Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

Deep brain stimulation of the subthalamic nucleus for primary Meige syndrome: clinical outcomes and predictive factors.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has demonstrated efficacy against multiple types of dystonia, but only a few case reports and small-sample studies have investigated the clinical utility of STN-DBS for Meige syndrome, a rare but distressing form of craniofacial dystonia. Furthermore, the effects of DBS on critical neuropsychological sequelae, such as depression and anxiety, are rarely examined. In this study, the authors investigated the therapeutic efficacy of STN-DBS for both motor and psychiatric symptoms of Meige syndrome. METHODS: The authors retrospectively reviewed consecutive patients with Meige syndrome receiving bilateral STN-DBS at their institution from January 2016 to June 2023. Motor performance and nonmotor features including mood, cognitive function, and quality of life (QOL) were evaluated using standardized rating scales at baseline and at final postoperative follow-up. Clinical and demographic factors influencing postoperative motor outcome were evaluated by uni- and multivariable linear regression models. RESULTS: Fifty-one patients were ultimately included, with a mean ± SD follow-up duration of 27.3 ± 18.0 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score improved from 12.9 ± 5.2 before surgery to 5.3 ± 4.2 at the last follow-up (mean improvement 58.9%, p < 0.001) and the mean BFMDRS disability score improved from 5.6 ± 3.3 to 2.9 ± 2.9 (mean improvement 44.6%, p < 0.001). Hamilton Depression and Anxiety Rating Scale scores also improved by 35.3% and 34.2%, respectively, and the postoperative 36-item Short-Form Health Survey score indicated substantial QOL enhancement. Global cognition remained stable after treatment. Multiple linear regression analysis identified disease duration (ß = -0.241, p = 0.027), preoperative anxiety severity (ß = -0.386, p = 0.001), and volume of activated tissue within the dorsolateral (sensorimotor) STN (ß = 0.483, p < 0.001) as independent predictors of motor outcome. CONCLUSIONS: These findings support STN-DBS as an effective and promising therapy for both motor and nonmotor symptoms of Meige syndrome. Timely diagnosis, treatment of preoperative anxiety, and precise electrode placement within the dorsolateral STN are essential for optimal clinical outcome.

Premature drug reduction after subthalamic nucleus deep brain stimulation leading to worse depression in patients with Parkinson's disease.

Background: Reduction of medication in Parkinson's disease (PD) following subthalamic nucleus deep brain stimulation (STN-DBS) has been recognized, but the optimal timing for medication adjustments remains unclear, posing challenges in postoperative patient management. Objective: This study aimed to provide evidence for the timing of medication reduction post-DBS using propensity score matching (PSM). Methods: In this study, initial programming and observation sessions were conducted over 1 week for patients 4-6 weeks postoperatively. Patients were subsequently categorized into medication reduction or non-reduction groups based on their dyskinesia evaluation using the 4.2-item score from the MDS-UPDRS-IV. PSM was employed to maintain baseline comparability. Short-term motor and neuropsychiatric symptom assessments for both groups were conducted 3-6 months postoperatively. Results: A total of 123 PD patients were included. Baseline balance in motor and non-motor scores was achieved between the two groups based on PSM. Short-term efficacy revealed a significant reduction in depression scores within the non-reduction group compared to baseline (P < 0.001) and a significant reduction compared to the reduction group (P = 0.037). No significant differences were observed in UPDRS-III and HAMA scores between the two groups. Within-group analysis showed improvements in motor symptoms, depression, anxiety, and subdomains in the non-reduction group, while the reduction group exhibited improvements only in motor symptoms. Conclusion: This study provides evidence for the timing of medication reduction following DBS. Our findings suggest that early maintenance of medication stability is more favorable for improving neuropsychiatric symptoms.

Optimal subthalamic stimulation sites and related networks for freezing of gait in Parkinson's disease.

Freezing of gait is a common and debilitating symptom in Parkinson's disease. Although high-frequency subthalamic deep brain stimulation is an effective treatment for Parkinson's disease, post-operative freezing of gait severity has been reported to alleviate, deteriorate or remain constant. We conducted this study to explore the optimal stimulation sites and related connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait in Parkinson's disease. A total of 76 Parkinson's disease patients with freezing of gait who underwent bilateral high-frequency subthalamic stimulation were retrospectively included. The volumes of tissue activated were estimated based on individual electrode reconstruction. The optimal and sour stimulation sites were calculated at coordinate/voxel/mapping level and mapped to anatomical space based on patient-specific images and stimulation settings. The structural and functional predictive connectivity networks for the change of the post-operative Freezing of Gait-Questionnaire were also identified based on normative connectomes derived from the Parkinson's Progression Marker Initiative database. Leave-one-out cross-validation model validated the above results, and the model remained significant after including covariates. The dorsolateral two-thirds of the subthalamic nucleus was identified as the optimal stimulation site, while the ventrocentral portion of the right subthalamic nucleus and internal capsule surrounding the left central subthalamic nucleus were considered as the sour stimulation sites. Modulation of the fibre tracts connecting to the supplementary motor area, pre-supplementary motor area and pedunculopontine nucleus accounted for the alleviation of freezing of gait, whereas tracts connecting to medial and ventrolateral prefrontal cortices contributed to the deterioration of freezing of gait. The optimal/sour stimulation sites and structural/functional predictive connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait are identified and validated through sizable Parkinson's disease patients in this study. With the growing understanding of stimulation sites and related networks, individualized deep brain stimulation treatment with directional leads will become an optimal choice for Parkinson's disease patients with freezing of gait in the future.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.

BACKGROUND: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. METHODS: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. RESULTS: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. CONCLUSION: Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Profiling the low-beta characteristics of the subthalamic nucleus in early- and late-onset Parkinson's disease.

Objectives: Low-beta oscillation (13-20 Hz) has rarely been studied in patients with early-onset Parkinson's disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson's disease (LOPD). Methods: We enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group. Results: We found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500-650 ms, p = 0.008), while LOPD had higher proportion of short burst (200-350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300-460 Hz) amplitude (p = 0.019). Conclusion: We found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.

Deep Brain Stimulation Electrode Reconstruction: Comparison between Lead-DBS and Surgical Planning System.

BACKGROUND: Electrode reconstruction for postoperative deep brain simulation (DBS) can be achieved manually using a surgical planning system such as Surgiplan, or in a semi-automated manner using software such as the Lead-DBS toolbox. However, the accuracy of Lead-DBS has not been thoroughly addressed. METHODS: In our study, we compared the DBS reconstruction results of Lead-DBS and Surgiplan. We included 26 patients (21 with Parkinson's disease and 5 with dystonia) who underwent subthalamic nucleus (STN)-DBS, and reconstructed the DBS electrodes using the Lead-DBS toolbox and Surgiplan. The electrode contact coordinates were compared between Lead-DBS and Surgiplan with postoperative CT and MRI. The relative positions of the electrode and STN were also compared between the methods. Finally, the optimal contact during follow-up was mapped onto the Lead-DBS reconstruction results to check for overlap between the contacts and the STN. RESULTS: We found significant differences in all axes between Lead-DBS and Surgiplan with postoperative CT, with the mean variance for the X, Y, and Z coordinates being -0.13, -1.16, and 0.59 mm, respectively. Y and Z coordinates showed significant differences between Lead-DBS and Surgiplan with either postoperative CT or MRI. However, no significant difference in the relative distance of the electrode and the STN was found between the methods. All optimal contacts were located in the STN, with 70% of them located within the dorsolateral region of the STN in the Lead-DBS results. CONCLUSIONS: Although significant differences in electrode coordinates existed between Lead-DBS and Surgiplan, our results suggest that the coordinate difference was around 1 mm, and Lead-DBS can capture the relative distance between the electrode and the DBS target, suggesting it is reasonably accurate for postoperative DBS reconstruction.

Prefrontal association of subthalamic deep brain stimulation with rapid eye movement sleep behavior disorder in Parkinson's disease.

OBJECTIVE: Subthalamic nucleus (STN)-deep brain stimulation (DBS) in Parkinson's disease (PD) patients affects not just focused target areas but also diffuse brain networks. The effect of this network modulation on nonmotor DBS effects is not fully understood. By concentrating on the sleep domain, the authors comprehensively determined the influence of electrode location and related structural/functional connections on changes in probable rapid eye movement (REM) sleep behavior disorder (pRBD) symptoms after STN-DBS, which has been reported to ameliorate, deteriorate, or remain constant. METHODS: Preoperative and postoperative pRBD symptoms were documented in 60 PD patients. The volumes of tissue activated (VTAs) were assessed on the basis of individual electrode reconstructions and merged with normative connectome data to identify structural/functional connections associated with VTAs. The entire cohort was used to construct connection models that explained changes in pRBD symptoms, as well as to perform cross-validations. RESULTS: Structural/functional connectivity was associated with pRBD symptom changes during STN-DBS. Changes in pRBD symptoms were predicted using an ideal structural connection map. Prefrontal connection was related with improved pRBD symptoms, whereas sensorimotor connectivity was associated with deterioration. CONCLUSIONS: Recovery of pRBD symptoms was predicted on the basis of the fibers connecting the STN electrode to prefrontal regions. These findings implied that the placement of STN-DBS leads influences the fibers to prefrontal regions and may be used to enhance treatment of pRBD symptoms; however, further prospective studies are needed to validate these findings.

Adaptive deep brain stimulation for Parkinson's disease: looking back at the past decade on motor outcomes.

BACKGROUND: Adaptive deep brain stimulation (aDBS) has been reported to be an effective treatment for motor symptoms in patients with Parkinson's disease (PD). However, it remains unclear whether and in which motor domain aDBS provides greater/less benefits than conventional DBS (cDBS). OBJECTIVE: To conduct a meta-analysis and systematic review to explore the improvement of the motor symptoms of PD patients undergoing aDBS and the comparison between aDBS and cDBS. METHODS: Nineteen studies from PubMed, Embase, and the Cochrane Library database were eligible for the main analysis. Twelve studies used quantitative plus qualitative analysis; seven studies were only qualitatively analyzed. The efficacy of aDBS was evaluated and compared to cDBS through overall motor function improvements, changes in symptoms of rigidity-bradykinesia, dyskinesia, tremor, and speech function, and total electrical energy delivered (TEED). The overall motor improvement and TEED were investigated through meta-analyses, while other variables were investigated by systematic review. RESULTS: Quantitative analysis showed that aDBS, with a reduction of TEED (55% of that of cDBS), significantly improved motor functions (33.9%, p < 0.01) and may be superior to cDBS in overall motor improvement (p = 0.002). However, significant publication bias was detected regarding the superiority (p = 0.006, Egger's test). In the qualitative analysis, rigidity-bradykinesia, dyskinesia, and speech function outcomes after aDBS and cDBS were comparable. Beta-based aDBS may not be as efficient as cDBS for tremor control. CONCLUSIONS: aDBS can effectively relieve the clinical symptoms of advanced PD as did cDBS, at least in acute trials, delivering less stimulation than cDBS. Specific symptoms including tremor and axial disability remain to be compared between aDBS and cDBS in long-term studies.

Effects of Subthalamic Nucleus Deep Brain Stimulation on Depression in Patients with Parkinson's Disease.

Objective: In this study, we aimed to investigate the effects of STN-DBS on PD patients with different levels of depression and to identify predictors of the effects of STN-DBS on PD depression. Methods: We retrospectively collected data for 118 patients with PD depression who underwent STN-DBS at Beijing Tiantan Hospital. Neuropsychological, motor, and quality of life assessments were applied preoperatively and postoperatively. All patients were divided into two groups according to their HAM-D24 total scores (group I: mild depression; group Ⅱ: moderate depression). A mixed repeated-measure analysis of variance (ANOVA) was performed to investigate whether there were differences in depression scores before and after STN-DBS between the two groups. The changes in depression scores were also compared between groups using ANCOVA, adjusting for gender and preoperative HAMA scores. Logistic regression was performed to identify predictors of STN-DBS's effects on PD depression. Results: Both groups showed significant improvement in depression symptoms after STN-DBS. Compared with patients in group I, patients in group Ⅱ showed greater reductions in their HAM-D24 total scores (p = 0.002) and in HAM-D24 subitems including cognitive disturbances (p = 0.026) and hopelessness symptoms (p = 0.018). Logistic regression indicated that gender (female) (p = 0.014) and preoperative moderate depression (p < 0.001) patients had greater improvements in depression after STN-DBS. Conclusions: Patients with moderate depression showed better improvement than patients with mild depression. Gender (female) and preoperative HAMA scores are predictors of STN-DBS's effects on PD depression.

Which one is the superior target? A comparison and pooled analysis between posterior subthalamic area and ventral intermediate nucleus deep brain stimulation for essential tremor.

BACKGROUND/AIMS: The efficacy and safety of posterior subthalamic area (PSA) and ventral intermediate nucleus (VIM) deep brain stimulation (DBS) in the treatment of essential tremor (ET) have not been compared in large-scale studies. We conducted a secondary analysis to identify the superior target of ET-DBS treatment. METHODS: PubMed, Embase, Cochrane Library, and Google Scholar were searched for relevant studies before September 2021. The tremor-suppression efficacy and rate of stimulation-related complications (SRCR) after PSA-DBS and VIM-DBS treating ET were quantitatively compared. Secondary outcomes, including tremor subitem scores and quality of life results, were also analyzed. Subgroup analyses were further conducted to stratify by follow-up (FU) periods and stimulation lateralities. This study was registered in Open Science Framework (DOI: 10.17605/OSF.IO/7VJQ8). RESULTS: A total of 23 studies including 122 PSA-DBS patients and 326 VIM-DBS patients were analyzed. The average follow-up time was 12.81 and 14.66 months, respectively. For the percentage improvement of total tremor rating scale (TRS) scores, PSA-DBS was significantly higher, when compared to VIM-DBS in the sensitivity analysis (p = 0.030) and main analysis (p = 0.043). The SRCR after VIM-DBS was higher than that of PSA-DBS (p = 0.022), and bilateral PSA-DBS was significantly superior to both bilateral and unilateral VIM-DBS (p = 0.001). CONCLUSIONS: This study provided level IIIa evidence that PSA-DBS was more effective and safer for ET than VIM-DBS in 12-24 months, although both PSA-DBS and VIM-DBS were effective in suppressing tremor in ET patients. Further prospective large-scale randomized clinical trials are warranted in the future.

Deep Brain Stimulation Modulates Multiple Abnormal Resting-State Network Connectivity in Patients With Parkinson's Disease.

Background: Deep brain stimulation (DBS) improves motor and non-motor symptoms in patients with Parkinson's disease (PD). Researchers mainly investigated the motor networks to reveal DBS mechanisms, with few studies extending to other networks. This study aimed to investigate multi-network modulation patterns using DBS in patients with PD. Methods: Twenty-four patients with PD underwent 1.5 T functional MRI (fMRI) scans in both DBS-on and DBS-off states, with twenty-seven age-matched healthy controls (HCs). Default mode, sensorimotor, salience, and left and right frontoparietal networks were identified by using the independent component analysis. Power spectra and functional connectivity of these networks were calculated. In addition, multiregional connectivity was established from 15 selected regions extracted from the abovementioned networks. Comparisons were made among groups. Finally, correlation analyses were performed between the connectivity changes and symptom improvements. Results: Compared with HCs, PD-off showed abnormal power spectra and functional connectivity both within and among these networks. Some of the abovementioned abnormalities could be corrected by DBS, including increasing the power spectra in the sensorimotor network and modulating the parts of the ipsilateral functional connectivity in different regions centered in the frontoparietal network. Moreover, the DBS-induced functional connectivity changes were correlated with motor and depression improvements in patients with PD. Conclusion: DBS modulated the abnormalities in multi-networks. The functional connectivity alterations were associated with motor and psychiatric improvements in PD. This study lays the foundation for large-scale brain network research on multi-network DBS modulation.

Deep Brain Stimulation Treating Dystonia: A Systematic Review of Targets, Body Distributions and Etiology Classifications.

Background: Deep brain stimulation (DBS) is a typical intervention treating drug-refractory dystonia. Currently, the selection of the better target, the GPi or STN, is debatable. The outcomes of DBS treating dystonia classified by body distribution and etiology is also a popular question. Objective: To comprehensively compare the efficacy, quality of life, mood, and adverse effects (AEs) of GPi-DBS vs. STN-DBS in dystonia as well as in specific types of dystonia classified by body distribution and etiology. Methods: PubMed, Embase, the Cochrane Library, and Google Scholar were searched to identify studies of GPi-DBS and STN-DBS in populations with dystonia. The efficacy, quality of life, mood, and adverse effects were quantitatively compared. Meta-regression analyses were also performed. This analysis has been registered in PROSPERO under the number CRD42020146145. Results: Thirty five studies were included in the main analysis, in which 319 patients underwent GPI-DBS and 113 patients underwent STN-DBS. The average follow-up duration was 12.48 months (range, 3-49 months). The GPI and STN groups were equivalent in terms of efficacy, quality of life, mood, and occurrence of AEs. The focal group demonstrated significantly better disability symptom improvement (P = 0.012) than the segmental and generalized groups but showed less SF-36 enhancement than the segmental group (P < 0.001). The primary groups exhibited significantly better movement and disability symptom improvements than the secondary non-hereditary group (P < 0.005), which demonstrated only disability symptom improvement compared with the secondary hereditary group (P < 0.005). The primary hereditary and idiopathic groups had a significantly lower frequency of AEs than the secondary non-hereditary group (P < 0.005). The correlation between disability symptom improvement and movement symptom improvement was also significant (P < 0.05). Conclusion: GPi-DBS and STN-DBS were both safe and resulted in excellent improvement in efficacy and quality of life in patients with dystonia. Compared with patients with segmental dystonia, patients with focal dystonia demonstrated better improvement in dystonia symptoms but less enhancement of quality of life. Those with primary dystonia had a better response to DBS in terms of efficacy than those with secondary dystonia. Patients who exhibit a significant improvement in movement symptoms might also exhibit excellent improvement in disability symptoms.

Levodopa Challenge Test Predicts STN-DBS Outcomes in Various Parkinson's Disease Motor Subtypes: A More Accurate Judgment.

Background: The relationship between the levodopa challenge test (LDCT) and postoperative subthalamic nucleus-deep brain stimulation (STN-DBS) benefits is controversial in patients with Parkinson's disease (PD). We aim to evaluate the value of total levodopa response (TLR) and symptom levodopa response (SLR) in predicting postoperative improvement in different PD motor subtypes. Methods: Studies were split into a training set (147 patients) and a validation set (304 patients). We retrospectively collected data from 147 patients who received the Unified Parkinson's Disease Rating Scale- (UPDRS-) III and the Parkinson's Disease Questionnaire- (PDQ-) 39 evaluation. Patients were classified into tremor-dominant (TD), akinetic-rigid-dominant (AR), and mixed (MX) groups. Clinically important difference (CID) was employed to dichotomize DBS effects. For patients in each subtype group from the training set, we used the correlation and receiver operator characteristic (ROC) curve analyses to explore the strength of their relations. Areas under the curve (AUCs) were calculated and compared through the DeLong test. Results developed from the training set were applied into the validation set to predict postoperative improvement in different PD motor subtypes. Results: In the validation cohort, TLR significantly correlated with postoperative motor (p < 0.001) and quality of life (QOL) (p < 0.001) improvement in the MX group. The AUC between TLR and UPDRS-III (TU) is 0.800. The AUC between TLR and PDQ-39 (TP) is 0.770. An associated criterion in both TU and TP is around 50%. In the AR group, strong correlation was only found in SLR and PDQ-39 (SP) (p < 0.001). And the AUC of SP is significantly larger than that in TLR and PDQ-39 (TP) (p = 0.034). An associated criterion in SP is around 37%. No significant correlation was found in the TD group. Conclusions: We provide a more accurate judgment for LDCT. TLR strongly correlated with postoperative UPDRS-III and PDQ-39 improvement in MX patients. A TLR > 50% may indicate a higher possibility of clinically meaningful benefits from STN-DBS comparing to medication only. SLR can well predict QOL improvement in AR patients. Similarly, a SLR > 37% may indicate a higher possibility of clinically significant benefits from STN-DBS. LDCT provides limited information for TD patients.

The Efficacy and Predictors of Using GPi-DBS to Treat Early-Onset Dystonia: An Individual Patient Analysis.

Objective: To compare the efficacy in patients with different genotypes, identify the potential predictive factors, and summarize the complications of globus pallidus deep brain stimulation (GPi-DBS) treating early-onset dystonia. Methods: Three electronic databases (PubMed, Embase, and Cochrane databases) were searched with no publication data restriction. The primary outcomes were the improvements in Burke-Fahn-Marsden Dystonia Rating Scale motor (BFMDRS-M) and disability (BFMDRS-D) score. Pearson's correlation coefficients and a metaregression analysis were used to identify the potential predictive factors. This article was registered in Prospero (CRD42020188527). Results: Fifty-four studies (231 patients) were included. Patients showed significant improvement rate in BFMDRS-M (60.6%, p < 0.001) and BFMDRS-D (57.5%, p < 0.001) scores after treatment with GPi-DBS. BFMDRS-M score improved greater in the DYT-1-positive (p = 0.001) and DYT-11-positive (p = 0.008) patients compared to DYT-6-positive patients. BFMDRS-D score improved greater in the DYT-11 (+) compared to DYT-6 (+) patients (p = 0.010). The relative change of BFMDRS-M (p = 0.002) and BFMDRS-D (p = 0.010) scores was negatively correlated with preoperative BFMDRS-M score. In the metaregression analysis, the best predictive model showed that preoperative BFMDRS-M, disease duration (p = 0.047), and the age at symptom onset (p = 0.027) were important. Conclusion: Patients with early-onset dystonia have a significant effect after GPi-DBS treatment, and DYT-1 (+) and DYT-11 (+) patients are better candidates for GPi-DBS. Lower preoperative score, later age of onset, and an earlier age at surgery probably predict better clinical outcomes.

Outcomes and Adverse Effects of Deep Brain Stimulation on the Ventral Intermediate Nucleus in Patients with Essential Tremor.

Objective: This study was aimed at identifying the potential outcome predictors, comparing the efficacy in patients with different tremor characteristics, and summarizing the adverse effect rates (AERs) of deep brain stimulation on the ventral intermediate nucleus (VIM-DBS) for essential tremor (ET). Methods: An extensive search of articles published to date in 2019 was conducted, and two main aspects were analyzed. Improvement was calculated as a percentage of change in any objective tremor rating scale (TRS) and analyzed by subgroup analyses of patients' tremor characteristics, laterality, and stimulation parameters. Furthermore, the AERs were analyzed as follows: the adverse effects (AEs) were classified as stimulation-related, surgical-related, or device-related effects. A simple regression analysis was used to identify the potential prognostic factors, and a two-sample mean-comparison test was used to verify the statistical significance of the subgroup analyses. Results: Forty-six articles involving 1714 patients were included in the meta-analysis. The pooled improvement in any objective TRS score was 61.3% (95% CI: 0.564-0.660) at the mean follow-up visit (20.0 ± 17.3 months). The midline and extremity symptoms showed consistent improvement (P = 0.440), and the results of the comparison of postural and kinetic tremor were the same (P = 0.219). In addition, the improvement in rest tremor was similar to that in action tremor (OR = 2.759, P = 0.120). In the simple regression analysis, the preoperative Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores and follow-up time were negatively correlated with the percentage change in any objective TRS score (P < 0.05). The most common adverse event was dysarthria (10.5%), which is a stimulation-related AE (23.6%), while the rates of the surgical-related and device-related AEs were 6.4% and 11.5%, respectively. Conclusion: VIM-DBS is an efficient and safe surgical method in ET, and the efficacy was not affected by the body distribution of tremor, age at surgery, and disease duration. Lower preoperative FTM-TRS scores likely indicate greater improvement, and the effect of VIM-DBS declines over time.

Predictive factors of outcome in cervical dystonia following deep brain stimulation: an individual patient data meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) therapy has been suggested to be a beneficial alternative in cervical dystonia (CD) for patients who failed nonsurgical treatments. This individual patient data meta-analysis compared the efficacy of DBS in the globus pallidus internus (GPi) versus subthalamic nucleus (STN) and identified possible predictive factors for CD. METHODS: Three electronic databases (PubMed, Embase and Web of Science) were searched for studies with no publication date restrictions. The primary outcomes were normalized by calculating the relative change in TWSTRS total scores and subscale scores at the last follow-up. Data were analyzed mainly using Pearson's correlation coefficients and a stepwise multivariate regression analysis. RESULTS: Thirteen studies (86 patients, 58 with GPi-DBS and 28 with STN-DBS) were eligible. Patients showed significant improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) (52.5 ± 11.6 vs 21.9 ± 14.9, P < 0.001) scores at the last follow-up (22.0 ± 14.3 months), compared with scores at baseline, with a mean improvement of 56.6% (P < 0.001) (54.9% in severity, 63.2% in disability, 41.7% in pain). There was no significant difference in the improvement (%) of the total TWSTRS scores in 3 years for the GPI and STN groups (58.1 ± 22.6 vs 47.5 ± 39.2, P > 0.05). Age at surgery and age at symptom onset were negatively correlated with the relative changes in TWSTRS scores at the last follow-up, while there was a positive correlation with preoperative TWSTRS scores. On the stepwise multivariate regression, only the age at surgery remained significant in the best predictive model. CONCLUSIONS: GPi-DBS and STN-DBS both provided a common great improvement in the symptoms of CD patients in 3 years. Earlier age at surgery may probably indicate larger improvement. More randomized large-scale clinical trials are warranted in the future.

Antibacterial Properties of Bilayer Biomimetic Nano-ZnO for Dental Implants.

Dental implant surgery has a relatively high incidence of peri-implantitis. In this research, ZnO nanorods and ZnO nanospheres were synthesized by a hydrothermal method. ZnO nanorods first covered the surface of Ti or Ti-Zr, and ZnO nanospheres were then modified as the outermost layer. By these means a dual antibacterial effect could be realized by the rapid release of ZnO nanospheres and the sustained release of ZnO nanorods. Subsequent studies implied that this ZnO nanorods-nanospheres hierarchical structure (NRS) could be stably loaded on the surface of roughened Ti and Ti-Zr slices. The modified materials not only showed excellent antibacterial activities against both Escherichia coli and Staphylococcus aureus but also showed low cellular cytotoxicity. This ZnO NRS structure is thus expected to be used as a general antimicrobial coating on the surface of Ti (Ti-Zr) in dental implant surgery.