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Journal of Neurosurgery Jun 2024Advancements in microsurgical technique and technology continue to improve outcomes in patients with skull base tumor. The primary cranial nerve eight monitoring systems...
OBJECTIVE
Advancements in microsurgical technique and technology continue to improve outcomes in patients with skull base tumor. The primary cranial nerve eight monitoring systems used in hearing preservation surgery for vestibular schwannomas (VSs) are direct cranial nerve eight monitoring (DCNEM) and auditory brainstem response (ABR), although current guidelines are unable to definitively recommend one over the other due to limited literature on the topic. Thus, further research is needed to determine the utility of DCNEM and ABR. The authors performed a retrospective cohort study and created an interactive model that compares hearing preservation outcomes based on tumor size in patients receiving ABR+DCNEM and ABR-only monitoring.
METHODS
Twenty-eight patients received ABR+DCNEM and 72 patients received ABR-only monitoring during VS hearing preservation surgery at a single tertiary academic medical center between January 2008 and November 2022. Inclusion criteria consisted of adult patients with a preoperative American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification of A or B. Tumor size was measured as the maximal medial to lateral length, including the internal auditory canal component.
RESULTS
Overall hearing preservation (word recognition score [WRS] > 0%) was achieved in 31 patients with ABR-only monitoring (43.1%) and in 18 patients with ABR+DCNEM (64.3%). Serviceable hearing preservation (AAO-HNS class A or B) was attained in 19 patients with ABR-only monitoring (26.4%) and in 11 patients with ABR+DCNEM (39.3%). There was no difference in overall hearing preservation between the two groups (p = 0.13). Change in tumor size was not associated with the odds of serviceable hearing preservation for the ABR-only group (p = 0.89); however, for ABR+DCNEM, there was some indication of an interaction between tumor size and the association of ABR+DCNEM versus ABR-only monitoring, with the odds of serviceable hearing preservation at p = 0.089. Furthermore, with ABR+DCNEM, every 0.5-cm increase in tumor size was associated with a decreased odds of serviceable hearing preservation on multivariable analysis (p = 0.05). For both overall and serviceable hearing preservation, a worse preoperative AAO-HNS classification was associated with a decreased odds of preservation (OR 0.43, 95% CI 0.19-0.97, p = 0.042; OR 0.17, 95% CI 0.053-0.55, p = 0.0031, respectively).
CONCLUSIONS
The result of this interactive model study proposes that there may be a higher chance of hearing preservation when using ABR+DCNEM rather than ABR alone for smaller tumors, with that relationship reversing as tumor size increases.
PubMed: 38941638
DOI: 10.3171/2024.4.JNS221868 -
Medicina (Kaunas, Lithuania) Jun 2024: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the...
: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the Hannover Classification. Microscope-based augmented reality (AR) can be beneficial in cerebellopontine angle and lateral skull base surgery, since these are small areas packed with anatomical structures and the use of this technology enables automatic 3D building of a model without the need for a surgeon to mentally perform this task of transferring 2D images seen on the microscope into imaginary 3D images, which then reduces the possibility of error and provides better orientation in the operative field. : All patients who underwent surgery for resection of ANs in our department were included in this study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. : A total of 43 consecutive patients (25 female, median age 60.5 ± 16 years) who underwent resection of ANs via retrosigmoid osteoclastic craniotomy with the use of intraoperative neuromonitoring (22 right-sided, 14 giant tumors, 10 cystic, 7 with hydrocephalus) by a single surgeon were included in this study, with a median follow up of 41.2 ± 32.2 months. A total of 18 patients underwent subtotal resection, 1 patient partial resection and 24 patients gross total resection. A total of 27 patients underwent resection in sitting position and the rest in semi-sitting position. Out of 37 patients who had no facial nerve deficit prior to surgery, 19 patients were intact following surgery, 7 patients had House Brackmann (HB) Grade II paresis, 3 patients HB III, 7 patients HB IV and 1 patient HB V. Wound healing deficit with cerebrospinal fluid (CSF) leak occurred in 8 patients (18.6%). Operative time was 317.3 ± 99 min. One patient which had recurrence and one further patient with partial resection underwent radiotherapy following surgery. A total of 16 patients (37.2%) underwent resection using fiducial-based navigation and microscope-based AR, all in sitting position. Segmented objects of interest in AR were the sigmoid and transverse sinus, tumor outline, cranial nerves (CN) VII, VIII and V, petrous vein, cochlea and semicircular canals and brain stem. Operative time and clinical outcome did not differ between the AR and the non-AR group. However, use of AR improved orientation in the operative field for craniotomy planning and microsurgical resection by identification of important neurovascular structures. : The single-center experience of resection of ANs showed a high rate of gross total (GTR) and subtotal resection (STR) with low recurrence. Use of AR improves intraoperative orientation and facilitates craniotomy planning and AN resection through early improved identification of important anatomical relations to structures of the inner auditory canal, venous sinuses, petrous vein, brain stem and the course of cranial nerves.
Topics: Humans; Female; Middle Aged; Male; Microsurgery; Neuroma, Acoustic; Aged; Adult; Augmented Reality; Neurosurgical Procedures; Microscopy; Treatment Outcome; Imaging, Three-Dimensional
PubMed: 38929549
DOI: 10.3390/medicina60060932 -
Brain Sciences Jun 2024Vestibular schwannoma (VS), also known as acoustic neuroma, is a benign, well-encapsulated, and slow-growing tumor that originates from Schwann cells, which form the...
BACKGROUND
Vestibular schwannoma (VS), also known as acoustic neuroma, is a benign, well-encapsulated, and slow-growing tumor that originates from Schwann cells, which form the myelin sheath around the vestibulocochlear nerve (VIII cranial nerve). The surgical treatment of this condition presents a challenging task for surgeons, as the tumor's location and size make it difficult to remove without causing damage to the surrounding structures. In recent years, fluorescein sodium (FS) has been proposed as a tool to enhance surgical outcomes in VS surgery. This essay will provide an analytical comparison of the use of FS in VS surgery, evaluating its benefits and limitations and comparing surgical outcomes with and without FS-assisted surgery.
METHODS
In a retrospective study conducted at San Filippo Neri Hospital, we examined VS cases that were operated on between January 2017 and December 2023. The patients were divided into two groups: group A, which consisted of patients who underwent surgery without the use of FS until January 2020 (102 cases), and group B, which included patients who underwent surgery with FS after January 2020 (55 cases). All operations were performed using the retrosigmoid approach, and tumor size was classified according to the Koos, et al. classification system. The extent of surgical removal was evaluated using both the intraoperative surgeon's opinion and postoperative MRI imaging. Preoperatively and postoperatively, facial nerve function and hearing were assessed. In group B, FS was used to assist the surgical procedures, which were performed using a surgical microscope equipped with an integrated fluorescein filter. Postoperative clinical and MRI controls were performed at six months and annually, with no patients lost to follow-up.
RESULTS
This study investigated the impact of intraoperative fluorescein exposure on tumor resection and clinical outcomes in patients with VS. The study found a statistically significant difference in the tumor resection rates between patients who received fluorescein intraoperatively ( = 0.037). Further analyses using the Koos classification system revealed a significant effect of fluorescein exposure, particularly in the Koos 3 subgroup ( = 0.001). Notably, no significant differences were observed in hearing loss or facial nerve function between the two groups. A Spearman correlation analysis revealed a positive correlation between tumor size and Koos, age, and size, but no significant correlation was found between facial nerve function tests.
CONCLUSIONS
FS-assisted surgery for VS may potentially enhance tumor resection, allowing for more comprehensive tumor removal.
PubMed: 38928571
DOI: 10.3390/brainsci14060571 -
International Journal of Molecular... Jun 2024NF2-related schwannomatosis (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular... (Review)
Review
NF2-related schwannomatosis (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.
Topics: Humans; Neurofibromatoses; Neurofibromin 2; Neurilemmoma; Skin Neoplasms; Animals; Neurofibromatosis 2; Mutation; Signal Transduction; Molecular Targeted Therapy
PubMed: 38928264
DOI: 10.3390/ijms25126558 -
Neurosurgical Review Jun 2024Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still,... (Comparative Study)
Comparative Study
Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still, there has not been a direct comparative study comparing both SRS and SURGERY effectiveness in cystic VS. This retrospective bi-center cohort study aims to analyze the management of cystic VS compared to solid VS in a dual center study with both microsurgery (SURGERY) and stereotactic radiosurgery (SRS). Cystic morphology was defined as presence of any T2-hyperintense and Gadolinium-contrast-negative cyst of any size in the pre-interventional MRI. A matched subgroup analysis was carried out by determining a subgroup of matched SURGERY-treated solid VS and SRS-treated solid VS. Functional status, and post-interventional tumor volume size was then compared. From 2005 to 2011, N = 901 patients with primary and solitary VS were treated in both study sites. Of these, 6% showed cystic morphology. The incidence of cystic VS increased with tumor size: 1.75% in Koos I, 4.07% in Koos II, 4.84% in Koos III, and the highest incidence with 15.43% in Koos IV. Shunt-Dependency was significantly more often in cystic VS compared to solid VS (p = 0.024) and patients with cystic VS presented with significantly worse Charlson Comorbidity Index (CCI) compared to solid VS (p < 0.001). The rate of GTR was 87% in cystic VS and therefore significantly lower, compared to 96% in solid VS (p = 0.037). The incidence of dynamic volume change (decrease and increase) after SRS was significantly more common in cystic VS compared to the matched solid VS (p = 0.042). The incidence of tumor progression with SRS in cystic VS was 25%. When comparing EOR in the SURGERY-treated cystic to solid VS, the rate for tumor recurrence was significantly lower in GTR with 4% compared to STR with 50% (p = 0.042). Tumor control in cystic VS is superior in SURGERY, when treated with a high extent of resection grade, compared to SRS. Therapeutic response of SRS was worse in cystic compared to solid VS. However, when cystic VS was treated surgically, the rate of GTR is lower compared to the overall, and solid VS cohort. The significantly higher number of patients with relevant post-operative facial palsy in cystic VS is accredited to the increased tumor size not its sole cystic morphology. Cystic VS should be surgically treated in specialized centers.
Topics: Humans; Radiosurgery; Microsurgery; Neuroma, Acoustic; Female; Male; Middle Aged; Adult; Retrospective Studies; Aged; Treatment Outcome; Magnetic Resonance Imaging; Cysts; Young Adult
PubMed: 38914785
DOI: 10.1007/s10143-024-02495-w -
Scientific Reports Jun 2024Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a...
Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.
Topics: Humans; Meningioma; Neuroma, Acoustic; Elasticity Imaging Techniques; Female; Male; Middle Aged; Biomarkers, Tumor; Aged; Prospective Studies; Adult; Meningeal Neoplasms; Treatment Outcome; Tumor Microenvironment; Magnetic Resonance Imaging
PubMed: 38914647
DOI: 10.1038/s41598-024-64597-1 -
The New England Journal of Medicine Jun 2024-related schwannomatosis (-SWN, formerly called neurofibromatosis type 2) is a tumor predisposition syndrome that is manifested by multiple vestibular schwannomas,...
BACKGROUND
-related schwannomatosis (-SWN, formerly called neurofibromatosis type 2) is a tumor predisposition syndrome that is manifested by multiple vestibular schwannomas, nonvestibular schwannomas, meningiomas, and ependymomas. The condition is relentlessly progressive with no approved therapies. On the basis of preclinical activity of brigatinib (an inhibitor of multiple tyrosine kinases) in -driven nonvestibular schwannoma and meningioma, data were needed on the use of brigatinib in patients with multiple types of progressive -SWN tumors.
METHODS
In this phase 2 platform trial with a basket design, patients who were 12 years of age or older with -SWN and progressive tumors were treated with oral brigatinib at a dose of 180 mg daily. A central review committee evaluated one target tumor and up to five nontarget tumors in each patient. The primary outcome was radiographic response in target tumors. Key secondary outcomes were safety, response rate in all tumors, hearing response, and patient-reported outcomes.
RESULTS
A total of 40 patients (median age, 26 years) with progressive target tumors (10 vestibular schwannomas, 8 nonvestibular schwannomas, 20 meningiomas, and 2 ependymomas) received treatment with brigatinib. After a median follow-up of 10.4 months, the percentage of tumors with a radiographic response was 10% (95% confidence interval [CI], 3 to 24) for target tumors and 23% (95% CI, 16 to 30) for all tumors; meningiomas and nonvestibular schwannomas had the greatest benefit. Annualized growth rates decreased for all tumor types during treatment. Hearing improvement occurred in 35% (95% CI, 20 to 53) of eligible ears. Exploratory analyses suggested a decrease in self-reported pain severity during treatment (-0.013 units per month; 95% CI, -0.002 to -0.029) on a scale from 0 (no pain) to 3 (severe pain). No grade 4 or 5 treatment-related adverse events were reported.
CONCLUSIONS
Brigatinib treatment resulted in radiographic responses in multiple tumor types and clinical benefit in a heavily pretreated cohort of patients with -SWN. (Funded by the Children's Tumor Foundation and others; INTUITT-NF2 ClinicalTrials.gov number, NCT04374305.).
Topics: Humans; Male; Adult; Female; Pyrimidines; Neurilemmoma; Adolescent; Organophosphorus Compounds; Young Adult; Middle Aged; Skin Neoplasms; Child; Neurofibromatoses; Neurofibromatosis 2; Antineoplastic Agents; Protein Kinase Inhibitors
PubMed: 38904277
DOI: 10.1056/NEJMoa2400985 -
Acta Medica Okayama Jun 2024We report a case of a large vestibular schwannoma in an 80-year-old female patient that shrank after palliative Gamma Knife radiosurgery (GKS). Neurological symptoms...
We report a case of a large vestibular schwannoma in an 80-year-old female patient that shrank after palliative Gamma Knife radiosurgery (GKS). Neurological symptoms included hearing deterioration and facial palsy. The tumor volume was 21.9 mL. Craniotomy was considered high-risk, and conventional GKS was risky, owing to the risk of transient enlargement. Therefore, GKS was performed on only a portion of the tumor. The marginal dose (12 Gy) volume was 3.8 mL (17.4%). The tumor began to shrink after transient enlargement. Sixty months later, the tumor volume was only 3.1 mL, and the patient was able to maintain independent activities of daily living without salvage treatment.
Topics: Humans; Radiosurgery; Female; Aged, 80 and over; Neuroma, Acoustic; Palliative Care
PubMed: 38902220
DOI: 10.18926/AMO/67207 -
Acta Oncologica (Stockholm, Sweden) Jun 2024
Topics: Humans; Neuroma, Acoustic; Finland; Incidence; Child; Adolescent; Female; Male
PubMed: 38899394
DOI: 10.2340/1651-226X.2024.40652 -
Scientific Reports Jun 2024This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and...
This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.
Topics: Humans; Neuroma, Acoustic; Female; Male; Middle Aged; Proteome; Perilymph; Hearing Loss; Adult; Aged; Cerebrospinal Fluid; Audiometry, Pure-Tone
PubMed: 38898156
DOI: 10.1038/s41598-024-64352-6