Telovelar vs. Transvermian approach for the fourth ventricle tumors: A systematic review and meta-analysis.

BACKGROUND: Tumors in the fourth ventricle can be critical due to the small size of the fourth ventricle, which causes symptoms to be detected even in the presence of lesser mass effects. A proper surgical approach to the fourth ventricle poses challenges due to its deep location and proximity to vital compartments within the brainstem. The two commonly used approaches to these tumors are the transvermian and telovelar approaches. METHODS: A comprehensive systematic study was conducted based on a literature search of the databases. All case controls, cohorts, and case series including patients with fourth ventricle tumors, who were operated on with either telovelar or transvermian approaches were considered eligible. The evaluated outcomes were comparative postoperative complications of the telovelar vs. transvermian approach. After screening and data extraction, a meta-analysis was performed whenever adequate quantitative data were available. RESULTS: Seven studies with a total number of 848 patients, discussed both telovelar and transvermian approaches, with comparative reporting of outcomes in each group. Postoperative outcomes including cranial nerve deficit, mutism, diplopia, CSF leak, need for CSF diversion, and postoperative gait disturbance were not significantly different between telovelar and transvermian approaches. CONCLUSION: Postoperative complications were not significantly different between telovelar and transvermian approaches. Moreover, it could be proposed that such complications would be more likely to be a multifactorial matter concerning the patient's clinical condition, tumor characteristics, and surgeon's experience, rather than the surgical approach alone.

Psychological and Psychiatric Aspects of Brain and Spinal Cord Tumors.

Central nervous system (CNS) tumors are mainly diagnosed by physical symptoms such as paralysis, visual field defect, seizure, and loss of consciousness. The psychological and psychiatric background of CNS tumors, whether in preoperative or postoperative period, has long been a neglected topic; however, lately, many authors and researchers have paid more attention to these manifestations. Neurocognition is a subset of parameters, including attention, memory, mood, emotions, language production, personality, executive function, problem-solving, calculation, and spatial cognition, making up the patient's cognitive performance. Also, it is worthy to say that neurocognition is considered a parameter of quality of life (QoL). Currently, we know that neurocognitive disorders are a group of symptoms presenting by the patients. These symptoms may be the first picture of CNS lesions, which result in incorrect treatment, a higher financial burden on the patient and health system, and finally, poorer QoL and performance scale if they are not diagnosed early. Psychological and psychiatric problems such as depression, anxiety, and phobia following the CNS tumors have two aspects. These may present before any treatment resulting from the tumoral mass effect, peritumoral edema, or cerebral tissue disruption due to the space-occupying lesion. On the other hand, we can see these features after a kind of therapy such as surgery, medical therapy, or adjuvant therapy. Sometimes, the CNS tumors lead to psychosocial complications postoperatively. Indeed, considering tumor surgery complications, some patients may find various degrees of deficits that make the patient isolated either socially or professionally. Obviously, the improvement rate and outcome of this specific situation depend on the mechanism of occurrence and its causes. For instance, postoperative symptom relief would be expected when the symptoms are related to the tumoral mass effect. Getting familiar with this constellation of the symptoms, realizing them, and then localizing them to the correct area of the CNS are very crucial. Accordingly, because of their importance in QoL, their influence on patient's survival even more than the extent of resection of the tumor, and somehow their ignorance, we will discuss different neurocognitive manifestations related to CNS tumors in this chapter.

Micro RNAs as a Diagnostic Marker between Glioma and Primary CNS Lymphoma: A Systematic Review.

Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL.

MGMT Gene rs1625649 Polymorphism in Iranian Patients with Brain Glioblastoma: A Case Control Study.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy.

Central nervous system hydatidosis around the world: a systematic review.

INTRODUCTION: Echinococcosis is a chronic disease caused by Echinococcus species. The central nervous system (CNS) hydatidosis is still a major concern, especially in endemic countries, due to non-specific features and late diagnosis and treatment. This study aimed to provide a systematic review to elucidate the epidemiology and clinical characteristics of CNS hydatidosis worldwide over the past decades. EVIDENCE ACQUISITION: PubMed, Scopus, EMBASE, Web of Science, Ovid, and Google Scholar were systematically searched. The gray literature and the references of included studies were searched as well. EVIDENCE SYNTHESIS: Our results showed that the CNS hydatid cyst was more prevalent in the male gender, and it is known as a recurrent disease with a rate of 26.5%. CNS hydatidosis was more common in the supratentorial region and was also significantly common in developing countries, including Türkiye and Iran. CONCLUSIONS: It was demonstrated that the disease would be more prevalent in developing countries. Also, there would be a trend toward a male predominance of CNS hydatid cyst, younger age involvement, and the recurrence rate of 25% in general. There is no consensus about chemotherapy unless in recurrent disease and the patients who experienced cyst rupture intraoperatively, recommended for a wide range of 3 to 12 months.

Brain and Spinal Cord Tumors Among the Life-Threatening Health Problems: An Introduction.

As one of the global concerns, cancers, including brain and spinal cord tumors, are responsible for mortalities and irreversible morbidities in the affected patients. Although advancements in molecular pathology and imaging of tumors may have influenced the incidence rate due to higher diagnosis in early stages, exposure to environmental risk factors could be another explanation for increased incidence of these tumors over the past decades. Similar to many other tumors, the CNS tumors begin in cellular dimension with activation of different molecular pathways. Several genetic, epigenetic, and immunologic pathways and processes are already discovered to play roles in pathophysiology of these tumors, which mostly will eventually become symptomatic. Each of these tumors may exhibit imaging characteristics, making it possible to list a series of differential diagnosis before histopathologic examination. Advances in molecular pathology have resulted in better understanding and categorization of CNS tumors, leading to better decision-making on the most appropriate therapeutic approach for each category, as well as proposing new therapeutic modalities to treat these tumors. As an introduction to the 2-volume book, this chapter addressed different types of human brain and spinal cord tumors based on the fifth version of WHO classification of CNS tumors.

The Epidemiology of Brain and Spinal Cord Tumors.

CNS tumors are a diverse group of neoplasms that emerge from a variety of different CNS cell types. These tumors may be benign, malignant, or borderline in nature. The majority of high grade glial tumors are fatal, with the exception of pilocytic astrocytoma. Primary malignant CNS tumors occur at a global annual rate of 2.1 to 5.8 per 100,000 persons. Males are more likely to develop malignant brain tumors than females, whereas benign meningiomas are more common in adult females. Additionally, gender inequalities in non-malignant tumors peak between the ages of 25 and 29 years. Only a small number of genetic variants have been associated with survival and prognosis. Notably, central nervous system (CNS) tumors exhibit significant age, gender, and race variation. Race is another factor that affects the incidence of brain and spinal cord tumors. Different races exhibit variation in terms of the prevalence of brain and CNS malignancies. This chapter discusses ongoing research on brain and spinal cord tumor epidemiology, as well as the associated risks and accompanied disorders.

Stem Cells and Targeted Gene Therapy in Brain and Spinal Cord Tumors.

The CNS tumors, in particular those with malignant characteristics, are prominent burdens around the world with high mortality and low cure rate. Given that, researchers were curious about novel treatments with promising effectiveness which resulted in shifting the dogmatism era of neurogenesis to the current concept of postnatal neurogenesis. Considering all existing stem cells, various strategies are available for treating CNS cancers, including hematopoietic stem cells transplantation, mesenchymal stem cells transplantation, neural stem cells (NSCs) transplantation, and using stem cells as genetic carriers called "suicide gene therapy". Despite some complications, this ongoing therapeutic method has succeeded in decreasing tumor volume, inhibiting tumor progression, and enhancing patients' survival. These approaches could lead to acceptable results, relatively better safety, and tolerable side effects compared to conventional chemo and radiotherapy. Accordingly, this treatment will be applicable to a wide range of CNS tumors in the near future. Furthermore, tumor genomic analysis and understanding of the underlying molecular mechanisms will help researchers determine patient selection criteria for targeted gene therapy.

Nutrition and Diet: A Double-Edged Sword in Development and Treatment of Brain Tumors.

Brain tumor (BT) is the second most common pediatric cancer, one of the most common cancers among adults, and the major cause of cancer-related morbidity and mortality worldwide. Both genetics and environment can contribute to BT induction. One of the environmental risks is diet which has not been proven as a certain hazard yet. The objective of the current chapter was to review the literature concerning both positive and negative effects of nutrition on BT risk.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

BACKGROUND: Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. METHODS: A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. RESULTS: The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). CONCLUSIONS: Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Complete Versus Incomplete Surgical Resection in Intramedullary Astrocytoma: Systematic Review with Individual Patient Data Meta-Analysis.

STUDY DESIGN: Systematic reviewBackground: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome. OBJECTIVE: To compare the overall survival (OS) and neurologic outcomes of complete vs incomplete surgical resection for patients with intramedullary astrocytoma. METHODS: A comprehensive search of MEDLINE, CENTRAL and EMBASE was conducted by two independent reviewers. Individual patient data (IPD) analysis and multivariate Cox Proportional Hazard Model was developed to measure the effect of surgical strategies on OS, post-operative neurological improvement (PNI), and neurological improvement in the last follow up (FNI). RESULTS: We included 1079 patients from 35 studies. Individual patient data of 228 patients (13 articles) was incorporated into the integrative IPD analysis. Kaplan-Meier survival analysis showed complete resection (CR) significantly improved OS in comparison with the incomplete resection (IR) (log-rank test, P = .004). In the multivariate IPD analysis, three prognostic factors had significant effect on the OS: (1) Extent of Resection, (2) pathology grade, and (3) adjuvant therapy. We observed an upward trend in the popularity of chemotherapy, but CR, IR, and radiotherapy had relatively stable trends during three decades. CONCLUSION: Our study shows that CR can improve OS when compared to IR. Patients with spinal cord astrocytoma undergoing CR had similar PNI and FNI compared to IR. Therefore, CR should be the primary goal of surgery, but intraoperative decisions on the extent of resection should be relied on to prevent neurologic adverse events. Due to significant effect of adjuvant therapy on OS, PNI and FNI, it could be considered as the routine treatment strategy for spinal cord astrocytoma.

Safety and efficacy of aprotinin versus tranexamic acid for reducing absolute blood loss and transfusion in pediatric patients undergoing craniosynostosis surgery: a randomized, double-blind, three-arm controlled trial.

OBJECTIVE: Craniosynostosis surgery is associated with considerable blood loss and need for transfusion. Considering the lower estimated blood volume (EBV) of children compared to adults, excessive blood loss may quickly lead to hypovolemic shock. Therefore, reducing blood loss is important in craniosynostosis surgery. This study was conducted to evaluate the efficacy of aprotinin or tranexamic acid (TXA) in blood loss reduction in these patients. METHODS: In the current randomized controlled trial, 90 eligible pediatric patients with craniosynostosis were randomly divided into three groups to receive either aprotinin, TXA, or no intervention. The absolute blood loss and transfusion amount were assessed for all patients both intraoperatively and 2 and 8 hours postoperatively. RESULTS: Although crude values of estimated blood loss were not significantly different between groups (p = 0.162), when adjusted to the patient's weight or EBV, the values reached the significance level (p = 0.018), particularly when the aprotinin group was compared to the control group (p = 0.0154). The EBV losses 2 hours and 8 hours postoperatively significantly dropped in the TXA and aprotinin groups compared to the control group (p = 0.001 and p < 0.001, respectively). Rates of postoperative blood transfusion were significantly higher in the control group (p = 0.024). Hemoglobin and hematocrit 8 hours postoperatively were lower in the control group than in the TXA or aprotinin treatment groups (p < 0.002 and p < 0.001, respectively). There were no serious adverse events associated with the interventions in this study. CONCLUSIONS: Aprotinin and TXA can reduce blood loss and blood transfusion without serious complications and adverse events in pediatric patients undergoing craniosynostosis surgery.

Stem cell transplantation as a progressing treatment for retinitis pigmentosa.

Retinal degenerative diseases such as retinitis pigmentosa (RP) are of the major causes of vision loss in developed countries. Despite the unclear pathophysiology, treatment methods have been investigated vastly in the past decades. This review article mainly discusses the advances in application of stem cell and progenitor transplantation for retinitis pigmentosa. Stem cell sources such as mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal progenitor cells, and olfactory ensheathing cells are discussed separately in addition to a brief description of two approaches for treatment of early-stage RP, including gene therapy and nutritional therapy.

VEGF levels in patients with glioma: a systematic review and meta-analysis.

Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with glioma, we conducted the current systematic review and meta-analysis to more clearly determine the VEGF level alterations in different grades of glioma. PubMed and Scopus databases were sensitively searched for all the possible keywords addressing glioma and VEGF. Case-control and cohort studies on human subjects, which measured VEGF levels were eligible to be included in the study. Out of a total number of 3,612 studies, 22 studies were included and 12 studies entered the meta-analysis. This review revealed that serum levels of VEGF in glioma patients were 1.56 pg/dL higher compared to healthy controls (P = 0.05). Besides, immunohistochemistry (IHC) measurement of VEGF in surgical biopsies indicated significant difference in these two groups as well (P = 0.02). Yet, there was not a significant difference between patients with low-grade gliomas (World Health Organization (WHO) grades I-II, LGG) and those with high-grade gliomas (WHO grades III-IV, HGG) (P = 0.43). The results of this systematic review and meta-analysis demonstrate that VEGF levels would significantly increase in glioma, and therefore, could be potentially considered as a biomarker for this cancer.

Complete Versus Incomplete Surgical Resection in Intramedullary Ependymomas: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review. OBJECTIVE: To compare outcomes of complete versus incomplete resection in primary intramedullary spinal cord ependymoma. METHODS: A comprehensive search of the MEDLINE, CENTRAL, and Embase databases was conducted by 2 independent investigators. Random-effect meta-analysis and meta-regression with seven covariates were performed to evaluate the reason for the heterogeneity among studies. We also used individual patient data in the integrative analysis to compare complete and incomplete resection based on 4 outcomes: progression-free survival (PFS), overall survival (OS), postoperative neurological improvement (PNI), and follow-up neurological improvement (FNI). RESULTS: A total of 23 studies were identified, including 407 cases. Significant heterogeneity among included studies was observed in risk estimates (I2 for PFS, FNI, and PNI were 49.5%, 78.3%, and 87.2%, respectively). The mean follow-up time across cases was 48.6 ± 2.35 months. Cox proportional multivariable analysis revealed that the complete resection can prolong PFS (model, hazard ratio = 0.18, CI 0.05-0.54, P = .004,) and improve the FNI (binary logistic regression, adjusted odds ratio = 16.5, CI 1.6-171, P = .019). However, PNI and OS were similar in patients with incomplete resected spinal cord ependymoma compared with complete resection (binary logistic regression respectively and Cox multivariable analysis, P > .5). CONCLUSION: The data presented in this study showed that OS was not significantly affected by the degree of surgery. However, complete resection of intramedullary ependymomas provides the optimal outcomes with longer PFS and better long-term neurological outcomes than incomplete resection.

Incidence of seroconversion and sero-reversion in patients with multiple sclerosis (MS) who had been treated with natalizumab: A systematic review and meta-analysis.

BACKGROUND: Natalizumab is a medication of choice for some patients with relapsing remitting (RR) form of multiple sclerosis (MS). John Cunningham virus (JCV) antibody status is important in cases who are treating with natalizumab. Different studies reported various rates of seroconversion and sero-reversion in patients who had been treated with natalizumab. As there is no systematic review reporting incidence of seroconversion and seroreversion in MS cases who were treated with natalizumab, we aimed to conduct this systematic review and meta-analysis to find pooled incidence of seroconversion and seroreversion in MS cases who were treated with natalizumab. METHODS: PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, and google scholar were systematically searched. We also searched the gray literature including references from included studies, and conference abstracts which were published up to April 2019. RESULTS: The incidence of seroconversion was reported between 6% and 41% and the incidence of seroreversion was reported between 1% and 11%. The pooled estimate of seroconversion incidence was 19% (95% CI: 13%-25%) (I2 = 96.8%, P < 0.001) and the pooled estimate of seroreversion incidence was 5% (95% CI: 3%-8%) (I2 = 72.2%, P < 0.001). Subgroup analysis by considering the country of the origin showed that the pooled incidence of seroconversion incidence during the studies was 6% in Asian countries and 21% in European/American countries. The incidence difference between subgroups was significant (p < 0.001). CONCLUSION: Incidence of seroconversion in MS patients who had been treated with natalizumab is higher in European/American countries than Asian countries.

State of the art in immunotherapy of neuroblastoma.

Neuroblastoma (NB) is a common and deadly malignancy mostly observed in children. Evolution of therapeutic options for NB led to the addition of immunotherapeutic modalities to the previously recruited chemotherapeutic options. Molecular studies of the NB cells resulted in the discovery of many tumor-associated genes and antigens such as MYCN gene and GD2. MYCN gene and GD2 surface antigen are two of the most practical discoveries regarding immunotherapy of neuroblastoma. The GD2 antigen has been targeted in many animal and human studies including Phase III clinical trials. Even though these antigens have changed the face of pediatric neuroblastoma, they do not take as much credit in immunotherapy of adult-onset neuroblastoma. Monoclonal antibodies have been designed to detect this antigen on the surface of NB tumor cells. Despite bettering the outcomes for NB patients, current therapies still fail in many cases. Studies are underway to discover more specific tumor-associated antigens and more effective treatment options. In the current narrative, immunotherapy of NB - from emerging of this therapeutic backbone in NB to the latest discoveries regarding this malignancy - has been reviewed.

Significant association of TNF-α, but not other pro-inflammatory cytokines, single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population.

OBJECTIVES: As the important role of inflammation in pathophysiology of intervertebral disc degeneration and inconsistency regarding the role of pro-inflammatory cytokine genes SNPs, the current case-control study was designed to assess this in Iranian population. PATIENTS AND METHODS: The genomic DNA of peripheral leukocytes of 76 patients and 140 healthy controls were investigated to sequence 9 SNPs of pro-inflammatory cytokine genes of interleukin 1 (IL-1), interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF-α) family. RESULTS: 'GA' and 'GG' genotype of TNF-α -308 G/A SNP were significantly associated with IVDD. While 'GA' was 1.93 times more frequent in patients, the 'GG' genotype was more common among healthy subjects (OR = 0.51, P = 0.03). The 'G' allele of TNF-α -238 G/A was 2.51 times more common in IVDD patients while the 'A' genotype was more frequent in controls with odds ratio of 0.39 (P = 0.001). Interestingly, the homozygote 'GG' genotype was 2.98 times more prevalent in patients (P = 0.001) while the 'GA' heterozygote genotype was more common in healthy individuals (OR = 0.34). The other investigated SNPs were not significantly associated with disease in this study population. CONCLUSION: Polymorphisms of pro-inflammatory cytokine genes could take part in IVDD pathophysiology as the result of alteration in their expression levels or structures. The current study indicated significant roles of TNF-α -308 G/A and TNF-α -238 G/A SNPs with IVDD among Iranian patients. However, this study did not show any significant association between IVDD and either of SNPs of IL-1 and IL-6 genes.

Frequently asked questions of individuals with spinal cord injuries: results of a web-based consultation service in Iran.

STUDY DESIGN: Descriptive study of the results of a web-based consultation service for individuals with spinal cord injury (SCI). OBJECTIVES: To review frequently asked questions (FAQ) among individuals with SCI and determine the most important topics. SETTING: Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran. METHODS: A cross-sectional study reviewing questions from patients with SCI that were collected from the Health and Safety Consultant Center (HSCC) between January and December 2015. The HSCC is a web-based medical consultation service that provides patients with information and counseling pertaining to SCI. RESULTS: A total of 113 questions were collected from 99 individuals. The mean age was 32.02 ± 13.28 years with a range of 3-70 years. Men accounted for 81.7% of the questions, while women accounted for 18.3%. The most common site of SCI was thoracic (40.6%), followed by lumbar (31.3%), and cervical (28.1%). Recovery potential (38.1%), sexual and reproductive issues (26.5%), urinary (10.6%), and motor (10.6%) problems were among the most commonly reviewed topics. CONCLUSIONS: FAQ provide insight on areas of concerns for individuals with SCI and help guide providers to determine high-yield topics. Discerning the specific areas of need or concern for patients is instrumental in developing pertinent educational materials and programs, in addition to efficiently counseling patients and caregivers on the aftercare of SCI.