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1.
J Clin Invest ; 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32603315

RESUMO

Immunotherapeutic strategies are increasingly important in neuro-oncology and the elucidation of escape mechanisms which lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing wildtype and Pd-1-/- mice survived significantly longer than immunodeficient Pfp-/- Rag2-/- mice. While tumors in Pfp-/- Rag2-/- mice were highly polyclonal, immunoedited tumors in WT and Pd-1-/- mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in wildtype mice were distinguished by an interferon-γ-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even stronger to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas.

2.
Cancer Lett ; 477: 10-18, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112900

RESUMO

Medulloblastoma (MB) is the most frequent malignant brain tumour in children with a poor outcome. Divided into four molecular subgroups, MB of the Sonic hedgehog (SHH) subgroup accounts for approximately 25% of the cases and is driven by mutations within components of the SHH pathway, such as its receptors PTCH1 or SMO. A fraction of these cases additionally harbour PIK3CA mutations, the relevance of which is so far unknown. To unravel the role of Pik3ca mutations alone or in combination with a constitutively activated SHH signalling pathway, transgenic mice were used. These mice show mutated variants within Smo, Ptch1 or Pik3ca genes in cerebellar granule neuron precursors, which represent the cellular origin of SHH MB. Our results show that Pik3ca mutations alone are insufficient to cause developmental alterations or to initiate MB. However, they significantly accelerate the growth of Shh MB, induce tumour spread throughout the cerebrospinal fluid, and result in lower survival rates of mice with a double Pik3caH1047R/SmoM2 or Pik3caH1047R/Ptch1 mutation. Therefore, PIK3CA mutations in SHH MB may represent a therapeutic target for first and second line combination treatments.

3.
Sci Rep ; 10(1): 4764, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179801

RESUMO

Prognosis of patients with high-grade aneurysmal subarachnoid hemorrhage (aSAH) is only insufficiently displayed by current standard prognostic scores. This study aims to evaluate the role of pupil status for mortality prediction and provide improved prognostic models. Anonymized data of 477 aSAH patients admitted to our medical center from November 2010 to August 2018 were retrospectively analyzed. Identification of variables independently predicting in-hospital mortality was performed by multivariable logistic regression analysis. Final regression models included Hunt & Hess scale (H&H), pupil status and age or in a simplified variation only H&H and pupil status, leading to the design of novel H&H-Pupil-Age score (HHPA) and simplified H&H-Pupil score (sHHP), respectively. In an external validation cohort of 402 patients, areas under the receiver operating characteristic curves (AUROC) of HHPA (0.841) and sHHP (0.821) were significantly higher than areas of H&H (0.794; p < 0.001) or World Federation of Neurosurgical Societies (WFNS) scale (0.775; p < 0.01). Accordingly, including information about pupil status improves the predictive performance of prognostic scores for in-hospital mortality in patients with aSAH. HHPA and sHHP allow simple, early and detailed prognosis assessment while predictive performance remained strong in an external validation cohort suggesting adequate generalizability and low interrater variability.

4.
Int J Mol Sci ; 21(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178271

RESUMO

Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.

5.
Clin Cancer Res ; 26(11): 2626-2639, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31988196

RESUMO

PURPOSE: Mesenchymal stem cells (MSCs) show an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive glioma. We assessed whether a motile MSC-based local immunomodulation is able to overcome the immunosuppressive glioblastoma microenvironment and to induce an antitumor immune response. EXPERIMENTAL DESIGN: We genetically modified MSCs to coexpress high levels of IL12 and IL7 (MSCIL7/12, Apceth-301). Therapeutic efficacy was assessed in two immunocompetent orthotopic C57BL/6 glioma models using GL261 and CT2A. Immunomodulatory effects were assessed by multicolor flow cytometry to profile immune activation and exhaustion of tumor-infiltrating immune cells. Diversity of the tumor-specific immune response as analyzed using T-cell receptor sequencing. RESULTS: Intratumoral administration of MSCIL7/12 induced significant tumor growth inhibition and remission of established intracranial tumors, as demonstrated by MR imaging. Notably, up to 50% of treated mice survived long-term. Rechallenging of survivors confirmed long-lasting tumor immunity. Local treatment with MSCIL7/12 was well tolerated and led to a significant inversion of the CD4+/CD8+ T-cell ratio with an intricate, predominantly CD8+ effector T-cell-mediated antitumor response. T-cell receptor sequencing demonstrated an increased diversity of TILs in MSCIL7/12-treated mice, indicating a broader tumor-specific immune response with subsequent oligoclonal specification during generation of long-term immunity. CONCLUSIONS: Local MSC-based immunomodulation is able to efficiently alter the immunosuppressive microenvironment in glioblastoma. The long-lasting therapeutic effects warrant a rapid clinical translation of this concept and have led to planning of a phase I/II study of apceth-301 in recurrent glioblastoma.

6.
Oncotarget ; 10(58): 6049-6061, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31692882

RESUMO

Glioblastoma are highly invasive and associated with limited therapeutic options and a grim prognosis. Using stem cells to extend current therapeutic strategies by targeted drug delivery to infiltrated tumors cells is highly attractive. This study analyzes the tumor homing and therapeutic abilities of clinical grade human mesenchymal stem cells (MSCs) in an orthotopic glioblastoma mouse model. Our time course analysis demonstrated that MSCs display a rapid targeted migration to intracerebral U87 glioma xenografts growing in the contralateral hemisphere within the first 48h hours after application as assessed by histology and 7T magnetic resonance imaging. MSCs accumulated predominantly peritumorally but also infiltrated the main tumor mass and targeted distant tumor satellites while no MSCs were found in other regions of the brain. Intratumoral application of MSCs expressing herpes simplex virus thymidine kinase followed by systemic prodrug application of ganciclovir led to a significant tumor growth inhibition of 86% versus the control groups (p<0.05), which translated in a significant prolonged survival time (p<0.05). This study demonstrates that human MSCs generated according to apceth's GMP process from healthy donors are able to target and provide a significant growth inhibition in a glioblastoma model supporting a potential clinical translation.

7.
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.

8.
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.

9.
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.

10.
Neurosurg Rev ; 42(2): 481-488, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29948495

RESUMO

Hyperactive delirium (agitation) is a common complication in patients on intensive care units and can be assessed by the Richmond Agitation and Sedation Scale (RASS) in principle. However, the role of agitation in patients with aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a retrospective analysis to identify risk factors for the development of a hyperactive delirium and its functional consequences for neurological outcome. Three hundred thirty-eight patients with SAH were screened in this study resulting in 212 patients which reached at least once a RASS of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up. We provide four independent risk factors for the development of agitation in SAH patients. Our study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients.


Assuntos
Delírio/etiologia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/psicologia , Agitação Psicomotora/etiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Escala de Resultado de Glasgow , Humanos , Hidrocefalia/complicações , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/cirurgia , Adulto Jovem
11.
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
12.
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
13.
Clin Case Rep ; 6(1): 185-188, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29375861

RESUMO

Grisel's syndrome presents a rare disease. Here, we present a peculiar case of Grisel's syndrome with an unfavorable course developing a basilar impression. This highlights the importance of close clinical and radiological follow-up even in cases where the course seems uncomplicated.

14.
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
15.
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
17.
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
18.
PLoS One ; 11(4): e0153405, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27070421

RESUMO

OBJECTIVE: Meningioma of the cranio-cervical junction is a rare diagnosis and demand a thorough surgical planning as radical excision of these tumors is difficult. In this context recurrence is most likely due to regrowth of residual tumor. The aim of this study was to evaluate the clinical course of patients operated for craniocervical meningioma (CCM) and to investigate the histological features of these tumors and their impact on recurrence rate. METHODS: All patients who were operated for CCM at our institution between 2003 and 2012 were identified. Presenting symptoms, MRI findings, surgical approaches and recurrence rate were reviewed retrospectively using medical charts. Histological features of the included tumors were studied focusing on subtypes and MIB-1 immunoreactivity and compared with MIB-1 immunoreactivity in an age and gender-matched control group of patients with supratentorial meningioma. RESULTS: 18 patients with CCM with a mean age of 56.2 years and median follow-up of 60 months were included in the study. Sensory or motor deficit was the most frequent presenting symptom followed by neck pain and lower cranial nerve palsy. Simpson grade II resection was achieved in 16 patients and Simpson grade III resection in two patients. Mortality, morbidity and recurrence rates were 16.7%, 5.5% and 5.5%, respectively. According to the WHO-grading all were found to be grade I meningiomas. Histological subtypes included meningotheliomatous (10), transitional (2), fibrillar (2), angiomatous (3) and secretory (1) meningioma. The mean MIB-1 labeling index in the study group was significantly higher than in the control group, (7.2% and 3.6%, respectively), p < 0.05. There was no correlation between MIB-1 levels and tumor recurrence. CONCLUSIONS: CCM seems to have a benign character. Despite a significantly higher MIB-1 index, a high rate of recurrence was not observed. Therefore, approaches with high morbidity are not justified. Nevertheless, in view of the challenging approaches with limited access to the lesion, CCM should be considered a distinctive clinical subgroup.


Assuntos
Encéfalo/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Crânio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Organização Mundial da Saúde
19.
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
20.
Neurosurg Focus ; 38(4): E10, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25828486

RESUMO

OBJECT: The surgical management of lesions ventral to the neuraxis at the level of the craniovertebral junction (CVJ) and upper cervical spine is challenging. Here, the authors describe a minimally invasive dorsal approach for small ventrally located intradural lesions at the CVJ as an alternative for the more extensive classic transoral approach or variants of suboccipital approaches. METHODS: Between 2012 and 2014, 6 symptomatic patients with a small lesion of the ventral aspect at the CVJ level were treated using a minimally invasive dorsal approach at the University Medical Center in Hamburg-Eppendorf, Germany. The anatomical distance between the posterior atlantooccipital membrane and the posterior atlantoaxial ligament, as determined by CT images, was assessed in the treated patients and in 100 untreated persons. RESULTS: The authors treated 6 patients (mean age 54.7 years) who had a clinical presentation of mild neurological symptoms that disappeared after resection. Minimally invasive surgical dorsal access was achieved by using tubular systems and using the natural space between the occiput (C-0) and C-1, and in 1 case between C-1 and C-2, without having to remove bony structures. The postoperative course in each of the 6 patients was uneventful. The neuropatho-logical findings confirmed a meningotheliomatous meningioma (WHO Grade I) in 5 cases and an extramedullary cavernous hemangioma in 1 case. MRI confirmed complete resection of all the lesions. The atlantooccipital distances ranged from 3 to 17 mm (mean 8.98 mm) in the supine neutral position, and the atlantoaxial distances ranged from 5 to 17 mm (mean 10.56 mm). There were no significant differences between women and men (atlantooccipital p = 0.14; atlantoaxial p = 0.72). CONCLUSIONS: The results of this study demonstrate that the minimally invasive dorsal approach using the space between C-0 and C-1 or C-1 and C-2 provides direct and sufficient exposure for the safe surgical resection of small ventrally located intradural lesions at the CVJ level while reducing the necessity for musculoskeletal preparation to a minimum.


Assuntos
Articulação Atlantoaxial/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/cirurgia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Coluna Vertebral/cirurgia
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