RESUMO
INTRODUCTION: Seizures are a common symptom of supratentorial meningiomas with pre- and postoperative seizure rates of approximately 30% and 12%, respectively, especially in parasagittal and convexity meningiomas. Less is known about the association between seizures and posterior fossa meningiomas. This study evaluates the prevalence, potential causes, and outcomes of seizures in patients who have undergone surgery for posterior fossa meningioma. METHODS: This is a retrospective, observational, single-center study of consecutive patients who underwent surgical resection of posterior fossa meningiomas between 2009 and 2017. We retrospectively identified patients with seizures and analyzed patient demographics, tumor characteristics, and procedural characteristics. RESULTS: A total of 44 patients (mean age: 59.8 ± 13.5 years) were included. Twenty-six tumors were located at the cerebellar convexity and tentorium (59.1%), 12 at the cerebellopontine angle (27.3%), four at the clivus (9.1%), and two at the foramen magnum (4.5%). Seizures were the presenting symptom of cerebellar meningioma in two patients. Patients were seizure-free after surgery. Three patients had their first seizure after surgery (interval between surgery and first seizure: two days to 17 months). Analysis of these three patients revealed possible causes of postoperative seizures: radiation necrosis and edema, hyponatremia, and preoperative hydrocephalus. In all patients with postoperative seizures, long-term seizure control was achieved with the administration of antiepileptic drugs. CONCLUSIONS: The incidence of seizures in patients with posterior fossa meningiomas is relatively low. Antiepileptic drugs can help to achieve seizure control.
RESUMO
Background and Objectives: Cavernous malformations (CM) are vascular malformations with low blood flow. The removal of brainstem CMs (BS) is associated with high surgical morbidity, and there is no general consensus on when to treat deep-seated BS CMs. The aim of this study is to compare the surgical outcomes of a series of deep-seated BS CMs with the surgical outcomes of a series of superficially located BS CMs operated on at the Department of Neurosurgery, College of Tuebingen, Germany. Materials and Methods: A retrospective evaluation was performed using patient charts, surgical video recordings, and outpatient examinations. Factors were identified in which surgical intervention was performed in cases of BS CMs. Preoperative radiological examinations included MRI and diffusion tensor imaging (DTI). For deep-seated BS CMs, a voxel-based 3D neuronavigation system and electrophysiological mapping of the brainstem surface were used. Results: A total of 34 consecutive patients with primary superficial (n = 20/58.8%) and deep-seated (n = 14/41.2%) brainstem cavernomas (BS CM) were enrolled in this comparative study. Complete removal was achieved in 31 patients (91.2%). Deep-seated BS CMs: The mean diameter was 14.7 mm (range: 8.3 to 27.7 mm). All but one of these lesions were completely removed. The median follow-up time was 5.8 years. Two patients (5.9%) developed new neurologic deficits after surgery. Superficial BS CMs: The median diameter was 14.9 mm (range: 7.2 to 27.3 mm). All but two of the superficial BS CMs could be completely removed. New permanent neurologic deficits were observed in two patients (5.9%) after surgery. The median follow-up time in this group was 3.6 years. Conclusions: The treatment of BS CMs remains complex. However, the results of this study demonstrate that with less invasive posterior fossa approaches, brainstem mapping, and neuronavigation combined with the use of a blunt "spinal cord" dissection technique, deep-seated BS CMs can be completely removed in selected cases, with good functional outcomes comparable to those of superficial BS CM.
RESUMO
Meningiomas are the most common brain tumor in adults with rising incidence rates due to an aging population globally, increased availability of neuroimaging, and increased awareness of this condition by treating clinicians and primary care physicians. Surgical resection remains the mainstay of treatment, with adjuvant radiotherapy reserved for higher grade meningiomas or tumors that undergo incomplete resections. Whereas these tumors were classically defined by their histopathological features and subtypes, recent work has uncovered the molecular alterations that may lead to tumor development and have important prognostic implications. However, there remain important clinical questions regarding the management of meningiomas and current clinical guidelines continue to evolve as additional studies add onto the growing body of work that enables us to better understand these tumors.
Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Adulto , Humanos , Idoso , Meningioma/terapia , Envelhecimento , Neuroimagem , Neoplasias Meníngeas/terapiaRESUMO
OBJECTIVE: To evaluate the safety and efficacy of the low-profile Acandis Acclino microstent for embolization of recurrent and residual intracranial aneurysms. METHODS: Consecutive patients treated with the Acclino for aneurysm remnants at three German neurovascular centers were enrolled. The technical success, complications, angiographic and clinical outcome were investigated. RESULTS: Nineteen patients (median age: 53 years) with 19 aneurysm remnants (median size: 5 mm, anterior circulation: 14) were included. Initial aneurysm treatment consisted of stand-alone coiling in 14 cases, stent-assisted coiling in 4 and clipping in 1. Acclino stent-assisted coil embolization was performed technically successfully in all patients. Morbidity occurred in one patient (5.3%) due to aneurysm perforation. At the angiographic follow-up with a median follow-up duration of 21 months (range: 5-37 months), complete occlusion was obtained in 76.9%. The retreatment rate was 7.7%. CONCLUSIONS: Retreatment of aneurysm remnants with the Acclino microstent was associated with high aneurysm occlusion rates and acceptable morbidity. Further studies will be necessary to draw a definite conclusion.
Assuntos
Embolização Terapêutica/instrumentação , Aneurisma Intracraniano/terapia , Stents , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity. The objective was to evaluate, whether specific morphological aneurysm characteristics could serve as predictive values for aSAH severity, disease-related complications and clinical outcome. METHODS: A total of 453 aSAH patients (mean age: 54.9⯱â¯13.8â¯years, mean aneurysm size: 7.5⯱â¯3.6â¯mm) treated at a single center were retrospectively included. A morphometric analysis was performed based on angiographic image sets, determining aneurysm location, aneurysm size, neck width, aneurysm size ratios, aneurysm morphology and vessel size. The following outcome measures were defined: World Federation of Neurosurgical Societies (WFNS) grade 4 and 5, Fisher grade 4, vasospasm, cerebral infarction and unfavorable functional outcome. RESULTS: Regarding morphology parameters, aneurysm neck width was an independent predictor for Fisher 4 hemorrhage (OR: 1.1, 95%CI: 1.0-1.3, pâ¯=â¯0.048), while dome width (OR: 0.92, 95%CI: 0.86-0.97, pâ¯=â¯0.005) and internal carotid artery location (OR: 2.1, 95%CI: 1.1-4.2, pâ¯=â¯0.028) predicted vasospasm. None of the analyzed morphological characteristics prognosticated functional outcome. Patient age (OR: 0.95, 95%CI: 0.93-0.96, pâ¯<â¯0.001), WFNS score (OR: 4.8, 95%CI: 2.9-8.0, pâ¯<â¯0.001), Fisher score (OR: 2.3, 95%CI: 1.4-3.7, pâ¯<â¯0.001) and cerebral infarction (OR: 4.5, 95%CI: 2.7-7.8, pâ¯<â¯0.001) were independently associated with unfavorable outcome. CONCLUSIONS: The findings indicate a correlation between aneurysm morphology, Fisher grade and vasospasm. Further studies will be required to reveal an independent association of aneurysm morphology with cerebral infarction and functional outcome.
Assuntos
Infarto Cerebral/patologia , Aneurisma Intracraniano/patologia , Hemorragia Subaracnóidea/patologia , Adulto , Idoso , Infarto Cerebral/epidemiologia , Infarto Cerebral/terapia , Humanos , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Although the superiority of clipping compared to coiling on the oculomotor nerve palsy (ONP) recovery for ruptured posterior communicating artery aneurysms (PcomAAs) has been widely accepted, which treatment modality is better in the treatment of ONP induced by unruptured PcomAAs still remains unclear. METHODS: A meta-analysis of studies that compared clipping with coiling was performed after a literature search. Perioperative data and clinical outcome were extracted. Analysis on the effect of the two treatment modalities was then performed. RESULTS: Nine eligible studies with a total of 136 patients met the inclusion criteria. There was a significant difference in the total efficiency (any degree of improvement) on ONP favoring clipping [RR= 1.21, 95%CI (1.01, 1.44), p = 0.04], the effect was most notable for complete recovery of ONP after having suffered preoperative partial palsy [RR= 0.72, 95%CI (0.55, 0.95), p = 0.02]. There was neither a significant difference regarding the complete recovery of ONP [RR= 1.11, 95%CI (0.77, 1.61), p = 0.58] nor the frequency of complications [RR= 0.07, 95%CI (0.00, 1.10), p = 0.06]. Also when subdividing there was no significant difference in complete recovery of ONP in patients who had initially suffered a complete ONP [RR= 0.79, 95%CI (0.38, 1.64), p = 0.53] and partial ONP [RR= 1.16, 95%CI (0.65, 2.08), p = 0.61] between clipping and coiling. CONCLUSIONS: A superiority of clipping over coiling for the improvement of ONP secondary to unruptured PcomAAs was found. Patients with partial ONP were more likely to attain a complete resolution of ONP, as compared to complete ONP.
Assuntos
Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Doenças do Nervo Oculomotor/etiologia , Procedimentos Cirúrgicos Vasculares/métodos , Estudos de Coortes , HumanosRESUMO
OBJECTIVE: Although intracranial aneurysms are increasingly treated endovascularly, microsurgical clipping has been the standard approach for middle cerebral artery (MCA) aneurysms. We compared microsurgical clipping and state-of-the-art endovascular treatment of unruptured MCA bifurcation aneurysms treated at a neurovascular center following a "coil-first" policy. METHODS: This single-center study included 148 patients treated for 160 unruptured MCA bifurcation aneurysms. Technical success, complications, clinical outcome, and angiographic results were retrospectively compared. RESULTS: Microsurgical clipping was performed for 120 MCA aneurysms (75%) and endovascular treatment for 40 (25%; conventional coiling: 8, stent-assisted coiling: 16, balloon-assisted coiling: 3, and flow-disruption: 13). Technical treatment success was higher in the clipping group (100%) than in the endovascular group (92.5%, P = 0.015). Overall, complications occurred in 16.7% for clipping and in 20.0% for endovascular treatment (P = 0.631). Major ischemic stroke rates were 4.2% in the clipping group and 7.5% in the endovascular group (P = 0.414). At 6 months, a favorable outcome was obtained by 99.2% after clipping and 95.0% after endovascular treatment (P = 0.154). The 6-month complete aneurysm occlusion rates were by trend higher in the clipping group (89.2%) than in the endovascular group (75.9%, P = 0.078). CONCLUSIONS: Microsurgical clipping was associated with a higher technical success rate and tendentially higher complete occlusion than endovascular treatment, with no additional morbidity and similar clinical outcome. On the basis of these results, clipping proves to be the standard treatment option for MCA bifurcation aneurysms. However, endovascular treatment represents a safe and efficient alternative treatment option for patients.
Assuntos
Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Microcirurgia/instrumentação , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Estudos Retrospectivos , Instrumentos CirúrgicosRESUMO
BACKGROUND: The importance of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status as a predictive factor for the response to chemotherapy with temozolomide is well established. Its significance though at stratifying glioblastoma (GBM) patients in regard to their prognostic factors and the impact of surgical approach on them has not been identified. OBJECTIVE: To reveal possible differences in the prognostic factors and the impact of surgery between GBM patients stratified according to their MGMT status. METHODS: The authors retrospectively analyzed 186 patients with a newly diagnosed primary supratentorial GBM treated with surgical resection followed by standard radiation and chemotherapy. A prospective quantitative volumetric analysis of tumor characteristics identified on magnetic resonance imaging was performed. RESULTS: For the 109 patients with unmethylated MGMT promoter, extent of resection (EOR) represented independent predictor of survival, whereas residual tumor volume (RTV), Karnofsky Performance Score, and age were found to be independent prognostic factors of survival for the 77 patients with methylated MGMT promoter. For the group of patients with unmethylated and the group with methylated MGMT promoter, an EOR threshold of 70% and 98% and an RTV threshold of 1.5 and 1 cm3 were identified, respectively. CONCLUSION: The selection of patients according to the MGMT promoter methylation status resulted in different prognostic factors and different resection thresholds for each patient population. A survival benefit seen from 70% EOR threshold in patients with MGMT unmethylated GBM supports the doctrine of maximum safe resection rather than the "all-or-nothing" approach.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/genética , Glioblastoma/cirurgia , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Metilação de DNA , Feminino , Glioblastoma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas/genética , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: The "weekend effect" describes the assumption that weekend and/or on-call duty admission of emergency patients is associated with increased morbidity and mortality rates. For aneurysmal subarachnoid hemorrhage, we investigated, whether presentation out of regular working hours and microsurgical clipping at nighttime correlates with worse patient outcome. METHODS: This is a retrospective review of consecutive patients that underwent microsurgical clipping of an acutely ruptured aneurysm at our institution between 2010 and 2019. Patients admitted during (1) regular working hours (Monday-Friday, 08:00-17:59) and (2) on-call duty and microsurgical clipping performed during (a) daytime (Monday-Sunday, 08:00-17:59) and (b) nighttime were compared regarding the following outcome parameters: operation time, treatment-related complications, vasospasm, functional outcome, and angiographic results. RESULTS: Among 157 enrolled patients, 104 patients (66.2%) were admitted during on-call duty and 48 operations (30.6%) were performed at nighttime. Admission out of regular hours did not affect cerebral infarction (p = 0.545), mortality (p = 0.343), functional outcome (p = 0.178), and aneurysm occlusion (p = 0.689). Microsurgical clipping at nighttime carried higher odds of unfavorable outcome at discharge (OR: 2.3, 95%CI: 1.0-5.1, p = 0.039); however, there were no significant differences regarding the remaining outcome parameters. After multivariable adjustment, clipping at nighttime did not remain as independent prognosticator of short-term outcome (OR: 2.1, 95%CI: 0.7-6.2, p = 0.169). CONCLUSIONS: Admission out of regular working hours and clipping at nighttime were not independently associated with poor outcome. The adherence to standardized treatment protocols might mitigate the "weekend effect."
Assuntos
Plantão Médico , Aneurisma Roto/mortalidade , Aneurisma Intracraniano/mortalidade , Aneurisma Intracraniano/cirurgia , Microcirurgia , Assistência Noturna , Idoso , Aneurisma Roto/complicações , Aneurisma Roto/cirurgia , Angiografia , Infarto Cerebral/mortalidade , Infarto Cerebral/prevenção & controle , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Admissão do Paciente , Estudos Retrospectivos , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Intrasaccular flow-disruption represents a new paradigm in endovascular treatment of wide-necked bifurcation aneurysms. OBJECTIVE: To retrospectively compare Woven Endobridge (WEB) embolization with microsurgical clipping for unruptured anterior circulation aneurysms using propensity score adjustment. METHODS: A total of 63 patients treated with WEB and 103 patients treated with clipping were compared based on the intention-to-treat principle. The primary outcome measures were immediate technical treatment success, major adverse events, and 6-mo complete aneurysm occlusion. RESULTS: The technical success rates were 83% for WEB and 100% for clipping. Procedure-related complications occurred more often in the clipping group (13%) than the WEB group (6%, adjusted P < .01). However, the rates of major adverse events were comparable in both groups (WEB: 3%, clip: 4%, adjusted P = .53). At the 6-mo follow-up, favorable functional outcomes were achieved in 98% of the WEB embolization group and 99% of the clipping group (adjusted P = .19). Six-month complete aneurysm occlusion was obtained in 75% of the WEB group and 94% of the clipping group (adjusted P < .01). CONCLUSION: Microsurgical clipping was associated with higher technical success and complete occlusion rates, whereas WEB had a lower complication rate. Favorable functional outcomes were achieved in ≥98% of both groups. The decision to use a specific treatment modality should be made on an individual basis and in accordance with the patient's preferences.
Assuntos
Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Microcirurgia/métodos , Pontuação de Propensão , Stents Metálicos Autoexpansíveis , Instrumentos Cirúrgicos , Adulto , Idoso , Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Microcirurgia/instrumentação , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Percutaneous pedicle screw fixation in obese patients remains a surgical challenge. We aimed to compare patient-reported outcomes and complication rates between obese and nonobese patients who were treated by minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: The authors retrospectively reviewed patients who underwent MIS-TLIF at a single institution between 2011 and 2014. Patients were classified as obese (body mass index [BMI] ≥30 kg/m2) or nonobese (BMI < 30 kg/m2), according to their BMI. Outcomes assessed were complications, numerical rating scale (NRS) scores for back and leg pain, Oswestry Disability Index (ODI), and 36-Item Short-Form Survey (SF-36) scores. RESULTS: The final study group consisted of 71 patients, 24 obese (33.8%, 34.8 ± 3.8 kg/m2) and 47 nonobese (66.2%, 25.4 ± 2.9 kg/m2). Instrumentation failures (13.6 vs. 17.0%), dural tears (17.2 vs. 4.0%), and revision rates (16.7 vs. 19.1%) were similar between both groups (p > 0.05). Perioperative improvements in back pain (4.3 vs. 5.4, p = 0.07), leg pain (3.8 vs. 4.2, p = 0.6), and ODI (13.3 vs. 22.5, p = 0.5) were comparable among the groups and persisted at long-term follow-up. Obese patients had worse postoperative physical component SF-36 scores than nonobese patients (36.4 vs. 42.7, p = 0.03), while the mental component scores were not statistically different (p = 0.09). CONCLUSION: Obese patients can achieve similar improvement of the pain intensity and functional status even at long-term follow-up. In patients with appropriate surgical indications, obesity should not be considered a contraindication for MIS-TLIF surgery.
Assuntos
Dor nas Costas/cirurgia , Vértebras Lombares/cirurgia , Obesidade/complicações , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Fusão Vertebral/efeitos adversos , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In aneurysmal subarachnoid hemorrhage (aSAH), accurate diagnosis of aneurysm is essential for subsequent treatment to prevent rebleeding. However, aneurysm detection proves to be challenging and time-consuming. The purpose of this study was to develop and evaluate a deep learning model (DLM) to automatically detect and segment aneurysms in patients with aSAH on computed tomography angiography. In this retrospective single-center study, three different DLMs were trained on 68 patients with 79 aneurysms treated for aSAH (2016-2017) using five-fold-cross-validation. Their outputs were combined to a single DLM via ensemble-learning. The DLM was evaluated on an independent test set consisting of 185 patients with 215 aneurysms (2010-2015). Independent manual segmentations of aneurysms in a 3D voxel-wise manner by two readers (neurosurgeon, radiologist) provided the reference standard. For aneurysms > 30 mm3 (mean diameter of ~ 4 mm) on the test set, the DLM provided a detection sensitivity of 87% with false positives (FPs)/scan of 0.42. Automatic segmentations achieved a median dice similarity coefficient (DSC) of 0.80 compared to the reference standard. Aneurysm location (anterior vs. posterior circulation; P = .07) and bleeding severity (Fisher grade ≤ 3 vs. 4; P = .33) did not impede detection sensitivity or segmentation performance. For aneurysms > 100 mm3 (mean diameter of ~ 6 mm), a sensitivity of 96% with DSC of 0.87 and FPs/scan of 0.14 were obtained. In the present study, we demonstrate that the proposed DLM detects and segments aneurysms > 30 mm3 in patients with aSAH with high sensitivity independent of cerebral circulation and bleeding severity while producing FP findings of less than one per scan. Hence, the DLM can potentially assist treating physicians in aSAH by providing automated detection and segmentations of aneurysms.
Assuntos
Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Aprendizado Profundo , Aneurisma Intracraniano/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Timely aneurysm occlusion and neurointensive care treatment are key principles in the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent secondary brain injury. Patients with early (EHA) and delayed hospital admission (DHA) were compared in terms of clinical presentation, treatment strategies, aSAH-related complications, and outcome. METHODS: In this retrospective study, consecutive aSAH patients were treated at a single neurovascular center between 2009 and 2019. Propensity score matching was performed to account for divergent baseline characteristics. RESULTS: Among 509 included patients, 55 were admitted more than 48 hours after ictus (DHA group). DHA patients were significantly younger (52 ± 11 vs 56 ± 14 years, p = 0.03) and had lower World Federation of Neurosurgical Societies scores (p < 0.01) than EHA patients. In 54.5% of the cases, DHA patients presented with neurological deterioration or aggravated symptoms. Propensity score matching revealed a higher vasospastic infarction rate in the DHA group (41.5%) than in the EHA group (22.6%) (p = 0.04). A similar portion of patients in both groups achieved favorable outcome at midterm follow-up (77.3% vs 73.6%, p = 0.87). DHA patients (62.3%) received conventional coiling more often than EHA patients (41.5%) (p = 0.03). CONCLUSIONS: DHA patients are at an increased risk of cerebral infarction. Nevertheless, state-of-the-art neurointensive care treatment can result in a good clinical outcome.
Assuntos
Procedimentos Neurocirúrgicos/métodos , Hemorragia Subaracnóidea/cirurgia , Tempo para o Tratamento , Adulto , Fatores Etários , Idoso , Infarto Encefálico/etiologia , Angiografia por Tomografia Computadorizada , Cuidados Críticos , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Admissão do Paciente , Pontuação de Propensão , Estudos Retrospectivos , Convulsões/etiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Resultado do Tratamento , Vasoespasmo Intracraniano/etiologia , Adulto JovemRESUMO
Meningioma represents the most common primary brain tumor in adults. Recently several non-NF2 mutations in meningioma have been identified and correlated with certain pathological subtypes, locations and clinical observations. Alterations of cellular pathways due to these mutations, however, have largely remained elusive. Here we report that the Krueppel like factor 4 (KLF4)-K409Q mutation in skull base meningiomas triggers a distinct tumor phenotype. Transcriptomic analysis of 17 meningioma samples revealed that KLF4K409Q mutated tumors harbor an upregulation of hypoxia dependent pathways. Detailed in vitro investigation further showed that the KLF4K409Q mutation induces HIF-1α through the reduction of prolyl hydroxylase activity and causes an upregulation of downstream HIF-1α targets. Finally, we demonstrate that KLF4K409Q mutated tumors are susceptible to mTOR inhibition by Temsirolimus. Taken together, our data link the KLF4K409Q mediated upregulation of HIF pathways to the clinical and biological characteristics of these skull base meningiomas possibly opening new therapeutic avenues for this distinct meningioma subtype.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Hipóxia Tumoral/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Camundongos , Camundongos Nus , Mutação , Transplante de Neoplasias , Prolil Hidroxilases , Inibidores de Proteínas Quinases/farmacologia , RNA-Seq , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Neoplasias da Base do Crânio , Regulação para CimaRESUMO
Objective Computer-aided design and manufacturing (CAD/CAM) implants are fabricated based on volumetric analysis of computed tomography (CT) scans and are routinely used for the reconstruction of orbital fractures. We present three cases of patients with sphenoorbital meningiomas that underwent tumor resection, orbital decompression, and orbital reconstruction with patient specific porous titanium or acrylic implants in a single procedure. Methods The extent of bone resection of the sphenoorbital meningiomas was planned in a virtual three-dimensional (3D) environment using preoperative thin-layer CT data. The anatomy of the orbital wall in the resection area was reconstructed by superimposing the contralateral unaffected orbit and by using the information of the neighboring bony structures. The customized implants and a corresponding craniotomy template were designed in the desired size and shape by the manufacturer. Results All patients presented with a sphenoorbital meningioma and exophthalmos. After osteoclastic craniotomy with the drilling template, orbital decompression was performed. Implant fitting was tight in two cases and could be easily fixated with miniplates and screws. In the third patient, a reoperation was necessary for additional bone resection, as well as drilling and repositioning of the implant. The postoperative CT scans showed an accurate reconstruction of the orbital wall. After surgery, exophthalmos was substantially reduced and a satisfying cosmetic result could be finally achieved in all patients. Conclusions The concept of preoperative 3D virtual treatment planning and single-step orbital reconstruction with CAD/CAM implants after tumor resection involving the orbit is well feasible and can lead to good cosmetic results.
RESUMO
PURPOSE: The management of residual or persistent intracranial aneurysms after flow-diversion therapy is not well defined in the literature. In this multicentric study, we report clinical and angiographic outcomes of 11 patients that underwent retreatment for 12 aneurysms initially treated with flow-diverter stents. METHODS: The median patient age was 53 years. Aneurysms (median size, 7.3 mm) were located at the internal carotid artery in 9 cases, and at the posterior circulation in 3. Treatment strategies, complications, and angiographic outcome were retrospectively assessed. RESULTS: Retreatment was feasible in all cases and performed by overlapping flow-diverter implantation. Overall, 12 side vessels were covered during retreatment, whereof 10 (83.3%) remained patent until mid-term follow-up. There were no further technical or symptomatic complications and no treatment-related morbidity. Angiographic follow-up (median, 17 months) showed improved aneurysm occlusion in all patients. Complete or near-complete aneurysm occlusion was achieved in 11 aneurysms (91.7%). CONCLUSION: Required retreatment after failed flow-diversion therapy can be performed with adequate safety and efficacy by placement of additional flow-diverter stents.