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Cerebral Cortex (New York, N.Y. : 1991) Jun 2024Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss...
Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss.
Topics: Humans; Female; Male; Hearing Loss, Unilateral; Middle Aged; Adult; Connectome; Brain; Neuroma, Acoustic; Neural Pathways; Magnetic Resonance Imaging; Aged; Diffusion Tensor Imaging; Functional Laterality; Nerve Net
PubMed: 38896551
DOI: 10.1093/cercor/bhae220 -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024The extended translabyrinthine approach to acoustic neuroma (AN) was created to allow improved visualization and access to larger tumors.1,2 The dural opening, however,...
The extended translabyrinthine approach to acoustic neuroma (AN) was created to allow improved visualization and access to larger tumors.1,2 The dural opening, however, remained confined to the presigmoid space. Other authors have introduced modifications to increase the dura exposure around the internal auditory canal (IAC).3-5 The extra-extended translabyrinthine approach was conceptualized by the senior author (CC) to maximize AN exposure and early cranial nerve identification. The tentorial peeling was added to allow extradural mobilization of the temporal lobe.6 This allows further safe bone removal around the IAC and petrous apex and consistent opening of the facial canal at IAC fundus. This modification creates 280-to-360-degree dura exposure at the IAC. The dural opening extends to the petrous apex superiorly and the prepontine arachnoid cistern inferiorly and includes resection of a tentorium dural flap created by the tentorial peeling.6 This exposure allows for near circumferential exposure of the tumor and early identification of the glossopharyngeal nerve in the cochlear aqueduct area, the trigeminal nerve at the porus trigeminal, and the facial nerve (FN) at IAC fundus. In addition, this ample exposure permits identification of the FN trajectory in the tumor capsule before any tumor dissection. We present a detailed video of extra-extended translabyrinthine approach technique in a patient with a large left AN (Hannover classification T4B).7 This video does not involve any human research projects not requiring Institutional Review Board/ethic committee approval. The patient consented to the procedure and to the publication of his image. Complete resection was obtained. The FN function was House-Brackman I/VI.
PubMed: 38888316
DOI: 10.1227/ons.0000000000001223 -
Nature Communications Jun 2024Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors,...
Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII.
Topics: Schwann Cells; Humans; CRISPR-Cas Systems; Glucosephosphate Dehydrogenase; Neurofibromin 2; Coenzyme A Ligases; Synthetic Lethal Mutations; Animals; Neurofibromatosis 2; NADP; Mice; Oxidation-Reduction
PubMed: 38879607
DOI: 10.1038/s41467-024-49298-7 -
PloS One 2024Vestibular schwannoma can cause vestibular dysfunction; however, conflicting evidence exists regarding whether this affects the incidence of fall-related injuries in...
Vestibular schwannoma can cause vestibular dysfunction; however, conflicting evidence exists regarding whether this affects the incidence of fall-related injuries in this patient population. This matched cross-sectional and cohort study assess the risk of fall-related injuries in patients with vestibular schwannoma. The study included patients with vestibular schwannoma treated at a tertiary referral hospital in Sweden between 1988 and 2014. Information on fall-related injuries was obtained from the National Patient Register, and matched population comparisons were randomly selected in a 1:25 ratio. Fall-related injuries occurring pre- (within 5 years before the diagnosis of vestibular schwannoma) and post-diagnostically (up to 3 years after diagnosis or intervention) were registered. The association between vestibular schwannoma and fall-related injuries was estimated using logistic regression and Cox proportional hazards analyses. We identified 1153 patients with vestibular schwannoma (569 [49%] women and 584 [51%] men), and 28815 population comparisons. Among the patients, 9% and 7% had pre- and post-diagnostic fall-related injuries, respectively, and among the comparisons, 8% and 6% had pre- and post-diagnostic fall-related injuries, respectively. There was no increased risk of pre- (OR 1.14; CI 0.92-1.41) or post-diagnostic 1 year (HR 1.16; CI 0.87-1.54) or 3 years (HR 1.11; CI 0.89-1.29) fall-related injury among the total patient cohort. In age-stratified analyses, we found an increased risk of pre-diagnostic fall-related injury among patients aged 50-69 years (OR 1.42; CI 1.10-1.88). Patients who underwent middle fossa surgery, regardless of age, had an increased risk of post-surgery fall-related injury within 3 years of follow-up (HR 2.68; CI 1.06-6.81). We conclude that patients with vestibular schwannoma have a low risk of enduring fall-related injuries. Middle-aged patients with dizziness and fall-related injuries should be considered for a vestibular clinical evaluation. Our results highlight the importance of rehabilitation in avoiding future fall-related injuries among patients undergoing middle fossa surgery.
Topics: Humans; Neuroma, Acoustic; Female; Male; Middle Aged; Aged; Accidental Falls; Sweden; Adult; Cross-Sectional Studies; Risk Factors; Cohort Studies
PubMed: 38875269
DOI: 10.1371/journal.pone.0304184 -
Science Progress 2024A vestibular schwannoma is a benign tumor; however, the schwannoma itself and interventions can cause sensorineural hearing loss. Most vestibular schwannomas are...
A vestibular schwannoma is a benign tumor; however, the schwannoma itself and interventions can cause sensorineural hearing loss. Most vestibular schwannomas are unilateral tumors that affect hearing only on one side. Attention has focused on improving the quality of life for patients with unilateral hearing loss and therapeutic interventions to address this issue have been emphasized. Herein, we encountered a patient who was a candidate for hearing preservation surgery based on preoperative findings and had nonserviceable hearing after the surgery, according to the Gardner-Robertson classification. Postoperatively, the patient had decreased listening comprehension and ability to localize sound sources. He was fitted with bilateral hearing aids, and his ability to localize sound sources improved. Although the patient had postoperative nonserviceable hearing on the affected side and age-related hearing loss on the unaffected side, hearing aids in both ears were useful for his daily life. Therefore, the patient was able to maintain a binaural hearing effect and the ability to localize the sound source improved. This report emphasizes the importance of hearing preservation with vestibular schwannomas, and the demand for hearing loss rehabilitation as a postoperative complication can increase, even if hearing loss is nonserviceable.
Topics: Humans; Hearing Aids; Neuroma, Acoustic; Male; Middle Aged; Hearing Loss, Sensorineural; Quality of Life; Hearing Loss; Postoperative Complications
PubMed: 38872447
DOI: 10.1177/00368504241262195 -
Otology & Neurotology : Official... Jul 2024To evaluate the impact of losartan on vestibular schwannoma (VS) growth and related hearing loss during observation.
OBJECTIVE
To evaluate the impact of losartan on vestibular schwannoma (VS) growth and related hearing loss during observation.
STUDY DESIGN
Retrospective cohort study.
SETTING
Tertiary referral center.
PATIENTS
Sporadic VS patients undergoing initial observation with at least two magnetic resonance imaging and audiologic examinations.
INTERVENTION
Losartan.
MAIN OUTCOME MEASURES
Endpoints included VS growth, quantitative audiologic changes, survival free of tumor growth, and survival free of nonserviceable hearing. Patient characteristics and endpoints were compared by losartan use.
RESULTS
Seventy-nine patients were included, of which 33% were taking losartan. Tumor growth was observed in 50% of patients in the losartan group and 36% in the non-losartan group (p = 0.329). Survival analysis failed to show a significant difference in the hazard rate of VS growth between groups (hazard ratio, 1.38; 95% confidence interval, 0.70-2.70; p = 0.346). Throughout observation, mean decreases in normalized pure-tone average were 5.5 and 9.3 dB in the losartan and non-losartan groups, respectively (p = 0.908). Mean decreases in normalized word recognition score were 11.0 and 16.6% in the losartan and non-losartan groups, respectively (p = 0.757). Nonserviceable hearing developed in 19% of patients in the losartan group and 28% in the non-losartan group (p = 0.734). Survival analysis did not demonstrate a significant difference in the hazard rate of developing nonserviceable hearing between groups (hazard ratio, 1.71; 95% confidence interval, 0.56-5.21; p = 0.337).
CONCLUSIONS
Losartan use may not reduce the risk of VS growth or hearing loss during observation. A randomized trial would be ideal to further identify the true effect on growth and hearing.
Topics: Humans; Losartan; Male; Neuroma, Acoustic; Female; Middle Aged; Retrospective Studies; Hearing Loss; Aged; Adult; Magnetic Resonance Imaging; Angiotensin II Type 1 Receptor Blockers; Treatment Outcome
PubMed: 38865728
DOI: 10.1097/MAO.0000000000004214 -
European Journal of Obstetrics,... Jun 2024Vestibular schwannomas - benign tumours originating from the vestibular nerve - are rare during pregnancy. The intricate interplay between the gravid uterus, maternal...
BACKGROUND
Vestibular schwannomas - benign tumours originating from the vestibular nerve - are rare during pregnancy. The intricate interplay between the gravid uterus, maternal physiology and neoplastic growth imposes complexities that demand a careful and tailored approach.
CASE REPORT
This article reports a case of a pregnant woman in her 30 s diagnosed with a large vestibular schwannoma exhibiting brainstem compression, peritumoral oedema and cranial nerve encasement at 36 + 5 weeks of gestation. A multi-disciplinary team collaborated to devise a treatment plan considering the delicate balance between fetal well-being and the urgent need for intervention. A conservative approach involving close monitoring, corticosteroid therapy to manage peritumoral oedema, and detailed fetal assessments was initially employed. As the patient neared full term, a carefully planned caesarean section was performed, followed by a successful craniotomy to resect the vestibular schwannoma. Both the mother and the newborn showed favourable outcomes postoperatively. In addition, a literature review of cases of vestibular schwannoma in pregnancy was undertaken to inform optimal management strategies and enhance understanding of this complex scenario.
CONCLUSION
This case highlights the complexity of managing vestibular schwannomas in pregnant women, and underscores the importance of a tailored, collaborative approach. The condition was resolved successfully, emphasizing the significance of timely diagnosis, meticulous planning and a patient-centred approach in these rare and intricate cases.
PubMed: 38852318
DOI: 10.1016/j.ejogrb.2024.06.003 -
Neurosurgical Review Jun 2024Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that...
Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients - results of a single-center retrospective analysis.
Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3-5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17-87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43-128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77-35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.
Topics: Humans; Neuroma, Acoustic; Female; Male; Retrospective Studies; Middle Aged; Adult; Aged; Tumor Burden; Age Factors; Young Adult; Aged, 80 and over; Adolescent; Hearing; Preoperative Period
PubMed: 38850456
DOI: 10.1007/s10143-024-02419-8 -
Nature Communications Jun 2024Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some...
Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.
Topics: Humans; Transcriptome; Single-Cell Analysis; Animals; Regeneration; Mice; Saccule and Utricle; Neuroma, Acoustic; Ear, Inner; Insulin-Like Growth Factor I; Male; Hair Cells, Vestibular; Female; Gene Expression Profiling
PubMed: 38844821
DOI: 10.1038/s41467-024-48491-y -
Scientific Reports Jun 2024Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve,...
Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients' quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II-VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures.
Topics: Humans; Neuroma, Acoustic; Male; Female; Middle Aged; Microsurgery; Machine Learning; Prognosis; Facial Nerve Injuries; Retrospective Studies; Adult; Aged; Algorithms
PubMed: 38839778
DOI: 10.1038/s41598-024-63161-1