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Evaluation of orbital proptosis and sutural synostosis pattern along the coronal ring in craniofaciosynostosis patients with or without fibroblastic growth factor receptor 2 (FGFR2) mutation. High-resolution computer tomography was used to assess, in children with or without FGFR2 mutation, the early synostotic involvement of the “major” and “minor” sutures/synchondroses of the coronal arch along with the following orbital parameters: interorbital angle, bone orbital cavity volume, globe volume, ventral globe volume, ventral globe index. Infants with FGFR2 mutation showed an increased number of closed minor sutures/synchondroses along the posterior coronal branch while both groups showed a comparable synostotic involvement of the minor sutures of the anterior coronal branch. FGFR2 infants with posterior coronal branch synostotic involvement showed a higher degree of proptosis due to both reduced bony cavity volume and increased globe volume (p

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.

The association between Chiari type I malformation (CIM) and hydrocephalus raises a great interest because of the still unclear pathogenesis and the management implications. The goal of this paper is to review the theories on the cause-effect mechanisms of such a relationship and to analyze the results of the management of this condition. A review of the literature has been performed, focusing on the articles specifically addressing the problem of CIM and hydrocephalus and on the series reporting about its treatment. Also, the personal authors’ experience is briefly discussed. As far as the pathogenesis is concerned, it seems clear that raised intracranial pressure due to hydrocephalus can cause a transient and reversible tonsillar caudal ectopia (“pressure from above” hypothesis), which is something different from CIM. A “complex” hypothesis, on the other hand, can explain the occurrence of hydrocephalus and CIM because of the venous engorgement resulting from the hypoplasia of the posterior cranial fossa (PCF) and the occlusion of the jugular foramina, leading to cerebellar edema (CIM) and CSF hypo-resorption (hydrocephalus). Nevertheless, such a mechanism can be advocated only in a minority of cases (syndromic craniosynostosis). In non-syndromic CIM subjects, the presence of hydrocephalus could be explained by an occlusion of the basal CSF pathways, which would occur completely in a minority of cases (only 7–10% of CIM patients show hydrocephalus) while it would be partial in the remaining cases (no hydrocephalus). This hypothesis still needs to be demonstrated. As far as the management is concerned, the strategy to treat the hydrocephalus first is commonly accepted. Because of the “obstructive” origin of CIM-related hydrocephalus, the use of endoscopic third ventriculostomy (ETV) is straightforward. Actually, the analysis of the literature, concerning 63 cases reported so far, reveals very high success rates of ETV in treating hydrocephalus (90.5%), CIM (78.5%), and syringomyelia symptoms (76%) as well as in giving a radiological improvement of both CIM (74%) and syringomyelia (89%). The failures of ETV were not attributable to CIM or syringomyelia. Only 11% of cases required PCF decompression after ETV. The association between CIM and hydrocephalus probably results from different, multifactorial, and not yet completely understood mechanisms, which place the affected patients in a peculiar subgroup among those constituting the heterogeneous CIM population. ETV is confirmed as the best first approach for this subset of patients.

The Dutch ophthalmologist, Jan van der Hoeve, first introduced the terms phakoma/phakomata (from the old Greek word "ϕαχοσ" = lentil, spot, lens-shaped) to define similar retinal lesions recorded in tuberous sclerosis (1920) and in neurofibromatosis (1923). He later applied this concept: (a) to similar lesions in other organs (e.g. brain, heart and kidneys) (1932) and (b) to other disorders (i.e. von Hippel-Lindau disease and Sturge-Weber syndrome) (1933), and coined the term phakomatoses. At the same time, the American neurologist Paul Ivan Yakovlev and psychiatrist Riley H. Guthrie (1931) established the key role of nervous systems and skin manifestations in these conditions and proposed to name them neurocutaneous syndromes (or ectodermoses, to explain the pathogenesis). The Belgian pathologist, Ludo van Bogaert, came to similar conclusions (1935), but used the term neuro-ectodermal dysplasias. In the 1980s, the American paediatric neurologist Manuel R. Gomez introduced the concept of "hamartia/hamartoma" instead of phakoma/phakomata. "Genodermatoses" and "neurocristopathies" were alternative terms still used to define these conditions. Nowadays, however, the most acclaimed terms are "phacomatoses" and "neurocutaneous disorders", which are used interchangeably. Phacomatoses are a heterogeneous group of conditions (mainly) affecting the skin (with congenital pigmentary/vascular abnormalities and/or tumours), the central and peripheral nervous system (with congenital abnormalities and/or tumours) and the eye (with variable abnormalities). Manifestations may involve many other organs or systems including the heart, vessels, lungs, kidneys and bones. Pathogenically, they are explained by interplays between intra- and extra-neuronal signalling pathways encompassing receptor-to-protein and protein-to-protein cascades involving RAS, MAPK/MEK, ERK, mTOR, RHOA, PI3K/AKT, PTEN, GNAQ and GNA11 pathways, which shed light also to phenotypic variability and overlapping. We hereby review the history, classification, genomics, clinical manifestations, diagnostic criteria, surveillance protocols and therapies, in phacomatoses: (1) predisposing to development of tumours (i.e. the neurofibromatoses and allelic/similar disorders and schwannomatosis; tuberous sclerosis complex; Gorlin-Goltz and Lhermitte-Duclos-Cowden syndromes); (2) with vascular malformations (i.e. Sturge-Weber and Klippel-Trenaunay syndromes; megalencephaly/microcephaly-capillary malformation syndromes; CLOVES, Wyburn-Mason and mixed vascular nevus syndromes; blue rubber bleb nevus syndrome; hereditary haemorrhagic telangiectasia); (3) with vascular tumours (von Hippel-Lindau disease; PHACE(S)); (4) with pigmentary/connective tissue mosaicism (incontinentia pigmenti; pigmentary/Ito mosaicism; mTOR-related megalencephaly/focal cortical dysplasia/pigmentary mosaicism; RHOA-related ectodermal dysplasia; neurocutaneous melanocytosis; epidermal/papular spilus/Becker nevi syndromes; PENS and LEOPARD syndromes; encephalocraniocutaneous lipomatosis; lipoid proteinosis); (5) with dermal dysplasia (cerebellotrigeminal dermal dysplasia); and (6) with twin spotting or similar phenomena (phacomatosis pigmentovascularis and pigmentokeratotica; and cutis tricolor).

Two degrees of posterior cranial fossa (PCF) maldevelopment can be hypothesized in children with myelomeningocele (MMC). This paper investigates the PCF deformation by quantitative magnetic resonance imaging analysis in MMC subjects with and without Chiari 2 malformation (CM2).PCF bone volume (PCFV), PCF brain volume (PCFBV), lengths of PCF, ventriculomegaly, level, and extension of the dysraphism were analyzed by magnetic resonance image scanning of 51 newborns with MMC surgically repaired at birth (and 41 controls). The possible correlation among PCF hypoplasia, level/extension of the spinal dysraphism, and ventriculomegaly was assessed.In MMC and CM2, the dysraphism level was above L4 in 30 and below L4 in 10 subjects. PCFV/PCFBV ratio and supraocciput and exocciput lengths were significantly reduced; foramen magnum diameters, mammillo-pontine distance, and pons length were significantly increased (P 0.05). In isolated MMC, the dysraphism level was below L4 in all cases. PCFV/PCFBV ratio and supraocciput length were significantly reduced; pons length was significantly increased (P0.05). The lower the MMC level, the lower the incidence of CM2. A positive correlation was found between PCF hypoplasia and MMC level above L4 (P0.001), while a negative correlation was found among PCF hypoplasia and MMC extension (P = 0.006), PCF hypoplasia, and ventriculomegaly (P = 0.02).PCF hypoplasia has to be considered a dynamic maldevelopment process in the 2 cohorts rather than 2 separated entities. The level of MMC is the main but not the unique cause influencing the severity of PCF maldevelopment.

The aim of this study was to identify quantitative tools to classify the severity of trigonocephaly to guide surgical management and predict outcome. METHODS We reviewed high-resolution computed tomography images of 59 patients with metopic synostosis. We assessed the craniofacial sutural pattern as well as interfrontal and metopic angles, and we related the frontal angulation degree with the sutural pattern, the surgical management, and clinical outcome. RESULTS We identified 3 groups according to the severity of trigonocephaly. No difference was found between the sutural pattern of nasion complex and severity, whereas the closure of zygomatic maxillary sutures increased with the severity degree (P < 0.05). The operative management was related to the severity degree (P < 0.001) and to the reduced age (P = 0.009). CONCLUSIONS Interfrontal and metopic angles are complementary measurements to evaluate with high accuracy the degree of frontal angulation. In preoperative assessment, they may guide surgery decision in particular when the choice is not straightforward.

For selected children with medically intractable epilepsy, hemispherectomy can be an excellent treatment option and its efficacy in achieving seizure freedom or reduction in seizure frequency has been shown in several studies, but patients’ selection could not be straightforward and often it is taken on subjective basis. We described a multimodal approach to assess patient eligible for hemispherectomy and possibly predicting post-surgical outcomes. We describe pre- and post-surgical clinical features along with neuroradiological results by magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MR-tractography (MRT), and neurophysiological study by single and paired pulses transcranial magnetic stimulation (TMS) in a child with cerebral palsy with epileptic encephalopathy, eligible for epilepsy surgery. Presurgical TMS evaluation showed a lateralization of motor function on the left motor cortex for both arms, and results were confirmed by MRI studies. Interestingly, after surgery, both epilepsy and motor performances improved and TMS showed enhancement of intracortical inhibition and facilitation activity. Functional hemispherectomy is an effective treatment for drug-resistant epilepsy, and multimodal presurgical assessment may be a useful approach to guide surgeons in selecting patients. Moreover, pre- and post-surgical evaluation of these patients may enhance our understanding of brain plasticity phenomena.

Neurocutaneous melanosis (NCM; MIM # 249400; ORPHA: 2481], first reported by the Bohemian pathologist Rokitansky in 1861, and now more precisely defined as neurocutaneous melanocytosis, is a rare, congenital syndrome characterised by the association of (1) congenital melanocytic nevi (CMN) of the skin with overlying hypertrichosis, presenting as (a) large (LCMN) or giant and/or multiple (MCMN) melanocytic lesions (or both; sometimes associated with smaller "satellite" nevi) or (b) as proliferative melanocytic nodules; and (2) melanocytosis (with infiltration) of the brain parenchyma and/or leptomeninges. CMN of the skin and leptomeningeal/nervous system infiltration are usually benign, more rarely may progress to melanoma or non-malignant melanosis of the brain. Approximately 12% of individuals with LCMN will develop NCM: wide extension and/or dorsal axial distribution of LCMN increases the risk of NCM. The CMN are recognised at birth and are distributed over the skin according to 6 or more patterns (6B patterns) in line with the archetypical patterns of distribution of mosaic skin disorders. Neurological manifestations can appear acutely in infancy, or more frequently later in childhood or adult life, and include signs/symptoms of intracranial hypertension, seizures/epilepsy, cranial nerve palsies, motor/sensory deficits, cognitive/behavioural abnormalities, sleep cycle anomalies, and eventually neurological deterioration. NMC patients may be symptomatic or asymptomatic, with or without evidence of the typical nervous system changes at MRI. Associated brain and spinal cord malformations include the Dandy-Walker malformation (DWM) complex, hemimegalencephaly, cortical dysplasia, arachnoid cysts, Chiari I and II malformations, syringomyelia, meningoceles, occult spinal dysraphism, and CNS lipoma/lipomatosis. There is no systemic involvement, or only rarely. Pathogenically, single postzygotic mutations in the NRAS (neuroblastoma RAS viral oncogene homologue; MIM # 164790; at 1p13.2) proto-oncogene explain the occurrence of single/multiple CMNs and melanocytic and non-melanocytic nervous system lesions in NCM: these disrupt the RAS/ERK/mTOR/PI3K/akt pathways. Diagnostic/surveillance work-ups require physical examination, ophthalmoscopy, brain/spinal cord magnetic resonance imaging (MRI) and angiography (MRA), positron emission tomography (PET), and video-EEG and IQ testing. Treatment strategies include laser therapy, chemical peeling, dermabrasion, and surgical removal/grafting for CMNs and shunt surgery and surgical removal/chemo/radiotherapy for CNS lesions. Biologically targeted therapies tailored (a) BRAF/MEK in NCM mice (MEK162) and GCMN (trametinib); (b) PI3K/mTOR (omipalisib/GSK2126458) in NMC cells; (c) RAS/MEK (vemurafenib and trametinib) in LCMNs cells; or created experimental NMC cells (YP-MEL).

Cranial repair after traumatic brain injury in children is still burdened by unsolved problems and controversial issues, mainly due to the high rate of resorption of autologous bone as well as the absence of valid alternative material to replace the autologous bone. Indeed, inert biomaterials are associated to satisfactory results in the short period but bear the continuous risk of complications related to the lack of osteointegration capacity. Biomimetic materials claiming osteoconductive properties that could balance their mechanical limits seem to allow good cranial bone reconstruction. However, these results should be confirmed in the long term and in larger series. Further complicating factors that may affect cranial reconstruction after head injury should be identified in the possible associated alterations of CSF dynamics and in difficulties to manage the traumatic skin lesion and the surgical wound, which also might impact on the cranioplasty outcome. All the abovementioned considerations should be taken into account when dealing with the cranial reconstruction after decompressive craniectomy in children.

Background Postoperative seizures (PSs) after neurosurgical operations are common but little is known about the role of surgical brain incision on their genesis. This topic has not been addressed so far. Objective To verify if the corticotomy affects the risk of PSs and postoperative epilepsy (PE) in children. Methods One hundred forty-three consecutive pediatric cases operated on for supratentorial lesions at the same institution in the last 15 yr have been retrospectively reviewed by dividing them into group A, 68 children who required brain corticotomy mainly for hemispheric tumors, and group B, 75 children treated through extracortical approaches mainly for suprasellar and optic tumors. Patients with possible "epileptic" biases, like preoperative seizures, were excluded. Results No significant differences have been found between group A and B as far as incidence of PSs (11.7% vs 14.5%) and PE (4.5% vs 6.5%), timing, and type of seizures are concerned after a mean 6.8 yr follow-up. The size of corticotomy in group A ( 3 cm2) had no impact on epileptogenesis as well as the other variables considered in both groups (age, sex, extent of lesion resection). Conclusion This study shows that the surgical cortical "trauma" would not represent a risk factor for PSs and PE. According to the present analysis and the literature, other causes seem to be involved (namely, electrolytic imbalance and brain gliosis). This information is important for preoperative surgical planning and postoperative management. A validation by both adult series and prospective studies is needed.

Craniofacial dysmorphology varies significantly along a wide spectrum of severity in metopic cranial synostosis (MCS). This study aimed to quantify craniofacial changes, in MCS, to investigate their relationships with the severity of trigonocephaly. By combining the metopic ridge and interfrontal angles, we identified three groups of trigonocephaly severity (mild group n.14, moderate group n.19, severe group n.18). We perform a quantitative analysis using high-resolution CT images evaluating (1) cranial fossae dimensions; (2) vault indices and ratios: interparietal/ intercoronal (IPD/ICD), interparietal/intertemporal (IPD/ITD), cephalic index, vertico-longitudinal index; (3) orbito-facial distances (midfacial depth, maxillary height, upper facial index, orbital distances, globe protrusions), maxilla and orbital volumes; (4) supratentorial (ICV) and infratentorial (PCFV) cranial volumes and supratentorial (WBV) and infratentorial (PCFBV) brain volumes. In all groups, middle skull base lengths and upper midface index were increased. In moderate and severe groups: anterior hemifossa lengths were reduced, IPD/ICD and vertico-longitudinal index were changed; midfacial depth, anterior, mild, and lateral interorbital distances were reduced; globe protrusions were increased. The comparison between moderate and severe groups showed an increase of both globe protrusions and IPD/ICD. Among all groups, ICV and WBV were reduced in the severe group. This morpho-volumetric study provides new insights in understanding the craniofacial changes occurring in infants at different severity of trigonocephaly. The increase of globe protrusions and the reduction of supratentorial volumes found in the severe group reflect the severity of trigonocephaly; these findings might have a clinical and surgical relevance.

This study aimed to develop a novel approach to assess the severity of skull dysmorphology in infants with isolated sagittal synostosis (ISS) and its relationship with the surgical results. We divided 66 infants with ISS into three groups by combining the scaphocephalic (SSI-A) and platycephalic (VLI) indices as descriptors of the relation between length, width, and height. We evaluated each skull for morphology as hyperdolichocephalic (

Cavum septi pellucidi (CSP) cysts have a very low incidence (0.04%). Symptomatic patients usually present aspecific symptoms. For this reason, the management of these patients is still debated.We selected the case of a ten year old patient, with a clinical history of frontal morning headaches and difficulty in concentration. Brain MRI documented a septum pellucidum cyst and a moderate biventricular dilation. We submitted the case, and a questionnaire concerning indications to surgery and management options to an international group of 54 pediatric neurosurgeons, analyzing the results and comparing them with the current literature.The majority of the participants (50%) indicated as appropriate at the early stage only a clinical observation. In case of persistence of clinical symptoms, 58% opted for intracranial pressure (ICP) monitoring, which, if raised, was considered by 91% as an adequate indication to proceed with surgical treatment. A total of 98% of the participants indicated endoscopic fenestration of the cyst as the preferred surgical strategy.The management of symptomatic patients with CSP cyst is controversial. Our results suggest that in most of the patients with aspecific symptoms, clinical observation and eventually ICP monitoring are adequate to identify patients for surgery.

Graphical abstract, Highlights • DAOY cells have been analyzed by top-down LC-high resolution-MS proteomic platform. • New protein identifications in medulloblastoma cells are reported. • PTMs, isoforms and naturally occurring peptide fragments were identified. • Most of the identified proteins were connected in a biological interacting network. • The data contribute to the further molecular characterization of medulloblastoma., The proteome of the DAOY medulloblastoma cell line has been investigated by an LC–MS top-down platform. This approach, unlike bottom-up ones, allows identifying proteins and peptides in their intact/native forms, disclosing post-translational modifications, proteoforms and naturally occurring peptides. Indeed, 25 out of the 53 proteins identified, were not previously characterized in DAOY cells. Most of them were functionally interconnected, being mainly involved in binding, catalytic and structural activities, and metabolic processes. The top-down approach, applied in this preliminary study, disclosed the presence of several naturally occurring peptide fragments that characterize DAOY cells.

The study aimed to identify premature synostosis of “major” and “minor” sutures of the coronal sutural arch and splanchnocranium sutures to evaluate the relationship between craniofacial dysmorphology and the sutural pattern in children with anterior plagiocephaly. A quantitative analysis of the skull base and facial changes was performed on preoperative high-resolution CT images in 18 children with anterior synostotic plagiocephaly and compared with imaging findings in 18 age-matched healthy subjects. All patients had patent splanchnocranium sutures. Fifteen out of 18 children showed early and isolated synostosis of the unicoronal suture (the major suture of the coronal ring) and were classified in groups II and III according to the classification scheme of anterior synostotic plagiocephaly based on the severity of craniofacial dysmorphology. Premature fusion of the unilateral coronal suture in groups II and III caused a marked asymmetry and reduced growth of the anterior and middle fossae on the synostotic side and a secondary varying severity in terms of asymmetric growth of the facial complex. Although both groups showed anterior displacement of the mandibular articulation on the synostotic side, group II showed only maxillary asymmetry, while group III showed maxillary and mandibular asymmetry. In anterior synostotic plagiocephaly, the severity of skull base changes and asymmetric growth of the facial complex is not caused by skull base sutural synostotic involvement but is probably related to the different timing of unilateral coronal suture closure.

The effects of premature fusion of one coronal suture cause skull and orbital alterations in term of side-to-side asymmetry. This study aimed to quantify the cranio-orbital complex changes related to the severity of skull base dysmorphology in patients with unicoronal synostosis. Twenty-four infants affected by unicoronal synostosis were subdivided in three subgroups according to the severity of skull base deformity and their high-resolution CT images were quantitatively analyzed (groups IIa, IIb, III). Dimensions of cranial fossae, intracranial volume (ICV), ICV synostotic and ICV non synostotic side, whole brain volume (WBV), orbital volumes (OV), ICV/WBV, ICVsynostotic/ICVnon-synostotic, and OVsynostotic/OVnon-synostotic were evaluated. Asymmetry and reduction in the growth of the anterior and middle fossae were found in all groups while asymmetry of the posterior cranial fossa was found only in IIb and III groups. In all groups, ICV, WBV, and ICV/WBV were not significantly different while ICVsynostotic/ICVnon-synostotic and OVsynostotic/OVnon-synostotic resulted significant difference (p

Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear. Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly. Cells from fused sutures displayed a reduced potential to form primary cilia compared to cells from control patent sutures of the same patient. We identified specific upregulated splice variants of the Bardet Biedl syndrome-associated gene 9 (BBS9), which encodes a structural component of the ciliary BBSome complex. BBS9 expression increased during in vitro osteogenic differentiation of suture-derived mesenchymal cells of NCS patients. Also, Bbs9 expression increased during in vivo ossification of rat sutures. BBS9 functional knockdown affected the expression of primary cilia on patient suture cells and their osteogenic potential. Computational modeling of the upregulated protein isoforms (observed in patients) predicted that their binding affinity within the BBSome may be affected, providing a possible explanation for the aberrant suture ossification in NCS.

Sinus histiocytosis (Rosai-Dorfman disease) with massive lymphadenopathy is a rare nonneoplastic and nonlangerhans cell proliferation disorder of the histiocytes. Extranodal location with or without lymphadenopathy occurs in about 40 % of the cases. Intracranial location is rare in children often mimicking meningiomas. The parasphenoidal region is more frequently involved though intraxial or intraventricular locations were described as well. Rarely, the surgical treatment allows the complete excision of the lesion; however, in symptomatic cases, partial resections of the tumor allow to counteract its mass effect. Long survivals are possible, even without radiotherapy or chemotherapy, due to the frequent spontaneous benign evolution of the lesions.A 2-year-10-month-old girl presented with high fever and vomiting. One year ago, she had a period of muscular weakness in both legs that recovered completely. MRI of the brain revealed an axial enhancing lesion with ventricular spreading mainly to the left occipital horn and bilateral frontal periventricular infiltration. After steroid therapy, all the symptoms recovered. Partial removal of the occipital intraventricular lesion was performed and the diagnosis of Rosai-Dorfman disease was established and confirmed by the reference center. At the latest follow-up (16 months), the girl is without any neurological symptoms and without any treatment.

The management of obstructive hydrocephalus associated to posterior cranial fossa tumor remains a controversial issue. In this context, the role of endoscopic third ventriculostomy (ETV) performed before tumor removal (the so-called preoperative ETV) is debated and its success rate is reported as being largely variable in the literature. We describe two children who experienced the closure of a preoperatively performed ETV after the surgical resection of their posterior fossa tumor. In both cases tumor removal was performed in the prone position. Radiological investigations and intraoperative evidence documented that the failure of the ETV was due to a blood clot which directly occluded the stoma. We speculate that the prone position favored the migration of blood, through the aqueduct, thereafter, clotting on the most declivous part of the third ventricle once the patient assumed the upright position, with the consequent occlusion of the stoma. Based on a gravitational hypothesis, we named this mechanism the "snow globe effect."

Background Myelomeningocele (MMC) is a rare but severe spinal defect resulting from a failed neurulation process. Surgical repair is a delicate procedure that needs accurate neuroanatomical knowledge and adequate surgical planning.

Background Intracranial pial arteriovenous fistulas (PAVFs) are direct communications between the arterial and venous system of the brain, with the characteristic absence of a plexiform nidus, as seen in the classic cerebral arteriovenous malformations. These vascular malformations, usually occurring in the pediatric population, very rarely are diagnosed in utero, because of a lack of understanding of the condition and because they may be hard to visualize. Case Description We report a rare case of a mass-effect PAVF diagnosed with fetal magnetic resonance imaging, involving the right cerebral hemisphere, fed by a pericallosal artery and associated with a giant venous dilatation. The PAVF initially was managed by the endovascular embolization. The recruitment of a middle cerebral artery feeder and the rapidly enlarging size of the venous pouch with mass effect required subsequent surgery. Conclusions The 2-stage multimodal treatment resulted in complete disappearance of the PAVF without complications.

Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications.

Object Functional involvement of the thalamus in cognitive processing has been only anecdotally reported in the literature, and these cases are mostly related to thalamic hemorrhages; there is no available information on cognitive development in children with thalamic tumors. Methods All children admitted with a diagnosis of thalamic tumor at the authors' institution between January 2008 and January 2011 were considered for the present study. Exclusion criteria were age less than 18 months and the presence of severe neurological deficits, both of which prevented a reliable neuropsychological evaluation. A complete preoperative neuropsychological evaluation was performed. Results Twenty children were selected (mean age 102.4 months). Total IQ was in the normal range in all patients (mean 90.1, SD 13.87) with a significant difference between verbal IQ (mean 97.70, SD 17.77) and performance IQ (mean 84.82, SD 17.01). A significant correlation was found between global cognitive impairment and a histological finding of low-grade tumors (p < 0.001). Children with a mesial thalamic tumor had a higher working memory deficit and delayed recall disorders (p < 0.001). Naming disorders were related to the presence of a bilateral (p < 0.001) or mesial (p < 0.001) thalamic tumor, without a significant difference between left or right hemisphere involvement. A significant correlation was also found between the presence of neurolinguistic disorders and mesially located tumors (p < 0.001). Children with right-sided tumors more frequently had constructional apraxia and executive function disorders (p < 0.001). Conclusions The present study suggests that thalamic tumors in different locations might have specific neuropsychological profiles.

Palsy of the abducens nerve is a neurological sign that has a wide range of causes due to the nerve's extreme vulnerability. Need of immediate neuroimaging is a matter of debate in the literature, despite the risks of delaying the diagnosis of a skull base tumor. The authors present 2 cases of skull base tumors in which the patients presented with recurrent and self-remitting episodes of sixth cranial nerve palsy (SCNP). In both cases the clinical history exceeded 1 year. In a 17-year-old boy the diagnosis was made because of the onset of headache when the tumor reached a very large size. In a 12-year-old boy the tumor was incidentally diagnosed when it was still small. In both patients surgery was performed and the postoperative course was uneventful. Pathological diagnosis of the tumor was consistent with that of a chondrosarcoma in both cases. Recurrent self-remitting episodes of SCNP, resembling transitory ischemic attacks, may be the presenting sign of a skull base tumor due to the anatomical relationships of these lesions with the petroclival segment of the sixth cranial nerve. Physicians should promptly recommend neuroimaging studies if SCNP presents with this peculiar course.

Background and importance The extracranial venous drainage of the brain is provided mainly by the jugular veins with the variable participation of extrajugular pathways. Clinical presentation Two cases of occipital sinus pericranii (SP) were observed. A 6-year-old girl presented with a progressively enlarging occipital lump; she was otherwise asymptomatic. An 8-year-old boy presented with mild nuchal headache. In the former case, neuroimaging examinations confirmed the diagnosis of SP; in the latter, SP was noticed on magnetic resonance imaging because it was neglected at physical examination. In both subjects, the radiological examination also showed bilateral occlusion of the jugular veins with ventricular dilation and herniation of cerebellar tonsils into the foramen magnum. Conclusion Exceptionally, SP was noticed to represent the main venous drainage of the underlying brain, thereby compensating for the intracranial hypertension due to venous engorgement. Preservation of SP was advised, and any surgical or endovascular treatment was contraindicated.

Background Single nucleotide polymorphisms (SNPs) on chromosome 9p21 have been recently associated with intracranial aneurysms and stroke. In this study, we tested the association between the rs1333040C>T polymorphism on the 9p21 locus and sporadic brain arteriovenous malformations (BAVMs). Methods We studied 78 patients with sporadic BAVMs and 103 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T polymorphism was assessed by PCR–restriction fragment length polymorphism using the BsmI restriction endonuclease. Results We found that the distribution of the three genotypes (TT/TC/CC) of the rs1333040 polymorphism was significantly different between cases and controls (p=0.02). Using dominant, recessive and additive genetic models, we found that the TT genotype and the T allele were significantly more common in the BAVM group than in controls. We also evaluated whether the rs1333040 polymorphism was associated with prototypical angio-architectural features of BAVMs (such as nidus size, venous drainage pattern and Spetzler–Martin grading) and with the occurrence of seizures and bleeding. We detected a significant association between the homozygous T allele in the recessive model and BAVMs with a nidus >4 cm in diameter. Deep venous drainage was significantly more frequent among subjects carrying at least one T allele in the dominant model. Patients with seizures showed a significant association with the TT genotype and the T allele in all genetic models examined whereas those who experienced intracranial bleeding showed a significant association with the T allele in the trend model. Conclusions This is the first study demonstrating an association between an SNP of the 9p21 region and sporadic BAVMs. Our results emphasise the relevance of this chromosomal locus as a common risk factor for various forms of cerebrovascular diseases.

Adamantinomatous craniopharyngioma is the third most recurrent paediatric brain tumour. Although histologically benign, it behaves aggressively as a malignant tumour due to invasion of the hypothalamus and visual pathways. Surgery is still the first and almost the only mode of treatment, although serious damage can occur as a consequence of tumour localization. The proteomic characterization of the intracystic tumoural fluid could contribute to the comprehension of the tumorigenesis processes and to the development of therapeutic targets to reduce cyst volume, allowing less invasive surgery and/or delay of the radical resection of the tumour mass and the collateral serious effects.Intracystic fluid was analysed by a LC-ESI-IT-MS top-down platform after acidification, deproteinization and chloroform liquid/liquid extraction.Thymosin β4 and β10 peptides were for the first time identified in the intracystic fluid of adamantinomatous craniopharyngioma by low- and high-resolution MS analysis coupled with LC. The two peptides showed the same distribution trend in the analysed samples. Thymosin β4 and β10 were present in 77 % of the analysed samples. These peptides were not found in the cerebrospinal fluid available for two patients.The presence of β-thymosins in the intracystic fluid of the tumour confirmed the secretion of these proteins in the extracellular environment. Due to their G-actin-sequestering activity and antiapoptotic and anti-inflammatory properties, these peptides could be strictly involved in both tumour progression and cyst development and growth.

Maxillary and mandibular alterations in children affected by anterior synostotic plagiocephaly have, until today, received only scarce attention. The goal of this paper is to focus on the mandibular alterations, persisting after the early correction of anterior plagiocephaly during the first year of life. Maxillary and mandibular metric measurements were performed on high resolution, thin slices CT scans; all images were reconstructed into 3D models which were used to perform the metrical assessments. Twelve patients were selected; all of them had been treated in early age with a neurosurgical intervention and had reached the end of maxillo-mandibular growth at the time of the evaluation. Significant discrepancies were documented between the two affected sides, with all measured distances being shorter on the synostotic side than the nonsynostotic one, the only exception being the vertical dimension of the mandibular ramus. Mandibular alterations resulted to be characterized by lower jaw hypoplasia on the side of the affected suture and anterior displacement of the glenoid fossa; these two entities compensated each other uncompletely, ending in a rotation of the mandibula towards the synostotic side.

OBJECTIVE The use of high-field intraoperative MRI has been largely studied for the treatment of intracranial tumors in adult patients. In this study, the authors investigated the safety, advantages, and limitations of high-field iMRI for cranial neurosurgical procedures in pediatric patients, with particular attention to craniopharyngiomas and gliomas. METHODS The authors performed 82 surgical procedures in patients under 16 years of age (range 0.8–15 years) over an 8-year period (2007–2014) using iMRI. The population was divided into 3 groups based on the condition treated: sellar region tumors (Group 1), gliomas (Group 2), and other pathological entities (Group 3). The patients' pre- and postoperative neurological status, the presence of residual tumor, the number of intraoperative scans, and complications were evaluated. RESULTS In Group 1, gross-total resection (GTR) was performed in 22 (88%) of the procedures and subtotal resection (STR) in 3 (12%). In Group 2, GTR, STR, and partial resection (PR) were performed, respectively, in 15 (56%), 7 (26%), and 5 (18%) of the procedures. In Group 3, GTR was performed in 28 (93%) and STR in 2 (7%) of the procedures. In cases of craniopharyngioma (Group 1) and glioma (Group 2) in which a complete removal was planned, iMRI allowed localization of residual lesions and attainment of the surgical goal through further resection, respectively, in 18% and 27% of the procedures. Moreover, in gliomas the resection could be extended from partial to subtotal in 50% of the cases. In 17% of the patients in Group 3, iMRI enabled the identification and further removal of tumor remnants. There was no intra- or postoperative complication related to the use of iMRI despite special technical difficulties in smaller children. CONCLUSIONS In this study, the use of iMRI in children proved to be safe. It was most effective in increasing the extent of tumor resection, especially in patients with low-grade gliomas and craniopharyngiomas. The most prominent disadvantage of high-field iMRI was the limitation with respect to operative positioning due to the configuration of the surgical table.

Primary intracranial anaplastic gangliogliomas are rare tumors in the pediatric patient group. Most of them present with symptoms of elevated pressure or symptomatic epilepsy. Extraaxial location is far more common than axial location. On MRI examination, they mimic pilocytic astrocytomas. The outcome after surgery depends mainly on the possible amount of surgical resection, and oncological therapy is necessary to prevent recurrence of the disease. An 11-year-old boy presented with headache and double vision due to obstructive hydrocephalus. MRI of the brain revealed an axial partially contrast enhancing lesion in the quadrigeminal plate extending from the cerebellum to the pineal gland and causing hydrocephalus. Subtotal removal of the lesion was performed, and the diagnosis of an anaplastic ganglioglioma was established and confirmed by the reference center. At the latest follow up (3 months), the boy is without any neurological symptoms and scheduled for radiation therapy as well as chemotherapy

The treatment of low-grade gliomas (LGGs) in pediatric age is still controversial. However, most authors report longer life expectancy in case of completely removed cerebral gliomas. Intraoperative magnetic resonance imaging (iMRI) is increasingly utilized in the surgical management of intra-axial tumor in adults following the demonstration of its effectiveness. In this article, we analyze the management of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population. We performed review of the literature regarding the treatment of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population. Some exemplary cases are also described. Intraoperative MRI allowed extension of tumor resection after the depiction of residual tumor at the intraoperative imaging control from 21 to 52 % of the cases in the published series. Moreover, the early reoperation rate was significantly lower when compared with the population treated without this tool (0 % vs 7–14 %). Some technical difficulties have been described in literature regarding the use of iMRI in the pediatric population especially for positioning due to the structure of the headrest coil designed for adult patients. The analysis of the literature and our own experience with iMRI in children indicates significant advantages in the resection of LGG offered by the technique. All these advantages are obtained without elongation of the surgical times or increased risk for complications, namely infection. The main limit for a wider diffusion of iMRI for the pediatric neurosurgical center is the cost required, for acquisition of the system, especially for high-field magnet, and the environmental and organizational changes necessary for its use.

Primary, adult-type bone fibrosarcoma is an uncommon, malignant spindle-cell tumor of fibroblastic origin, rarely affecting children. Most frequently diagnosed among bone malignancies in the past, improved diagnostic techniques and further restrictive classification criteria have currently made the diagnosis of fibrosarcoma very unusual. We hereby report the case of a 7-year-old child with a right frontal swelling mass. A computed tomography scan showed an osteolytic lesion of the right frontal bone, involving the diploe and the outer table of the skull. An en bloc surgical excision, followed by a thorough immunohistological evaluation, led to the diagnosis of fibroblastic proliferation, with low cellularity and minimal atypias. The patient had four recurrences during the 4-year follow-up. With an increasing histological grade at recurrences, a diagnosis of adult-type fibrosarcoma was made. To the best of the authors’ knowledge, this is the first reported case of an adult-type fibrosarcoma arising in the frontal bone of a child.