伴顽固性癫痫的脑肿瘤的病理分析

目的 分析伴顽固性癫痫患者的脑肿瘤病理特点,探讨最适合的手术方式.方法 在符合顽固性癫痫并进行手术治疗的病例中,回顾分析45例病理证实存在脑肿瘤的病例资料.结果 癫痫灶位于额叶8例,颞叶34例,顶枕叶3例;病理证实神经元和混合性神经元-胶质肿瘤35例(78%).WHO Ⅰ级36例,WHO Ⅰ～Ⅱ4例,WHO Ⅱ级5例.术后随访1年以上的42例,全部生存.癫痫发作控制结果 显示Engel Ⅰ级32例(76%),Ⅱ级5例,Ⅲ级4例,Ⅳ级1例.结论 与顽固性癫痫相关的脑肿瘤是一类特殊的病理组群,手术切除包括肿瘤在内的癫痫灶,效果满意.     

导致难治性癫痫的颞叶肿瘤特点分析

目的 分析导致难治性癫痫的颞叶肿瘤的临床特征、病理类型及手术疗效.方法 回顾手术治疗的难治性颞叶癫痫病例,分析其中73例病理证实存在颞叶肿瘤的病例的临床病理特点及手术疗效.结果 术前MRI显示有占位效应的病例23例;占位效应不明显,仅出现局部信号异常的病例50例.病理检查显示最主要的肿瘤类型为混合性胶质-神经元肿瘤59例,其中WHO Ⅰ级63例;行前颞叶切除术的70例,局部病灶切除术的3例.术后1例死亡,余术后随访2～10年,因非肿瘤相关性原因死亡1例,Engel＇s Ⅰ级55例,Ⅱ级9例,Ⅲ级5例,Ⅳ级2例.结论 与难治性颞叶癫痫相关的脑肿瘤是一类特殊的病理组群,表现相对良性的生物学特性,手术切除包括肿瘤在内的癫痫灶效果满意.     

The surgical management of pediatric brain tumors causing epilepsy: consideration of the epileptogenic zone

Objective

Children suffering from epilepsy with suspected low-grade tumors may benefit from a surgical approach that considers the epileptogenic zone, which can be more extensive than the tumor region. This study aimed to determine the prevalence of epilepsy in children undergoing supratentorial tumor resection and the factors predictive of postoperative seizure freedom in children with low-grade tumors.

Methods

Subjects 3 months to 21 years undergoing supratentorial brain tumor resection between 2007 and 2011 were included in this retrospective study. Children with supratentorial, cortically based tumors and a preoperative diagnosis of epilepsy were considered epilepsy surgery candidates. Pre- and postoperative MRI were reviewed and scored for extent of resection, adjacent dysplasia, and remaining abnormal cortex postoperatively.

Results

The prevalence of seizures in all cases of supratentorial tumors was 46/87 (53 %). Eighteen were epilepsy surgery candidates. Eight of 18 (44 %) were seizure-free postoperatively with a mean follow-up of 39 months. Children who were seizure free postoperatively had tried fewer anticonvulsants than those with continued seizures (1.7 v. 2.9, p?=?0.01). Presurgical evaluation was nonstandardized, and a more extensive workup and resection were performed in children who continued to have seizures postoperatively.

Conclusions

All epilepsy surgery candidates had low-grade tumors on histological evaluation, indicating that a surgical approach that takes into consideration the epileptogenic zone is reasonable in this population. Gross total resection should be the goal, with additional attention to resection of the epileptogenic zone when located in the noneloquent cortex.     

Epilepsy in patients with brain tumors and other cancers

Epilepsy is common among patients with supratentorial, especially slow-growing tumors. Several newer antiepileptic drugs have fewer side effects and drug interactions than do older drugs. Seizure control, however, may require complete lesion resection, with or without removal of an additional "epileptogenic zone." Among patients with systemic cancer, parenchymal or leptomeningeal metastases can cause epilepsy, and potentially reversible medical and neurologic perturbations can lead to acute symptomatic seizures.     

Second primary brain tumors following cranial irradiation for pediatric solid brain tumors

Purpose

We describe our institution’s experience with seven patients who developed second brain tumors following cranial irradiation.

Methods

The median age at first irradiation was 8 years (range, 3–20 years). Initial diagnoses were two cases of germinoma, one non-germinomatous germ cell tumor (NGGCT), three cases of medulloblastoma, and one pineal gland tumor (pathology undetermined). All patients received craniospinal irradiation followed by local boost and the median dose to the initial tumor area was 54.0 Gy (range, 49.8–60.6 Gy). Four patients (two medulloblastomas, one germinoma, and one NGGCT) received chemotherapy.

Results

Second brain tumors were diagnosed a median of 114 months (range, 64–203) after initial radiation. Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma. Five patients underwent surgical resection with subsequent radiotherapy. One anaplastic astrocytoma patient received chemotherapy only following stereotactic biopsy. The meningioma patient was alive 32 months after total resection and radiosurgery for subsequent recurrences. Six patients died within 18 months and most deaths were due to disease progression.

Conclusions

Most patients diagnosed with second brain tumors had received high-dose, large-volume radiotherapy with chemotherapy at a young age. Further studies are required to determine the relationship between radiotherapy/chemotherapy and the development of secondary brain tumors.     

Epilepsy surgery after treatment of pediatric malignant brain tumors

Epilepsy surgery is common in the face of benign brain tumors, but rarely for patients with a history of malignant brain tumors. Seizures are a common sequelae in survivors of malignant pediatric brain tumors. Medical management alone may not adequately treat epilepsy, including in this group. We report four cases of patients who previously underwent gross total resection, radiation therapy, and chemotherapy for successful treatment of malignant brain neoplasia, yet suffered from medically intractable seizures. All underwent surgery for treatment of epilepsy with extension of the original resection. Despite the aggressive primary treatment of the neoplasm, and the potential for diffuse cerebral insults, all benefited from focal surgical resection. Aggressive surgical management of intractable epilepsy can be considered in survivors of malignant brain tumors.     

18Fluoroethyl-L-tyrosine-PET in long-term epilepsy associated glioneuronal tumors

Purpose: Long‐term epilepsy associated tumors (LEATs) are a frequent cause of drug‐resistant partial epilepsy. A reliable tumor diagnosis has an important impact on therapeutic strategies and prognosis in patients with epilepsy, but often is difficult by magnetic resonance imaging (MRI) only. Herein we analyzed a large LEAT cohort investigated by ¹⁸fluoroethyl‐l ‐tyrosine–positron emission tomography (FET‐PET). Methods: Thirty‐six patients with chronic partial epilepsy and a LEAT‐suspect MRI lesion were analyzed by FET‐PET using visual inspection and quantitative analysis of standard uptake values (SUV). PET results were correlated with clinical and histopathologic data. Results: FET‐PET study was positive in 22 of 36 analyzed lesions and in 14 of 22 histologically verified LEAT lesions. The precise World Health Organization (WHO) tumoral entity was not predicted by FET‐PET. Notably, FET uptake correlated strikingly with age at epilepsy onset (p = 0.001). Further correlations were seen for age at surgery (p = 0.007) and gadolinium‐contrast enhancement on MRI (p < 0.05). Discussion: FET‐PET is a helpful tool for LEAT diagnosis, particularly when MRI readings are ambiguous. FET uptake, which is likely mediated by the l ‐amino acid transporter (LAT) family, might indicate a principally important biologic property of certain LEATs, since LAT molecules also are involved in cell growth regulation.     

New classification of epilepsy-related neoplasms: The clinical perspective

Neoplastic CNS lesions are a common cause of focal epilepsy refractory to anticonvulsant treatment, i.e. long-term epilepsy-associated tumors (LEATs). Epileptogenic tumors encompass a variety of intriguing lesions, e.g. dysembryoplastic neuroepithelial tumors or gangliogliomas, which differ from more common CNS neoplasms in their clinical context as well as on histopathology. Long-term epilepsy-associated tumor classification is a rapidly evolving issue in surgical neuropathology, with new entities still being elucidated. One major issue to be resolved is the inconsistent tissue criteria applied to LEAT accounting for high diagnostic variability between individual centers and studies, a problem recently leading to a proposal for a new histopathological classification by Blümcke et al. in Acta Neuropathol. 2014; 128: 39–54. While a new approach to tissue diagnosis is appreciated and needed, histomorphological criteria alone will not suffice and we here approach the situation of encountering a neoplastic lesion in an epilepsy patient from a clinical perspective. Clinical scenarios to be supported by an advanced LEAT classification will be illustrated and discussed.     

Finding a better drug for epilepsy: antiinflammatory targets

This monograph summarizes one of the sessions of the XI Workshop on Neurobiology of Epilepsy (WONOEP), and provides a critical review of the current state of the field. Speakers and discussants focused on several broad topics: (1) the coexistence of inflammatory processes encompassing several distinct signal-transduction pathways with the epileptogenic process; (2) evidence for the contribution of specific inflammatory molecules and processes to the onset and progression of epilepsy, as well as to epilepsy-related morbidities including depression; (3) the complexity and intricate cross-talk of the pathways involved in inflammation, and the discrete, often opposite roles of a given mediator in neurons versus other cell types. These complexities highlight the challenges confronting the field as it aims to define inflammatory molecules as promising targets for epilepsy prevention and treatment.     

Optical imaging of human epileptogenic tissues in vitro

Epilepsy is a chronic disorder characterized by abnormal spatiotemporal neural activities. To clarify its physiological mechanisms and associated morphological features, we investigated neuronal activities using the flavoprotein fluorescence imaging technique and histopathological changes in epileptogenic tissue resected from patients with epilepsy. We applied an imaging technique suitable for examining human brain slices, and as a consequence achieved sufficient responses with high reproducibility. Moreover, we detected significant alterations in neuronal morphology associated with the acquired responses. Therefore, this strategy is useful for gaining a better understanding of the pathomechanisms underlying intractable epilepsy.     

Prevention of Epilepsy: Issues and Innovations

Epilepsy is a common brain disease and preventing epilepsy is a very relevant public health concern and an urgent unmet need. Although 40 % of all epilepsy cases are thought to have acquired causes, there is a roadblock for successful prevention. Efforts to protect the brain from epileptogenic insults are severely hampered by our lack of biomarkers to identify the few percent at high risk meriting treatment among those exposed. Preventing brain injury has been moderately effective from around birth to middle age; however, the strategy has failed to stop a substantial increase over the last decades in symptomatic epilepsy in those aged 65 and above. The traditional concept of repurposing anti-seizure drugs used for symptomatic seizure relief to prevent the onset of epilepsy has completely failed up to now. More recently, however, hope is on the horizon with a search for biomarkers and discovery of a new class of agents, called anti-epileptogenic drugs, which were specifically developed for prevention of epilepsy.     

An insight into electrical resistivity of white matter and brain tumors

BackgroundThere is a lack of information regarding electrical properties of white matter and brain tumors.ObjectiveTo investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter.MethodsA bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω1m) were compared between different intracranial tissues and brain tumors.ResultsNinety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω1m) than within peritumoral edema (8.5 ± 1.6 Ω1m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω1m, WHO III:6.3 ± 0.9 Ω1m), enhancing (WHO IV:5 ± 1 Ω1m, metastasis:5.4 ± 1.3 Ω1m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω1m, metastasis:4.3 ± 1.3 Ω1m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively.ConclusionsThe technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors.     

Expression of vascular endothelial growth factor in human brain tumors

Compared to normal brain an increased expression of vascular endothelial growth factor (VEGF) has been reported in many types of brain tumors. However, the numbers of samples analyzed and information about the cellular distribution of VEGF have been limited. Here we used novel monochlonal antibodies against VEGF to analyze, using immunohistochemistry, Western blotting and enzyme-linked immunosorbent assay, its expression in 108 human brain tumors that included astrocytic tumors, meningiomas, pituitary adenomas, primary intracranial germ cell tumors and neuronal tumors. The results showed that 37 of 48 astrocytic tumors (77%) and 15 of 19 meningiomas (79%) were immunoreactive for VEGF, consistent with previous reports. However, in contrast to a previous report that analyzed only VEGF mRNA; all of our 15 pituitary adenomas showed specific immunoreactivity for VEGF. We also extended the studies to previously unanalyzed neoplasms: 13 of 15 primary intracranial germ cell tumors (82%), and 7 of 10 neuronal tumors (70%) were immunoreactive for VEGF. Direct protein analysis by Western blotting confirmed the expression of VEGF in those tumors, and showed differential expression of the isoforms of VEGF protein; a pituitary adenoma expressed both VEGF₁₆₅ and VEGF₁₈₉ proteins, a central neurocytoma expressed only VEGF₁₆₅, while an immature teratoma expressed only VEGF₁₈₉. The data herein show that VEGF is expressed in a wide spectrum of brain tumors and suggest differences among tumor entities in the mechanisms of VEGF up-regulation as well as their employment of distinct VEGF isoforms for neovascularization. Received: 26 January 1998 / Revised, accepted: 15 April 1998     

Distribution of immunoreactive S-100 protein in pediatric brain tumors

The distribution of S-100 proteins was examined in 98 pediatric brain neoplasms with rabbit antiserum to S-100 protein, utilizing the peroxidase-antiperoxidase (PAP) immunohistochemical technique. Positive cytoplasmic immunoreactivity was present in 22 of 24 astrocytomas, both oligodendrogliomas, eight of 13 ependymomas, all 11 choroid plexus tumors, all nine schwannomas, two of six meningiomas, and both meningeal melanomas. Mixed cytoplasmic immunoreactivity was present in both gangliogliomas, all seven craniopharyngiomas, and the only hemangioblastoma. No cytoplasmic immunoreactivity was found in primitive neuroectodermal tumors or germinoma. Nuclear immunoreactivity was present in some cases. Because of the broad spectrum of apparent immunoreactivity with S-100 antiserum, S-100 protein cannot be used as a specific marker of glial or Schwann cell tumors.     

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the tumors of central nervous system (CNS)

Malignant neoplasms of the central nervous system (CNS) account for about 1.3 % of all tumors and 2.2 % of all cancer-related deaths. CNS tumors consist of heterogeneous group of neoplasms, including different variants of primary brain tumors and metastatic neoplasms. Advanced imaging techniques improved the neuroradiological diagnostic accuracy, although these methods are not specific enough for differentiation of CNS tumors, thus new approaches of patients’ diagnosis are critically needed. The best solution for the diagnosis of patients with CNS tumors could be easily available biomarkers, which could be useful for the management of CNS neoplasms. Biomarkers should facilitate the diagnosis, monitor of treatment response and assess the prognosis of patients’ survival. Currently, except for rare germ cell tumors, there is a lack of knowledge on biochemical markers for CNS neoplasms. Therefore, in this paper we summarized and referred a number of comprehensive reviews concerning the role of matrix metalloproteinases (MMPs) and their tissue inhibitors in tumor progression, including CNS neoplasms as well as described the general biochemistry of MMPs and their tissue inhibitors. Moreover, we presented the wide variety of previous findings, where authors suggested the significance of selected MMPs and their tissue inhibitors as potential biomarkers of human tumors, including CNS tumors. However, future investigations are needed to be performed before some of these enzymes could finally be used as biomarkers of specific types of CNS neoplasms.     

Pediatric brain tumors and epilepsy

Seizures are a common complication of pediatric brain tumors and their treatment. This article reviews the epidemiology, evaluation, and treatment of seizures in children with brain tumors. Seizures in known brain tumor patients may signify tumor progression or recurrence, or treatment-related brain damage, as well as other causes, including low drug levels and metabolic disturbances. Careful selection of antiepileptic medications is needed in this population. There are advantages to nonenzyme-inducing antiepileptic drugs including valproic acid, which has potential antitumoral properties as a histone deacetylase inhibitor. Tumor surgery cures many cases of pediatric tumor-associated seizures, and some children are controlled with anti-epileptic medication, however additional epilepsy surgery may be needed for refractory cases.     

Pediatric brain tumors in Nigeria: clinical profile, management strategies, and outcome

Introduction

Although modern neuroimaging has facilitated early care of brain tumors in children worldwide, there are, however, few published reports on clinical profile, treatment, and outcome of brain tumors in children from our subregion.

Purpose

We aimed to retrospectively study the clinical profile and outcome of pediatric brain tumors in a tertiary referral center from a developing country.

Methods

Forty pediatric patients with histologically verified brain tumors managed by the authors over a 13-year period (May1994–April 2006) were studied. Patients' data from clinical, radiological, and pathology records were analyzed using the statistical package for social sciences version 16.

Results

The mean age was 9.75 years (range 1–15 years). Twenty-two males, 18 females. Common presenting symptoms were headaches (23 patients, 57.5 %) and seizures (15 patients, 37.5 %). Hyperreflexia (72.5 %) and focal motor deficits (62.5 %) were the most common neurologic signs. The mean interval from onset of symptoms to neurosurgical diagnosis was 13.4 months (95 % CI). All patients had tumor resection, while 11 (27.5 %) patients received adjuvant radiotherapy. Hydrocephalus occurred in 19 (47.5 %) patients and was associated with early presentation (X²?=?10.65, p?<?0.01). Low-grade astrocytoma (25 %) and medulloblastoma (25 %) were the most common tumors. Survival at 1 and 5 years were 56 and 47 %, respectively.

Conclusion

Focal motor signs and elevated intracranial pressure are the salient presenting features of brain tumors in children seen in Nigeria. Those of them with hydrocephalus are likely to present early. The outcome for pediatric brain tumors remains poor.     

Nitric oxide synthase expression and enzymatic activity in human brain tumors

Nitric oxide (NO) is synthesized by NO synthases (NOS), existing in 3 isoforms. NO influences a great variety of vital functions including vascular tone and neurotransmission. Under conditions of excessive formation, NO emerges as an important mediator of neurotoxicity in a variety of disorders of the central nervous system (CNS). Inhibitors of NOS are available that may modify the activity of all isoforms, which may be of clinical relevance. The expression of the 3 NOS isoforms nNOS, iNOS and eNOS and NOS enzymatic activity was examined in 40 patients with primary CNS tumors (gliomas WHO grades I - IV and meningeomas WHO grades I - III) and in 13 patients with metastases from adenocarcinomas or malignant melanomas. A polyclonal antibody directed against nNOS and monoclonal antibodies directed against iNOS and eNOS were used for immunohistochemical staining. NOS enzymatic activity, measured by labeled arginine to citrulline conversion, was assessed in tissue specimens obtained from the same tumors. NOS data were compared with clinical variables and the degree of edema as judged from MR scanning. nNOS expression was increased in tumor cells of glial neoplasms and most pronounced in high-grade tumors, WHO grades III and IV, and in the carcinoma and melanoma metastases. Low-grade gliomas, WHO grades I and II and meningeomas expressed no or only little nNOS. iNOS was only expressed in a few tumors. eNOS was expressed sporadically in the tumor cells while the expression was increased in vascular endothelial cells in both the tumor itself and the peritumoral area of glial neoplasms, and in metastases. eNOS expression was sporadic in endothelial cells of meningeomas. NOS enzymatic activities were heterogeneous among tumor types (0 - 13.8 pmol/min/mg of protein) without correlation to the NOS expression found by immunohistochemical techniques. Likewise, NOS activity and expression was not correlated to the clinical scores or brain edema. In conclusion, nNOS expression may be a putative useful indicator of brain tumor differentiation and malignancy. The enhanced expression of eNOS in vascular endothelial cells of glial neoplasms and metastases raises the possibility that NO production in tumor endothelial cells may contribute to tumor blood flow regulation and possibly brain edema.     

The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy

Epilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex; Greenwich Biosciences) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.