective/Hypothesis: To evaluate the subacute effect of 10Hz stimulation at bilateral ventral subthalamic nucleus on emotional processing in PD patients using an affective task, compared to that of clinical-frequency stimulation and off-stimulation. Methods: Twenty PD patients with bilateral subthalamic deep brain stimulation for more than six months were tested with the affective task under three stimulation conditions (10Hz, 130Hz, and off-stimulation) in a double-blinded randomized design. Results: While 130Hz stimulation reduced arousal ratings in all patients, 10Hz stimulation increased arousal selectively in patients with higher depression scores. Furthermore, 10Hz stimulation induced a positive shift in valence rating to negative emotional stimuli in patients with lower apathy scores, and 130Hz stimulation led to more positive valence to emotional stimuli in the patients with higher apathy scores. Notably, we found correlational relationships between stimulation site and affective rating: arousal ratings increase with stimulation from anterior to posterior site, and positive valence ratings increase with stimulation from dorsal to ventral site of the ventral subthalamic nucleus. Conclusions: Our findings highlight the distinctive role of 10Hz stimulation on subjective emotional experience and unveil the spatial organization of the stimulation effect.

Objectives. The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Methods. Ninety-three patients diagnosed with Parkinson’s disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson’s Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson’s Disease Questionnaire (PDQ-8), respectively. Results. Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (β = 0.869, P

BackgroundSubthalamic nucleus (STN) and globus pallidus interna (GPi) are two main structures primarily targeted by deep brain stimulation (DBS) to treat advanced Parkinson's disease (PD). A subset of cases with unsatisfactory outcomes may benefit from rescue DBS surgery targeting another structure, while these patients' characteristics have not been well described and this phenomenon has not been well reviewed.MethodsThis monocentric retrospective study included patients with PD, who underwent rescue STN DBS following an unsatisfactory outcome of the initial bilateral GPi DBS in a retrospective manner. A short review of the current literature was conducted to report the clinical outcome of rescue DBS surgeries.ResultsEight patients were identified, and six of them were included in this study. The rescue STN DBS was performed 19.8 months after the initial GPi DBS. After 8.8 months from the rescue STN DBS, patients showed a significant off-medication improvement by 29.2% in motor symptoms compared to initial GPi DBS. Non-motor symptoms and the health-related quality of life were also significantly improved.ConclusionOur findings suggest that the rescue STN DBS may improve off-medication motor and non-motor symptoms and quality of life in patients with failure of initial GPi DBS. The short review of the current literature showed that the target switching from GPi to STN was mainly due to poor initial outcomes and was performed by target substitution, whereas the switching from STN to GPi was mainly due to a gradual waning of benefits, long-term axial symptoms, dyskinesia, and dystonia and was performed by target addition.

Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson’s disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients’ caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient’s nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM’s symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients’ suffering.

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

IntroductionDeep brain stimulation (DBS) studies in Parkinson's Disease (PD) targeting the subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8–12 Hz) event-related de-synchronization (ERD) (reduced power) has been demonstrated. The time-locked stimulation of STN relative to stimuli onset has shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation on power modulation have not been investigated. We aim to investigate effects of acute stimulation of the right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous study, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation would be also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation was to be associated with enhanced alpha power given the shift in behavioral valence ratings.MethodsTwenty-four subjects with STN DBS underwent emotional picture-viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 or 130 Hz. Power of signals was estimated relative to the baseline and subjected to non-parametric statistical testing.ResultsAs hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative vs. neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects.ConclusionAcute alpha-specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time-locked stimulation has the potential to provide causal insights into the spectral frequencies and temporal dynamics of emotional processing.

ObjectivesSacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China.Materials and methodsWe retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject.ResultsA total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients.ConclusionRemote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.

Abstract Deep brain stimulation (DBS) of structures in the brain’s reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain’s anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB–DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients’ left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients’ health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB–DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB–DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB–DBS for treatment-refractory mood disorders in a more rigorous fashion.

Abstract The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.

ObjectiveWe aimed to compare the motor effect of bilateral globus pallidus interna (GPi) deep brain stimulation (DBS) on motor subtypes of Parkinson’s disease (PD) patients and identify preoperative predictive factors of short-term motor outcome.MethodsWe retrospectively investigated bilateral GPi DBS clinical outcomes in 55 PD patients in 1 year follow up. Motor outcome was measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III before and 1 year after surgery. Clinical outcomes were compared among different motor subtypes. Preoperative predictors of motor outcome were assessed by performing univariate and multivariate linear regression and logistic regression analyses.ResultsAt 1 year following implantation, GPi DBS significantly improved the off-medication MDS-UPDRS III scores in all motor subtype cohorts, with prominent improvement in tremor. No significant difference of postoperative motor symptoms changes was found except greater tremor improvement achieved in both the tremor-dominant (TD) and indeterminate (IND) patients compared to the postural instability and gait difficulty (PIGD) patients. High percentage of PIGD patients were weak responders to DBS. Better levodopa responsiveness and more severe tremor predicted greater overall improvement of motor function in the entire cohort. Similarly, both levodopa responsiveness and tremor improvement were confirmed as predictors for motor improvement in PIGD patients.ConclusionBilateral GPi DBS could effectively improve motor outcomes in PD patients regardless of motor subtypes. Both TD and IND patients obtained larger tremor improvement. The intensity of levodopa responsiveness and the severity of tremor could serve as predictors of motor improvement 1 year after GPi DBS.

In Parkinson’s disease (PD), beta frequency oscillations are synchronised across the cortico-basal-ganglia circuit. The authors show in human participants that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway, indicating a pathophysiological role for this pathway in PD.

BackgroundAs coronavirus disease 2019 (COVID-19) vaccination campaign underway, little is known about the vaccination coverage and the underlying barriers of the vaccination campaign in patients with Parkinson's disease (PD).ObjectiveTo investigate the vaccination status and reasons for COVID-19 vaccine acceptance and hesitancy among PD patients.MethodsIn concordance with the CHERRIES guideline, a web-based, single-center survey was promoted to patients with PD via an online platform from April 2022 and May 2022. Logistic regression models were used to identify factors related to COVID-19 vaccine hesitancy.ResultsA total of 187 PD cases participated in this online survey (response rate of 23%). COVID-19 vaccination rate was 54.0%. Most participants had a fear of COVID-19 (77.5%) and trusted the efficacy (82.9%) and safety (66.8%) of COVID-19 vaccine. Trust in government (70.3%) and concerns about the impact of vaccine on their disease (67.4%) were the most common reasons for COVID-19 vaccine acceptance and hesitancy, respectively. COVID-19 vaccine hesitancy was independently associated with the history of flu vaccination (OR: 0.09, p < 0.05), trust in vaccine efficacy (OR: 0.15, p < 0.01), male gender (OR: 0.47, p < 0.05), disease duration of PD (OR: 1.08, p < 0.05), and geographic factor (living in Shanghai or not) (OR: 2.87, p < 0.01).ConclusionsThe COVID-19 vaccination rate remained low in PD patients, however, most individuals understood benefits of vaccination. COVID-19 vaccine hesitancy was affected by multiple factors such as geographic factor, history of flu vaccination, disease duration and trust in efficacy of vaccine. These findings could help government and public health authorities to overcome the barrier to COVID-19 vaccination and improve vaccine roll-out in PD patients.

IntroductionGlobus pallidus internus (GPi) deep brain stimulation (DBS) is widely used in patients with dystonia. However, 10–20% of patients receive insufficient benefits. The objectives of this study are to evaluate the effectiveness of bilateral subthalamic nucleus (STN) DBS along with unilateral posteroventral pallidotomy (PVP) in patients with dystonia who experienced unsatisfactory GPi-DBS and to address the reported rescue procedures after suboptimal DBS or lesion surgery in dystonia patients.MethodsSix patients with isolated dystonia who had previously undergone bilateral GPi-DBS with suboptimal improvement were included. Standardized assessments of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and quality of life using SF-36 were evaluated before surgery and 1, 6 months, and last follow-up (LFU) after surgery. STN bilateral OFF (bi-OFF), unilateral ON (uni-ON), and bilateral ON (bi-ON) states were recorded at LFU. Specific items were used to find publications published before 10 April 2022 regarding rescue procedures after suboptimal DBS or lesion surgery in patients with dystonia for reference. Eleven original studies including case reports/series were identified for discussion.ResultsSubstantial clinical benefits were achieved in all six patients. Significant amelioration was achieved during the 1-month (6.5 ± 7.45; p = 0.0049), 6-month (5.67 ± 6.3; p = 0.0056) follow-ups, and at LFU (4.67 ± 4.72; p = 0.0094) when compared with the baseline (LFU of GPi DBS with on status) (17.33 ± 11.79) assessed by BFMDRS. The percentage of improvement reached 70.6, 74.67, and 77.05%, respectively. At LFU, significant differences were found between the stimulation bi-OFF and uni-ON (11.08 ± 8.38 vs. 9 ± 8.52, p = 0.0191), and between the stimulation bi-OFF and bi-ON (11.08 ± 8.38 vs. 4.67 ± 4.72, p = 0.0164). Trends depicting a better improvement in stimulation bi-ON compared with uni-ON (4.67 ± 4.72 vs. 9 ± 8.52, p = 0.0538) were observed.ConclusionOur results suggest that bilateral STN-DBS plus unilateral PVP may be an effective rescue procedure for patients with isolated dystonia who experienced suboptimal movement improvement following GPi-DBS. However, given the heterogeneity of patients and the small sample size, these findings should be interpreted with caution.

Abstract The bilateral effects of deep brain stimulation (DBS) on motor and non-motor symptoms of Parkinson’s disease (PD) have been extensively studied and reviewed. However, the unilateral effects—in particular, the potential lateralized effects of left- versus right-sided DBS—have not been adequately recognized or studied. Here we summarized the current evidence and controversies in the literature regarding the lateralized effects of DBS on motor and non-motor outcomes in PD patients. Publications in English language before February 2021 were obtained from the PubMed database and included if they directly compared the effects of unilateral versus contralateral side DBS on motor or non-motor outcomes in PD. The current literature is overall of low-quality and is biased by various confounders. Researchers have investigated mainly PD patients receiving subthalamic nucleus (STN) DBS while the potential lateralized effects of globus pallidus interna (GPi) DBS have not been adequately studied. Evidence suggests potential lateralized effects of STN DBS on axial motor symptoms and deleterious effects of left-sided DBS on language-related functions, in particular, the verbal fluency, in PD. The lateralized DBS effects on appendicular motor symptoms as well as other neurocognitive and neuropsychiatric domains remain inconclusive. Future studies should control for varying methodological approaches as well as clinical and DBS management heterogeneities, including symptom laterality, stimulation parameters, location of active contacts, and lead trajectories. This would contribute to improved treatment strategies such as personalized target selection, surgical planning, and postoperative management that ultimately benefit patients.

The subthalamic nucleus (STN) and globus pallidus internus (GPi) are the two most common and effective target brain areas for deep brain stimulation (DBS) treatment of advanced Parkinson's disease. Although DBS has been shown to restore functional neural circuits of this disorder, the changes in topological organization associated with active DBS of each target remain unknown. To investigate this, we acquired resting-state functional magnetic resonance imaging (fMRI) data from 34 medication-free patients with Parkinson's disease that had DBS electrodes implanted in either the subthalamic nucleus or internal globus pallidus (n = 17 each), in both ON and OFF DBS states. Sixteen age-matched healthy individuals were used as a control group. We evaluated the regional information processing capacity and transmission efficiency of brain networks with and without stimulation, and recorded how stimulation restructured the brain network topology of patients with Parkinson's disease. For both targets, the variation of local efficiency in motor brain regions was significantly correlated (p < 0.05) with improvement rate of the Uniform Parkinson's Disease Rating Scale-III scores, with comparable improvements in motor function for the two targets. However, non-motor brain regions showed changes in topological organization during active stimulation that were target-specific. Namely, targeting the STN decreased the information transmission of association, limbic and paralimbic regions, including the inferior frontal gyrus angle, insula, temporal pole, superior occipital gyri, and posterior cingulate, as evidenced by the simultaneous decrease of clustering coefficient and local efficiency. GPi-DBS had a similar effect on the caudate and lenticular nuclei, but enhanced information transmission in the cingulate gyrus. These effects were not present in the DBS-OFF state for GPi-DBS, but persisted for STN-DBS. Our results demonstrate that DBS to the STN and GPi induce distinct brain network topology reconstruction patterns, providing innovative theoretical evidence for deciphering the mechanism through which DBS affects disparate targets in the human brain.

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.

Abstract Camptocormia is a common and often debilitating postural deformity in Parkinson’s disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.

The understanding of brain structural abnormalities across different clinical forms of dystonia and their contribution to clinical characteristics remains unclear. The objective of this study is to investigate shared and specific gray matter volume (GMV) abnormalities in various forms of isolated idiopathic dystonia. We collected imaging data from 73 isolated idiopathic dystonia patients and matched them with healthy controls to explore the GMV alterations in patients and their correlations with clinical characteristics using the voxel-based morphometry (VBM) technique. In addition, we conducted an activation likelihood estimation (ALE) meta-analysis of previous VBM studies. Our study demonstrated widespread morphometry alterations in patients with idiopathic dystonia. Multiple systems were affected, which mainly included basal ganglia, sensorimotor, executive control, and visual networks. As the result of the ALE meta-analysis, a convergent cluster with increased GMV was found in the left globus pallidus. In subgroup VBM analyses, decreased putamen GMV was observed in all clinic forms, while the increased GMV was observed in parahippocampal, lingual, and temporal gyrus. GD demonstrated the most extensive GMV abnormalities in cortical regions, and the aberrant GMV of the posterior cerebellar lobe was prominent in CD. Moreover, trends of increased GMV regions of the left precuneus and right superior frontal gyrus were demonstrated in the moderate-outcome group compared with the superior-outcome group. Results of our study indicated shared pathophysiology of the disease-centered on the dysfunction of the basal ganglia-thalamo-cortical circuit, impairing sensorimotor integration, high-level motor execution, and cognition of patients. Dysfunction of the cerebello-thalamo-cortical circuit could also be involved in CD especially. Finally, the frontal-parietal pathway may act as a potential marker for predicting treatment outcomes such as deep brain stimulation.

Background: Given that anorexia nervosa (AN) is a life-threatening mental disorder and has poor clinical outcomes, novel effective treatments are warranted, especially for severe and persistent cases. Objective: To investigate the safety, feasibility, and clinical outcomes of using deep brain stimulation (DBS) of the nucleus accumbens (NAcc) in treatment-refractory AN patients. Methods: A total of 28 women with refractory AN underwent NAcc-DBS and completed this 2-year follow-up study. The clinical outcomes, including body mass index (BMI) and mood, anxiety, and obsessive symptoms, were assessed using a series of psychiatric scales at 6 and 24 months post operation. Results: While no fatalities were reported during this study, 1 patient showed device rejection. The most common short-term side effect observed was varying degrees of pain at the incision sites (n = 22), which usually disappeared 3–4 days following the operation. No severe surgical adverse events were observed. Compared to presurgical levels, significant increases in BMI and improvement in psychiatric scale scores were noted during the 6-month follow-up and were maintained at the 2-year review. Finally, a post-hoc analysis revealed that the NAcc-DBS was less effective for weight restoration in patients with the binge-eating/purge subtype of AN than in those with the restricting subtype (R-AN). Conclusion: Our long-term follow-up study suggests that NAcc-DBS is safe and effective for improving the BMI and psychiatric symptoms of patients with refractory AN. Although NAcc-DBS appears to be more suitable for patients with R-AN, strict inclusion criteria must be applied considering surgery-related complications.

IntroductionPrevious studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms.MethodsIn this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med–STN+GPi–, (2) Med–STN–GPi+, (3) Med+STN+GPi–, and (4) Med+STN–GPi+.ResultsEight patients had completed 30 trials of assessment. Compared with the preoperative Med– state, in the Med–STN+GPi– condition, the cardinal symptoms in both sides of the body were all improved. In the Med–STN–GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi– state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN–GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med– and Med+ states. No side effects associated with this study were seen.ConclusionsImprovement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side.

BackgroundEmerging evidence indicates that iron distribution is heterogeneous within the substantia nigra (SN) and it may reflect patient-specific trait of Parkinson’s Disease (PD). We assume it could account for variability in motor outcome of subthalamic nucleus deep brain stimulation (STN-DBS) in PD.ObjectiveTo investigate whether SN susceptibility features derived from radiomics with machine learning (RA-ML) can predict motor outcome of STN-DBS in PD.MethodsThirty-three PD patients underwent bilateral STN-DBS were recruited. The bilateral SN were segmented based on preoperative quantitative susceptibility mapping to extract susceptibility features using RA-ML. MDS-UPDRS III scores were recorded 1–3 days before and 6 months after STN-DBS surgery. Finally, we constructed three predictive models using logistic regression analyses: (1) the RA-ML model based on radiomics features, (2) the RA-ML+LCT (levodopa challenge test) response model which combined radiomics features with preoperative LCT response, (3) the LCT response model alone.ResultsFor the predictive performances of global motor outcome, the RA-ML model had 82% accuracy (AUC = 0.85), while the RA-ML+LCT response model had 74% accuracy (AUC = 0.83), and the LCT response model alone had 58% accuracy (AUC = 0.55). For the predictive performance of rigidity outcome, the accuracy of the RA-ML model was 80% (AUC = 0.85), superior to those of the RA-ML+LCT response model (76% accuracy, AUC = 0.82), and the LCT response model alone (58% accuracy, AUC = 0.42).ConclusionOur findings demonstrated that SN susceptibility features from radiomics could predict global motor and rigidity outcomes of STN-DBS in PD. This RA-ML predictive model might provide a novel approach to counsel candidates for STN-DBS.

Background: Deep brain stimulation (DBS) is a well-established treatment for a variety of movement disorders. Rechargeable cell technology was introduced to pulse generator more than 10 years ago and brought great benefits to patients. However, with the widespread use of rechargeable implanted pulse generators (r-IPGs), a new hardware complication, when charging the r-IPG has been difficult, was encountered.Objective: The aims of this study were to report five cases confronted with r-IPG charging difficulty postoperatively and to explore the predisposing factors and treatment strategies for this rare complication.Methods: We retrospectively reviewed our DBS patient database for those who were implanted with r-IPGs. From 2012, we identified a total of 1,226 patients, with five of them experiencing charging difficulties after surgery. Detailed patient profiles and clinical procedures were scrutinized and reviewed.Results: All the charging problems were resolved by reoperation. Cases 1 and 2 required their r-IPGs to be anchored to the muscle and fascia. Cases 3 and 4 had their r-IPGs inserted in the wrong orientation at the initial surgery, which was resolved by turning around the r-IPGs at the revision surgery. Case 5, in which we propose that the thick subcutaneous fat layer blocked the connection between the r-IPG and the recharger, required a second operation to reposition the r-IPG in a shallow layer underneath the skin. For all cases, the charging problems were resolved without reoccurrences to date.Conclusion: Our case series indicates a novel hardware complication of DBS surgery, which had been rarely reported before. In this preliminary study, we describe several underlying causes of this complication and treatment methods.

High cervical spinal cord stimulation (HCSCS) was found to have therapeutic effects on Parkinsonian gait disturbance. However, the results were inconsistent and confounded with symptoms of pain. This study aimed to reveal the gait and dysarthric effects of HCSCS in PD (Parkinson’s disease) and MSA-P (Parkinson variant of multiple system atrophy) patients without pain. Three PD and five MSA-P patients without painful comorbidities were assessed for gait performance and speech before SCS surgery and at 3- and 6-month follow-up. Stride length and the time spent in the Timed Up-and-Go task showed little change after HCSCS surgery. Overall voice quality (measured by dysphonia severity index) and perceptual speech intelligence improved significantly at 3 months, but improvements slightly diminished at 6 months postoperatively. Change in quality of life (measured by 8-item Parkinson’s disease questionnaire) was also notable at 3 months but narrowed over time following HCSCS. In conclusion, HCSCS showed therapeutic effects in improving the dysarthria but not gait disturbance in pain-free PD and MSA-P patients.

Lateral habenula is believed to encode negative motivational stimuli and plays key roles in the pathophysiology of psychiatric disorders. However, how habenula activities are modulated during the processing of emotional information is still poorly understood. We recorded local field potentials from bilateral habenula areas with simultaneous cortical magnetoencephalography in nine patients with psychiatric disorders during an emotional picture-viewing task. Transient activity in the theta/alpha band (5–10 Hz) within the habenula and prefrontal cortical regions, as well as the coupling between these structures, is increased during the perception and processing of negative emotional stimuli compared to positive emotional stimuli. The increase in theta/alpha band synchronization in the frontal cortex-habenula network correlated with the emotional valence but not the arousal score of the stimuli. These results provide direct evidence for increased theta/alpha synchrony within the habenula area and prefrontal cortex-habenula network in the perception of negative emotion in human participants.

Introduction: DBS is a widely used therapy for PD. There is now a choice between fixed-life implantable pulse generators (IPGs) and rechargeable IPGs, each having advantages and disadvantages. This study aimed to evaluate the preference and satisfaction of Chinese patients with Parkinson's disease (PD) who were treated with deep brain stimulation (DBS).Materials and Methods: Two hundred and twenty PD patients were treated with DBS and completed a self-reported questionnaire to assess their long-term satisfaction and experience with the type of battery they had chosen and the key factors affecting these choices. The survey was performed online and double-checked for completeness and accuracy.Results: The median value of the postoperative duration was 18 months. The most popular way for patients to learn about DBS surgery was through media (79/220, 35.9%) including the Internet and television programs. In total, 87.3% of the DBS used rechargeable IPGs (r-IPG). The choice between rechargeable and non-rechargeable IPGs was significantly associated with affordability (χ(1)2 = 19.13, p < 0.001). Interestingly, the feature of remote programming significantly affected patients' choices between domestic and imported brands (χ(1)2 = 16.81, p < 0.001). 87.7% of the patients were satisfied with the stimulating effects as well as the implanted device itself. 40.6% of the patients with r-IPGs felt confident handling devices within 1 week after discharge. More than half of the patients checked their batteries every week. The mean interval for battery recharge was 4.3 days. 57.8% of the patients spent around 1 h recharging, and 71.4% of them recharged the battery independently.Conclusions: Most patients were satisfied with their choice of IPGs. The patients' economic status and the remote programming function of the device were the two most critical factors in their decision. The skill of recharging the IPG was easy to master for most patients.

The habenula, located in the epithalamus, has been implicated in various psychiatric disorders including mood disorders and schizophrenia. This study explored the transient effects of deep brain stimulation in the habenula. Each of the four patients (two with bipolar disorder and two with schizophrenia) was tested with eight deep brain stimulation contacts. Patients were examined via transient electrical stimulation 1 month after deep brain stimulation surgery. The pulse width was 60 μs and the voltage ranged from 0 V to a maximum of 10 V, increasing in increments of 1 V. Each patient received stimulation at two frequencies, 60 and 135 Hz. A total of 221 out of 385 active trials elicited stimulation-induced effects. The three most common transient effects were numbness, heart rate changes, and pain. The incidence of numbness, heart rate changes, pain, and involuntary movements increased with the increase in stimulation voltage. Through contralateral stimulation, numbness was triggered in all parts of the body except the scalp. The obtained stimulus-response maps suggested a possible somatosensory organization of the habenula.

Background: Deep brain stimulation (DBS) is an established treatment for hyperkinetic movement disorders. Patients undergoing DBS can choose between the use of a rechargeable or non-rechargeable battery for implanted pulse generators (IPG).Objectives: In this study, we aimed to evaluate patient preferences and satisfaction with rechargeable and non-rechargeable batteries for IPGs after undergoing DBS.Methods: Overall, 100 patients with hyperkinetic movement disorders (dystonia: 79, Tourette syndrome: 21) who had undergone DBS took a self-designed questionnaire to assess their satisfaction and experience with the type of battery they had chosen and the factors influencing their choice.Results: Of the participants, 87% were satisfied with the stimulating effects of the treatment as well as the implanted device; 76% had chosen rechargeable devices (r-IPGs), 71.4% of whom recharged the battery themselves. Economic factors were the main reason for choosing both r-IPG and non-rechargeable IPG (nr-IPG). The questionnaire revealed that 66% of the patients checked their r-IPG battery every week. The mean interval for battery recharge was 4.3 days.Conclusions: The majority of the patients were satisfied with their in-service-IPG, regardless of whether it was a r-IPG or nr-IPG. Affordability was the main factor influencing the choice of IPG. The majority of the patients were confident in recharging the battery of their r-IPG themselves; only 11% of patients experienced difficulties. Understanding the recharge process remains difficult for some patients and increasing the number of training sessions for the device may be helpful.

Abstract Background The accuracy of deep brain stimulation (DBS) depends on precise electrode positioning, which has been pursued for ideal treatment outcomes. As a critical component of DBS, the fixation performance of lead anchoring devices has been widely studied. Possible reasons for lead shift were analyzed in the current study and we further provided effective solutions to reduce potential manual errors. Methods Seventy-nine patients who received DBS implantations at the Ruijin Hospital from April to November 2017 were retrospectively reviewed. Intraoperative lead shifts were measured by C-arm fluoroscopy. Lead adjustment counts were recorded and compared among three lead fixation devices: Stimloc™ (Medtronic, Minneapolis, MN, USA), TouchLoc (SceneRay, Suzhou, China), and the traditional lead anchoring device. Results Mean (± SD) distances of lead shifts were 0.29 ± 2.42 mm in Stimloc devices, 0.43 ± 0.55 mm in TouchLoc devices, and 1.52 ± 1.05 mm in traditional devices (p

BackgroundPublic health guidelines have recommended that elective medical procedures, including deep brain stimulation (DBS) surgery for Parkinson’s disease (PD), should not be scheduled during the coronavirus (COVID-19) pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.MethodsWe administered a newly developed phone questionnaire to 20 consecutive patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic. The questionnaire was designed to gather the patients’ experiences and perceptions on the impact of COVID-19 on their everyday activities and access to medical care.ResultsMost of the patients felt confident about the preventive measures taken by the government and hospitals, and they have changed their daily living activities accordingly. Moreover, a large majority of patients felt confident obtaining access to regular and COVID-19-related health care services if needed. Routine clinical referral, sense of security in the hospital during the outbreak, and poor control of PD symptoms were the three main reasons given by patients for seeking DBS surgery during the COVID-19 pandemic.ConclusionThe COVID-19 pandemic has considerably impacted medical care and patients’ lives but elective procedures, such as DBS surgery for PD, do not need to be rescheduled when the health care system is not overloaded and adequate public health regulations are in place.

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania.Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India.Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited.Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases.

BackgroundSome patients suffer from persistent and severely disabling Obsessive-Compulsive Disorder (OCD) symptoms that cannot be alleviated by conventional treatments or neuroablative interventions targeting cortico-striatal loop circuits. Currently, it is unclear how to manage the clinical symptoms of these unique patients. We reasoned that deep brain stimulation (DBS) of the habenula (HB) could be a valuable subsequent treatment option for these otherwise medically intractable cases of severe OCD. The HB is an epithalamic structure critically involved in the encoding and responding to aversive stimulus events, cognitive and brain processes known to be impaired in many patients with OCD. Similarly, HB DBS can alleviate depression and anxiety, which often co-occur with OCD. Here, we explore the clinical benefits and risks of HB DBS treatment in a patient with severe and refractory OCD.Case PresentationA 30-year-old male patient presented with persistent and severely disabling OCD symptoms that were refractory to previous psychological and pharmacological treatments as well as to neuroablative surgical interventions involving both capsulotomy and cingulotomy. After HB DBS, however, the severity of the patient's OCD symptoms was markedly reduced at 1-month follow-up, which was sustained until the final (at 12-month) follow-up. The patient also reported enduring improvements in depression, anxiety, and health-related quality of life after several months of HB DBS treatment.ConclusionsThis case report provides the first clinical evidence suggesting that HB DBS could serve as a safe and effective alternative neurosurgical intervention for severe and refractory OCD. The present findings are promising and warrant further research into the role of the HB in pathophysiology and treatment of OCD.

BackgroundDeep brain stimulation (DBS) of the posterior subthalamic area (PSA) provides a potentially effective treatment for medication-refractory essential tremor (ET).ObjectiveTo study the clinical benefits and adverse-event profile of bilateral PSA-DBS for refractory ET.MethodsSeven patients with refractory ET underwent bilateral PSA-DBS surgery under general anesthesia between September 2017 and May 2018. Clinical outcome assessments, using the Essential Tremor Rating Scale, were performed at 1-, 6-, and 12-month follow-up, except for the last assessment of one patient who was followed up to 9 months. Analysis was focused on changes in patients’ motor symptoms and quality of life following surgery as well as documenting the adverse-event profile associated with the surgical PSA-DBS treatment.ResultsAfter surgery, patients’ motor symptoms, including upper limb tremor and head tremor, were improved by 84.2% and their quality of life by 81.25% at 1-month follow-up. The clinical benefits to patients were maintained at 6-month and last follow-up. Adverse side effects included dysarthria (n = 4), balance disorder (n = 2), and paresthesia of the right limb (n = 1). No habituation effects were observed throughout the follow-up.ConclusionBilateral PSA-DBS seems to offer an effective and safe alternative treatment for medically intractable ET, warranting further research into its clinical utility, adverse-event profile, and comparative effectiveness.

In this retrospective study, by assuming that the therapeutic impedances were equal to 1 kΩ, we found that the mechanism by which deep brain stimulation of the subthalamic nucleus (STN) changed the motor laterality in Parkinson's disease (PD) may not be related to the difference in weighted average of the total electrical energy delivered to each side of STN.

Background. Deep brain stimulation (DBS) for Parkinson’s disease (PD) has evolved as a well-established treatment in neurosurgery, and identifying appropriate surgical candidates could contribute to better DBS outcomes. The Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD) is a reasonable screening tool for assessing DBS candidacy in PD patients; however, a Chinese version of FLASQ-PD is needed for functional neurosurgery units in China. In this study, we translated the FLASQ-PD to Chinese and assessed its reliability and validity for Chinese PD patients. Methods. The FLASQ-PD was translated before the study formally started. A single-center retrospective analysis of FLASQ-PD was performed at the Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine, between July and December 2019. The Unified Parkinson Disease Rating Scale III (UPDRS-III) was also used to assess PD patients on and off medication. All patients were evaluated for surgical candidacy by specialists. Results. Overall, 115 PD patients, 25 with parkinsonism and six with multiple system atrophy were consecutively included. Internal consistency of the Chinese FLASQ-PD was roughly adequate (Cronbach’s alpha = 0.664). There were significant differences in mean total scores of the Chinese FLASQ-PD between the diagnostic (Kruskal–Wallis H value = 37.450, p≤0.001) and surgery-candidacy groups (H = 48.352, p≤0.001). Drug improvements in UPDRS-III scores were mildly correlated with the Chinese FLASQ-PD scores in the surgery-ready group (Pearson correlation = 0.399, p=0.001). Conclusions. The Chinese FLASQ-PD, which is a simple and efficient screening tool for clinicians, was developed and initially validated in this retrospective single-center study.

The centromedian (CM) nucleus is an intralaminar thalamic nucleus that is considered as a potentially effective target of deep brain stimulation (DBS) and ablative surgeries for the treatment of multiple neurological and psychiatric disorders. However, the structure of CM is invisible on the standard T1- and T2-weighted (T1w and T2w) magnetic resonance images, which hamper it as a direct DBS target for clinical applications. The purpose of the current study is to demonstrate the use of quantitative susceptibility mapping (QSM) technique to image the CM within the thalamic region. Twelve patients with Parkinson’s disease, dystonia, or schizophrenia were included in this study. A 3D multi-echo gradient recalled echo (GRE) sequence was acquired together with T1w and T2w images on a 3-T MR scanner. The QSM image was reconstructed from the GRE phase data. Direct visual inspection of the CM was made on T1w, T2w, and QSM images. Furthermore, the contrast-to-noise ratios (CNRs) of the CM to the adjacent posterior part of thalamus on T1w, T2w, and QSM images were compared using the one-way analysis of variance (ANOVA) test. QSM dramatically improved the visualization of the CM nucleus. Clear delineation of CM compared to the surroundings was observed on QSM but not on T1w and T2w images. Statistical analysis showed that the CNR on QSM was significantly higher than those on T1w and T2w images. Taken together, our results indicate that QSM is a promising technique for improving the visualization of CM as a direct targeting for DBS surgery.

Parkinson's disease (PD) is a movement disorder caused by dopaminergic neurodegeneration. Levodopa (L-dopa) is an effective medication for alleviating motor symptoms in PD that has been shown previously to reduce subcortical beta (13–30 Hz) oscillations. How L-dopa influences oscillations in the motor cortex is unclear. In this study, 21 PD patients were recorded with magnetoencephalography (MEG) in L-dopa ON and OFF states. Oscillatory components of resting-state power spectra were compared between the two states and the significant effect was localized using beamforming. Unified Parkinson's Disease Rating Scale (UPDRS) III akinesia and rigidity sub-scores for the most affected hemibody were correlated with source power values for the contralateral hemisphere. An L-dopa-induced power increase was found over the central sensors significant in the 18–30 Hz range (F(1,20) > 14.8, PFWE corr