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Nature Communications Jan 2024Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME)...
Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.
Topics: Humans; Neuroma, Acoustic; Ecosystem; Multiomics; Schwann Cells; Signal Transduction; Single-Cell Analysis; Tumor Microenvironment
PubMed: 38216553
DOI: 10.1038/s41467-023-42762-w -
The Annals of Otology, Rhinology, and... Jul 2023To determine the natural history of cystic vestibular schwannomas (VS).
OBJECTIVE
To determine the natural history of cystic vestibular schwannomas (VS).
STUDY DESIGN
Retrospective cohort.
SETTING
Single tertiary academic hospital.
PATIENTS
Adults diagnosed with cystic VS who had at least 2 MRIs performed at least 6 months apart between 2008 and 2016 with no intervening treatment.
MAIN OUTCOME MEASURES
Volumetric growth rates of both the entire tumor and individual cystic and solid components were measured. Linear growth rate of the entire tumor was assessed using the largest diameter parallel to the petrous face at the cerebellopontine angle (CPA).
RESULTS
Twenty-one patients met inclusion criteria. The average volumetric growth rate of the tumor was 1.1 ± 2 (range: -1.2 to 7.8), while the average growth rate of the cystic component was 0.8 ± 1.6 (range: -0.5 to 5.3) cm/year. The CPA diameter of the tumor demonstrated an average linear growth rate of was 1.2 ± 4.4 (range: -8to 13.5) mm/year. With regards to tumor diameter, 9/21 (42.9%) remained stable, 3/21 (14.2%) decreased in size, while 9/21 (42.9%) increased in size.
CONCLUSIONS
Cystic tumors demonstrate a wide variability in growth rate. Larger, multi-center studies will be required to further compare this relationship to solid tumors.
Topics: Adult; Humans; Neuroma, Acoustic; Retrospective Studies; Treatment Outcome; Magnetic Resonance Imaging; Tertiary Care Centers
PubMed: 35993287
DOI: 10.1177/00034894221119613 -
Frontiers in Neurology 2023Brain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been...
BACKGROUND
Brain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been gradually revealed.
OBJECTIVE
This study aimed to explore the potential value of several reported peripheral blood parameters as comprehensively as possible, with preoperative diagnosis and identification of brain tumors (focus on gliomas).
METHODS
Patients with central nervous system tumors (craniopharyngioma, ependymoma, spinal meningioma, acoustic neuroma, brain metastases, meningioma, and glioma) or primary trigeminal neuralgia admitted to our hospital were retrospectively analyzed. The results of the routine coagulation factor test, serum albumin test, and blood cell test in peripheral blood were recorded for each group of patients on admission. Neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and their pairings were calculated. Their ability to identify brain tumors and their correlation with glioma grade were analyzed.
RESULTS
A total of 698 patients were included in this retrospective case-control study. Glioma patients had higher NLR, SII, and PIV but lower LMR. The NLR in the brain metastasis group was lower than that in the control, meningioma, and acoustic neuroma groups, but the SII and PIV were higher than those in the ependymoma group. Fibrinogen, white blood cell count, neutrophil count, NLR, SII, and PIV in the GBM group were higher than those in the control group. In all comparisons, NLR and NLR + dNLR showed the greatest accuracy, with areas under the curve (AUCs) of 0.7490 (0.6482-0.8498) and 0.7481 (0.6457-0.8505), respectively. PIV, dNLR + PIV, and LMR + PIV ranked second, with AUCs of 0.7200 (0.6551-0.7849), 0.7200 (0.6526-0.7874), 0.7204 (0.6530-0.7878) and 0.7206 (0.6536-0.7875), respectively.
CONCLUSION
NLR, PIV, and their combinations show high sensitivity and specificity in the diagnosis of brain tumors, especially gliomas. Overall, our results provide evidence for these convenient and reliable peripheral blood markers.
PubMed: 37936915
DOI: 10.3389/fneur.2023.1297835 -
Laryngo- Rhino- Otologie Mar 2024The treatment of vestibular schwannomas (VS) has always posed a challenge for physicians. Three essential treatment principles are available: wait-and-scan, surgery, and... (Review)
Review
The treatment of vestibular schwannomas (VS) has always posed a challenge for physicians. Three essential treatment principles are available: wait-and-scan, surgery, and stereotactic radiotherapy. In addition to the type of treatment, decisions must be made regarding the optimal timing of therapy, the combination of different treatment modalities, the potential surgical approach, and the type and intensity of radiation. Factors influencing the therapy decision include tumor location and size or stage, patient age, comorbidities, symptoms, postoperative hearing rehabilitation options, patient preferences, and, not least, the experience of the surgeons and the personnel and technical capabilities of the clinical site. This article begins with a brief overview of vestibular schwannomas, then outlines the fundamental interdisciplinary treatment options, and finally discusses the ENT (ear, nose, and throat)-relevant factors in the therapy decision.
Topics: Humans; Hearing; Neuroma, Acoustic; Radiosurgery; Treatment Outcome
PubMed: 38128578
DOI: 10.1055/a-2222-0878 -
Cancers Sep 2023Vestibular schwannoma (VS) are equally common in men and woman. A number of epidemiological studies have reported on sex-specific aspects of incidence, tumor size,...
Vestibular schwannoma (VS) are equally common in men and woman. A number of epidemiological studies have reported on sex-specific aspects of incidence, tumor size, tinnitus and hearing loss. However, data on sex-specific, pre- and post-surgically quality of life (QoL) are rare. The objective of the present study was to determine sex-specific aspects on QoL in VS. Health-related QoL was analyzed in 260 patients (112 male/148 female) with unilateral sporadic VS using general (SF-36: general Short-Form Health Survey), disease-specific (PANQOL: Penn Acoustic Neuroma Quality-of-Life Scale, PANQOL) and symptom-specific (DHI: Dizziness Handicap Inventory; HHI: Hearing Handicap Inventory; THI: Tinnitus Handicap Inventory; FDI: Facial Disability Index) QoL questionnaires. Sex differences were evaluated pre- and postoperative by multi- and univariate analyses based on 200 preoperative and 88 postoperative questionnaires. Female patients were significantly more affected by dizziness, headaches, reduced energy and anxiety. Energy and balance changed similarly in both sexes after surgery. However, postoperative women tended to be more affected by facial palsy and headaches than men. Despite the greater physical impairment, general health improved equivalently or even more in female patients than in males. In conclusion, self-rated QoL in VS is significantly affected by sex and surgery. This should be taken into account when counseling VS patients regarding observation, radiotherapy, and surgery.
PubMed: 37686642
DOI: 10.3390/cancers15174365 -
Journal of Clinical Neuroscience :... Oct 2023Acoustic neuroma (AN) research largely employs a medical framework to understand health outcomes. An alternative is to examine quality of life (QOL) outcomes. This study...
INTRODUCTION
Acoustic neuroma (AN) research largely employs a medical framework to understand health outcomes. An alternative is to examine quality of life (QOL) outcomes. This study explored whether mental well-being (i.e., anxiety and depression) were predictive of QOL in those with AN over and above symptomatology.
METHODS
A nationwide online survey was distributed to 24 community organisations. The inclusion criteria were a diagnosis of AN irrespective of the treatment approach. There were 52 respondents. Mental well-being was assessed using the Hospital Anxiety and Depression Scale (HADS), and quality of life was assessed using Penn Acoustic Neuroma QOL scale (PANQOL).
RESULTS
The most frequently reported symptoms reported were poor balance, tinnitus, hearing loss, and headache. Preliminary analyses suggested that headaches, tinnitus and mental well-being were significantly correlated with QOL. Hierarchical regression revealed that these two symptoms and mental well-being accounted for 18.7% and 51.1% of the variance in QOL, respectively. In addition, there was a significant difference in depression scores between management types, with the surgery group having a significantly higher depression score than the radiation group.
CONCLUSION
Symptoms and mood contribute to QOL for those diagnosed with AN. This can be understood through the common-sense model and fear of cancer recurrence. Screening for psychological difficulties should be provided from the point of diagnosis to post-treatment to allow for targeted management plans to mitigate the effects of these on QOL.
Topics: Humans; Quality of Life; Neuroma, Acoustic; Tinnitus; Psychological Well-Being; Mental Health; Headache
PubMed: 37597328
DOI: 10.1016/j.jocn.2023.08.005 -
Frontiers in Neuroscience 2023To investigate potential differences in absolute deviation values of subjective visual vertical and horizontal between unilateral acoustic neuroma patients and healthy...
OBJECTIVE
To investigate potential differences in absolute deviation values of subjective visual vertical and horizontal between unilateral acoustic neuroma patients and healthy young adults under varying degrees of static head tilt, as well as the impact of proprioception on these values, with the aim of determining the effect of acoustic neuroma on gravity sensory pathway function in patients.
METHODS
We recruited 22 patients diagnosed with unilateral acoustic neuroma and 25 healthy young adults and employed virtual reality technology to assess the absolute deviation values of subjective visual vertical (SVV) and subjective visual horizontal (SVH) under eight different static tilted head positions (Head centered (0° tilt), PdP, Head tilt 15°, 30°, 45° to the left and right), then compare and analyze intergroup differences.
RESULTS
In the Head-centered position, both SVV and SVH absolute deviated values were significantly higher in the AN group compared to healthy young adults. The AN group exhibited significantly higher absolute deviation values of SVV compared to the healthy group when tilting their head 30° left and right. Additionally, when tilting their heads to the right at 15° and 45° the AN group showed significant increases in SVH absolute deviated values compared to healthy adults. The SVV and SVH absolute deviation values of LAN and SAN groups did not reach statistical significance. The results of the SVV test for PDP position did not show any significant differences among all groups. However, the SVH test revealed that the absolute deviation values of the LAN group was significantly higher than that of healthy individuals.
CONCLUSION
Our study shows that the gravity sensing function of patients with unilateral acoustic neuroma is affected to different degrees, however, the degree of gravity sensing function damage of patients has little relationship with tumor size. When acoustic neuroma is larger than 2 cm, the effect of proprioception on patients' SVH outcome is noteworthy. So, we should pay attention to the postoperative follow-up of patients with acoustic neuroma and the evaluation of vestibular rehabilitation effect. Meanwhile, for patients opting for conservative treatment, it is imperative to monitor the dynamic changes in vestibular function and seize timely opportunities for intervention.
PubMed: 37954872
DOI: 10.3389/fnins.2023.1264585 -
Scientific Reports Dec 2023It is difficult to distinguish other pathologies mimicking Ménière's disease (MD) clinically. This study aims to investigate the differences of imaging findings and...
It is difficult to distinguish other pathologies mimicking Ménière's disease (MD) clinically. This study aims to investigate the differences of imaging findings and features between MD and other menieriform diseases via intravenous gadolinium-enhanced magnetic resonance imaging (MRI). 426 patients with menieriform symptoms, including MD, vestibular migraine (VM), and vestibular schwannoma (VS), underwent 3D-FLAIR and 3D-T2WI MRI 6 h after the intravenous gadolinium injection. MR images were analyzed for inner ear morphology, perilymphatic enhancement (PE), EH and other abnormalities. EH was observed at a higher rate in MD patients (85.71%) than patients with other menieriform diseases (VM group = 14.75%, VS group = 37.50%). The prevalence of unilateral EH as well as both cochlear and vestibular EH showed significant differences between MD and VM groups. The prevalence of cochlear EH (I and II) and vestibular EH (II and III) was different between MD and VM groups. The prevalence of PE was higher in MD than VM group. The degrees of cochlear and vestibular hydrops were higher in the definite than probable MD group (P < 0.05). Using these imaging features, MRI can be used to help differentiate MD from other menieriform diseases.
Topics: Humans; Meniere Disease; Endolymphatic Hydrops; Gadolinium; Vestibule, Labyrinth; Vertigo; Magnetic Resonance Imaging; Neuroma, Acoustic; Migraine Disorders
PubMed: 38057393
DOI: 10.1038/s41598-023-49066-5 -
Audiology Research Jul 2023to evaluate recent contributions to the literature on prognostic factors of hearing preservation in small vestibular schwannoma microsurgery. (Review)
Review
OBJECTIVE
to evaluate recent contributions to the literature on prognostic factors of hearing preservation in small vestibular schwannoma microsurgery.
METHODS
review of the most recent studies.
RESULTS
factors such as tumor size, preoperative hearing status, tumor growth rate, tumor origin, surgical approach, radiological characteristics, results of preoperative neurophysiological tests, preoperative symptoms and demographic features have been investigated and some of them reported to be significant in the prediction of hearing preservation.
CONCLUSIONS
tumor size and preoperative hearing status are the most impactful factors and play a key role in patient selection for hearing preservation surgery. Other features such as fundal extension, tumor origin and impaired ABR could have prognostic value on hearing preservation. Tumor growth rate, preoperative impedance, cVEMPs and age have also recently been found to be significant, but more studies are needed. The role of preoperative tinnitus, vertigo and gender is lacking and controversial, whereas the differences between available surgical approaches have been smoothed out in recent years.
PubMed: 37489378
DOI: 10.3390/audiolres13040042 -
Molecular Cancer Therapeutics Nov 2023Neurofibromatosis Type 2 (NF2) is a tumor predisposition syndrome caused by germline inactivating mutations in the NF2 gene encoding the merlin tumor suppressor....
Neurofibromatosis Type 2 (NF2) is a tumor predisposition syndrome caused by germline inactivating mutations in the NF2 gene encoding the merlin tumor suppressor. Patients develop multiple benign tumor types in the nervous system including bilateral vestibular schwannomas (VS). Standard treatments include surgery and radiation therapy, which may lead to loss of hearing, impaired facial nerve function, and other complications. Kinase inhibitor monotherapies have been evaluated clinically for NF2 patients with limited success, and more effective nonsurgical therapies are urgently needed. Schwannoma model cells treated with PI3K inhibitors upregulate activity of the focal adhesion kinase (FAK) family as a compensatory survival pathway. We screened combinations of 13 clinically relevant PI3K and FAK inhibitors using human isogenic normal and merlin-deficient Schwann cell lines. The most efficacious combination was PI3K/mTOR inhibitor omipalisib with SRC/FAK inhibitor dasatinib. Sub-GI50 doses of the single drugs blocked phosphorylation of their major target proteins. The combination was superior to either single agent in promoting a G1 cell-cycle arrest and produced a 44% decrease in tumor growth over a 2-week period in a pilot orthotopic allograft model. Evaluation of single and combination drugs in six human primary VS cell models revealed the combination was superior to the monotherapies in 3 of 6 VS samples, highlighting inter-tumor variability between patients consistent with observations from clinical trials with other molecular targeted agents. Dasatinib alone performed as well as the combination in the remaining three samples. Preclinically validated combination therapies hold promise for NF2 patients and warrants further study in clinical trials.
Topics: Humans; Neurofibromatosis 2; Neurofibromin 2; Phosphatidylinositol 3-Kinases; Focal Adhesion Protein-Tyrosine Kinases; Dasatinib; Phosphatidylinositol 3-Kinase; Neurilemmoma; Antineoplastic Agents; Cell Proliferation
PubMed: 37527526
DOI: 10.1158/1535-7163.MCT-23-0135