Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Establishment and validation of a multivariate logistic model for risk factors of thyroid nodules using lasso regression screening.

Objective: This study aims to analyze the association between the occurrence of thyroid nodules and various factors and to establish a risk factor model for thyroid nodules. Methods: The study population was divided into two groups: a group with thyroid nodules and a group without thyroid nodules. Regression with the least absolute shrinkage and selection operator (Lasso) was applied to the complete dataset for variable selection. Binary logistic regression was used to analyze the relationship between various influencing factors and the prevalence of thyroid nodules. Results: Based on the screening results of Lasso regression and the subsequent establishment of the Binary Logistic Regression Model on the training dataset, it was found that advanced age (OR=1.046, 95% CI: 1.033-1.060), females (OR = 1.709, 95% CI: 1.342-2.181), overweight individuals (OR = 1.546, 95% CI: 1.165-2.058), individuals with impaired fasting glucose (OR = 1.590, 95% CI: 1.193-2.122), and those with dyslipidemia (OR = 1.588, 95% CI: 1.197-2.112) were potential risk factors for thyroid nodule disease (p<0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the Binary Logistic Regression Model is 0.68 (95% CI: 0.64-0.72). Conclusions: advanced age, females, overweight individuals, those with impaired fasting glucose, and individuals with dyslipidemia are potential risk factors for thyroid nodule disease.

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette's syndrome: Experience and evidence.

OBJECTIVES: To evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette's syndrome (TS). METHODS: This retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. RESULTS: In total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28-74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67-25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26-23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90-15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68-52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5-87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. CONCLUSIONS: Combined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

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.

CircIRAK3 exerts negative feedback regulation on inflammation by binding to HNRNP U and destabilizing proinflammatory cytokine mRNA in osteoarthritis and chondrogenesis.

Osteoarthritis (OA) is the most prevalent age-related and degenerative joint disease with limited treatment options. Previous studies have identified the therapeutic effects of mesenchymal stem cells (MSCs) therapy. Nevertheless, chronic inflammation impedes MSCs therapeutic effect. There have been reports suggesting that circular RNAs (circRNAs) are involved in OA and chondrogenesis. The combination of MSCs and circRNAs in therapies appears to be a promising option. In this study, we identified circIRAK3 as a significant regulator in cartilage degeneration and chondrogenesis through high-throughput sequencing analyses. We observed increased circIRAK3 in OA cartilage and during MSCs chondrogenesis. Knockdown of circIRAK3 resulted in excessive apoptosis, inhibited proliferation, and degradation of chondrocytes, along with the inhibition of MSCs chondrogenesis. Mechanistically, circIRAK3 bound to HNRNP U and competitively prevented its binding to IL-1ß, TNFα, and IL6 mRNA, thereby promoting mRNA degradation. Notably, circIRAK3 expression in plasma increased with higher OARSI scores. Intra-articular injection of adeno-associated virus-circIRAK3 delayed cartilage degeneration and reduced inflammation in DMM mouse model. Our study highlights a compensatory regulation network of circIRAK3 in chondrocytes in response to inflammation. CircIRAK3 has the potential to serve as a new therapeutic target for OA. Furthermore, therapies targeting circIRAK3 combined with MSCs hold promise.

Transcriptome sequencing of circular RNA reveals the involvement of hsa-SCMH1_0001 in the pathogenesis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease. Exosomes are endosome-derived extracellular vesicles that can take part in intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs characterized by covalently closed-loop structures, which perform a crucial function in many diseases. AIM: To clarify the expression and function of exosomal circRNSs of PD patients and look for circRNAs that might be related to the pathogenesis of PD. MATERIALS AND METHODS: We examined circRNA and mRNA expression profiles in peripheral exosomes from PD patients (n = 23) and healthy controls (n = 15) using next-generation sequencing (NGS) technology, functional annotation, and quantitative polymerase chain reaction. Correlation analysis was performed between the expression levels of the circRNAs and the clinical characteristics of PD patients. The binding miRNAs and target genes were predicted using TargetScanHuman, miRDB, and miRTarBase. The predicted target genes were compared with the differentially expressed mRNAs in sequencing results. RESULTS: According to the NGS, 62 upregulated and 37 downregulated circRNAs in the PD group were screened out. Correlation analysis revealed that hsa-SCMH1_0001 has strong clinical relevance. We identified 17 potential binding miRNAs of hsa-SCMH1_0001 with 149 potential target genes. ARID1A and C1orf115 belong to the intersection of the predicted target genes and the differentially expressed mRNAs obtained by sequencing. CONCLUSION: This study suggested that hsa-SCMH1_0001 and its target genes ARID1A and C1orf115 are downregulated in PD patients and may be involved in the occurrence of PD.

Neurosurgical robots in China: State of the art and future prospect.

Neurosurgical robots have developed for decades and can effectively assist surgeons to carry out a variety of surgical operations, such as biopsy, stereo-electroencephalography (SEEG), deep brain stimulation (DBS), and so forth. In recent years, neurosurgical robots in China have developed rapidly. This article will focus on several key skills in neurosurgical robots, such as medical imaging systems, automatic manipulator, lesion localization techniques, multimodal image fusion technology, registration method, and vascular imaging technology; introduce the clinical application of neurosurgical robots in China, and look forward to the potential improvement points in the future based on our experience and research in the field.

The NONRATT023402.2/rno-miR-3065-5p/NGFR axis affects levodopa-induced dyskinesia in a rat model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson's disease. However, few studies have focused on the pathogenesis of LID at the transcriptional level. NONRATT023402.2, a long non-coding RNA (lncRNA) that may be related to LID was discovered in our previous study and characterized in rat models of LID. In the present study, NONRATT023402.2 was overexpressed by injection of adeno-associated virus (AAV) in striatum of LID rats, and 48 potential target genes, including nerve growth factor receptor (NGFR) were screened using next-generation sequencing and target gene predictions. The NONRATT023402.2/rno-miR-3065-5p/NGFR axis was verified using a dual luciferase reporter gene. Overexpression of NONRATT023402.2 significantly increased the abnormal involuntary movements (AIM) score of LID rats, activated the PI3K/Akt signaling pathway, and up-regulated c-Fos in the striatum. NGFR knockdown by injection of ShNGFR-AAV into the striatum of LID rats resulted in a significant decrease in the PI3K/Akt signaling pathway and c-Fos expression. The AIM score of LID rats was positively correlated with the expressions of NONRATT023402.2 and NGFR. A dual luciferase reporter assay showed that c-Fos, as a transcription factor, bound to the NONRATT023402.2 promoter and activated its expression. Together, the results showed that NONRATT023402.2 regulated NGFR expression via a competing endogenous RNA mechanism, which then activated the PI3K/Akt pathway and promoted c-Fos expression. This suggested that c-Fos acted as a transcription factor to activate NONRATT023402.2 expression, and form a positive feedback regulation loop in LID rats, thus, aggravating LID symptoms. NONRATT023402.2 is therefore a possible novel therapeutic target for LID.

Associated factors with stimulation induced seizures and the relevance with surgical outcomes.

OBJECTIVE: To analyze the associated factors with stimulation-induced seizures (SIS) and the relevant factors in predicting surgical outcomes. METHODS: We analyzed 80 consecutive epilepsy patients explored by stereo-electroencephalography with routine electrical stimulation mapping (ESM). If seizures induced by ESM, patients were classified as SIS-positive (SIS-P); otherwise, SIS-negative (SIS-N). Patients received radical surgery were further classified as favorable (Engel I) and unfavorable (Engel II-IV) groups. RESULTS: Of the 80 patients included, we identified 44 (55.0%) and 36(45.0%) patients in the SIS-P and SIS-N groups, respectively. Multivariate analysis revealed that the seizure onset pattern (SOP) of preceding repetitive epileptiform discharges following LVFA (PRED→LVFA) (OR 3.319, 95% CI 1.200-9.183, P = 0.021) and pathology of focal cortical dysplasia (FCD) type II (OR 3.943, 95% CI 1.093-14.226, P = 0.036) were independent factors influencing whether the electrical stimulation can induce a seizure. Among the patients received radical surgery, there were 55 and 15 patients in the favorable and unfavorable groups separately. Multivariate analysis revealed that the SOP of PRED→LVFA induced seizures by stimulation (OR 11.409, 95% CI 1.182-110.161, P = 0.035) and bilateral implantation (OR 0.048, 95% CI 0.005-0.497, P = 0.011) were independent factors affecting surgical outcomes. The previous epilepsy surgery had a trend to be a negative factor with SIS (OR 0.156, 95% CI 0.028-0.880, P = 0.035) and surgical outcomes (OR 0.253, 95% CI 0.053-1.219, P = 0.087). CONCLUSION: ESM is a highly valuable method for localizing the seizure onset zone. The SOP of PRED→LVFA and FCD type II were associated with elicitation of SIS by ESM, whereas a previous epilepsy surgery showed a negative association. Furthermore, the SOP of PRED→LVFA together with SIS in the same patient predicted favorable surgical outcomes, whereas bilateral electrode implantation predicted unfavorable outcomes.

Utilization, surgical populations, centers, coverages, regional balance, and their influential factors of deep brain stimulation for Parkinson's disease: a large-scale multicenter cross-sectional study from 1997 to 2021.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( ß =5.041, 3.324-6.758 and ß =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( ß =3.596, 0.353-6.839; P =0.031 and ß =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( ß =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.

Sleep outcomes and related factors in Parkinson's disease after subthalamic deep brain electrode implantation: a retrospective cohort study.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves sleep qualities in Parkinson's disease (PD) patients; however, it remains elusive whether STN-DBS improves sleep by directly influencing the sleep circuit or alleviates other cardinal symptoms such as motor functions, other confounding factors including stimulation intensity may also involve. Studying the effect of microlesion effect (MLE) on sleep after STN-DBS electrode implantation may address this issue. Objective: To examine the influence of MLE on sleep quality and related factors in PD, as well as the effects of regional and lateral specific correlations with sleep outcomes after STN-DBS electrode implantation. Study Design: Case-control study; Level of evidence, 3. Data Sources and Methods: In 78 PD patients who underwent bilateral STN-DBS surgery in our center, we compared the sleep qualities, motor performances, anti-Parkinsonian drug dosage, and emotional conditions at preoperative baseline and postoperative 1-month follow-up. We determined the related factors of sleep outcomes and visualized the electrodes position, simulated the MLE-engendered volume of tissue lesioned (VTL), and investigated sleep-related sweet/sour spots and laterality in STN. Results: MLE improves sleep quality with Pittsburgh Sleep Quality Index (PSQI) by 13.36% and Parkinson's Disease Sleep Scale-2 (PDSS-2) by 17.95%. Motor (P = 0.014) and emotional (P = 0.001) improvements were both positively correlated with sleep improvements. However, MLE in STN associative subregions, as an independent factor, may cause sleep deterioration (r = 0.348, P = 0.002), and only the left STN showed significance (r = 0.327, P = 0.004). Sweet spot analysis also indicated part of the left STN associative subregion is the sour spot indicative of sleep deterioration. Conclusion: The MLE of STN-DBS can overall improve sleep quality in PD patients, with a positive correlation between motor and emotional improvements. However, independent of all other factors, the MLE in the STN associative subregion, particularly the left side, may cause sleep deterioration.

Serum thyroglobulin as a biomarker of iodine excess and thyroid disease occurrence in adults.

BACKGROUND: Thyroglobulin (Tg) is considered a sensitive indicator of iodine deficiency. However, the usefulness of Tg as a biomarker of excess iodine is uncertain. The present study aimed to determine the influence of different iodine intake on serum Tg levels, evaluate the influence of thyroid diseases on the distribution of Tg, and identify the factors that may affect Tg levels. METHODS: A cross-sectional survey with a total of 1208 adults was conducted in different water iodine areas in China. Urinary iodine concentration (UIC), water iodine concentration (WIC), serum Tg, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. The thyroid volumes and nodules were measured by B-scan ultrasound. RESULTS: Based on the WIC data, subjects were divided into three groups. Based on the median urinary iodine concentration (MUIC) data, the iodine levels were adequate, more than adequate, and excess for the WIC < 10 µg/L group, 10 µg/L ≤ WIC ≤ 100 µg/L g, and WIC > 100 µg/L groups, respectively. The median Tg was significantly higher in the excess iodine group than in the adequate iodine group and the more than adequate iodine group (14.6 µg/L vs.12.7 µg/L, P = 0.042; 14.6 µg/L vs.12.5 µg/L, P = 0.004). Multiple linear regression analysis showed that excess iodine intake, goitre, thyroid nodules, and hypothyroidism were significantly related to higher serum Tg levels. CONCLUSION: Serum Tg level can be a promising biomarker of excessive iodine intake, but other factors, especially the presence of thyroid disease, should be considered when using this parameter.

Application of the robot-assisted implantation in deep brain stimulation.

Introduction: This work aims to assess the accuracy of robotic assistance guided by a videometric tracker in deep brain stimulation (DBS). Methods: We retrospectively reviewed a total of 30 DBS electrode implantations, assisted by the Remebot robotic system, with a novel frameless videometric registration workflow. Then we selected 30 PD patients who used stereotactic frame surgery to implant electrodes during the same period. For each electrode, accuracy was assessed using radial and axial error. Results: The average radial error of the robot-assisted electrode implantation was 1.28 ± 0.36 mm, and the average axial error was 1.20 ± 0.40 mm. No deaths or associated hemorrhages, infections or poor incision healing occurred. Conclusion: Robot-assisted implantation guided by a videometric tracker is accurate and safe.

Comparison of dural puncture and dural incision in deep brain stimulation surgery: A simple but worthwhile technique modification.

Background: The accuracy of the deep brain stimulation (DBS) electrode placement is influenced by a myriad of factors, among which pneumocephalus and loss of cerebrospinal fluid that occurs with dural opening during the surgery are considered most important. This study aimed to describe an effective method for decreasing pneumocephalus by comparing its clinical efficacy between the two different methods of opening the dura. Materials and methods: We retrospectively compared two different methods of opening the dura in 108 patients who underwent bilateral DBS surgery in our center. The dural incision group comprised 125 hemispheres (58 bilateral and 9 unilateral) and the dural puncture group comprised 91 (41 bilateral and 9 unilateral). The volume of intracranial air, dural opening time, intraoperative microelectrode recordings (MERs), postoperative electrode displacement, clinical efficacy, and complications were examined. Spearman correlation analysis was employed to identify factors associated with the volume of intracranial air and postoperative electrode displacement. Results: The volume of intracranial air was significantly lower (0.35 cm3 vs. 5.90 cm3) and dural opening time was significantly shorter (11s vs. 35s) in the dural puncture group. The volume of intracranial air positively correlated with dural opening time. During surgery, the sensorimotor area was longer (2.47 ± 1.36 mm vs. 1.92 ± 1.42 mm) and MERs were more stable (81.82% vs. 47.73%) in the dural puncture group. Length of the sensorimotor area correlated negatively with the volume of intracranial air. As intracranial air was absorbed after surgery, significant anterior, lateral, and ventral electrode displacement occurred; the differences between the two groups were significant (total electrode displacement, 1.0mm vs. 1.4mm). Electrode displacement correlated positively with the volume of intracranial air. Clinical efficacy was better in the dural puncture group than the dural incision group (52.37% ± 16.18% vs. 43.93% ± 24.50%), although the difference was not significant. Conclusion: Our data support the hypothesis that opening the dura via puncture rather than incision when performing DBS surgery reduces pneumocephalus, shortens dural opening time, enables longer sensorimotor area and more stable MERs, minimizes postoperative electrode displacement, and may permit a better clinical efficacy.

The Thyroid Condition and Residual Clinical Signs in 31 Existing Endemic Neurological Cretins After 42 Years of Iodine Supplementation in China.

Backgroud: Endemic cretinism is the most severe manifestation among the iodine deficiency-related disorders. The clinical status of the cretins may be modified subsequently by the duration and severity of the disease. We aimed to reassess the clinical status and thyroid function of 31 surviving "neurological cretins" after 42 years of iodine supplementation in a historically severely iodine deficiency area of China. Methods: It was a cross-sectional study in design and we investigated all 31 surviving neurological cretins and 85 controls. A detailed neurological examination was conducted on each patients. All the participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum levels of thyroid hormones, thyroid antibodies, serum iodine concentration (SIC) and urine iodine concentration (UIC) were measured. Results: The neurological cretins had shorter stature than that of the control. Neurological damage is still present in patients with cretinism. The prevalence of subclinical hypothyroidism and thyroid nodule in the cretins was significantly higher (χ2 =4.766, P=0.029 and χ2 =17.077, P<0.0001, respectively) compared with the control. After adjusting for confounding factors, endemic neurocretinism was found to be an independent risk factor for subclinical hypothyroidism (OR=4.412; 95% CI: 1.358-14.334; P=0.014) and thyroid nodule (OR=6.433; 95% CI: 2.323-17.816; P<0.0001). Conclusions: Iodine supplementation after birth does not reverse the neurological damage that results from maternal/foetal hypothyroidism in utero and is subsequently manifested as neurological cretinism. There is a cross-sectional association between endemic neurocretinism and subclinical hypothyroidism and thyroid nodule.

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.

Correlation between Electrode Location and Anxiety Depression of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

Objectives: our group explored the correlation between postoperative coordinates of the electrode contacts, VTA, and anxiety and depression symptoms in Parkinson's disease (PD) patients after subthalamic nucleus deep brain stimulation (STN-DBS). Methods: STN-DBS was conducted on PD patients (n = 57) for six months with follow-up. Clinical outcomes were explored using the unified Parkinson's disease rating scale Part III (UPDRS-III), the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D) before and after surgery. At the Montreal Neurological Institute (MNI), the location of active contacts and the volume of tissue activated (VTA) were calculated. Results: patient evaluations took place preoperatively and follow-ups took place at 1 month, 3 months, and 6 months. The average patient improvement rates for HAM-A and HAM-D scores at the 6-month follow-up were 41.7% [interquartile range (IQR) 34.9%] and 37.5% (IQR 33.4%), respectively (both p < 0.001). In medication-off, there were negative correlations between the HAM-A improvement rate and the Z-axis coordinate of the active contact (left side: r = −0.308, p = 0.020; right side: r = −0.390, p = 0.003), and negative correlations between the HAM-D improvement rate and the Z-axis coordinate of the active contact (left side: r = −0.345, p = 0.009; right side: r = −0.521, p = 0.001). There were positive correlations between the HAM-A and HAM-D scores improvement rate at 6 months after surgery and bilateral VTA in the right STN limbic subregion (HAM-A: r = 0.314, p = 0.018; HAM-D: r = 0.321, p = 0.015). Conclusion: bilateral STN-DBS can improve anxiety and depression symptoms in PD patients. The closer the stimulation to the ventral limbic region of the STN, the more significant the improvement in anxiety and depression symptoms of PD patients.

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

OBJECTIVE: We investigated the differences in motor symptom change outcomes after bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in well-defined motor subtypes of Parkinson's disease (PD) to improve clinical decision making. METHODS: We included 114 patients who had undergone STN-DBS and 65 patients who had undergone GPi-DBS. The patients were classified as having akinetic-rigid type (ART), tremor-dominant type (TDT), and mixed type (MT) using the preoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) scores in the no-medication state. The outcome measures included the no-medication MDS-UPDRS-III scores and subscore changes at the last follow-up after surgery. The outcomes were compared among the different motor subtypes and between STN-DBS and GPi-DBS. RESULTS: At the last follow-up (14.92 ± 8.35 months), the TDT patients had had a greater median overall motor improvement in the no-medication MDS-UPDRS-III scores compared with the ART patients (62.90% vs. 46.67%; P < 0.001), regardless of the stimulation target. The ART patients showed greater improvement after STN-DBS than after GPi-DBS (54.44% vs. 37.21%; P < 0.001), with improvements in rigidity, akinesia, and posture and gait disorders accounting for the difference. CONCLUSIONS: Our results suggest that the different PD motor subtypes will have differential responses to STN-DBS and GPi-DBS, that TDT patients will experience greater improvement than ART patients, and that STN-DBS provides better effects for ART patients than does GPi-DBS. In addition, different motor symptoms among the different motor subtypes might respond differently to STN-DBS than to GPi-DBS. All these factors could reflect the heterogeneity of PD. Longer-term outcomes across the different motor subtypes and stimulation targets should be studied further.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait.

Freezing of gait is a debilitating symptom in advanced Parkinson's disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson's disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait. Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson's disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking. We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials. These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel 'bandwidth model,' which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.