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George A. Alexiou, Maria Moschovi and Neofytos Prodromou

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George A. Alexiou and Spyridon Voulgaris

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George A. Alexiou, Maria Moschovi, George Georgoulis, Rosalia Neroutsou, Kalliopi Stefanaki, George Sfakianos and Neofytos Prodromou

Radiation-induced brain tumors are suggested to be the late complication of acute lymphoblastic leukemia (ALL) treatment. High-grade gliomas, meningiomas, and sarcomas are the most frequent neoplasms. Secondary anaplastic oligodendrogliomas are exceedingly rare. Five cases of pure anaplastic oligodendroglioma have been reported in the literature, and only 1 case was in a child after ALL treatment. The authors present 2 cases of pediatric anaplastic oligodendroglioma after treatment of ALL. Furthermore, they performed a molecular cytogenetic study and found loss of 1p in both cases. The authors provide a review of the previous cases and discuss their findings.

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Aristotelis V. Kalyvas, Theodosis Kalamatianos, Mantha Pantazi, Georgios D. Lianos, George Stranjalis and George A. Alexiou

OBJECTIVE

Congenital hydrocephalus (CH) is one of the most frequent CNS congenital malformations, representing an entity with serious pathological consequences. Although several studies have previously assessed child-related risk factors associated with CH development, there is a gap of knowledge on maternal environmental risk factors related to CH. The authors have systematically assessed extrinsic factors in the maternal environment that potentially confer an increased risk of CH development.

METHODS

The Cochrane Library, MEDLINE, and EMBASE were systematically searched for works published between 1966 and December 2015 to identify all relevant articles published in English. Only studies that investigated environmental risk factors concerning the mother—either during gestation or pregestationally—were included.

RESULTS

In total, 13 studies (5 cohorts, 3 case series, 3 case-control studies, 1 meta-analysis, and 1 case report) meeting the inclusion criteria were identified. Maternal medication or alcohol use during gestation; lifestyle modifiable maternal pathologies such as obesity, diabetes, or hypertension; lack of prenatal care; and a low socioeconomic status were identified as significant maternal environmental risk factors for CH development. Maternal infections and trauma to the mother during pregnancy have also been highlighted as potential mother-related risk factors for CH.

CONCLUSIONS

Congenital hydrocephalus is an important cause of serious infant health disability that can lead to health inequalities among adults. The present study identified several maternal environmental risk factors for CH, thus yielding important scientific information relevant to prevention of some CH cases. However, further research is warranted to confirm the impact of the identified factors and examine their underlying behavioral and/or biological basis, leading to the generation of suitable prevention strategies.

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Dimitrios Panagopoulos, George A. Alexiou, George Sfakianos and Neofytos Prodromou

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George A. Alexiou, George Vartholomatos, Spyridon Voulgaris and Athanassios P. Kyritsis

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Maria Varela, George A. Alexiou, Magda Liakopoulou, Evaggelos Papakonstantinou, Dimitra Pitsouni and Giorgos A. Alevizopoulos

Object

The biogenic amines (dopamine, epinephrine, norepinephrine, and serotonin) are involved in the regulation of multiple neuronal functions, and changes in monoamine concentrations in the CSF have been detected in several disorders. The aim of the present study was to investigate the role of biogenic amines in the ventricular CSF of children suffering from posterior fossa tumors and their possible correlation with tumor histology and cognitive functioning.

Methods

Twenty-two children with posterior fossa tumors who were treated surgically at Children's Hospital “Agia Sofia” were studied. Patients ranged in age from 5.5 to 15 years. The study population included patients who suffered from hydrocephalus and were treated by ventriculoperitoneal shunt placement. During the operation for shunt placement, a CSF sample was obtained for the assessment of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). Simultaneously, a blood sample was also obtained for assessment of the same metabolites in the serum. The concentration of vanillylmandelic acid (VMA) was evaluated in 24-hour urine samples in 11 patients. Cerebrospinal fluid from a control group of children was also studied. Executive functions were assessed using the short form of the Wechsler Intelligence Scale for Children (WISC).

Results

Twelve patients suffered from astrocytomas, 9 from medulloblastomas, and 1 from an ependymoma. The MHPG concentration in CSF was significantly higher in patients with astrocytomas compared with patients with medulloblastomas. Twenty-four-hour urine samples of VMA were significantly higher in patients with astrocytomas compared with patients with medulloblastomas. The MHPG concentration in CSF was negatively correlated with the verbal scale of the WISC and there was a trend toward a significant negative correlation with the total WISC score. Homovanillic acid in CSF was positively correlated with the performance scale of the WISC. There was a significant correlation between HVA and MHPG levels in CSF. The CSF concentration of 5-HIAA was significantly correlated with the HVA concentration in serum. Twenty-four-hour urine VMA samples were statistically significantly correlated with HVA concentration in both CSF and serum, with MHPG in CSF, and with 5-HIAA in serum.

Conclusions

This study showed that children with posterior fossa tumors have differences in the levels of monoamine metabolites in CSF. Further studies with a larger number of patients are obviously needed to verify these observations as well as studies to correlate the monoamine metabolite levels with the neuropsychological and behavioral findings in children with posterior fossa tumors.

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Maria Varela, Magda Liakopoulou, George A. Alexiou, Dimitra Pitsouni and Giorgos A. Alevizopoulos

Object

Brain tumors are associated with behavioral and neuropsychological effects. Most available data are focused on the posttreatment neurological and cognitive deficits of these patients. The aim of the present study was to investigate the pretreatment neuropsychological and behavioral impairment in children with posterior fossa tumors.

Methods

The authors studied 24 children with posterior fossa tumors who were between 4 and 15 years of age, and who were surgically treated at the authors' institute. During the period prior to the tumor excision, neuropsychological and behavioral assessments were performed. A control group of age-matched children was also studied. The children's executive functions were assessed using the short form of the Wechsler Intelligence Scale for Children (WISC). For the assessment of visuospatial functions, spatial memory, and visuomotor integration skills, the Bender-Gestalt Test (BGT) was used. For assessment of the visual perception and visual memory, the authors used the Benton Visual Retention Test (BVRT). Furthermore, parents or caregivers completed the Child Behavior Checklist (CBCL).

Results

The WISC revealed no significant difference between patients and the control group. The CBCL revealed significant somatic concerns compared with the measure's norms. Furthermore, the patients differed in aggressiveness, somatic concerns, anxiety symptoms, internalizing of problems, and total problems. In the BGT and the BVRT results, no significant difference was observed between patients and the control group. Furthermore, no significant correlation was found between neuropsychological scores and sex, age at diagnosis, histological diagnosis, presence of hydrocephalus, degree of hydrocephalus, tumor size, and tumor location.

Conclusions

Children with posterior fossa tumors suffer more frequently from somatic concerns, aggressiveness, anxiety, and internalizing disorders compared with controls. No difference was found with respect to intelligence scores.

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George Vartholomatos, George A. Alexiou, Anna Batistatou, Athanassios P. Kyritsis and Spyridon Voulgaris

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George A. Alexiou, George Vartholomatos, Kalliopi Stefanaki, Amalia Patereli, Lefkothea Dova, Achilleas Karamoutsios, George Lallas, George Sfakianos, Maria Moschovi and Neofytos Prodromou

Object

Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis.

Methods

The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed.

Results

Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer15) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer82), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer15) and Ki-67 index (r = −0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076).

Conclusions

A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.