Neuroimaging in Nonsyndromic Craniosynostosis: Key Concepts to Unlock Innovation.

Craniosynostoses (CRS) are caused by the premature fusion of one or more cranial sutures, with isolated nonsyndromic CRS accounting for most of the clinical manifestations. Such premature suture fusion impacts both skull and brain morphology and involves regions far beyond the immediate area of fusion. The combined use of different neuroimaging tools allows for an accurate depiction of the most prominent clinical-radiological features in nonsyndromic CRS but can also contribute to a deeper investigation of more subtle alterations in the underlying nervous tissue organization that may impact normal brain development. This review paper aims to provide a comprehensive framework for a better understanding of the present and future potential applications of neuroimaging techniques for evaluating nonsyndromic CRS, highlighting strategies for optimizing their use in clinical practice and offering an overview of the most relevant technological advancements in terms of diagnostic performance, radiation exposure, and cost-effectiveness.

Selective dorsal rhizotomy after baclofen intrathecal pump removal: a single-center experience and review of the literature.

PURPOSE: Selective dorsal rhizotomy (SDR) and intrathecal baclofen (ITB) pump placement are two surgical options in children affected by spasticity secondary to cerebral palsy 1. The latest literature is an enlarging indication for SDR in case of ITB failure in non-ambulant patients as an alternative to pump reimplantation to reduce spasticity and facilitate patients' care. METHODS: A retrospective single-center study has screened all children diagnosed with spastic tetraparesis who underwent in the last 10 years SDR and had previously ITB pump implanted. A cohort of six patients was pooled out. Furthermore, pertinent literature has been reviewed. RESULTS: Indication for pump removal was pump pocket infection, parents' decision, and poor response to ITB. Patients' amount of lifetime with the pump implanted has been 6.9 years. The preoperative and postoperative Ashworth scores were statistically different in both procedures (p = 0.005 and p = 0.,02). CONCLUSIONS: Only two studies investigated the pediatric population undergoing SDR in the occurrence of ITB pump removal. Authors are offering SDR to all children, regardless of GMFCS groups and previous ITB pump placement. In conclusion, SDR represents a valid tool in neurosurgeon's hands to help ameliorate patients' long-lasting quality of life, reducing the severity of the spasticity and leading to better management by caregivers.

Giant tumefactive mesencephalothalamic Virchow-Robin space with triventricular hydrocephalus: a case-based systematic literature review.

BACKGROUND: The perivascular spaces of the brain are also known as Virchow-Robin spaces (VRSs). Dilated Virchow-Robin spaces in the brainstem are rare and mainly cause symptoms due to obstructive hydrocephalus, less frequently because of their size, mass effect, and impact on eloquent structures. CASE ILLUSTRATION: We present a patient with giant tumefactive VRS with hydrocephalus and neurological symptoms who was treated with endoscopic third ventriculostomy (ETV) followed by microscopic cyst fenestration. On the basis of this observation, we performed a thorough review of the literature to evaluate different treatment options. RESULTS: An 11-year-old girl presented with a headache for 3 months. The patient had a giant tumefactive mesencephalothalamic VRS with triventricular hydrocephalus. She was initially treated with endoscopic third ventriculostomy and multiple cyst fenestration. Symptomatic cyst regrowth required multiple cyst fenestrations via transcallosal transchoroidal (N = 2) and subtemporal approaches (N = 1) at the 2- and 4-year follow-ups. A literature review of these conditions allowed the detection of 12 cases (including our index case), and only 25% (3/12) of the patients underwent cyst fenestration 16.7% (2/12) required endoscopic fenestration and 8.3% (1/12) required microscopic fenestration. CONCLUSION: Giant mesencephalothalamic dVRSs are rare in the pediatric population. These patients are usually symptomatic due to obstructive hydrocephalus. Surgical options are endoscopic third ventriculostomy, ventricular shunt procedures, or direct cyst fenestration (microscopic or endoscopic). Close follow-up is mandatory owing to the risk of progression of the disease. Cyst fenestration resolves symptoms immediately, as it addresses both hydrocephalus and mass effects due to the cystic lesion in the same setting.

Simultaneous robotic-assisted laser thermal ablation of multiple cortical tubers for drug-resistant epilepsy in a 17-year-old patient with Tuberous Sclerosis Complex.

Magnetic resonance guided laser interstitial thermal therapy (MRgLITT) is a new minimally invasive treatment for Tuberous Sclerosis Complex (TSC) associated epilepsy in children. This video describes a case of a 17-year-old girl with TSC-associated drug resistant epilepsy treated with robotic-assisted MRgLITT. In our case, MRgLITT was safe and effective in simultaneous targeting multiple epileptic tubers in one single procedure, leading to a marked decrease in seizure frequency. MRgLITT could be a promising and more appealing treatment option for children who may need multiple surgeries over their lifetime due to the progressive nature of TSC.

Biobank for craniosynostosis and faciocraniosynostosis, rare pediatric congenital craniofacial disorders: a study protocol.

PURPOSE: Craniosynostosis (CRS) is a rare congenital cranial malformation in which 1 or more cranial or facial sutures are fused in utero or rapidly fused in early infancy. The cranial sutures separate the skull bone plates and enable rapid growth of the skull in the first 2 years of life, in which growth is largely dictated by growth of the brain. CRS is a rare disease that occurs in 1 in 2100 to 1 in 2500 births and may be either nonsyndromic (also referred to as isolated) or syndromic. In syndromic CRS, other birth defects are present next to the CRS. The distinction between nonsyndromic and syndromic manifestations is made on the basis of dysmorphologic evaluation and genetic evaluation. Owing to advances in genetic diagnostics, nonsyndromic patients are increasingly recognized as syndromic patients. CRS treatment is almost entirely surgical and is sometimes paired with postoperative helmet therapy for maintenance. Corrective procedures are complex, long, and associated with the risk of numerous complications, including heavy blood loss and its sequelae. Although surgery may restore a normal appearance, even in nonsyndromic patients, patients may experience persistent deficits in intellectual ability and cognitive function. The European Commission (EC) has prioritized rare diseases in recent horizon European research programs; indeed, collections or even individual samples may be extremely valuable for research. METHODS AND RESULTS: Here, we present a study protocol in which the combined expertise of clinicians and researchers will be exploited to generate a biobank dedicated to CRS. The generation of the CRS biobank presented in this study will include the collection of different types of biological materials as well as advanced radiological images available to the scientific community. CONCLUSION: The activation of a CRS biobank will provide an opportunity to improve translational research on CRS and to share its benefits with the scientific community and patients and their families.

Occipital Interhemispheric Retrocallosal Transtentorial Approach to a Tectal Tumor in an 8-Year-Old Girl: Operative Video.

Tectal plate tumors are a rare subset of midbrain tumors in pediatric populations. They are slow growing and low grade, with indolent and subtle manifestation unless they cause hydrocephalus.1-5 We present a tectal tumor in an 8-year-old girl (Video 1). Her clinical onset occurred with headache, vomiting, and seizure secondary to intracranial hypertension. MRI revealed a ring-enhanced, roundish lesion of tectal plate, with posterior displacement of quadrigeminal corpora determining aqueductal stenosis and obstructive triventricular hydrocephalus. First, to restore CSF circulation, we performed an endoscopic third-ventriculostomy without lesion's biopsy, since there was normal brain tissue within the third ventricle and the tumor. Tumoral marker values were in the average range, so surgery was planned to remove the tumor. The patient, after the positioning of external lumbar drainage, underwent an occipital posterior interhemispheric retrocallosal transtentorial approach, which represents a direct surgical corridor to quadrigeminal cistern and quadrigeminal plate. Arachnoidal dissection of mesencephalic cistern and cutting of the tentorium are mandatory to obtain adequate exposure of quadrigeminal region, control over vascular structures, and lesser brain retraction. Identification of anatomical components and relationships between quadrigeminal plate with vein of Galen, PCA branches, tentorium, and medial occipital veins represents a crucial point. When this approach is selected, the venous anatomy must be navigated with caution. Angiography's venous phase may provide additional planning information.6 Coagulation of vascular structures such as occipital veins is carefully avoided since it creates risk of venous infarction, leading to visual loss. Histologic examination revealed a rosette-forming glioneuronal tumor (grade I WHO 20217).

Low-grade epilepsy-associated tumors: Epilepsy outcome and antiseizure medication discontinuation after lesionectomies as first-line surgical approach in pediatric population.

OBJECTIVE: This study aimed to evaluate epilepsy outcome and antiseizure medication (ASM) discontinuation after lesionectomies as first surgical approach in pediatric population diagnosed with low-grade epilepsy-associated neuroepithelial tumors (LEATs). METHODS: We conducted a retrospective study. Thirty-six consecutive patients with histological diagnoses of LEATs who underwent surgery between 2018 and 2021 at our institution were included. The clinical and surgical data were retrospectively analyzed. RESULTS: Thirty (83.3%) of 36 patients are free of disabling seizures (Engel class I) and 19 (63,4%) of them are classified as Engel Ia. In 17 (47.2%) patients, ASM could be discontinued. The mean age at surgery was 8.6 years (±4.04) and the mean age at onset of epilepsy was 7.2 years (±3.8), whereas the mean duration of epilepsy in months at the time of surgery was 21.3 months (±23.7). The epileptogenic tumor was in the temporal lobe in 20 (55.5%) patients. Because of seizure persistence, a second or a third surgery was necessary for six patients (16.7%) and four of them had residual lesions (three in temporal and one in extratemporal site). No perioperative complications were recorded, including acute seizures, with a median hospitalization time of 7 days. Shorter epilepsy duration at time of surgery as long as a single ASM was significantly correlated with an Engel class I outcome (p-value = .01 and p-value = .016, respectively). Focal seizure semeiology was associated with an increased probability of antiseizure medication discontinuation (p-value = .042). SIGNIFICANCE: Our findings confirm that shorter epilepsy disease duration, monotherapy before surgery, and seizure semeiology are determinant factors for a positive seizure outcome and medication discontinuation, also with less invasive surgical approaches such as lesionectomies. However, considering the intrinsic multifactorial epileptogenic nature of LEATs, a tailored surgical approach should be considered to optimize clinical and seizure outcome, especially for lesions located in the temporal lobe.

Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules.

Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression. In this paper, we found that PRUNE-1 was transcriptionally regulated by lysine demethylase LSD1/KDM1A. This study aimed to investigate the therapeutic potential of inhibiting both PRUNE-1 and LSD1/KDM1A with the selective inhibitors AA7.1 and SP-2577, respectively. We found that the pharmacological inhibition had a substantial efficacy on targeting the metastatic axis driven by PRUNE-1 (PRUNE-1-OTX2-TGFß-PTEN) in Gr3 MB. Using RNA seq transcriptomic feature data in Gr3 MB primary cells, we provide evidence that the combination of AA7.1 and SP-2577 positively affects neuronal commitment, confirmed by glial fibrillary acidic protein (GFAP)-positive differentiation and the inhibition of the cytotoxic components of the tumor microenvironment and the epithelial-mesenchymal transition (EMT) by the down-regulation of N-Cadherin protein expression. We also identified an impairing action on the mitochondrial metabolism and, consequently, oxidative phosphorylation, thus depriving tumors cells of an important source of energy. Furthermore, by overlapping the genomic mutational signatures through WES sequence analyses with RNA seq transcriptomic feature data, we propose in this paper that the combination of these two small molecules can be used in a second-line treatment in advanced therapeutics against Gr3 MB. Our study demonstrates that the usage of PRUNE-1 and LSD1/KDM1A inhibitors in combination represents a novel therapeutic approach for these highly aggressive metastatic MB tumors.

Jugular foramen stenosis in external hydrocephalus in infants.

OBJECTIVE: To measure the size of jugular foramina in infants affected by external hydrocephalus (EH) and in a control group, to support the hypothesis that a jugular foramen (JF) stenosis may determine dural venous sinus alterations and increased venous outflow resistance as main pathophysiological factor. METHODS: Minimum, maximum, and mean values of JF areas were measured in a series of phase-contrast magnetic resonance venous angiography (angio MRV PCA3D) performed on 81 infants affected by EH. Results were compared with a group of 54 controls. RESULTS: Smaller JF area was significantly smaller in patients versus controls (43.1 ± 14.6 vs. 52.7 ± 17.8; p < 0.001) resulting in a significantly smaller mean JF areas in patients vs. controls (51.6 ± 15.8 vs. 57.0 ± 18.3; p = 0.043). In patients, smaller JF areas were significantly associated with higher venous obstruction grading score (VOGS) both on the right (p = 0.018) and on the left side (p = 0.005). Positional plagiocephaly (cranial vault asymmetry index > 3.5%) was more frequent among EH patients than controls (38/17) but the difference was not significant (p = 0.07). In the 38 plagiocephalic patients, JF area was smaller on the flattened side than the contralateral in a significant number of cases both in right (21/7) and left (9/1) plagiocephaly (p < 0.0005) as well as the mean area (48.2 + 16.4 mm2 vs. 57.5 + 20.7 mm2, p = 0.002) and VOGS was significantly higher on the plagiocephalic side than on the contralateral side (1.6 ± 1.1 vs. 1.1 ± 0.9, p = 0.019). CONCLUSION: In this series of infants affected by EH, the mean size of the ostium of both JF resulted significantly smaller than controls. JF stenosis was significantly associated with higher degrees of venous obstruction on both sides, suggesting a direct extrinsic effect of JF size on dural sinus lumen and possible consequent effect on venous outflow resistance. Positional plagiocephaly, when present, was associated with a decreased JF area and increased VOGS on the flattened side.

Pineocytoma in a child with Pallister-Killian syndrome: a case report and review of the literature.

Pallister-Killian syndrome (PKS; OMIM #601803) is a rare genetic disorder typically characterized by developmental delay, seizures, sparse temporal hair, and facial dysmorphisms. PKS is most frequently caused by mosaic supernumerary isochromosome 12p. Here, we report a 27-month-old girl with a prenatal diagnosis of PKS and a histopathological diagnosis of pineocytoma.

Cylinder tumor surgery in pediatric low-grade gliomas.

BACKGROUND: Periventricular pediatric low-grade gliomas (pLGG) present a surgical challenge due to their deep-seated location, accessibility, and relationship with the subcortical network connections. Minimally invasive parafascicular approaches with tubular brain retractors (port brain surgery) have emerged, in recent years, as an alternative to conventional microsurgical and endoscopic approaches for removal of periventricular tumors. OBJECTIVES: To describe the minimally invasive approach with tubular brain retractors for periventricular pLGG, its technique, applications, safety, and efficacy. METHODS: In this article, we describe the port brain surgery techniques for periventricular pLGG as performed in different centers, with different commercialized tubular retractor systems. Illustrative cases followed by a literature review are analyzed, with a detailed description of different approaches or techniques, comparing their advantages and disadvantages with contemporary microsurgical and endoscopic approaches. CONCLUSIONS: The port brain surgery with micro-exoscopic vision and endoscopic assistance, for the treatment of deep-seated lesions such as periventricular pLGG, is an alternative for achieving a functionally safe-gross total or subtotal-tumor resection, obtaining adequate tissue for pathological examination. This technique could offer a new dimension for a less-invasive, safe, and effective access to deep-seated tumors, offering the possibility to lower morbidity in experienced hands.

Image-guided biopsy of intracranial lesions in children, with a small robotic device: a case series.

BACKGROUND AND OBJECTIVES: Robot-assisted biopsies have gained popularity in the last years. Most robotic procedures are performed with a floor-based robotic arm. Recently, Medtronic Stealth Autoguide, a miniaturized robotic arm that work together with an optical neuronavigation system, was launched. Its application in pediatric cases is relatively unexplored. In this study, we retrospectively report our experience using the Stealth Autoguide, for frameless stereotactic biopsies in pediatric patients. METHODS: Pediatric patients who underwent stereotactic biopsy using the Stealth Autoguide cranial robotic platform from July 2020 to May 2023 were included in this study. Clinical, neuroradiological, surgical, and histological data were collected and analyzed. RESULTS: Nineteen patients underwent 20 procedures (mean age was 9-year-old, range 1-17). In four patients, biopsy was part of a more complex surgical procedure (laser interstitial thermal therapy - LITT). The most common indication was diffuse intrinsic brain stem tumor, followed by diffuse supratentorial tumor. Nine procedures were performed in prone position, eight in supine position, and three in lateral position. Facial surface registration was adopted in six procedures, skull-fixed fiducials in 14. The biopsy diagnostic tissue acquisition rate was 100% in the patients who underwent only biopsy, while in the biopsy/LITT group, one case was not diagnostic. No patients developed clinically relevant postoperative complications. CONCLUSION: The Stealth Autoguide system has proven to be safe, diagnostic, and highly accurate in performing stereotactic biopsies for both supratentorial and infratentorial lesions in the pediatric population.

Systematic review of transcranial and endoscopic endonasal approaches for craniopharyngiomas in children: is there an evolution?

OBJECTIVE: The optimal surgical approach for pediatric craniopharyngiomas (CPs) remains a matter of debate, with selection bias classically precluding a fair comparison of outcomes between the transcranial approach (TCA) and endoscopic endonasal approach (EEA). The purpose of this systematic review was to analyze the current role of EEA in the treatment of pediatric CPs and to determine whether, upon expansion of its indications, a comparison with TCA is valid. METHODS: A systematic review of English-language articles published between February 2010 and June 2022 was performed to identify studies in the MEDLINE (PubMed) and Embase databases reporting on the resection of pediatric CPs. Included were articles reporting on pediatric CPs removed through TCA or EEA. Case reports, review articles, and earlier or less comprehensive series by the same center were excluded. Baseline characteristics and outcomes were analyzed. Prediction intervals (PIs), heterogeneity (Q, I2, and τ2 statistics), and publication bias (funnel plot analysis) were assessed. RESULTS: A total of 835 patients underwent TCA (18 articles) and 403 patients underwent EEA (19 articles). Preoperatively, the mean patient age (p = 0.055, PI = 5.05-15.11), visual impairment (p = 0.08, PI = 19.1-90.5, I2 = 80%), and hypothalamic syndrome (p = 0.17, PI = 6.5-52.2, I2 = 62%) did not significantly differ between the EEA and TCA groups. Endocrine deficit (anterior pituitary deficit [p < 0.001, PI = 16.5-92.9, I2 = 81%] and diabetes insipidus [p < 0.001, PI = 6.3-60.6, I2 = 43%]) was more frequent in the EEA group. Hydrocephalus and signs/symptoms of raised intracranial pressure were significantly higher (p < 0.001, PI = 5.2-73.3, I2 = 70% vs p < 0.001, PI = 4.6-73, I2 = 62%, respectively) in the TCA group. Recurrent lesions (p = 0.52, PI = 2.7-87.3, I2 = 13%), tumor size (p = 0.25, PI = 22.1-56.8), third ventricle involvement (p = 0.053, PI = 10.9-81.3, I2 = 69%), and hypothalamic involvement (p = 0.06, PI = 8.5-83.6, I2 = 79%) did not differ significantly between the approaches. EEA was preferred (p = 0.006, PI = 26.8-70.8, I2 = 40%) for sellar-suprasellar CPs, whereas TCA was preferred for purely suprasellar CPs (p = 0.007, PI = 13.5-81.1, I2 = 61%). There was no difference between the approaches for purely intrasellar lesions (p = 0.94, PI = 0-62.7, I2 = 26%). The breadth of PIs, I2 values, and analysis of publication bias showed substantial variability among the pooled data, hindering the possibility of outcome meta-analyses. CONCLUSIONS: With the adoption of extended approaches, the use of EEA became appropriate for a wider spectrum of pediatric CPs, with associated excellent outcomes. Although a fair comparison between outcomes in the EEA and TCA groups was hindered because of the differences in patient populations and tumor subtypes, given the increased versatility of EEA and improved expertise in its use, surgeons can now select the optimal surgical approach based on the unique benefits and drawbacks of each pediatric CP.

Endoscopic Ultrasonic Aspiration of Brain Abscess.

Brain abscess is a focal infection occurring within the brain parenchyma consisting of a pus collection surrounded by a vascularized capsule and a fibrinous-caseous layer between the pus and capsule. Surgery is indicated for lesions with a diameter >25 mm. Different surgical approaches have been described, including puncturing of the abscess (under neuronavigation, stereotactic or echographic guidance) with aspiration of the purulent fluid through a catheter and craniotomy with microsurgical removal of the purulent material and surrounding capsule. In recent years, the endoscopic approach has become more frequently used to treat brain abscesses. The theoretical advantages are visual awareness of the completeness of pus removal and the possibility of also removing the more solid fibrinoid component, which could be the source of recurrence. Craniotomy is likewise avoided. We present the case of an 11-year-old boy affected by a parieto-occipital brain abscess and initial ventriculitis who underwent endoscopic surgery. An ultrasonic aspirator was used to wash and suck the purulent material and fragment and remove the more solid fibrinoid component. The occipital horn of the lateral ventricle was also entered, and pus was removed. At the end of the procedure, a ventricular drainage tube was left in the surgical cavity. It was removed 1 day later, because the cavity had completely collapsed. The key surgical steps are presented in Video 1.1-9 The procedure was uneventful, with very good clinical and radiological results. The endoscopic technique has been shown to be a safe and effective treatment option for intracranial abscess. In the case of large superficial lesions, the surgical risks appear similar to those of simple drainage through catheters, with a possible reduction of the 20% reported recurrence rate. The use of an ultrasonic aspirator could facilitate complete and faster pus removal, increasing the efficacy of the procedure. The patient and his parents consented to the procedure and the report of the patient's case details and imaging studies. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Removal of a thoracic intramedullary epidermoid tumor in a child.

Epidermoid cysts are rare, benign neoplasms that account for less than 1% of all intraspinal tumors. The most common localization is in the lumbar area, and one-third of the tumors are intramedullary. In this video, the authors present removal of a thoracic intramedullary epidermoid tumor in a 6-year-old boy, carrier of a 22q11 gene duplication and affected by psychomotor retardation. He presented a 1-year history of progressive gait impairment. No history of lumbar puncture or trauma was reported. The procedure was performed under neurophysiological monitoring, and it was uneventful with complete recovery of neurological function. Technical nuances are illustrated.

Surgical Approaches to the Third Ventricle: An Update.

The third ventricle is located in the deepest part of the brain and is delimited by both telencephalic and diencephalic structures. Its location makes every surgical procedure inside or around it quite challenging, due to the distance from the surface to the fragility of the neurovascular structures that is necessary to dissect before entering its cavity and to the narrow surgical corridors through which it is necessary to work. Its geometric localization inside the cranial cavity and the anatomical relationship with the interhemispheric fissure offers nevertheless to the surgeon an impressive variety of surgical approaches, which allow to reach every millimeter of the third ventricle lumen. Mastering properly all these approaches requires an impressive anatomical knowledge, the best available technology, and most refined technical skills, making the surgery of the third ventricle a point of excellence in the evolution of each neurosurgeon. The development of neuronavigation and neuroendoscopy has been a revolution in neurosurgery in the last 20 years and offered special advantages for the surgery of the third ventricle. In fact, the narrow corridors of approach make the precision of the neuronavigation and the enlightenment and magnification of the neuroendoscopy especially useful to reach the third ventricle cavity and working inside or around it. This chapter reviews the history of the surgery of the third ventricle and offers an update of the variety of surgical corridors identified and of the technology now available to properly work through them and inside the third ventricle cavity.

SHH medulloblastoma and very early onset of bowel polyps in a child with PTEN hamartoma tumor syndrome.

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a cancer predisposition syndrome characterized by an increased risk of developing benign and malignant tumors, caused by germline pathogenic variants of the PTEN tumour suppressor gene. PTEN gene variants often present in childhood with macrocephaly, developmental delay, and/or autism spectrum disorder while tumors and intestinal polyps are commonly detected in adults. PHTS is rarely associated with childhood brain tumors with only two reported cases of medulloblastoma (MB). We report the exceptional case of an infant carrying a germline and somatic pathogenic variant of PTEN and a germline and somatic pathogenic variant of CHEK2 who developed a MB SHH in addition to intestinal polyposis.

Extra-neural metastases in pediatric diffuse midline gliomas, H3 K27-altered: presentation of two cases and literature review.

Introduction: Pediatric diffuse midline gliomas (DMG), H3 K27- altered, are the most aggressive pediatric central nervous system (CNS) malignancies. Disease outcome is dismal with a median survival of less than one year. Extra-neural metastases are an unusual occurrence in DMG and have been rarely described. Methods and results: Here, we report on two pediatric patients affected by DMG with extra-neural dissemination. Their clinical, imaging, and molecular characteristics are reported here. An 11-year-old male 5 months after the diagnosis of diffuse intrinsic pontine glioma (DIPG) developed metastatic osseous lesions confirmed with computed tomography (CT) guided biopsy of the left iliac bone. The patient died one month after the evidence of metastatic progression. Another 11-year-old female was diagnosed with a cerebellar H3K27- altered DMG. After six months, she developed diffuse sclerotic osseous lesions. A CT-guided biopsy of the right iliac bone was non-diagnostic. She further developed multifocal chest and abdominal lymphadenopathy and pleural effusions. Droplet digital polymerase chain reaction (ddPCR) on pleural effusion revealed the presence of H3.3A mutation (c.83A>T, p.K28M). The patient died 24 months after the diagnosis of DMG and 3 months after the evidence of metastatic pleural effusion. Discussion: Extra-neural metastasis of DMG is a rare event and no standard therapy exists. An accurate and early diagnosis is necessary in order to develop a personalized plan of treatment. Further research is needed to gain further insights into the molecular pathology of DMG, H3K27- altered and improve the quality of life and the final outcome of patients with this deadly disease.

Neuroendoscopy: intraventricular and skull base tumor resection in children.

During the last 30 years, the neurosurgeons have witnessed a revolution in the practice of interventricular surgery. The advent of neuroendoscopy at the end of the 1980s has allowed a minimally invasive management of a very large series of pathologies in pediatric neurosurgery ranging from hydrocephalus to arachnoid cyst to intraventricular tumors. The progresses in the management of hydrocephalus, intracranial cyst, and the fluid filled collection nevertheless has been more rapid and radical due to the simpler equipment that is necessary to perform this kind of surgery. The intraventricular tumors instead have been addressed in a slower way, and for many years, the only endoscopic procedure that was allowed on interventricular tumors was a biopsy associated with the management of hydrocephalus. Only very small tumors have been considered operable for complete removal during many years due to the limitations of the neuroendoscopic equipment and to the small calibers of the working channel. More recently, the advent of new devices and new surgical techniques are offering new perspectives on the possibility of intraventricular tumor surgery in children. In this review, we describe the historical perspective of the learning curve of intraventricular tumor surgery under neuroendoscopic control and try to offer a view of the future perspective in the removal of larger intraventricular tumors, analyzing the main indications for intraventricular endoscopic tumor surgery. We offer as well an historical perspective of the evolution of skull base surgery and endonasal transsphenoidal approach for skull-based tumors in children. This kind of surgery that has acquired widespread acceptance for many pathologies in adult age has diffused more slowly in pediatric neurosurgery due to the anatomical limitation observed in these age range. Also in this field, the slow evolution of the technique and of the technology available to neurosurgeons has allowed a very significant expansion of indication for the minimally invasive removal of skull base tumors in children.