Atypical and anaplastic meningiomas in the later decades of life: A national cancer database analysis.

PURPOSE: We conducted a National Cancer Database (NCDB) study to investigate the epidemiological characteristics and identify predictors of outcomes associated with geriatric meningiomas. METHODS: The NCDB was queried for adults aged 60-89 years diagnosed between 2010 and 2017 with grade 2 and 3 meningiomas. The patients were classified into three age groups based on their age: 60-69 (hexagenarians), 70-79 (septuagenarians), and 80-89 (octogenarians). The log-rank test was utilized to compare the differences in overall survival (OS). Univariate and multivariate Cox proportional hazards regressions were used to evaluate the mortality risk associated with various patient and disease parameters. RESULTS: A total of 6585 patients were identified. Hexagenerians were the most common age group (49.8%), with the majority of meningiomas being classified as grade 2 (89.5%). The incidence of high-grade meningiomas increased in all age groups during the study period. Advanced age, male sex, black race, lower socioeconomic status, Charlson-Deyo score ≥ 2, and higher tumor grade were independent factors of poor survival. Among the modes of treatment, the extent of surgical resection, adjuvant radiotherapy, and treatment at a noncommunity cancer program were linked with better outcomes. CONCLUSION: In geriatric patients with high-grade meningiomas, the greater extent of surgical resection and radiotherapy are associated with improved survival. However, the management and outcome of geriatric patients with higher-grade meningiomas are also associated with several socioeconomic factors.

The Role of Novel Imaging and Biofluid Biomarkers in Traumatic Axonal Injury: An Updated Review.

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Traumatic axonal injury (TAI) is a subtype of TBI resulting from high-impact forces that cause shearing and/or stretching of the axonal fibers in white matter tracts. It is present in almost half of cases of severe TBI and frequently associated with poor functional outcomes. Axonal injury results from axonotomy due to mechanical forces and the activation of a biochemical cascade that induces the activation of proteases. It occurs at a cellular level; hence, conventional imaging modalities often fail to display TAI lesions. However, the advent of novel imaging modalities, such as functional magnetic resonance imaging and fiber tractography, has significantly improved the detection and characteristics of TAI. Furthermore, the significance of several fluid and structural biomarkers has also been researched, while the contribution of omics in the detection of novel biomarkers is currently under investigation. In the present review, we discuss the role of imaging modalities and potential biomarkers in diagnosing, classifying, and predicting the outcome in patients with TAI.

Ependymomas in Children and Adults.

Ependymomas account for approximately 5% of all CNS tumors in adults and around 10% in the pediatric population. Contrary to traditional theories supporting that ependymomas arise from ependymal cells, recent studies propose radial glial cells as the cells of origin. In adults, half of the ependymomas arise in the spinal cord, whereas in the pediatric population, almost 90% of ependymomas are located intracranially. Most of the ependymomas are usually low-grade tumors except anaplastic variants and some cases of RELA-fusion-positive ependymomas, a molecular variant consisting the most recent addition to the 2016 World Health Organization (WHO) classification. Of note, the recently described molecular classification of ependymomas into nine distinct subgroups appears to be of greater clinical utility and prognostic value compared to the traditional histopathological classification, and parts of it are expected to be adopted by the WHO in the near future. Clinical manifestations depend on the location of the tumor with infratentorial ependymomas presenting with acute hydrocephalus. Gross total resection should be the goal of treatment. The prognostic factors of patients with ependymomas include age, grade, and location of the tumor, with children with intracranial, anaplastic ependymomas having the worst prognosis. In general, the 5-year overall survival of patients with ependymomas is around 60-70%.

Brain and Spinal Cord Tumors of Embryonic Origin.

Embryonal tumors (ETs) of the central nervous system (CNS) comprise a large heterogeneous group of highly malignant tumors that predominantly affect children and adolescents. Currently, the neoplasms classified as ET are the medulloblastoma (MB), embryonal tumors with multilayered rosettes (ETMR), medulloepithelioma (ME), CNS neuroblastoma (NB), CNS ganglioneuroblastoma (GNB), atypical teratoid/rhabdoid tumors (AT/RT), and CNS embryonal tumors with rhabdoid features. All these tumors are classified as malignant-grade IV neoplasms, and the prognosis of patients with these neoplasms is very poor. Currently, except for the histological classification of MB, the recently utilized WHO classification accepts a novel molecular classification of MBs into four distinct molecular subgroups: wingless/integrated (WNT)-activated, sonic hedgehog (Shh), and the numerical Group3 and Group 4. The combination of both histological and genetic classifications has substantial prognostic significance, and patients are categorized as low risk with over 90% survival, the standard risk with 75-90% survival, high risk with 50-75% survival, and very high risk with survival rate lower than 50%. Children under three years are predominantly affected by AT/RT and represent about 20% of all CNS tumors in this age group. AT/RT is typically located in the posterior fossa (mainly in cerebellopontine angle) in 50-60% of the cases. The pathogenesis of this neoplasm is strongly associated with loss of function of the SMARCB1 (INI1, hSNF5) gene located at the 22q11.23 chromosome, or very rarely with alterations in (SMARCA4) BRG1 gene. The cells of this neoplasm resemble those of other neuronal tumors, and hence, immunochemistry markers have been utilized, such as smooth muscle actin, epithelial membrane antigen, vimentin, and lately antibodies for INI1. ETMRs are characterized by the presence of ependymoblastic rosettes formed by undifferentiated neuroepithelial cells and neuropil. The tumorigenesis of ETMRs is strongly related to the amplification of the pluripotency factor Chr19q13.41 miRNA cluster (C19MC) present in around 90% of the cases. Additionally, the expression of LIN28A is a highly sensitive and specific marker of ETMR diagnosis, as it is overexpressed in almost all cases of ETMR and is related to poor patient outcomes. The treatment of patients with ETs includes a combination of surgical resection, radiotherapy (focal or craniospinal), and chemotherapeutic agents. Currently, there is a trend to reduce the dose of craniospinal irradiation in the treatment of low-risk MBs. Novel targeted therapies are expected in the treatment of patients with MBs due to the identification of the main driver genes. Survival rates vary between ET types and their subtypes, with ganglioneuroblastoma having over 95% 5-year survival rate, while ATRT is probably linked with the worst prognosis with a 30% 5-year survival rate.

Stereotactic radiosurgery versus whole-brain radiotherapy after resection of solitary brain metastasis: A systematic review and meta-analysis.

Objective: The standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline. Methods: We performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients' neurocognitive function and quality of life after each postoperative radiation form. Results: Four studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51-1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49-2.98, p = 0.67, I2 = 18%), neither in the patients' overall survival (HR = 1.06, CI = 0.61-1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94-4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group. Conclusions: Although SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

Blood biomarkers for predicting coagulopathy occurrence in patients with traumatic brain injury: a systematic review.

Purpose: The occurrence of coagulopathy in patients with traumatic brain injury (TBI) is related to severe complications. The authors performed the first systematic review to investigate whether biomarkers can predict the occurrence of hypocoagulopathy or progressive hemorrhagic injury in patients with TBI. Methods: The authors included studies that performed a receiver operating characteristics analysis for the biomarker and provided a clear value along with the respective sensitivity and specificity. Additionally, they attempted to classify each biomarker, taking into account its physiological role. Results: Twelve studies were included. All biomarkers were protein molecules, except in one study that examined the prognostic role of glucose. Copeptin had the highest sensitivity, and S100A12 had the highest specificity in predicting coagulopathy, while IL-33 had the highest sensitivity and GALECTIN-3 had the highest specificity in predicting progressive hemorrhagic injury. Conclusion: The study of the role of biomarkers in predicting the occurrence of coagulopathy in patients with TBI remains in its infancy.

Primary Intraosseous Cavernous Hemangioma of the Cranium: A Systematic Review of the Literature.

Primary intraosseous cavernous hemangioma (PICH) is a rare, benign tumor of vascular origin, typically arising in the vertebral body. Its presence in the skull is exceedingly rare, with only a few cases being reported worldwide. We carried out the first systematic review of the literature, covering the epidemiology, clinical and imaging features, management, and prognosis of cranial PICH. The literature search revealed 51 studies with 77 patients; the mean age of the patients was 32.7 years with a female predominance of 1.4:1. The majority of cranial PICHs were located in the calvarium, primarily in the frontal and parietal regions, with only a few located in the skull base. The most common initial clinical manifestation was local growth or swelling, followed by a headache. Radiographically, PICHs represented osteolytic, intradiploic masses, which in many cases displayed trabeculations, leading to the so-called "honeycomb" or "starburst" pattern. After contrast administration, PICHs typically enhance. Tumor removal, with craniectomy or en bloc resection and subsequent skull reconstruction, was selected for calvarial PICHs, whereas a transsphenoidal approach, with only partial resection, was applied for clival/sella PICHs. Preoperative embolization, aiming to minimize intraoperative blood loss, was performed in the case of large tumors. At a mean follow-up of 39 months, no patient experienced tumor recurrence, even after subtotal resection. Owing to the benign nature of the tumor, maximal safe resection is recommended as the treatment of choice for patients with cranial PICH.

The Role of Hsp27 in Chemotherapy Resistance.

Heat shock protein (Hsp)-27 is a small-sized, ATP-independent, chaperone molecule that is overexpressed under conditions of cellular stress such as oxidative stress and heat shock, and protects proteins from unfolding, thus facilitating proteostasis and cellular survival. Despite its protective role in normal cell physiology, Hsp27 overexpression in various cancer cell lines is implicated in tumor initiation, progression, and metastasis through various mechanisms, including modulation of the SWH pathway, inhibition of apoptosis, promotion of EMT, adaptation of CSCs in the tumor microenvironment and induction of angiogenesis. Investigation of the role of Hsp27 in the resistance of various cancer cell types against doxorubicin, herceptin/trastuzumab, gemcitabine, 5-FU, temozolomide, and paclitaxel suggested that Hsp27 overexpression promotes cancer cell survival against the above-mentioned chemotherapeutic agents. Conversely, Hsp27 inhibition increased the efficacy of those chemotherapy drugs, both in vitro and in vivo. Although numerous signaling pathways and molecular mechanisms were implicated in that chemotherapy resistance, Hsp27 most commonly contributed to the upregulation of Akt/mTOR signaling cascade and inactivation of p53, thus inhibiting the chemotherapy-mediated induction of apoptosis. Blockage of Hsp27 could enhance the cytotoxic effect of well-established chemotherapeutic drugs, especially in difficult-to-treat cancer types, ultimately improving patients' outcomes.

Neutrophil to lymphocyte ratio in the prediction of coagulopathy in traumatic brain injury.

Aim: Traumatic brain injury (TBI) is a public health issue of increasing incidence. Coagulopathy after TBI is a frequent event, associated with a poor prognosis, and biomarkers that could predict coagulopathy occurrence are needed. The neutrophil-to-lymphocyte ratio (NLR) is useful as a cost-effective biomarker to assess prognosis and the need for cranial computed tomography in patients with mild TBI. As no study has yet evaluated the association of NLR with coagulopathy, we investigated whether the NLR at presentation could predict coagulopathy occurrence after TBI. Materials & methods: A retrospective study was conducted of patients aged >18 years who attended the emergency department (ED) with TBI, over a 3-year period. We included all patients for whom the NLR at presentation was available, and who underwent a brain CT scan. Results: The study included 173 patients (mean age 57.4 ± 21.1 years) with TBI, the most frequent cause of which was a fall. According to the Glasgow Coma Scale, 37 patients had severe TBI, 19 moderate and 117 mild TBI and 40 patients (23.1%) developed coagulopathy. Their mean NLR was 7.5 ± 6.7. Using receiver operating characteristic curve analysis, a cut-off value of 4.2 for NLR had 87.5% sensitivity and 52.9% specificity for predicting coagulopathy occurrence. Conclusion: Coagulopathy occurs frequently after TBI. This study investigated the value of NLR as a biomarker to predict coagulopathy occurrence, and concluded that NLR might be a novel and inexpensive biomarker for decision making in the management of TBI. Combination of NLR with other low-cost biomarkers and the clinical findings might further increase accuracy in the prediction of coagulopathy.

Plain language summary Traumatic brain injury (TBI) is a public health issue of increasing incidence. Coagulopathy after TBI is a frequent event, associated with a poor prognosis and biomarkers that could predict coagulopathy occurrence are needed. The neutrophil-to-lymphocyte ratio (NLR) is useful as a cost-effective biomarker to assess prognosis and the need for cranial computed tomography in patients with mild TBI. We found that NLR could additionally predict which TBI patients might develop coagulopathy with a 87.5% sensitivity and 52.9% specificity. Combination of NLR with other low-cost biomarkers and the clinical findings might further increase accuracy in the prediction of coagulopathy.

Anaplastic gangliogliomas of the spinal cord: a scoping review of the literature.

Gangliogliomas (GGs) are rare, usually low-grade tumors that account for 1-2% of all central nervous system (CNS) neoplasms. Spinal GGs are exceedingly rare (1% of all spinal tumors) and the presentation of anaplastic features in them is even rarer. According to the last World Health Organization (WHO) classification of CNS neoplasms, anaplastic GG (AGG) is classified as a malignant neoplasm (grade III). We performed a scoping review of the literature to elucidate the epidemiology, clinical features, histopathology, treatment, and outcome of primary spinal AGGs, which, to the best of our knowledge, is the first such review. Relevant studies were identified by a search of the MEDLINE and SCOPUS databases, using the following combination of search strings: (anaplastic ganglioglioma or malignant ganglioglioma or high grade ganglioglioma) AND (spine or spinal or spinal cord). We included studies related to primary or recurrent AGGs and malignant transformation of low-grade GGs. The search produced 15 eligible studies, plus two studies from the references, all of which were case reports of patients with spinal AGGs (17 studies with 22 patients). The mean age of the patients was 21.4 years and the sex ratio was 1:1, with male predominance. Motor impairment was the most common presentation, followed by sensory impairment, gait problems, urinary disturbances, and back pain. The thoracic spine was the most frequently involved area (14/22) followed by the cervical (6/22) and lumbar (5/22) spine. In terms of histology, the anaplastic features were usually predominant in the glial element, resembling high-grade astrocytomas, while the neuronal element was composed of the so-called dysplastic ganglion (neuronal) synaptophysin-positive cells, without mitotic figures. Complete surgical resection of the tumor without neurological compromise, plus adjuvant chemotherapy and radiotherapy, was the treatment protocol implemented in the two patients with the best outcome. Primary spinal AGG is an exceedingly rare entity, with only 22 cases being retrieved after an extensive literature search. They appear to affect children and young adults and tend to manifest aggressive behavior. Most studies report that only the glial component of AGGs presents high-grade malignant features, with low mitotic activity in the neuronal component. We therefore suggest that, pending novel targeted therapy, AGGs should be treated as high-grade gliomas, with an aggressive treatment protocol consisting of maximal safe resection and adjuvant chemotherapy and radiotherapy.

Repurposing Antipsychotics for Cancer Treatment.

Cancer is a leading cause of death worldwide, with approximately 19 million new cases each year. Lately, several novel chemotherapeutic drugs have been introduced, efficiently inhibiting tumor growth and proliferation. However, developing a new drug is a time- and money-consuming process, requiring around 1 billion dollars and nearly ten years, with only a minority of the initially effective anti-cancer drugs experimentally finally being efficient in human clinical trials. Drug repurposing for cancer treatment is an optimal alternative as the safety of these drugs has been previously tested, and thus, in case of successful preclinical studies, can be introduced faster and with a lower cost into phase 3 clinical trials. Antipsychotic drugs are associated with anti-cancer properties and, lately, there has been an increasing interest in their role in cancer treatment. In the present review, we discussed in detail the in-vitro and in-vivo properties of the most common typical and atypical antipsychotics, along with their mechanism of action.

Transcutaneous Vagus Nerve Stimulation (t-VNS) and epilepsy: A systematic review of the literature.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (t-VNS) has been proposed as an alternative method for the treatment of various neurological and psychiatric disorders. Contrary to the classic invasive vagus nerve stimulation (i-VNS), t-VNS does not require surgical intervention. The application of t-VNS for the treatment of epilepsy has been poorly studied. Hence, we performed a systematic review of the literature to elucidate efficacy, adverse effects and technical features of t-VNS in patients with epilepsy. MATERIAL AND METHODS: We systematically searched MEDLINE and SCOPUS databases using the following keywords: [TRANSCUTANEOUS VAGUS NERVE STIMULATION OR TRANSCUTANEOUS VAGAL NERVE STIMULATION] AND [EPILEPSY OR SEIZURES]. We searched for observational studies in English concerning the application of t-VNS for the treatment of epilepsy in humans. The full-text version of relevant studies was obtained and reviewed. Technical parameters of the stimulation, percentage of seizure frequency reduction, QOLIE-31(Quality of Life In Epilepsy-31) and LSSS (Liverpool Seizure Severity Scale) questionnaires and adverse effects were recorded and analyzed. RESULTS: A total of 10 studies with 350 patients were included. Both bilateral and unilateral placement of the electrode were applied. Stimulation frequency varied from 10-30Hz, while treatment intensity was usually adjusted according to patients' preferences and tolerance (around 1mA) and below the pain threshold. In the clinical trials included in our review, the mean seizure frequency reduction varied from 30 to 65%. Eight and four studies provided information about QOLIE-31 and LSSS questionnaires respectively. Three studies reported a statistically significant (p<0,05) improvement in patients' quality of life and two studies reported statistically significant (p<0,05) seizure severity reduction. The most common side effect was headache (8,9%), followed by skin irritation at the placement site (7,1%) and nasopharyngitis (5,1%). No serious or life-threatening side effects were reported. CONCLUSION: Due to the heterogeneity of the included studies, no safe conclusions could be extracted concerning the efficacy of t-VNS. However, the results of this review suggest that patients with epilepsy could possibly benefit from the use of t-VNS. The present study also emphasizes the limitations of previous clinical trials concerning the applications of t-VNS in people with epilepsy and thus could be a guidance for the conduction of future trials.

Extraventricular neurocytomas: a systematic review of the literature in the pediatric population.

Extraventricular neurocytomas (EVNs) are rare neuroepithelial neoplasms of the central nervous system that were first described in 1997. Most studies in patients with EVNs have incorporated mixed age groups. The tumor's clinical behavior specifically in children has not been explored in depth, while a detailed statistical analysis has never been performed in this age group. Hence, we performed a systematic review to address possible prognostic factors and the appropriate management in children with EVNs. Relevant studies were identified by searching the MEDLINE and SCOPUS databases. We included studies concerning patients 18 years of age or younger who were histologically diagnosed with EVNs. A total of 52 studies with 79 patients were included. The mean age of the patients was ~ 10 years with a male predilection (~ 2:1). Most of these tumors were located in the frontal (49%) lobe. We observed that gross total resection of the tumor was significantly lower in cases of atypical EVNs (p < 0.05). Additionally, atypical EVNs were associated with worse overall survival compared to typical EVNs (p = 0.05). Children 4 years of age or under had a worst outcome (p = 0.001). The patient's sex and the extent of the tumor's resection did not appear to affect the prognosis in a statistically significant manner. Contrary to the results of previous studies, the use of adjuvant radiotherapy or chemotherapy for the treatment of EVNs was not associated with better outcomes in the pediatric population. Thus, a less aggressive management of children with EVNs compared to the adult population is suggested.