ABSTRACT
PURPOSE: Glioblastoma prognosis remains grim despite maximal, multimodal management. Recent literature has demonstrated an increase in research devoted to experimental treatments, particularly those relying on the foundations of active immunotherapy with promising results. We hypothesize that the utilization of bioengineered recombinant vault nanoparticles coupled with glioma-associated antigens, such as the NY-ESO-1 peptide, may be capable of stimulating native dendritic cell (DC) maturation and inducing an anti-tumor response. METHODS: Immature DCs were cultured from the bone marrow of 4-6-week-old C57BL/6 mice. The three treatment groups consisted of: (1) DC and media, (2) DC with mCherry vault, and (3) DC with NYESO and vault. DC maturity was assessed via flow cytometric evaluation of CD11c, CD86, and MHC-II. Increase in CD86 Median Fluorescence Intensity (MFI) was analyzed in the CD11c+CD86+MHC-II+ population to determine the extent of maturation RESULTS: Our findings suggest that CP-MVP-NY-ESO-1-INT recombinant vault nanoparticles are efficiently bioengineered with exceptional integrity, are quickly internalized by immature DCs for antigen processing, and result in DC maturation. CONCLUSION: This study reports our preliminary results, which demonstrate the feasibility and progress regarding our immunotherapeutic technique utilizing NY-ESO-1 packaged vault nanoparticles to prime DCs for subsequent anti-cancer therapies.
Subject(s)
Antigens, Neoplasm/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Dendritic Cells/immunology , Glioma/immunology , Glioma/therapy , Nanoparticles/administration & dosage , Animals , Antibodies , Bioengineering , Drug Delivery Systems/methods , Mice, Inbred C57BL , Recombinant Proteins/administration & dosageABSTRACT
PURPOSE: Glioblastoma (GBM) is the most common and malignant primary adult brain tumor. Current care includes surgical resection, radiation, and chemotherapy. Recent clinical trials for GBM have demonstrated extended survival using interventions such as tumor vaccines or tumor-treating fields. However, prognosis generally remains poor, with expected survival of 20 months after randomization. Chemokine-based immunotherapy utilizing CCL21 locally recruits lymphocytes and dendritic cells to enhance host antitumor response. Here, we report a preliminary study utilizing CPZ-vault nanoparticles as a vehicle to package, protect, and steadily deliver therapy to optimize CCL21 therapy in a murine flank model of GBM. METHODS: GL261 cells were subcutaneously injected into the left flank of eight-week-old female C57BL/6 mice. Mice were treated with intratumoral injections of either: (1) CCL21-packaged vault nanoparticles (CPZ-CCL21), (2) free recombinant CCL21 chemokine empty vault nanoparticles, (3) empty vault nanoparticles, or 4) PBS. RESULTS: The results of this study showed that CCL21-packaged vault nanoparticle injections can decrease the tumor volume in vivo. Additionally, this study showed mice injected with CCL21-packaged vault nanoparticle had the smallest average tumor volume and remained the only treatment group with a negative percent change in tumor volume. CONCLUSIONS: This preliminary study establishes vault nanoparticles as a feasible vehicle to increase drug delivery and immune response in a flank murine model of GBM. Future animal studies involving an intracranial orthotopic tumor model are required to fully evaluate the potential for CCL21-packaged vault nanoparticles as a strategy to bypass the blood brain barrier, enhance intracranial immune activity, and improve intracranial tumor control and survival.
Subject(s)
Brain Neoplasms/immunology , Brain Neoplasms/pathology , Chemokine CCL21/administration & dosage , Drug Delivery Systems/methods , Glioblastoma/immunology , Glioblastoma/pathology , Immunotherapy/methods , Animals , Brain Neoplasms/therapy , Cell Line, Tumor , Chemokine CCL21/immunology , Female , Glioblastoma/therapy , Mice, Inbred C57BL , NanoparticlesABSTRACT
Neurofibromatosis type 2 (NF2) is a genetic neoplastic disorder that presents with hallmark bilateral vestibular schwannomas and multiple meningiomas. Though the current standard of care for meningiomas includes surgery, the multiplicity of meningiomas in NF2 patients renders complete resection of all developing lesions infeasible. Stereotactic radiosurgery (SRS) may be a viable non-invasive therapeutic alternative to surgery. We describe a particularly challenging case in a 39-year-old male with over 120 lesions who underwent more than 30 surgical procedures, and review the literature. We also searched three popular databases and compared outcomes of SRS versus surgery for the treatment of multiple meningiomas in patients with NF2. A total of 50 patients (27 radiosurgical and 23 surgical) were identified. For patients treated with SRS, local tumor control was achieved in 22 patients (81.5%) and distal control was achieved in 14 patients (51.8%). No malignant inductions were observed at an average follow-up duration of 90 months. Complications in the SRS-treated cohort were reported in 9 patients (33%). Eight patients (29.6%) died due to disease progression. Six patients experienced treatment failure and required further management. For NF2 patients treated with surgery, 11 patients (48%) showed tumor recurrence and 10 patients (43.5%) died due to neurological complications. SRS may be a safe and effective alternative for NF2-associated meningiomas. Further studies are required to identify the ideal radiosurgical candidate.
Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Neurofibromatosis 2/complications , Radiosurgery , Adult , Humans , Male , Meningeal Neoplasms/complications , Meningioma/complications , Treatment FailureABSTRACT
BACKGROUND: Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. METHODS: As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. RESULTS: A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. CONCLUSIONS: In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to exhaustively independently validate a commercial genomic profiling assay, examination of a few markers provides some reassurance of its robustness. While potential targeted drugs are recommended based on genetic alterations, to date most targeted therapies have failed in glioblasomas so the usefulness of such recommendations will increase with development of novel and efficacious drugs.
Subject(s)
Formaldehyde/chemistry , Gene Expression Profiling , Genomics , Glioma/diagnosis , Paraffin/chemistry , Adolescent , Adult , Aged , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Class I Phosphatidylinositol 3-Kinases , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Glioma/genetics , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/metabolism , Male , Middle Aged , Mutation , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Real-Time Polymerase Chain Reaction , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Young AdultABSTRACT
BACKGROUND: The popularity of unmanned aerial vehicles, or drones, raises safety concerns as they become increasingly common for commercial, personal, and recreational use. Collisions between drones and people may result in serious injuries. CASE REPORT: A 13-year-old male presented with a comminuted depressed skull fracture causing effacement of the superior sagittal sinus secondary to a racing drone impact. The patient experienced a brief loss of consciousness and reported lower extremity numbness and weakness after the accident. Imaging studies revealed bone fragments crossing the superior sagittal sinus with a short, focal segment of blood flow interruption. Neurosurgical intervention was deferred given the patient's improving neurological deficits, and the patient was treated conservatively. He was discharged home in stable condition. CONCLUSION: Drones may represent a hazard when operated inappropriately due to their capacity to fly at high speeds and altitudes. Impacts from drones can carry enough force to cause skull fractures and significant head injuries. The rising popularity of drones likely translates to an increased incidence of drone-related injuries. Thus, clinicians should be aware of this growing trend.
Subject(s)
Aircraft , Skull Fracture, Depressed/etiology , Adolescent , Humans , Male , Skull Fracture, Depressed/pathology , Skull Fracture, Depressed/surgery , Superior Sagittal Sinus/pathologyABSTRACT
BACKGROUND: Cerebellopontine angle (CPA) lipomas are rare, benign, slow-growing masses. Resections are considered in symptomatic patients who are refractory to targeted medical therapies, but at those stages the lipomas have often reached considerable sizes and encompass critical neurovascular structures. The objective of this study is to develop and to evaluate the utility of a scoring system for CPA lipomas. The hypothesis is that CPA lipomas with lower scores are probably best managed with early surgery. METHODS: The PubMed database was searched using relevant terms. Data on patient and lipoma characteristics were extracted and used to design a scoring system. CPA lipomas were stratified by scores with corresponding managements and outcomes analyzed. RESULTS: One hundred and seventeen patients with CPA lipomas were identified and 40 CPA lipomas were scored. The remaining CPA lipomas were deficient in data and not scored. No lipomas were scored as 1. Score 2 lipomas (n = 12; 30%) most often underwent serial surveillances (n = 5; 41.6%), with the majority of symptoms remaining unimproved (n = 2; 40%). Patients with score 2 CPA lipomas treated with medical therapies (n = 3; 25%) often experienced symptom resolution (n = 2; 66.6%) (p = 0.0499). Patients with score 2 CPA lipomas undergoing surgical resections (n = 3; 25%) all experienced symptom resolution (n = 3; 100%) (p = 0.0499). Score 3 was most common (n = 16; 40%) and these lipomas were often surgically resected (n = 10; 62.5%). The majority of patients with score 3 CPA lipomas having undergone surgical resections (n = 10; 62.5%) experienced symptom improvement (n = 1; 10%) or resolution (n = 4; 40%). CONCLUSIONS: Score 2 CPA lipomas are smaller and would be deemed non-surgical in general practice. However, our data suggest that these lipomas may benefit from either medical therapies or early surgical resections. The advantages of early surgery are maximal resection, decreased surgical morbidity, and improved symptom relief.
Subject(s)
Cerebellar Neoplasms/pathology , Cerebellopontine Angle/pathology , Lipoma/pathology , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Neoplasm Grading/standardsABSTRACT
BACKGROUND: Teratomas of the cranial vault are divided into histopathological subtypes and grouped by prognoses: mature (good prognosis), mixed/malignant and immature teratomas (intermediate prognosis). This schema also includes non-teratomatous tumors. The authors of this study sought to elucidate histologically dependent predictors of survival and further clarify the classification system of intracranial teratomas. METHODS: We performed a systematic analysis of the published literature to identify studies describing patients with intracranial teratomas diagnosed with magnetic resonance imaging (MRI) and presenting definite information on histologies, therapies, and outcomes at a minimum follow-up of 2 years. Disease-free (DFS) and overall survival (OS) were evaluated. RESULTS: A total of 18 articles comprised of 134 patients were included. On univariate analysis, male sex and gross-total resection (GTR) were associated with high mean DFS (p = 0.0362 and p < 0.0001, respectively). On multivariate analysis, mature teratomas located in the pineal, and those having undergone subtotal resection (STR) demonstrated high mean OS (p = 0.0023 and p = 0.0044, respectively). Mature and mixed/malignant suprasellar teratomas had equally higher mean OS versus immature suprasellar teratomas (p < 0.0001). Mature and immature teratomas treated with adjuvant therapy had significantly higher mean OS compared to those managed with surgery alone (p = 0.0421 and p = 0.0423, respectively). Males with immature teratomas had the highest mean OS (p < 0.0001). Immature teratomas managed with surgery alone had higher mean DFS, but lower mean OS, compared to those treated with adjuvant therapy (p = 0.0176 and p = 0.0423, respectively). CONCLUSIONS: Our data highlight the divergent nature of the different histopathological subtypes of teratomas, and suggest that survival outcomes are multifactorial. Specifically, male sex, pineal, suprasellar, GTR, and STR were dependent predictors of OS, while histopathology was an independent predictor of OS.
Subject(s)
Brain Neoplasms , Teratoma , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Female , Humans , Male , Teratoma/mortality , Teratoma/pathology , Teratoma/therapyABSTRACT
OBJECTIVE: We evaluated the contributions of chronological age, comorbidity burden, and/or frailty in predicting 90-day readmission in patients undergoing degenerative scoliosis surgery. METHODS: Patients were identified through the Healthcare Cost and Utilization Project Nationwide Readmissions Database. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. Comorbidity was assessed using the Elixhauser Comorbidity Index (ECI). Generalized linear mixed-effects models were created to predict readmission using age, frailty, and/or ECI. Area under the curve (AUC) was compared using DeLong's test. RESULTS: A total of 8104 patients were identified. Readmission rate was 9.8%, with infection representing the most common cause (3.5%). Our first model utilized chronological age, ECI, and/or frailty as primary predictors. The combination of ECI + frailty + age performed best, but the inclusion of chronological age did not significantly improve performance compared to ECI + frailty alone (AUC 0.603 vs. 0.599, P = 0.290). A second model using only chronological age and frailty as primary predictors performed better, however the inclusion of chronological age worsened performance when compared to frailty alone (AUC 0.747 vs. 0.743, P = 0.043). CONCLUSIONS: These data support frailty as a predictor of 90-day readmission within a nationally representative sample. Frailty alone performed better than combinations of ECI and age. Interestingly, the integration of chronological age did not dramatically improve the model's performance. Limitations include the use of a national registry and a single frailty index. This provides impetus to explore biological age, rather than chronological age, as a potential tool for surgical risk assessment.
Subject(s)
Comorbidity , Frailty , Patient Readmission , Scoliosis , Humans , Patient Readmission/statistics & numerical data , Scoliosis/surgery , Female , Male , Frailty/epidemiology , Aged , Middle Aged , Age Factors , Postoperative Complications/epidemiology , Aged, 80 and overABSTRACT
Play has been defined as apparently functionless behaviour, yet since play is costly, models of adaptive evolution predict that it should have some beneficial function (or functions) that outweigh its costs. We provide strong evidence for a long-standing, but poorly supported hypothesis: that early social play is practice for later dominance relationships. We calculated the relative dominance rank by observing the directional outcome of playful interactions in juvenile and yearling yellow-bellied marmots (Marmota flaviventris) and found that these rank relationships were correlated with later dominance ranks calculated from agonistic interactions, however, the strength of this relationship attenuated over time. While play may have multiple functions, one of them may be to establish later dominance relationships in a minimally costly way.
Subject(s)
Marmota/physiology , Social Behavior , Social Dominance , Aging , Animals , Colorado , Female , Male , Play and PlaythingsABSTRACT
BACKGROUND: Post-traumatic cerebrospinal fluid (CSF) leaks of the anterior skull base may arise after traumatic brain injury (TBI). Onset of CSF rhinorrhea may be delayed after TBI and without prompt treatment may result in debilitating consequences. Operative repair of CSF leaks caused by anterior skull base fractures may be performed via open craniotomy or endoscopic endonasal approaches (EEAs). The authors' objective was to review their institutional experience after EEA for repair of TBI-related anterior skull base defects and CSF leaks. OBSERVATIONS: A retrospective review of prospectively collected data from a major level 1 trauma center was performed to identify patients with TBI who developed CSF rhinorrhea. Persistent or refractory post-traumatic CSF leaks and anterior skull base defects were repaired via EEA in four patients. Intrathecal fluorescein was administered before EEA in three patients (75%) to help aid identification of the fistula site(s). CSF leaks were eventually repaired in all patients, though one reoperation was required. During a mean follow-up of 8.75 months, there were no instances of recurrent CSF leakage. LESSONS: Refractory, traumatic CSF leaks may be effectively repaired via EEA using a multilayer approach and nasoseptal flap reconstruction, thereby potentially obviating the need for additional craniotomy in the post-TBI setting.
ABSTRACT
BACKGROUND: Impairment of facial nerve (FN) function is a common postoperative complication in surgical resections of Vestibular Schwannomas (VS). Diffusion tensor imaging (DTI) tractography creates in vivo imaging of the anatomical location of white matter tracts that can be preoperatively used to visualize the displaced FN. We present an analysis of patients who underwent DTI tractography imaging prior to VS resection. METHODS: Patient charts were reviewed from March 2012 to April 2015 who underwent DTI tractography prior to surgical resection for VS. Reliability of this measure was compared to the intraoperative FN location as determined by the surgeon. House Brackmann (HB) score was used to assess facial nerve function. RESULTS: A total of 11 patients were included with a mean age of 43 years (range: 19-64) and mean follow-up length of 11.9 months (range: 3.1-34.2). The average maximum tumor diameter was 2.82 cm (range: 1.7-4.2). DTI tractography was accurate in 90.9% (10/11) of patients. Postoperatively, 72.7% (8/11) had a HB score of I or II, 18.2% (2/11) had a HB score of III, and 9.1% (1/11) had a HB score of IV. CONCLUSIONS: Facial nerve visualization for VS resection can be accurately visualized using DTI tractography. This modality may lead to reduction of postoperative FN damage.
Subject(s)
Facial Nerve Injuries , Neuroma, Acoustic , Adult , Diffusion Tensor Imaging , Facial Nerve/diagnostic imaging , Facial Nerve/surgery , Facial Nerve Injuries/etiology , Facial Nerve Injuries/prevention & control , Humans , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/surgery , Neurosurgical Procedures , Reproducibility of Results , Retrospective Studies , Treatment OutcomeABSTRACT
Objective Dermoid cysts are benign, congenital malformations that account for â¼0.5% of intracranial neoplasms. The authors describe a 42-year-old female with a prepontine dermoid cyst who underwent apparent gross total resection (GTR) but experienced cyst recurrence. To date, very few cases of prepontine dermoid cysts have been reported. The prevalent region where these cysts are located can be difficult to determine. In addition, the authors systematically review the literature to characterize the clinical presentation, anatomical distribution, and surgical outcomes of intracranial dermoid cysts. Design Systematic review. Setting/Participants PubMed, Web of Science, and Scopus databases. Main Outcome Measures Extent of resection, symptom improvement, and recurrence rates. Results A total of 69 patients with intracranial dermoid cysts were identified. Three (4.3%) intracranial dermoid cysts were located in the prepontine cistern. The average age of patients was 33.3 years. The most common presenting symptoms were headache (52.2%) and visual disturbances (33.3%). Intracranial dermoid cysts were distributed similarly throughout the anterior, middle, and posterior cranial fossae (29.0%, 36.2%, and 29.0%, respectively). GTR was achieved in 42.0% of cases. Thirty-four (49.3%) patients experienced symptom resolution. Recurrence rate was 5.8% at a mean follow-up of 2.1 years. Conclusions Intracranial dermoid cysts most often present as headaches and visual disturbances. Intracranial dermoid cysts were found in the anterior, middle, and posterior cranial fossae at similar frequencies but with clear predilections for the Sylvian fissure, sellar region, and cerebellar vermis. Outcomes following surgical excision of intracranial dermoid cysts are generally favorable despite moderate rates of GTR.
ABSTRACT
OBJECTIVE: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas (VSs). NF2-associated VSs (NF2-VSs) are routinely treated with microsurgery; however, stereotactic radiosurgery (SRS) has emerged as an effective alternative in recent decades. To elucidate the role of SRS in NF2-VSs, a systematic review of the literature was conducted to compare outcomes of SRS versus surgery. METHODS: PubMed, Web of Science, Scopus, Embase, and Cochrane databases were queried using relevant search terms. Retrospective studies investigating outcomes of NF2-VS patients treated with either SRS or surgery were included. Single-patient case reports were excluded. Outcome measures between the SRS and surgery groups were compared using χ2 2-sample tests for equality of proportions on the pooled patient data. RESULTS: A total of 974 patients (485 SRS, 489 surgery) were identified. The mean 5-year local control rate for SRS was 75.1%, and the mean recurrence rate for surgery was 8.1%. The mean hearing and facial nerve preservation rates were 40.1% and 92.3%, respectively, for SRS and 52.0% and 75.7%, respectively, for surgery. Rates of hearing preservation were higher after surgery than after SRS (P = 0.006), whereas rates of facial nerve preservation were higher after SRS than after surgery (P < 0.001). CONCLUSIONS: SRS appears to be a safe and effective alternative to surgery for NF2-VS. Although rates of hearing preservation were higher in the surgery cohorts, SRS demonstrated high rates of local control and significantly lower facial nerve complications. Certain patients may therefore benefit more from SRS than surgery.
Subject(s)
Neuroma, Acoustic/therapy , Neurosurgical Procedures/methods , Radiosurgery/methods , Facial Nerve Diseases/epidemiology , Hearing Loss/epidemiology , Humans , Neoplasm Recurrence, Local/epidemiology , Neurofibromatosis 2/complications , Neuroma, Acoustic/etiology , Postoperative Complications/epidemiologyABSTRACT
BACKGROUND: Superior semicircular canal dehiscence (SSCD) is an osseous defect of the arcuate eminence of the petrous temporal bone. Strategies for measuring dehiscence size are variable, and the usefulness of such parameters remains in clinical equipoise. OBJECTIVE: To present a novel method of measuring dehiscence volume and to evaluate its potential as a predictor of symptom outcomes after surgical repair of SSCD. METHODS: High-resolution computed tomographic temporal bone images were imported into a freely available segmentation software. Dehiscence lengths and volumes were ascertained by independent authors. Inter-rater observer reliability was assessed using Cronbach's alpha. Correlation and regression analyses were performed to evaluate for relationships between dehiscence size and symptoms (pre- and post-operative). RESULTS: Thirty-seven dehiscences were segmented using the novel volumetric assessment. Cronbach's alpha for dehiscence lengths and volumes were 0.97 and 0.95, respectively. Dehiscence lengths were more variable as compared to dehiscence volumes (σ2 8.92 vs σ2 0.55, F = 1.74). The mean dehiscence volume was 2.22 mm3 (0.74, 0.64-0.53 mm3). Dehiscence volume and headache at presentation were positively correlated (Rpb = 0.67, P = .03). Dehiscence volume and vertigo improvement after surgery were positively correlated, although this did not reach statistical significance (Rpb = 0.46, P = .21). CONCLUSION: SSCD volumetry is a novel method of measuring dehiscence size that has excellent inter-rater reliability and is less variable compared to dehiscence length, but its potential as a predictor of symptom outcomes is not substantiated. However, the study is limited by low power.
Subject(s)
Semicircular Canals/diagnostic imaging , Semicircular Canals/pathology , Semicircular Canals/surgery , Adult , Aged , Aged, 80 and over , Craniotomy/methods , Female , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Temporal Bone/surgery , Tomography, X-Ray Computed , Young AdultABSTRACT
Objective The objective of this study was to examine the effect of cochlear dose on hearing preservation in stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) for vestibular schwannoma (VS). Design This is a retrospective case-control study. Setting This study was completed at the Ronald Reagan UCLA Medical Center, a university-affiliated tertiary care center. Participants Patients who underwent SRS (marginal dose of 12 Gy) or fSRT (marginal dose of 50.4 Gy) procedures for VS were included in the study. Main Outcome Measures The main outcome measure was hearing preservation. Audiometric data, when available, were used to determine the level of hearing according to the Gardner Robertson scale. Results A total of 38 patients (14 SRS and 24 fSRT) were analyzed. SRS patients with decreased hearing received a significantly higher minimum cochlear dose (7.41 vs. 4.24 Gy, p = 0.02) as compared with those with stable hearing. In fSRT patients, there were no significant differences in cochlear dose for patients with decreased hearing as compared with those with stable hearing. For SRS patients, who received a minimum cochlear dose above 6 Gy, there was a significant risk of decreased hearing preservation (odds ratio: 32, p = 0.02). Conclusion Higher minimum cochlear dose was predictive of decreased hearing preservation following SRS. Though the study is low powered, the radiation dose to the cochlea should be a parameter that is considered when planning SRS or fSRT therapies for patients with VS.
ABSTRACT
Epithelial membrane protein-2 (EMP2) expression is noted in many human cancers. We evaluated EMP2 as a biomarker in gliomas. A large tissue microarray of lower grade glioma (WHO grades II-III, n = 19 patients) and glioblastoma (GBM) (WHO grade IV, n = 50 patients) was stained for EMP2. EMP2 expression was dichotomized to low or high expression scores and correlated with clinical data. The mean EMP2 expression was 1.68 in lower grade gliomas versus 2.20 in GBMs (P = 0.01). The percentage of samples with high EMP2 expression was greater in GBMs than lower grade gliomas (90.0 vs. 52.6%, P = 0.001). No significant difference was found between median survival among patients with GBM tumors exhibiting high EMP2 expression and survival of those with low EMP2 expression (8.38 vs. 10.98 months, P = 0.39). However, EMP2 expression ≥2 correlated with decreased survival (r = -0.39, P = 0.001). The EMP2 expression level also correlated with Ki-67 positivity (r = 0.34, P = 0.008). The mortality hazard ratio for GBM patients with EMP2 score of 3 or higher was 1.92 (CI 0.69-5.30). Our findings suggest that elevated EMP2 expression is associated with GBM. With other biomarkers, EMP2 may have use as a molecular target for the diagnosis and treatment of gliomas.
Subject(s)
Biomarkers, Tumor/analysis , Brain Neoplasms/diagnosis , Glioma/diagnosis , Membrane Glycoproteins/analysis , Tissue Array Analysis/methods , Adult , Aged , Aged, 80 and over , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Female , Gene Expression , Glioma/genetics , Glioma/metabolism , Glioma/pathology , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Male , Membrane Glycoproteins/genetics , Middle Aged , Molecular Targeted Therapy , Neoplasm StagingABSTRACT
Superior semicircular canal dehiscence (SSCD) is a bony defect in the middle cranial fossa floor that results in an abnormal connection between the inner ear and cranial vault. Although the etiology of SSCD remains unclear, an inappropriately thin or fragile temporal bone likely predisposes an individual towards developing SSCD. Ehlers-Danlos syndrome (EDS) constitutes a group of genetic connective tissue disorders caused by a defect in the production, processing, or structure of collagen, or its associated proteins. The possible association between SSCD and EDS has not been previously described in the literature. We herein report a case of a 50-year-old female with EDS-hypermobility type who presented with a 15-year history of migraines, vertigo, and tinnitus. The patient was subsequently diagnosed with bilateral SSCD and underwent a right middle fossa (pre-auricular infratemporal) craniotomy for SSCD repair. She reported significant improvement in her auditory and vestibular symptoms, with the exception of continued mild dizziness and disequilibrium at the 3-month follow-up. Due to the rare reports of auditory symptoms in EDS, this case study highlights the importance of considering an otological consultation for auditory manifestations in a patient with EDS and illustrates a potential association between EDS and SSCD.
ABSTRACT
OBJECTIVE: To assess the use of functional scores in the evaluation of patients with dural arteriovenous fistula and Foix-Alajouanine syndrome. METHODS: We systematically surveyed the literature to identify relevant patients. Aminoff-Logue Scale (ALS) and modified Rankin Scale (mRS) scores were ascertained and combined to form a novel functional score, the Aminoff-Rankin Composite (ARC) score. We compared functional scores between surgery and embolization groups and ran one-sided point-biserial analyses to test our expectation that positive correlations exist between functional scores and treatment outcomes. Finally, we reviewed the pathogenesis of dural arteriovenous fistula formation. RESULTS: The quantitative synthesis included 18 patients. Surgery alone was performed in 11 patients (61.11%); 7 patients underwent embolization alone (38.89%). There were no significant differences in functional scores or symptom outcomes when we compared surgery to embolization. The pre-intervention ALS gait, mRS, and ARC scores were correlated with improved symptoms (rpb = 0.43, P = 0.04; rpb = 0.47, P = 0.02; rpb = 0.48, P = 0.04, respectively). In patients whose symptoms were improved, post-intervention ALS gait and micturition scores (2.55 vs. 4.43, P = 0.02 and 1.09 vs. 2.71, P = 0.01, respectively) and post-intervention ARC scores (6.66 vs. 11.57, P = 0.01) were on average lower than in patients whose symptoms were unimproved. CONCLUSIONS: We believe that patients with dAVF and Foix-Alajouanine syndrome present with worse function (higher functional scores) as a result of an acute myelopathic episode, and that if diagnosed and treated appropriately, will experience some level of symptom improvement that is evidenced by reduced post-intervention functional scores.
Subject(s)
Central Nervous System Vascular Malformations/therapy , Embolization, Therapeutic , Neurosurgical Procedures , Spinal Cord Diseases/therapy , Central Nervous System Vascular Malformations/complications , Central Nervous System Vascular Malformations/physiopathology , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Humans , Paraplegia/etiology , Paraplegia/physiopathology , Spinal Cord Diseases/etiology , Spinal Cord Diseases/physiopathology , Syndrome , Treatment Outcome , Urination/physiologyABSTRACT
OBJECTIVE: To present an illustrative case of fourth ventricular epidermoid cyst and review the literature to identify predictors of surgical outcomes. METHODS: A case of fourth ventricular epidermoid cyst is presented and a systematic review of 5 popular databases was performed by independent authors. Stepwise logistic regression was performed to identify clinical predictors of outcomes. RESULTS: A 21-year-old woman presented with 3 months of headaches and visual obscurations and was diagnosed with a multilobulated mass in the fourth ventricle. The patient underwent suboccipital craniotomy. Complete removal of the mass was achieved and the final diagnosis was consistent with an epidermoid cyst. The systematic review identified 23 studies that reported 37 patients. Mean age was 42.8 years. Mean length of time between symptom onset and diagnosis was 4.43 years. Age (P = 0.049) and duration of symptoms (P < 0.001) were significantly different between patients who experienced symptom improvement and those who did not. Duration of symptom onset to diagnosis was a significant predictor of poor outcomes (odds ratio, 1.19, 95% confidence interval, 1.003-4.785). CONCLUSIONS: Our review found that in patients with fourth ventricular epidermoid cysts, unfavorable outcomes were predicted by older age and by longer intervals from symptom onset to diagnosis. Clinicians should maintain a high index of suspicion for fourth ventricular epidermoid cysts in patients presenting with cerebellar signs and visual disturbances.