Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastomas

We monitored the expression of glycan-binding sites on a panel of 10 biotinylated neoglycoconjugates by means of quantitative computer-assisted microscopy to further study the molecular mechanisms in the extensive infiltration of the surrounding brain parenchyma by most astrocytic tumors. Three distinct histological compartments were analyzed for each of the 108 astrocytic tumors (15 pilocytic astrocytomas (WHO grade I), 25 astrocytomas (WHO grade II), 30 anaplastic astrocytomas (WHO grade III), and 38 glioblastomas (WHO grade IV) included in our series. These compartments were tumors (nonperivascular tumor astrocytes), perivascular tumor astrocytes, and blood vessel walls. Clear differences were observed between the pilocytic and the diffuse astrocytic tumors. Furthermore, malignant progression in the latter category was paralleled by a decrease in cells' ability to bind distinct sugar epitopes, especially the D-GalNAc(alpha1-3)-D-GalNAc-beta1-R determinant of the Forssman pentasaccharide in tumors, the alpha-L-fucose in perivascular tumor areas, and the beta-D-glucose in tumor vessel walls. Markedly, the level of binding site expression for alpha-D-mannose decreased in the tumors, the perivascular tumor areas, and the vessel walls. These glycohistochemical results imply the functional relevance of protein-carbohydrate interactions in this tumor system.     

Perfusion-diffusion 1H spectroscopy: role in the diagnosis and follow-up of supratentorial brain tumours in adults

INTRODUCTION: In a few years, magnetic resonance imaging (MRI) has evolved from a morphology-based examination to one that encompasses metabolism and function. STATE OF ART: MRI is a well-established tool for the initial evaluation of brain tumors, but conventional MR sequences have some limitations. Conventional MRI is unable to distinguish high-grade glioma from metastasis and abscess, to define precisely the histopathological grade of gliomas, to determine exactly the limits of tumor extension, to characterize meningeal tumors. Differentiation of tumor recurrence from treatment-related changes may be difficult with standard MR imaging because the interpretation is essentially based on volume analysis. PERSPECTIVES: 1H Spectroscopy, diffusion and perfusion imaging become possible with the development of MR imagers and can be routinely performed in clinical settings. They give complementary information about tumor metabolism and vascularity and allow a better analysis of post-treatment modifications. Functional and metabolic explorations should be used to characterize brain tumors.     

Low-grade glioma: Supratentorial astrocytoma,oligodendroglioma, and oligoastrocytoma in adults

Low-grade glioma is not a single diagnosis but a category of biologically diverse neoplasms. They are indolent, progressive, and, following anaplastic transformation, invariably fatal. Neuro-oncologists have not established a treatment standard for these tumors. However, it is clear that "low-grade" is not synonymous with "benign," and treatment is required sometime in the course of the disease. Previously, achieving a consensus had been limited by a lack of class I evidence. Physicians treated patients based on retrospective series and personal experience. Currently, results from prospective clinical trials are becoming available. These studies have provided data that may serve as treatment guidelines. Additional results regarding the identification of prognostic variables have raised more questions to be answered. Attention is now directed to the importance of translational research to better define these neoplasms. In the future, it will be necessary to distinguish among low-grade gliomas and identify therapies that may differ between them.     

Low-grade gliomas in adults

PURPOSE OF REVIEW: This paper aims to summarize the current thinking about the management of adult supratentorial low-grade gliomas. These are well differentiated primary brain tumours that typically develop in young adults. Their biological behaviour is poorly understood but the majority of these tumours grow slowly, infiltrate surrounding normal brain, and show an intrinsic tendency to undergo malignant transformation to high-grade gliomas. Surgery and radiotherapy are the main treatment options, but their precise role and timing are controversial. RECENT FINDINGS: Resective surgery is at best regarded as a practice option because there is a paucity of good quality evidence to show that extent of resection correlates with survival. Radiotherapy prolongs progression-free survival but not overall survival and may lead to long-term cognitive deficits, although not as widespread as had previously been thought. A minority of tumours with oligodendroglial differentiation are chemosensitive and this correlates with allelic loss of chromosomes 1p and 19q. New imaging and molecular techniques, in particular gene microarray studies, are providing more information about these tumours, although they have yet to have a significant impact on clinical management. SUMMARY: The best management of low-grade gliomas is still unknown but advances in molecular genetics and imaging are improving our ability to prognosticate and follow the natural history of these tumours.     

First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas

At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.     

Cystic cerebral astrocytomas in infancy and childhood: long-term results

24 cases of cystic cerebral astrocytoma represent 11% of 217 supratentorial tumors of the pediatric age group operated. Both macro- and microscopically, such tumors resembled in most cases the well-known cerebellar astrocytoma, presenting as a large cyst with a mural nodule with the pattern of a pilocytic astrocytoma (i.e. spongioblastoma of the German school). The preferential site of incidence was the temporal lobe and the age peaks were of 7 and 16 years without sex prevalence. The surgical technique consisted in the extirpation of the mural nodule, preceded by emptying the cyst, followed by opening the contiguous ventricular wall. The extirpation was partial in one-third of the cases of whom the minority underwent radiotherapy. 1 patient died after the operation while 2 others died from tumor recurrence after 3 and 4 years, respectively, both being mixed tumors (oligoastrocytoma) that were irradiated postoperatively. The follow-up ranged from 10 to 29 years in 70% of the cases. The long-term functional results of the available 17 patients are as follows: good (perfectly well), 12 cases (70%); fair (minor troubles), 5 cases (30%). 3 of the 5 cases with a fair result all had a partial resection.     

Very long-term follow-up of adults treated in infancy for hydrocephalus

Purpose  

The purpose of this study is to perform a population-based, very long-term follow-up of adults who had been shunt treated for hydrocephalus in infancy.     

Fatigue at long-term follow-up in young adults with cerebral infarction

BACKGROUND: To study the impact of fatigue in young ischaemic stroke patients. METHODS: The Fatigue Severity Scale score was obtained in 192 patients (mean time 6.0 years after the stroke) and 212 controls. RESULTS: Fatigue was associated with cerebral infarction in a multivariate analysis of patients and controls (p = 0.002). Fatigue was independently associated with unfavourable functional outcome (p = 0.001), depression (p < 0.001), and basilar artery infarction through interaction with the modified Rankin Scale score (p = 0.047) in patients. CONCLUSION: Fatigue is frequent in young adults with cerebral infarction. Stroke-related factors independently associated with fatigue include functional outcome. Stroke location may influence fatigue.     

Cerebellar astrocytomas in children and young adults.

A clinical and pathological review of 43 cases of cerebellar astrocytomas in children and young adults was undertaken. Thirty-one of the 36 surviving patients were examined by computed tomography. Twelve patients with asymptomatic tumour were detected. Histology was necessary to identify the higher risk "diffuse" group, but no histological features helped to identify tumours liable to recur. Improvements in the prognosis may occur with long term CT scanning.     

Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study

Purpose: To evaluate the long‐term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE). Methods: This phase III, open‐label, long‐term, follow‐up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic–clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000–4,000 mg/day; 20–80 mg/kg/day for children/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention‐to‐treat (ITT) population, N = 217] and subpopulations with tonic–clonic (n = 152), myoclonic (n = 121), and/or absence (n = 70) seizures at baseline. Key Findings: One hundred twenty‐five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg/day. Median (Q1–Q3) exposure to LEV was 2.1 (1.5–2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124/217, 57.1%) or ≥2 (92/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of ≥6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of ≥6 months from tonic–clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment‐emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16/217, 7.4%), insomnia (9/217, 4.1%), nervousness (8/217, 3.7%), and anxiety (7/217, 3.2%). Significance: Adjunctive LEV (range 1,000–4,000 mg/day) demonstrated efficacy as a long‐term treatment for primary generalized seizures in children, adolescents, and adults with IGE, and was well tolerated.     

幕上星形细胞瘤的凋亡及相关基因p53、bcl—2的表达

目的 探讨幕上星形细胞瘤的细胞凋亡以及p53、bcl-2在凋亡中的意义。方法 免疫组化TUNEL法检测细胞凋亡,SP法检测p53、bcl-2,实验数据由SPSS软件包分析处理。结果 细胞凋亡指数（AI）随着肿瘤级别的增高而增加,各级别肿瘤间AI的差异均有显著性意义（P＜0．01）;死亡组与存活组的AI的差异有显著性意义（P＜0．01）,AI＞0．5％组与AI＜0．5％组的术后1年生存率的差异有显著性意义（P＜0．05）;AI／MI（分裂指数）在高、低级别的星形细胞瘤中的差异有显著性意义（P＜0．05）。p53阳性组与p53阴性组的AI、MI术后1年生存率的差异均有显著性意义（均P＜0．05）。bcl-2阳性组与阴性组的AI、MI、预后均无统计学意义（均P＞0．05）。多因素logistic回归分析年龄分组、AI、AI／MI、放疗均与预后优劣相关。结论 AI可以作为提示预后的指标,并对判断幕上星形细胞瘤的生物学行为及肿瘤分级有指导意义;AI／MI值越小,肿瘤的恶性转化能力越强,预后越差;p53过度表达提示肿瘤恶性程度高、预后差;AI＜0．5％、AI／MI值大的、年龄较轻的、术后放疗病人预后较好。     

Spinal cord astrocytomas: long-term results comparing treatments in children

Technology enabling radical resection has expanded treatment options for children with spinal cord astrocytomas. Comparison of long-term survival and neurological function after complete tumor removal with more conservative treatment may determine whether radical surgery can improve outcome in well-differentiated and anaplastic spinal cord astrocytomas. In all, 18 children with spinal cord astrocytomas were initially treated between 1976 and 1992 with biopsy in 6, subtotal removal in 7, and complete resection in 5. Seven had anaplastic tumors. Nine children treated before 1988 received radiotherapy. Survival after a median follow-up of 11 years was 82% (9/11). Five patients with anaplastic tumors are alive between 12 and 18 years after treatment. No patient relapsed after total resection, whereas more than two-thirds treated with other than complete resection relapsed within 3 years (P=0.029). All but 1 patient with symptomatic relapse received radiotherapy (P=0.059). Magnetic resonance imaging more than 3 years postoperatively showed no recurrences in 13 of the 15 survivors and asymptomatic progression in the other 2. Although excellent long-term survival was seen, frequent relapse was associated with either incomplete resection or radiotherapy. Prolonged relapse-free survival was observed in all patients treated with complete resection, including 3 with anaplastic tumors. Received: 31 January 1997     

Mild depression in young adults with cerebral infarction at long-term follow-up: A population-based study

We sought to evaluate the prevalence of and risk factors for post-stroke depression (PSD) at long-term follow-up in young adults aged 15-49 years with first-ever cerebral infarction in a population-based study. Scores on Montgomery-Asberg Depression Rating Scale (MADRS) were obtained at follow-up (mean time 6.0 years after the stroke) and analysed in subgroups. MADRS scores were obtained in 196 of 209 surviving patients. PSD (MADRS>or=7) was detected in 56 patients (28.6%). None had severe PSD. Alcoholism (P=0.006), depressive symptoms any time before the index stroke (P=0.016), and severe neurological deficits on admission for the index stroke (P=0.043) were independently associated with PSD. PSD seems milder in young ischaemic stroke patients compared with older patients. Alcoholism, depression any time before the index stroke, and severity of neurological deficits on admission for the stroke increased the risk of developing PSD in the long run.     

Very long-term follow-up of cognitive function in adults treated in infancy for hydrocephalus

Purpose  

The aim was to investigate the very long-term cognitive outcome in adults who had been shunt treated for hydrocephalus during their first year of life.     

Joubert syndrome: long-term follow-up

Twenty-nine patients (16 males, 13 females) with Joubert syndrome were identified from ophthalmology, neurology, and genetic databases covering a 15-year period at Great Ormond Street Hospital, London. Criteria for diagnosis included absent or markedly hypoplastic cerebellar vermis, abnormal eye movements, and developmental delay. Five patients had died. Scans and notes were available for 22 patients, and 18 cases were clinically reviewed. The median age was 10 years 10 months (range 3mo to 19y) and the median follow-up was 8 years 5 months (range 3mo to 19y, with one new patient seen at 3mo of age). Cerebellar vermis hypoplasia/aplasia with 'molar tooth sign' in the axial plane was present in 22 of 22 patients, coloboma in 6 of 22, and polydactyly in 6 of 22. In the 18 clinically reviewed, apnoea occurred in 13 patients. Five had renal problems with cysts and 4 of 5 had abnormal electroretinograms (ERGs). Visual electrophysiology was abnormal in 14 of 18 patients, and in 6 there was evidence of deterioration in the ERG. Blood investigations of organic acids, phytanic acid, very-long-chain fatty acid, and transferrin were normal in 12 patients tested. Developmental assessment showed that 6 of 15 patients aged more than 5 years were at mainstream school, and 12 of 18 had started walking between 22 months and 10 years. Speech difficulties and behavioural problems were prominent.     

Landau-Kleffner syndrome: long-term follow-up

Purpose

Landau–Kleffner syndrome (LKS) is a rare entity characterized by epilepsy and aphasia. It occurs in previously normal children, usually between three and seven years of age. The long-term outcome of LKS is not completely clear. The aim of this study is to verify the long-term follow-up of a group of patients with LKS, focusing on clinical and electroencephalographic (EEG) aspects, and quality of life. Methods: This was a transversal study. Between November 2006 and April 2007 seven patients with previous diagnosis of LKS were interviewed. They had had a follow-up of three to 16 years after their disease onset. They were all males between the ages of eight and 27 years old. All patients had normal MRI. Parents and/or patients were interviewed by one of the authors using a structured questionnaire. The Vineland Adaptive Behavior Scales, the Conner’s Rating Scales – Revised, and Short-Form Health Survey (SF 36) were used. Each patient had a prolonged interictal EEG recording. All patients had normal MRI. Results: The present investigation revealed that two patients still have seizures several years after epilepsy onset. One patient had total and three others had partial remission of language disturbance, while three patients still have aphasia and verbal auditory agnosia. With respect to quality of life, only one of our patients has a normal life at present. The remaining six patients with some sort of limitation consider the aphasia/agnosia to be the main difficulty in their lives. Five patients have normal EEGs. Conclusions: The long-term follow-up of patients with LKS shows that epilepsy and EEG abnormalities do not always disappear. Language disturbances tend to persist in most patients. The age of onset of language dysfunction does not seem to correlate with the prognosis for recovery of language function. Patients with LKS have an overall poor quality of life, mostly due to language difficulties.     

Treatment and survival of supratentorial and posterior fossa ependymomas in adults

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan–Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3 years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p < 0.0001), high tumor grade (HR 1.82, p = 0.005), and large tumor size (HR 1.66, p = 0.008) were associated with poor survival. Females compared to males (HR 0.67, p = 0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p = 0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.