-
Brazilian Journal of Otorhinolaryngology 2023To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. (Review)
Review
OBJECTIVES
To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery.
METHODS
A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128.
RESULTS
From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis.
CONCLUSION
It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.
Topics: Adult; Female; Humans; Male; Deafness; Hearing Loss; Neuroma, Acoustic; Radiation Dosage; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 37579571
DOI: 10.1016/j.bjorl.2023.101300 -
Acta Neurochirurgica Oct 2023Vestibular schwannoma (VS) is the most common benign tumour arising in the lateral skull base. Reported incidence rates of VS vary across geographical locations and over...
BACKGROUND
Vestibular schwannoma (VS) is the most common benign tumour arising in the lateral skull base. Reported incidence rates of VS vary across geographical locations and over time. There is scarce updated evidence over the past decade on the epidemiology and mode of presentation of VS.
OBJECTIVE
To describe the epidemiology and mode of presentation of VS in the East of England between 2013 and 2016.
METHODS
A retrospective epidemiological analysis of data from a national VS registry and electronic patient records was conducted, including all newly diagnosed adult patients in a UK tertiary referral centre, between April 1st, 2013, and March 31st, 2016.
RESULTS
There were 391 new cases identified resulting in an overall mean incidence of 2.2 VS cases per 100,000 person-year. The incidence rate for all patients in the <40 age group ranged between 0.3 and 0.7 per 100,000 person-year, increasing to a range of 5.7 to 6.1 per 100,000 person-year in the 60-69 age group. The top three combinations of symptoms on presentation per patient were hearing loss and tinnitus (97, 24.8%), hearing loss alone (79, 20.2%) and hearing loss, tinnitus, and balance symptoms (61, 15.6%). The median duration of symptoms was 12 months, with a wide range from 1.4 to 300 months. Age was negatively correlated with tumour size (r = -0.14 [-0.24 to -0.04], p=0.01) and positively correlated with symptom duration (r = 0.16 [0.03-0.29], p=0.02).
CONCLUSIONS
The incidence of vestibular schwannoma has increased compared to previous studies in the UK and is similar to incidence rates reported in other countries during the past decade. It peaks in the seventh decade of life, mainly because of an increase in the diagnosis of small tumours with a long duration of audio-vestibular symptoms in older patients, compared to earlier studies.
Topics: Adult; Humans; Aged; Neuroma, Acoustic; Incidence; Retrospective Studies; Tinnitus; Cohort Studies; Registries; Hearing Loss
PubMed: 37452904
DOI: 10.1007/s00701-023-05665-9 -
Neuro-oncology Advances 2023Both stereotactic radiosurgery () and microsurgical resection () are available as treatment options for sporadic vestibular schwannoma (VS). There are very few direct...
BACKGROUND
Both stereotactic radiosurgery () and microsurgical resection () are available as treatment options for sporadic vestibular schwannoma (VS). There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. This present study aimed to compare the nuances in the treatment of VS by and in 2 highly specialized neurosurgical centers.
METHODS
This is a retrospective bicentric cohort study. Data from patients treated between 2005 and 2011 were collected retrospectively. Recurrence-free survival (RFS) was assessed radiographically by contrast-enhanced magnetic resonance imaging.
RESULTS
The study population included = 901 patients with a mean follow-up of 7 years. Overall, the incidence of recurrence was 7% after , and 11% after with superior tumor control in in the Kaplan-Meier-analysis ( = 0.031). In small tumors (Koos I and II), tumor control was equivalent in both treatment arms. In large VS (Koos III and IV), however, RFS was superior in . The extent of resection correlated with RFS ( < .001). Facial and hearing deterioration was similar in both treatment arms in small VS, but more pronounced in of large VS. Tinnitus, vertigo, imbalance, and trigeminal symptoms were more often improved by than .
CONCLUSIONS
can achieve similar tumor control compared to in smaller VS (Koos I and II)-with similar postinterventional morbidities. In large VS (Koos III and IV), long-term tumor control of is inferior to . Based on these results, we suggest that if combination therapy is chosen, the residual tumor should not exceed the size of Koos II.
PubMed: 38024239
DOI: 10.1093/noajnl/vdad146 -
Acta Neuropathologica Communications Sep 2023Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with...
Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages.
Topics: Humans; Macrophages; Meningeal Neoplasms; Meningioma; Neurofibromatosis 2; Retrospective Studies
PubMed: 37752594
DOI: 10.1186/s40478-023-01645-3 -
Neurosurgical Review Jul 2023Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic radiosurgery (SRS). Here, we performed a systematic review and meta-analysis of proton beam for VSs, evaluating tumor control and cranial nerve preservation rates, particularly with regard to facial and hearing preservation.
METHODS
We reviewed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) articles published between 1968 and September 30, 2022. We retained 8 studies reporting 587 patients.
RESULTS
Overall rate of tumor control (both stability and decrease in volume) was 95.4% (range 93.5-97.2%, p heterogeneity= 0.77, p<0.001). Overall rate of tumor progression was 4.6% (range 2.8-6.5%, p heterogeneity < 0.77, p<0.001). Overall rate of trigeminal nerve preservation (absence of numbness) was 95.6% (range 93.5-97.7%, I = 11.44%, p heterogeneity= 0.34, p<0.001). Overall rate of facial nerve preservation was 93.7% (range 89.6-97.7%, I = 76.27%, p heterogeneity<0.001, p<0.001). Overall rate of hearing preservation was 40.6% (range 29.4-51.8%, I = 43.36%, p heterogeneity= 0.1, p<0.001).
CONCLUSION
Proton beam therapy for VSs achieves high tumor control rates, as high as 95.4%. Facial rate preservation overall rates are 93%, which is lower compared to the most SRS series. Compared with most currently reported SRS techniques, proton beam radiation therapy for VSs does not offer an advantage for facial and hearing preservation compared to most of the currently reported SRS series.
Topics: Humans; Neuroma, Acoustic; Proton Therapy; Hearing; Cranial Nerves; Facial Nerve; Radiosurgery; Treatment Outcome; Follow-Up Studies; Retrospective Studies
PubMed: 37402894
DOI: 10.1007/s10143-023-02060-x -
European Journal of Medical Genetics Jul 2023This paper focuses on genetic counselling in Phelan-McDermid syndrome (PMS), a rare neurodevelopmental disorder caused by a deletion 22q13.3 or a pathogenic variant in... (Review)
Review
This paper focuses on genetic counselling in Phelan-McDermid syndrome (PMS), a rare neurodevelopmental disorder caused by a deletion 22q13.3 or a pathogenic variant in SHANK3. It is one of a series of papers written by the European PMS consortium as a consensus guideline. We reviewed the available literature based on pre-set questions to formulate recommendations on counselling, diagnostic work-up and surveillance for tumours related to ring chromosome 22. All recommendations were approved by the consortium, which consists of professionals and patient representatives, using a voting procedure. PMS can only rarely be diagnosed based solely on clinical features and requires confirmation via genetic testing. In most cases, the family will be referred to a clinical geneticist for counselling after the genetic diagnosis has been made. Family members will be investigated and, if indicated, the chance of recurrence discussed with them. Most individuals with PMS have a de novo deletion or a pathogenic variant of SHANK3. The 22q13.3 deletion can be a simple deletion, a ring chromosome 22, or the result of a parental balanced chromosomal anomaly, influencing the risk of recurrence. Individuals with a ring chromosome 22 have an increased risk of NF2-related schwannomatosis (formerly neurofibromatosis type 2) and atypical teratoid rhabdoid tumours, which are associated with the tumour-suppressor genes NF2 and SMARCB1, respectively, and both genes are located on chromosome 22. The prevalence of PMS due to a ring chromosome 22 is estimated to be 10-20%. The risk of developing a tumour in an individual with a ring chromosome 22 can be calculated as 2-4%. However, those individuals who do develop tumours often have multiple. We recommend referring all individuals with PMS and their parents to a clinical geneticist or a comparably experienced medical specialist for genetic counselling, further genetic testing, follow-up and discussion of prenatal diagnostic testing in subsequent pregnancies. We also recommend karyotyping to diagnose or exclude a ring chromosome 22 in individuals with a deletion 22q13.3 detected by molecular tests. If a ring chromosome 22 is found, we recommend discussing personalised follow-up for NF2-related tumours and specifically cerebral imaging between the age of 14 and 16 years.
Topics: Adolescent; Female; Humans; Pregnancy; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 22; Counseling; Neurofibromatosis 2; Ring Chromosomes
PubMed: 37120077
DOI: 10.1016/j.ejmg.2023.104773 -
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 -
Otolaryngology--head and Neck Surgery :... Sep 2023Intracochlear schwannoma is very rare, and complete loss of hearing is inevitable after the removal of this tumor. Here, we discuss cochlear implantation (CI) performed...
OBJECTIVE
Intracochlear schwannoma is very rare, and complete loss of hearing is inevitable after the removal of this tumor. Here, we discuss cochlear implantation (CI) performed simultaneously with the removal of an intracochlear schwannoma.
STUDY DESIGN
Retrospective single-center study.
SETTING
Tertiary medical institute.
METHODS
Simultaneous CI and intracochlear schwannoma removal were performed in 4 subjects. After subtotal cochleostomy, the tumors were removed meticulously, with preservation of the modiolus. A new slim modiolar electrode (Nucleus CI632) was placed in a manner that hugged the modiolus. The surgical outcomes of functional gain, word recognition score (WRS), sound localization, and hearing in noise and speech intelligibility tests were investigated.
RESULTS
Intracochlear schwannomas were removed successfully from the 4 patients, with no remnant tumor. The mean aided hearing threshold 6 months after surgery was 25.0 ± 1.8 dB, and the mean-aided WRS with a 60 dB stimulus was 36.0 ± 18.8% (range 16%-60%). The Categorical Auditory Performance (CAP) score of the 3 single-sided deafness patients under contralateral ear masking was 7. The CAP score of the patient with bilateral sensorineural hearing loss was 6, which improved from a preoperative score of 0.
CONCLUSION
When an intracochlear schwannoma does not completely invade the modiolus, CI with simultaneous tumor removal can be performed successfully, resulting in good hearing performance. A slim modiolar electrode can be placed stably at the modiolus after schwannoma removal.
Topics: Humans; Cochlear Implantation; Cochlear Implants; Neuroma, Acoustic; Retrospective Studies; Neurilemmoma; Treatment Outcome
PubMed: 36807253
DOI: 10.1002/ohn.300 -
European Radiology Nov 2023Surgical planning of vestibular schwannoma surgery would benefit greatly from a robust method of delineating the facial-vestibulocochlear nerve complex with respect to...
OBJECTIVES
Surgical planning of vestibular schwannoma surgery would benefit greatly from a robust method of delineating the facial-vestibulocochlear nerve complex with respect to the tumour. This study aimed to optimise a multi-shell readout-segmented diffusion-weighted imaging (rs-DWI) protocol and develop a novel post-processing pipeline to delineate the facial-vestibulocochlear complex within the skull base region, evaluating its accuracy intraoperatively using neuronavigation and tracked electrophysiological recordings.
METHODS
In a prospective study of five healthy volunteers and five patients who underwent vestibular schwannoma surgery, rs-DWI was performed and colour tissue maps (CTM) and probabilistic tractography of the cranial nerves were generated. In patients, the average symmetric surface distance (ASSD) and 95% Hausdorff distance (HD-95) were calculated with reference to the neuroradiologist-approved facial nerve segmentation. The accuracy of patient results was assessed intraoperatively using neuronavigation and tracked electrophysiological recordings.
RESULTS
Using CTM alone, the facial-vestibulocochlear complex of healthy volunteer subjects was visualised on 9/10 sides. CTM were generated in all 5 patients with vestibular schwannoma enabling the facial nerve to be accurately identified preoperatively. The mean ASSD between the annotators' two segmentations was 1.11 mm (SD 0.40) and the mean HD-95 was 4.62 mm (SD 1.78). The median distance from the nerve segmentation to a positive stimulation point was 1.21 mm (IQR 0.81-3.27 mm) and 2.03 mm (IQR 0.99-3.84 mm) for the two annotators, respectively.
CONCLUSIONS
rs-DWI may be used to acquire dMRI data of the cranial nerves within the posterior fossa.
CLINICAL RELEVANCE STATEMENT
Readout-segmented diffusion-weighted imaging and colour tissue mapping provide 1-2 mm spatially accurate imaging of the facial-vestibulocochlear nerve complex, enabling accurate preoperative localisation of the facial nerve. This study evaluated the technique in 5 healthy volunteers and 5 patients with vestibular schwannoma.
KEY POINTS
• Readout-segmented diffusion-weighted imaging (rs-DWI) with colour tissue mapping (CTM) visualised the facial-vestibulocochlear nerve complex on 9/10 sides in 5 healthy volunteer subjects. • Using rs-DWI and CTM, the facial nerve was visualised in all 5 patients with vestibular schwannoma and within 1.21-2.03 mm of the nerve's true intraoperative location. • Reproducible results were obtained on different scanners.
Topics: Humans; Neuroma, Acoustic; Prospective Studies; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Facial Nerve; Vestibulocochlear Nerve
PubMed: 37328641
DOI: 10.1007/s00330-023-09736-4 -
Oncogene Mar 2024Neurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and...
Neurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and diagnostic tumor type is bilateral vestibular schwannoma. There is no cure or drug therapy for NF2. Recommended treatments include surgical resection and radiation, both of which can leave patients with severe neurological deficits or increase the risk of future malignant tumors. Results of our previous pilot high-throughput drug screen identified phosphoinositide 3-kinase (PI3K) inhibitors as strong candidates based on loss of viability of mouse merlin-deficient Schwann cells (MD-SCs). Here we used novel human schwannoma model cells to conduct combination drug screens. We identified a class I PI3K inhibitor, pictilisib and p21 activated kinase (PAK) inhibitor, PF-3758309 as the top combination due to high synergy in cell viability assays. Both single and combination therapies significantly reduced growth of mouse MD-SCs in an orthotopic allograft mouse model. The inhibitor combination promoted cell cycle arrest and apoptosis in mouse merlin-deficient Schwann (MD-SCs) cells and cell cycle arrest in human MD-SCs. This study identifies the PI3K and PAK pathways as potential targets for combination drug treatment of NF2-related schwannomatosis.
Topics: Humans; Animals; Mice; Neurofibromatosis 2; Neurofibromin 2; Phosphatidylinositol 3-Kinases; p21-Activated Kinases; Phosphatidylinositol 3-Kinase; Neurilemmoma; Indazoles; Skin Neoplasms; Sulfonamides; Neurofibromatoses
PubMed: 38336988
DOI: 10.1038/s41388-024-02958-w