Analysis of surgical treatment of cervical spondylotic amyotrophy.

Background: Cervical spondylotic amyotrophy (CSA) is a special type of cervical spondylosis based on cervical degeneration, which is mainly manifested by weakness and atrophy of upper limb muscles without obvious sensory impairment. Various diagnostic and treatment strategies used; however, discrepancies exist. We tried to discuss diagnosing and treating CSA. Methods: 15 patients with CSA were diagnosed in the Orthopedics Department of the First Affiliated Hospital of Zhengzhou University, aged 42-70 years old. The duration of preoperative symptoms of amyotrophy was 6 to 240 months. 12 patients received surgical treatment, and 3 patients received conservative treatment. The patients were divided into two groups according to the site of preoperative amyotrophy. The manual muscle test was used to evaluate the patients' muscle strength pre-and postoperatively. Results: During postoperative follow-up, the muscle strength of 12 patients improved to different degrees compared to before surgery. The improvement effect was excellent in 2 cases, good in 6, and moderate in 4. There was no decrease in postoperative muscle strength compared with that before surgery. The satisfaction rate of the effect was 66.7%. The two groups had no statistically significant difference in preoperative muscle strength. The postoperative muscle strength of the proximal group was significantly better than that of the distal group. Conclusion: The surgical effect of CSA of the proximal type is significantly better than that of the distal type. The recovery effect of amyotrophy after surgery for distal type CSA is poor; thus, surgical treatment should be carefully considered.

Surgical treatment of mixed cervical spondylosis with spontaneous cerebrospinal fluid leakage: A case report.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks associated with cervical spondylosis are rare. To our knowledge, only a few cases have been reported in which treatment is challenging and varies from case to case. Here, we review the literature and describe the surgical treatment of a 70-year-old woman who presented with a CSF leak due to a cervical spine spur. CASE SUMMARY: A 70-year-old female patient who was treated for a cerebral infarction, presented with complains of weakness in the right lower extremity and a feeling of stepping on cotton. The patient underwent regular neck massage and presented with neck and right shoulder pain radiating to the right upper extremity one-month ago. Magnetic resonance imaging showed a strip of leaking cerebrospinal fluid posterior to the C1-4 vertebrae, and computed tomography showed a "sickle-shaped" disc prolapse with calcification in C4/5. We chose to perform an anterior cervical discectomy. When the prolapsed C4/5 disc was scraped, clear fluid leakage was observed, and exploration revealed a 1 mm diameter rupture in the anterior aspect of the dura mater, which was compressed continuously with cotton patties, with no significant cerebrospinal fluid leakage after 1 h. CONCLUSION: Three months after surgery, the patient was asymptomatic and follow-up imaging demonstrated complete resolution.

Cervical Spondylotic Amyotrophy Initially Misdiagnosed as Amyotrophic Lateral Sclerosis.

A 63-year-old man diagnosed with mixed-type cervical spondylotic amyotrophy exhibited severe atrophy in the right biceps brachii, teres major, and intrinsic hand muscles, resulting in level 3 muscle weakness. Magnetic resonance imaging showed symmetrical high signal, also referred to as the snake eye sign. Previously, he was erroneously diagnosed with amyotrophic lateral sclerosis. He had undergone anterior cervical surgery 7 years prior. At present, his right upper limb muscles display minimal atrophy compared with the left, with muscle strength nearing level 4, which is considered normal. We believe that prompt surgical intervention on diagnosis of cervical spondylotic amyotrophy, along with comprehensive postsurgery rehabilitation, can halt further deterioration of the condition and accelerate recovery.

Identification of INSRR as an immune-related gene in the tumor microenvironment of glioblastoma by integrated bioinformatics analysis.

Gliomas are the most common malignant tumors in the central nervous system. The tumor microenvironment (TME) plays a crucial role in tumor proliferation, invasion, angiogenesis, and immune escape. However, little is known about TME in gliomas. The purpose of this study was to explore the biomarkers associated with TME in glioblastoma (GBM) to predict immunotherapy effectiveness and prognosis in patients. Based on RNA-seq transcriptome data and clinical features of 1222 samples (113 normal samples and 1109 tumor samples) in The Cancer Genome Atlas (TCGA) database, the ImmuneScore, StromalScore, and ESTIMATEScore were calculated by ESTIMATE algorithm. The differentially expressed genes (DEGs) and differentially mutated genes (DMGs) were determined in the TCGA GBM cohort. Furthermore, gene set enrichment analysis (GSEA) was used to investigate the enrichment pathways of INSRR genes with abnormal expression. The proportion of tumor-infiltrating immune cells (TIICs) was evaluated by CIBERSORT. Frequent mutations of TP53, EGFR, and PTEN occurred in high and low immune scores. The cross-analysis of DEGs and DMGs revealed that INSRR was an immune-related biomarker in the TCGA GBM cohort. According to GSEA, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway with INSRR abnormal expression were IgA-produced intestinal immune network and Alzheimer's disease, oxidative phosphorylation, and Parkinson's disease, respectively. Additionally, INSRR expression was correlated with dendritic cells activated, dendritic cells resting, T cells CD8, and T cell gamma delta. INSRR is associated with the immune microenvironment in GBM and is used as a biomarker to predict immune invasion.

Pulsed Electromagnetic Fields Protect Against Brain Ischemia by Modulating the Astrocytic Cholinergic Anti-inflammatory Pathway.

Neuroinflammation is one of the most important pathological processes following brain ischemia. Pulsed electromagnetic fields (PEMFs) protect against brain ischemia, but their role in regulating neuroinflammation remains unclear. In the present study, we investigated the biological effects of PEMF exposure on brain ischemia-induced neuroinflammation through the astrocytic cholinergic anti-inflammatory pathway. PEMF exposure reduced the activation of astrocytes and neuroinflammation following brain ischemia by directly modulating astrocytic injury and inflammatory cytokine release. Inhibition of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) by a specific antagonist reversed the regulatory effects of PEMF on astrocytes. Furthermore, negative regulation of signal transducer and activator of transcription 3 (STAT3) by α7nAChR was found to be an important downstream mechanism through which PEMF regulates astrocyte-related neuroinflammation. PEMF suppressed STAT3 phosphorylation and nuclear translocation by activating α7nAChR. These results demonstrate that PEMF exerts anti-inflammatory effects in the context of brain ischemia by modulating astrocytic α7nAChR/STAT3 signaling.

The role of s-palmitoylation in neurological diseases: implication for zDHHC family.

S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer's disease), HD (Huntington's disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

Identification of a Fibroblast-Related Prognostic Model in Glioma Based on Bioinformatics Methods.

BACKGROUND: Glioma is the most common primary tumor of the central nervous system with a high lethality rate. This study aims to mine fibroblast-related genes with prognostic value and construct a corresponding prognostic model. METHODS: A glioma-related TCGA (The Cancer Genome Atlas) cohort and a CGGA (Chinese Glioma Genome Atlas) cohort were incorporated into this study. Variance expression profiling was executed via the "limma" R package. The "clusterProfiler" R package was applied to perform a GO (Gene Ontology) analysis. The Kaplan-Meier (K-M) curve, LASSO regression analysis, and Cox analyses were implemented to determine the prognostic genes. A fibroblast-related risk model was created and affirmed by independent cohorts. We derived enriched pathways between the fibroblast-related high- and low-risk subgroups using gene set variation analysis (GSEA). The immune infiltration cell and the stromal cell were calculated using the microenvironment cell populations-counter (MCP-counter) method, and the immunotherapy response was assessed with the SubMap algorithm. The chemotherapy sensitivity was estimated using the "pRRophetic" R package. RESULTS: A total of 93 differentially expressed fibroblast-related genes (DEFRGs) were uncovered in glioma. Seven prognostic genes were filtered out to create a fibroblast-related gene signature in the TCGA-glioma cohort training set. We then affirmed the fibroblast-related risk model via TCGA-glioma cohort and CGGA-glioma cohort testing sets. The Cox regression analysis proved that the fibroblast-related risk score was an independent prognostic predictor in prediction of the overall survival of glioma patients. The fibroblast-related gene signature revealed by the GSEA was applicable to the immune-relevant pathways. The MCP-counter algorithm results pointed to significant distinctions in the tumor microenvironment between fibroblast-related high- and low-risk subgroups. The SubMap analysis proved that the fibroblast-related risk score could predict the clinical sensitivity of immunotherapy. The chemotherapy sensitivity analysis indicated that low-risk patients were more sensitive to multiple chemotherapeutic drugs. CONCLUSION: Our study identified prognostic fibroblast-related genes and generated a novel risk signature that could evaluate the prognosis of glioma and offer a theoretical basis for clinical glioma therapy.

A systematic review and meta-analysis of surgeries performed for cerebral cavernous malformation-related epilepsy in pediatric patients.

Background: The clinical benefit of surgery for the treatment of cerebral cavernous malformation (CCM)-related epilepsy in pediatric patients is still controversial. Although surgical treatment of CCM-related epilepsy in children is widely recognized, the clinical benefits of controlling the seizure rate must be balanced against the risk of leading to perioperative morbidity. Methods: We conducted a comprehensive search to identify relevant studies via Ovid Medline, Web of Science and PubMed (January 1995-June 2020). The following search terms were used: "hemangioma, cavernous, central nervous system," "brain cavernous hemangioma," "cerebral cavernous hemangioma," "CCM," "epilepsy," and "seizures." The seizure control rate and the risk of postoperative adverse outcomes along with their 95% confidence intervals (CIs) were calculated. Results: A total of 216 patients across 10 studies were included in meta-analysis. The results showed that the control rate of epilepsy was 88% (95% CI: 76-95%). Four percent (95% CI: 2-10%) of the patients experienced temporary symptomatic adverse effects following surgical resection, and 3% (95% CI: 0-26%) of the patients developed permanent symptomatic adverse effects in the long-term follow-up after surgical excision of the CCMs. None of the patients died as a result of the CCMs or surgical treatment. Conclusion: Surgery is an effective and safe treatment for CCM -related epilepsy in pediatric patients with a low risk of postoperative complications and death.

Top-down stepwise refinement identifies coding and noncoding RNA-associated epigenetic regulatory maps in malignant glioma.

With the emergence of the molecular era and retreat of the histology epoch in malignant glioma, it is becoming increasingly necessary to research diagnostic/prognostic/therapeutic biomarkers and their related regulatory mechanisms. While accumulating studies have investigated coding gene-associated biomarkers in malignant glioma, research on comprehensive coding and noncoding RNA-associated biomarkers is lacking. Furthermore, few studies have illustrated the cross-talk signalling pathways among these biomarkers and mechanisms in detail. Here, we identified DEGs and ceRNA networks in malignant glioma and then constructed Cox/Lasso regression models to further identify the most valuable genes through stepwise refinement. Top-down comprehensive integrated analysis, including functional enrichment, SNV, immune infiltration, transcription factor binding site, and molecular docking analyses, further revealed the regulatory maps among these genes. The results revealed a novel and accurate model (AUC of 0.91 and C-index of 0.84 in the whole malignant gliomas, AUC of 0.90 and C-index of 0.86 in LGG, and AUC of 0.75 and C-index of 0.69 in GBM) that includes twelve ncRNAs, 1 miRNA and 6 coding genes. Stepwise logical reasoning based on top-down comprehensive integrated analysis and references revealed cross-talk signalling pathways among these genes that were correlated with the circadian rhythm, tumour immune microenvironment and cellular senescence pathways. In conclusion, our work reveals a novel model where the newly identified biomarkers may contribute to a precise diagnosis/prognosis and subclassification of malignant glioma, and the identified cross-talk signalling pathways would help to illustrate the noncoding RNA-associated epigenetic regulatory mechanisms of glioma tumorigenesis and aid in targeted therapy.

Alpha/Beta-Hydrolase Domain-Containing 6: Signaling and Function in the Central Nervous System.

Endocannabinoid (eCB) signaling plays an important role in the central nervous system (CNS). α/ß-Hydrolase domain-containing 6 (ABHD6) is a transmembrane serine hydrolase that hydrolyzes monoacylglycerol (MAG) lipids such as endocannabinoid 2-arachidonoyl glycerol (2-AG). ABHD6 participates in neurotransmission, inflammation, brain energy metabolism, tumorigenesis and other biological processes and is a potential therapeutic target for various neurological diseases, such as traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, mental illness, and pain. This review summarizes the molecular mechanisms of action and biological functions of ABHD6, particularly its mechanism of action in the pathogenesis of neurological diseases, and provides a theoretical basis for new pharmacological interventions via targeting of ABHD6.

Microsurgery vs. Gamma Knife Radiosurgery for the Treatment of Brainstem Cavernous Malformations: A Systematic Review and Meta-Analysis.

Background: Brainstem cavernous malformations (BSCMs) are a subset of cerebral cavernous malformations with precarious locations and potentially devastating clinical courses. The effects and outcomes of treating BSCMs by microsurgery or gamma knife radiosurgery (GKRS) vary across studies. Methods: We searched the Medline, Web of Science, The Cochrane Library, PubMed, and China Biology Medicine disc databases for original articles published in peer-reviewed journals of cohort studies reporting on 20 or more patients of any age with BSCMs with at least 80% completeness of follow-up. Results: We included 43 cohorts involving 2,492 patients. Both microsurgery (RR = 0.04, 95% CI 0.01-0.16, P < 0.01) and GKRS (RR = 0.11, 95% CI 0.08-0.16, P < 0.01) demonstrated great efficacy in reducing the rehemorrhage rate after treatment for BSCMs. The incidence rates of composite outcomes were 19.8 (95% CI 16.8-22.8) and 15.7 (95% CI 11.7-19.6) after neurosurgery and radiosurgery, respectively. In addition, we found statistically significant differences in the median numbers of patients between neurosurgical and radiosurgical cohorts in terms of symptomatic intracranial hemorrhage (ICH; neurosurgical cohorts: median 0, range 0-33; radiosurgical cohorts: median 4, range 1-14; P < 0.05) and persistent focal neurological deficit (FND; neurosurgical cohorts: median 5, range 0-140; radiosurgical cohorts: median 1, range 0-3; P < 0.05). Conclusions: The reported effects of treating BSCMs by microsurgery or GKRS are favorable for reducing recurrent hemorrhage from BSCMs. Patients in the neurosurgery cohort had a lower incidence of symptomatic ICH, while patients in the radiosurgical cohort had a lower incidence of persistent FND.

Treatment of Cerebral Cavernous Malformations Presenting With Seizures: A Systematic Review and Meta-Analysis.

Background: Cerebral cavernous malformations (CCMs) presenting with seizures can be treated with neurosurgery or radiosurgery, but the ideal treatment remains unclear. Currently, there is no adequate randomized controlled trial comparing surgical treatment and radiotherapy for epileptogenic CCMs. Therefore, we conducted a systematic review and meta-analysis of available data from published literature to compare the efficacy and safety of neurosurgery and radiosurgery for epileptogenic CCMs. Methods: We performed a comprehensive search of the Ovid MEDLINE, Web of Science, PubMed, China Biological Medicine and China National Knowledge Infrastructure databases for studies published between January 1994 and October 2019. The search terms were as follows: "epilepsy," "seizures," "brain cavernous hemangioma," "cerebral cavernous malformation," "cerebral cavernous hemangioma," "hemangioma, cavernous, central nervous system." Two researchers independently extracted the data and reviewed all the articles. We compared the advantages and disadvantages of the two treatments. Results: A total of 45 studies were included in our analysis. Overall, the seizure control rate was 79% (95% CI: 75-83%) for neurosurgery and 49% (95% CI: 38-59%) for radiosurgery. In the neurosurgery studies, 4.4% of patients experienced permanent morbidity, while no patients in the radiotherapy studies had permanent morbidity. In addition, the results of subgroup analysis showed that ethnicity, CCMs location and average lesion number are likely significant factors influencing the seizure outcome following treatment. Conclusions: The epilepsy control rate after neurosurgery was higher than that after radiosurgery, but neurosurgery also had a relatively higher rate of permanent morbidity.