Neuroendoscopy: history, endoscopes, and instrumentation.

INTRODUCTION: Endoscopy was first employed in the surgical treatment of neurosurgical diseases early in the twentieth century, but did not become an established practice for a long time, mainly because of poor technology and clinical results. After a slow re-appearance in the 1980s, the 1990s saw an explosion of techniques and instrumentation. Continuing technological improvement has led to further expansion of surgical techniques and indications for use of neuroendoscopy. DISCUSSION: The expansion of ventricular endoscopy has led to significant understanding of CSF disorders. Aqueduct stenosis as cause of hydrocephalus and arachnoid cysts are an example of pathologies, the concept and understanding of which now is considerably enhanced, due to the application of neuroendoscopy in their treatment. Management of loculated hydrocephalus has been facilitated considerably with the use of the endoscope. The concepts of aqueductoplasty, septostomy, and foraminoplasty of the foramina of Monro and Magendie emerged, which were previously unknown. Skull base surgery, especially surgery for craniopharyngioma, has seen dramatic improvement in results with the use of the endoscope. Coupling of the endoscope with neuronavigation has expanded technical capabilities even further. Overall, we can do a lot more with the endoscope now in comparison to 30 years ago. CONCLUSION: We should always remember that the endoscope is only a tool. Its use has indications and limitations related to its design and our ability to extract the maximum, in the context of its shortcomings. Further technological advances will push surgical frontiers even more in years to come.

Histone H3K9 methyltransferase SETDB1 overexpression correlates with pediatric high-grade gliomas progression and prognosis.

Pediatric high-grade gliomas (pHGGs) are heterogeneous, diffuse, and highly infiltrative tumors with dismal prognosis. Aberrant post-translational histone modifications with elevated histone 3 lysine trimethylation (H3K9me3) have been recently implicated in pHGGs' pathology, conferring to tumor heterogeneity. The present study investigates the potential involvement of H3K9me3 methyltransferase SETDB1 in the cellular function, progression, and clinical significance of pHGG. The bioinformatic analysis detected SETDB1 enrichment in pediatric gliomas compared to the normal brain, as well as positive and negative correlations with a proneural and mesenchymal signature, respectively. In our cohort of pHGGs, SETDB1 expression was significantly increased compared to pLGG and normal brain tissue and correlated with p53 expression, as well as reduced patients' survival. In accordance, H3K9me3 levels were also elevated in pHGG compared to the normal brain and were associated with worse patient survival. Gene silencing of SETDB1 in two patient-derived pHGG cell lines showed a significant reduction in cell viability followed by reduced cell proliferation and increased apoptosis. SETDB1 silencing further reduced cell migration of pHGG cells and the expression of the mesenchymal markers N-cadherin and vimentin. mRNA analysis of epithelial-mesenchymal transition (EMT) markers upon SETDB1 silencing showed a reduction in SNAI1 levels and downregulation of CDH2 along with the EMT regulator gene MARCKS. In addition, SETDB1 silencing significantly increased the bivalent tumor suppressor gene SLC17A7 mRNA levels in both cell lines, indicating its implication in the oncogenic process.Altogether, our findings demonstrate a predominant oncogenic role of SETDB1 in pHGG which along with elevated H3K9me3 levels correlate significantly to tumor progression and inferior patients' survival. There is evidence that targeting SETDB1 may effectively inhibit pHGG progression, providing a novel insight into the therapeutic strategies for pediatric gliomas. KEY MESSAGES: SETDB1 gene expression is enriched in pHGG compared to normal brain. SETDB1 expression is increased in pHGG tissues and associates with reduced patients' survival. Gene silencing of SETDB1 reduces cell viability and migration. SETDB1 silencing affects mesenchymal markers expression. SETDB1 silencing upregulates SLC17A7 levels. SETDB1 has an oncogenic role in pHGG.

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1.

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.

Nanotechnology in neurosurgery: a systematic review.

BACKGROUND: The application of nanotechnology in medicine encompasses an interdisciplinary field of sciences for the diagnosis, treatment, and monitoring of medical conditions. This study aims to systematically review and summarize the advances of nanotechnology applicable to neurosurgery. METHODS: We performed a PubMed advanced search of reports exploring the advances of nanotechnology and nanomedicine relating to diagnosis, treatment, or both, in neurosurgery, for the last decade. The search was performed according to PRISMA guidelines, and the following data were extracted from each paper: title; authors; article type; PMID; DOI; year of publication; in vitro, in vivo model; nanomedical, nanotechnological material; nanofield; neurosurgical field; the application of the system; and main conclusions of the study. RESULTS: A total of 78 original studies were included in this review. The results were organized into the following categories: functional neurosurgery, head trauma, neurodegenerative diseases, neuro-oncology, spinal surgery and peripheral nerves, vascular neurosurgery, and studies that apply to more than one field. A further categorization applied in terms of nanomedical field such as neuroimaging, neuro-nanotechnology, neuroregeneration, theranostics, and neuro-nanotherapy. CONCLUSION: In reviewing the literature, significant advances in imaging and treatment of central nervous system diseases are underway and are expected to reach clinical practice in the next decade by the application of the rapidly evolving nanotechnology techniques.

Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS).

PURPOSE: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. METHODS: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. RESULTS: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. CONCLUSION: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

TROPHY registry study design: a prospective, international multicenter study for the surgical treatment of posthemorrhagic hydrocephalus in neonates.

INTRODUCTION: Among children with hydrocephalus, neonates with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PH) are considered a group with one of the highest complication rates of treatment. Despite continued progress in neonatal care, a standardized and reliable guideline for surgical management is missing for this challenging condition. Thus, further research is warranted to compare common methods of surgical treatment. The introduction of neuroendoscopic lavage has precipitated the establishment of an international registry aimed at elaborating key elements of a standardized surgical treatment. METHODS: The registry is designed as a multicenter, international, prospective data collection for neonates aged 41 weeks gestation, with an indication for surgical treatment for IVH with ventricular dilatation and progressive hydrocephalus. The following initial temporizing surgical interventions, each used as standard treatment at participating centers, will be compared: external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). Type of surgery, perioperative data including complications and mortality, subsequent shunt surgeries, ventricular size, and neurological outcome will be recorded at 6, 12, 36, and 60 months. RESULTS: An online, password-protected website will be used to collect the prospective data in a synchronized manner. As a prospective registry, data collection will be ongoing, with no prespecified endpoint. A prespecified analysis will take place after a total of 100 patients in the NEL group have been entered. Analyses will be performed for safety (6 months), shunt dependency (12, 24 months), and neurological outcome (60 months). CONCLUSION: The design and online platform of the TROPHY registry will enable the collection of prospective data on different surgical procedures for investigation of safety, efficacy, and neurodevelopmental outcome of neonates with IVH and hydrocephalus. The long-term goal is to provide valid data on NEL that is prospective, international, and multicenter. With the comparison of different surgical treatment modalities, we hope to develop better therapy guidelines for this complex neurosurgical condition.

International Infant Hydrocephalus Study (IIHS): 5-year health outcome results of a prospective, multicenter comparison of endoscopic third ventriculostomy (ETV) and shunt for infant hydrocephalus.

INTRODUCTION: One of the most important unanswered questions in pediatric hydrocephalus is determining whether treatment with endoscopic third ventriculostomy (ETV) versus shunt results in improved health status and quality of life (QOL). To answer this, the International Infant Hydrocephalus Study (IIHS) was started in 2005 as a prospective, multicenter study to compare ETV and shunt in infants (< 24 months old) with symptomatic triventricular hydrocephalus from aqueductal stenosis. Herein, we present the 5-year primary outcome results. METHODS: IIHS utilized a prospective comprehensive cohort design, in which patients received ETV or shunt, based on either randomization or parental preference. For this analysis, we pooled the randomized arm and the parental preference arm, analyzing them together. At 5 years of age, children were assessed with the Health Utilities Index Mark 2 (HUI-2) (primary outcome) and the Hydrocephalus Outcome Questionnaire (HOQ), a measure of QOL. Results were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and baseline development status. RESULTS: From a total of 158 patients who met eligibility criteria, complete 5-year outcomes were available on 78 (19 treated initially with shunt, 61 treated initially with ETV), assessed at a mean age of 62.1 months (SD 6.3). The mean 5-year HUI-2 utility score was 0.90 (SD 0.19) for ETV and 0.94 (SD 0.10) for shunt (p = 0.21). The mean 5-year HOQ overall score was 0.81 (SD 0.15) for ETV and 0.85 (SD 0.12) for shunt (p = 0.42). Similarly, there were no significant differences noted between 5-year HOQ subscores (cognitive, social-emotional, physical) or developmental measures at 1, 2, and 3 years. CONCLUSIONS: This is the first prospective direct comparison of long-term outcomes of ETV and shunt for infant hydrocephalus. These results suggest that overall health status and quality of life in this cohort of infants treated for aqueductal stenosis are high, with no significant difference between those treated initially with ETV or shunt. TRIAL REGISTRATION: NCT00652470.

Outcome of treatment after failed endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: results from the International Infant Hydrocephalus Study (IIHS).

INTRODUCTION: After an endoscopic third ventriculostomy (ETV) fails, it is unclear how well subsequent treatment fares, especially in comparison to shunts inserted as primary treatment. In this study, we present a further analysis of the infants enrolled a prospective multicentre study who failed ETV and describe the outcome of their subsequent treatment, comparing this to those who received shunt as their primary treatment. METHODS: This was a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicentre study of infants with hydrocephalus from aqueductal stenosis who received either an ETV or shunt. In the current analysis, we compared the results of the 38 infants who failed ETV and the 43 infants who received primary shunt. Patients were followed prospectively for time to treatment failure, defined as the need for repeat CSF diversion procedure (shunt or ETV) or death due to hydrocephalus. RESULTS: There were a total of 81 patients: 43 primary shunts, 34 shunt post-ETV, and 4 repeat ETV. The median time between the primary ETV and the second intervention was 29 days (IQR 14-69), with no significant difference between repeat ETV and shunt post-ETV. Median length of available follow-up was 800 days (IQR 266-1651), during which time, failure was noted in 3 (75.0%) repeat ETV patients, 10 (29.4%) shunt post-ETV patients, and 9 (20.9%) primary shunt patients. In an adjusted Cox regression model, the risk of failure was higher for repeat ETV compared to primary shunt, but there was no significant difference between primary shunt and shunt post-ETV. No other variable showed statistical significance. CONCLUSIONS: In our prospective study of infants with aqueductal stenosis, there was no significant difference in failure outcome of shunts inserted after a failed ETV and primary shunts. Therefore, our data do not support the notion that previous ETV confers either a protective or negative effect on subsequently-placed shunts. Larger studies, in a wider ranging population, are required to establish how widely these data apply. TRIAL REGISTRATION: NCT00652470.

Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US.

Pilocytic astrocytomas (PA) comprise the most common childhood central nervous system (CNS) tumor. Exploiting registry-based data from Southern and Eastern Europe (SEE) and SEER, US, we opted to examine incidence, time trends, survival and tentative outcome disparities of childhood PA by sociodemographic and clinical features. Childhood PA were retrieved from 12 SEE registries (N = 552; 1983-2014) and SEER (N = 2723; 1973-2012). Age-standardized incidence rates (ASR) were estimated and survival was examined via Kaplan-Meier and Cox regression analysis. ASR of childhood PA during 1990-2012 in SEE was 4.2/106, doubling in the USA (8.2/106). Increasing trends, more prominent during earlier registration years, were recorded in both areas (SEE: +4.1 %, USA: +4.6 %, annually). Cerebellum comprised the most common location, apart from infants in whom supratentorial locations prevailed. Age at diagnosis was 1 year earlier in SEE, whereas 10-year survival was 87 % in SEE and 96 % in SEER, improving over time. Significant outcome predictors were age <1 year at diagnosis diagnosis (hazard ratio, HR [95% confidence intervals]: 3.96, [2.28-6.90]), female gender (HR: 1.38, [1.01-1.88]), residence in SEE (HR: 4.07, [2.95-5.61]) and rural areas (HR: 2.23, [1.53-3.27]), whereas non-cerebellar locations were associated with a 9- to 12-fold increase in risk of death. The first comprehensive overview of childhood PA epidemiology showed survival gains but also outcome discrepancies by geographical region and urbanization pointing to healthcare inequalities. The worse prognosis of infants and, possibly, females merits further consideration, as it might point to treatment adjustment needs, whereas expansion of systematic registration will allow interpretation of incidence variations.

International Infant Hydrocephalus Study: initial results of a prospective, multicenter comparison of endoscopic third ventriculostomy (ETV) and shunt for infant hydrocephalus.

INTRODUCTION: The IIHS is an international, prospective, multicenter study to compare endoscopic third ventriculostomy (ETV) and shunt in infants (<24 months old) with symptomatic triventricular hydrocephalus from aqueductal stensosis. Recruitment started in 2004, and here, we present the first results of IIHS. METHODS: IIHS utilized a prospective comprehensive cohort design, which contained both a randomized and a non-randomized arm. Patients received either an ETV or shunt, based on randomization or parental preference. Patients were followed prospectively for time to treatment failure, defined as the need for repeat CSF diversion procedure (shunt or ETV) or death due to hydrocephalus. Survival analysis was used to compare time to failure for ETV versus shunt. The trial was registered at clinicaltrials.gov (NCT00652470). RESULTS: A total of 158 patients met eligibility criteria (median age at surgery 3.6 months, IQR 1.6-6.6 months) across 27 centers in 4 continents. Since only 52 patients (32.9 %) were randomized, all 158 patients were analyzed together (115 ETV, 43 shunt). Actuarial success rates for ETV vs shunt at 3, 6, and 12 months were as follows: 68 vs 95 %, 66 vs 88 %, and 66 vs 83 %. The 6-month ETV success rate of 66 % was slightly higher than would have been predicted by the ETV Success Score (57 %).The hazard ratio for time to treatment failure favored shunt over ETV (3.17, 95 % CI 1.45-6.96, p = 0.004), after adjusting for age at surgery, history of previous hemorrhage or infection, continent, and randomization status. Patients younger than 6 months of age appeared to do relatively worse with ETV than older patients. CONCLUSIONS: The IIHS has provided the first prospective direct comparison of ETV and shunt for infant hydrocephalus. These initial results suggest that shunting has a superior success rate compared to ETV, although the success rate for both was relatively high. This patient cohort continues to be followed, and we will await the results of the important primary outcome of health status at 5 years of age.

Childhood central nervous system tumour mortality and survival in Southern and Eastern Europe (1983-2014): Gaps persist across 14 cancer registries.

AIM: Childhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region. METHODS: Average age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan-Meier curves were derived for the maximum and the more recent (10 and 5 year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants. RESULTS: Variations in mortality (8-16 per million) and survival (5-year: 35-69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (-2.4%, p=0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1-1.4). CONCLUSION: Cross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe.

Childhood central nervous system tumours: Incidence and time trends in 13 Southern and Eastern European cancer registries.

AIM: Following completion of the first 5-year nationwide childhood (0-14 years) registration in Greece, central nervous system (CNS) tumour incidence rates are compared with those of 12 registries operating in 10 Southern-Eastern European countries. METHODS: All CNS tumours, as defined by the International Classification of Childhood Cancer (ICCC-3) and registered in any period between 1983 and 2014 were collected from the collaborating cancer registries. Data were evaluated using standard International Agency for Research on Cancer (IARC) criteria. Crude and age-adjusted incidence rates (AIR) by age/gender/diagnostic subgroup were calculated, whereas time trends were assessed through Poisson and Joinpoint regression models. RESULTS: 6062 CNS tumours were retrieved with non-malignant CNS tumours recorded in eight registries; therefore, the analyses were performed on 5191 malignant tumours. Proportion of death certificate only cases was low and morphologic verification overall high; yet five registries presented >10% unspecified neoplasms. The male/female ratio was 1.3 and incidence decreased gradually with age, apart from Turkey and Ukraine. Overall AIR for malignant tumours was 23/10(6) children, with the highest rates noted in Croatia and Serbia. A statistically significant AIR increase was noted in Bulgaria, whereas significant decreases were noted in Belarus, Croatia, Cyprus and Serbia. Although astrocytomas were overall the most common subgroup (30%) followed by embryonal tumours (26%), the latter was the predominant subgroup in six registries. CONCLUSION: Childhood cancer registration is expanding in Southern-Eastern Europe. The heterogeneity in registration practices and incidence patterns of CNS tumours necessitates further investigation aiming to provide clues in aetiology and direct investments into surveillance and early tumour detection.

Spinal dysraphism.

In the last decade there have been significant improvements in all the fields of management of patients with spinal dysraphism, which have increased dramatically the quality of life of these children. Prevention of spina bifida with food fortification is becoming increasingly practiced worldwide. As result, in many parts of the world the frequency of myelomeningocele has decreased. Intrauterine closure of myelomeningocele has been attempted in many institutions with variable results. While it is still at the sphere of experimental therapy, it is reasonable to anticipate progress in this field in the next decade. Antenatal MR imaging is already providing very high level of detail even before the child is born. This creates new ethical dilemmas and requires additional care, but has improved significantly the overall management of patients and their families. Further improvements are anticipated in this field. Management of neuropathic bladder has improved significantly in the last decade and is anticipated to play an increasing role in the long term follow up. Surgery for spinal cord tethering in all its forms has improved in the last decade, with far more chances of complete untethering now in comparison to 10-15 years ago, with the use of micro-neurosurgical techniques and intraoperative monitoring. It is reasonable to expect that in the next decade, intraoperative neurophysiological monitoring during spinal cord surgery will become mandatory. In the 2013 Annual Special Issue we have assembled a team of authors distinguished in their fields, who bring us up to date with all the latest developments.

Syringomyelia and tethered cord in children.

INTRODUCTION: The presence of syringomyelia varies in patients with different forms of dysraphism; from 21 % to 67 %. Only around 60 % of patients with syringomyelia is likely to experience symptoms related to it. PATHOPHYSIOLOGY: Many theories have been outlined for the creation of syringomyelia. The one most applicable to tethered cord dictates that tensile radial stress may create a syrinx in a previously normal cord tissue and transiently lower pressure may draw in interstitial fluid, causing the syrinx to enlarge if fluid exit is inhibited. In addition, arachnoiditis increases flow resistance in the spinal subarachnoid space, altering temporal CSF pulse pressure dynamics, which promotes entry of CSF in to the spinal cord. CLINICAL PRESENTATION: There is a significant overlap between the symptoms that are due to tethered cord and syringomyelia, both in newly presenting patients with coexisting syringomyelia, and in previously treated patients who during follow-up present recurrent symptoms and a new syringomyelia cavity. TREATMENT: The treatment of patients with tethered cord and syringomyelia is directed towards untethering the cord from its most caudal region upwards and restoring spinal anatomy with reestablishment of unobstructed CSF flow in the subarachnoid space. Only if complete untethering has been ensured and syringomyelia deteriorates, then surgical treatment can be directed against the syrinx. In patients with spinal dysraphism and coexisting hydrocephalus, radiological presentation of new syringomyelia or deterioration of previously known syringomyelia may signify shunt obstruction "until proven otherwise". CONCLUSION: In most occasions, satisfactory cord untethering addresses the development of syringomyelia.

Safety and diagnostic accuracy of neuroendoscopic biopsies: an international multicenter study.

OBJECT: Analysis of the safety and morbidity of neuroendoscopic biopsies (NEBs), as well as the reliability in obtaining an accurate diagnosis, has until now been based on studies with relatively small sample sizes. Through the cooperative efforts of several international medical centers, authors of the present study collected data on a large number of patients to obtain better insight into this issue. When possible, they compared pathology obtained through an NEB with the "gold-standard" pathology obtained in open surgery. METHODS: Thirteen randomly chosen medical centers in 9 countries collected data for patients who had undergone NEB, which were then analyzed for universal complications, bleeding, navigation technique, pathology, mismatch between biopsy results and final diagnosis, and a number of other potentially influential factors. RESULTS: Data for 293 patients were analyzed. Sixty percent of the patients were male, and patient ages ranged from 0.1 to 78.7 years (median age 20.4 years). The most common tumor locations were pineal (33.1%), thalamic (16.7%), tectal (13%), and hypothalamic (4.4%). Fifty percent of the tumors were larger than 20 mm, 36% were between 10 and 20 mm, and 14% were smaller than 10 mm. Intraoperative bleeding was seen in 275 patients (94%). The amount of blood was noted as mild in 75%, moderate in 13%, and severe in 6%. Infection occurred in 8 patients (3%). Death occurred in 1 patient (0.3%), which was caused by severe intraoperative bleeding. Biopsies were informative in 265 patients (90.4%). Seventy-eight patients (26.6%) had open surgery following the NEB. For these patients, the pathology results from the NEB were compared with those from the open surgery that followed. In 14 cases (17.9%) there was disagreement on the pathology. Of these cases, a meaningful mismatch, in which the erroneous NEB pathology could have led to an inappropriate management decision, occurred in 9 cases (11.5%). Most of these meaningful mismatches were lesions diagnosed as low-grade or pilocytic astrocytoma on the NEB and later proved to be high-grade astrocytoma (4 cases) and 1 case each of meningioma, cavernoma, primitive neuroectodermal tumor, neurocysticercosis, and pineocytoma. CONCLUSIONS: In experienced hands, NEBs can be performed with low morbidity and mortality, providing meaningful pathological data for the majority of patients with a wide range of tumor types, locations, and presentations. These biopsies also offer other advantages, such as the ability to perform concomitant endoscopic third ventriculostomy and septum pellucidotomy. However, due caution must be maintained, since pathology obtained from an NEB, as with stereotactic biopsies, may be subject to sampling errors, especially when the results seem to indicate a low-grade glial tumor.

Intrauterine grade IV intraventricular hemorrhage in a full-term infant leading to hydrocephalus.

INTRODUCTION: Peri/intraventricular hemorrhage (PIVH) is more often seen in premature neonates and can lead to posthemorrhagic hydrocephalus, characterized by high mortality rate and neurodevelopmental delay. CASE REPORT: We report a case of in utero PIVH in a full-term neonate, which led to hydrocephalus. The infant developed at 8 months of gestational age intracerebral/intraventricular hemorrhage at the regions of the left basal ganglia and thalamus with significant intraventricular extension and ventriculomegaly, which was diagnosed with fetal MR scan, and progressed post partum to active multiloculated hydrocephalus. At the age of 3 months, the infant was operated on with endoscopic fenestration of the ventricular septations at the left side and ventriculoperitoneal shunt insertion at the right side. A follow-up MR scan after 4 months showed improvement of the ventriculomegaly and the multiloculated hydrocephalus. Up to a period of 6 months follow up, there have been no shunt-related problems. DISCUSSION: The complications of a grade IV intraventricular hemorrhage are well documented in premature infants. It is difficult to know to what extent these apply equally to full-term infants with intraventricular hemorrhage. Ventricular hemorrhage is very rarely reported in full-term neonates, and even more rarely in the intrauterine period.