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1.
Acta Neuropathol Commun ; 8(1): 28, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32151286

RESUMO

Peripheral metastases of glioblastoma (GBM) are very rare despite the ability of GBM cells to pass through the blood-brain barrier and be disseminated through the peripheral blood. Here, we describe a detailed genetic and immunological characterization of a GBM metastasis in the skeleton, which occurred during anti-PD-1 immune checkpoint therapy. We performed whole genome sequencing (WGS) and 850 K methylation profiling of the primary and recurrent intracranial GBM as well as one of the bone metastases. Copy number alterations (CNA) and mutational profiles were compared to known genomic alterations in the TCGA data base. In addition, immunophenotyping of the peripheral blood was performed. The patient who was primarily diagnosed with IDH-wildtype GBM. After the resection of the first recurrence, progressive intracranial re-growth was again detected, and chemotherapy was replaced by PD-1 checkpoint inhibition, which led to a complete intracranial remission. Two months later MR-imaging revealed multiple osseous lesions. Biopsy confirmed the GBM origin of the skeleton metastases. Immunophenotyping reflected the effective activation of a peripheral T-cell response, with, however, increase of regulatory T cells during disease progression. WGS sequencing demonstrated distinct genomic alterations of the GBM metastasis, with gains along chromosomes 3 and 9 and losses along chromosome 4, 10, and 11. Mutational analysis showed mutations in potentially immunologically relevant regions. Additionally, we correlated tumour-infiltrating lymphocyte and microglia presence to the occurrence of circulating tumour cells (CTCs) in a larger cohort and found a decreased infiltration of cytotoxic T cells in patients positive for CTCs. This study exemplifies that the tumour microenvironment may dictate the response to immune checkpoint therapy. In addition, our study highlights the fact that despite an effective control of intracranial GBM, certain tumour clones have the ability to evade the tumour-specific T-cell response and cause progression even outside of the CNS.

2.
Neurosurg Rev ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502028

RESUMO

In medical refractory temporal lobe epilepsy (TLE), the epileptogenic zone can be difficult to identify and therefore difficult to treat, especially in the absence of clear MRI pathologies and specific results from presurgical evaluation. Invasive monitoring with stereo-electroencephalography (sEEG) is a tool for a better determination of the epileptogenic zone. Here, we investigate the impact of sEEG on decision-making in temporal lobe epilepsy surgery. We reviewed patients with TLE who underwent further investigation with sEEG in our epilepsy unit. We examined specifically how sEEG findings influenced our decision regarding indication for a surgical procedure and resection volume. From 2013 to 2017, we performed 152 temporal resections in epilepsy patients. Twenty-one of these patients were designated for further preoperative investigation with sEEG due to incongruent findings in presurgical evaluation. Six patients were implanted bitemporally. In five cases, the hypothesis for the epileptogenic zone and localization had to be changed due to sEEG findings and resulted in a different tailored resection than intended. In three cases, sEEG findings led to the cancelation of the originally intended temporal resection as the epileptogenic zone was not definable or bilateral. In another three cases, the prognosis for reduction of seizures postoperatively had to be reduced due to the sEEG findings. However, the resection was performed after interdisciplinary discussion and informed consent of the patient. The examination by sEEG led to a change of plan for further treatment in 13 patients (61.9%) suffering TLE in total. Invasive monitoring with sEEG electrodes had a strong impact on decision-making for further treatment in patients suffering from temporal lobe epilepsy with incongruent findings in presurgical examination designated for epilepsy surgery. This applies to resection volumes as well as to prediction of seizure outcome.

3.
J Neurosurg ; : 1-10, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226688

RESUMO

OBJECTIVE: Primary intraosseous meningioma (PIM) is a rare manifestation of meningioma, a benign, neoplastic lesion of the meninges. Its characteristic appearance is hyperostosis, while no or only minimal dural changes can be observed. This study aims to characterize this rare entity from both a clinical and histopathological point of view in order to improve clinical management. METHODS: In the years 2009-2017, 26 cases of PIM were diagnosed using MRI and CT scans. In 16 cases the indication for resection was given, and specimens were further examined using a multilevel approach, including histological and immunohistochemical analyses. Additionally, the local database was searched for all cases of meningiomas, as well as osteosclerotic differential diagnoses-i.e., fibrous dysplasia, Paget's disease of bone, and other benign osteosclerotic lesions. RESULTS: In this study, PIM represented 2.4% of all meningiomas with a predominant occurrence in females (85%). Regarding the initial manifestation, PIMs show a slightly earlier onset than meningiomas. While most PIMs are located in the sphenoid bone, associated calcifications were visible in 58% of the cases on CT scans. Most of the cases were classified as WHO grade I (93%) and meningotheliomatous meningiomas (91%). Tumor growth was associated with an increased bone resorption followed by massive osteoid deposition and consecutive sclerosis. The frequently observed frayed appearance results from multiple bony canals, which contain blood vessels for the blood supply of the highly vascularized tumor tissue. CONCLUSIONS: PIM is a rare but important differential diagnosis for osteosclerotic lesions of the skull, especially in women. Tumor-induced, cellular-mediated bone resorption and formation may play a central role in the underlying pathogenesis.

4.
J Extracell Vesicles ; 8(1): 1588555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949309

RESUMO

Cells release heterogeneous nano-sized vesicles either as exosomes, being derived from endosomal compartments, or through budding from the plasma membrane as so-called microvesicles, commonly referred to as extracellular vesicles (EVs). EVs are known for their important roles in mammalian physiology and disease pathogenesis and provide a potential biomarker source in cancer patients. EVs are generally often analysed in bulk using Western blotting or by bead-based flow-cytometry or, with limited parameters, through nanoparticle tracking analysis. Due to their small size, single EV analysis is technically highly challenging. Here we demonstrate imaging flow cytometry (IFCM) to be a robust, multiparametric technique that allows analysis of single EVs and the discrimination of distinct EV subpopulations. We used IFCM to analyse the tetraspanin (CD9, CD63, CD81) surface profiles on EVs from human and murine cell cultures as well as plasma samples. The presence of EV subpopulations with specific tetraspanin profiles suggests that EV-mediated cellular responses are tightly regulated and dependent on cell environment. We further demonstrate that EVs with double positive tetraspanin expression (CD63+/CD81+) are enriched in cancer cell lines and patient plasma samples. In addition, we used IFCM to detect tumour-specific GFP-labelled EVs in the blood of mice bearing syngeneic intracerebral gliomas, indicating that this technique allows unprecedented disease modelling. In summary, our study highlights the heterogeneous and adaptable nature of EVs according to their marker profile and demonstrates that IFCM facilitates multiparametric phenotyping of EVs not only in vitro but also in patient plasma at a single EV level, with the potential for future functional studies and clinically relevant applications. Abbreviation: EDTA = ethylenediamine tetraacetic acid.

5.
Childs Nerv Syst ; 35(6): 1029-1033, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30796558

RESUMO

BACKGROUND: Recent studies on medulloblastomas (MB) suggest that a large fraction of tumors appearing as late recurrence turn out to be secondary malignancies, e.g., malignant gliomas, after thorough molecular investigation. RESULTS: Here, we report of a patient with a group 4 MB that developed a distant recurrence after more than 18 years. The recurrent tumor was confirmed by histology and genome-wide DNA methylation profiling. CONCLUSION: Our case not only illustrates the potential of very late recurrences after seemingly cured group 4 MB, but also illustrates that detailed molecular analyses are indispensable in patients with a history of a previous malignancy.

6.
J Neurooncol ; 141(1): 183-194, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30390175

RESUMO

INTRODUCTION: With the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), diagnosis of glioma is based on molecular parameters in addition to histology potentially leading to additional demands on quality of tissue samples. This may challenge the role of minimally invasive biopsy procedures. This study aims to evaluate the diagnostic yield of glioma samples from frameless stereotactic biopsies with focus on molecular information and explore the neuromolecular profile of a glioma biopsy cohort. METHODS: In a case series analysis, 180 consecutive frameless stereotactic biopsies with the Brainlab® Varioguide system from January 2011 to October 2017 were reviewed and patients with suspected or verified glioma were identified. Neuropathological samples were reprocessed in accordance with 2016 CNS WHO standards. RESULTS: One hundred nineteen glioma patients were identified. Analysis of IDH status could be performed in 95.8% resulting in a cumulative mutation rate of 9.6%. A complete diagnosis according to 2016 CNS WHO including grading and molecular features was achieved in 110 cases (92.4%). Entities were revised in four cases. Most common diagnosis was IDH-wildtype glioblastoma (66.4%) followed by IDH-wildtype anaplastic astrocytoma (21.8%). CONCLUSIONS: A formally complete diagnosis according to 2016 CNS WHO was achieved in the majority of cases. The biopsy cohort showed a prognostically unfavorable distribution of diagnoses and molecular features. Frameless stereotactic biopsy seems to be confirmed as a useful diagnostic tool in contemporary neuro-oncology-however, certain potential limitations should be considered.


Assuntos
Biópsia/métodos , Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , Neuronavegação/métodos , Idoso , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico
7.
Epilepsia ; 60(1): 149-154, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30536819

RESUMO

OBJECTIVE: The clinical course and underlying molecular causes in patients with glioblastoma presenting with seizures are poorly understood. Here we investigated clinical features and carrier systems as well as a transaminase relevant in glutamate homeostasis in patients with glioblastoma. METHODS: We performed a retrospective analysis of our clinical glioma database for clinical data during a 2-year period. Patients with glioblastoma were divided into 2 groups: symptomatic and asymptomatic for seizures. Magnetic resonance imaging (MRI) scans and tissue samples from both groups were investigated. A Cox regression analysis was performed for survival and clinical and molecular features. RESULTS: One hundred three patients diagnosed with glioblastoma in this period were identified. Twenty-three patients were symptomatic with seizures (22.3%). All were IDH-1/2 wild-type. We found no significant difference in the tumor localization between the groups. Patients with seizures from glioblastoma had significantly smaller tumors, which caused less edema compared to nonepileptogenic tumors. A significantly increased up-regulation of glutamate carrier systems was evident in symptomatic tumors compared to asymptomatic tumors. Moreover, there seems to be an oversupply of glutamate in symptomatic tumors due to dysregulation in glutamate synthesis. SIGNIFICANCE: Glioblastoma presenting with seizures is morphologically different from asymptomatic tumors. Furthermore, we were able to show that the molecular profile of these tumors, particularly glutamate homeostasis controlling systems, is significantly different.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/complicações , Glioblastoma/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Convulsões/etiologia , Idoso , Bases de Dados Factuais/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Tumoral/fisiologia
8.
J Neurosurg ; 131(3): 740-749, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30192199

RESUMO

OBJECTIVE: The aim of this study was to compare sensitivity and specificity between the novel threshold and amplitude criteria for motor evoked potentials (MEPs) monitoring after transcranial electrical stimulation (TES) during surgery for supratentorial lesions in the same patient cohort. METHODS: One hundred twenty-six patients were included. All procedures were performed under general anesthesia. Craniotomies did not expose motor cortex, so that direct mapping was less suitable. After TES, MEPs were recorded bilaterally from abductor pollicis brevis (APB), from orbicularis oris (OO), and/or from tibialis anterior (TA). The percentage increase in the threshold level was assessed and considered significant if it exceeded by more than 20% on the affected side the percentage increase on the unaffected side. Amplitude on the affected side was measured with a stimulus intensity of 150% of the threshold level set for each muscle. RESULTS: Eighteen of 126 patients showed a significant change in the threshold level as well as an amplitude reduction of more than 50% in MEPs recorded from APB, and 15 of the patients had postoperative deterioration of motor function of the arm (temporary in 8 cases and permanent in 7 [true-positive and false-negative results]). Recording from TA was performed in 66 patients; 4 developed postoperative deterioration of motor function of the leg (temporary in 3 cases and permanent in 1), and showed a significant change in the threshold level, and an amplitude reduction of more than 50% occurred in 1 patient. An amplitude reduction of more than 50% occurred in another 10 patients, without a significant change in the threshold level or postoperative deterioration. Recording from OO was performed in 61 patients; 3 developed postoperative deterioration of motor function of facial muscles (temporary in 2 cases and permanent in 1) and had a significant change in the threshold level, and 2 of the patients had an amplitude reduction of more than 50%. Another 6 patients had an amplitude reduction of more than 50% but no significant change in the threshold level or postoperative deterioration.Sensitivity of the threshold criterion was 100% when MEPs were recorded from APB, OO, or TA, and its specificity was 97%, 100%, and 100%, respectively. Sensitivity of the amplitude criterion was 100%, 67%, and 25%, with a specificity of 97%, 90%, and 84%, respectively. CONCLUSIONS: The threshold criterion was comparable to the amplitude criterion with a stimulus intensity set at 150% of the threshold level regarding sensitivity and specificity when recording MEPs from APB, and superior to it when recording from TA or OO.


Assuntos
Potencial Evocado Motor/fisiologia , Glioma/fisiopatologia , Glioma/cirurgia , Complicações Pós-Operatórias/etiologia , Neoplasias Supratentoriais/fisiopatologia , Neoplasias Supratentoriais/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Sensibilidade e Especificidade , Estimulação Transcraniana por Corrente Contínua
9.
Neurosurg Focus ; 44(6): E15, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29852760

RESUMO

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/terapia , Gerenciamento Clínico , Progressão da Doença , Qualidade de Vida , Teto do Mesencéfalo/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Neurocirugía (Soc. Luso-Esp. Neurocir.) ; 29(2): 86-92, mar.-abr. 2018. graf, tab
Artigo em Inglês | IBECS | ID: ibc-171433

RESUMO

Introduction: Chronic subdural hematoma (cSDH) is a common pathology encountered in neurosurgical practice, especially in elderly patients, who frequently require antithrombotic agents. The aim of this study was to investigate the influence of antithrombotic agents on recurrence rates and clinical outcomes in patients operated for cSDH. Methods: A cohort of patients operated for cSDH at one center during a 5 years period was analyzed retrospectively. Presenting symptoms, coagulation testing, history of antithrombotic agents and comorbidities were obtained from the patient charts. The standard neurosurgical procedure was a single burr hole under local anesthesia with insertion of a subdural drainage. Questionnaires and telephone interviews were used to assess the clinical outcome using the modified Rankin Scale (mRS). Good outcome was defined as mRS 0 to 3 and poor outcome as mRS 4 to 6. Results: 201 patients with cSDH underwent initial surgical treatment and were enrolled in the study. The median follow-up was 81 weeks. 41 patients (20.4%) were on antiplatelet drug and 43 (21.4%) were on phenprocoumon. A recurrent hematoma required surgery in 37 patients (18.4%). A poor outcome was seen in 36 patients (17.9%). Each of older age and administration of phenprocoumon at admission was an independent risk factor predictive of poor outcome, (p = 0.001 and p = 0.031, respectively)) Administration of antithrombotic agents had no impact on hematoma recurrence. Conclusion: Administration of phenprocoumon and older age might increase the risk of poor outcome in patients with cSDH. Neither the administration of phenprocoumon nor antiplatelet drug influenced the recurrence rate of subdural hematoma in our patient cohort


Introducción: El hematoma subdural crónico (HSC) es una enfermedad común en la práctica neuro-quirúgica, especialmente en pacientes mayores, quienes requieren con frecuencia agentes anti-trombóticos. El objetivo de este estudio fue investigar la influencia de los agentes anti-trombóticos en las tasas de recidiva y los resultados clínicos en los pacientes operados de HSC. Métodos: Se analizó retrospectivamente una cohorte de pacientes operados de HSC en un único centro, durante un periodo de 5 años. Se obtuvieron de las historias de los pacientes los síntomas de presentación, las pruebas de coagulación, el historial de agentes anti-trombóticos y las comorbilidades. El procedimiento quirúrgico estándar consistió en una trepanación bajo anestesia local, con inserción de un drenaje subdural. Se utilizaron cuestionarios y entrevistas telefónicas para valorar el resultado clínico mediante la Escala de Rankin modificada (mRS). El resultado favorable se definió como el valor de 0 a 3 de mRS, y el resultado desfavorable el valor de 4 a 6. Resultados: Doscientos uno pacientes con HSC fueron sometidos a tratamiento quirúrgico inicial, y fueron incluidos en el estudio. El seguimiento medio fue de 81 semanas. A 41 pacientes (20,4%) se les administró tratamiento anti-plaquetario y a 43 (21,4%) fenprocumón. El hematoma recurrente requirió cirugía en 37 pacientes (18,4%). Se observaron resultados desfavorables en 36 pacientes (17,9%). La avanzada edad y la administración de fenprocumón al ingreso resultaron factores predictivos independientes del resultado desfavorable (p = 0,001 y p = 0,031, respectivamente). La administración de agentes antitrombóticos no tuvo impacto sobre la recidiva del hematoma. Conclusión: La administración de fenprocumón y la edad avanzada pueden incrementar el riesgo de resultado desfavorable en los pacientes con HSC. Ni la administración de fenprocumón ni la de fármacos anti-plaquetarios influyeron en la tasa de hematomas subdurales en nuestra cohorte de pacientes


Assuntos
Humanos , Masculino , Feminino , Idoso , Hematoma Subdural Crônico/complicações , Hematoma Subdural Crônico/cirurgia , Fibrinolíticos/uso terapêutico , Recidiva , Hematoma Subdural Crônico/induzido quimicamente , Hematoma Subdural Crônico/diagnóstico por imagem , Fibrinolíticos/efeitos adversos , Femprocumona/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Comorbidade , Inquéritos e Questionários , Análise Estatística , Razão de Chances
11.
Clin Cancer Res ; 24(17): 4187-4200, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29444930

RESUMO

Purpose: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion.Experimental Design: We used flow cytometry and cytokine assays to profile TILs and peripheral blood lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM.Results: We identified a clear immune signature of exhaustion and clonal restriction in the TILs of patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression, and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors; however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TILs from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8+ T cells.Conclusions: TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T cells in recurrent tumors. Clin Cancer Res; 24(17); 4187-200. ©2018 AACRSee related commentary by Jackson and Lim, p. 4059.


Assuntos
Glioblastoma/imunologia , Imunofenotipagem , Linfócitos do Interstício Tumoral/imunologia , Recidiva Local de Neoplasia/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/genética , Apirase/genética , Antígenos CD57/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Glioblastoma/genética , Glioblastoma/patologia , Antígenos HLA-DR/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Humanos , Lectinas Tipo C/genética , Antígenos Comuns de Leucócito/genética , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Receptor de Morte Celular Programada 1/genética , Transativadores/genética
12.
J Neurosurg ; 128(6): 1668-1673, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28753112

RESUMO

OBJECTIVE Temporal lobe epilepsy (TLE) is the most common type of pharmacoresistant focal epilepsy, for which anterior mesial temporal lobe resection (AMTLR) is a treatment option. Focal cortical dysplasia Type IIIa (FCD IIIa), a developmental lesion resulting from defects in neuronal formation and migration into the temporal pole (FCD I) combined with hippocampal sclerosis (HS), can be a neuropathological finding. In this study, the authors investigate the impact of FCD IIIa on seizure outcome in patients with TLE who underwent AMTLR. METHODS The authors performed a retrospective analysis of all patients with TLE who underwent AMTLR at their institution between June 2011 and April 2014. Histopathological analysis was used to determine whether patients had HS together with FCD I (FCD IIIa) or HS alone. The groups were compared with regard to age, sex, years of epilepsy, and seizure outcome using the Engel classification. RESULTS A total of 51 patients with TLE underwent AMTLR at the authors' institution. FCD IIIa was diagnosed in 13 cases. The patients experienced seizures for a mean duration of 31.1 years. The mean length of follow-up after the procedure was 18 months. All patients with FCD IIIa had a favorable seizure outcome (Engel Class I or II) compared with 71% of the patients with no pathological findings in the temporal pole (p < 0.01). CONCLUSIONS Patients with histopathologically proven FCD IIIa had a significantly better seizure outcome after AMTLR than patients with HS alone. Further effort should be made during presurgical evaluation to detect FCD IIIa so that the most suitable resection technique can be chosen and postoperative seizure outcome can be predicted for patient counseling.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Malformações do Desenvolvimento Cortical/complicações , Convulsões/cirurgia , Lobo Temporal/cirurgia , Adulto , Idoso , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Epilepsia do Lobo Temporal/patologia , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Resultado do Tratamento , Adulto Jovem
13.
Neurocirugia (Astur) ; 29(2): 86-92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29122534

RESUMO

INTRODUCTION: Chronic subdural hematoma (cSDH) is a common pathology encountered in neurosurgical practice, especially in elderly patients, who frequently require antithrombotic agents. The aim of this study was to investigate the influence of antithrombotic agents on recurrence rates and clinical outcomes in patients operated for cSDH. METHODS: A cohort of patients operated for cSDH at one center during a 5 years period was analyzed retrospectively. Presenting symptoms, coagulation testing, history of antithrombotic agents and comorbidities were obtained from the patient charts. The standard neurosurgical procedure was a single burr hole under local anesthesia with insertion of a subdural drainage. Questionnaires and telephone interviews were used to assess the clinical outcome using the modified Rankin Scale (mRS). Good outcome was defined as mRS 0 to 3 and poor outcome as mRS 4 to 6. RESULTS: 201 patients with cSDH underwent initial surgical treatment and were enrolled in the study. The median follow-up was 81 weeks. 41 patients (20.4%) were on antiplatelet drug and 43 (21.4%) were on phenprocoumon. A recurrent hematoma required surgery in 37 patients (18.4%). A poor outcome was seen in 36 patients (17.9%). Each of older age and administration of phenprocoumon at admission was an independent risk factor predictive of poor outcome, (p=0.001 and p=0.031, respectively)) Administration of antithrombotic agents had no impact on hematoma recurrence. CONCLUSION: Administration of phenprocoumon and older age might increase the risk of poor outcome in patients with cSDH. Neither the administration of phenprocoumon nor antiplatelet drug influenced the recurrence rate of subdural hematoma in our patient cohort.


Assuntos
Anticoagulantes/efeitos adversos , Drenagem , Fibrinolíticos/efeitos adversos , Hematoma Subdural Crônico/cirurgia , Inibidores da Agregação de Plaquetas/efeitos adversos , Trepanação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Dano Encefálico Crônico/etiologia , Comorbidade , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Femprocumona/efeitos adversos , Femprocumona/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Z Geburtshilfe Neonatol ; 221(6): 276-282, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29041013

RESUMO

Maternal aneurysmal subarachnoid hemorrhage (aSAH) during pregnancy presents a challenge regarding treatment and management. Due to the limited number of cases there are no treatment guidelines available. Thus, treatment is usually done on a case-by-case basis. Here we report on four cases of aSAH during pregnancy, describing the different management strategies and suggesting a possible treatment algorithm. Patients treated between 2003 and 2013 in our center were included in this retrospective study. Clinical data focused on time management concerning gestation week (GW), microsurgical or endovascular treatment, and outcome of the patients and the fetuses. Results were compared to the present literature on this issue. Mean age was 30.8 years, initial Hunt & Hess (H&H) grade ranged from III to V. All patients suffered from aSAH during the 3rd trimester of pregnancy. In the four cases, two emergency Caesarean sections (CS) were performed. Two aneurysms were occluded by microsurgical clipping and one was treated endovascularly. One patient died before definitive treatment of the aneurysm could be achieved, whereas fetal mortality was 0%. The mean follow-up was 83 months. aSAH during pregnancy needs individualized interdisciplinary management. Efforts must focus on the mother so that a delay in the best available treatment for the pregnant patient is avoided. Therefore treatment modality should be primarily determined by the aneurysm itself. However, timing in terms of delivery of the fetus and aneurysm treatment is a crucial point.


Assuntos
Comunicação Interdisciplinar , Colaboração Intersetorial , Complicações Cardiovasculares na Gravidez/terapia , Hemorragia Subaracnóidea/terapia , Adulto , Algoritmos , Cesárea , Embolização Terapêutica , Feminino , Seguimentos , Alemanha , Escala de Resultado de Glasgow , Humanos , Recém-Nascido , Microcirurgia , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Hemorragia Subaracnóidea/diagnóstico , Instrumentos Cirúrgicos
15.
J Neurosurg Anesthesiol ; 29(4): 393-399, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27482981

RESUMO

BACKGROUND: Rising threshold level during monitoring of motor-evoked potentials (MEP) using transcranial electrical stimulation (TES) has been described without damage to the motor pathway in the cranial surgery, suggesting the need for monitoring of affected and unaffected hemisphere. We aimed to determine the factors that lead to a change in threshold level and to establish reliable criteria for adjusting stimulation intensity during surgery for supratentorial lesions. MATERIALS AND METHODS: Between October 2014 and October 2015, TES-MEP were performed in 143 patients during surgery for unilateral supratentorial lesions in motor-eloquent brain areas. All procedures were performed under general anesthesia using a strict protocol to maintain stable blood pressure. MEP were evaluated bilaterally to assess the percentage increase in threshold level, which was considered significant if it exceeded 20% on the contralateral side beyond the percentage increase on the ipsilateral side. Patients who developed a postoperative motor deficit were excluded. Volume of subdural air was measured on postoperative magnetic resonance imaging. Logistic regression was performed to identify factors associated with the intraoperative recorded changes in threshold level. RESULTS: A total of 123 patients were included in the study. On the affected side, 82 patients (66.7%) showed an increase in threshold level, which ranged from 2% to 48% and 41 patients (33.3%) did not show any change. The difference to the unaffected side was under 20% in all patients. The recorded range of changes in the systolic and mean pressure did not exceed 20 mm Hg in any of the patients. Pneumocephalus was detected on postoperative magnetic resonance imaging scans in 87 patients (70.7%) and 81 of them (93.1%) had an intraoperative increase in threshold level on either sides. Pneumocephalus was the only factor associated with an increase in threshold level on the affected side (P<0.001), while each of pneumocephalus and length of the procedure correlated with a change in threshold level on the unaffected side (P<0.001 and 0.032, respectively). CONCLUSIONS: Pneumocephalus was the only factor associated with increase in threshold level during MEP monitoring without damaging motor pathway. Threshold level on the affected side can rise up to 48% without being predictive of postoperative paresis, as long as the difference between the increased threshold of the affected and unaffected side is within 20%. Changes in systolic or mean blood pressure within a range of 20 mm Hg do not seem to influence intraoperative MEP.


Assuntos
Encéfalo/cirurgia , Estimulação Elétrica/métodos , Potencial Evocado Motor , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Pressão Sanguínea , Feminino , Lateralidade Funcional , Humanos , Complicações Intraoperatórias/diagnóstico por imagem , Complicações Intraoperatórias/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Paralisia/etiologia , Pneumocefalia/diagnóstico por imagem , Pneumocefalia/etiologia , Pneumocefalia/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Espaço Subdural/diagnóstico por imagem
16.
Epilepsia ; 57(11): 1789-1797, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27677727

RESUMO

OBJECTIVE: Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). METHODS: Patients' characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. RESULTS: Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. SIGNIFICANCE: Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.


Assuntos
Tonsila do Cerebelo/cirurgia , Lobectomia Temporal Anterior/efeitos adversos , Transtornos Cognitivos/etiologia , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Adolescente , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Adulto Jovem
17.
J Neurosurg ; 125(4): 795-802, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26799297

RESUMO

OBJECTIVE Warning criteria for monitoring of motor evoked potentials (MEP) after direct cortical stimulation during surgery for supratentorial tumors have been well described. However, little is known about the value of MEP after transcranial electrical stimulation (TES) in predicting postoperative motor deficit when monitoring threshold level. The authors aimed to evaluate the feasibility and value of this method in glioma surgery by using a new approach for interpreting changes in threshold level involving contra- and ipsilateral MEP. METHODS Between November 2013 and December 2014, 93 patients underwent TES-MEP monitoring during resection of gliomas located close to central motor pathways but not involving the primary motor cortex. The MEP were elicited by transcranial repetitive anodal train stimulation. Bilateral MEP were continuously evaluated to assess percentage increase of threshold level (minimum voltage needed to evoke a stable motor response from each of the muscles being monitored) from the baseline set before dural opening. An increase in threshold level on the contralateral side (facial, arm, or leg muscles contralateral to the affected hemisphere) of more than 20% beyond the percentage increase on the ipsilateral side (facial, arm, or leg muscles ipsilateral to the affected hemisphere) was considered a significant alteration. Recorded alterations were subsequently correlated with postoperative neurological deterioration and MRI findings. RESULTS TES-MEP could be elicited in all patients, including those with recurrent glioma (31 patients) and preoperative paresis (20 patients). Five of 73 patients without preoperative paresis showed a significant increase in threshold level, and all of them developed new paresis postoperatively (transient in 4 patients and permanent in 1 patient). Eight of 20 patients with preoperative paresis showed a significant increase in threshold level, and all of them developed postoperative neurological deterioration (transient in 4 patients and permanent in 4 patients). In 80 patients no significant change in threshold level was detected, and none of them showed postoperative neurological deterioration. The specificity and sensitivity in this series were estimated at 100%. Postoperative MRI revealed gross-total tumor resection in 56 of 82 patients (68%) in whom complete tumor resection was attainable; territorial ischemia was detected in 4 patients. CONCLUSIONS The novel threshold criterion has made TES-MEP a useful method for predicting postoperative motor deficit in patients who undergo glioma surgery, and has been feasible in patients with preoperative paresis as well as in patients with recurrent glioma. Including contra- and ipsilateral changes in threshold level has led to a high sensitivity and specificity.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Potencial Evocado Motor , Glioma/fisiopatologia , Monitorização Intraoperatória/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , Vias Eferentes/fisiopatologia , Estudos de Viabilidade , Glioma/cirurgia , Humanos , Pessoa de Meia-Idade , Estimulação Transcraniana por Corrente Contínua
18.
Epilepsy Res ; 117: 29-34, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26370915

RESUMO

PURPOSE: Focal cortical dysplasias (FCD) type IIb and cortical tubers in tuberous sclerosis complex (TSC) are histopathologically similar and are both epileptogenic lesions frequently causing pharmacoresistant epilepsies. Morphometric analysis of T1- and T2-weighted MRI volume data sets can enhance visualization of FCD. Here, we retrospectively investigated whether morphometric MRI analysis is of equal benefit for visualizing cortical tubers. MATERIALS AND METHODS: Morphometric analysis was applied to T1- and partly also T2-weighted 1.5T or 3T MRI volume data sets of 15 TSC patients using a fully automated MATLAB(®) script (i.e. MAP07) commonly used for FCD detection. In this study, focus was on the most sensitive of the resulting morphometric feature maps (i.e. the 'junction image') which highlights blurring of the gray-white matter junction in comparison to a normal database. The visualization of tubers in these 'junction images' was quantitatively compared with that in conventional MR sequences. RESULTS: In all patients, morphometric analysis visualized almost all tubers detected in the normal MRI, and additionally highlighted on average 23% (range 3-50%) more tubers which were not detected by visual analysis of the conventional MR sequences. When T2 volume data sets from a 3T scanner were available for postprocessing, the rate of additionally detected tubers increased to 29% on average. These formerly overlooked tubers were usually smaller than the tubers already found in the conventional MRI. CONCLUSION: Morphometric analysis of MRIs in TSC can highlight cortical tubers which are likely to be overlooked in conventional MRI sequences alone. Additionally detected tubers may be of potential importance for both presurgical evaluation and initial diagnosis of TSC.


Assuntos
Encéfalo/patologia , Esclerose Tuberosa/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Estudos Retrospectivos , Adulto Jovem
19.
Acta Neuropathol ; 129(5): 679-93, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25783747

RESUMO

Cerebral gliomas of World Health Organization (WHO) grade II and III represent a major challenge in terms of histological classification and clinical management. Here, we asked whether large-scale genomic and transcriptomic profiling improves the definition of prognostically distinct entities. We performed microarray-based genome- and transcriptome-wide analyses of primary tumor samples from a prospective German Glioma Network cohort of 137 patients with cerebral gliomas, including 61 WHO grade II and 76 WHO grade III tumors. Integrative bioinformatic analyses were employed to define molecular subgroups, which were then related to histology, molecular biomarkers, including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutations, and patient outcome. Genomic profiling identified five distinct glioma groups, including three IDH1/2 mutant and two IDH1/2 wild-type groups. Expression profiling revealed evidence for eight transcriptionally different groups (five IDH1/2 mutant, three IDH1/2 wild type), which were only partially linked to the genomic groups. Correlation of DNA-based molecular stratification with clinical outcome allowed to define three major prognostic groups with characteristic genomic aberrations. The best prognosis was found in patients with IDH1/2 mutant and 1p/19q co-deleted tumors. Patients with IDH1/2 wild-type gliomas and glioblastoma-like genomic alterations, including gain on chromosome arm 7q (+7q), loss on chromosome arm 10q (-10q), TERT promoter mutation and oncogene amplification, displayed the worst outcome. Intermediate survival was seen in patients with IDH1/2 mutant, but 1p/19q intact, mostly astrocytic gliomas, and in patients with IDH1/2 wild-type gliomas lacking the +7q/-10q genotype and TERT promoter mutation. This molecular subgrouping stratified patients into prognostically distinct groups better than histological classification. Addition of gene expression data to this genomic classifier did not further improve prognostic stratification. In summary, DNA-based molecular profiling of WHO grade II and III gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification as well as IDH1/2 mutation and 1p/19q co-deletion status.


Assuntos
Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Glioma/genética , Isocitrato Desidrogenase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glioma/classificação , Glioma/patologia , Glioma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores/métodos , Prognóstico , Regiões Promotoras Genéticas , Deleção de Sequência , Organização Mundial da Saúde , Adulto Jovem
20.
Neuro Oncol ; 17(8): 1076-85, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25543125

RESUMO

BACKGROUND: Signaling by insulin-like growth factor 1 receptor (IGF-1R) can contribute to the formation and progression of many diverse tumor types, including glioblastoma. We investigated the effect of the IGF-1R blocking antibody IMC-A12 on glioblastoma growth in different in vivo models. METHODS: U87 cells were chosen to establish rapidly growing, angiogenesis-dependent tumors in the brains of nude mice, and the GS-12 cell line was used to generate highly invasive tumors. IMC-A12 was administered using convection-enhanced local delivery. Tumor parameters were quantified histologically, and the functional relevance of IGF-1R activation was analyzed in vitro. RESULTS: IMC-A12 treatment inhibited the growth of U87 and GS-12 tumors by 75% and 50%, respectively. In GS-12 tumors, the invasive tumor extension and proliferation rate were significantly reduced by IMC-A12 treatment, while apoptosis was increased. In IMC-A12-treated U87 tumors, intratumoral vascularization was markedly decreased, and tumor cell proliferation was moderately reduced. Flow cytometry showed that <2% of U87 cells but >85% of GS-12 cells expressed IGF-1R. Activation of IGF-1R by IGF-1 and IGF-2 in GS-12 cells was blocked by IMC-A12. Both ligands stimulated GS-12 cell proliferation, and IGF-2 also stimulated migration. IMC-A12 inhibited these stimulatory effects and increased apoptosis. In U87 cells, stimulation with either ligand had no functional effect. CONCLUSIONS: IGF-1R blockade can inhibit glioblastoma growth by different mechanisms, including direct effects on the tumor cells as well as indirect anti-angiogenic effects. Hence, blocking IGF-1R may be useful to target both the highly proliferative, angiogenesis-dependent glioblastoma core component as well as the infiltrative periphery.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/antagonistas & inibidores , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glioblastoma/fisiopatologia , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/imunologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Camundongos , Neovascularização Patológica , Ensaios Antitumorais Modelo de Xenoenxerto
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