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1.
Aging (Albany NY) ; 16(10): 9023-9046, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38809507

RESUMEN

Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1ß (IL-1ß). Molecular docking analyses revealed an average affinity of -8.633 kcal/mol, indicating a binding strength of less than -5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.


Asunto(s)
Barrera Hematoencefálica , Hemorragia Cerebral , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Medicamentos Herbarios Chinos/farmacología , Masculino , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Fármacos Neuroprotectores/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Ratas , Antiinflamatorios/farmacología , Farmacología en Red , Modelos Animales de Enfermedad
2.
J Affect Disord ; 354: 483-490, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38484892

RESUMEN

OBJECTIVE: To investigate whether the number of years of schooling are causally associated traumatic brain injury (TBI). We aimed to investigate whether the number of years of schooling are causally associated TBI. METHODS: We investigate the prospective causal effect of years of schooling on TBI using summary statistical data. The statistical dataset comprising years of schooling (n = 293,723) from genome-wide association studies (GWASs) deposited in the UK Biobank was used for exposure. We used the following GWAS available in the FinnGen dataset: individuals with TBI (total = 13,165; control = 136,576; number of single nucleotide polymorphisms [SNPs] = 16,380,088). RESULTS: Seventy significant genome-wide SNPs from GWAS datasets with annotated years of schooling were selected as instrumental variables. The inverse variance weighted method results supported a causal relationship between years of schooling and TBI (odds ratio (OR), 0.78; 95 % confidence interval (CI), 0.62-0.98; P = 0.029). MR-Egger regression showed that polydirectionality was unlikely to bias the results (intercept = 0.007, SE = 0.01, P = 0.484) and demonstrated no causal relationship between years of schooling and TBI (OR, 0.52; 95%CI, 0.17-1.64; P = 0.270). The weighted median method revealed a causal relationship with TBI (OR, 0.73; 95%CI, 0.55-0.98; P = 0.047). A Cochran's Q test and funnel plot did not show heterogeneity nor asymmetry, indicating no directional pleiotropy. CONCLUSIONS: The current investigation yields substantiation of a causal association between years of schooling and TBI development. More years of schooling may be causally associated with a reduced risk of TBI, which has implications for clinical and public health practices and policies.


Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Estudios Prospectivos , Causalidad , Escolaridad
3.
J Neurosci Res ; 102(1): e25283, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38284859

RESUMEN

Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.


Asunto(s)
Edición Génica , Traumatismos de la Médula Espinal , Animales , Humanos , Regeneración Nerviosa , Neuroglía , Neuroprotección , Traumatismos de la Médula Espinal/terapia
4.
Artículo en Inglés | MEDLINE | ID: mdl-38243987

RESUMEN

Subarachnoid Haemorrhage (SAH) is a medical emergency with potentially devastating outcomes. It is without doubt that over the past decades, there has been a radical change in the approach towards patients with SAH, both in terms of the surgical as well as of the pharmacological treatments offered. The present review aims to outline the principal data regarding the best practice in the pharmacotherapy of SAH, as well as to sum up the emerging evidence from the latest clinical trials. To date, nimodipine is the only evidence-based treatment of vasospasm. However, extensive research is currently underway to identify novel substances with magnesium sulphate, cilostazol, clazosentan and fasudil, demonstrating promising results. Antifibrinolytic therapy could help reduce mortality, and anticoagulants, in spite of their associated hazards, could actually reduce the incidence of delayed cerebral ischemia. The effectiveness of triple-H therapy has been challenged, yet evidence on the optimal regimen is still pending. Statins may benefit some patients by reducing the incidence of vasospasm and delayed ischemic events. As several clinical trials are underway, it is expected that in the years to come, more therapeutic options will be added to the attending physician's armamentarium.

5.
PLoS One ; 18(3): e0282726, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37000863

RESUMEN

BACKGROUND: Although some studies have shown that tranexamic acid is beneficial to patients with intracranial haemorrhage, the efficacy and safety of tranexamic acid for intracranial haemorrhage remain controversial. METHOD: The PubMed, EMBASE, and Cochrane Library databases were systematically searched. The review followed PRISMA guidelines. Data were analyzed using the random-effects model. RESULTS: Twenty-five randomized controlled trials were included. Tranexamic acid significantly inhibited hematoma growth in intracranial hemorrhage (ICH) and traumatic brain injury (TBI) patients. (ICH: mean difference -1.76, 95%CI -2.78 to -0.79, I2 = 0%, P < .001; TBI: MD -4.82, 95%CI -8.06 to -1.58, I2 = 0%, P = .004). For subarachnoid hemorrhage (SAH) patients, it significantly decreased the risk of hydrocephalus (OR 1.23, 95%CI 1.01 to 1.50, I2 = 0%, P = .04) and rebleeding (OR, 0.52, 95%CI 0.35 to 0.79, I2 = 56% P = .002). There was no significance in modified Rankin Scale, Glasgow Outcome Scale 3-5, mortality, deep vein thrombosis, pulmonary embolism, or ischemic stroke/transient ischemic. CONCLUSION: Tranexamic acid can significantly reduce the risk of intracranial haemorrhage growth in patients with ICH and TBI. Tranexamic acid can reduce the incidence of complications (hydrocephalus, rebleeding) in patients with SAH, which can indirectly improve the quality of life of patients with intracranial haemorrhage.


Asunto(s)
Antifibrinolíticos , Lesiones Traumáticas del Encéfalo , Hidrocefalia , Hemorragia Subaracnoidea , Ácido Tranexámico , Humanos , Antifibrinolíticos/efectos adversos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Hidrocefalia/complicaciones , Calidad de Vida , Hemorragia Subaracnoidea/complicaciones , Ácido Tranexámico/efectos adversos
7.
Neurosurg Rev ; 45(6): 3489-3498, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36129583

RESUMEN

Endovascular treatment is widely used in the treatment of intracranial aneurysms. However, neurosurgeons are sceptical about endovascular access via the radial artery. We performed a systematic review and meta-analysis to compare the effectiveness and safety of transradial and transfemoral artery access in patients with intracranial aneurysms. We systematically searched the PubMed, Embase, and Cochrane databases for studies comparing the two approaches. The primary outcome was total complications, and the secondary outcomes were access site complications, intracranial haemorrhage, stroke, thromboembolism, silent infarct, re-treatment rate, mortality, complete occlusion of intracranial aneurysms, procedure duration, and length of hospital stay. A random-effects model was used to assess the pooled data. Of the 100 identified studies, 6 were eligible (a total of 3764 participants). There were no significant differences in total complications(odds ratio [OR] = 0.69, 95% confidence interval [CI] [0.33, 1.45], p = 0.32), complete occlusion of intracranial aneurysms (OR = 1.02, 95%CI [0.77,1.37], p = 0.87), procedure duration (mean difference [MD] = - 6.24, 95%CI [- 14.75, - 1.54], p = 0.95), or length of hospital stay (MD = 2.204, 95%CI [- 0.05, 4.45], p = 0.95), access site complications (OR = 0.49, 95%CI [0.16, 1.52], p = 0.22), intracranial haemorrhage (OR = 1.07, 95%CI [0.49, 2.34], p = 0.86), stroke (OR = 0.59, 95%CI [0.20, 1.77], p = 0.35), thromboembolism (OR = 0.85, 95%CI [0.33, 2.17], p = 0.74), silent infarct (OR = 0.69, 95%CI [0.04, 11.80], p = 0.80), retreatment rate (OR = 1.32, 95%CI [0.70, 2.48], p = 0.39), mortality (OR = 1.41, 95%CI [0.06, 5.20], p = 0.61), immediate occlusion (OR = 0.99, 95%CI [0.64, 1.51], p = 0.95), and occlusion during follow-up (OR = 1.10, 95%CI [0.56, 2.16], p = 0.74) between the transradial and transfemoral groups. This study showed comparable safety and efficacy outcomes between transradial and transfemoral access in patients with intracranial aneurysms treated endovascularly. Future large randomised trials are warranted to confirm these findings.


Asunto(s)
Procedimientos Endovasculares , Aneurisma Intracraneal , Accidente Cerebrovascular , Tromboembolia , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/etiología , Arteria Femoral/cirugía , Resultado del Tratamiento , Estudios de Cohortes , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/etiología , Hemorragias Intracraneales/etiología , Infarto/etiología
8.
Brain Sci ; 12(9)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36138920

RESUMEN

This study aimed to investigate the association between serum iron (SI) and postoperative delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively analyzed 985 consecutive adult patients diagnosed with aSAH. Demographic, clinical, and laboratory data were recorded. Univariate and multivariate analyses were employed to assess the association between SI and DCI. Propensity-score matching (PSM) analysis was implemented to reduce confounding. Postoperative DCI developed in 14.38% of patients. Lower SI upon admission was detected in aSAH patients with severe clinical conditions and severe aSAH. SI was negatively correlated with WFNS grade (r = −0.3744, p < 0.001) and modified Fisher (mFisher) grade (r = −0.2520, p < 0.001). Multivariable analysis revealed lower SI was independently associated with DCI [odds ratios (OR) 0.281, 95% confidence interval (CI) 0.177−0.448, p < 0.001], while WFNS grade and mFisher grade were not. The receiver-operating characteristics (ROC) curve analysis of SI for DCI gave an area under the curve (AUC) of 0.7 and an optimal cut-off of 7.5 µmol/L (95% CI 0.665 to 0.733, p < 0.0001). PSM demonstrated the DCI group had a significantly lower SI than the non-DCI group (10.91 ± 6.86 vs. 20.34 ± 8.01 µmol/L, p < 0.001). Lower SI remained a significant independent predictor for DCI and an independent poor prognostic factor of aSAH in multivariate analysis (OR 0.363, 95% CI 0.209−0.630, p < 0.001). The predictive performance of SI for poor outcome had a corresponding AUC of 0.718 after PSM. Lower SI upon admission is significantly associated with WFNS grade, mFisher grade, and predicts postoperative DCI and poor outcome at 90 days following aSAH.

9.
World Neurosurg ; 166: e841-e849, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35948218

RESUMEN

OBJECTIVE: The anterior petrosectomy, also known as the Kawase approach, and the retrosigmoid intradural suprameatal approach (RISA) have both been used to reduce the petrous apex and access the petroclival region. Our goal was to compare the volumes and 3-dimensional shapes of bony resection obtained through each approach while trying to resemble realistic surgical settings. METHODS: Five cadaveric specimens totaling 10 sides were dissected and analyzed. In every specimen, 1 side was used for the Kawase approach while the opposite side was used for the RISA. Petrosectomy volumes were assessed by comparing preoperative and postoperative thin-sliced computed tomography scans. RESULTS: Petrosectomy volumes were significantly larger through the Kawase approach than through the RISA (0.82 ± 0.11 vs. 0.49 ± 0.07 cm3, P < 0.001). In addition, surgical maneuverability and freedom were greater in the Kawase operative variant. Lastly, the morphology of the bony window achieved through each approach was clearly different: trapezoid for the anterior petrosectomy versus elongated ellipsoid for the RISA. CONCLUSIONS: The Kawase approach invariably results in larger volumes of bony removal than the RISA operative variant, and the volume of petrosectomy that is spatially congruent is only partially identical. The Kawase corridor is best suited for middle fossa lesions that extend into the posterior fossa, while the RISA is suitable for pathologies mainly residing in the posterior fossa and extending into the Meckel cave.


Asunto(s)
Procedimientos Neuroquirúrgicos , Hueso Petroso , Cadáver , Fosa Craneal Posterior/anatomía & histología , Fosa Craneal Posterior/diagnóstico por imagen , Fosa Craneal Posterior/cirugía , Craneotomía , Humanos , Procedimientos Neuroquirúrgicos/métodos , Hueso Petroso/anatomía & histología , Hueso Petroso/diagnóstico por imagen , Hueso Petroso/cirugía , Tomografía Computarizada por Rayos X
11.
Stem Cell Res Ther ; 13(1): 281, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35765072

RESUMEN

Non-traumatic intracerebral hemorrhage is a highly destructive intracranial disease with high mortality and morbidity rates. The main risk factors for cerebral hemorrhage include hypertension, amyloidosis, vasculitis, drug abuse, coagulation dysfunction, and genetic factors. Clinically, surviving patients with intracerebral hemorrhage exhibit different degrees of neurological deficits after discharge. In recent years, with the development of regenerative medicine, an increasing number of researchers have begun to pay attention to stem cell and exosome therapy as a new method for the treatment of intracerebral hemorrhage, owing to their intrinsic potential in neuroprotection and neurorestoration. Many animal studies have shown that stem cells can directly or indirectly participate in the treatment of intracerebral hemorrhage through regeneration, differentiation, or secretion. However, considering the uncertainty of its safety and efficacy, clinical studies are still lacking. This article reviews the treatment of intracerebral hemorrhage using stem cells and exosomes from both preclinical and clinical studies and summarizes the possible mechanisms of stem cell therapy. This review aims to provide a reference for future research and new strategies for clinical treatment.


Asunto(s)
Exosomas , Animales , Hemorragia Cerebral/etiología , Hemorragia Cerebral/terapia , Factores de Riesgo , Trasplante de Células Madre/efectos adversos
12.
Front Neurosci ; 16: 899887, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35585925

RESUMEN

Ischemic stroke is defined as an infarction in the brain, caused by impaired cerebral blood supply, leading to local brain tissue ischemia, hypoxic necrosis, and corresponding neurological deficits. At present, revascularization strategies in patients with acute ischemic stroke include intravenous thrombolysis and mechanical endovascular treatment. However, due to the short treatment time window (<4.5 h) and method restrictions, clinical research is focused on new methods to treat ischemic stroke. Exosomes are nano-sized biovesicles produced in the endosomal compartment of most eukaryotic cells, containing DNA, complex RNA, and protein (30-150 nm). They are released into surrounding extracellular fluid upon fusion between multivesicular bodies and the plasma membrane. Exosomes have the characteristics of low immunogenicity, good innate stability, high transmission efficiency, and the ability to cross the blood-brain barrier, making them potential therapeutic modalities for the treatment of ischemic stroke. The seed sequence of miRNA secreted by exosomes is base-paired with complementary mRNA to improve the microenvironment of ischemic tissue, thereby regulating downstream signal transduction activities. With exosome research still in the theoretical and experimental stages, this review aims to shed light on the potential of exosomes derived from mesenchymal stem cells in the treatment of ischemic stroke.

13.
World Neurosurg ; 154: e665-e670, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34343686

RESUMEN

BACKGROUND: Meningioma is the most common primary brain tumor in adults. In recent years, several non-neurofibromin 2 mutations, i.e., AKT1, SMO, TRAF7, and KLF4 mutations, specific for meningioma have been identified. This study aims to analyze the clinical impact and imaging characteristics of the KLF4K409Q mutation in meningioma. METHODS: Clinical, neuropathologic, and imaging data of 170 patients who underwent meningioma resection between 2013 and 2018 were retrospectively collected and tumors were analyzed for the presence of the KLF4K409Q mutation. We collected imaging characteristics, performed volumetric analysis of tumor size and peritumoral edema (PTBE), and calculated the edema index (EI, i.e., ratio of PTBE to tumor volume). Receiver operating characteristic curve analysis was performed to identify cut-off EI values to predict the mutational status of KLF4. RESULTS: Eighteen (10.6%) of the meningiomas carried the KLF4K409Q mutation; these were significantly associated with a secretory subtype (P < 0.001) and sphenoid wing location (P = 0.029). Smaller tumor size (P = 0.007), an increased PTBE (P = 0.012), and an increased EI (P = 0.001) proved to be significantly associated with the KLF4K409Q mutation. In receiver operating characteristic curve analysis, EI predicted the KLF4K409Q mutation with an area under the curve of 0.728 (P = 0.0016). CONCLUSIONS: The KLF4K409Q mutation is associated with a distinct small tumor subtype, prone to substantial PTBE. EI is a reliable parameter to predict the KLF4K409Q mutation in meningioma, thus providing a tool for improvement of pre- and perioperative medical management.


Asunto(s)
Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/genética , Meningioma/diagnóstico por imagen , Meningioma/genética , Femenino , Humanos , Factor 4 Similar a Kruppel/genética , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Mutación , Estudios Retrospectivos
14.
Neuro Oncol ; 23(11): 1821-1834, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34181733

RESUMEN

Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in variations of management approaches across countries and centers. However, recent advances in molecular genetics and clinical trial results help to refine the diagnostic and therapeutic approach to meningioma. Accordingly, the European Association of Neuro-Oncology (EANO) updated its recommendations for the diagnosis and treatment of meningiomas. A provisional diagnosis of meningioma is typically made by neuroimaging, mostly magnetic resonance imaging. Such provisional diagnoses may be made incidentally. Accordingly, a significant proportion of meningiomas, notably in patients that are asymptomatic or elderly or both, may be managed by a watch-and-scan strategy. A surgical intervention with tissue, commonly with the goal of gross total resection, is required for the definitive diagnosis according to the WHO classification. A role for molecular profiling including gene panel sequencing and genomic methylation profiling is emerging. A gross total surgical resection including the involved dura is often curative. Inoperable or recurrent tumors requiring treatment can be treated with radiosurgery, if the size or the vicinity of critical structures allows that, or with fractionated radiotherapy (RT). Treatment concepts combining surgery and radiosurgery or fractionated RT are increasingly used, although there remain controversies regard timing, type, and dosing of the various RT approaches. Radionuclide therapy targeting somatostatin receptors is an experimental approach, as are all approaches of systemic pharmacotherapy. The best albeit modest results with pharmacotherapy have been obtained with bevacizumab or multikinase inhibitors targeting vascular endothelial growth factor receptor, but no standard of care systemic treatment has been yet defined.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Radiocirugia , Anciano , Humanos , Imagen por Resonancia Magnética , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/terapia , Meningioma/diagnóstico , Meningioma/genética , Meningioma/terapia , Factor A de Crecimiento Endotelial Vascular
15.
Neurosurgery ; 88(4): E323-E329, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33432978

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirugía , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/genética , Glioblastoma/cirugía , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Metilación de ADN , Femenino , Glioblastoma/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas/genética , Estudios Prospectivos , Estudios Retrospectivos
16.
J Neurol Surg A Cent Eur Neurosurg ; 82(2): 147-153, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33352610

RESUMEN

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.


Asunto(s)
Dolor de Espalda/cirugía , Vértebras Lumbares/cirugía , Obesidad/complicaciones , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Fusión Vertebral/efectos adversos , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Recuperación de la Función , Estudios Retrospectivos , Resultado del Tratamiento
17.
Acta Neuropathol Commun ; 8(1): 41, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32245394

RESUMEN

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.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Hipoxia Tumoral/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/efectos de los fármacos , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Ratones , Ratones Desnudos , Mutación , Trasplante de Neoplasias , Prolil Hidroxilasas , Inhibidores de Proteínas Quinasas/farmacología , RNA-Seq , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Sirolimus/análogos & derivados , Sirolimus/farmacología , Neoplasias de la Base del Cráneo , Regulación hacia Arriba
18.
J Neurol Surg B Skull Base ; 81(2): 142-148, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32206532

RESUMEN

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.

19.
Neuro Oncol ; 22(1): 31-45, 2020 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-31504802

RESUMEN

The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular schwannoma task force of the European Association of Neuro-Oncology assessed the data available in the literature and composed a set of recommendations for health care professionals. The radiological diagnosis of vestibular schwannoma is made by magnetic resonance imaging. Histological verification of the diagnosis is not always required. Current treatment options include observation, surgical resection, fractionated radiotherapy, and radiosurgery. The choice of treatment depends on clinical presentation, tumor size, and expertise of the treating center. In small tumors, observation has to be weighed against radiosurgery, in large tumors surgical decompression is mandatory, potentially followed by fractionated radiotherapy or radiosurgery. Except for bevacizumab in neurofibromatosis type 2, there is no role for pharmacotherapy.


Asunto(s)
Neuroma Acústico/diagnóstico , Neuroma Acústico/terapia , Humanos
20.
J Neurosurg Sci ; 64(2): 133-140, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28707859

RESUMEN

BACKGROUND: Chronic subdural hematoma (CSDH) is a common indication for undergoing neurosurgery, but the outcome may remain limited despite timely surgical treatment. The factors potentially associated with the functional outcome have not been sufficiently investigated. We set out to identify independent predictors associated with the functional outcome after surgical treatment of CSDH, avoiding arbitrary classifications and thresholds or subjective imaging assessment. METHODS: We retrospectively reviewed 197 consecutive surgical cases of CSDH. Univariate and multivariate analyses were performed to identify the relationship between clinical plus radiographic factors and outcome. Imaging analysis was performed using computer-assisted 3D-volumetric analysis. RESULTS: One-hundred and sixty-four (83.2%) patients had a favorable (GOS grade 5 and 4) and 33 (16.8%) an unfavorable clinical outcome (GOS grade 1-3). The multivariate logistic regression analysis determined 4 independent prognostic factors: age over or under 77 years, preoperative clinical condition (Markwalder Score), recurrence and surgical technique applied. Patients treated with mini-craniotomy procedures had worse outcomes than those treated with single or two burr-hole craniostomies. The percentage of the hematoma drained correlated strongly with recurrence and was by itself not an independent predictor for outcome. CONCLUSIONS: In our study age, preoperative neurological status, surgical technique and recurrence were found to be independent prognostic factors for the functional outcome in patients with CSDH.


Asunto(s)
Hematoma Subdural Crónico/diagnóstico por imagen , Hematoma Subdural Crónico/cirugía , Modelos Logísticos , Procedimientos Neuroquirúrgicos , Adulto , Anciano , Anciano de 80 o más Años , Drenaje/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trepanación/métodos
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