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Aim To evaluate the efficacy of using a neuronavigation system for demonstrating the relationship between the basilar artery (BA) and ventricular floor during endoscopic third ventriculostomy (ETV). Material and methods Records of 28 patients (16 females and 12 males) diagnosed with obstructive hydrocephalus who had undergone a neuroendoscopic procedure were retrospectively examined. Patient age ranged from 1 to 76 years (median 24.46 years). The BA was marked with using the neuronavigation system in all cases to visualise its relationship to the floor of the third ventricle in real time. Results ETV was successfully performed in 28 patients with obstructive hydrocephalus. Of these, 13 (46.4%) patients had a thickened tuber cinereum (TC) membrane and 3 (10.7%) showed lateralization of the BA under the ventricular floor. No contact with the BA or related complications (e.g., major bleeding) was encountered with BA marking by using neuronavigation. Conclusion Even though thickening of the TC membrane and/or displacement of the BA might be seen otherwise, we describe a new method that combines marking the BA and using neuronavigation to provide greater safety in the area where the ventriculostomy will be performed. This permits clearer orientation for the surgeon which significantly contributes to minimizing surgical morbidity.

Simple Summary Melanotic neuroectodermal tumor of infancy (MNTI) is a rare tumor of uncertain origin, morphologically overlapping other rare neoplasms such as pineal anlage tumor (PAT) and a subset of medulloblastomas (i.e., melanotic medulloblastoma). Despite the similarities with MNTI, their possible histogenetic relationship has been traditionally disregarded based on their aggressive behavior and dismal prognosis. The aim of this study was to further characterize the molecular features of MNTI and PAT based on DNA-methylation and copy number variation profiling analysis. We found that MNTI shares a methylation profile with group 3 high-risk medulloblastoma, and potentially with PAT, suggesting a common histogenesis. Most MNTIs in our series lacked copy number variation alterations, whereas their presence in the one PAT deserves further study in larger cohorts to better determine their impact in prognosis and biologic behavior. Abstract MNTI is a rare tumor of indeterminate histogenesis and molecular signature. We performed methylation and copy number variation (CNV) profiles in patients with MNTI (n = 7) and PAT (n = 1) compared to the methylation brain tumor classifier v11b4 (BT-C) and the medulloblastoma (MB) classifier group 3/4 v1.0 (MB3/4-C). The patients’ mean age was 8 months (range: 4–48). The BT-C classified five MNTIs and one PAT (relapse) as class family MB-G3/G4, subclass group 3 (score: >0.9). The remaining two MNTIs and PAT (primary) were classified as class family plexus tumor, subclass pediatric (scores: >0.45). The MB3/4-C classified all MNTIs as high-risk MB-G3, Subtype II (score: >0.45). The primary PAT was classified as subtype III (score: 0.99) and its relapse as subtype II/III. MNTI and PAT clustered close to MB-G3. CNV analysis showed multiple rearrangements in one PAT and two MNTIs. The median follow-up was 54 months (four MNTIs in remission, one PAT died). In conclusion, we demonstrated that MNTI shares a homogenous methylation profile with MB-G3, and possibly with PAT. The role of a multipotent progenitor cell (i.e., early cranial neural crest cell) in their histogenesis and the influence of the anatomical site, tumor microenvironment, and other cytogenetic events in their divergent biologic behavior deserve further investigation.

Since the first edition of this book, the impressive development of neuroendoscopy has dramatically changed the surgical approach to hydrocephalus, the main pathology pediatric neurosurgeons worldwide have to deal with. This revised and updated second edition, written by worldwide leaders in the field, fully reflects this progress: not only existing chapters have been reviewed whenever required, but new ones have been added thus taking into consideration every aspect of hydrocephalus, even when associated with the rarest pathologies. The general part include now more data on history, biomechanics, circulation and molecular basis. Special consideration for fetal surgery has been added, whereas the section on neonatal hydrocephalus has been further developed. Section 4, on the different pathologies associated with hydrocephalus, has been significantly expanded. and is now amazingly detailed, as well as the section on shunt treatment. Infections are now dealt with in two different chapters, and special attention to shunt complications (the nightmare of every Pediatric Neurosurgeon.) is paid in five different chapters. A very complete overview of the endoscopic treatment, that will surely draw the reader’s attention thanks to the wonderful full color images, is also included. Written by acknowledged experts in the field, this title is an indispensable tool for all those facing this pathology in their daily practice.

Background Diagnosis and treatment of primary lung adenocarcinoma in children remains challenging given its rarity. Here we highlight the clinical history, pathological evaluation, genomic findings, and management of a very young patient with metastatic lung adenocarcinoma. Case presentation A 10-year-old white girl presented with brain metastases due to primary pulmonary adenocarcinoma. Next generation sequencing analysis with “Comprehensive Cancer Panel” highlighted the presence of multiple non-targetable mutations in the FLT4, UBR5, ATM, TAF1, and GUCY1A2 genes. She was treated aggressively with chemotherapy, surgery, and radiation therapy for local and distant recurrence. Eventually, therapy with nivolumab was started compassionately, and she died 23 months after diagnosis. Conclusions Extremely rare cancers in children such as lung adenocarcinoma need accurate and specific diagnosis in order to develop an optimal plan of treatment. It is also necessary to underline that “children are not little adults,” thus implying that an adult-type cancer in the pediatric population might have a different etiopathogenesis. Diagnostic confirmation and primary treatment of such rare conditions should be centralized in reference centers, collaborative networks, or both, with multidisciplinary approaches and very specific expertise.

BACKGROUND: Neurofibromatosis type 1 (NF1) is related to a generally increased prevalence of seizures. The mechanism underlying the increased predisposition to seizures has not been fully elucidated. The aim of the study was to evaluate the role of NF1 in seizures pathogenesis in a cohort of children with NF1 and seizures. METHODS: The medical records of 437 children (0-18 years old) with NF1 were reviewed. All children with at least one afebrile seizure were included. Demographic, clinical, neurological, NF1 mutation status, and EEG data were collected along with brain magnetic resonance imaging. Depending on etiology, structural seizures have been identified and were further classified as NF1 related or not. RESULTS: Nineteen patients (4.3%; 13 males) were included. NF1 was inherited in 7 (37.5%), with 3 maternal forms. Ten children with structural seizures were identified. Seven forms were identified someway related to NF1, two of which were associated to 17q11.2 microdeletion and hypoxic-ischemic encephalopathy. Any brain lesion that could explain seizures was found in nine patients, two third of these patients had a familiar history of epilepsy. CONCLUSIONS: Our results suggest seizures are more frequent in NF1 children (4.3%) than in general pediatric population (0.3-0.5%) and that are someway related to NF1 in half of patients. Facing seizures in NF1, the clinician should first exclude brain tumors but also other, and rarer NF1-related scenarios, such as hydrocephalous and vasculopathies. Children with non-structural seizures frequently had a family history of epilepsy, raising questions about the pathogenic role of NF1. They should be approached as for the general population.

Although the association between hydrocephalus and epilepsy is well recognized, much controversy still exists about the incidence of epilepsy amongst hydrocephalic children. The reported occurrence varies from 6% to 59% in the literature [4, 6, 7, 12, 14, 16, 18, 22, 28–30, 36, 39, 41–>43]. There are many factors that may account for this, including the etiology of the hydrocephalus, its subsequent treatment and any resulting complications. A few studies indicate that the presence of a shunt [2, 13, 16, 26, 39], the number of shunt revisions [5, 6, 7, 13, 16, 28, 41], a history of shunt infection [2, 4, 5, 6, 16, 28, 39] and perhaps the shunt location [3, 7] increase the risk of developing seizures. However, long-term follow-up has rarely been provided and a number of important questions still remain unanswered. For example, the relationship between raised intracranial pressure and seizures and the way in which seizures in hydrocephalic children may affect developmental outcome have been poorly documented.

Purpose: The aims of patients’ radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. Methods: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. Results: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5–104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. Conclusions: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI

OBJECTIVEIn the past, the outcome of surgical treatment for thalamic tumor was poor. These lesions were often considered inoperable. However, contemporary microsurgical techniques, together with improvements in neuroimaging that enable accurate presurgical planning, allow resection to be accomplished in a safer way.METHODSThe medical records, imaging studies, and operative and pathology reports obtained for pediatric patients who were treated for thalamic tumors at the authors’ department were reviewed. Neuronavigation and intraoperative monitoring of motor and somatosensory evoked potentials were used. Preoperative tractography, which helped to identify internal capsule fibers, was very important in selecting the surgical strategy. Postoperatively, an MRI study performed within 24 hours was used to assess the extent of tumor resection as partial (≤ 90%), subtotal (> 90%), or gross total (no residual tumor).RESULTSSince 2002, 27 children with thalamic tumors have been treated at the authors’ department. There were 9 patients with unilateral thalamic tumors, 16 with thalamopeduncular tumors, and 2 with a bilateral tumor. These last 2 patients underwent endoscopic biopsy and implantation of a ventriculoperitoneal shunt. Thirty-nine tumor debulking procedures were performed in the remaining 25 patients. Different surgical approaches were chosen according to tumor location and displacement of the posterior limb of the internal capsule (as studied on axial T2-weighted MRI) and corticospinal tract (as studied on diffusion tensor imaging with tractography, after it became available). In 12 cases, multiple procedures were performed; in 7 cases, these were done as part of a planned multistage resection. In the remaining 5 cases, the second procedure was necessary because of late recurrence or regrowth of residual tumor.At the end of the surgical phase, of 25 patients, 15 (60%) achieved a gross-total resection, 4 (16%) achieved a subtotal resection, and 6 (24%) achieved a partial resection. Eighteen patients harbored low-grade tumors in our series. In this group, the mean follow-up was 45 months (range 4–132 months). At the end of follow-up, 1 patient was dead, 12 patients were alive with no evidence of disease, 4 patients were alive with stable disease, and 1 was lost to follow-up. All patients were independent in their daily lives. The outcome of high-grade tumors in 9 patients was very poor: 2 patients died immediately after surgery, 6 died of progressive disease, and 1 was alive with residual disease at the time of this report.CONCLUSIONSThis institutional review seems to offer further evidence in favor of attempts at radical resection in pediatric patients harboring unilateral thalamic or thalamopeduncular tumors. In low-grade gliomas, radical resection in a single or staged procedure can be curative without complementary treatment. Recurrences or residual regrowth can be safely managed surgically. In high-grade tumors, the role of and opportunity for radical or partial resection remains a matter of debate.

Subdural fluid collections following intraventricular and/or paraventricular procedures in pediatric neurosurgery are common and can be hard to treat. We describe our technique to close cortical defects by the aid of a fibrin adhesive and subsequent Ringer inflation with the aim to avoid cortical mantle collapse and to prevent the development of subdural fluid collections. We report the preliminary results of a prospective study on a consecutive series of 29 children who underwent 37 transcortical or transcallosal surgical procedures since 2008 in our department. In 17 procedures, we performed a transcortical approach on lesions, and in other 19 operations, we operated by a transcallosal. In 5/17 transcortical approaches (29 %) and in 3/20 transcallosal approaches (15 %), we observed a 5-mm-thick subdural fluid collection of the 5 patients with subdural fluid collections in the transcortical group, 3 patients (17 %) underwent surgery for symptomatic or progressive subdural fluid collections. Of the 3 patients in the transcallosal group, a subduro-peritoneal shunt was necessary only for 1 patient (5 %). At the very end of the treatment (including chemotherapy and radiotherapy), it was possible to remove the subduro-peritoneal shunt in all these patients because of disappearance of the subdural fluid collections. In pediatric patients after transcortical or transcallosal procedures, the use of a fibrin adhesive to seal surgical opening and subsequent inflation of the residual cavity with Ringer lactate solution to avoid cortical mantle collapse seems safe and appears to prevent the development of subdural fluid collections.

Arachnoid cysts are fluid-filled sacs, located between the brain or spinal cord and the arachnoid membrane. Their prevalence in children is between 1% and 3%. Quadrigeminal arachnoid cysts represent 1% to 10% of them and are often associated with hydrocephalus, mostly by an obstructive mechanism, explained by compression of the tectum of the midbrain. When an indication for treatment is retained, 3 surgical options are available: microsurgical excision/fenestration, endoscopic fenestration, and shunt placement. Endoscopic treatment is considered the best compromise of definitive treatment with least surgical morbidity, especially because quadrigeminal cysts are located close to the midline, in intimate relationships with basal cisterns and ventricles. We here present the endoscopic treatment of a prenatally diagnosed quadrigeminal arachnoid cyst type III1 with right lateral extension into the middle cerebral fossa, and associated hydrocephalus, treated at the age of 18 mo.Step-by-step detail of surgical technique is presented in original anatomic conditions. Restoration of better cerebrospinal fluid pathways being the objective of this surgery, ventriculocystic, and cyst-cisternal fenestrations were made. Secondary obstruction of the cyst occurred a few months later, requiring further endoscopic treatment to obtain a larger fenestration that allowed good long-term clinical and radiological outcome. The key point of this video is to compare the 2 procedures, stressing the importance of the dimension of fenestrations, to ensure a long-term patency of both stomas.The patient being a child, both parents gave their consent for publication and signed a form.

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3. Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3. 10.1093/brain/awy039-video1 awy039media1 5742053534001

OBJECTIVEHydrocephalus remains one of the more common pathologies managed in pediatric neurosurgical units. Endoscopic third ventriculostomy (ETV) has an advantage over ventriculoperitoneal shunting as it enables patients to remain device free. Multiple shunt devices with various valve designs exist, with no one valve proven to be superior to another. The aim of this study was to describe the management of hydrocephalus and its long-term outcome.METHODSThe authors retrospectively reviewed the medical records of all patients who had been treated for hydrocephalus at the Hôpital Necker-Enfants Malades in the period from 1985 to 1995.RESULTSNine hundred seventy-five children had been treated for hydrocephalus. The mean follow-up was 11 ± 7.4 years (mean ± standard deviation). The most common cause of hydrocephalus was tumor related (32.3%), followed by malformative (24.5%) and inflammatory (20.9%) causes. Two hundred eighty patients underwent ETV as the first-line treatment. The procedure was effective in controlling hydrocephalus due to posterior fossa tumors and aqueductal stenosis. Six hundred ninety-five children had initial shunt insertion, with the majority receiving an Orbis-Sigma valve (OSV). The overall OSV shunt survival was 70% at 1 year, 58% at 10 years, and 49% at 20 years. The most common cause for mechanical shunt failure was obstruction (50.7%). Overall shunt survival was statistically different between the OSV and the differential-pressure valve (p = 0.009).CONCLUSIONSEndoscopic third ventriculostomy is effective in the management of childhood hydrocephalus. Its success is directly related to the underlying pathology. In the long term, the OSV has significantly higher event-free shunt survival than the classic differential-pressure valve systems

Melanotic neuroectodermal tumor of infancy is a rare congenital pigmented neoplasm of neural crest origin, locally aggressive, growing rapidly and developing during the 1st year of life. It most commonly arises from the maxilla, cranial vault, and mandible. Occasionally, it exhibits malignant behavior with local lymph nodes involvement. Cases misdiagnosed and left untreated for a long time can present challenges due to the tumor mass and infiltration. In these cases, adjuvant chemotherapy can be extremely helpful before radical excision.Authors of this report describe a 4-year-old boy from a developing country who was referred to their hospital with an ulcerated bulging lesion in the midline/right parietooccipital region, extending to the right laterocervical and parotid regions, resulting in significant craniofacial deformation. Magnetic resonance imaging of the brain revealed a highly enhancing tumor with intracranial and extracranial development extending mainly at the level of the right parietooccipital region, with lytic and hypertrophic alterations of the skull. The patient was managed with neoadjuvant and adjuvant chemotherapy and radically resective surgery on metastatic lymph nodes and the primary tumor of the skull. Scheduled radiotherapy was not performed, according to the parents' wishes. The patient returned to his native country where the lesion recurred, and he ultimately died approximately 10 months after the end of the treatment.The literature indicates that tumor removal alone has been the treatment of choice in most isolated cases, but in cases of highly advanced tumor with involvement of the skull and cervical lymph nodes, it is preferable to proceed with preoperative chemotherapy with the aim of reducing the tumor volume, allowing better technical conditions for complete surgical removal, and decreasing the risk of local recurrence or metastasis.

BACKGROUND: Growing demand for transparent and standardized methods for evaluating surgical competence prompted the construction of the Neuro-Endoscopic Ventriculostomy Assessment Tool (NEVAT).OBJECTIVE: To provide validity evidence of the NEVAT by reporting on the tool's internal structure and its relationship with surgical expertise during simulation-based training.METHODS: The NEVAT was used to assess performance of trainees and faculty at an international neuroendoscopy workshop. All participants performed an endoscopic third ventriculostomy (ETV) on a synthetic simulator. Participants were simultaneously scored by 2 raters using the NEVAT procedural checklist and global rating scale (GRS). Evidence of internal structure was collected by calculating interrater reliability and internal consistency of raters' scores. Evidence of relationships with other variables was collected by comparing the ETV performance of experts, experienced trainees, and novices using Jonckheere's test (evidence of construct validity).RESULTS: Thirteen experts, 11 experienced trainees, and 10 novices participated. The interrater reliability by the intraclass correlation coefficient for the checklist and GRS was 0.82 and 0.94, respectively. Internal consistency (Cronbach's alpha) for the checklist and the GRS was 0.74 and 0.97, respectively. Median scores with interquartile range on the checklist and GRS for novices, experienced trainees, and experts were 0.69 (0.58-0.86), 0.85 (0.63-0.89), and 0.85 (0.81-0.91) and 3.1 (2.5-3.8), 3.7 (2.2-4.3) and 4.6 (4.4-4.9), respectively. Jonckheere's test showed that the median checklist and GRS score increased with performer expertise (P=.04 and.002, respectively).CONCLUSION: This study provides validity evidence for the NEVAT to support its use as a standardized method of evaluating neuroendoscopic competence during simulation-based training.

Pure aqueductal tumors (ATs) differ from pineal region and tectal/tegmental tumors in that they are epicentered within the aqueduct. Nevertheless, these tumors are rarely described as a separate type of tumor, and are often grouped with other lesions located in the same vicinity. The present multicenter study focuses on our experience treating patients with pure ATs. Data from three large tertiary centers was collected retrospectively, including presenting symptoms, treatment paradigm, surgical approaches, pathology, and outcome. Between 1999 and 2013, 16 patients with AT were diagnosed and treated at the three tertiary centers. Ages at presentation ranged from 5.5 to 57 years. Thirteen patients presented with hydrocephalus-related symptoms, and two were identified incidentally. Thirteen patients underwent an endoscopic third ventriculostomy, and two of these underwent a simultaneous endoscopic biopsy (one grade II ependymoma, one non-specified low-grade glioma). Two others underwent shunt placement. Three patients underwent resection due to tumor progression. Pathologies included glioblastoma multiforme, glioneural tumor, and ependymoma grade II. All non-resected tumors remained stable or grew only minimally. ATs are a rare entities that usually present with obstructive hydrocephalus. Treatment includes primarily cerebrospinal fluid drainage (preferably via an endoscopic third ventriculostomy). Simultaneous endoscopic biopsy may be done in selected cases. Tumor resection should be reserved for growing tumors; the trans-fourth ventricular or trans-choroidal approaches are probably safer than other approaches used to reach the tectal region.

Aims of patient follow-up are: discovering relapse to apply second-line therapy for possible cure, accruing patients in phase 1/2 protocols if second-line therapy is not standardized/curative, evaluating/treating iatrogenic effects. To lessen the patient/family emotional and social economic burdens, we should ideally understand if scheduled radiological follow-up has a better rationale/outcome than the symptomatic relapse. We analyzed the Italian series of 2016 (doi:10.1093/neuonc/now108) comprehending 160 newly diagnosed pediatric/adolescent patients with intracranial ependymoma (EPD) according to relapse status (recurrence at scheduled exam [RECPT]/sign-symptomatic recurring [SYMPPT]). RECPT and SYMPPT were assessed in Cox model as time-dependent variables for overall survival (OS). Differences in characteristics between RECPT and SYMPPT subgroups were assessed by Wilcoxon-Mann-Whitney or Fisher Exact tests. Kaplan-Meier curves depicted event-free survival (EFS) and OS after recurrence according to signs/symptoms. There were 16 SYMPPT /34 RECPT, at a median follow-up of 55 months. No significant differences were found between SYMPPT/RECPT for gender, age, tumor grade/site, shunt, residual disease, radiation boost, type of relapse (local/distant/combined). Time-to-relapse (median:19 months, range 5–104) and treatment adoption did not differ between SYMPPT/RECPT while signs/symptoms depicted an unfavorable factor for OS after relapse (5-year OS: 8% vs 37%). Adjusted model in multivariate analysis confirmed that presence of signs/symptoms was prognostically unfavorable. In order to improve the OS in symptomatic patients, their early identification-in the first two/three years after diagnosis- would be desirable. Perhaps, this could be obtained paying attention to “heuristically detected” subgroup of patients, not just describing general prognostic variables but discovering possible biology differences according to signs/symptoms.

Endoscopic third ventriculostomy (ETV) is a safe and less-invasive treatment strategy for patients with obstructive hydrocephalus and provides excellent outcome. Nevertheless, repeat ETV in cases of ETV failure is a controversial issue.Between 1993 and 1999, 113 patients underwent a total of 126 ETVs at the Department of Neurosurgery, Mainz University Hospital. Obstructive hydrocephalus was the causative pathology in all cases. A very long-term follow-up of up to 16 years could be achieved. All medical reports of patients who received ETV were reviewed and analyzed with focus on ETV failure with following repeat ETV and its initial as well as very long-term success.Thirty-one events of ETV failure occurred during the follow-up period. Thirteen patients underwent repeat ETV: 3 patients during the first 3 months (early repeat ETV), the other 10 patients after 7-78 months (late repeat ETV, mean 33 months). All repeat ETV were performed without complications. Follow-up evaluation after successful repeat ETV ranged from1 month up to 14 years (mean 7 years). Of the 3 early revisions, 2 failed and 1 other patient died during follow-up whereas only 2 of the late repeat ETV failed. Very long-term success rate of late repeat ETV up to 14 years yielded 80%.Repeat ETV in cases of late ETV failures represents an excellent option for cerebrospinal fluid circulation restoration up to 14 years of follow-up. Repeat ETV in early ETV failure in contrast is not favored by the performing surgeons; and factors of ETV failure should be analyzed very carefully before a decision for repeat ETV is made.

Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered. This study included 18 children. The mean age was 2.93 ± 3.03 years at the NF1 diagnosis and 7.43 ± 4.27 years at the MMS diagnosis. In seven patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was performed in 10 patients due to clinical symptoms, including headache (n = 6), cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining eight children (47%) had MMS diagnosed incidentally. Sixteen children were characterized molecularly. The features of MMS were similar between patients with and without NF1. Additionally, the NF1 phenotype and genotype were similar between children with and without MMS. Interestingly, three children experienced tumors with malignant histology or behavior. The presence of two first cousins in our cohort suggested that there may be potential genetic factors, not linked to NF1, with an additional role respect of NF1 might play a role in MMS pathogenesis. The incidental diagnosis of MMS, and the observation that, among children with NF1, those with MMS were clinically indistinguishable from those without MMS, suggested that it might be worthwhile to add an angiographic sequence to brain MRIs requested for children with NF1. A MMS diagnosis may assist in properly addressing an NF1 diagnosis in very young children who do not fulfill diagnostic criteria.

EPN-02. FINAL RESULTS OF THE 2ND AIEOP PROTOCOL FOR INTRACRANIAL EPENDYMOMA (EPD) Maura Massimino1, Rosalba Miceli1, Felice Giangaspero2,3, Luna Boschetti1, Paolo Ferroli4, Paola Peretta5, Emilia Pecori1, Laura Valentini4, Veronica Biassoni1, Maria Luisa Garre6, Elisabetta Schiavello1, Iacopo Sardi7, Armando Cama6, Silvia Scoccianti8, Maurizio Mascarin9, Lorenzo Genitori7, Daniele Bertin5, Anna Mussano10, Elisabetta Viscardi11, Piergiorgio Modena12, GiuseppinaCalareso1, Salvina Barra13, Giovanni Scarzello14, LuciaQuaglietta15, Giuseppe Cinalli15, Angela Mastronuzzi16, Carlo Giussani17, Carlo Marras16, Rita Balter18, Patrizia Bertolini19, Ermanno Giombelli19, Francesca Buttarelli2, Manila Antonelli2, and Lorenza Gandola1; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Universita Sapienza Roma, Roma, Italy; Neuromed Pozzilli, Pozzilli, Italy; Fond IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; Ospedale Infantile Regina Margherita, Torino, Italy; Istituto Giannina Gaslini, Genova, Italy; Ospedale Pediatrico Meyer, Firenze, Italy; OspedaleCareggi,Firenze, Italy;CRO,Aviano, Italy;OspedaleS.Anna, Torino, Italy; Clinica di Oncoematologia Pediatrica, Padova, Italy; Genetica, Osp S. Anna, Como, Italy; Istituto dei Tumori, Genova, Italy; Istituto Oncologico del Veneto, Padova, Italy; Ospedale Pausillipon, Napoli, Italy; Ospedale Bambino Gesu, Roma, Italy; Ospedale S. Gerardo, Monza, Italy; Ospedale Borgo Roma, Verona, Italy; Ospedale, Parma, Italy This study stratified patients after surgical resection (complete 1⁄4 NED vs incomplete 1⁄4 ED) and centrally reviewed histology(gr.2 vs gr. 3). Gr2 tumors/NEDpts were focally irradiated with a 3D-conformal technique 1.8Gy/d up to 59.4 Gy, gr3/NED received also 4 VEC(Cyclo,VP16,VCR) after irradiation. EDpts received 1-4 VEC, second-look surgery whenever possible,59.4 Gy followed by 8 Gy boost into 2 fractions on still measurable residue. Children aged 1-3 yrs received the same treatment but for those gr2/NED who could receive only 6 VEC. Between January 2002/December 2014, 160 consecutive children, median age 4.9 years, entered the protocol; follow-up was a median 67 months. M/F was 100/60, infratentorial origin in 110(2 plus metastasis). After surgery, NEDpts were 110,grade 3 was assessed in 84. 100 resections were performed in 46/160 children with another 12 rendered NED after first excision,10 after 1-4 VEC,2 after radiation. Boost was applied to 24/40 still ED patients after surgery/ies and VEC obtaining PFS/OS of 58.1%/68.7% in this severe prognosis subgroup. For the whole series,5-year PFS/OS were 65.4%/81.1% with no toxic deaths. In univariable analysis, female gender, supratentorial origin, NED status before RT, grade 2, shunt absence were favourable for OS, in multivariable NED status and grade 2 were. For PFS, female gender, NED status before RT, grade 2 were significant in univariable, only grade in multivariable. In a multicentric collaboration this trial accrued the highest patient number so far published with comparable results to best monoinstitutional series. Radiation boost was feasible and efficacious in improving local control. Complete surgery, also through multiple excisions, still confirmed its prognostic strength as well as grade. Further biological parameter definition on this series will be the object of next coming studies. Neuro-Oncology 18:iii30–iii39, 2016. doi:10.1093/neuonc/now070.2 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chiari malformation type I (CM-I) and hydrocephalus are often associated with complex craniosynostosis. On the contrary, their simultaneous occurrence in monosutural synostosis is extremely rare. The pathophysiological hypothesis is that they may alter posterior fossa growth and lead to cerebellar tonsil herniation also without skull base primary involvement. Hydrocephalus is multifactorial and may be secondary to fourth ventricle outlet obstruction. The management of these cases is quite complex and not well defined. Cranial vault remodeling should be the only treatment when CM-I is asymptomatic and not related to syringomyelia. Suboccipital decompression should be reserved only in complicated CM-I, usually as a second surgical step following the correction of the supratentorial deformity. In our opinion, the associated hydrocephalus should be treated first in order to normalize intracranial hypertension before opening the cranial sutures. We report the case of a 26-month-old child that presented with sagittal craniosynostosis, hydrocephalus, and CM-I. He was managed by performing endoscopic third ventriculostomy (ETV) first and cranial vault remodeling thereafter. Clinico-radiological outcome was very satisfying. Concerning literature is reviewed; physiopathology and surgical management are discussed.