Enhancing meningioma resection: a comprehensive study on the safety and effectiveness of Onyx™ presurgical embolization.

Presurgical embolization (PE) has emerged as an interesting strategy to help turn brain tumor resection more amenable. This study aims to systematically review the safety and effectiveness of Onyx™ PE in meningioma resection. We followed Cochrane Collaboration and PRISMA for systematic review and meta-analysis, querying PUBMED, Cochrane Library, Web of Science, and Embase databases. Major complications were defined as other artery occlusion, visual deficits due to PE, or non temporary nerve damage, while minor included transitory conditions and others without clinical implications. A total of 186 patients were included, in which 120 were WHO grade I (80%), II (16%), and III (4%). Patient baseline characteristics and complications were distributed in groups without or with individual patient data analysis. Individual Patient Data Meta-Analysis (IPDMA) was performed on the last category, comprising 51 meningiomas that underwent Onyx™ PE. Among available data, 70%, 17%, and 13% were WHO grade I, II, and III, respectively. Considering all studies, tumor characteristics regarding grade underscored a certain homogeneity. Complications occurred at a rate of 9% (95% CI, 4 to 14%; I2 = 35%), with the rate of major complications significantly lower at only 1% (95% CI, 0 to 3%; I2 = 32%), whereas of minor complications was 7% (95% CI, 3 to 10%; I2 = 0%). Mean surgery blood loss was 668.7 (95% CI, 534.9 to 835.8; I2 = 0%) in IPDMA. Onyx™ PE is promising for safer surgical meningioma resection, despite limitations. Further studies are required to validate efficacy, enhance patient selection, and refine techniques.

Intranasal perillyl alcohol therapy improves survival of patients with recurrent glioblastoma harboring mutant variant for MTHFR rs1801133 polymorphism.

BACKGROUND: Polymorphisms in MTHFR gene influence risk and overall survival of patients with brain tumor. Global genomic DNA (gDNA) methylation profile from tumor tissues is replicated in peripheral leukocytes. This study aimed to draw a correlation between rs1801133 MTHFR variants, gDNA methylation and overall survival of patients with recurrent glioblastoma (rGBM) under perillyl alcohol (POH) treatment. METHODS: gDNA from whole blood was extracted using a commercially available kit (Axygen) and quantified by spectrophotometry. Global gDNA methylation was determined by ELISA and rs1801133 polymorphism by PCR-RFLP. Statistical analysis of gDNA methylation profile and rs1801133 variants included Mann-Whitney, Kruskal-Wallis, Spearman point-biserial correlation tests (SPSS and Graphpad Prism packages; significant results for effect size higher than 0.4). Prognostic value of gDNA methylation and rs1801133 variants considered survival profiles at 25 weeks of POH treatment, having the date of protocol adhesion as starting count and death as the final event. RESULTS: Most rGBM patients showed global gDNA hypomethylation (median = 31.7%) and a significant, moderate and negative correlation between TT genotype and gDNA hypomethylation (median = 13.35%; rho = - 0.520; p = 0.003) compared to CC variant (median = 32.10%), which was not observed for CT variant (median = 33.34%; rho = - 0.289; p = 0.06). gDNA hypermethylated phenotype (median = 131.90%) exhibited significant, moderate and negative correlations between TT genotype (median = 112.02%) and gDNA hypermethylation levels when compared to CC (median = 132.45%; rho = - 0,450; p = 0.04) or CT (median = 137.80%; rho = - 0.518; p = 0.023) variants. TT variant of rs1801133 significantly decreased gDNA methylation levels for both patient groups, when compared to CC (d values: hypomethylated = 1.189; hypermethylated = 0.979) or CT (d values: hypomethylated = 0.597; hypermethylated = 1.167) variants. Positive prognostic for rGBM patients may be assigned to gDNA hypermethylation for survivors above 25 weeks of treatment (median = 88 weeks); and TT variant of rs1801133 regardless POH treatment length. CONCLUSION: rGBM patients under POH-based therapy harboring hypermethylated phenotype and TT variant for rs1801133 had longer survival. Intranasal POH therapy mitigates detrimental effects of gDNA hypomethylation and improved survival of patients with rGBM harboring TT mutant variant for MTHFR rs1801133 polymorphism. TRIAL REGISTRATION: CONEP -9681- 25,000.009267 / 2004. Registered 12th July, 2004.

Emerging Treatments for Neuropathic Pain.

Neuropathic pain is a series of well-known conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of the pathophysiology of neuropathic pain, previously unexplored therapies have been used with encouraging results. As such, Acetyl-L-carnitine (ALC), Alpha-lipoic-acid (ALA), cannabinoids, Clonidine, EMA401, Botulinum Toxin type A, and new voltage-gated sodium channel blockers, can be cited. Furthermore, new modalities in neuromodulation such as high-frequency spinal cord stimulation, burst stimulation, dorsal root ganglion stimulation, transcranial direct current stimulation, and many others have been showing exciting results. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation. This article reviews the published literature on the treatment of NP. Despite the interesting results, randomized controlled trials are demanded for the majority of the therapies previously mentioned.

Cerebrovascular Disease Mortality Trends in Brazil: An In-Depth Joinpoint Analysis.

Background Cerebrovascular disease is the second leading cause of death and the third leading cause of disability following heart disease. In 2019, there were over 101 million people living with a stroke and 12.2 million incidents of stroke globally. For the past three decades, stroke has remained the leading cause of death in Brazil, causing over 100,000 fatalities annually, along with numerous functional impairments among those who survive. The Brazilian healthcare system has witnessed notable advancements in the last decade, including the establishment of additional hospitals and a rise in the count of healthcare professionals specializing in cardiovascular and neurological surgery. However, there exists a gap in the research landscape for continuous comprehensive studies aimed at exploring the evolving mortality rates related to cerebrovascular diseases, of which the last one included data up to 2019. This study aimed to address this gap by meticulously analyzing the trends in cerebrovascular disease mortality in Brazil from 2000 to 2021, for the variables age, sex, state of residence, and geographic region. Methods This is a descriptive, ecological, and time series study. Nationwide data for annual cerebrovascular mortality from Brazil were used for the period 2000-2021. Age-adjusted mortality rates (AAMRs) by direct standardization, encompassing people above 20 years of age, were calculated and expressed per 100,000 persons. Mortality trends were assessed using joinpoint regression analysis by calculating the annual percentage change (APC) and its corresponding 95% confidence interval (CI) across categories of age, sex, and state and region of residence. Results The mortality rates decreased for the sex categories over the analyzed years. The AAMR for the categories decreased as follows: males and females (95 deaths/100,000 to 52 deaths/100,000 inhabitants), males (108 deaths/100,000 to 63 deaths/100,000 inhabitants), and females (83 deaths/100,000 to 44 deaths/100,000 inhabitants). The most substantial reduction in AAMR for males occurred in the 30-39-year age group (APC: -4.10), while the smallest decline was observed in the 20-29-year age group (APC: -1.44). All five macro-regions demonstrated statistically significant and downward AAPC values in mortality rates. The south and midwest regions decreased at a stable rate, as denoted by the same APC and AAPC values (-4.05 and -3.11, respectively). The north and northeast regions exhibited an increase in AAMR, followed by a decrease (APC: 0.68 to -1.42 and 2.63 to -2.35, respectively). Conclusions Our comprehensive analysis revealed a downward trend in cerebrovascular disease mortality rates across diverse demographic groups and macro-regions. Females experienced a more substantial reduction compared to males. Despite higher mortality rates among individuals aged 50 and above, all age groups displayed a marked decrease. The continuous decline can be attributed to policy interventions aimed at enhancing healthcare delivery, increased awareness, and healthier diets and lifestyles. With regard to the macro-regions, the regions in the southern zone demonstrated a more significant decrease as compared to the northern part. In Brazil, a more significant decline in cerebrovascular disease mortality rates could be achieved through increased focus on prevention measures and efforts toward mitigating disparities and inequalities between macro-regions.

Neuropathic Pain Treatment: Still a Challenge.

Neuropathic pain (NP) is the result of a series of conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of NP pathophysiology previously unexplored therapies have been used with encouraging results. In this group, acetyl-L-carnitine, alpha-lipoic-acid, cannabinoids, clonidine, EMA401, botulinum toxin type A and new voltage-gated sodium channel blockers, can be included. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation. We reviewed the published literature on the pharmacological treatment of NP. Despite the interesting results, randomized controlled trials are demanded the majority of the therapies previously mentioned. In spite of several studies for the relief of NP, pain control continues being a challenge.

True Cervicothoracic Meningocele: A Rare and Benign Condition.

Cervical meningoceles are rare spinal dysraphism, accounting for approximately 7% of all cystic spinal dysraphism. In spite of the rarity, the clinical course is most of the times benign. The surgical treatment includes resection of the lesion and untethering, when presented. We present a 14-day-old female child with true meningoceles who underwent to surgical excision and dura-mater repair. Retrospect analysis of the literature concerning true cervical meningocele is performed. By reporting this illustrative case, we focus on its classification and its differentiation from other types of cervical spinal dysraphism, such as myelocystocele and myelomeningocele. Although its course is benign, it is mandatory a continuum follow up with periodic magnetic resonance imaging of spinal cord, since late neurological deterioration has been described.