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Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh) pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH) activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.

A hemisferectomia é realizada em muitos casos de hemimegalencefalia para controlar a epilepsia refratária ao tratamento medicamentoso. No entanto, apesar de haver concordância sobre a efetividade desse procedimento para controle das crises, a escolha da técnica cirúrgica utilizada ainda é motivo de debate. Relatamos os casos de três crianças com hemimegalencefalia submetidas à hemisferectomia para tratamento de suas crises refratárias: uma foi submetida à hemisferectomia anatômica e as outras duas, à hemisferectomia funcional. Os resultados confirmam a efetividade da hemisferectomia para o controle das crises epilépticas nesses casos.

Abstract  In a selected patient population, we evaluated the glycemic response to different infusional policies in the management of posterior cranial fossa tumor (PFT) removal. We analyzed the perioperative course, prospectically collected, of 137 children undergoing 150 surgical procedures. Patients were divided in two groups according to different intraoperative fluids (group A, 2.5% glucose; group B, crystalloids). In group B glycemia remained below 125 mg dl−1, while group A showed persistently supranormal glycemic plasma values, reaching statistical significance at the end of surgery (P P = 0.004). Our clinical experience suggests that both intraoperative glucose-free solutions are safe, and GSI can be a useful tool to identify prolonged PICU stay patients. [ABSTRACT FROM AUTHOR]

Abstract   Objective To evaluate perioperative management, early outcomes and hemocoagulative disorders in infants up to 1 year old, undergoing neurosurgery for brain tumors removal. Design Retrospective evaluation of prospectively collected data regarding all infants aged Interventions none. Setting University Hospital PICU in a tertiary neurosurgical referral centre. Patients and participants All eligible infants were enrolled in the study. Population was constituted by 43 infants and subdivided in two groups, according to their intra-operative blood loss. Babies having blood loss exceeding the preoperative estimated volemia were classified in group A; the remaining babies were included in group B. Results Intraoperative transfusions, PICU length of stay, need for post-operative mechanical ventilation and cardiovascular support were all significantly higher in group A than in group B. No early postoperative mortality occurred. ROC analysis and multiple logistic regression showed the age as the only variable independently associated with blood loss exceeding preoperative volemia (cut-off 60.3 days; OR = 0.11, CI 0.02–0.55, sensitivity 82.4%; specificity 67%). Postoperatively, platelet count, prothrombin activity and fibrinogen resulted significantly depressed in group A, representing a dilutional coagulopathy. A marked dispersion of aPTT values was recorded in group B, where most infants exhibit aPTT shortening, suggesting a hypercoagulability status. Three episodes of clinical disseminated intravascular coagulation (DIC) were registered in group B. Conclusions We illustrated the relationships between intraoperative blood loss, transfusions and haemostatic impairment in babies following brain tumor removal. Youngest infants had the higher risk to experience hemocoagulative disorders. These infants showed significantly higher impact on the global PICU burden of care, as represented by the need of mechanical ventilation, cardiovascular support and PICU length of stay. [ABSTRACT FROM AUTHOR]

Abstract Objects  Radiation-induced cerebral tumours constitute a significant risk for subjects undergoing radiotherapy for the management of cerebral neoplasms. Age-related cerebral vulnerability could be a specific factor in the genesis of these complications. Methods  The pertinent literature of both paediatric and adult series has been reviewed. Three personal cases were added. Results  One hundred forty-two paediatric second brain tumours were evaluated. Out of them, 69 were malignant gliomas, 33 meningiomas, 8 sarcomatous lesions and 13 low-grade astrocytomas. The average latency period for the appearance of the second tumour was 8 years. Among the second tumours occurring in adults, meningioma is the most common. In this subgroup, the latency period ranged between 16 and 30 years. Conclusion  Paediatric radiation-induced brain tumours differ from the adult counterpart for both the histological subtypes. These figures indicate a specific vulnerability of the infantile brain demonstrated by the most frequent occurrence of highly malignant lesions. [ABSTRACT FROM AUTHOR]

Abstract Background  The management of Sylvian arachnoid cysts in children is still a matter of debate. Diagnosis is often incidental, and symptoms are frequently aspecific in symptomatic cases. Suggested diagnostic investigation results have been often unclear. Surgical treatment is also controversial, pure, and assisted endoscopic cyst marsupialization having entered in the traditional debate between craniotomic and shunting approach Purpose  The objective of the present study was to survey if (and, eventually, which) agreement points do actually exist between internationally recognized pediatric neurosurgery centers in the management of children with a controversial type of Sylvian arachnoid cyst (Type II cyst). Methods  Contributors were asked to answer to a six-separate-part multiple choice questionnaire related to the case of a 2.7-year-old boy with a Type II left Sylvian arachnoid cyst presented in different clinical situations. If surgery was indicated, it was asked which surgical procedure the authors would have suggested as first option. Results and conclusions  The option of the mere clinical observation was chosen by the majority of surgeons in case of asymptomatic clinical discovery. On the other hand, a constantly high percentage of participants suggested direct surgical treatment based on clinical manifestations or as a preventive measure justified by the risk of spontaneous or traumatic intracranial bleeding. The only diagnostic investigation result which significantly influenced the surgical indication was a localizing electroencephalography, if the child presented with seizures. The result is that in most cases the surgical indication was based on aspecific clinical manifestations and laboratory data. Craniotomy and arachnoid cyst marsupialization represented the preferred surgical option (66.6%), 28.8% of the participants suggesting pure or assisted endoscopic cyst marsupialization as primary surgical procedure. Cyst shunting was suggested by only three centers. [ABSTRACT FROM AUTHOR]

Abstract  The aim of this study was to evaluate longitudinally functional and neuro-radiologic findings in childhood optic gliomas (OG), by comparing flicker visual evoked potentials (F-VEPs) with brain magnetic resonance imaging (MRI) changes. Fourteen children (age range: 1–13 years) with OGs underwent serial F-VEP, MRI and neuro-ophthalmic examinations over a 38 month (median, range: 6–76) follow-up. F-VEPs were elicited by 8 Hz sine-wave flicker stimuli presented in a mini-Ganzfeld. Contrast-enhanced MRI examinations were performed. Results of both tests were blindly assessed by independent evaluators. F-VEPs were judged to be improved, stable or worsened if changes in the amplitude and/or phase angle of the response exceeded the limits of test–retest variability (±90th percentile) established for the same patients. MRI results were judged to show regression, stabilization or progression of OG based on its changes in size (±20%) or extension. Two to seven pairs of F-VEP/MRI examinations per patient (median: 4) were collected. Based on a total of 38 pairs of F-VEP/MRI examinations, both tests agreeed in showing worsening (progression), stabilization and improvement (regression) in 5, 15 and 10 cases, respectively. In 3 cases, F-VEPs showed a worsening and MRI a stabilization, while in 5 cases F-VEPs showed an improvement and MRI a stabilization. Agreement between F-VEP and MRI changes was 78.9% (95% CI: ± 37%, K statistics = 0.67, P  [ABSTRACT FROM AUTHOR]

Abstract Background  Pain is the most common discomfort experienced by children undergoing major operations. It is most often not adequately treated because of inexperience and unfounded fears related to the use of opioid drugs. In adults, patient-controlled analgesia (PCA) is widely administered, while in children, its use with opioid drugs is still under evaluation for safety and efficacy. Objectives  The objective of the study is to evaluate the safety and efficacy of an opioid drug (fentanil) administered by PCA associated with a sedative-adjuvant drug (midazolam) administered by continuous infusion in children having undergone major neurosurgical procedures. Materials and methods  Sixteen children with moderate to severe postoperative pain were treated with fentanil by PCA (booster doses of 1 μg/kg) plus continuous infusion of midazolam (2 μg/kg per min) by an intravenous route. To evaluate safety and efficacy of this analgesic protocol, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients’ satisfaction was assessed by a questionnaire at the end of the treatment. Main results  All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment, and no major side effects occurred. The analysis of the answers of the questionnaire administered to the children showed a high grade of satisfaction. Conclusions  PCA with fentanil plus continuous infusion of midazolam is a safe and efficacious method for analgesia in children with moderate to severe postoperative neurosurgical pain. The association of midazolam to fentanil also contributes to control anxiety and stress in this subset of patients and does not show any important side effects. [ABSTRACT FROM AUTHOR]

Abstract Background  Syndromic craniosynostoses (Saethre–Chotzen, Pfeiffer 1, 2, 3, Apert, Crouzon, mainly) are particular in this that a single gene defect (mostly fibroblast growth factor receptor [FGFR] 2) generates different clinical phenotypes that characterize these syndromes. Significant brain abnormalities have been reported in all syndromes. However, whether these abnormalities are secondary to the bone disease or primary (e.g. callosal agenesis) is still controversial. Recent evidence suggests that the white matter defect might be a primary disorder. Review of literature  From the review of the literature and the analysis of our cases, it appears that three categories of brain abnormalities can be found. (1) The global distortion of the brain is likely mechanical and in keeping with the deformity of the skull. (2) The chronic tonsillar herniation (Chiari I deformity) is likely mechanical also and a consequence of the small size of the posterior fossa, especially after an early closure (before 24 m) of the lambdoid suture. (3) On the contrary, the constellation of abnormalities that selectively involve the white matter (non-progressive, non-destructive ventriculomegaly, callosal agenesis or thinning, agenesis of septum pellucidum, paucity of the antero-mesial temporal white matter, pyramidal hypoplasia) is much more likely to constitute a primary disorder. Conclusions  Recent neurobiological evidence supports this point of view. L1 cell adhesion molecule (L1CAM) gene plays a major role in the development of the white matter and its mutation in humans (callosal agenesis, retardation, adducted thumbs, spasticity, and hydrocephalus syndrome, Bickers–Adams syndrome) or in mice causes similar defects of the corpus callosum, septum pellucidum, centrum semi-ovale, and cortico-spinal tracts. To operate, L1CAM need interactions with FGFRs, whose defects are causal to the syndromic craniosynostoses. It seems logical to assumes that the FGFR defects generate both the skull abnormalities and, by lack of interaction with L1CAM, the primary defect of the white matter. The mental deficiency that is common in these patients therefore is likely to be part of the disease (through the L1CAM–FGFR interaction) rather than a consequence of the skull size or of the associated hydrocephalus. [ABSTRACT FROM AUTHOR]

Abstract Background  Several surgical techniques have been proposed for the correction of sagittal craniosynostosis. Extensive procedures seem to ensure the most stable long-term results and are more indicated in the older age group. Mini-invasive approaches are particularly useful in the very young infant as they are associated with a minor surgical risk. Furthermore, they are weighted by a minor cosmetic impact related to a less extended surgical scar. Materials and methods  Data of the last 94 consecutively operated on scaphocephalic patients have been reviewed to verify the effectiveness of a personal limited-invasive approach based on four to six short linear scalp incisions vs the traditional bicoronal skin flap. The patients have been divided in two groups: (1) the control group (2000–2002): 45 children, operated on by means of a traditional bicoronal skin incision, and (2) the study group (2002–2004): 49 children, treated through four to six linear scalp incisions. The patients’ variables were comparable. The results were evaluated in terms of duration of the surgical procedure, estimated blood loss (EBL), transfusion risk, postoperative complication rate, length of hospital stay, and postoperative cephalic index and cosmetic outcome as perceived by the patients’ families. Results  No significant differences between the two groups were found about the early and the long-term surgical results; however, about one third of the subjects of the control group complained about the visibility of the surgical scar. In the study group, a significant reduction in the duration of the operation (p p p = 0.011), transfusion risk (p = 0.018), and complication rate (p = 0.016) was observed. Conclusion  The current trend in the management of scaphocephaly is to favor simplified surgical procedures to be performed in the younger ages prevalently. The technique here presented allows achieving a stable long-term cranial reshaping, even when performed in the very young patient. The technique can be utilized also in older subjects with results comparable to those of more extensive surgical procedures. This less invasive technique is weighted by minor complication rates and minor impact of the surgical scar. [ABSTRACT FROM AUTHOR]

Background Neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) are growth factors implicated in the growth and differentiation of brain nerve cells. An involvement of these factors in the biology and progression of some specific tumours has been suggested. In accordance with the role of neurotrophic factors in tumour behaviour the aim of the present study was to investigate their expression in two childhood brain neoplasms, namely low-grade astrocytomas and ependymomas. Materials and methods We investigated the NGF, BDNF, GDNF and NGF receptors (TrkA and p75) expression in the tumour tissues, cerebrospinal fluid (CSF) and plasma of ten children affected by low-grade astrocytomas and ependymomas. Control tissue samples (together with CSF and plasma samples) were obtained from patients who underwent surgery for cerebral vascular or epileptogenic lesions. Results The expression of NGF decreases both in tumour samples and in the CSF of affected children compared with controls. BDNF instead increases in CSF, while the expression of GDNF remains unchanged both in tissues and in CSF. No differences were found in neurotrophic factor plasma levels in patients or in controls. Gene expression of NGF and its high-affinity receptor (TrkA) are reduced in tumour tissues, whereas the number of cells immunopositive to the low-affinity NGF receptor (p75) is increased. Conclusion Reduced expression of NGF and TrkA has been shown in low-grade astrocytomas and ependymomas. These findings may be related to the role of this neurotrophin in cell differentiation and apoptosis. The different expression of NGF, BDNF, and GDNF in low-grade astrocytomas and ependymomas suggests that a different degree of redundancy exists among members of the neurotrophic factor family and that their expression may be correlated with the biology and the behaviour of these tumours. [ABSTRACT FROM AUTHOR]

Introduction Acquired Chiari type-I malformation in hydrocephalic patients who have undergone surgical treatment was initially thought to depend on a craniocephalic disproportion induced by the cerebrospinal (CSF) shunt. However, most of the reports in the literature deal with children with lumbo-peritoneal shunts and emphasize the pathogenic role of the cranio?spinal pressure differential across the foramen magnum brought about by this type of shunt. Method In the present report, the authors describe two further cases of symptomatic acquired Chiari type-I malformation observed in two adolescents operated on for correction of pseudotumor cerebri in one (lumbo-peritoneal shunt) and of a suprasellar arachnoid cyst (cysto-ventriculo-peritoneal shunt) in the other. Results In both subjects, both the clinical manifestations and the cerebellar tonsillar herniation regressed after supratentorial cranial expansion, without the need for any manipulation of the shunt devices implanted earlier. Discussion These results, together with the observation of the concomitant upward and downward herniation of the cerebellum in both patients, indicate that secondary craniocephalic disproportion plays a relevant role in the genesis of acquired Chiari type-I malformation in children bearing extrathecal CSF shunts. [ABSTRACT FROM AUTHOR]

Object Anterior sacral meningocele (ASM) is a rare congenital malformation. Often while still asymptomatic, ASM may achieve a considerably size, to the extent of exerting a mass effect on the pelvic structures. Spontaneous rupture with subsequent septic meningitis is the most frequent and dangerous complication. The meningocelic sac is usually isolated by a surgical procedure that requires a sacral laminectomy or a transabdominal approach. Recently an alternative surgical technique, the posterior sagittal approach, has been proposed. Methods We report on a 15-year-old girl with a long clinical history of constipation and sporadic cystitis. Radiological examinations showed progressive enlargement of a presacral lipomeningocele, which grew to 12Ö14 cm. A posterior sagittal approach was performed; the stalk was ligated, the sac totally excised and a small associated tumour removed. No intra-/post-operative complications were observed. Conclusion The posterior sagittal approach is an easy and safe surgical technique for the treatment of ASM, as it allows a complete isolation of the lesion and the removal of associated tumors without significant morbidity. [ABSTRACT FROM AUTHOR]

Abstract Object. Vertebro-basilar dissecting aneurysms (VDAs) are very rare in children. Strokes or subarachnoid hemorrhage are characteristic clinical manifestations, but often only non-specific symptoms are found. Radiological diagnosis may be difficult to obtain and therapy hard to perform. We report on a child who presented with an intracranial mass effect due to a giant VDA. Methods. The patient was a 8-year-old girl with right hemiparesis, ataxia, dysphagia and dysphonia and worsening of her neurological deficits. Neuroimaging discovered a giant dissecting aneurysm arising from the left vertebral artery and involving the vertebro-basilar junction. Endovascular treatment by coil embolization was performed. The post-operative course initially showed a remarkable improvement in her clinical condition. Afterwards, she developed cerebral hemorrhage and died. Conclusion. VDAs may have an unusual presentation and their therapy still remains a challenge. Endovascular embolization is a valid option but, as it is surgery, it may cause the death of the patient. [ABSTRACT FROM AUTHOR]