Microstructural Alteration of Trigeminal Nerve in Patients with Classic Trigeminal Neuralgia Shown by Diffusion Tensor Imaging and Its Correlation with Vascular Compression and Pain.

OBJECTIVE: To investigate the value of magnetic resonance diffusion tensor imaging in evaluating the microstructural alteration of trigeminal nerve in patients with classic trigeminal neuralgia (CTN) and its correlation with the degree of vascular compression and patient pain. METHODS: A total of 108 patients with CTN were enrolled in this study. Patients were divided into 2 groups according to whether the asymptomatic side trigeminal nerve had neurovascular compression (NVC) or not: group A (32 cases) with NVC and group B (76 cases) without NVC. The anisotropy fraction (FA) and apparent diffusion coefficient of bilateral trigeminal nerves were measured. A visual analog scale (VAS) was used to evaluate the pain degree of the patients. The severity of NVC on the symptomatic side was classified as grade I, II, or III by neurosurgeons according to the findings during microvascular decompression. RESULTS: The FA values of the trigeminal nerve on the symptomatic side were significantly lower than those on the asymptomatic side in group A (P < 0.001) and group B (P < 0.001). Thirty-six patients were treated with microvascular decompression. The FA values of the trigeminal nerve were grade I 0.309 ± 0.011, grade II 0.295 ± 0.015, and grade III 0.286 ± 0.022. The difference was statistically significant (P = 0.011). The FA of the trigeminal nerve on the symptomatic side was negatively correlated with the degree of NVC and pain (P < 0.05). CONCLUSIONS: Patients with NVC had significant decreases in FA and it negatively correlated with NVC and VAS scores.

Microglia-mediated inflammatory destruction of neuro-cardiovascular dysfunction after stroke.

Stroke, a serious systemic inflammatory disease, features neurological deficits and cardiovascular dysfunction. Neuroinflammation is characterized by the activation of microglia after stroke, which disrupts the cardiovascular-related neural network and the blood-brain barrier. Neural networks activate the autonomic nervous system to regulate the cardiac and blood vessels. Increased permeability of the blood-brain barrier and the lymphatic pathways promote the transfer of the central immune components to the peripheral immune organs and the recruitment of specific immune cells or cytokines, produced by the peripheral immune system, and thus modulate microglia in the brain. In addition, the spleen will also be stimulated by central inflammation to further mobilize the peripheral immune system. Both NK cells and Treg cells will be generated to enter the central nervous system to suppress further inflammation, while activated monocytes infiltrate the myocardium and cause cardiovascular dysfunction. In this review, we will focus on microglia-mediated inflammation in neural networks that result in cardiovascular dysfunction. Furthermore, we will discuss neuroimmune regulation in the central-peripheral crosstalk, in which the spleen is a vital part. Hopefully, this will benefit in anchoring another therapeutic target for neuro-cardiovascular dysfunction.

Spinal subdural hematoma in a patient with immune thrombocytopenic purpura following microvascular decompression: a rare case report.

This article reports a case of spontaneous spinal subdural hematoma (SSDH) after brain surgery in a patient with immune thrombocytopenic purpura (ITP), reviews the relevant literature, and discusses the etiology, pathogenesis, and clinical features of SSDH in patients with ITP. A male patient in his early 50 s with an 8-year history of ITP and suffering from coexistent hemifacial spasm and trigeminal neuralgia underwent microvascular decompression in our department. His preoperative corrected platelet count was within the normal range. On postoperative day 2, the patient complained of acute low back pain and sciatica. Lumbar magnetic resonance imaging demonstrated an SSDH extending from L3 to L4 with a significantly decreased platelet count (30.0 × 109/L). The pain was gradually relieved after 2 weeks of conservative treatment, and no neurological deficit occurred during the 1-year follow-up. Brain surgery may increase the risk of postoperative SSDH in patients with ITP. Clinicians planning brain surgery must conduct a rigorous assessment through detailed physical examination, laboratory tests, and medical history records and maintain perioperative platelet counts within the normal range to prevent various risks associated with spinal cord compression.

Diagnostic utility of GDF15 in neurodegenerative diseases: A systematic review and meta-analysis.

INTRODUCTION: GDF15 may be a potential biomarker for neurodegenerative diseases. In this analysis, we aimed to quantitative analysis the levels of GDF15 in patients with neurological diseases and in health control, and then to determine its potential diagnostic utility. METHODS: Two researchers separately conducted a systematic search of the relevant studies up to January 2021 in Embase, PubMed, and Web of Science. Effect sizes were estimated to use the standardized mean difference (SMD) with 95% confidence interval (CI). Sensitivity and specificity were calculated by the summary receiver operating characteristics curve (SROC) method. The sensitivity analysis was performed by the "one-in/one-out" approach. Considering the considerable heterogeneity among studies, random-effects model was used for the meta-analysis investigation. RESULTS: A total of eight articles were included in this meta-analysis and systematic review. The pooled results of the random effect model indicated GDF15 levels were significantly higher in patients with neurodegenerative disease than healthy people (SMD = 0.92, 95% CI: 0.44-1.40, Z = 3.75, p < 0.001). Sensitivity and specificity of biomarker of GDF15 were 0.90 (95% CI: 0.75-0.97), 0.77 (95% CI: 0.67-0.65), and AUC = 0.87 (95% CI: 0.84-0.90), respectively. CONCLUSIONS: GDF15 levels were higher in patients with neurodegenerative disease than healthy people. And serum levels of GDF15 were a better marker for diagnostic utility of neurodegenerative disease.

Recharging Difficulty With Pulse Generator After Deep Brain Stimulation: A Case Series of Five Patients.

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

Pallidal stimulation as treatment for camptocormia in Parkinson's disease.

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

Asleep Deep Brain Stimulation in Patients With Isolated Dystonia: Stereotactic Accuracy, Efficacy, and Safety.

OBJECTIVES: Lead placement for deep brain stimulation (DBS) is routinely performed using neuroimaging or microelectrode recording (MER). Recent studies have demonstrated that DBS under general anesthesia using an imaging-guided target technique ("asleep" DBS) can be performed accurately and effectively with lower surgery complication rates than the MER-guided target method under local anesthesia ("awake" DBS). This suggests that asleep DBS may be a more acceptable method. However, there is limited direct evidence focused on isolated dystonia using this method. Therefore, this study aimed to investigate the clinical outcomes and targeting accuracy in patients with dystonia who underwent asleep DBS. MATERIALS AND METHODS: We examined 56 patients (112 leads) with isolated dystonia who underwent asleep DBS targeting in the globus pallidus internus (GPi) and subthalamic nucleus (STN). The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were assessed preoperatively and at 12-month follow-up (12 m-FU). The lead accuracy was evaluated by comparing the coordinates of the preoperative plan with those of the final electrode implantation location. Other measures analyzed included stimulation parameters and adverse events (AEs). RESULTS: For both GPi and STN cohorts, mean BFMDRS motor scores were significantly lower at 12 m-FU (8.9 ± 10.9 and 4.6 ± 5.7 points) than at baseline (22.6 ± 16.4 and 16.1 ± 14.1 points, p < 0.001). The mean difference between the planned target and the distal contact of the leads was 1.33 ± 0.54 mm for the right brain electrodes and 1.50 ± 0.57 mm for the left, determined by Euclidian distance. No perioperative complications or AEs related to the device were observed during the complete follow-up. However, AEs associated with stimulation occurred in 12 and 6 patients in the GPi and STN groups, respectively. CONCLUSIONS: Asleep DBS may be an accurate, effective, and safe method for treating patients with isolated dystonia regardless of the stimulation target.

Long-Noncoding RNA FGD5-AS1 Enhances the Viability, Migration, and Invasion of Glioblastoma Cells by Regulating the miR-103a-3p/TPD52 Axis.

PURPOSE: This study was designed to explore the functional role of FYVE, RhoGEF, and PH domain containing 5 antisense RNA 1 (FGD5-AS1) and the underlying regulatory mechanism in the progression of glioblastoma (GBM). MATERIALS AND METHODS: FGD5-AS1 expression was analyzed in The Cancer Genome Atlas (TCGA), and then detected in GBM tissues and cells by quantitative reverse-transcription polymerase chain reaction. Viability, migration, and invasion of GBM cells were assessed using the MTT, wound healing, and transwell assays, respectively. StarBase/TargetScan analysis and dual-luciferase reporter gene (DLR) assay were performed to investigate the relationship between FGD5-AS1/tumor protein D52 (TPD52) and miR-103a-3p. A xenograft tumor model was established to evaluate the role of FGD5-AS1 in GBM tumorigenesis in vivo. RESULTS: FGD5-AS1 was overexpressed in GBM tissues and cells, and silencing of FGD5-AS1 expression resulted in the inhibition of the viability, migration, and invasion of GBM cells. miR-130-3p was a target of FGD5-AS1, and its expression was negatively regulated by FGD5-AS1. Silencing miR-103a-3p expression resulted in the abrogation of the inhibitory effects of si-FGD5-AS1 on the viability, migration, and invasion of GBM cells. TPD52 was a target of miR-103a-3p and suppressed the antitumor effects of FGD5-AS1 silencing on GBM cells. In addition, FGD5-AS1 silencing inhibited the growth of xenograft tumors in vivo by modulating the miR-103a-3p/TPD52 axis. CONCLUSION: Silencing of FGD5-AS1 inhibited the viability, migration, and invasion of GBM cells by regulating the miR-103a-3p/TPD52 axis.

Deep Brain Stimulation and Thalamotomy for the Treatment of Dystonia Acquired by Moyamoya Disease with Stroke.

Background: Moyamoya disease (MMD) is a type of chronic cerebrovascular disease. Currently, revascularization surgery including direct/indirect procedure is recommended for symptomatic patients. However, some patients still respond poorly to the treatment or develop secondary symptoms. Case report: We report the first case of an MMD patient treated with deep brain stimulation (DBS) and thalamotomy. Symptoms of dystonia due to hemorrhage in the thalamus responded poorly to revascularization surgery, but were considerably alleviated by stereotactic neurosurgery. Discussion: Our case report provides a potential strategy for management of refractory symptomatic MMD patients with dystonia and also supports the combined efficacy of DBS with thalamotomies. Highlights: Approximately 30% of patients with Moyamoya disease (MMD) presenting movement symptoms do not respond well to revascularization surgery. We reported an MMD patient treated with deep brain stimulation (DBS) and thalamotomy with significant dystonia and dystonic tremor symptom amelioration. It indicates that DBS or stereotactic lesioning might be a potential treatment for the refractory movement symptoms of MMD.

Phoenixin 14 inhibits ischemia/reperfusion-induced cytotoxicity in microglia.

The process of ischemia/reperfusion (IR) in ischemic stroke often leads to significant cell death and permanent neuronal damage. Safe and effective treatments are urgently needed to mitigate the damage caused by IR injury. The naturally occurring pleiotropic peptide phoenixin 14 (PNX-14) has recently come to light as a potential treatment for IR injury. In the present study, we examined the effects of PNX-14 on several key processes involved in ischemic injury, such as pro-inflammatory cytokine expression, oxidative stress, and the related cascade mediated through the toll-like receptor 4 (TLR4) pathway, using BV2 microglia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Our results demonstrate an acute ability of PNX-14 to regulate the expression levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). PNX-14 also prevented oxidative stress by reducing the generation of reactive oxygen species (ROS) and increasing the level of the antioxidant glutathione (GSH). Importantly, PNX-14 inhibited high-mobility group box 1 (HMGB1)/TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway, by inhibiting the activation of TLR4 and preventing the nuclear translocation of p65 protein. We further confirmed the cerebroprotective effects of PNX-14 in an MCAO rat model, which resulted in reduced infarct volume and decreased microglia activation. Together, the results of this study implicate a possible protective role of PNX-14 against various aspects of IR injury in vitro.

Long Non-coding RNAMALAT1 Knockdown Alleviates Cerebral Ischemia/Reperfusion Injury of Rats Through Regulating the miR-375/PDE4D Axis.

Objectives: Cerebral ischemic/reperfusion injury (CI/RI) is the clinical manifestation of cerebral ischemic stroke, which severely affects the health and life of the patients. We aimed to investigate the regulatory mechanism of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on CI/RI in this study. Methods: The expression of lncRNA MALAT1 and miR-375 was detected by qRT-PCR. MTT was utilized to measure the viability of PC-12 cells. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and reactive oxygen species (ROS) were detected by LDH assay, SOD assay, and ROS assay, respectively. The apoptosis rate of PC-12 cells was measured by flow cytometry analysis. Through enzyme-linked immunosorbent assay, the levels of NF-α, IL-1ß, and IL-6 were determined. The interactions between miR-375 and MALAT1/PDE4D were predicted by Starbase/Targetscan software and verified by the dual-luciferase reporter assay. Western blot assay was performed to determine the protein expression of Bcl-2, Caspase-3, and PDE4D. Results: LncRNA MALAT1 expression was highly upregulated in the middle cerebral artery occlusion (MCAO)/reperfusion (R) model of rats. Both MALAT1 downregulation and miR-375 upregulation reversed the inhibitory effect of oxygen and glucose deprivation (OGD)/R on cell viability and the promoting effects on LDH level, cell apoptosis, and inflammatory factors levels. MALAT1 targeted miR-375, whereas miR-375 targeted PDE4D. Overexpression of miR-375 attenuated OGD/R-induced injury in PC-12 cells by targeting PDE4D. Both the low expression of miR-375 and high expression of PDE4D reversed the promoting effect of MALAT1 knockdown on SOD level and the inhibitory effects on ROS level, inflammatory factor levels, and cell apoptosis. Conclusion: Suppression of MALAT1 alleviates CI/RI of rats through regulating the miR-375/PDE4D axis. This study provides a possible therapeutic strategy for human CI/RI in clinic.

Human umbilical vein-derived dopaminergic-like cell transplantation with nerve growth factor ameliorates motor dysfunction in a rat model of Parkinson's disease.

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.