We report the clinical case of a 43year old Italian woman and her family with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. PLOSL is a unique disease clinically characterized by a progressive presenile frontal-lobe dementia and multiple cystic bone lesions, typically leading to fractures of the limbs in the third decade of life. This rare recessively inherited disease is caused by mutations in one of two genes encoding different subunits of a receptor signalling complex, TYROBP and TREM2. In the present case fractures after microtrauma were not diagnosed, despite a radiological demonstration of the characteristic bone lesions in PLOSL. Further investigation led to the same diagnosis in her brother, with similar clinical presentation and the same mutation. Therefore a diagnosis of PLOSL should be considered in cases of presenile frontal-lobe dementia, even if the hallmark of pathological fractures is absent.
Bevacizumab has been introduced in the management of high-grade gliomas after preliminary studies that showed an acceptable safety and a marked increase in clinico-radiological responses in comparison with second-line chemotherapy. The objective is to synthetically review the present use of bevacizumab--alone or in combination--in the context of recurrent high-grade glioma and highlight the future developments. The methodology of this study is to analyse and discuss relevant literature studies using bevacizumab in recurrent high-grade glioma. Bevacizumab may be used as single-agent therapy in recurrent high-grade glioma, with good clinico-radiological responses having little effect on survival. The open questions and developments include new MRI criteria for evaluation of response to anti-angiogenic agents, the identification of putative factors predicting response/failure of bevacizumab and the introduction of bevacizumab in first-line management of high-grade glioma.
Quality of life and well-being in caregivers are usually partly neglected since all attention is focused on patients and the way they react to the illness. Carers also usually neglect their own needs, especially when the illness of the patient is as complex as a brain tumor. The aim of this study is to investigate how caregivers deal with a diagnosis of brain tumor in their relatives and how they manage their quality of life and psychosocial well-being. One hundred primary caregivers of patients with brain tumors were interviewed and were asked to fill in self-administered questionnaires detecting multidimensional levels of quality of life, anxiety, depression, and psychosocial reaction to the patients illness. Data were related with some functional and psychosocial information collected about the patients disease. Caregivers try to react to the illness of their relatives by mobilizing their physical reaction and growing their self-esteem, but they live with a clinically significant impairment of their quality of life, and experience a deep level of anxiety and depression. The caregivers burden appears mainly in their ability to provide care and in financial strain. The length of disease and the functional status of patients significantly influence caregivers psychosocial well-being. Despite the appearance they want to show their affected relatives, caregivers suffer from deep limitation in their quality of life. The relevance of caregivers burden suggests the importance of psychological support to improve reaction to the illness.
Despite advances in therapies that offer improved survival rates, clinical course of brain tumours leads to a progressive functional deterioration in patients with modifications in their psychological reaction to the disease. Patients with brain tumours are rarely assessed for quality of life and psychological variables, and even fewer studies have assessed patients who have experienced a recurrence of brain tumours. Therefore, the aim of the present study is to investigate the patients with recurrent brain tumours and their reaction to the illness.
It has been demonstrated that sagopilone (ZK-EPO) has antitumor activity in human orthotopic glioma models in vitro and in vivo. The objective of this study was to evaluate the safety and efficacy of ZK-EPO in patients with pretreated, recurrent malignant gliomas. Fifteen patients with recurrent malignant gliomas who had received prior surgery, radiotherapy, and >or=2 lines of alkylating chemotherapy were recruited. ZK-EPO (16 mg/m(2)) was administered iv for 3 h every 21 days. The primary end point was six months progression-free survival (PFS-6); secondary end points were safety, toxicity, response rate, and median time to progression (TTP). Magnetic resonance imaging (MRI) evaluations were performed every two cycles and toxicity was evaluated at each cycle using common terminology criteria for adverse events (CTCAE 3.0). A median of four cycles was administered. The median TTP was 13 weeks. PFS-6 was achieved in five patients (33%), three with glioblastoma multiforme and two with anaplastic astrocytoma. The most common treatment-related adverse event was neuropathy, which occurred in 6/15 patients. ZK-EPO had an acceptable safety profile and clinically relevant activity in patients with pretreated, recurrent malignant gliomas.
Epilepsy occurs in glioma, especially in low-grade glioma (LGG), but also in glioblastoma (GBM). In about 20 % of patients pharmacological treatment with anti-epileptic drugs (AEDs) fails. Refractory epilepsy is a multifactorial phenomenon not yet completely understood. The multidrug resistance phenotype was initially associated to P-glycoprotein (Pgp), an ATP-dependent transporter belonging to the same superfamily of multidrug resistance-associated proteins (MRPs). Glutathione-S-transferase-? (GST-?) is also involved in refractory epilepsy. In the present work we investigated the expression of Pgp, MRP1, MRP3 and GST-? in surgical specimens obtained from 35 patients with glioma and epilepsy. We observed MRP1 expression in tumor and endothelial cells (EC), MRP3 and Pgp expression mainly in ECs and GST-? predominantly in tumor cells (TC). MRP1 and MRP3 were more expressed in high grade glioma (HGG) than in LGG. In 6 cases we could compare tumor and periphery detecting the same MRP1 and Pgp expression, while MRP3 was mainly expressed in the tumor. We observed a trend of a better outcome in seizure control associated with a lower expression of MRP1 and MRP3. MRP3 was statistically more expressed in TCs of HGG than LGG (p = 0.0401) and more expressed in tumor than in periphery, in agreement with recent works that identify MRP3 as a potential target in GBM. Moreover, MRP3 was investigated in association with refractory epilepsy for the first time in our study and it was less expressed in patients with complete response to AEDs (p = 0.0550). Our preliminary data show an association between multidrug resistance transporters and refractory epilepsy in glioma.
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