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Cancer Medicine Jan 2024The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding...
INTRODUCTION
The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs.
METHODS
A total of 37 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed.
RESULTS
The median age was 55 years old. The median tumor volume was 0.089 cm , and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. In a multivariate analysis, only baseline pure tone average > 30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratio. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm , and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration.
CONCLUSIONS
Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS.
Topics: Humans; Middle Aged; Neuroma, Acoustic; Radiosurgery; Retrospective Studies; Hearing; Hearing Loss; Treatment Outcome; Follow-Up Studies
PubMed: 38348957
DOI: 10.1002/cam4.6990 -
Scientific Reports Feb 2024The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we...
The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we examined the effects of vestibular loss on head-on-trunk kinematics during voluntary behavior. Head and trunk movements were measured in individuals with vestibular schwannoma before and then 6 weeks after unilateral vestibular deafferentation via surgical resection of the tumor. Movements were recorded in 6 dimensions (i.e., 3 axes of rotation and 3 axes of translation) using small light-weight inertial measurement units while participants performed balance and gait tasks. Kinematic measures differed between individuals with vestibular schwannoma (at both time points) and healthy controls for the more challenging exercises, namely those performed in tandem position or on an unstable surface without visual input. Quantitative assessment of the vestibulo-ocular reflex (VOR) revealed a reduction in VOR gain for individuals with vestibular schwannoma compared to control subjects, that was further reduced following surgery. These findings indicated that the impairment caused by either the tumor or subsequent surgical tumor resection altered head-on-trunk kinematics in a manner that is not normalized by central compensation. In contrast, we further found that head-on-trunk kinematics in individuals with vestibular schwannoma were actually comparable before and after surgery. Thus, taken together, our results indicate that vestibular loss impacts head-on-trunk kinematics during voluntary balance and gait behaviors, and suggest that the neural mechanisms mediating adaptation alter the motion strategies even before surgery in a manner that may be maladaptive for long-term compensation.
Topics: Humans; Neuroma, Acoustic; Reflex, Vestibulo-Ocular; Vestibule, Labyrinth; Neck; Gait; Head Movements
PubMed: 38347021
DOI: 10.1038/s41598-024-53512-3 -
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 -
Photodiagnosis and Photodynamic Therapy Feb 2024Brain tumors have serious adverse effects on public health and social economy. Accurate detection of brain tumor types is critical for effective and proactive treatment,...
BACKGROUND
Brain tumors have serious adverse effects on public health and social economy. Accurate detection of brain tumor types is critical for effective and proactive treatment, and thus improve the survival of patients.
METHODS
Four types of brain tumor tissue sections were detected by Raman spectroscopy. Principal component analysis (PCA) has been used to reduce the dimensionality of the Raman spectra data. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) methods were utilized to discriminate different types of brain tumors.
RESULTS
Raman spectra were collected from 40 brain tumors. Variations in intensity and shift were observed in the Raman spectra positioned at 721, 854, 1004, 1032, 1128, 1248, 1449 cm for different brain tumor tissues. The PCA results indicated that glioma, pituitary adenoma, and meningioma are difficult to differentiate from each other, whereas acoustic neuroma is clearly distinguished from the other three tumors. Multivariate analysis including QDA and LDA methods showed the classification accuracy rate of the QDA model was 99.47 %, better than the rate of LDA model was 95.07 %.
CONCLUSIONS
Raman spectroscopy could be used to extract valuable fingerprint-type molecular and chemical information of biological samples. The demonstrated technique has the potential to be developed to a rapid, label-free, and intelligent approach to distinguish brain tumor types with high accuracy.
Topics: Humans; Spectrum Analysis, Raman; Photochemotherapy; Photosensitizing Agents; Brain Neoplasms; Meningeal Neoplasms
PubMed: 38336147
DOI: 10.1016/j.pdpdt.2024.104010 -
Clinical Trials (London, England) Feb 2024Neurofibromatosis type 2-related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and...
BACKGROUND
Neurofibromatosis type 2-related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and cataracts. Mild to profound hearing loss and tinnitus are common symptoms reported by individuals with neurofibromatosis type 2. While tinnitus is known to have a significant and negative impact on the quality of life of individuals from the general population, the impact on individuals with neurofibromatosis type 2 is unknown. Consensus regarding the selection of suitable patient-reported outcome measures for assessment could advance further research into tinnitus in neurofibromatosis type 2 patients. The purpose of this work is to achieve a consensus recommendation by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration for patient-reported outcome measures used to evaluate quality of life in the domain of tinnitus for neurofibromatosis type 2 clinical trials.
METHODS
The Response Evaluation in Neurofibromatosis and Schwannomatosis Patient-Reported Outcomes Communication Subgroup systematically evaluated patient-reported outcome measures of quality of life in the domain of tinnitus for individuals with neurofibromatosis type 2 using previously published Response Evaluation in Neurofibromatosis and Schwannomatosis rating procedures. Of the 19 identified patient-reported outcome measures, 3 measures were excluded because they were not validated as an outcome measure or could not have been used as a single outcome measure for a clinical trial. Sixteen published patient-reported outcome measures for the domain of tinnitus were scored and compared on their participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials.
RESULTS
The Tinnitus Functional Index was identified as the most highly rated measure for the assessment of tinnitus in populations with neurofibromatosis type 2, due to strengths in the areas of item content, psychometric properties, feasibility, and available scores.
DISCUSSION
Response Evaluation in Neurofibromatosis and Schwannomatosis currently recommends the Tinnitus Functional Index for the assessment of tinnitus in neurofibromatosis type 2 clinical trials.
Topics: Humans; Neurofibromatosis 2; Tinnitus; Quality of Life; Neurofibromatoses; Patient Reported Outcome Measures; Neurilemmoma; Skin Neoplasms
PubMed: 38321701
DOI: 10.1177/17407745231217279 -
Frontiers in Oncology 2024Primary central nervous system, diffuse large B-cell lymphoma, post-transplant lymphoproliferative disorder in the cerebellopontine angle after an allogeneic stem cell...
PURPOSE
Primary central nervous system, diffuse large B-cell lymphoma, post-transplant lymphoproliferative disorder in the cerebellopontine angle after an allogeneic stem cell transplantation has never been reported in the literature. Typically, diffuse large B-cell lymphoma is non-polyploid. We report the first case of a patient with polyploid post-transplant lymphoproliferative disorder in the cerebellopontine angle who presented with back pain.
CASE PRESENTATION
A 45-year-old man with a history of nodular sclerosing classic Hodgkin lymphoma stage IIB treated with systemic chemotherapy, external radiation and autologous stem cell transplant and double umbilical cord allogeneic transplant presented with several weeks of back pain. He was found to have a small right cerebellopontine angle mass thought to be consistent with a meningioma. Patient presented again two weeks later with acute onset of severe headache, right sided ptosis, right facial numbness, weakness and possible seizure event. Repeat MRI scans showed an interval and significant increase of the right cerebellopontine angle lesion. Biopsy of the cerebellopontine angle lesion was planned with suspicion of lymphoma. Intraoperative pathology consultation findings were not consistent with an acoustic neuroma, meningioma, or epidermoid cyst. Lymphoma could not be definitively identified by intra-operative frozen section. However, it was suspected, and a portion of fresh specimen was submitted for flow cytometry analysis. A near total resection of the tumor and decompression of the brainstem was achieved. Final pathologic analysis was positive for post-transplant lymphoproliferative disorder, monomorphic type, diffuse large B-cell lymphoma, non-germinal center B-cell type, EBV+, post-transplant (allogeneic stem cell) setting (post-transplant lymphoproliferative disorder (PTLD), monomorphic type, diffuse large B-cell lymphoma, non-germinal center B-cell type (non-GCB), EBV-positive under pre-2022 WHO terminology). The patient began a high-dose methotrexate-based regimen (the MATRIX regimen).
CONCLUSIONS
Our case illustrates an unusual presentation of post-transplant lymphoproliferative disorder in the cerebellopontine angle in a patient with a remote history of allogeneic stem cell transplantation. It demonstrates the importance of keeping primary central nervous system post-transplant lymphoproliferative disorder on the differential for patients who present with back pain or headache that have a history of allogeneic stem cell transplant.
PubMed: 38313803
DOI: 10.3389/fonc.2024.1284577 -
Radiology Case Reports Apr 2024Vestibular Schwannoma (VS) is a benign nerve sheath tumors comprised of Schwann cells. This tumor is encapsulated, slow-growing, and originates from the internal...
Vestibular Schwannoma (VS) is a benign nerve sheath tumors comprised of Schwann cells. This tumor is encapsulated, slow-growing, and originates from the internal auditory canal, extending into the cerebellopontine angle (CPA). The incidence in individuals aged 20-44 is 0.75 per 100,000 cases, with bilateral VS incidence of 0.8 per 50,000 cases. Tumors in CPA are the most common type in the posterior fossa and cause serious neurological symptoms or become life-threatening when tumors enlarge and compress the brainstem. The majority of tumors are VS (acoustic neuromas), accounting for 80%-90% of cases. Common clinical symptoms include hearing loss, tinnitus, and vertigo. Additionally, these tumors cause compression of the trigeminal and facial nerves. Advances in rapidly evolving imaging technology and surgical methods have improved diagnosis and management. A 24-year-old male complained of hearing impairment for the past 3 years alongside headaches, and dizziness leading to a feeling of imbalance, double, and blurry vision, as well as a sensation of facial thickness on the left side. Neurological examination showed cranial nerve abnormalities, including bilateral paresis of cranial nerves III, IV, VI, left cranial nerves V and VII, bilateral cranial nerve VIII, right cranial nerve XII, and cerebellar abnormalities such as intention tremor, dysmetria, dysdiadokokinesia, wide-based gait, and falling to the right during Romberg testing with both eyes open and closed. The patient underwent a contrast-enhanced MRI of the head, followed by a right CPA tumors excision through craniotomy. A detailed understanding of the medical history, physical examination, and radiological proved to be crucial in establishing an accurate diagnosis and appropriate management. This was considered essential to minimize a worse prognosis.
PubMed: 38292801
DOI: 10.1016/j.radcr.2023.12.042 -
Case Reports in Ophthalmological... 2024Specific retinal abnormalities of neurofibromatosis type 2 (NF2) commonly include retinal astrocytoma and combined hamartoma of the retina and retinal pigment...
Specific retinal abnormalities of neurofibromatosis type 2 (NF2) commonly include retinal astrocytoma and combined hamartoma of the retina and retinal pigment epithelium. Vasculopathy is an uncommon manifestation of NF2. We reported an NF2 patient presenting with retinal ischemia. An 18-year-old healthy Chinese female with acute decreased vision. The fundus examination and optical coherence tomography revealed optic disc hamartoma in the right eye and paracentral acute middle maculopathy (PAMM) and cotton wool spot indicating retinal ischemia in the left eye. Brain MRI showed bilateral acoustic neuroma, parasellar meningioma, and cervical extramedullary tumor. The genetic test confirmed the diagnosis of NF2. Our case suggests that retinal ischemia could be the presenting sign of NF2. NF2 could be associated with retinal vasculopathy in addition to retina tumors.
PubMed: 38292257
DOI: 10.1155/2024/9133929 -
Journal of Neurological Surgery. Part... Feb 2024The evolution of acoustic neuroma (AN) care continues to shift focus on balancing optimized tumor resection and control with preservation of neurological function....
The evolution of acoustic neuroma (AN) care continues to shift focus on balancing optimized tumor resection and control with preservation of neurological function. Prior learning curve analyses of AN resection have demonstrated a plateau between 20 and 100 surgeries. In this study of 860 consecutive AN surgeries, we investigate the presence of an extended learning curve tail for AN resection. A retrospective cohort study of AN resections by a single interdisciplinary team between 1988 and 2018 was performed. Proportional odds models and restricted cubic splines were used to determine the association between the timing of surgery and odds of improved postoperative outcomes. The likelihood of improved postoperative House-Brackmann (HB) scores increased in the first 400 procedures, with HB 1 at 36% in 1988 compared with 79% in 2004. While the probability of a better HB score increased over time, there was a temporary decrease in slope of the cubic spline between 2005 and 2009. The last 400 cases continued to see improvement in optimal HB outcomes: adjusted odds of HB 1 score were twofold higher in both 2005 to 2009 (adjusted odds ratio [aOR]: 2.11, 95% confidence interval [CI]: 1.38-3.22, < 0.001) and 2010 to 2018 (aOR: 2.18, 95% CI: 1.49-3.19, < 0.001). In contrast to prior studies, our study demonstrates the steepest growth for learning, as measured by rates of preservation of facial function outcomes (HB 1), occurs in the first 400 AN resections. Additionally, improvements in patient outcomes continued even 30 years into practice, underlining the importance of lifelong learning.
PubMed: 38274479
DOI: 10.1055/a-1993-7906