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1.
Neurosurg Rev ; 47(1): 344, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034333

RESUMO

The pterional approach has traditionally been employed for managing middle cerebral artery (MCA) aneurysms. With potential benefits like reduced surgical morbidity and improved postoperative recovery, the lateral supraorbital approach (LSO) should be considered individually based on aneurysm morphology, location and patient-specific variations of the MCA anatomy, which requires considerable technical expertise traditionally acquired through years of experience. The goal of this study was the development and evaluation of a novel phantom simulator in the context of clinical decision-making in the managmement of MCA aneurysms. For this purpose, high-fidelity simulators inclusive of MCA models with identical M1- and bifurcation aneurysms were manufactured employing 3D reconstruction techniques, additive manufacturing and rheological testings. Medical students, neurosurgical residents, and seasoned neurosurgeons (n = 22) tested and evaluated both approaches. Participants' performances and progress over time were assessed based on objective metrics. The simulator received positive ratings in face and content validity, with mean scores of 4.9 out of 5, respectively. Objective evaluation demonstrated the model's efficacy as a practical training tool, particularly among inexperienced participants. While requiring more technical expertise, results of the comparative analysis suggest that the LSO approach can improve clipping precision and outcome particularly in patients with shorter than average M1-segments. In conclusion, the employed methodology allowed a direct comparison of the pterional and LSO approaches, revealing comparable success rates via the LSO approach while reducing operation time and complication rate. Future research should aim to establish simulators in the context of clinical decision making.


Assuntos
Aneurisma Intracraniano , Artéria Cerebral Média , Procedimentos Neurocirúrgicos , Humanos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Artéria Cerebral Média/cirurgia , Neurocirurgiões , Imagens de Fantasmas
2.
Neurosurg Rev ; 47(1): 76, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324094

RESUMO

Intracranial aneurysms (IAs) located in the anterior and posterior circulations of the Circle of Willis present differential rupture risks. This study aimed to compare the rupture risk and clinical outcomes of anterior communicating artery aneurysms (AcomA) and basilar tip aneurysms (BAs); two IA types located along the midline within the Circle of Willis. We retrospectively collected data from 1026 patients presenting with saccular IAs. Only AcomA and BAs with a 3D angiography were included. Out of 186 included IAs, a cohort of 32 BAs was matched with AcomA based on the patients' pre-existing conditions and morphological parameters of IAs. Clinical outcomes, including rupture risk, hydrocephalus development, vasospasm incidence, and patients' outcome, were compared. The analysis revealed no significant difference in rupture risk, development of hydrocephalus, need for ventricular drainage, or vasospasm incidence between the matched AcomA and BA cohorts. Furthermore, the clinical outcomes post-rupture did not significantly differ between the two groups, except for a higher Fisher Grade associated with BAs. Once accounting for morphological and patient factors, the rupture risk between AcomA and BAs is comparable. These findings underscore the importance of tailored management strategies for specific IA types and suggest that further investigations should focus on the role of individual patient and aneurysm characteristics in IA rupture risk and clinical outcomes.


Assuntos
Hidrocefalia , Aneurisma Intracraniano , Humanos , Estudos Retrospectivos , Angiografia
3.
Fortschr Neurol Psychiatr ; 91(3): 104-119, 2023 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-36917974

RESUMO

Intracerebral hemorrhage (ICB) causes approximately 12% of all strokes in Germany and 9-27% of all strokes worldwide 1 2. Epidemiological studies show a decrease in younger individuals mainly due to better antihypertensive management, but there is also an increase in incidence in older individuals due to cerebral amyloid angiopathy and increasing use of anticoagulants 3.


Assuntos
Hemorragia Cerebral , Acidente Vascular Cerebral , Idoso , Humanos , Anticoagulantes/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Angiopatia Amiloide Cerebral/epidemiologia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Fatores Etários
4.
Neuropathol Appl Neurobiol ; 48(2): e12780, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34837233

RESUMO

AIMS: Meningiomas are the most frequent primary brain tumours. Recently, knowledge about the molecular drivers underlying aggressive meningiomas has been expanded. A hotspot mutation in the AKT1 gene (AKT1E17K ), which is found in meningiomas at the convexity and especially at the skull base, has been associated with earlier tumour recurrence. METHODS: Here, we analysed the effects of the AKT1E17K mutation and treatment response to the Akt inhibitor AZD5363 in transgenic meningioma cell clones and mouse xenografts modelling convexity or skull base meningiomas. RESULTS: We show that the AKTE17K mutation significantly enhances meningioma cell proliferation and colony size in vitro, resulting in significantly shortened survival times of mice carrying convexity or skull base AKT1E17K xenografts. Treatment of mutant cells or xenografts (150 mg/kg/d) with AZD5363 revealed a significant decrease in cell proliferation and colony size and a prolongation of mouse survival. Western blots revealed activation of AKT1 kinase (phosphorylation at Ser273 and Thr308) by the E17K mutation in human meningioma samples and in our in vitro and in vivo models. CONCLUSIONS: Our data suggest that AKT1E17K mutated meningiomas are a promising selective target for AZD5363.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias Meníngeas/genética , Meningioma/genética , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Neoplasias da Base do Crânio/genética , Animais , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Humanos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Pirimidinas/farmacologia , Pirróis/farmacologia , Neoplasias da Base do Crânio/patologia
5.
Clin Neuropathol ; 41(4): 174-178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35575414

RESUMO

Meningiomas are the most common primary intracranial tumors, of which atypical meningiomas account for ~ 20%. A loss of NF2 has been proven to be an initial step for meningioma development; however, the role of non-NF2 alterations is unknown. Here we report a case of an atypical meningioma with a NF2 splice donor mutation and four recurrences. Using a custom NGS panel, further complex heterogenic molecular alterations were discovered. At first, one subclone of the initial tumor showed an additional PIK3CA variant, most likely of no pathogenic relevance. Then, the first and second recurrences no longer harbored the PIK3CA variant and no tumor heterogeneity was found. The tumor-driving NF2 mutation persisted, however. The latest, third recurrence showed a remarkable genetic heterogeneity with multiple, additional non-NF2 variants and a pathogenic PIKC3A mutation. In detail, one subclone showed a SUFU and two SMARCE1 variants. Another, geographically separate tumor subclone, in contrast, showed several different non-NF2 variants in SMO, PIK3CA and SUFU. Most important, one of the newly acquired PIK3CA alterations in the kinase domain (L1006F) is likely to be an additional tumor-driving mutation, which activates the PI3K-AKT-mTOR pathway. The reported genetic heterogeneity in meningiomas has been addressed in only a few studies. Although some of the detected variants in our case are expected to have biochemical consequences, these consequences are usually not likely to promote tumor development, when taking into account the suggested role of the altered proteins in tumorigenic pathways. However, the occurrence of a single oncogenic missense mutation in a subclone of the third recurrence may indicate a clonal change towards enhanced aggressiveness. Taken together, our case supports the need to perform in-depth studies to clarify the role of non-NF2 mutations for meningioma growth and development.


Assuntos
Neoplasias Meníngeas , Meningioma , Proteínas Cromossômicas não Histona/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas de Ligação a DNA/genética , Humanos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Mutação , Recidiva Local de Neoplasia/genética , Fosfatidilinositol 3-Quinases/genética
6.
Neurosurg Rev ; 45(1): 421-427, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34398385

RESUMO

In light of our own experiences, we value the existing literature to critically point out possible "near" future applications of optical coherence tomography (OCT) as an intraoperative neurosurgical guidance tool. "Pub Med", "Cochrane Library", "Crossref Metadata Search", and "IEEE Xplore" databases as well as the search engine "Google Scholar" were screened for "optical coherence tomography + neurosurgery", "optical coherence tomography + intraoperative imaging + neurosurgery", and "microscope integrated optical coherence tomography + neurosurgery". n = 51 articles related to the use of OCT as an imaging technique in the field of neurosurgery or neurosurgical research. n = 7 articles documented the intraoperative use of OCT in patients. n = 4 articles documented the use of microscope-integrated optical coherence tomography as a neurosurgical guidance tool. The Results demonstrate that OCT is the first imaging technique to study microanatomy in vivo. Postoperative analysis of intraoperative scans holds promise to enrich our physiological and pathophysiological understanding of the human brain. No data exists to prove that OCT-guided surgery minimizes perioperative morbidity or extends tumor resection. But results suggest that regular use of microscope-integrated OCT could increase security during certain critical microsurgical steps like, e.g., dural dissection at cavernous sinus, transtentorial approaches, or aneurysm clip placement. Endoscopy integration could aid surgery in regions which are not yet accessible to real-time imaging modalities like the ventricles or hypophysis. Theranostic instruments which combine OCT with laser ablation might gain importance in the emerging field of minimal invasive tumor surgery. OCT depicts vessel wall layers and its pathologies uniquely. Doppler OCT could further visualize blood flow in parallel. These abilities shed light on promising future applications in the field of vascular neurosurgery.


Assuntos
Neurocirurgia , Tomografia de Coerência Óptica , Humanos , Microscopia , Procedimentos Neurocirúrgicos , Medicina de Precisão
7.
Medicina (Kaunas) ; 58(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36363510

RESUMO

Background and Objectives: Spinal meningiomas, which are well characterized and are most frequently intradural extramedullary tumors, represent 25% of all intradural spinal tumors. The goal of this study was to compare the outcomes of surgically treated patients with spinal meningiomas in two time intervals with special emphasis on postoperative functional outcomes. Methods: Patients with spinal meningiomas admitted to our department between 1990 and 2020 were enrolled and divided into a historic cohort (HC; treated 1990−2007) and a current cohort (CC; treated 2008−2020). Patients' clinical data and surgical and radiological reports were retrospectively analyzed up to 5 years. Preoperative and postoperative neurological function were assessed using the modified McCormick Scale (mMCS). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities on the preoperative status and postoperative outcome. Results: We included 300 patients. Participants in the CC (n = 144) were significantly younger compared to those in the HC (n = 156), with twice as many patients <50 years of age (p < 0.001). The most common tumor location was the thoracic spine (n = 204). The median follow-up was 38.1 months (±30.3 standard deviation). A symptom duration until surgery <12 months was significantly associated with an earlier improvement in the mMCS (p = 0.045). In the CC, this duration was shorter and patients' neurological function at the first and last follow-ups was significantly better than for those in the HC (p < 0.001 for both). Conclusions: Our study results suggested that the impact of surgical management and postoperative rehabilitation on spinal meningioma patients' long-term neurological outcome has reached important milestones over the last decades. An earlier diagnosis led to earlier surgical treatment and improved patients' postoperative neurological recovery. Our results exposed that surgical therapy for spinal meningioma should be performed within 12 months after appearance of symptoms to achieve a better recovery.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Medula Espinal , Humanos , Meningioma/cirurgia , Meningioma/diagnóstico , Meningioma/patologia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/etiologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia
8.
Neurosurg Rev ; 44(5): 2889-2898, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33495921

RESUMO

There has been an increase in the use of acetylsalicylic acid (ASA, Aspirin®) among patients with stroke and heart disease as well as in aging populations as a means of primary prevention. The potentially life-threatening consequences of a postoperative hemorrhagic complication after neurosurgical operative procedures are well known. In the present study, we evaluate the risk of continued ASA use as it relates to postoperative hemorrhage and cardiopulmonary complications in patients undergoing cerebral aneurysm surgery. We retrospectively analyzed 200 consecutive clipping procedures performed between 2008 and 2018. Two different statistical models were applied. The first model consisted of two groups: (1) group with No ASA impact - patients who either did not use ASA at all as well as those who had stopped their use of the ASA medication in time (> = 7 days prior to operation); (2) group with ASA impact - all patients whose ASA use was not stopped in time. The second model consisted of three groups: (1) No ASA use; (2) Stopped ASA use (> = 7 days prior to operation); (3) Continued ASA use (did not stop or did not stop in time, <7 days prior to operation). Data collection included demographic information, surgical parameters, aneurysm characteristics, and all hemorrhagic/thromboembolic complications. A postoperative hemorrhage was defined as relevant if a consecutive operation for hematoma removal was necessary. An ASA effect has been assumed in 32 out of 200 performed operations. A postoperative hemorrhage occurred in one out these 32 patients (3.1%). A postoperative hemorrhage in patients without ASA impact was detected and treated in 5 out of 168 patients (3.0%). The difference was statistically not significant in either model (ASA impact group vs. No ASA impact group: OR = 1.0516 [0.1187; 9.3132], p = 1.000; RR = 1.0015 [0.9360; 1.0716]). Cardiopulmonary complications were significantly more frequent in the group with ASA impact than in the group without ASA impact (p = 0.030). In this study continued ASA use was not associated with an increased risk of a postoperative hemorrhage. However, cardiopulmonary complications were significantly more frequent in the ASA impact group than in the No ASA impact group. Thus, ASA might relatively safely be continued in patients with increased cardiovascular risk and cases of emergency cerebrovascular surgery.


Assuntos
Aspirina , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Neurocirurgiões , Inibidores da Agregação Plaquetária , Estudos Retrospectivos
9.
Cerebrovasc Dis ; 48(1-2): 26-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473731

RESUMO

OBJECTIVE: The present study was conducted to explore the value of 3-dimensional microscope integrated extravascular optical coherence tomography (OCT) as the first suitable intraoperative imaging modality of cerebral aneurysm (CA) and parent vessel wall morphology. METHODS: Incidental CAs (n = 16) of the anterior circulation with indication for microsurgical clipping were scanned. RESULTS: Analysis revealed that intraoperative OCT achieved to delineate the microstructural composition of the parent vessel in all cases and the CA wall in 68.8%. Clinical relevant characteristics such as thickness, calcification, residual tunica media, and atherosclerotic plaque of CA wall could be demonstrated with high image quality approaching the spatial resolution of histopathology. CONCLUSION: Our findings demonstrate that intraoperative OCT may hold promise as an additional imaging tool during neurovascular procedures.


Assuntos
Artérias Cerebrais/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Microscopia , Tomografia de Coerência Óptica , Artérias Cerebrais/patologia , Artérias Cerebrais/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/cirurgia , Cuidados Intraoperatórios , Masculino , Valor Preditivo dos Testes
10.
BMC Neurol ; 19(1): 226, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526396

RESUMO

BACKGROUND: Due to improvements in both the quality and availability of intracranial imaging as well as the evolution of surgical and endovascular techniques during the last decade, the number of treatments of unruptured intracranial aneurysms (UIA) has increased steadily. However, it is not generally known that vasospasm can arise after an uneventful clipping. CASE PRESENTATION: We present a case of a 69-year-old woman who suffered from vasospasm and delayed cerebral ischemia that occurred after an uneventful clipping of a UIA. The aneurysm of the right middle cerebral artery was found incidentally via magnetic resonance imaging ordered after the patient complained of a short period of slight gait disturbances. To avoid a subarachnoid hemorrhage and consecutive complications like vasospasms, the patient elected microsurgical treatment. Clipping was managed by keyhole approach. Temporal clipping of the M1 was not necessary. After clip placement, appropriate flow in all distal segments was confirmed by indocyanine green video-angiography and micro-Doppler. The patient was discharged seven days after surgery without neurological deficits. After 12 days, the patient developed at home a sudden drooping on the left side of the face. Upon admission to the emergency room, the patient was alert but slightly confused. Neurological examination revealed a left-sided hemiparesis and motor speech disorder. In contrast to the preoperative transfemoral catheter angiography, the subsequent right internal carotid angiogram showed clear signs of vasospasm along the M1 and M2 segments of the right middle cerebral artery. Antithrombotic treatment with acetylsalicylic acid was begun. In accordance with guidelines for the treatment of subarachnoid hemorrhage and vasospasm, nimodipine was added. After 11 days the patient was discharged with no symptoms. CONCLUSION: Cerebral vasospasm as a cause of ischemic stroke after uneventful surgery for a UIA seems to be a rare but possibly underestimated etiology that demands particular attention with respect to providing appropriate treatment. In future, it may be prudent to perform follow-up transcranial ultrasonography testing after the clipping of a UIA, especially considering the availability of potentially neuroprotective medications like nimodipine.


Assuntos
Isquemia Encefálica/etiologia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Vasoespasmo Intracraniano/etiologia , Idoso , Feminino , Humanos
11.
Neurosurg Rev ; 42(2): 489-492, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29948496

RESUMO

The PHASES score was developed to determine the risk of rupture of un-ruptured intracranial aneurysms (UIAs). The purposes of the current study were to apply this score on patients with actually ruptured intracranial aneurysms and to analyze the hypothetically prediction of the risk in this particularly patient group. We extracted the data of 100 recently treated patients (23 male, 77 female, mean age 56.4 years, range 17-93 years) with ruptured saccular intracranial aneurysms from our prospectively maintained neurovascular database according to the parameters used in the PHASES score (population, hypertension, age, earlier SAH, size and site of the aneurysm). Descriptive statistical analysis was performed using SPSS for Windows version 18.0 (SPSS Inc., Chicago, Illinois, USA). Ninety-nine percent of the patients were European and 1% Japanese in our series. Pre-existing arterial hypertension was found in 59%. Fifteen percent of the patients were > 75 years. Earlier SAH was found in 1%. The site of the aneurysms were the internal carotid artery (ICA) in 10%, the middle cerebral artery (MCA) in 14%, and arteries of the anterior and posterior circulation (PC) including the posterior communicating artery (PCOM) in 76%. Sixty-six percent of the aneurysms were smaller than 7 mm, 18% ranged between 7 and 9.9 mm, 14% were between 10 and 19.9 mm, and 2% were larger than 20 mm. European population, aneurysm size < 7 mm, and age < 75 years scored with 0 point in the PHASES study occurred most frequently in our series. The distribution of the aneurysm site to the anterior and posterior circulation scored with 4 points occurred most frequently. Considering the 5-year risk of rupture, 70% of our patient collective would have an estimated risk of < 2%. Interestingly, 70% of the patients with aneurysmal SAH had a low risk profile and would have a low risk of rupture according to the PHASES score in our series. This observation underlines the discrepancy of the estimated low risk of rupture for UIAs in young and healthy patients and the obvious fact the majority of the SAH patients are actually young with low risk factors. Parameters beyond the features of the PHASES score are needed to determine the risk of rupture of intracranial aneurysms.


Assuntos
Aneurisma Roto/complicações , Aneurisma Intracraniano/complicações , Hemorragia Subaracnóidea/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média , Fatores de Risco , Adulto Jovem
12.
Neurosurg Rev ; 42(3): 765-768, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172378

RESUMO

Cerebral cavernous malformations are focal vascular lesions of the brain, occurring sporadically or as an autosomal dominant familial form. The genetic background influences not only the clinical course but also patients' consultation and the indication to treat. We here present the rare case of monozygotic male twins of a polyzygotic triplet birth, carrying a CCM1 mutation, inherited from the mother. Both twins showed an identical site and size of a large frontobasal lesion. The genetic segregation and the clinical course in affected family members are presented and discussed.


Assuntos
Doenças em Gêmeos/genética , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Proteína KRIT1/genética , Mutação/genética , Gêmeos Monozigóticos/genética , Criança , Doenças em Gêmeos/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Masculino , Linhagem , Radiografia
13.
Acta Neuropathol ; 134(6): 905-922, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29030706

RESUMO

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.


Assuntos
Adenosina Desaminase/genética , Predisposição Genética para Doença , Interferon Tipo I/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Ligação a RNA/genética , Ribonuclease H/genética , Adenosina Desaminase/metabolismo , Adulto , Animais , Células Cultivadas , Estudos de Coortes , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Fibroblastos/metabolismo , Humanos , Isocitrato Desidrogenase/genética , Masculino , Camundongos Knockout , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Estabilidade Proteica , Proteínas de Ligação a RNA/metabolismo , Proteínas Supressoras de Tumor/genética
14.
Neuropathology ; 37(1): 3-11, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27388534

RESUMO

Hemangioblastoma (HB) is mainly located in the brain and the spinal cord. The tumor is composed of two major components, namely neoplastic stromal cells and abundant microvessels. Thus, hyper-vascularization is the hallmark of this tumor. Despite the identification of germline and/or epigenetic mutations of Von Hippel Lindau (VHL) gene as an important pathogenic mechanism of HB, little is known about the molecular signaling involved in this highly vascularized tumor. The present study investigated the key players of multiple angiogenic signaling pathways including VEGF/VEGFR2, EphB4/EphrinB2, SDF1α/CXCR4 and Notch/Dll4 pathways in surgical specimens of 22 HB. The expression of key angiogenic factors was detected by RT2 -PCR and Western blot. Immunofluorescent staining revealed the cellular localization of these proteins. We demonstrated a massive upregulation of mRNA levels of VEGF and VEGFR2, CXCR4 and SDF1α, EphB4 and EphrinB2, as well as the main components of Dll4-Notch signaling in HB. An increase in the protein expression of VEGF, CXCR4 and the core-components of Dll4-Notch signaling was associated with an activation of Akt and Erk1/2 and accompanied by an elevated expression of PCNA. Immuofluorescent staining revealed the expression of VEGF and CXCR4 in endothelial cells as well as in tumor cells. Dll4 protein was predominantly found in tumor cells, whereas EphB4 immunoreactivity was exclusively detected in endothelial cells. We conclude that multiple key angiogenic pathways were activated in HB, which may synergistically contribute to the abundant vascularization in this tumor. Identification of these aberrant pathways provides potential targets for a possible future application of anti-angiogenic therapy for this tumor, particularly when a total surgical resection becomes difficult due to the localization or multiplicity of the tumor.


Assuntos
Fossa Craniana Posterior/metabolismo , Regulação Neoplásica da Expressão Gênica , Hemangioblastoma/metabolismo , Neovascularização Patológica/metabolismo , Transdução de Sinais/fisiologia , Neoplasias da Base do Crânio/metabolismo , Neoplasias da Coluna Vertebral/metabolismo , Adolescente , Adulto , Idoso , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Fossa Craniana Posterior/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Efrina-B2/genética , Efrina-B2/metabolismo , Feminino , Hemangioblastoma/genética , Hemangioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Receptor EphB4/genética , Receptor EphB4/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Neoplasias da Base do Crânio/genética , Neoplasias da Base do Crânio/patologia , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/patologia , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
15.
Neurosurg Rev ; 40(1): 129-134, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27215911

RESUMO

Brain arteriovenous malformations (bAVMs) are severe conditions which, upon rupture, cause debilitating neurological deficits and even death. The exact cellular and molecular mechanisms associated with bAVM rupture are currently unclear. The objective of this study was to explore the potential role of CEA-related cell adhesion molecule-1 (CEACAM1) in bAVM pathophysiology. Expression and localization of CEACAM1 were assessed immunohistochemically in tissue microarrays from bAVM patients (n = 60). The association of CEACAM1 with clinical parameters was analyzed with Spearman's rank correlation coefficient and chi-square test. The predictive value of CEACAM1 was tested using logistic regression analysis. CEACAM1 was highly expressed in tissue-infiltrating neutrophil granulocytes. High levels of CEACAM1-positive cells were associated with bAVM rupture (hemorrhage), but not with arteriovenous malformation (AVM) size, preoperative embolization, or seizure. This association was significant (p = 0.029, chi-square) in male but not in female patients, and high CEACAM1-positive immune infiltration showed predictive significance for hemorrhage in male bAVM patients only (OR = 6.50, 95 % CI 1.09-38.63, p = 0.040). Within the ruptured bAVM group, patients with a short hemorrhage to surgery (HTS) time interval had higher levels of CEACAM1 immune infiltration than patients with long HTS. This decrease in the levels of CEACAM1 immune infiltration between the HTS short and HTS long groups was, however, significant only in female patients (p = 0.022, chi-square). Our findings substantiate the role of inflammation in the pathophysiology of bAVM and suggest the presence of sexual dimorphism in this disease.


Assuntos
Antígenos CD/metabolismo , Encéfalo/cirurgia , Moléculas de Adesão Celular/metabolismo , Angiografia Cerebral , Malformações Arteriovenosas Intracranianas/cirurgia , Hemorragias Intracranianas/etiologia , Tomografia Computadorizada por Raios X/efeitos adversos , Encéfalo/fisiopatologia , Angiografia Cerebral/efeitos adversos , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Caracteres Sexuais
16.
Eur Radiol ; 26(3): 829-39, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26080795

RESUMO

OBJECTIVE: To evaluate prospectively 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) and 7 Tesla non-contrast-enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of intracerebral arteriovenous malformations (AVMs) in comparison to 1.5 Tesla TOF MRA and digital subtraction angiography (DSA). METHODS: Twenty patients with single or multifocal AVMs were enrolled in this trial. The study protocol comprised 1.5 and 7 Tesla TOF MRA and 7 Tesla non-contrast-enhanced MPRAGE sequences. All patients underwent an additional four-vessel 3D DSA. Image analysis of the following five AVM features was performed individually by two radiologists on a five-point scale: nidus, feeder(s), draining vein(s), relationship to adjacent vessels, and overall image quality and presence of artefacts. RESULTS: A total of 21 intracerebral AVMs were detected. Both sequences at 7 Tesla were rated superior over 1.5 Tesla TOF MRA in the assessment of all considered AVM features. Image quality at 7 Tesla was comparable with DSA considering both sequences. Inter-observer accordance was good to excellent for the majority of ratings. CONCLUSION: This study demonstrates excellent image quality for depiction of intracerebral AVMs using non-contrast-enhanced 7 Tesla MRA, comparable with DSA. Assessment of untreated AVMs is a promising clinical application of ultra-high-field MRA. KEY POINTS: • Non-contrast-enhanced 7 Tesla MRA demonstrates excellent image quality for intracerebral AVM depiction. • Image quality at 7 Tesla was comparable with DSA considering both sequences. • Assessment of intracerebral AVMs is a promising clinical application of ultra-high-field MRA.


Assuntos
Malformações Arteriovenosas Intracranianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital/métodos , Angiografia Digital/normas , Artefatos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Angiografia por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Sensibilidade e Especificidade , Adulto Jovem
17.
Acta Neurochir (Wien) ; 158(12): 2399-2407, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27766428

RESUMO

BACKGROUND: Multiple AVMs are exceptionally rare lesions and only a few larger series have been published, including other vascular pathologies, such as arterio-venous fistulae (AVF) or patients with hereditary syndromes. Our study presents clinical, angiographic, and therapeutic characteristics of patients harboring sporadic multiple AVMs. METHODS: Basic demographic data, vascular architecture, clinical presentation, treatment strategies, and treatment outcome were analyzed retrospectively from patients with cerebral AVMs treated in our department between 1990 and 2015. RESULTS: Six out of 539 patients (1.1 %) harbored 15 multiple and distinct cerebral lesions. Nidus size was predominantly small, consequently determining a Spetzler-Martin grade °I-°II (three-tier grading system). In three patients, AVMs shared a proximal feeding artery supply, whereas each AVM displayed its own venous drainage. Five of six patients (83 %) presented with hemorrhage. Four patients received therapy of the AVMs with complete elimination in 3/4 patients (75 %) and 8/9 treated AVMs (89 %). All patients with treatment of the AVM showed good-to-excellent recovery (n = 4, mRS ≤ 2). CONCLUSIONS: Multiple cerebral AVMs are complex vascular lesions. The multiplicity of hemodynamic and malformation-related variables influence treatment strategy and sequence. Thus, awareness of these parameters (of various malformations before and during treatment) is important. The high number of hemorrhagic events in the present series might justify a more aggressive treatment of multiple AVMs than previously thought.


Assuntos
Embolização Terapêutica/efeitos adversos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Complicações Pós-Operatórias , Radiocirurgia/efeitos adversos , Adulto , Idoso , Angiografia Cerebral , Criança , Feminino , Hemodinâmica , Humanos , Malformações Arteriovenosas Intracranianas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Cerebrovasc Dis ; 39(2): 122-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25660640

RESUMO

BACKGROUND: Associated aneurysms (AAs) are presumed to represent an additional risk factor for intracranial haemorrhage from cerebral arterio-venous malformations (AVMs). To date, efforts to capture their natural history, as well as to identify aneurysms with the potential capability of regression after AVM treatment remain incomprehensive. As the aneurysm size represents an important aspect for the treatment indication of incidental saccular aneurysms, this factor has rarely been encountered for the treatment of AAs so far. The present study aims to determine the angiographic and clinical characteristics of AAs with special focus on aneurysm size and their consequences for treatment. METHODS: Patients with cerebral AVMs, treated in our department between 1990 and 2013, were analyzed retrospectively. Only patients with supratentorial AVMs and flow-related AAs of the feeding arteries were evaluated. Thus, patients harboring AVMs of the cerebellum and the brain stem and patients with intranidal, venous or remote aneurysms were excluded. Treatment strategies were assessed with special attention on bleeding source and on AA size. RESULTS: In 59 of 409 patients (14%) with supratentorial AVMs, a total of 85 AAs of the feeding arteries were identified. 14 of 59 individuals (24%) presented with multiple AAs. Of 85 AA, 58 aneurysms (68%) were classified as proximal and 27 aneurysms (32%) as distal. The most common location of AAs was the middle cerebral artery (MCA, 39%), followed by the internal carotid artery (ICA, 27%) and the anterior cerebral artery (ACA, 21%). The mean AA size was 4.4 mm ± 3.4 mm. Intracranial haemorrhage was found in 21 of 59 patients (36%) with coexisting AAs. Among these, 10 individuals (17%) suffered from rupture of an AA, accounting for nearly half of all bleedings in this subgroup. Among those patients bearing a single AA, the size of ruptured aneurysms differed significantly from those unruptured (6.6 mm vs. 4.4 mm, p = 0.0046). Nineteen patients (32%) received treatment of 22 AAs, whereas sole AVM treatment was adopted in 26 patients (44%) and conservative management in 14 patients (24%). The main reasons to leave AAs untreated were the small AA size (<5 mm), poor clinical state or treatment denial by the patients. CONCLUSIONS: The aneurysm size of AAs in AVM influences the risk of haemorrhage. Therefore, the treatment of larger (diameter ≥5 mm) AAs should be considered, even if a treatment indication of the associated AVM is not given.


Assuntos
Aneurisma Roto/diagnóstico , Hemorragia Cerebral/diagnóstico , Aneurisma Intracraniano/diagnóstico , Malformações Arteriovenosas Intracranianas/diagnóstico , Adolescente , Adulto , Idoso , Aneurisma Roto/complicações , Angiografia Digital , Angiografia Cerebral , Hemorragia Cerebral/etiologia , Criança , Feminino , Humanos , Aneurisma Intracraniano/complicações , Malformações Arteriovenosas Intracranianas/complicações , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto Jovem
19.
Childs Nerv Syst ; 31(7): 1139-48, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25894756

RESUMO

PURPOSE: Spinal injuries are rarely seen in pediatric patients and therapeutic options are still poorly defined. The present study is aimed to present our experience with a rather large series of children and young adults suffering from traumatic spinal injury. PATIENTS AND METHODS: Between 1990 and 2010, 75 consecutive pediatric patients with spinal injuries were treated in our institution. Mean age was 15 years, ranging from 3 months to 21 years. Radiological findings, treatment strategies, and clinical outcome were evaluated retrospectively and compared with literature. Forty (53.3%) patients were treated conservatively and 35 patients (47%) surgically using anterior or posterior approaches. Subgroup analysis was performed depending on age groups, severity of neurological symptoms, and localization. RESULTS: Main trauma mechanisms were fall in 24 patients (38%) and motor vehicle accidents in 21 patients (28%). Complete neurological deficits were present in 17 individuals (23%) and incomplete in 36 patients (48%). Fractures were most frequently localized at the cervical region (56%) with predilection of the C 5/6 segment. Odontoid fractures were seen in 10 (13%) patients. Fractures of the lumbar and thoracic region were rare. Level of injury or clinical course did not differ between the subgroups (≤15 years versus >15 years). CONCLUSION: Nearly three fourths of all radiologically detected spinal injuries are located at the cervical spine. Complete neurological deficits after trauma was associated with a poor outcome, in particular for patients with injuries of the upper cervical spine. The use of autologous bone graft was associated with favorable long-term results and should be considered as the material of first choice for vertebral body and disc replacement.


Assuntos
Gerenciamento Clínico , Traumatismos da Coluna Vertebral/diagnóstico , Traumatismos da Coluna Vertebral/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
Neurosurg Rev ; 37(4): 643-51, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25005630

RESUMO

The rupture of an intracranial aneurysm leads to subarachnoid hemorrhage (SAH). To prevent SAH, unruptured lesions can be treated by either endovascular or microsurgical approach. Due to their complex anatomy, middle cerebral artery (MCA) aneurysms represent a unique subgroup of intracranial aneurysms. Primary objective was to determine radiological and clinical outcomes in patients with middle cerebral artery aneurysms who were interdisciplinary treated by either endovascular or microsurgical approach in a single center. Secondary objective was to determine the impact of the lesions' angiographic characteristics on treatment outcome. Clinical and radiological data of 103 patients interdisciplinary treated for unruptured MCA aneurysms over a 5-year period were analyzed in endovascular (n = 16) and microsurgical (n = 87) cohorts. Overall morbidity (Glasgow Outcome Score <5) after 12-month follow-up was 9 %. There was no significant difference between the two cohorts. Complete or "near complete" aneurysm occlusion was achieved in 97 and 75 % in the microsurgical, respective endovascular cohort. A "complex" aneurysm configuration had a significant impact on complete aneurysm occlusion in both cohorts, however, not on clinical outcome. Treatment of unruptured MCA aneurysms can be performed with a low risk of repair using both approaches. However, the risk for incomplete occlusion was higher for the endovascular approach in this series.


Assuntos
Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Artéria Cerebral Média/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Aneurisma Roto/cirurgia , Angiografia Cerebral , Estudos de Coortes , Procedimentos Endovasculares/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Instrumentos Cirúrgicos , Resultado do Tratamento
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