Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Ruptured Sylvian arachnoid cysts: an update on a real problem.

PURPOSE: Sylvian arachnoid cysts (SACs) are the most common type of arachnoid cysts and the most prone to undergo a rupture. This event is considered rare but potentially severe. No definite information is available on its occurrence or management. The goal of the present article is to provide an update on the epidemiological, etiological, and clinical aspects and the management of this peculiar clinical condition. METHODS: A comprehensive review of the English literature of the last 40 years on this topic has been realized. Moreover, a personal series of children investigated and treated in the last 20 years is presented. These patients were managed as follows: (1) treatment of the subdural collection; (2) identification of candidates for surgical treatment of the residual cyst (brain MRI, perfusion brain MRI, prolonged invasive ICP monitoring (selected cases), EEG, neuropsychological tests); (3) surgical treatment of the cyst in the patients with pathological perfusion MRI and/or ICP measurement and/or clear neurophysiological and neuropsychological correlations. RESULTS: A total of 446 patients (430 from the literature and 16 from the personal series), mainly children, adolescents, and young adults, have been analyzed leading to the following results: (1) SAC rupture is rare but not negligible (yearly risk of rupture: 0.04%; overall risk up to 10% in children affected by SCAs). Prophylactic surgery in asymptomatic cases is not advisable. (2) The mechanism of rupture is not known but an impact of SAC against the sphenoid wing and/or a direct injury on SAC through a thinned temporal bone, with possible laceration of the cyst wall vessels and/or tear of the bridging veins, can be hypothesized. A head injury is often not reported (may be misdiagnosed). (3) Subdural collection (hygroma > chronic hematoma) is the most common finding followed by intracystic bleeding, extradural hematoma, and other types of bleeding. Signs or symptoms of raised intracranial pressure are the most frequent ones. (4) The complication of the rupture is usually treated in emergency or in the acute period by burr hole or craniotomic evacuation of the subdural collection, although a conservative management is possible in some cases. Following the rupture, the majority of SACs are treated (70%), often at the same time of the complication, but no specific investigations are routinely performed to select candidates. According to our protocol, only 43.7% of SACs needed to be treated. CONCLUSIONS: The "spontaneous" or posttraumatic rupture of SACs is a rare but potentially significant complication followed by a generally good outcome. The course of the cyst is independent from the outcome of the complication, consequently requiring specific investigations for individuating those lesions interfering with CSF dynamics and/or cerebral blood flow.

Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study.

PURPOSE: Craniopharyngiomas (CPGs) are aggressive brain tumors responsible of severe morbidity in children. The best treatment strategies are under debate. Our study evaluates surgical, pituitary, and hypothalamic outcomes of a tailored staged-surgical approach compared to a single-stage radical approach in children with CPGs. METHODS: Multicenter retrospective study enrolling 96 children treated for CPGs in the period 2010-2022. The surgical management was selected after a multidisciplinary evaluation. Primary endpoint includes the inter-group comparison of preservation/improvement of hypothalamic-pituitary function, the extent of resection, and progression-free survival (PFS). Secondary endpoints include overall survival (OS), morbidity, and quality of life (QoL). RESULTS: Gross Total Resection (GTR) was reached in 46.1% of cases in the single-stage surgery group (82 patients, age at surgery 9 ± 4.7 years) and 33.3% after the last operation in the staged surgery group (14 patients age 7.64 ± 4.57 years at first surgery and 9.36 ± 4.7 years at the last surgery). The PFS was significantly higher in patients addressed to staged- compared to single-stage surgery (93.75% vs 70.7% at 5 years, respectively, p = 0.03). The recurrence rate was slightly higher in the single-stage surgery group. No significant differences emerged in the endocrinological, visual, hypothalamic outcome, OS, and QoL comparing the two groups. CONCLUSIONS: In pediatric CPGs' surgical radicality and timing of intervention should be tailored considering both anatomical extension and hypothalamic-pituitary function. In selected patients, a staged approach offers a safer and more effective disease control, preserving psychophysical development.

Neuropsychological profiles in children and young adults with spina bifida.

PURPOSE: A total of 43 Italian children, aged between 6 and 16 years, diagnosed with spina bifida, myelomeningocele, and shunted hydrocephalus have been described clinically and completed a neuropsychological battery in order to evaluate their cognitive, personality, and behavior profile. METHODS: Enrolled children underwent cognitive assessment by means of the Weschler WISC-IV cognitive test and assessment of the attention sustained through the LEITER test. In addition, parents were asked, in order to obtain a personality and behavior profile of the children, to fill in a "CBCL 6-18 years" questionnaire and to fill in a Barthel Index questionnaire. RESULTS: Processing Speed Index of the WISC-IV QI scale was statistically significant (p = 0.027), with the highest value presented by autonomous patients (95.8 ± 12.8) and the lowest by patients using a wheelchair (75.5 ± 19). WISC-IV QI mean value is 98 (±15.7) for lipoma patients and 78.7 (±17.6) for LMMC and MMC patients (p = 0.001). In more detail, Perceptual Reasoning (p < 0.0005), Working Memory (p = 0.01), and Processing Speed Index (p = 0.001) highlighted a significant difference between the groups. The attention sustained subscale of the LEITER presented a mean of 6.9 (±3.1) for lipoma patients and a men value of 4.6 (±3.1) for LMMC and MMC patients (p = 0.024). Patients with hydrocephalus had statistically significant worse cognition and autonomy (Barthel Index) score (p < 0.001) compared with those without hydrocephalus, and normal scores regarding attention and depression scales. CONCLUSION: These results can be useful in planning dedicated therapeutic protocols such as suitable rehabilitation treatments, speech therapy, psychomotor skills, and cognitive enhancement and to develop prevention protocols particularly tailored for children with hydrocephalus who appear to have the more deficient skills.

Post-traumatic hematoma of the "transdural" virtual space. A possible cause of incorrect surgical treatment of epidural hematomas.

The space existing between the external and internal dural layer has been anatomically described as a virtual space; no clear clinical significance has been given to it to date. We hereby describe a case of a child with what was expected to be a purely epidural hematoma, at surgery, was found to be composed of two equally coexistent components, one in the epidural space and the second one between the two dural layers. The recognition of a possible involvement of the transdural space in the case of post-traumatic epidural hematomas is relevant for a correct conclusion of the surgical treatment of epidural hematomas, extensively considered basic practice among neurosurgical procedures.

Nitric oxide alleviates cadmium- but not arsenic-induced damages in rice roots.

Nitric oxide (NO) has signalling roles in plant stress responses. Cadmium (Cd) and arsenic (As) soil pollutants alter plant development, mainly the root-system, by increasing NO-content, triggering reactive oxygen species (ROS), and forming peroxynitrite by NO-reaction with the superoxide anion. Interactions of NO with ROS and peroxynitrite seem important for plant tolerance to heavy metal(oid)s, but the mechanisms underlying this process remain unclear. Our goal was to investigate NO-involvement in rice (Oryza sativa L.) root-system after exposure to Cd or As, to highlight possible differences in NO-behaviour between the two pollutants. To the aim, morpho-histological, chemical and epifluorescence analyses were carried out on roots of different origin in the root-system, under exposure to Cd or As, combined or not with sodium nitroprusside (SNP), a NO-donor compound. Results show that increased intracellular NO levels alleviate the root-system alterations induced by Cd, i.e., inhibition of adventitious root elongation and lateral root formation, increment in lignin deposition in the sclerenchyma/endodermis cell-walls, but, even if reducing As-induced endodermis lignification, do not recover the majority of the As-damages, i.e., enhancement of AR-elongation, reduction of LR-formation, anomalous tissue-proliferation. However, NO decreases both Cd and As uptake, without affecting the pollutants translocation-capability from roots to shoots. Moreover, NO reduces the Cd-induced, but not the As-induced, ROS levels by triggering peroxynitrite production. Altogether, results highlight a different behaviour of NO in modulating rice root-system response to the toxicity of the heavy metal Cd and the metalloid As, which depends by the NO-interaction with the specific pollutant.

Single-suture craniosynostosis: is there a correlation between preoperative ophthalmological, neuroradiological, and neurocognitive findings?

BACKGROUND: In spite of literature data stating that children with single-suture craniosynostosis have an increased risk for neuropsychological deficits, no data are present clarifying the potential risk factors. METHODS: All children with non-syndromic single-suture craniosynostosis operated on from January 2014 to January 2017 were enrolled. A comprehensive neurocognitive and neuro-ophthalmological evaluation was performed before surgery and 6 months after surgery. A further neurocognitive evaluation was performed 12 months after surgery. All children had a preoperative CT/MR study. RESULTS: One hundred forty-two patients were enrolled; 87 are affected by sagittal craniosynostosis, 38 by trigonocephaly, and 17 by plagiocephaly. A global neurocognitive impairment was documented in 22/87 children with scaphocephaly, 5/38 children with trigonocephaly, and 6/17 children with anterior plagiocephaly. There was a significant relationship between results of the ophthalmological evaluation, global IQ, and CT findings at diagnosis (r = 0.296, p < 0.001; r =0.187, p 0.05). Though a significant recovery was documented after surgery, a persistence of eye coordination deficits was present at 6 months in 1 out of 3 children with abnormal preoperative exams. A significant correlation was found between pathological CT findings and persistence of below average neuro-ophthalmological and neurocognitive findings 6 months after surgery, as well as between CT findings and neurocognitive scores at the 1 year follow-up (r = 0.411; p < 0.01). CONCLUSION: The presence of neuroradiological abnormalities appears to be related to both ophthalmological and neurocognitive deficits at diagnosis. This relationship is maintained in spite of the surgical treatment in children who show the persistence of ophthalmological and neurocognitive deficits during the follow-up.

Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children.

BACKGROUND AND AIMS: Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions-as in major neurosurgical procedures-eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children. METHODS: Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6-74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines. RESULTS: An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2-5.5 d.), and postoperative ventilation need was 24 h (IQL range 20-61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded. CONCLUSIONS: Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

Imaging in craniosynostosis: when and what?

PURPOSE: Currently, the interest on craniosynostosis in the clinical practice is raised by their increased frequency and their genetic implications other than by the still existing search of less invasive surgical techniques. These reasons, together with the problem of legal issues, make the need of a definite diagnosis for a crucial problem, even in single-suture craniosynostosis (SSC). Although the diagnosis of craniosynostosis is primarily the result of physical examination, craniometrics measuring, and observation of the skull deformity, the radiological assessment currently plays an important role in the confirmation of the diagnosis, the surgical planning, and even the postoperative follow-up. On the other hand, in infants, the use of radiation or the need of sedation/anesthesia raises the problem to reduce them to minimum to preserve such a delicate category of patient from their adverse effects. METHODS, RESULTS AND CONCLUSIONS: This review aims at summarizing the state of the art of the role of radiology in craniosynostosis, mainly focusing on indications and techniques, to provide an update not only to pediatric neurosurgeons or maxillofacial surgeons but also to all the other specialists involved in their management, like neonatologists, pediatricians, clinical geneticists, and pediatric neurologists.

Occult spinal dysraphisms in newborns with skin markers: role of ultrasonography and magnetic resonance imaging.

PURPOSE: The purpose of this paper is to investigate occult spinal dysraphisms (OSD) using lumbar ultrasonography (LUS) in newborns presenting with specific skin markers or sacrococcygeal dimple. METHOD: From 2012 to 2015, we performed LUS in newborns with cutaneous stigmata and/or sacroccygeal dimple. Magnetic resonance imaging (MRI) was performed in all patients with abnormal ultrasound or features of neurological involvement in order to detect spinal lesions. RESULTS: We prospectively evaluated 475 newborns who presented cutaneous stigmata performing LUS during their 4 weeks of life though 439 completed the study. All patients had a follow-up of almost 12 months. Of these, 39 presented abnormal ultrasonography and underwent MRI. In this group, spinal dysraphism was confirmed in 12 patients. When considering skin markers, dermal sinus correlated with higher risk of spinal cord lesions, on the other hand the presence of simple sacral dimple alone denoted a very low risk of occult spinal dysraphism. The simultaneous presence of more skin markers and/or the presence of lumbar ultrasonography abnormality regarding the level of the conus, pulsatility, and the position of the cord, thickness of the filum terminale, or the presence of an intratecal mass, lipoma, or dermal sinus tract indicated the necessity to perform MRI in order to detect spinal cord abnormalities because of higher risk of spinal lesions. CONCLUSION: LUS in newborns with specific skin markers is a valid method to select patients in which MRI can be performed to detect OSD. The presence of a simple sacral dimple alone is a negligible marker for occult neural pathology while the presence of isolated dermal sinus or more than one cutaneous marker could be considered indicative of higher risk of spinal dysraphism.

X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model.

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

Supratentorial tumors typical of the infantile age: desmoplastic infantile ganglioglioma (DIG) and astrocytoma (DIA). A review.

OBJECT: Desmoplastic infantile gangliogliomas (DIGs) and desmoplastic infantile astrocytomas (DIAs) are tumors typical of the infantile age. A large size, with a mixed solid and cystic component, clinical presentation with progressing signs of increased intracranial pressure, a prominent benign desmoplastic structure at histological examination, and a favorable clinical course in the majority of cases are the prominent features of these tumors. The objective of the present paper was to review the pertinent literature on the topic together with our personal experience, with the aim of an updated review of the subject. RESULTS AND CONCLUSIONS: Only 28 papers are present in the literature devoted to DIGs and DIAs, most of them reporting on single cases or small series, with a total of 107 patients aged from 5 days to 48 months with a slight male prevalence. Most of the reported cases refer to supratentorial and hemispheric locations, a few cases involving the hypothalamic region, the posterior fossa, and the spinal cord. The typical MRI appearance is of large mixed solid and cystic tumors with a spontaneous hyperintense T2 appearance of the solid part which also shows a strong contrast enhancement. Mixed ganglionic and astrocytic cells are identifiable in DIGs, whereas DIAs are typically featured by the exclusive presence of glial cells. In both cases, more primitive cells may be observed, which present a higher number of mitoses and these areas can mimic the features of malignant astrocytomas. Surgery represents the treatment of choice; however, radical removal has been reported as possible only in around 30 % of the cases: the low age of the patients together with their low weight and the large size of and the hyper-vascularized structure of the tumors represent the main factors limiting surgery. Pure observation is considered as first choice in children undergoing a partial/subtotal tumor resection, chemotherapic regimens being considered in cases of recurrences after a second look surgery. Long-term prognosis is favorable with mortality being related mostly to the rare midline (i.e., hypothalamic) locations, which beyond the functionally relevant site, tend to have an unusually more aggressive histological behavior.

Cerebellar mutism.

INTRODUCTION: Cerebellar mutism (CM) is defined as a peculiar form of mutism that may complicate the surgical excision of posterior cranial fossa tumor. The incidence is variable in the literature, occurring in up to one third of cases in some series. Commonly occurring peculiar features of CM are delayed onset following surgery, limited duration, and spontaneous recovery usually associated with dysarthria. METHODS: A review has been performed concerning anatomical substrates and circuits actually considered to be involved in the development of cerebellar mutism, as well as risk factors for its development that have been documented in the literature. Attention has also been given to the long-term prognosis and the possibilities of rehabilitation that can be considered in these children, which has been compared with the authors' institutional experience. RESULTS AND CONCLUSIONS: Tumor infiltration of the brainstem seems to represent the most relevant feature related to the development of CM, along with the histological diagnosis of medulloblastoma. On the other hand, hydrocephalus does not represent an independent risk factor. The higher rate of CM in children seems to be related to the higher incidence in children of tumors with malignant histology and brain stem involvement. Surgical technique does not seem to have a definite role; in particular, the use of a telovelar approach as compared to vermian split to reach the fourth ventricle extension of the tumor has not been demonstrated to prevent the development of cerebellar mutism. Concerning long-term prognosis, around one third of the children who develop cerebellar mutism after surgery have a persistent dysarthria, the remaining ones showing a residual phonological impairment. Long-term dysarthric features tend to be more severe and less prone to recovery in children presenting at diagnosis with associated combined procedural memory and defective neurocognitive functions.

Surgery for posterior quadrantic cortical dysplasia. A review.

BACKGROUND: Posterior quadrant dysplastic lesions represent 3-15 % of multilobar cortical developmental pathologies, 3-5 % of all the indications to surgery for epilepsy resistant to medical treatment. OBJECTIVE AND METHODS: The objective of this study is to review the pertinent literature related to the presurgical clinical, neurophysiological, and neuroradiological evaluation of children affected by posterior quadrant dysplasia in order to discuss the intraoperative management and the different surgical techniques that have been proposed to treat this condition as well as factors related with postsurgical seizure outcome. RESULTS AND CONCLUSIONS: Seizures appear most commonly in infants and rapidly progress to a catastrophic course. They are mostly represented by focal seizures and spasms. Surface interictal video-EEG is characterized by background flattening and paroxysmal discharges prevalent on the affected side but not unusually extending to the controlateral hemisphere. The last occasionally shows an independent irritative activity in spite of the absence of further visible structural abnormalities. Most of the patients have visual field or visual attention deficits at diagnosis. Resective as well as disconnective surgical procedures have been proposed for the management of this condition, none of them having shown clear advantages in terms of seizure outcome and complications. Intraoperative electrocorticography (EcoG) and sensorimotor monitoring have been successfully used to improve the localization of the epileptic focus and reduce surgical complication rates. Undistincted lesion borders, independent controlateral ictal or/and interictal EEG activity, and incomplete resections/disconnections are among the main factors that have resulted to be associated with a worse seizure outcome.

Surgical treatment of posthemorrhagic infantile hydrocephalus.

The incidence of post-hemorrhagic hydrocephalus (PHH) remains stable over the time since the improvement in the perinatal assistance permits to reduce the risk of preterm brain hemorrhage and, at the same time, to increase the rate of surviving children potentially developing PHH. Children showing symptomatic ventriculomegaly (usually following Papile's grade III or IV hemorrhage) are candidate to treatment. Temporary treatment is based on medical therapy or on transient surgical manoeuvres (lumbar tapping, subcutaneous reservoir, external ventricular drainage, brain wash) with the goal of avoiding or to postponing the definitive surgical operation. Ventriculo-peritoneal shunt still represents the main surgical procedure for PHH. Especially in low-weight babies, however, this procedure is burdened by a high rate of complications as shunt infection or obstruction, skin erosion. PHH is actually one of the types of hydrocephalus more frequently requiring multiple operations (about 30% of the cases). The advent of neuroendoscopy reduced the risk of complications but did not affect the risk of reoperations significantly. Endoscopy is useful in treating the complications of the hemorrhage, for example by aspirating ventricular blood clots, by fenestrating intraventricular cysts or septa, or by treating isolated ventricles (septostomy, aqueductoplasty). These procedures allows the patient to avoid multiple shunts and, therefore, to reduce the risk of complications. However, endoscopic third ventriculostomy, which is the endoscopic definitive option for PHH, is effective in about one third of the cases, thus resulting in the need of reoperation. Immaturity of the CSF re-adsorption pathways, obstruction of the subarachnoid spaces and low intracranial pressure are the main causes of endoscopy failures.

ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis.

Grade IV astrocytoma or glioblastoma multiforme (GBM) is one of the most aggressive and lethal tumors affecting humans. ADAR2-mediated A-to-I RNA editing, an essential post-transcriptional modification event in brain, is impaired in GBMs and astrocytoma cell lines. However, the role of ADAR2 editing in astrocytomas remains to be defined. Here, we show that ADAR2 editing rescue in astrocytomas prevents tumor growth in vivo and modulates an important cell cycle pathway involving the Skp2/p21/p27 proteins, often altered in glioblastoma. We demonstrate that ADAR2 deaminase activity is essential to inhibit tumor growth. Indeed, we identify the phosphatase CDC14B, which acts upstream of the Skp2/p21/p27 pathway, as a novel and critical ADAR2 target gene involved in glioblastoma growth. Specifically, ADAR2-mediated editing on CDC14B pre-mRNA increases its expression with a consequent reduction of the Skp2 target protein, as shown both in vitro and in vivo. We found that, compared to normal brain, both CDC14B editing and expression are progressively impaired in astrocytomas from grade I to IV, being very low in GBMs. These findings (1) demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, (2) identify ADAR2-editing enzyme as a novel candidate tumor suppressor gene and (3) provide proof of principle that ADAR2 or its substrates may represent a suitable target(s) for possible novel, more effective and less toxic approaches to the treatment of GBMs.

Subcutaneous blood patch for iatrogenic suboccipital pseudomeningocele following decompressive suboccipital craniectomy and enlarging duroplasty for the treatment of Chiari I malformation. Technical note.

PURPOSE: Epidural blood patch (EBP) represents one of the best nonsurgical treatment for intracranial hypotension syndrome. Orthostatic headache caused by reduced intracranial cerebrospinal fluid (CSF) pressure, like in "spontaneous" intracranial hypotension or as consequence of lumbar puncture or anesthesiological procedure, can be managed with the injection of autologous blood on the epidural space with a successful rate of 89%, increased to 97% after a second application. MATERIALS AND METHODS: This 9-year-old girl was admitted to our department because of a suboccipital pseudomeningocele. She was previously operated on for a Chiari type I malformation by suboccipital craniectomy, C1 laminectomy and duraplasty. At the admission, she complained for nucal pain. Brain MRI showed a large suboccipital fluid collection that persisted even after the revision of the duraplasty and the placement of an external lumbar drainage. The child underwent a first injection of a mixture of blood (10 ml) and fibrin glue (10 ml) within the subcutaneous space after needle-aspiration of the collection. The same treatment was repeated 3 weeks later. RESULTS: The procedures were well tolerated and no local or systemic complications occurred. The fluid collection was significantly reduced after the first injection and it was completely effaced following the second one. Such a result remained stable after 3 months, as demonstrated by MRI. No recurrence of the pseudomeningocele was detected at the last clinical control (8-month follow-up). CONCLUSION: Subcutaneous blood patch could represent a safe and effective option for the treatment of CSF fistula, especially in case of failure of the traditional management.

Epilepsy surgery of posterior quadrant dysplasia in the first year of life: experience of a single centre with long term follow-up.

Posterior quadrant dysplasia (PQD) is a rare variant of cortical dysplasia involving the posterior regions of a single hemisphere. It is always associated with early onset, refractory epilepsy often characterized by a "catastrophic" evolution. The experience on its surgical management during the first year of life is limited to sporadic, isolated cases. Between 2002 and 2005, four children less than one-year-old and affected by drug-resistant epilepsy associated with PQD were admitted to our Institution and underwent surgical treatment. One patient remained seizure-free during all the follow-up (Engel I). The remaining three children showed a recurrence of the seizures, requiring subsequent surgical procedures in two cases. In one case (Engel II), the seizure control has been obtained thanks to pharmacological treatment. The other two patients respectively had only a partial (Engel III) and a less relevant reduction of the number of seizures (Engel IV). Both the epileptic and the neuropsychological outcome of our series were significantly influenced by persistent contralateral interictal anomalies rather than by the timing of the surgical procedure. Unpredictable results should be expected in this kind of patients if there is the detection of contralateral independent epileptiform activities on the EEG at diagnosis. Parents and relatives should be aware of the results' variability, even though a reduction of seizures may be expected, enabling an easier handling of the child's condition.

Survival following treatment for intracranial ependymoma: a review.

The actual definition of survival rates following treatment for intracranial ependymomas is substantially influenced by the strict interaction among different factors. Age, location, and grading, for example, act together, negatively influencing the prognosis of younger children also invariably influenced by the more demanding role of surgery and the still limited use, up to recently, of radiotherapy under 3 years of age. In the same direction, the worse prognosis in most series of infratentorial ependymomas if compared with their supratentorial counterpart should be cautiously considered, midline posterior fossa tumors having completely different implications from those originating or predominantly extending to the cerebellopontine angle, where the extent of surgery has more invariably to compare with patients' quality of life. New radiotherapic regimens and their applications in infancy are promisingly demonstrating an improvement of present prognostic criteria, with the limit of still insufficient information on their long-term secondary effects. Similarly, molecular biology research studies, though still in their preclinical stage, are prompting to change the concept of a substantially chemoresistant tumor helping to stratify these lesions with the final aim of targeted pharmacological therapies. In the present review paper, we investigated singularly the role that the more commonly considered prognostic factors have had in the literature on survival of children affected by intracranial ependymomas, trying to elucidate their cumulative effect on the actual knowledge of this issue.

Endoscopic third ventriculostomy: the best option in the treatment of persistent hydrocephalus after posterior cranial fossa tumour removal?

BACKGROUND: Ten to 40% of children operated on for a posterior fossa tumour require a further surgical procedure for the management of a persisting active ventricular dilation. The management of this kind of hydrocephalus is still controversial. OBJECTIVE: To prospectively evaluate the effectiveness of post-operative endoscopic third ventriculostomy (ETV) in the management of persistent active hydrocephalus in a series of children operated on for a posterior cranial fossa tumour. METHODS: The management protocol consisted of: (1) placement of a peri-operative antibiotic impregnated external ventricular catheter (Bactiseal) and tumour removal, (2) post-operative intracranial pressure (ICP) monitoring through the external ventricular drainage, (3) ETV in case of persistent ventricular dilation and persistently abnormal high ICP values and (4) ventriculoperitoneal shunt implantation in case of ETV failure. RESULTS: Thirty on a total of 104 children (28.8%) operated on between January 2001 and February 2007 at our institution needed a further surgical treatment for the persistence of the hydrocephalus after the removal of their posterior cranial fossa tumour. They were sub-divided in two groups according to the early (group 1--21 patients) or later (group 2--nine patients) definition of the persistence of an active ventricular dilation based on clinical, radiological and ICP monitoring data. ETV was successful in 90.0% of the patients in the present series (27/30 patients), without statistically significant differences among the two groups considered. CONCLUSIONS: Post-operative ETV should be considered the best option to treat persistent hydrocephalus after the removal of posterior fossa tumours.