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INTRODUCTION: Although recent trends currently favor the endoscopic endonasal transcavernous approach (EETA) over the pretemporal transcavernous approach (PTA) for certain cavernous sinus pathologies, dedicated assessment of the surgical exposure and maneuverability is wanting. Toward this aim, this morphometric study quantifies these variables within four cavernous sinus compartments by comparing the PTA, EETA, and a combined approach to achieve a circumferential dissection (EETA-PTA). MATERIAL: In five latex-injected specimens, exposure volumes of the EETA, PTA, and circumferential EETA-PTA approaches were quantified; the latter combined the most conservative options of both the endoscopic and open approaches. Two clinical cases illustrate the combined approach. RESULTS: EETA-PTA provided the largest volume of exposure (65.6% vs 35% PTA vs 44.6% EETA, P = 0.01) and eliminated the need to mobilize the ICA or cross cranial nerves. Although EETA and PTA approaches afforded comparable exposure volumes along the entire cavernous sinus (34.9 vs 44.6%), the EETA better exposed medial and inferior compartments (whereas the PTA exposed larger volumes in the lateral and superior compartments. The combined EETA-PTA yielded 66% of total cavernous sinus exposure volumes and eliminated the need to mobilize the ICA or cross cranial nerves. CONCLUSIONS: Our methodology aligns with strategies that use a modular concept to divide the skull base into compartments for maximal safe resection. Excluding soft tumors, the EETA is preferred for medial and inferior lesions and the PTA for superior and lateral lesions. A staged combined EETA-PTA may safely yield a 360-degree access for extensive multi-compartment lesions that span neurovascular structures within the cavernous sinus.
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Seio Cavernoso , Humanos , Seio Cavernoso/cirurgia , Seio Cavernoso/patologia , Masculino , Feminino , Procedimentos Neurocirúrgicos/métodos , Pessoa de Meia-Idade , Neuroendoscopia/métodos , Endoscopia/métodos , Idoso , Adulto , Cadáver , Sela Túrcica/cirurgia , Sela Túrcica/patologiaRESUMO
BACKGROUND: We describe techniques for safe resection of a Type 3 foramen magnum meningioma with dorsal displacement of the accessory nerve rootlets and vertebral artery which limits ventral access to the tumor. METHOD: Partial sectioning of the accessory nerve rootlets may help create larger working space. Topical lidocaine placement on the rootlets of the spinal accessory nerve may mitigate trapezius muscle contraction and facilitates further progress throughout tumor resection. CONCLUSION: Creating safe working corridors between the lower cranial nerves through mobilization or partial sectioning of rootlets in the case of CN XI facilitates tumor resection through a far lateral approach.
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Forame Magno , Neoplasias Meníngeas , Meningioma , Procedimentos Neurocirúrgicos , Humanos , Meningioma/cirurgia , Meningioma/patologia , Meningioma/diagnóstico por imagem , Forame Magno/cirurgia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Nervo Acessório/cirurgia , Artéria Vertebral/cirurgia , Feminino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Investigate the relationship between word recognition score (WRS) and pure tone average (PTA) after hearing preservation surgery for vestibular schwannomas (VS) as well as evaluate the consistency of hearing classification systems. STUDY DESIGN: A retrospective chart review was performed. SETTING: This study included patients from a single academic tertiary referral hospital. PATIENTS: Patients with VS and serviceable hearing who underwent hearing preservation surgery 2014-2023. Patients excluded for neurofibromatosis 2 and lacking pre/postop audiograms. INTERVENTIONS: All patients underwent resection of vestibular schwannoma. MAIN OUTCOME MEASURES: Pre/postop WRS, PTA, and AAO-HNS, Gardner-Robertson (GR), and WRS Class (WRSC) hearing classifications. RESULTS: Seventy-five patients were included. Average preop and postop PTA and WRS were 26 ± 12 dB, 79 ± 39 dB, 92 ± 12%, and 33 ± 43%, respectively. Postop PTAs were distributed along the complete testable decibel range, while the postop WRS displayed a bimodal distribution, with WRS >50% or <20%. Worsening intraop ABR changes were significantly associated with poorer hearing outcomes ( p = 0.005). With increasing Koos grades, intraop ABRs were significantly more likely to exhibit changes ( p = 0.005). AAO-HNS and GR classified patients nearly identically, while the WRSC resulted in more class I and fewer class II. The cutoff of serviceable hearing was comparable across all classification systems. CONCLUSIONS: Effects on the brainstem component of Koos 3-4 tumors may particularly disturb speech processing. This effect seems amplified by surgical dissection. AAO-HNS, GR, and WRSC hearing classifications are comparable in describing serviceable hearing in vestibular schwannoma patients.
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Audiometria de Tons Puros , Neuroma Acústico , Percepção da Fala , Humanos , Neuroma Acústico/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Percepção da Fala/fisiologia , Adulto , IdosoRESUMO
BACKGROUND AND OBJECTIVES: Beyond qualitative evidence legitimizing endoscopic corridors through contralateral transmaxillary (CTM) and endonasal ipsilateral transpterygoid (ITP) corridors to the petrous apex and petroclival region, surgical feasibility by direct quantitative comparative anatomy is sparse. Our cadaveric study addresses this by performing the CTM approach followed by ITP extension to quantify the extent of petrous apex resection, instrument maneuverability, and working distance to petrous apex. METHODS: Anatomic dissections were performed bilaterally on 5 latex-injected human cadaveric heads (10 petrous bones). After CTM dissections were quantified, the ITP approach was added enlarging initial exposure. Differences were measured with statistical significance when P values are < .05. RESULTS: The mean petrosectomy volume was 0.958 cm3 with CTM and 1.987 cm3 with CTM + ITP, corresponding to 14.53% and 30.52% petrous apex resection, respectively. Craniocaudal instrument mobility was more limited in the lateral extent of dissection compared with the midline for both CTM (8.062° vs 14.416°) and CTM + ITP (5.4° vs 14.4°). The CTM approach achieved the lateral-most dissection at the body of the petrous apex (15.936 mm), with lateralization more limited in the superior petroclival region (9.628 mm) and the inferior petroclival region (8.508 mm). Angle of surgical maneuverability increased superiorly vs inferiorly in the CTM approach (mean 12.596° vs 8.336°, respectively). The CTM approach offered the shortest mean working distance (88.624 mm) to the petroclival region compared with the bi-nares approach (100.5 mm). CTM + ITP achieved greater lateralization in the superior (21.237 mm) and inferior (22.087 mm) aspects of the petroclival region compared with the CTM approach. CONCLUSION: Operative considerations are discussed in accessing target neurovascular structures through the uniquely shaped corridors formed by the CTM or combined CTM + ITP. Allowing mobilization of the internal carotid artery laterally and eustachian tube inferiorly, addition of the ITP allowed for larger petrosectomy than CTM alone, especially in the inferior and lateral aspects of the petrous bone.
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PURPOSE: Sinus thrombosis is a common post-operative finding after posterior fossa surgery performed in the vicinity of the dural venous sinuses. The SARS-CoV-2 virus has been shown to confer an increased risk of venous thromboembolic events owing to eliciting a hyper-inflammatory and pro-thrombotic state. In this study, we examine the incidence of post-operative venous sinus thrombosis in patients undergoing peri-sigmoid posterior fossa surgery in the pre- and post-COVID era and investigate whether COVID infection confers an increased risk of sinus thrombosis. METHODS: A retrospective review of a single institution case series of patients underwent peri-sigmoid surgery (retrosigmoid, translabyrinthine, or far lateral) approach. Relevant clinical variables were investigated that may confer an increased risk of sinus thrombosis. RESULTS: A total of 311 patients (178 in the pre-COVID era, and 133 operated on after the pandemic began in March 2020) are included in the study. The composite incidence of sinus thrombosis seen on post-operative imaging was 7.8%. The incidence of sinus thrombosis in the pre-COVID cohort was N = 12 patients (6.7%) versus N = 12 (9%) in the post-COVID cohort (p = 0.46). A history of COVID infection was not shown to confer an increased risk of post-operative sinus thrombosis (OR: 0.61; 95% CI: 0.08-4.79, p = 0.64). Only a small number of patients (N = 7, 2.3%) required either medical or surgical intervention for post-operative sinus thrombosis. CONCLUSION: The overall incidence of post-operative sinus thrombosis is similar in the pre- and post-COVID era. The findings of this study suggest that COVID infection is not associated with a higher risk of venous sinus thrombosis.
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COVID-19 , Complicações Pós-Operatórias , Trombose dos Seios Intracranianos , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Incidência , Estudos Retrospectivos , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Adulto , Base do Crânio/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Fatores de RiscoRESUMO
Corticotroph adenomas/pituitary neuroendocrine tumors (PitNETs) are associated with significant morbidity and mortality. Predictors of tumor behavior have not shown high prognostic accuracy. For somatotroph adenomas/PitNETs, E-cadherin expression correlates strongly with prognosis. E-cadherin expression has not been investigated in other PitNETs. A retrospective chart review of adults with corticotroph adenomas/PitNETs was conducted to assess correlation between E-cadherin expression and tumor characteristics. In addition, gene expression microarray was performed in subset of tumors (n = 16). Seventy-seven patients were identified; 71% were female, with median age of cohort 45.2 years. Seventy-five percent had macroadenomas, of which 22% were hormonally active. Ninety-five percent of microadenomas were hormonally active. Adrenocorticotropic hormone granulation pattern by IHC identified 63% as densely granulated (DG) and 34% as sparsely granulated (SG). All microadenomas were DG (p < .001); 50% of macroadenomas were DG associated with increased tumor invasion compared to SG. E-cadherin IHC was positive in 80%, diminished in 17%, and absent in 20% and did not correlate with corticotroph PitNETs subtype, size, or prognosis. In contrast to the distinct transcriptomes of corticotroph PitNETs and normal pituitaries, a comparison of clinically active and silent corticotroph PitNETs demonstrated similar molecular signatures indicating their common origin, but with unique differences related to their secretory status.
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Adenoma Hipofisário Secretor de ACT , Caderinas , Tumores Neuroendócrinos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Adenoma Hipofisário Secretor de ACT/genética , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma Hipofisário Secretor de ACT/metabolismo , Caderinas/genética , Caderinas/biossíntese , Caderinas/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/metabolismo , Estudos Retrospectivos , TranscriptomaRESUMO
PURPOSE: Proximity to critical neurovascular structures can create significant obstacles during surgical resection of foramen magnum meningiomas (FMMs) to the detriment of treatment outcomes. We propose a new classification that defines the tumor's relationship to neurovascular structures and assess correlation with postoperative outcomes. METHODS: In this retrospective review, 41 consecutive patients underwent primary resection of FMMs through a far lateral approach. Groups defined based on tumor-neurovascular bundle configuration included Type 1, bundle ventral to tumor; Type 2a-c, bundle superior, inferior, or splayed, respectively; Type 3, bundle dorsal; and Type 4, nerves and/or vertebral artery encased by tumor. RESULTS: The 41 patients (range 29-81 years old) had maximal tumor diameter averaging 30.1 mm (range 12.7-56 mm). Preoperatively, 17 (41%) patients had cranial nerve (CN) dysfunction, 12 (29%) had motor weakness and/or myelopathy, and 9 (22%) had sensory deficits. Tumor type was relevant to surgical outcomes: specifically, Type 4 demonstrated lower rates of gross total resection (65%) and worse immediate postoperative CN outcomes. Long-term findings showed Types 2, 3, and 4 demonstrated higher rates of permanent cranial neuropathy. Although patients with Type 4 tumors had overall higher ICU and hospital length of stay, there was no difference in tumor configuration and rates of postoperative complications or 30-day readmission. CONCLUSION: The four main types of FMMs in this proposed classification reflected a gradual increase in surgical difficulty and worse outcomes. Further studies are warranted in larger cohorts to confirm its reliability in predicting postoperative outcomes and possibly directing management decisions.
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Forame Magno , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirurgia , Meningioma/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Feminino , Masculino , Forame Magno/cirurgia , Forame Magno/patologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Apparent diffusion coefficient (ADC) in MRI has been shown to correlate with postoperative House-Brackmann (HB) scores in patients with vestibular schwannoma despite limited methodology. To rectify limitations of single region of interest (ROI) sampling, we hypothesize that whole-tumor ADC histogram analysis will refine the predictive value of this preoperative biomarker related to postoperative facial nerve function. METHODS: Of 155 patients who underwent resection of vestibular schwannoma (2014-2020), 125 patients were included with requisite clinical and radiographic data. After volumetric analysis and whole-tumor ADC histogram, regression tree analysis identified ADC cutoff for significant differences in HB grade. Outcomes were extent of resection, facial nerve function, hospital length of stay (LOS), and complications. RESULTS: Regression tree analysis defined three quantitative ADC groups (× 10-6 mm2/s) as high (> 2248.77; HB 1.7), mid (1468.44-2248.77; HB 3.1), and low (< 1468.44; HB 2.3) range (p 0.04). The mid-range ADC group had significantly worse postoperative HB scores and longer hospital LOS. Large tumor volume was independently predictive of lower rates of gross total resection (p <0.0001), higher postoperative HB score (p 0.002), higher rate of complications (p 0.04), and longer LOS (p 0.003). CONCLUSIONS: Whole-tumor histogram yielded a robust regression tree analysis that defined three ADC groups with significantly different facial nerve outcomes. This likely reflects tumor heterogeneity better than solid-tumor ROI sampling. Whole-tumor ADC warrants further study as a useful radiographic biomarker in patients with vestibular schwannoma who are considering surgical resection.
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Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia , Nervo Facial/diagnóstico por imagem , Nervo Facial/cirurgia , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética , Biomarcadores , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: To improve hearing function after resection of large vestibular schwannomas, we describe a strategy of vestibular-nerve-fiber preservation. Anatomical considerations and stepwise dissection are described. METHOD: Steps include locating the vestibular nerve at the brainstem and identifying a dissection plane between nerve fibers and tumor capsule. Using this plane to mobilize and resect tumor reduced manipulation and maintained vascularity of underlying cochlear and facial nerves. CONCLUSION: Preservation of hearing function is feasible in large vestibular schwannomas with vestibular-nerve-fiber preservation. Reducing manipulation and ischemic injury of underlying cochlear and facial nerves thereby helped facilitate hearing preservation, even in large tumors.
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Neuroma Acústico , Humanos , Neuroma Acústico/cirurgia , Neuroma Acústico/patologia , Nervo Vestibular/cirurgia , Audição , Nervo Facial/cirurgia , Testes Auditivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
Background Epigenetics may predict treatment sensitivity and clinical course for patients with meningiomas more accurately than histopathology. Nonetheless, targeting epigenetic mechanisms is understudied for pharmacotherapeutic development for these tumors. The bio-molecular insights and potential therapeutic development of meningioma epigenetics led us to investigate epigenetic inhibition in meningiomas. Methods We screened a 43-tumor cohort using a 139-compound epigenetic inhibitor library to assess sensitivity of relevant meningioma subgroups to epigenetic inhibition. The cohort was composed of 5 cell lines and 38 tumors cultured directly from surgery; mean patient age was 56.6 years ± 13.9 standard deviation. Tumor categories: 38 primary tumors, 5 recurrent; 33 from females, 10 from males; 32 = grade 1; 10 = grade 2; 1 = grade 3. Results Consistent with our previous results, histone deacetylase inhibitors (HDACi) were the most efficacious class. Panobinostat significantly reduced cell viability in 36 of 43 tumors; 41 tumors had significant sensitivity to some HDACi. G9a inhibition and Jumonji-domain inhibition also significantly reduced cell viability across the cohort; tumors that lost sensitivity to panobinostat maintained sensitivity to either G9a or Jumonji-domain inhibition. Sensitivity to G9a and HDAC inhibition increased with tumor grade; tumor responses did not separate by gender. Few differences were found between recurrent and primary tumors, or between those with prior radiation versus those without. Conclusions Few efforts have investigated the efficacy of targeting epigenetic mechanisms to treat meningiomas, making the clinical utility of epigenetic inhibition largely unknown. Our results suggest that epigenetic inhibition is a targetable area for meningioma pharmacotherapy.
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PURPOSE: Large (> 3 cm) vestibular schwannomas pose complexity in surgical management because of narrow working corridors and proximity to the cranial nerves, brainstem, and inner ear structures. With current vestibular schwannoma classifications limited in information regarding cerebellopontine edema, our retrospective series examined this radiographic feature relative to clinical outcomes and its possible role in preoperative scoring. METHODS: Of 230 patients who underwent surgical resection of vestibular schwannoma (2014-2020), we identified 107 patients with Koos grades 3 or 4 tumors for radiographic assessment of edema in the middle cerebellar peduncle (MCP), brainstem, or both. Radiographic images were graded and patients grouped into Koos grades 3 or 4 or our proposed grade 5 with edema. Tumor volumes, radiographic features, clinical presentations, and clinical outcomes were evaluated. RESULTS: The 107 patients included 22 patients with grade 3 tumors, 39 with grade 4, and 46 with grade 5. No statistical differences were noted among groups for demographic data or complication rates. Unlike grades 3 and 4 patients, grade 5 patients presented with worse hearing (p < 0.001), larger tumors (p < 0.001), lower rates of gross total resection (GTR), longer hospital stays, and higher rates of balance dysfunction. CONCLUSION: With edema detected in 43% of this cohort, special considerations are warranted for grade 5 vestibular schwannomas given the preoperative findings of worse hearing, lower GTR rates, longer hospital stays, and 96% who pursued postoperative balance therapy. We propose that grade 5 with edema offers a more nuanced interpretation of a radiographic feature that holds relevance to treatment selection and patient outcomes.
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Orelha Interna , Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia , Neuroma Acústico/patologia , Estudos Retrospectivos , Edema , Resultado do TratamentoRESUMO
Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor. Extracellular vesicles (EVs) released by tumor cells play a critical role in cellular communication in the tumor microenvironment promoting tumor progression and invasion. We hypothesized that GBM EVs possess unique characteristics which exert effects on endogenous CNS cells including neurons, producing dose-dependent neuronal cytotoxicity. We purified EVs from the plasma of 20 GBM patients, 20 meningioma patients, and 21 healthy controls, and characterized EV phenotypes by electron microscopy, nanoparticle tracking analysis, protein concentration, and proteomics. We evaluated GBM EV functions by determining their cytotoxicity in primary neurons and the neuroblastoma cell line SH-SY5Y. In addition, we determined levels of IgG antibodies in the plasma in GBM (n = 82), MMA (n = 83), and controls (non-tumor CNS disorders and healthy donors, n = 50) with capture ELISA. We discovered that GBM plasma EVs are smaller in size and had no relationship between size and concentration. Importantly, GBM EVs purified from both plasma and tumor cell lines produced IgG-mediated, complement-dependent apoptosis and necrosis in primary human neurons, mouse brain slices, and neuroblastoma cells. The unique phenotype of GBM EVs may contribute to its neuronal cytotoxicity, providing insight into its role in tumor pathogenesis.
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A case of a recurrent sphenocavernous meningioma is presented. The patient is a 42-year-old male who presented with an episode of transient right-sided numbness. A magnetic resonance imaging (MRI) revealed a large left sphenocavernous meningioma. The patient underwent a frontotemporal craniotomy for tumor resection. Near total resection was achieved with minimal residual in the left cavernous sinus (CS) and orbital apex. The pathology was consistent with meningioma, World Health Organization (WHO) grade I. A follow-up MRI was done 9 months after surgery and showed a growth of the residual tumor, which was treated with intensity modulated radiotherapy. Tumor growth was detected on serial imaging over a 4-year period. Surgical resection was offered. A left frontotemporal craniotomy with pretemporal transcavernous approach was performed. The bone flap was reopened and the dura was opened in a Y-shaped fashion. The roof of the optic canal was drilled off, and the falciform ligament was opened to decompress the optic nerve. The tumor was disconnected from the anterior clinoid region (the anterior clinoid process was eroded by the tumor) and reflected off the wall of the lateral CS. Tumor was adherent to the V2 fascicles (the lateral CS wall was resected in the first surgery) and was sharply dissected off. Gross total resection was achieved. The pathology was consistent with meningioma, WHO grade I. The patient had an unremarkable postoperative course without any new neurological deficits. The link to the video can be found at: https://youtu.be/KVBVw_86JqM .
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OBJECT: The pretemporal transcavernous anterior petrosal (PTAP) approach and the combined petrosal (CP) approach have been used to resect petroclival meningiomas (PCMs). In this cadaveric anatomical study, a two-stage combined PTAP and endoscopic endonasal far medial (EEFM) approach (the PTAPE approach) was compared morphometrically to the CP approach. A case study provides a clinical example of using the PTAPE approach to treat a patient with a PCM. The key elements of the approach selection process are outlined. METHODS: Five cadaveric specimens underwent a CP approach and 5 underwent a PTAPE approach. The area of drilled clivus, length of multiple cranial nerves (CNs), and the area of brain stem exposure were measured, reported as means (standard deviations) by group, and compared. RESULTS: The total area of the clivus drilled in the PTAPE group (695.3 [121.7] mm2) was greater than in the CP group (88.7 [17.06] mm2, P < 0.01). Longer segments of CN VI were exposed via the PTAPE than the CP approach (35.6 [9.07] vs. 16.3 [6.02] mm, P < 0.01). CN XII (8.8 [1.06] mm) was exposed only in the PTAPE group. Above the pontomedullary sulcus, the total area of brain stem exposed was greater with the PTAPE than the CP approach (1003.4 [219.5] mm2 vs. 437.6 [83.7] mm2, P < 0.01). Similarly, the total exposure of the medulla was greater after the PTAPE than the CP exposure (240.2 [57.06] mm2 vs. 48.1 [19.9] mm2, P < 0.01). CONCLUSION: A combined open-endoscopic paradigm is proposed for managing large PCMs. This approach incorporates the EEFM approach to address the limitations of the PTAP and the CP approach in a systematic fashion. Understanding the anatomical findings of this study will aid in tailoring surgical approaches to patients with these complex lesions.
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Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Cadáver , Fossa Craniana Posterior/anatomia & histologia , Fossa Craniana Posterior/cirurgia , Humanos , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Osso Petroso/cirurgia , Neoplasias da Base do Crânio/cirurgiaRESUMO
OBJECTIVE: Meningiomas are a common primary central nervous system tumor that lack a U.S. Food and Drug Administration-approved pharmacotherapy. Approximately 20%-35% of meningiomas are classified as higher grade with poor outcome, whereas patients with lower-grade meningiomas are known to have long-term neurologic deficits and reduced overall survival. Recent efforts to understand the epigenetic landscape of meningiomas have highlighted the importance of DNA methylation for predicting tumor outcomes and prognosis; therefore, inhibition of these pathways may present a viable therapy for these tumors. METHODS: In this study, we perform dose-response curves of decitabine, a DNA methyltransferase inhibitor, on patient-cultured tumors and meningioma cell lines. RESULTS: Thirty total samples were evaluated, including 24 patient-cultured tumors and 6 established meningioma cell lines. Meningiomas were found to have a significant reduction in cell viability after decitabine treatment in a dose dependent manner. The effect was primarily driven by 11 of the 30 tumors in our cohort, or 36.7%. Decitabine significantly reduced cell viability across all grades, tumors from different sexes, recurrent and primary tumors, as well as tumors without a history of previous radiation. Surprisingly, our single radiation-induced tumor did demonstrate greater viability after decitabine treatment. CONCLUSIONS: Our work has identified a potential drug candidate in decitabine for the treatment of meningiomas regardless of clinical subgroup. These data require further evaluation in preclinical models, and the conclusions based on clinical subgroups need to be evaluated in a larger cohort to achieve appropriate statistical power.
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Neoplasias Meníngeas , Meningioma , DNA , Metilação de DNA , Decitabina , Humanos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Meningioma/tratamento farmacológico , Meningioma/genética , Meningioma/patologia , TransferasesRESUMO
Tuberculum sellae meningiomas (TSMs) arise from the anterior skull base. Endocrine status after TSM resection is an important determinant of quality of life. We sought to better characterize the risk of postoperative endocrinopathy for patients with TSM undergoing open transcranial approach (TCA) microsurgical resection. A systematic review was conducted following MOOSE and PRISMA guidelines. Results were screened against predefined criteria, which included studies evaluating endocrinopathy rates after open transcranial microsurgery for TSM. Outcome incidence was calculated using random-effect meta-analysis of proportions. Eight studies met the inclusion criteria, comprising 406 patients. The average age of the cohort was 52.2 years, and a majority (70%) of the patients were female. The pooled incidence of postoperative transient diabetes insipidus (DI) was 7.5% (95% CI 2.9-12%; p = 0.001; I2 = 75.9%) and permanent DI was 1.6% (95% CI 0.3-2.7%; p = 0.01; I2 = 0%). The pooled rate of postoperative hypopituitarism was 3.6% (95% CI 1.6-5.7%; p < 0.001; I2 = 22.2%), while the incidence of hyperprolactinemia was 1.3% (95% CI 0.1 = 2.6%; p = 0.036; I2 = 8.74%). The incidence of SIADH was 4% in one study but was not included in the meta-analysis. Endocrinopathy after TSM microsurgical resection is rare, but the available studies' poor quality of evidence and inconsistent methodology may reflect that it is underreported in the literature. Nevertheless, clinicians should consider the risk of hormonal impairment and counsel their patients accordingly when selecting a TCA for these lesions.
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Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Qualidade de Vida , Estudos Retrospectivos , Sela Túrcica , Neoplasias da Base do Crânio/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: Nervus intermedius (NI) dysfunction after the management of vestibular schwannoma (VS) is underreported and is experienced by patients undergoing stereotactic radiosurgery and surgical resection. The aim of this study was to present NI outcomes in a series of patients who underwent all treatment modalities for VS and to review the existing literature. METHODS: We performed a retrospective review of all patients with VS who were treated at our institution between January 1, 2008, and December 31, 2018. Demographic data, tumor size, Koos grade, treatment modality, extent of resection, postoperative facial nerve function, and hearing function were collected. NI outcomes were determined from phone interview using a previously published functional questionnaire. RESULTS: Of 222 patients who were reviewed, 98 patients responded to the questionnaire. Patients were stratified into 3 groups: group 1, 54 patients who underwent radiation; group 2, 27 patients who underwent surgical treatment; group 3, 17 patients who underwent both radiation and surgery. Of patients, 28% presented with preoperative NI dysfunction, most commonly dry eye followed by taste dysfunction and lacrimation dysfunction. Following treatment, 79% of patients experienced NI dysfunction, most commonly dry eye. Statistical differences in dry eye and taste dysfunction were observed when comparing the treatment groups. CONCLUSIONS: NI dysfunction is common following treatment for VS and should be included in pretreatment counseling of patients, as it may impact treatment choice and quality of life. Additional studies are warranted to fully characterize NI dysfunction after treatment.
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Neuroma Acústico , Radiocirurgia , Nervo Facial/cirurgia , Humanos , Neuroma Acústico/patologia , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Translabyrinthine approaches (TLAs) for resection of skull base neoplasms are complex with variable reconstruction techniques. Fat grafts in conjunction with hydroxyapatite bone cement techniques have seldom been described in terms of possible superiority to other skull base reconstruction techniques. We sought to determine the impact of this skull base reconstruction technique on clinical outcomes and patient's satisfaction. METHOD: We performed a retrospective analysis of all patients who underwent translabyrinthine approaches for resection of CPA lesions over a 5-year period. Both post-op objective and subjective markers of reconstruction, as well as postoperative complications, were collected and analyzed. RESULTS: Sixty-nine patients were included, 34 underwent reconstruction with hydroxyapatite and fat (rHAC) and 35 with fat alone (rF). rHAC was associated with fewer cranial wound superficial infection/dehiscence (0% vs 14.3%; p = 0.029) and shorter length of stay (mean ± standard deviation) (6.9 ± 7.4 vs 4.4 ± 3.7 days, p = 0.008). Postoperative subjective characterization of rHAC demonstrated improved satisfaction scores (1.38 ± 0.5 vs 1.83 ± 1; p = 0.049) and fewer reports of post-operative irregularities (11.5% vs 37.5%; p = 0.017). CONCLUSION: The use of hydroxyapatite for cranial reconstruction after translabyrinthine approaches has improved patient satisfaction and decreased cranial defects in our small series. Postoperative complications are consistent with other described methods, but with shorter hospital stay, decreased risk of superficial wound dehiscence/infection, and a perceived superiority in preventing percutaneous post-op CSF leaks.