Fourth ventricle rosette-forming glioneuronal tumour in children: an unusual presentation in an 8-year-old patient, discussion and review of the literature

Introduction

Rosette-forming glioneuronal tumour of the fourth ventricle is a rarely described entity. While usually having an indolent course and hence classified as a WHO grade 1 tumour, the precise characteristics and risk of recurrence of this tumour are still unknown. In addition, the preferred treatment modality remains unclear.

Discussion

We present a case of an 8-year old with an early recurrence of 9 months after undergoing a sub-total resection of her tumour. Following further resection, there was no tumour present on the 3-month follow-up. In order to better characterise this tumour entity, we performed a review of the available literature on the subject. We found that it mainly affected young adults and had a female predominance. While initially these tumours were described in the fourth ventricle, the current literature suggests that they may be found in a larger variety of sites within the brain and spinal cord. There are several reports of recurrence occurring between 9 months and 10 years following surgery. There is as yet no feature of the tumour that appears to predict the risk of recurrence.

Conclusion

This phenomenon warrants further examination to discover if there is a sub-section of tumours that is likely to recur, and until this is established, all patients should be followed up at regular intervals.     

PACAP promotes neural stem cell proliferation in adult mouse brain

In recent years, it has become evident that neural stem cells in the adult mammalian brain continuously generate new neurons, mainly in the hippocampus and olfactory bulb. Although different growth factors have been shown to stimulate neurogenesis in the adult brain, very little is known about the role of neuropeptides in this process. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic effects acting through three receptors to which it has high affinity, namely, PACAP receptor 1 (PAC1), vasoactive intestinal peptide (VIP) receptor 1, and VIP receptor 2. We show that PAC1 is expressed in the neurogenic regions of the adult mouse brain, namely the ventricular zone of the lateral ventricle and the hippocampal dentate gyrus. Cultured neural stem cells isolated from the lateral ventricle wall of adult mice express PAC1 and proliferate in vitro in response to two PAC1 agonists, PACAP and Maxadilan, but not VIP at physiologic concentrations, indicating PAC1 as a mediator of neural stem cell proliferation. Pharmacologic and biochemical characterization of PACAP-induced neural stem cell proliferation revealed the protein kinase C pathway as the principal signaling pathway, whereas addition of epidermal growth factor synergistically enhanced the proliferating effect of PACAP. Further in vitro characterization of the effect of PACAP on neural stem cells showed PACAP capable of stimulating ex novo in vitro formation of multipotent neurospheres with the capacity to generate both neuronal and glial cells. Finally, intracerebroventricular infusion of PACAP increases cell proliferation in the ventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus. We conclude that PACAP, through PAC1, is a potent mediator of adult neural stem cell proliferation.     

Measuring stigma in children with epilepsy and their parents: instrument development and testing

PURPOSE: The goal of this work is to describe psychometric properties of two scales measuring perceived stigma in children with epilepsy and their parents. METHODS: Data were collected for the parent scale in two samples: parents of 173 children with epilepsy and of 224 children with new-onset seizures. The child scale was tested in the chronic sample. Content validity, internal consistency reliability, and construct validity were tested. RESULTS: Both scales had strong internal consistency reliability and construct validity. Higher scores were associated with greater seizure severity scores. In the parent scale, lower scores were associated with more positive mood, less worry, and more family leisure activities. In the child scale, higher scores were correlated with more negative attitude, greater worry, poorer self-concept, and more depression symptoms. CONCLUSIONS: Both scales were found to have strong psychometric properties. They are short, and items are easy to understand. These scales have potential for use in research and in the clinical setting to measure stigma.     

The toppler mouse: a novel mutant exhibiting loss of Purkinje cells

We describe the genetic and neurological features of toppler, a spontaneous autosomal mutation that appeared in a colony of FVB/N mice and that manifests as severe ataxia appearing at around 12 days of age, worsening with age. The lifespan of affected mice is 8-12 months, with occasional mice living longer. Both homozygous males and females are fertile, and females are able to nurture litters. Histological examination of brain revealed no striking abnormalities other than the loss of cerebellar Purkinje cells. The toppler mutation was mapped to mouse chromosome 8, and to assess whether it was novel or a recurrence of a previously described chromosome 8 mouse mutant, toppler mice were crossed with the nervous and tottering mouse mutants. These studies demonstrate that toppler is a unique mouse mutation. Purkinje cell abnormalities in toppler mice were obvious around postnatal day (P) 14, i.e., toppler Purkinje cells already exhibited abnormal morphology. Staining for calbindin, a calcium binding protein enriched in Purkinje cells, showed altered dendritic morphology. Between P14 and P30, dramatic Purkinje cell loss occurred, although there were differences in the degree of Purkinje cell loss in each lobule. At P30, the surviving Purkinje cells expressed zebrin II. From P30 through 6 months, many of the remaining Purkinje cells gradually degenerated. Purkinje cell loss was analyzed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), and Purkinje cells were TUNEL-positive most abundantly at P21. In addition, Bergmann glia were TUNEL positive at P21, and they expressed activated caspase-3 at earlier time points. Interestingly, despite the apparent death of some Bergmann glia, there was up-regulation of glial fibrillary acidic protein, expressed in astrocytes as well as Bergmann glia. Given the changes in both Purkinje cells and glia in toppler cerebellum, this may be a very useful model in which to investigate the developmental interaction of Purkinje cells and Bergmann glia.     

Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible

Acute stress suppresses new cell birth in the hippocampus in several species. Relatively little is known, however, on how chronic stress affects the turnover, i.e. proliferation and apoptosis, of the rat dentate gyrus (DG) cells, and whether the stress effects are lasting. We investigated how 3 weeks of chronic unpredictable stress would influence the structural dynamic plasticity of the rat DG, and studied newborn cell proliferation, survival, apoptosis, volume and cell number in 10-week-old animals. To study lasting effects, another group of animals was allowed to recover for 3 weeks. Based on two independent parameters, bromodeoxyuridine (BrdU) and Ki-67 immunocytochemistry, our results show that both chronic and acute stress decrease new cell proliferation rate. The reduced proliferation after acute stress normalized within 24 h. Interestingly, chronically stressed animals showed recovery after 3 weeks, albeit with still fewer proliferating cells than controls. Apoptosis, by contrast, increased after acute but decreased after chronic stress. These results demonstrate that, although chronic stress suppresses proliferation and apoptosis, 3 weeks of recovery again normalized most of these alterations. This may have important implications for our understanding of the reversibility of stress-related hippocampal volume changes, such as occur, for example, in depression.     

A comparison of physiological variables in aged and young women during and following submaximal exercise

Previously, we have examined how aging affects the physiological responses of men to endurance exercise. In the present investigation, we aimed to extend our assessment of the influence of aging on exercise‐induced responses by focusing on women. Ten young (20.3 ± 0.3 years; mean ± SE) and 10 aged (75.5 ± 1.2 years) women performed 30 min of cycling at 60–65% of their predetermined peak oxygen uptake. Data for respiratory exchange ratio (RER), heart rate, blood pressure, rectal temperature, and plasma metabolites were collected before exercise, at the 15th and 30th min of exercise, and at 5 and 15 min postexercise. A two‐way, repeated measures ANOVA with main effects of age and time was conducted on each variable. Our findings showed that age affected exercise‐induced responses of each variable quantified. Although RER, heart rate, temperature, and lactate were significantly (P < 0.05) higher among young women, blood pressure and glucose values were greater among aged women. Moreover, unlike previous results noted among men where age‐related differences primarily occurred during postexercise recovery, in women the effect of aging was detected during exercise itself. The data presented here indicate that aging impacts physiological responses of women to prolonged endurance exercise even when relative intensity (% of peak oxygen uptake) is held constant. Combined with our earlier study on men, these findings suggest that gender interacts with aging to determine whether age‐related differences are manifested during exercise itself, or during postexercise recovery. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.     

Skin immune surveillance by T cells—A new order?

Although studies of the skin have provided fundamental models for innate and adaptive immune surveillance of body surfaces, there remains relatively little understanding of the role that epithelial cells play in sensing infection and/or organ dysfunction, and the pathways available to them to communicate with local and systemic immune cells. In particular, evidence is emerging for a novel stress response initiated by local lymphocytes, rather than dendritic cells, and based on their recognition of epithelial stress-induced antigens. Its consequences are to sustain tissue integrity by providing immunoprotection and novel modes of immunoregulation, whereas its dysregulation may promote body surface immunopathologies.     

Screening HIV-infected patients for non-AIDS-defining malignancies

The use of antiretroviral therapy has reduced mortality and shifted the spectrum of malignancies affecting people living with HIV/AIDS (PLWH). We review guidelines and evidence for screening PLWH for non-AIDS-defining malignancies as compared with the general population. Cervical cancer screening clearly differs for HIV-seropositive women, with two Pap tests 6 months apart in the first year and then annually if normal. The role of cervical human papillomavirus screening has not yet been defined in HIV-seropositive women. Anal cancer screening consists of an annual digital rectal examination, and some (but not all) guidelines also recommend annual anal Pap tests. Screening for breast and colorectal cancer should follow standard, age-appropriate screening recommendations that apply to the general population. Screening HIV-infected men for prostate cancer, as with the general population, lacks a clear benefit. Despite increasing rates of hepatocellular carcinoma and lung cancers among PLWH, there is insufficient evidence to support routine screening.     

Myeloma cells exhibit an increase in proteasome activity and an enhanced response to proteasome inhibition in the bone marrow microenvironment in vivo

The proteasome inhibitor bortezomib has a striking clinical benefit in patients with multiple myeloma. It is unknown whether the bone marrow microenvironment directly contributes to the dramatic response of myeloma cells to proteasome inhibition in vivo. We have used the well‐characterized 5TGM1 murine model of myeloma to investigate myeloma growth within bone and response to the proteasome inhibitor bortezomib in vivo. Myeloma cells freshly isolated from the bone marrow of myeloma‐bearing mice were found to have an increase in proteasome activity and an enhanced response to in vitro proteasome inhibition, as compared with pre‐inoculation myeloma cells. Treatment of myeloma‐bearing mice with bortezomib resulted in a greater reduction in tumor burden when the myeloma cells were located within the bone marrow when compared with extra‐osseous sites. Our results demonstrate that myeloma cells exhibit an increase in proteasome activity and an enhanced response to bortezomib treatment when located within the bone marrow microenvironment in vivo. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.