Plasma Insulin Predicts Early Amyloid-ß Pathology Changes in Alzheimer's Disease.

Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-ß (Aß)+ participants (e.g., as reflected by CSF Aß42) exhibited significantly lower plasma insulin levels compared to non-demented Aß-participants (p < 0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aß42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aß42 levels (p < 0.001) across all participants. This association was particularly significant in the Aß-group (p = 0.002) and among non-demented individuals (p < 0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aß42 (p = 0.006), whereas baseline CSF Aß42 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early Aß pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aß pathology.

Outcomes after surgical and nonsurgical treatment of pediatric cerebral cavernous malformation.

Importance: Pediatric cerebral cavernous malformation (CCM) is a rarely encountered vascular entity. Comparative study on surgical excision and nonsurgical management outcomes of CCM in pediatrics is limited. Objective: To determine the demographic characteristics, hemorrhage rate, and long-term outcomes of pediatric patients with CCM. Methods: A retrospective study of pediatric patients with CCM in Chinese PLA General Hospital was conducted between January 2004 and January 2019. We compared the clinical characteristics, radiological features, and outcomes of the surgical and nonsurgical groups. Results: Seventy-nine children were included, with 69.6% being boys, and the average age was 11.8 ± 5.5 years. The annual retrospective hemorrhagic rate was 5.7% per patient per year. Fifty-six children (70.9%) underwent surgical excision, and they were more likely to present with seizure symptoms (P = 0.011), have a higher proportion of larger lesion size (P = 0.008), less likely to have durations ≤10 days (P = 0.048), and less likely to have supratentorial deep CCM (P = 0.014) compared to children who received nonsurgical management. Total resection was achieved in most surgical cases (55, 98.2%). During the 143.9 ± 50.8 months of follow-up, 44 patients (78.6%) achieved improvement, 12 patients (17.8%) remained the same, and two (3.6%) experienced worsening. In the nonsurgical management group, 14 children (60.9%) experienced symptom improvement, eight (34.8%) remained the same, and one (4.3%) worsened, with a re-hemorrhagic risk of 8.7%. Interpretation: Surgical removal of pediatric CCM can eliminate the risk of hemorrhage and lead to satisfactory outcomes. For children undergoing nonsurgical management, long-term close monitoring is essential due to the life-long risk of hemorrhage.

Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.

Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs.

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.

Structural network topologies are associated with deep brain stimulation outcomes in Meige syndrome.

Deep brain stimulation (DBS) is an effective therapy for Meige syndrome (MS). However, the DBS efficacy varies across MS patients and the factors contributing to the variable responses remain enigmatic. We aim to explain the difference in DBS efficacy from a network perspective. We collected preoperative T1-weighted MRI images of 76 MS patients who received DBS in our center. According to the symptomatic improvement rates, all MS patients were divided into two groups: the high improvement group (HIG) and the low improvement group (LIG). We constructed group-level structural covariance networks in each group and compared the graph-based topological properties and interregional connections between groups. Subsequent functional annotation and correlation analyses were also conducted. The results indicated that HIG showed a higher clustering coefficient, longer characteristic path length, lower small-world index, and lower global efficiency compared with LIG. Different nodal betweennesses and degrees between groups were mainly identified in the precuneus, sensorimotor cortex, and subcortical nuclei, among which the gray matter volume of the left precentral gyrus and left thalamus were positively correlated with the symptomatic improvement rates. Moreover, HIG had enhanced interregional connections within the somatomotor network and between the somatomotor network and default-mode network relative to LIG. We concluded that the high and low DBS responders have notable differences in large-scale network architectures. Our study sheds light on the structural network underpinnings of varying DBS responses in MS patients.

PAllidal versus SubThalamic deep brain Stimulation for Cervical Dystonia (PASTS-CD): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Deep brain stimulation (DBS) has been validated as a safe and effective treatment for refractory cervical dystonia (CD). Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the two main stimulating targets. However, there has been no prospective study to clarify which target is the better DBS candidate for CD. The objective of this trial is to compare directly the efficacy and safety of GPi-DBS and STN-DBS, thereby instructing the selection of DBS target in clinical practice. METHODS AND ANALYSIS: This multicentre, prospective, randomised, controlled study plans to enrol 98 refractory CD patients. Eligible CD patients will be randomly allocated to GPi-DBS group or STN-DBS group, with the DBS electrodes implanted into the posteroventral portion of GPi or the dorsolateral portion of STN, respectively. The primary outcome will be the improvement of symptomatic severity, measured by the changes in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale and the Tsui scale at 3 months, 6 months and 12 months after surgery. The secondary outcomes include the improvement of the TWSTRS-disability subscale, TWSTRS-pain subscale, quality of life, mental and cognitive condition, as well as the differences in stimulation parameters and adverse effects. In addition, this study intends to identify certain predictors of DBS efficacy for CD. ETHICS AND DISSEMINATION: The trial has been approved by the Medical Ethics Committee of Chinese PLA General Hospital (S2022-613-01). The results of this study will be published in international peer-reviewed journals and shared in professional medical conferences. TRIAL REGISTRATION NUMBER: NCT05715138.

Long-term efficacy of deep brain stimulation of the subthalamic nucleus in patients with pharmacologically intractable epilepsy: A case series of six patients.

OBJECTIVE: Epilepsy is one of the widespread neurological illnesses, and about 20%-40% of epilepsy patients are pharmacoresistant. We aimed to assess the long-term efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) for drug-resistant epilepsy. METHODS: We included pharmacologically intractable epilepsy patients who had STN-DBS at the Chinese People's Liberation Army General Hospital between June 2016 and December 2018. We retrospectively evaluated pre- and postoperative clinical outcomes, including seizure frequency, seizure type, anti-seizure medication, cognitive function, anatomical target coordinates, stimulation parameters, and adverse events following the surgical procedure. Six patients with a mean follow-up of 49.3 ± 10.2 months, were included. RESULTS: Seizure frequency decreased by an average of 64.0% after STN-DBS at last year follow-up (p = .046), and one patient (1/6) achieved seizure-free status. For seizure type, anti-seizure medication, and cognitive function, there were no significant differences between pre-and post-operation (p > .05). In terms of stimulation parameters, the pulse width, amplitude, and frequency were 58.3 ± 9.4 µs, 2.5 ± .7 V, and 122.5 ± 15.7 Hz, respectively. None of the patients showed normal electroencephalography during the electroencephalography reexamination. There were no surgery-related complications, and chronic STN stimulation was generally well tolerated in five patients. However, one patient (1/6) had a difficulty of dyskinesia in the right arm. SIGNIFICANCE: In conclusion, neuromodulation of the STN by DBS is a promising option for patients with pharmacologically intractable epilepsy, especially for whose epileptic zone originates mainly from the frontoparietal region and who are unsuitable for resective surgery. Further prospective multicenter studies with a larger sample size are necessary for further exploration.

Cerebellar gray matter alterations predict deep brain stimulation outcomes in Meige syndrome.

BACKGROUND: The physiopathologic mechanism of Meige syndrome (MS) has not been clarified, and neuroimaging studies centering on cerebellar changes in MS are scarce. Moreover, even though deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been recognized as an effective surgical treatment for MS, there has been no reliable biomarker to predict its efficacy. OBJECTIVE: To characterize the volumetric alterations of gray matter (GM) in the cerebellum in MS and to identify GM measurements related to a good STN-DBS outcome. METHODS: We used voxel-based morphometry and lobule-based morphometry to compare the regional and lobular GM differences in the cerebellum between 47 MS patients and 52 normal human controls (HCs), as well as between 31 DBS responders and 10 DBS non-responders. Both volumetric analyses were achieved using the Spatially Unbiased Infratentorial Toolbox (SUIT). Further, we performed partial correlation analyses to probe the relationship between the cerebellar GM changes and clinical scores. Finally, we plotted the receiver operating characteristic (ROC) curve to select biomarkers for MS diagnosis and DBS outcomes prediction. RESULTS: Compared to HCs, MS patients had GM atrophy in lobule Crus I, lobule VI, lobule VIIb, lobule VIIIa, and lobule VIIIb. Compared to DBS responders, DBS non-responders had lower GM volume in the left lobule VIIIb. Moreover, partial correlation analyses revealed a positive relationship between the GM volume of the significant regions/lobules and the symptom improvement rate after DBS surgery. ROC analyses demonstrated that the GM volume of the significant cluster in the left lobule VIIIb could not only distinguish MS patients from HCs but also predict the outcomes of STN-DBS surgery with high accuracy. CONCLUSION: MS patients display bilateral GM shrinkage in the cerebellum relative to HCs. Regional GM volume of the left lobule VIIIb can be a reliable biomarker for MS diagnosis and DBS outcomes prediction.

Volume of tissue activated within subthalamic nucleus and clinical efficacy of deep brain stimulation in Meige syndrome.

OBJECTIVE: The clinical efficacy of deep brain stimulation (DBS) relies on the optimal electrode placement in a large extent. Subthalamic nucleus (STN) DBS was recognized as clinically effective for Meige syndrome. This study identified the correlations of volume of tissue activated (VTA) within the motor STN and the final efficacy of the surgical procedure. METHODS: Clinical outcomes of the patients (n=25) were evaluated with the percentage improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) scores at the last follow-up (LFU) visit. Pearson's correlation coefficients were calculated to identify the relationship of the final clinical outcomes with the VTA within the STN, VTA within the different STN territories, and other clinical variables. RESULTS: On the whole, the patients showed an average of 59.21% improvement at the LFU visit relative to the baseline (5.72 ± 7.31 vs. 13.70 ± 7.36, P ˂ 0.001). Active electrode contacts mainly clustered in the STN motor territories. There were significant positive correlations between the BFMDRS-M percentage improvement and VTA within the STN (Pearson r = 0.434, P = 0.039) and the STN motor territories (r = 0.430, P = 0.041), but not associative or limbic STN. Other basic clinical characteristics including age, disease duration, and preoperative scores were not significantly correlated with the final outcomes. CONCLUSIONS: Our study further validated the efficacy of STN-DBS in even the cases with intractable Meige syndrome. Furthermore, VTA within the motor STN could serve as a potential prognostic factor for the final clinical outcomes.

One-pass deep brain stimulation of subthalamic nucleus and ventral intermediate nucleus for levodopa-resistant tremor-dominant Parkinson's disease.

Objective: Tremor-dominant Parkinson's disease (TD-PD) can be further separated into levodopa-responsive and levodopa-resistant types, the latter being considered to have a different pathogenesis. Previous studies indicated that deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus internus (GPi) individually was not sufficient for tremor control, especially for the levodopa-resistant TD-PD (LRTD-PD). The thalamic ventral intermediate nucleus (VIM) has been regarded as a potent DBS target for different kinds of tremors. Therefore, we focused on the LRTD-PD subgroup and performed one-pass combined DBSs of STN and VIM to treat refractory tremors, aiming to investigate the safety and effectiveness of this one-trajectory dual-target DBS scheme. Methods: We retrospectively collected five LRTD-PD patients who underwent a one-pass combined DBS of STN and VIM via a trans-frontal approach. The targeting of VIM was achieved by probabilistic tractography. Changes in severity of symptoms (measured by the Unified Parkinson Disease Rating Scale part III, UPDRS-III), levodopa equivalent daily doses (LEDD), and disease-specific quality of life (measured by the 39-item Parkinson's Disease Questionnaire, PDQ-39) were evaluated. Results: Three-dimensional reconstruction of electrodes illustrated that all leads were successfully implanted into predefined positions. The mean improvement rates (%) were 53 ± 6.2 (UPDRS-III), 82.6 ± 11.4 (tremor-related items of UPDRS), and 52.1 ± 11.4 (PDQ-39), respectively, with a mean follow-up of 11.4 months. Conclusion: One-pass combined DBS of STN and VIM via the trans-frontal approach is an effective and safe strategy to alleviate symptoms for LRTD-PD patients.

Effects of STN-DBS on cognition and mood in young-onset Parkinson's disease: a two-year follow-up.

Background: The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on the cognition and mood of patients with PD are still not uniformly concluded, and young-onset Parkinson's disease (YOPD) is even less explored. Objective: To observe the effectiveness of STN-DBS on the cognition and mood of YOPD patients. Methods: A total of 27 subjects, with a mean age at onset of 39.48 ± 6.24 and age at surgery for STN-DBS of 48.44 ± 4.85, were followed up preoperatively and for 2 years postoperatively. Using the Unified Parkinson disease rating scale (UPDRS), H&Y(Hoehn and Yahr stage), 39-Item Parkinson's Disease Questionnaire (PDQ-39), Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) to assess motor, cognition, and mood. Results: At the 2-year follow-up after STN-DBS, YOPD patients showed significant improvements in motor and quality of life (UPDRS III: p < 0.001, PDQ-39: p < 0.001); overall cognition was not significantly different from preoperative (MMSE: p = 0.275, MoCA: p = 0.913), although language function was significantly impaired compared to preoperative (MMSE: p = 0.004, MoCA: p = 0.009); depression and anxiety symptoms also improved significantly (HAMD: p < 0.001, HAMA: p < 0.001) and the depression score correlated significantly with motor (preoperative: r = 0.493, p = 0.009), disease duration (preoperative: r = 0.519, p = 0.006; postoperative: r = 0.406, p = 0.036) and H&Y (preoperative: r = 0.430, p = 0.025; postoperative: r = 0.387, p = 0.046); total anxiety scores were also significantly correlated with motor (preoperative: r = 0.553, p = 0.003; postoperative: r = 0.444, p = 0.020), disease duration (preoperative: r = 0.417, p = 0.031), PDQ-39 (preoperative: r = 0.464, p = 0.015) and H&Y (preoperative: r = 0.440, p = 0.022; postoperative: r = 0.526, p = 0.005). Conclusion: STN-DBS is a safe and effective treatment for YOPD. The mood improved significantly, and overall cognition was not impaired, were only verbal fluency decreased but did not affect the improvement in quality of life.

Transcranial alternating current stimulation combined with sound stimulation improves the cognitive function of patients with Alzheimer's disease: A case report and literature review.

Transcranial alternating current stimulation (tACS) is a relatively new non-invasive brain electrical stimulation method for the treatment of patients with Alzheimer's disease (AD), but it has poor offline effects. Therefore, we applied a new combined stimulation method to observe the offline effect on the cognitive function of patients with AD. Here, we describe the clinical results of a case in which tACS combined with sound stimulation was applied to treat moderate AD. The patient was a 73-year-old woman with a 2-year history of persistent cognitive deterioration despite the administration of Aricept and Sodium Oligomannate. Therefore, the patient received tACS combined with sound stimulation. Her cognitive scale scores improved after 15 sessions and continued to improve at 4 months of follow-up. Although the current report may provide a new alternative therapy for patients with AD, more clinical data are needed to support its efficacy. Trial registration: Clinicaltrials.gov, NCT05251649.

The relationship between Parkinson's disease and gastrointestinal diseases.

An increasing number of studies have provided evidence for the hypothesis that the pathogenesis of Parkinson's disease (PD) may derive from the gut. Firstly, Lewy pathology can be induced in the enteric nervous system (ENS) and be transported to the central nervous system (CNS) via the vagal nerve. Secondly, the altered composition of gut microbiota causes an imbalance between beneficial and deleterious microbial metabolites which interacts with the increased gut permeability and the gut inflammation as well as the systemic inflammation. The activated inflammatory status then affects the CNS and promotes the pathology of PD. Given the above-mentioned findings, researchers start to pay attention to the connection between PD and gastrointestinal diseases including irritable bowel syndrome, inflammatory bowel disease (IBD), microscopic colitis (MC), gastrointestinal infections, gastrointestinal neoplasms, and colonic diverticular disease (CDD). This review focuses on the association between PD and gastrointestinal diseases as well as the pathogenesis of PD from the gut.

The Long-Term Efficacy, Prognostic Factors, Safety, and Hospitalization Costs Following Denervation and Myotomy of the Affected Muscles and Deep Brain Stimulation in 94 Patients with Spasmodic Torticollis.

The surgical methods for treating spasmodic torticollis include the denervation and myotomy (DAM) of the affected muscles and deep brain stimulation (DBS). This study reports on the long-term efficacy, prognostic factors, safety, and hospitalization costs following these two procedures. We collected data from 94 patients with spasmodic torticollis, of whom 41 and 53 were treated with DAM and DBS, respectively, from June 2008 to December 2020 at the Chinese People's Liberation Army General Hospital. We used the Tsui scale and the global outcome score of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to evaluate the preoperative and postoperative clinical conditions in all patients. We also determined the costs of hospitalization, prognostic factors, and serious adverse events following the two surgical procedures. The mean follow-up time was 68.83 months (range = 13-116). Both resection surgery and DBS showed good results in terms of Tsui (Z = -5.103, p = 0.000; Z = -6.210, p = 0.000) and TWSTRS scores (t = 8.762, p = 0.000; Z = -6.308, p = 0.000). Compared with the DAM group, the preoperative (47.71, range 24-67.25) and postoperative (18.57, range 0-53) TWSTRS scores in the DBS group were significantly higher (Z = -3.161, p = 0.002). We found no correlation between prognostic factors and patient age, gender, or disease duration for either surgical procedure. However, prognostic factors were related to the length of the postoperative follow-up period in the DBS surgery group (Z = -2.068, p = 0.039; Z = -3.287, p = 0.001). The mean hospitalization cost in the DBS group was 6.85 times that found in the resection group (Z = -8.284, p = 0.000). The total complication rate was 4.26%. We found both resection surgery and DBS showed good results in the patients with spasmodic torticollis. Compared with DAM, DBS had a greater improvement in TWSTRS score; however, it was more expensive. Prognostic factors were related to the length of the postoperative follow-up period in patients who underwent DBS surgery.

Long-term efficacy, prognostic factors, and safety of deep brain stimulation in patients with refractory Tourette syndrome: A single center, single target, retrospective study.

BACKGROUND: To evaluate the long-term efficacy, prognostic factors, and safety of posteroventral globus pallidus internus deep brain stimulation (DBS) in patients with refractory Tourette syndrome (RTS). METHODS: This retrospective study recruited 61 patients with RTS who underwent posteroventral globus pallidus internus (GPi) DBS from January 2010 to December 2020 at the Chinese People's Liberation Army General Hospital. The Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Beck Depression Inventory (BDI), Gilles de la Tourette Syndrome Quality-of-Life Scale (GTS-QOL) were used to evaluate the preoperative and postoperative clinical condition in all patients. Prognostic factors and adverse events following surgery were analyzed. RESULTS: Patient follow up was conducted for an average of 73.33 ± 28.44 months. The final postoperative YGTSS (32.39 ± 22.34 vs 76.61 ± 17.07), YBOCS (11.26 ± 5.57 vs 18.31 ± 8.55), BDI (14.36 ± 8.16 vs 24.79 ± 11.03) and GTS-QOL (39.69 ± 18.29 vs 78.08 ± 14.52) scores at the end of the follow-up period were significantly lower than those before the surgery (p < 0.05). While age and the duration of follow-up were closely related to prognosis, the disease duration and gender were not. No serious adverse events were observed and only one patient exhibited symptomatic deterioration. CONCLUSIONS: Posteroventral-GPI DBS provides long-term effectiveness, acceptable safety and can improve the quality of life in RTS patients. Moreover, DBS is more successful among younger patients and with longer treatment duration.

Transcranial alternating current stimulation combined with sound stimulation improves cognitive function in patients with Alzheimer's disease: Study protocol for a randomized controlled trial.

Background: The number of patients with Alzheimer's disease (AD) worldwide is increasing yearly, but the existing treatment methods have poor efficacy. Transcranial alternating current stimulation (tACS) is a new treatment for AD, but the offline effect of tACS is insufficient. To prolong the offline effect, we designed to combine tACS with sound stimulation to maintain the long-term post-effect. Materials and methods: To explore the safety and effectiveness of tACS combined with sound stimulation and its impact on the cognition of AD patients. This trial will recruit 87 patients with mild to moderate AD. All patients were randomly divided into three groups. The change in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scores from the day before treatment to the end of treatment and 3 months after treatment was used as the main evaluation index. We will also explore the changes in the brain structural network, functional network, and metabolic network of AD patients in each group after treatment. Discussion: We hope to conclude that tACS combined with sound stimulation is safe and tolerable in 87 patients with mild to moderate AD under three standardized treatment regimens. Compared with tACS alone or sound alone, the combination group had a significant long-term effect on cognitive improvement. To screen out a better treatment plan for AD patients. tACS combined with sound stimulation is a previously unexplored, non-invasive joint intervention to improve patients' cognitive status. This study may also identify the potential mechanism of tACS combined with sound stimulation in treating mild to moderate AD patients. Clinical Trial Registration: Clinicaltrials.gov, NCT05251649. Registered on February 22, 2022.

Role of High-Frequency Oscillation in Locating an Epileptogenic Zone for Radiofrequency Thermocoagulation.

Radiofrequency thermocoagulation (RFTC) has been proposed as a first-line surgical treatment option for patients with drug-resistant focal epilepsy (DRE) that is associated with gray matter nodular heterotopia (GMNH). Excellent results on seizures have been reported following unilateral RFTC performed on ictal high-frequency-discharge, fast-rhythm, and low-voltage initiation areas. Complex cases (GMNH plus other malformations of cortical development) do not have good outcomes with RFTC. Yet, there is little research studying the effect of high-frequency oscillation in locating epileptogenic zones for thermocoagulation on unilateral, DRE with bilateral GMNH. We present a case of DRE with bilateral GMNH, treated using RFTC on unilateral GMNH and the overlying cortex, guided by stereotactic electroencephalogram (SEGG), and followed up for 69 months. Twenty-four-hour EGG recordings, seizure frequency, post-RFTC MRI, and neuropsychological tests were performed once yearly. To date, this patient is seizure-free, the electroencephalogram is normal, neuropsychological problems have not been found, and the trace of RFTC has been clearly identified on MRI. His dosage of antiepileptic medication has, furthermore, been significantly reduced. It is concluded that RFTC on unilateral DRE with bilateral GMNH may achieve good long-term effects, lasting up to, and perhaps longer than, 69 months. Ictal high-frequency oscillation (fast ripple) inside the heterotopia and the overlying cortex may be the key to this successful effect.

Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation.

Lupeol has been reported to exhibit anti-inflammatory and anti-tumor activities in many diseases, but its potential effects in cerebral ischemia injury have not been studied to date. In this work we present evidence for a beneficial effect of lupeol in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) injury and provide some histological and biochemical evidence for its mechanism of action. A cerebral MCAO rat model was established by vascular occlusion for 2 h, followed by 24 h reperfusion period. The infarct volume, neurological deficits, and brain water content were compared with animals treated during reperfusion with different concentrations of lupeol. Macroscopic parameters, cell viability, pro-inflammatory factors generation, as well as oxidative stress parameters and associated apoptotic signaling cascades were evaluated. Treatment with lupeol significantly reduced the cerebral infarct volume and water content and recovered neuro behavioral functions in affected rats. Lupeol treatment down-regulated the expression of oxidative stress and inflammation factors. In addition, lupeol activated Nrf2, suppressed caspase-3 activity, reduced BAX/Bcl-2 ratio and inhibited phosphorylation of p38 MAPK. The data suggest that lupeol may exert protective effects against cerebral ischemia by suppressing oxidative stress and reduction of inflammation factors possible via activation of nuclear transcription factors and inhibition of cell death pathways.

Predictive factors for outcome of pallidal deep brain stimulation in cervical dystonia.

OBJECTIVE: Primary cervical dystonia (CD) is characterized by abnormal contractions of neck muscles. Globus pallidus internus deep brain stimulation (GPi-DBS) is recognized as an effective therapy for patients with refractory CD, but the prognostic factors need further research. Our study investigated the predictive factors of clinical outcomes in CD patients who underwent GPi-DBS. PATIENTS AND METHODS: Patients (n = 23) who underwent GPi-DBS at Chinese PLA General Hospital from March 2012 to April 2018 were included in our analysis. Their scores of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui were acquired at baseline and at the last follow-up visit. Percent improvement in these scores were compared between the categorical variables. Correlations between outcomes and continuous demographic and clinical variables were calculated. RESULTS: Patients showed significant improvement in TWSTRS total (55.71 %), severity (48.75 %), disability (57.05 %), pain (63.67 %) scores and total Tsui score (46.07 %, all P ﹤0.001). Follow-up duration was positively correlated with percent improvement in TWSTRS total (rho = 0.594, P = 0.003), severity (rho = 0.581, P = 0.004) and disability (rho = 0.470, P = 0.023) scores. No significant differences in the outcomes were found between any pair of the categorical variables. CONCLUSIONS: Follow-up duration was the only independent factor correlated to the outcomes of GPi-DBS for CD patients. However, follow-up duration is an indefinite factor prior to surgery, thus further studies are needed before the final conclusions of prognostic factors are established.

The role of noninvasive brain stimulation for behavioral and psychological symptoms of dementia: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed at evaluating and comparing the efficacy of noninvasive brain stimulation (NIBS) techniques on the behavioral and psychological symptoms of dementia (BPSD). METHODS: An exhaustive literature retrieval was performed on PubMed, Embase, Cochrane Library, and Web of Science until October 2019. The primary outcome was the relative changes in BPSD severity scores immediately after NIBS and at the last follow-up visit. Subgroup analyses were conducted to compare the efficacy of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Changes in the severity scores after NIBS were also analyzed with restriction to patients with Alzheimer's disease (AD). RESULTS: Ten studies with 324 patients were included, out of which 7 studies involved patients with AD. The analysis results indicated that NIBS significantly improved the BPSD outcome immediately after stimulation (SMD, 0.31; 95% CI, 0.10-0.52; P = 0.005), but not at the last follow-up visit (0.15; - 0.11-0.41; 0.25). Our subgroup analyses suggested that the favorable effects of rTMS remained significant at the last follow-up visit (0.57; 0.18-0.96; 0.004). This discrepancy maybe caused by the continuously insignificant outcomes of tDCS on the whole data. The results for AD patients immediately after stimulation (0.37; 0.12-0.61; 0.003) and at the last follow-up visit (0.29; - 0.19-0.76; 0.24) were both largely similar to those in the whole patient group with dementia. CONCLUSIONS: rTMS, rather than tDCS, was capable of persistently improving the BPSD at an early stage after treatment. More trials are warranted to confirm our results before the establishment of final conclusions.