Deep Residual Learning-Based Classification with Identification of Incorrect Predictions and Quantification of Cellularity and Nuclear Morphological Features in Digital Pathological Images of Common Astrocytic Tumors.

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.

Management of Idiopathic Intracranial Hypertension: A Case Report.

ABSTRACT: BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by elevated intracranial pressure, affecting predominantly obese women of childbearing age. Early recognition and comprehensive management are vital for preventing severe complications, particularly vision loss. METHODS: This study reports a case of a 27-year-old woman who presented with chronic headaches and blurred vision. Notable findings included headaches that were intensified upon waking and exacerbated by activities that elevated intracranial pressure. The patient also reported nausea, vomiting, transient visual obscurations, and pulsatile tinnitus. After a clinical examination, she was given a diagnosis of IIH. RESULTS: The patient underwent a lumbar-peritoneal shunt procedure to alleviate her symptoms in conjunction with medication treatment. This case study highlights the importance of a multidisciplinary approach in diagnosing and treating IIH. In particular, weight management emerged as a crucial preventive measure against IIH recurrence. CONCLUSION: A multidisciplinary team strategy can enhance outcomes and quality of life, accentuating the need for continued research into IIH recurrence, treatments, and wider implications.

Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

Neuromodulation techniques in poststroke motor impairment recovery: Efficacy, challenges, and future directions.

Cerebrovascular accidents, also known as strokes, represent a major global public health challenge and contribute to substantial mortality, disability, and socioeconomic burden. Multidisciplinary approaches for poststroke therapies are crucial for recovering lost functions and adapting to new limitations. This review discusses the potential of neuromodulation techniques, repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, spinal cord stimulation (SCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), as innovative strategies for facilitating poststroke recovery. Neuromodulation is an emerging adjunct to conventional therapies that target neural plasticity to restore lost function and compensate for damaged brain areas. The techniques discussed in this review have different efficacies in enhancing neural plasticity, optimizing motor recovery, and mitigating poststroke impairments. Specifically, rTMS has shown significant promise in enhancing motor function, whereas SCS has shown potential in improving limb movement and reducing disability. Similarly, VNS, typically used to treat epilepsy, has shown promise in enhancing poststroke motor recovery, while DBS may be used to improve poststroke motor recovery and symptom mitigation. Further studies with standardized protocols are warranted to elucidate the efficacy of these methods and integrate them into mainstream clinical practice to optimize poststroke care.

Cerebrospinal fluid shunt surgery reduces the risk of developing dementia and Alzheimer's disease in patients with idiopathic normal pressure hydrocephalus: a nationwide population-based propensity-weighted cohort study.

BACKGROUND: Patients with idiopathic normal-pressure hydrocephalus (iNPH) are predisposed to developing dementing disorders. Cerebrospinal fluid (CSF) shunt implantation is a treatment used to improve the motor and cognitive disabilities of these patients; however, its effect on the risk of developing dementing disorders remains unclear. We conducted a population-based propensity-weighted cohort study to investigate whether CSF shunt surgery may reduce the risk of subsequently developing dementia, Alzheimer's disease (AD), and vascular dementia in iNPH patients. METHODS: Patients aged ≥ 60 years who were diagnosed with iNPH (n = 2053) between January 2001 and June 2018 were identified from the Taiwan National Health Insurance Research Database. Various demographic characteristics (age, sex, and monthly income) and clinical data (incidence year, comorbidities, and Charlson comorbidity index) were collected and divided into the shunt surgery group (SSG) and the non-shunt surgery group (NSSG). Stabilized inverse probability of treatment weighting by using the propensity score was performed to achieve a balanced distribution of confounders across the two study groups. The cumulative incidence rate and risk of dementing disorders were estimated during a 16-year follow-up period. RESULTS: After weighting, the data of 375.0 patients in SSG and 1677.4 patients in NSSG were analyzed. Kaplan-Meier curve analysis indicated that the cumulative incidence rate of AD (p = 0.009), but not dementia (p = 0.241) and vascular dementia (p = 0.761), in SSG was significantly lower than that in NSSG over the 16-year follow-up period. Cox proportional hazards regression analysis revealed that SSG had a reduced hazard ratio (HR) for developing AD [HR (95% CI) 0.17 (0.04-0.69)], but not for dementia [HR (95% CI) 0.83 (0.61-1.12)] and vascular dementia [HR (95% CI) 1.18 (0.44-3.16)], compared with NSSG. Further Fine-Gray hazard regression analysis with death as a competing event demonstrated that SSG had a reduced subdistribution HR (sHR) for developing dementia [sHR (95% CI) 0.74 (0.55-0.99)] and AD [sHR (95% CI) 0.15 (0.04-0.61)], but not for vascular dementia [sHR (95% CI) 1.07 (0.40-2.86)]. CONCLUSION: CSF shunt surgery is associated with reduced risks of the subsequent development of dementia and AD in iNPH patients. Our findings may provide valuable information for assessing the benefit-to-risk profile of CSF shunt surgery.

Successful Ultrasound-Guided Superficial Cervical Plexus Block Treatment for Head and Neck Pain with an Unusually Delayed Onset Following Ventriculoperitoneal Shunt: A Case Report.

Background and Objectives: Ventriculoperitoneal (VP) shunt placement is the most common treatment for cerebrospinal fluid diversion. Head and neck pain occurring after a long period following VP shunt insertion is rarely reported. Here, we present a rare case of head and neck pain occurring 2 years after surgery due to irritation of the superficial cervical plexus by the VP shunt. Case Description: A 46-year-old female patient received VP shunt placement surgery. Two years after the surgery, she experienced a left temporal headache with neck pain on the left side, which extended to the left para-auricular and fascial region. Ultrasound (US) scanning revealed that the VP shunt passed within the superficial cervical fascia and through the left sternocleidomastoid muscle (SCM). Additionally, friction of the branches of the superficial cervical plexus and of the greater auricular and lesser occipital nerves caused by the VP shunt was found underneath the lateral border of the SCM. Subsequently, the blocking and hydro-release of the left superficial cervical plexus were performed. After four series of treatments, the patient's head and neck pain vanished, and the frequency of the headaches was substantially reduced. The patient was regularly followed-up in the outpatient department of neurosurgery. Conclusions: Head and neck pain caused by the malpositioning of a VP shunt catheter with an unusually delayed onset is a rarely reported complication and could be easily neglected. Patients with head and neck pain following VP shunt insertion should be checked using US scanning to identify the potential origin of the pain and receive adequate treatments. Intraoperative US-guided tunnelling is suggested to avoid the malpositioning of the VP shunt catheter.

Network pharmacology implicates traditional Chinese medicine in regulating systemic homeostasis to benefit Alzheimer's disease.

Traditional Chinese medicine (TCM) has the characteristics of multi-component, multi-target, and biological systems coordination, which meet the criteria of the network pharmacological application. Therefore, using network pharmacology to discover the relationship between TCM, diseases, and cellular responses is easily achievable. Aging-induced imbalanced homeostasis is a risk factor for Alzheimer's disease (AD), a neuronal disease regulated by multiple genes. Meta-analysis of TCM in metabolic regulation to improve symptoms of AD helps understand the pharmacological effects. The drug targets of TCM can be investigated using a holistic network pharmacology approach to find potential modulators involved in AD-related metabolic pathways. Based on the theoretical prediction of TCM for AD, experimental validation is needed to develop pure compounds for specific treatments.

Potential benefits of spinal cord stimulation treatment on quality of life for paralyzed patients with spinal cord injury.

Spinal cord injury (SCI) is a severe central nervous system injury that can cause sensory or motor dysfunction. Although mortality rates for people with spinal cord injuries have dropped dramatically with advances in medicine, chronic long-term sequelae after SCI persist. The most bothersome problems reported by patients include pain, spasticity, urinary dysfunction, and loss of motor function. Thus, quality of life (QoL) is an essential issue in chronic SCI. Spinal cord stimulation (SCS) applies an adjustable, nondamaging electrical pulse that can reduce uncomfortable comorbidities and improve mobility, thus enhancing the QoL of patients with SCI. This review summarizes pivotal breakthroughs from SCS for individual clinical impairment from SCI. We conclude that careful evaluation of SCS can help improve neuropathic pain, spasms, motor symptoms, and voiding dysfunction in patients with SCI, thus improving QoL.

The emergent neurosurgical outcome of spontaneous intracranial hemorrhage in patients with chronic liver disease.

Objectives: The influence of chronic liver disease (CLD) on emergent neurosurgical outcomes in patients with spontaneous intracerebral hemorrhage (ICH) remains unclear. CLD is usually associated with coagulopathy and thrombocytopenia, which contribute to a high rebleeding rate and poor prognosis after surgery. This study aimed to confirm the outcomes of spontaneous intracranial hemorrhage in patients with CLD after emergent neurosurgery. Materials and Methods: We reviewed the medical records of all patients with spontaneous ICH from February 2017 to February 2018 at the Buddhist Tzu Chi Hospital, Hualien, Taiwan. This study was approved by the Review Ethical Committee/Institutional Board Review of Hualien Buddhist Tzu Chi Hospital (IRB111-051-B). Patients with aneurysmal subarachnoid hemorrhage, tumors, arteriovenous malformations, and those younger than 18 years were excluded. Duplicate electrode medical records were also removed. Results: Among the 117 enrolled patients, 29 had CLD and 88 did not. There were no significant differences in essential characteristics, comorbidities, biochemical profile, Glasgow coma scale (GCS) score at admission, or ICH sites. The length of hospital stay (LOS) and length of intensive care unit stay (LOICUS) are significantly longer in the CLD group (LOS: 20.8 vs. 13.5 days, P = 0.012; LOICUS: 11 vs. 5 days, P = 0.007). There was no significant difference in the mortality rate between the groups (31.8% vs. 28.4%, P = 0.655). The Wilcoxon rank-sum test for liver and coagulation profiles between survivors and the deceased revealed significant differences in the international normalized ratio (P = 0.02), including low platelet counts (P = 0.03) between survivors and the deceased. A multivariate analysis of mortality found that every 1 mL increase in ICH at admission increased the mortality rate by 3.9%, and every reduction in GCS at admission increased the mortality rate by 30.7%. In our subgroup analysis, we found that the length of ICU stay and LOS are significantly longer in patients with CLD who underwent emergent neurosurgery: 17.7 ± 9.9 days versus 7.59 ± 6.68 days, P = 0.002, and 27.1 ± 7.3 days versus 16.36 ± 9.08 days, P = 0.003, respectively. Conclusions: From our study's perspective, emergent neurosurgery is encouraged. However, there were more prolonged ICU and hospital stays. The mortality rate of patients with CLD who underwent emergent neurosurgery was not higher than that of patients without CLD.

Experimental animal models and evaluation techniques in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal type of cerebral stroke without effective therapy. Although clinical trials with various surgeries have been conducted, none have improved clinical outcomes compared to the current medical management for ICH. Several ICH animal models, including autologous blood injection, collagenase injection, thrombin injection, and microballoon inflation methods, have been developed to elucidate the underlying mechanisms of ICH-induced brain injury. These models could also be used for discovering new therapy for ICH preclinically. We summarize the existing ICH animal models and the evaluation parameters used to measure the disease outcomes. We conclude that these models, resembling the different aspects of ICH pathogenesis, have their advantages and disadvantages. None of the current models closely represent the severity of ICH seen in clinical settings. More appropriate models are needed to streamline ICH's clinical outcomes and be used for validating newly developed treatment protocols.

Rodent models of senile normal-pressure hydrocephalus.

Cerebrospinal fluid (CSF) and its drainage are crucial in clearing metabolic waste and maintaining the microenvironment of the central nervous system for proper functioning. Normal-pressure hydrocephalus (NPH) is a serious neurological disorder of the elderly with obstruction of CSF flow outside the cerebral ventricles, causing ventriculomegaly. The stasis of CSF in NPH compromises brain functioning. Although treatable, often with shunt implantation for drainage, the outcome depends highly on early diagnosis, which, however, is challenging. The initial symptoms of NPH are hard to be aware of and the complete symptoms overlap with those of other neurological diseases. Ventriculomegaly is not specific to NPH as well. The lack of knowledge on the initial stages in its development and throughout its progression further deters early diagnosis. Thus, we are in dire need for an appropriate animal model for researches into a more thorough understanding of its development and pathophysiology so that we can enhance the diagnosis and therapeutic strategies to improve the prognosis of NPH following treatment. With this, we review the few currently available experimental rodent NPH models for these animals are smaller in sizes, easier in maintenance, and having a rapid life cycle. Among these, a parietal convexity subarachnoid space kaolin injection adult rat model appears promising as it shows a slow onset of ventriculomegaly in association with cognitive and motor disabilities resembling the elderly NPH in humans.

Long-Term Effects of Subthalamic Stimulation on Motor Symptoms and Quality of Life in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting both motor functions and quality of life (QoL). This study compared motor symptoms and QoL in patients with PD before and at 1 and 5 years after subthalamic nucleus deep brain stimulation (STN-DBS) surgery in Taiwan. This study included 53 patients with PD undergoing STN-DBS. The motor symptoms improved by 39.71 ± 26.52% and 18.83 ± 37.15% in the Unified Parkinson's Disease Rating Scale (UPDRS) part II and by 36.83 ± 22.51% and 22.75 ± 36.32% in the UPDRS part III at 1 and 5 years after STN-DBS in the off-medication/on-stimulation state, respectively. The Hoehn and Yahr stage significantly improved at the 1-year follow-up but declined progressively and returned to the baseline stage 5 years post-surgery. The Schwab and England Activities of Daily Living improved and sustained for 5 years following STN-DBS. Levodopa equivalent daily dose decreased by 35.32 ± 35.87% and 15.26 ± 65.76% at 1 and 5 years post-surgery, respectively. The QoL revealed significant improvement at 1 year post-surgery; however, patients regressed to near baseline levels 5 years post-surgery. The long-term effects of STN-DBS on motor symptoms were maintained over 5 years after STN-DBS surgery. At the same time, STN-DBS had no long-lasting effect on QoL. The study findings will enable clinicians to become more aware of visible and invisible manifestations of PD.

Effectiveness and safety of ventriculoperitoneal shunt versus lumboperitoneal shunt for communicating hydrocephalus: A systematic review and meta-analysis with trial sequential analysis.

INTRODUCTION: The current standard surgical treatment for cerebrospinal fluid diversion is a ventriculoperitoneal shunt (VPS) implantation. Lumboperitoneal shunts (LPS) are an alternative treatment for communicating hydrocephalus. Prior studies comparing these two included a limited number of participants. METHODS: We performed a meta-analysis determined the treatment failure, complications and effectiveness of lumboperitoneal shunt for communicating hydrocephalus. We reviewed studies with clinical and imaging diagnoses of communicating hydrocephalus, all causes and subtypes of communicating hydrocephalus, and studies that analyzed the primary and secondary outcomes listed below. We included randomized controlled trials (RCTs), non-RCTs and retrospective studies. We performed the meta-analysis in R, using a random-effects model and reporting 95% confidence intervals. RESULTS: Data from 25 studies, including 3654 patients, were analyzed. The total complication rates were 12.98% (188/1448) for lumboperitoneal shunt and 23.80% (398/1672) for ventriculoperitoneal shunt. The odds ratio for lumboperitoneal shunt versus ventriculoperitoneal shunt complication rates was 0.29 (95% CI 0.19 to 0.45, p < 0.0001), and the I2 was 72%. The shunt obstruction/malfunction rate was 3.99% (48/1204) for lumboperitoneal shunt and 8.31% (115/1384) for ventriculoperitoneal shunt (Odds ratio 0.54, 95% CI 0.37 to 0.79, p = 0.002, I2  = 0%). Based on the Modified Rankin Scale score, there were no differences in effectiveness between lumboperitoneal shunt and ventriculoperitoneal shunt. Nevertheless, lumboperitoneal shunt improved radiological outcomes. CONCLUSIONS: This analysis demonstrated that lumboperitoneal shunt is a safe and equally effective choice for treating communicating hydrocephalus. More studies are needed to confirm the safety of lumboperitoneal shunt.

Lumbar-peritoneal shunt for idiopathic normal pressure hydrocephalus and secondary normal pressure hydrocephalus.

Objectives: Normal-pressure hydrocephalus is a clinical syndrome consisting of dilated cerebral ventricles with the clinical triad of gait disturbance, cognitive impairment and/or urinary dysfunction. Lumbar-peritoneal (LP) shunt could improve idiopathic normal pressure hydrocephalus (iNPH) while its effectiveness on secondary NPH (sNPH) is elusive. We compared the clinical results of the patients who received LP shunt surgery between iNPH and sNPH. Materials and Methods: We retrospectively analyzed the patients who received LP shunt surgery in a single center from January 1, 2017, to June 30, 2017. Patients selected for LP shunt placement had at least two of three cardinal symptoms of iNPH. The symptoms should persist for more than 3 months with compatible brain magnetic resonance imaging findings. All patients were followed up with iNPH grading scale (iNPHGS) and Modified Rankin Scale (MRS) for evaluation. Results: Thirty-three patients (23 male and 10 female patients) with mean age 76-year-old completed follow-up in this study, and 17 patients received lumbar drainage tests and intracranial pressure measurements. Both iNPH (n = 22) and sNPH (n = 11) groups did not have major complications such as infection, nerve root injury, or shunt failure. Both groups have significant improvement in iNPHGS and MRS. Interestingly, we found the correlation between both opening intracranial pressure and pressure gradient difference to the improvement percentage from LP shunt. Conclusion: The safety and effectiveness for sNPH patients who received LP shunt placement are equivalent to the iNPH patients. Lumbar drainage test provides prerequisite outcome prediction and should be considered to identify NPH patients planned to receive LP shunt.

Diagnosis and treatment for normal pressure hydrocephalus: From biomarkers identification to outcome improvement with combination therapy.

Idiopathic normal pressure hydrocephalus (iNPH), albeit characterized by gait impairment, cognitive decline, and urinary incontinence, in clinical diagnosis is poorly defined and is usually coexistent with other neurodegenerative diseases. Surgical operation with shunt implantation is the primary treatment but leads to variable outcomes. Recent studies demonstrated that the pathophysiology of iNPH may include both preceding cerebrovascular events and concomitant Alzheimer's dementia or dopaminergic degenerative neuropathology in patients' brain. These factors not only help differentiate iNPH from its mimics but also associated with the extent of symptomatic improvement after surgery. In this review, we examined these mechanisms underlying the development of iNPH and the beneficial effects of shunt surgery. Furthermore, the increasing identification and importance of biomarkers from cerebrospinal fluid and neural imaging could also predict the responsiveness of treatment. Finally, these progresses suggest that combination therapy would be necessary for iNPH treatment in the future.

Intracerebral transplantation of autologous adipose-derived stem cells for chronic ischemic stroke: A phase I study.

Current therapy does not provide significant benefits for patients with chronic stroke. Pre-clinical studies suggested that autologous adipose-derived stem cells have benefits for the treatment of chronic stroke. This Phase I open-label study was conducted to demonstrate the safety and efficacy of autologous adipose-derived stem cells (GXNPC1) in chronic stroke. Three patients with chronic stroke were treated with stereotactic implantation of autologous adipose-derived stem cells (1 × 108 cells). The primary endpoints of safety evaluation included adverse events, over a 6 months post-implantation period. The secondary endpoints included improvements in neurological functions. Evolutional change of brain parenchyma was also followed with magnetic resonance imaging (MRI). All three participants improved significantly at 6 months follow-up. The extent of improvement from pre-treatment was: National Institutes of Health Stroke Scale improved 5-15 points, Barthel Index: 25-50 points, Berg balance scale 0-21 points and Fugl-Meyer modified sensation 3-28 points. All three patients had signal change along the implantation tract on MRI one month after surgery. There is no related safety issue through 6 months observation. Clinical measures of neurological symptoms of these patients with chronic stroke improved at 6 months without adverse effects after implantation of autologous adipose-derived stem cells (GXNPC1), which might be correlated with post-implantation changes on brain MRI. Clinical Trial Registration-URL: https://clinicaltrials.gov/ct2/show/NCT02813512?term=ADSC&cond=Stroke&cntry=TW&draw=2&rank=1 Unique identifier: NCT02813512.

Effect of deep brain stimulation on brain network and white matter integrity in Parkinson's disease.

AIMS: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS. METHODS: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics. RESULTS: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores. CONCLUSION: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.

Complete Restoration of Motor Function in Acute Cerebral Stroke Treated with Allogeneic Human Umbilical Cord Blood Monocytes: Preliminary Results of a phase I Clinical Trial.

Stem cell therapy has been explored for the treatment of cerebral stroke. Several types of stem cells have been investigated to ensure the safety and efficacy in clinical trials.Cryopreserved umbilical cord blood (UCB) mononuclear cells (MNCs) obtained from healthy donors have a more stabilized quality, thereby ensuring a successful therapy. A phase I study was conducted on patients aged 45-80 years who sustained acute ischemic stroke. An UCB unit was obtained from a public cord blood bank based on ABO/Rh blood type, HLA matching score (6/6), and cell dose (total MNC count of 0.5-5 × 107 cells/kg). In addition, to facilitate blood brain barrier penetration of UCB, 4 doses of 100 mL mannitol was administered intravenously after 30 min after UCB transplantation and every 4 h thereafter. The primary outcomes were the number of disease (GVHD) within 100 days after transfusion. The secondary outcomes were changes in the National Institutes of Health Stroke Scale (NIHSS), Barthel index, and Berg Balance Scale scores. A 46-year-old male patient with identical ABO/Rh blood type, HLA matching score of 6/6, and MNC count of 2.63 × 108 cells/kg was enrolled. The patient did not present with serious AEs or GVHD during the 12-month study period. The patient's NIHSS score decreased from 9 to 1. Moreover, the Berg Balance Scale score increased from 0 to 48 and the Barthel index score from 0 to 90. This preliminary study showed that an adult patient with hemiplegia due to ischemic stroke completely recovered within 12 months after receiving allogeneic UCB therapy.

Granulocyte Colony-Stimulating Factor for Treatment of Patients with Chronic Traumatic Brain Injury: A Preliminary Pre-Post Study.

Chronic traumatic brain injury (TBI) can cause permanent disability and thereby negatively affect patients, families, and society. Currently, there is no effective treatment for patients with chronic TBI. One possible option is granulocyte colony-stimulating factor (G-CSF), which has potential neuroregenerative and neuroprotective effects through its ability to mobilize hematopoietic stem cells and increase neurogenic growth factor levels. Previous studies have shown that G-CSF administration is safe for patients with neurological diseases such as stroke and dementia. The present study aimed to explore the safety and efficacy of G-CSF use in patients with chronic TBI. METHODS: 38 patients with chronic TBI were administered 3-day rounds of G-CSF (10 µg/kg per day) once a month for 6 months. These patients were clinically evaluated using the modified Rankin scale (mRS) and Karnofsky Performance Score (KPS). Laboratory measures of the leucocyte counts and differential count percentage were also assessed. RESULTS: At the 6-month follow-up, further assessment showed that patients tolerated the treatment well with only mild and transient side effects being observed. Further clinical evaluation showed significant improvements in mRS and KPS after G-CSF treatment. Laboratory results also confirmed the action of the medication, with increased leukocytosis and band forms. CONCLUSIONS: The results suggest that 6-month chronic G-CSF treatment is safe for patients with chronic TBI and may provide clinical benefits and neurological improvements. The adverse effects of the treatment, however, are transient and usually tolerable. Thus, these preliminary findings suggest that future clinical trials of G-CSF use in patients with chronic TBI are warranted.

Spinal cord stimulation for spinal cord injury patients with paralysis: To regain walking and dignity.

Spinal cord injury (SCI) usually leads to disconnection between traversing neuronal pathway. The impairment of neural circuitry and its ascending and descending pathway usually leave severe SCI patients with both motor disability and loss of sensory function. In addition to poor quality of life, SCI patients not only have disabling respiratory function, urinary retention, impaired sexual function, autonomic dysregulation but also medical refractory neuropathic pain in the long term. Some translational studies demonstrated that spinal networks possess a dynamic state of synaptic connection and excitability that can be facilitated by epidural spinal cord stimulation. In addition, preliminary human studies also confirmed that spinal cord stimulation enables stepping or standing in individuals with paraplegia as well. In this review, we examined the plausible interventional mechanisms underlying the effects of epidural spinal cord stimulation in animal studies. Following the success of translational research, chronic paralyzed subjects due to SCI, defined as motor complete status, regained their voluntary control and function of overground walking and even stepping for some. These progresses lead us into a new hope to help SCI patients to walk and regain their independent life again.