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1.
Neurosurg Focus ; 56(5): E2, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38691870

RESUMEN

OBJECTIVE: The aim of this study was to describe the natural history of incidental benign-appearing notochordal lesions of the skull base with specific attention to features that can make differentiation from low-grade chordoma more difficult, namely contrast uptake and bone erosion. METHODS: In this retrospective case series, the authors describe the clinical outcomes of 58 patients with incidental benign-appearing notochordal lesions of the clivus, including those with minor radiological features of bone erosion or contrast uptake. RESULTS: All lesions remained stable during a median follow-up of almost 3 years. Thirty-seven (64%) patients underwent contrast-enhanced MRI; lesions in 14 (38%) of these patients exhibited minimal contrast enhancement. Twenty-seven (47%) patients underwent CT; lesions in 6 (22%) of these patients exhibited minimal bone erosion. CONCLUSIONS: These data make the case for monitoring selected cases of benign-appearing notochordal lesions of the clivus in the first instance even when there is minor contrast uptake or minimal bone erosion.


Asunto(s)
Hallazgos Incidentales , Imagen por Resonancia Magnética , Notocorda , Neoplasias de la Base del Cráneo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Notocorda/diagnóstico por imagen , Anciano , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Cordoma/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Estudios de Seguimiento , Adulto Joven , Fosa Craneal Posterior/diagnóstico por imagen
2.
Sci Adv ; 10(20): eadj3301, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758780

RESUMEN

Myeloid cells are highly prevalent in glioblastoma (GBM), existing in a spectrum of phenotypic and activation states. We now have limited knowledge of the tumor microenvironment (TME) determinants that influence the localization and the functions of the diverse myeloid cell populations in GBM. Here, we have utilized orthogonal imaging mass cytometry with single-cell and spatial transcriptomic approaches to identify and map the various myeloid populations in the human GBM tumor microenvironment (TME). Our results show that different myeloid populations have distinct and reproducible compartmentalization patterns in the GBM TME that is driven by tissue hypoxia, regional chemokine signaling, and varied homotypic and heterotypic cellular interactions. We subsequently identified specific tumor subregions in GBM, based on composition of identified myeloid cell populations, that were linked to patient survival. Our results provide insight into the spatial organization of myeloid cell subpopulations in GBM, and how this is predictive of clinical outcome.


Asunto(s)
Glioblastoma , Células Mieloides , Microambiente Tumoral , Glioblastoma/patología , Glioblastoma/metabolismo , Humanos , Células Mieloides/metabolismo , Células Mieloides/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Análisis de la Célula Individual , Hipoxia/metabolismo , Perfilación de la Expresión Génica
3.
Neuro Oncol ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695575

RESUMEN

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

4.
Acta Neurochir (Wien) ; 166(1): 165, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38565732

RESUMEN

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.


Asunto(s)
Embolia Pulmonar , Tromboembolia Venosa , Adulto , Humanos , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/tratamiento farmacológico , Estudios Prospectivos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/tratamiento farmacológico , Factores de Riesgo , Anticoagulantes/uso terapéutico , Hemorragia Cerebral/tratamiento farmacológico , Estudios Retrospectivos , Hematoma , Base del Cráneo/cirugía
5.
Sci Rep ; 14(1): 4905, 2024 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418818

RESUMEN

A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.


Asunto(s)
Neoplasias Encefálicas , Medios de Contraste , Humanos , Estudios de Factibilidad , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología
6.
Brain Commun ; 5(4): fcad197, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680691

RESUMEN

Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develops sporadically in non-NF2-related schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-related schwannomatosis tumours. However, differences between NF2-related schwannomatosis and the more common sporadic disease include NF2-related schwannomatosis patients presenting an increased number of tumours, multiple tumour types and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-related schwannomatosis tumours is therefore required to underpin the development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-related schwannomatosis and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-related schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-related schwannomatosis vestibular schwannoma and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-related schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-related schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising one-third of the cell mass in both NF2-related schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell type abundance or imaging mass cytometry staining between NF2-related schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-related schwannomatosis and sporadic vestibular schwannoma.

7.
Neurooncol Adv ; 5(1): vdad089, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37547267

RESUMEN

Background: Our neurosurgical unit adopted a model of shared decision-making (SDM) based on multidisciplinary clinics for vestibular schwannoma (VS). A unique feature of this clinic is the interdisciplinary counseling process with a surgeon presenting the option of surgery, an oncologist radiosurgery or radiotherapy, and a specialist nurse advocating for the patient. Methods: This is a retrospective cohort study. All new patients seen in the combined VS clinic and referred from the skull base multidisciplinary team (MDT) from beginning of June 2013 to end of January 2019 were included. Descriptive statistics and frequency analysis were carried out for the full cohort. Results: Three hundred and fifty-four patients presenting with new or previously untreated VS were included in the analysis. In our cohort, roughly one-third of patients fall into each of the treatment strategies with slightly smaller numbers of patients undergoing surgery than watch, wait and rescan (WWR) ,and SRS (26.6% vs. 32.8% and 37.9%, respectively). Conclusion: In our experience, the combined surgery/oncology/specialist nurse clinic streamlines the patient experience for those with a VS suitable for either microsurgical or SRS/radiotherapy treatment. Decision-making in this population of patients is complex and when presented with all treatment options patients do not necessarily choose the least invasive option as a treatment. The unique feature of our clinic is the multidisciplinary counseling process with a specialist nurse advocating and guiding the patient. Treatment options are likely to become more rather than less complex in future years making combined clinics more valuable than ever in the SDM process.

9.
Neurooncol Adv ; 5(Suppl 1): i26-i34, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37287572

RESUMEN

The widespread availability and use of brain magnetic resonance imaging and computed tomography has led to an increase in the frequency of incidental meningioma diagnoses. Most incidental meningioma are small, demonstrate indolent behavior during follow-up, and do not require intervention. Occasionally, meningioma growth causes neurological deficits or seizures prompting surgical or radiation treatment. They may cause anxiety to the patient and present a management dilemma for the clinician. The questions for both patient and clinician are "will the meningioma grow and cause symptoms such that it will require treatment within my lifetime?" and "will deferment of treatment result in greater treatment-related risks and lower chance of cure?." International consensus guidelines recommend regular imaging and clinical follow-up, but the duration is not specified. Upfront treatment with surgery or stereotactic radiosurgery/radiotherapy may be recommended but this is potentially an overtreatment, and its benefits must be balanced against the risk of related adverse events. Ideally, treatment should be stratified based on patient and tumor characteristics, but this is presently hindered by low-quality supporting evidence. This review discusses risk factors for meningioma growth, proposed management strategies, and ongoing research in the field.

10.
Neurooncol Adv ; 5(Suppl 1): i94-i104, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37287576

RESUMEN

NF2-schwannomatosis is the most common genetic predisposition syndrome associated with meningioma. Meningioma in NF2-schwannomatosis is a major source of morbidity and mortality. This is due to accumulative tumor burden in patients with synchronous schwannomas and ependymomas, sometimes including complex collision tumors. Balancing the impact of multiple interventions against the natural history of various index tumors, and the ongoing risk of de novo tumors over an individual's lifetime makes decision-making complex. The management of any given individual meningioma is often different from a comparable sporadic tumor. There is typically a greater emphasis on conservative management and tolerating growth until a risk boundary is reached, whereby symptomatic deterioration or higher risk from anticipated future treatment is threatened. Management by high-volume multidisciplinary teams improves quality of life and life expectancy. Surgery remains the mainstay treatment for symptomatic and rapidly enlarging meningioma. Radiotherapy has an important role but carries a higher risk compared to its use in sporadic disease. Whilst bevacizumab is effective in NF2-associated schwannoma and cystic ependymoma, it has no value in the management of meningioma. In this review, we describe the natural history of the disease, underlying genetic, molecular, and immune microenvironment changes, current management paradigms, and potential therapeutic targets.

11.
J Neurosurg ; 139(6): 1613-1618, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37178029

RESUMEN

OBJECTIVE: Skull base meningiomas (SBMs) involving the cavernous sinus encase the internal carotid artery (ICA) and may lead to stenosis of the vessel. Although ischemic stroke has been reported in the literature, there are to the authors' knowledge no reported studies quantifying the risk of stroke in these patients. The authors aimed to determine the frequency of arterial stenosis in patients with SBMs that encase the cavernous ICA and to estimate the risk of ischemic stroke in these patients. METHODS: Records of all patients with SBM encasing the ICA whose cases were managed by the skull base multidisciplinary team at Salford Royal Hospital between 2011 and 2017 were reviewed using a two-stage approach: 1) clinical and radiological strokes were identified from electronic patient records, and 2) cases were reviewed to examine the correlation between ICA stenosis associated with SBM encasement and anatomically related stroke. Strokes that were caused by another pathology or did not occur in the perfusion territory were excluded. RESULTS: In the review of patient records the authors identified 118 patients with SBMs encasing the ICA. Of these, 62 SBMs caused stenosis. The median age at diagnosis was 70 (IQR 24) years, and 70% of the patients were female. The median follow-up was 97 (IQR 101) months. A total of 13 strokes were identified in these patients; however, only 1 case of stroke was associated with SBM encasement, which occurred in the perfusion territory of a patient without stenosis. Risk of acute stroke during the follow-up period for the entire cohort was 0.85%. CONCLUSIONS: Acute stroke in patients with ICA encasement by SBMs is rare despite the propensity of these tumors to stenose the ICA. Patients with ICA stenosis secondary to their SBM did not have a higher incidence of stroke than those with ICA encasement without stenosis. The results of this study demonstrate that prophylactic intervention to prevent stroke is not necessary in ICA stenosis secondary to SBM.


Asunto(s)
Estenosis Carotídea , Accidente Cerebrovascular Isquémico , Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Meningioma/epidemiología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/epidemiología , Constricción Patológica/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Neoplasias de la Base del Cráneo/complicaciones , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Neoplasias de la Base del Cráneo/patología , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/epidemiología , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/patología , Estudios Retrospectivos
12.
Neurooncol Adv ; 5(1): vdad025, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37051330

RESUMEN

Background: Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from treatment centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation treatment in NF2-related schwannomatosis patients is associated with increased rates of subsequent malignancy (M)/malignant progression (MP). Methods: All UK patients with NF2 were eligible if they had a clinical/molecular diagnosis. Cases were NF2 patients treated with radiation for benign tumors. Controls were matched for treatment location with surgical/medical treatments based on age and year of treatment. Prospective data collection began in 1990 with addition of retrospective cases in 1969. Kaplan-Meier analysis was performed for malignancy incidence and survival. Outcomes were central nervous system (CNS) M/MP (2cm annualized diameter growth) and survival from index tumor treatment. Results: In total, 1345 NF2 patients, 266 (133-Male) underwent radiation treatments between 1969 and 2021 with median first radiotherapy age of 32.9 (IQR = 22.4-46.0). Nine subsequent CNS malignancies/MPs were identified in cases with only 4 in 1079 untreated (P < .001). Lifetime and 20-year CNS M/MP was ~6% in all irradiated patients-(4.9% for vestibular schwannomas [VS] radiotherapy) versus <1% in the non-irradiated population (P < .001/.01). Controls were well matched for age at NF2 diagnosis and treatment (Males = 133%-50%) and had no M/MP in the CNS post-index tumor treatment (P = .0016). Thirty-year survival from index tumor treatment was 45.62% (95% CI = 34.0-56.5) for cases and 66.4% (57.3-74.0) for controls (P = .02), but was nonsignificantly worse for VS radiotherapy. Conclusion: NF2 patients should not be offered radiotherapy as first-line treatment of benign tumors and should be given a frank discussion of the potential 5% excess absolute risk of M/MP.

13.
Clin Immunol ; 249: 109287, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36907540

RESUMEN

Sensorineural hearing loss is the most common type of hearing loss in adults and occurs due to damage of the inner ear caused by a range of factors including ageing, excessive noise, toxins, and cancer. Auto-inflammatory disease is also a cause of hearing loss and there is evidence that inflammation could contribute to hearing loss in other conditions. Within the inner ear there are resident macrophage cells that respond to insults and whose activation correlates with damage. The NLRP3 inflammasome is a multi-molecular pro-inflammatory protein complex that forms in activated macrophages and may contribute to hearing loss. The aim of this article is to discuss the evidence for the NLRP3 inflammasome and associated cytokines as potential therapeutic targets for sensorineural hearing loss in conditions ranging from auto-inflammatory disease to tumour-induced hearing loss in vestibular schwannoma.


Asunto(s)
Oído Interno , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Adulto , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/metabolismo , Oído Interno/metabolismo , Pérdida Auditiva/complicaciones
14.
J Neurosurg ; 139(4): 972-983, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36933255

RESUMEN

OBJECTIVE: Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS: Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS: Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS: Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.


Asunto(s)
Neoplasias de los Nervios Craneales , Neurilemoma , Neuroma Acústico , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Neurilemoma/diagnóstico por imagen , Neurilemoma/cirugía , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/cirugía , Neoplasias de los Nervios Craneales/diagnóstico por imagen , Neoplasias de los Nervios Craneales/cirugía , Nervio Facial/diagnóstico por imagen , Nervio Facial/cirugía , Nervio Facial/patología , Resultado del Tratamiento , Estudios Multicéntricos como Asunto
15.
Brain ; 146(7): 2861-2868, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-36546557

RESUMEN

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.


Asunto(s)
Neurilemoma , Neurofibromatosis , Neurofibromatosis 2 , Neuroma Acústico , Neoplasias Cutáneas , Humanos , Neuroma Acústico/genética , Estudio de Asociación del Genoma Completo , Neurilemoma/genética , Neurilemoma/patología , Neurofibromatosis/genética , Neoplasias Cutáneas/genética , Neurofibromatosis 2/genética , Factores de Transcripción/genética
16.
J Neurol Surg B Skull Base ; 83(4): 367-373, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35903657

RESUMEN

Objective The study aimed to determine long-term outcomes in patients with intraoperative electrical conduction block in an anatomically intact facial nerve (FN). Methods Single center retrospective review of prospectively collected database of all vestibular schwannoma surgeries between January 1, 2008 and August 25, 2015. Operative notes were reviewed and patients with anatomically intact FNs, but complete conduction block at the end of surgery were included for analysis. Results In total, 371 patients had vestibular schwannoma surgery of which 18 met inclusion criteria. Mean follow-up was 34.28 months and average tumor size was 28.00 mm. Seventeen patients had House-Brackmann Grade VI facial palsy immediately postoperatively and one patient was grade V. At 1 year, three patients remained grade VI (17%), two improved to grade V (11%), seven to grade IV (39%), six to grade III (33%), and one patient to grade II (6%). On extended follow-up, five patients (28%) had additional 1 to 2 score improvement in facial function. Subset analysis revealed no correlation of tumor size, vascularity, adherence to nerve, operative approach, extent of resection, splaying of FN, and recurrent tumor or sporadic tumors to the extent of FN recovery. Conclusion Intraoperative conduction block does not condemn a patient to permanent FN palsy. There is potential for a degree of recovery comparable with those undergoing nerve grafting. Our data do not clearly support a policy of same-surgery or early-postoperative primary nerve grafting in the event of a complete conduction block, and instead we favor monitoring for recovery in an anatomically intact nerve.

17.
J Neurol Surg B Skull Base ; 83(1): 1-10, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35155063

RESUMEN

Introduction Vestibular schwannomas (VS) are histologically benign tumors arising from cranial nerve VIII. Far from a homogenous proliferation of Schwann cells, mounting evidence has highlighted the complex nature of the inflammatory microenvironment in these tumors. Methods A review of the literature pertaining to inflammation, inflammatory molecular pathways, and immune-related therapeutic targets in VS was performed. Relevant studies published up to June 2020 were identified based on a literature search in the PubMed and MEDLINE databases and the findings were synthesized into a concise narrative review of the topic. Results The VS microenvironment is characterized by a dense infiltrate of inflammatory cells, particularly macrophages. Significantly higher levels of immune cell infiltration are observed in growing versus static tumors, and there is a demonstrable interplay between inflammation and angiogenesis in growing VS. While further mechanistic studies are required to ascertain the exact role of inflammation in angiogenesis, tumor growth, and Schwann cell control, we are beginning to understand the key molecular pathways driving this inflammatory microenvironment, and how these processes can be monitored and targeted in vivo . Conclusion Observational research has revealed a complex and heterogeneous tumor microenvironment in VS. The functional landscape and roles of macrophages and other immune cells in the VS inflammatory infiltrate are, however, yet to be established. The antiangiogenic drug bevacizumab has shown the efficacy of targeted molecular therapies in VS and there is hope that agents targeting another major component of the VS microenvironment, inflammation, will also find a place in their future management.

18.
Acta Neurochir (Wien) ; 164(4): 1115-1123, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35039959

RESUMEN

INTRODUCTION: Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively. METHODS: Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up. RESULTS: One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups. CONCLUSION: Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.


Asunto(s)
Apoplejia Hipofisaria , Neoplasias Hipofisarias , Accidente Cerebrovascular , Humanos , Apoplejia Hipofisaria/diagnóstico por imagen , Apoplejia Hipofisaria/cirugía , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento
19.
World Neurosurg ; 157: 48-53, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34601172

RESUMEN

OBJECTIVE: Spinal meningiomas are one of the frequently seen intradural extramedullary spinal tumors. They are almost always World Health Organization grade I, and a complete removal of the tumor can be curative. However, ventrally located spinal meningioma removal can be challenging due to the position in front of the spinal cord through a narrow corridor provided by routine dorsal approaches. Incomplete excision of the relatively inaccessible dural attachment can consequently lead to recurrence. We describe a safe and reproducible technique used to achieve Simpson grade I removal of ventrally located spinal meningioma. METHODS: Since the spinal dura can be easily divided into inner and outer layers and the tumor usually spares the outer layer, we developed a simple technique to achieve total resection of the tumor and involved dura while leaving the outer dural layer intact. RESULTS: An advantage of this procedure is that it exploits an interdural approach to allow early devascularization of the tumor without cord manipulation and provides access to the ventral dura to achieve Simpson grade I excision. Another advantage is complete dural closure to minimize postoperative cerebrospinal fluid leak or ventral cord herniation without the need for dural substitutes. CONCLUSION: Its novel interdural approach can be used for all ages and all spinal meningiomas.


Asunto(s)
Duramadre/cirugía , Meningioma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Neoplasias de la Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/cirugía , Pérdida de Líquido Cefalorraquídeo/prevención & control , Duramadre/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Resultado del Tratamiento
20.
Pituitary ; 25(2): 267-274, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34843070

RESUMEN

PURPOSE: There is no compelling outcome data or clear guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using low molecular weight heparin (chemoprophylaxis) in patients undergoing pituitary surgery. Here we describe our experience of early chemoprophylaxis (post-operative day 1) following trans-sphenoidal pituitary surgery. METHODS: Single-centre review of a prospective surgical database and VTE records. Adults undergoing first time trans-sphenoidal pituitary surgery were included (2009-2018). VTE was defined as either deep vein thrombosis and/or pulmonary embolism within 3 months of surgery. Postoperative haematomas were those associated with a clinical deterioration together with radiological evidence. RESULTS: 651 Patients included with a median age of 55 years (range 16-86 years). Most (99%) patients underwent trans-sphenoidal surgery using a standard endoscopic single nostril or bi-nostril trans-sphenoidal technique. More than three quarters had pituitary adenomas (n = 520, 80%). Postoperative chemoprophylaxis to prevent VTE was administered in 478 patients (73%). Chemoprophylaxis was initiated at a median of 1 day post-procedure (range 1-5 days postoperatively; 92% on postoperative day 1). Tinzaparin was used in 465/478 patients (97%) and enoxaparin was used in 14/478 (3%). There were no cases of VTE, even in 78 ACTH-dependent Cushing's disease patients. Six patients (1%) developed postoperative haematomas. Chemoprophylaxis was not associated with a significantly higher rate of postoperative haematoma formation (Fisher's Exact, p = 0.99) or epistaxis (Fisher's Exact, p > 0.99). CONCLUSIONS: Chemoprophylaxis after trans-sphenoidal pituitary surgery on post-operative day 1 is a safe strategy to reduce the risk of VTE without significantly increasing the risk of postoperative bleeding events.


Asunto(s)
Embolia Pulmonar , Tromboembolia Venosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/prevención & control , Factores de Riesgo , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Adulto Joven
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