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The respiratory tract is commonly affected in multisystem disorders. Although many drugs have been developed to target various components of these diseases, there is still a need for effective treatments that can address both respiratory and non-respiratory symptoms. Bromhexine and ambroxol are mucolytic agents with a good safety profile that are widely used to treat respiratory conditions. These compounds seem to present several unresolved questions when carrying out their therapeutic effects, suggesting that they may not merely improve mucociliary clearance. These assumptions have provided the basis for researchers to investigate the specific characteristics of bromhexine and ambroxol. This has led to the emergence of several repositionings for this compound. Accordingly, these compounds have also shown potential benefits in the treatment of various extrapulmonary disorders, including neurological disorders, and inflammatory bowel disease. We gathered findings from relevant studies published in English between 1970 and December 2023 by searching databases including PubMed, Google Scholar, Scopus, Embase, and the Cochrane Library. Our findings revealed that most of the research on extrapulmonary uses has been conducted at the preclinical level. Accordingly, more clinical studies are needed to determine the effectiveness of bromhexine and ambroxol in these conditions. This article provides an overview of the potential extrapulmonary applications of bromhexine and ambroxol and discusses the potential advantages of using these drugs in multisystem disorders., Competing Interests: Declaration of competing interest The authors declare that they do not have any competing financial interests or other relationships that may have influenced the work reported here., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Glioma grading transformed in World Health Organization (WHO) 2021 CNS tumor classification, integrating molecular markers. However, the impact of this change on radiomics-based machine learning (ML) classifiers remains unexplored., Purpose: To assess the performance of ML in classifying glioma tumor grades based on various WHO criteria., Study Type: Retrospective., Subjects: A neuropathologist regraded gliomas of 237 patients into WHO 2016 and 2021 from 2007 criteria., Field Strength/sequence: Multicentric 0.5 to 3 Tesla; pre- and post-contrast T1-weighted, T2-weighted, and fluid-attenuated inversion recovery., Assessment: Radiomic features were selected using random forest-recursive feature elimination. The synthetic minority over-sampling technique (SMOTE) was implemented for data augmentation. Stratified 10-fold cross-validation with and without SMOTE was used to evaluate 11 classifiers for 3-grade (2, 3, and 4; WHO 2016 and 2021) and 2-grade (low and high grade; WHO 2007 and 2021) classification. Additionally, we developed the models on data randomly divided into training and test sets (mixed-data analysis), or data divided based on the centers (independent-data analysis)., Statistical Tests: We assessed ML classifiers using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC). Top performances were compared with a t-test and categorical data with the chi-square test using a significance level of P < 0.05., Results: In the mixed-data analysis, Stacking Classifier without SMOTE achieved the highest accuracy (0.86) and AUC (0.92) in 3-grade WHO 2021 grouping. The results of WHO 2021 were significantly better than WHO 2016 (P-value<0.0001). In the 2-grade analysis, ML achieved 1.00 in all metrics. In the independent-data analysis, ML classifiers showed strong discrimination between grade 2 and 4, despite lower performance metrics than the mixed analysis., Data Conclusion: ML algorithms performed better in glioma tumor grading based on WHO 2021 criteria. Nonetheless, the clinical use of ML classifiers needs further investigation., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: Brain metastases (BM) often leave residual tumors despite having visible margins, which increases the risk of local tumor recurrence and can impact overall patient survival rates. Fluorescence-guided surgery (FGS) utilizing sodium fluorescein (FL) has been reported as an effective technique in recent studies. This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival., Methods: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our primary focus was on gross total resection (GTR). Additionally, we extracted survival data and evaluated the risk of bias using a modified version of the Joanna Briggs Institute critical appraisal tool., Results: The study comprised 970 patients with brain metastases through eight different studies. The study found that patients who underwent FL-guided resection had a significantly higher rate of GTR (OR: 2.02, 95% CI: 1.14-3.56, p = 0.0156, I2 = 41.5%). Additionally, the study concluded that FL-guided resection is associated with better overall survival rates (HR: 0.61, 95%CI: 0.47 0.80, p = 0.0003, I2 = 41.5%)., Conclusion: Our research suggests that the use of FL is associated with a higher rate of GTR and improved overall patient survival. None of the studies we reviewed reported significant complications associated with the use of FL in patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the brain of individuals with OCD has not yet been fully clarified. We conducted a systematic search on PubMed, Scopus, Embase, and Web of Science to explore the effects of antidepressants on neuroimaging findings in OCD. Thirteen neuroimaging investigations were included. After antidepressant treatment, structural magnetic resonance imaging studies suggested thalamic, amygdala, and pituitary volume changes in patients. In addition, the use of antidepressants was associated with alterations in diffusion tensor imaging metrics in the left striatum, the right midbrain, and the posterior thalamic radiation in the right parietal lobe. Finally, functional magnetic resonance imaging highlighted possible changes in the ventral striatum, frontal, and prefrontal cortex. The small number of included studies and sample sizes, short durations of follow-up, different antidepressants, variable regions of interest, and heterogeneous samples limit the robustness of the findings of the present review. In conclusion, our review suggests that antidepressant treatment is associated with brain changes in individuals with OCD, and these results may help to deepen our knowledge of the pathophysiology of OCD and the brain mechanisms underlying the effects of antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Intraventricular meningioma (IVM) is a rare subtype of intracranial meningioma, accounting for 9.8 to 14% of all intraventricular tumors. Currently, there is no clear consensus on which patients with IVM should receive conservative treatment, surgery, or stereotactic radiosurgery (SRS). This research aims to analyze the outcomes, including survival and recurrence rates of patients who undergo SRS for IVM as a primary or adjuvant treatment., Methods: A systematic search was conducted in Scopus, Web of Science, PubMed, and Embase till June 5th 2023. Screening and data extraction were performed by two independent authors. Random-effect meta-analysis was performed to determine the tumor control proportion of IVM cases treated with SRS. Individual patient data (IPD) meta-analysis was performed for the progression-free survival (PFS) of the patients in the follow-up time. All analyses were performed using the R programming language., Results: Out of the overall 132 records, 14 were included in our study, of which only 7 had enough data for the meta-analysis. The tumor control proportion was 0.92 (95% CI, 0.69-0.98) in patients who underwent SRS for primary IVM. The overall tumor control in both primary and adjuvant cases was 0.87 (95% CI, 0.34-0.99). the heterogeneity was not significant in both meta-analyses (P = 0.73 and P = 0.92, respectively). Post-SRS perifocal edema occurred in 16 out of 71 cases (0.16; 95% CI, 0.03-0.56), with no significant heterogeneity (P = 0.32). IPD meta-analysis showed a PFS of 94.70% in a 2-year follow-up. Log-rank test showed better PFS in primary SRS compared to adjuvant SRS (P < 0.01)., Conclusions: According to this study, patients with IVM can achieve high rates of tumor control with a low risk of complications when treated with SRS, regardless of whether they have received prior treatment. Although SRS could be a promising first-line treatment option for asymptomatic IVM, its efficacy in symptomatic patients and its comparison with resection require further investigation., (© 2024. The Author(s).)

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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deep-seated unruptured AVMs located in the thalamus, basal ganglia, or brainstem have a higher risk of hemorrhage compared to superficial AVMs and surgical resection is more challenging. Our systematic review and meta-analysis provide a comprehensive summary of the stereotactic radiosurgery (SRS) outcomes for deep-seated AVMs. This study follows the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We conducted a systematic search in December 2022 for all reports of deep-seated arteriovenous malformations treated with SRS. Thirty-four studies (2508 patients) were included. The mean obliteration rate in brainstem AVM was 67% (95% CI: 0.60-0.73), with significant inter-study heterogeneity (tau 2 = 0.0113, I 2 = 67%, chi 2 = 55.33, df = 16, p-value < 0.01). The mean obliteration rate in basal ganglia/thalamus AVM was 65% (95% CI: 0.58-0.72) with significant inter-study heterogeneity (tau 2 = 0.0150, I 2 = 78%, chi 2 = 81.79, df = 15, p-value < 0.01). The presence of deep draining veins (p-value: 0.02) and marginal radiation dose (p-value: 0.04) were positively correlated with obliteration rate in brainstem AVMs. The mean incidence of hemorrhage after treatment was 7% for the brainstem and 9% for basal ganglia/thalamus AVMs (95% CI: 0.05-0.09 and 95% CI: 0.05-0.12, respectively). The meta-regression analysis demonstrated a significant positive correlation (p-value < 0.001) between post-operative hemorrhagic events and several factors, including ruptured lesion, previous surgery, and Ponce C classification in basal ganglia/thalamus AVMs. The present study found that radiosurgery appears to be a safe and effective modality in treating brainstem, thalamus, and basal ganglia AVMs, as evidenced by satisfactory rates of lesion obliteration and post-surgical hemorrhage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The most common surgical technique for the management of pituitary adenomas is the endoscopic endonasal transsphenoidal approach (EEA). preoperative neuroimaging along with detecting surgical landmarks of the sphenoid sinus during surgery is important for making a successful operation., Method: This study includes 1009 patients with pituitary adenomas who underwent EEA between 2013 and 2020. We evaluated the anatomical features of the sphenoid sinus through a panel of items obtained from imaging and intra-operative findings., Results: Our result includes 57.38% nonfunctional, 8.42% cushing, 12.39% prolactinoma, and 21.8% acromegaly patients who had undergone endoscopic endonasal transsphenoidal surgery. The mean age of the patients was 45 with a male to female ratio of 1.2:1. Sellar sphenoid type was the most common (91.8%) with only 12% symmetrical inter sphenoid septa, Internal carotid artery dehiscence was found in 1.7% of the cases. Apoplexy was present in 6.3% of patients, which was found more prevalent in nonfunctional adenomas (9.67%, Odds ratio: 4.85, 95% CI 2.24-11.79) and further investigation revealed a significant association between apoplexy and sphenoid mucosal edema and hemorrhage (Odds ratio: 43.0, 95% CI 22.50-84.26), and between apoplexy and cystic lesions (OR = 4.14, 95% CI 1.87-8.45, P-value < 0.0001). Acromegaly is associated with the increased number of lateral recces (Odds ratio: 11.41, 95% CI 7.54-17.52), septation of the sphenoid sinus (Marginal mean: 3.92, 95% CI 3.69-4.14), edematous sinonasal mucosa (Odds ratio: 6.7; 95% CI 4.46-10.08), and higher bony (OR: 4.81, 95% CI 2.60-8.97, P-value < 0.001) and cavernous (OR: 1.7, 95% CI 1.13-2.46, P-value < 0.01) invasion., Conclusion: The present study provides anatomical data about the sphenoid sinus and its adjacent vital structures with adenomal specific changes that are necessary to prevent complications during endoscopic advanced transsphenoidal surgery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multiple sclerosis (MS) is a neuroinflammatory disorder damaging structural connectivity. Natural remodeling processes of the nervous system can, to some extent, restore the damage caused. However, there is a lack of biomarkers to evaluate remodeling in MS. Our objective is to evaluate graph theory metrics (especially modularity) as a biomarker of remodeling and cognition in MS. We recruited 60 relapsing-remitting MS and 26 healthy controls. Structural and diffusion MRI, plus cognitive and disability evaluations, were done. We calculated modularity and global efficiency from the tractography-derived connectivity matrices. Association of graph metrics with T2 lesion load, cognition, and disability was evaluated using general linear models adjusting for age, gender, and disease duration wherever applicable. We showed that MS subjects had higher modularity and lower global efficiency compared with controls. In the MS group, modularity was inversely associated with cognitive performance but positively associated with T2 lesion load. Our results indicate that modularity increase is due to the disruption of intermodular connections in MS because of the lesions, with no improvement or preserving of cognitive functions., (© 2022 Massachusetts Institute of Technology.)

Apathy is present at the onset in nearly half the patients with schizophrenia. Current therapies lack the efficiency to improve apathy in patients. The presence of apathy is also associated with poorer outcomes. Despite its clinical importance, the underlying mechanism of apathy in schizophrenia is unclear, but it seems frontostriatal connections play a role. In this study, we investigated whole-brain white matter microstructural properties associated with the severity of apathy-avolition in schizophrenia. We included 80 schizophrenia patients (60 Male, 20 Female) from the Mind Clinical Imaging Consortium database and associated Apathy-Avolition score of "Scale for Assessment of Negative Symptoms" with fiber integrity measures derived from diffusion-weighted imaging using Tract-Based Spatial Statistics (TBSS). We also did tractography on eight tracts, including bilateral superior longitudinal fasciculus, uncinate fasciculus, cingulum, genu and splenium of the corpus callosum. Age, gender, years of education, chlorpromazine equivalent cumulative dose, and acquisition site were inserted as covariates. We showed a widespread association between lower fiber integrity (by measures of increased mean diffusivity and decreased fractional anisotropy) and increased apathy-avolition in TBSS, which we also validated in tractography. Moreover, mean diffusivity, and not fractional anisotropy, was associated with apathy independent of disease severity. In conclusion, we propose diffuse white-matter pathology, within the corpus callosum, limbic system, and the frontostriatal circuit is involved in apathy-avolition in schizophrenia. Also, we suggest that diffuse neuroinflammatory processes may play a part in apathy-avolition, independent of disease severity., (Copyright © 2021. Published by Elsevier Ltd.)