Rapid DNA methylation-based classification of pediatric brain tumors from ultrasonic aspirate specimens.

BACKGROUND: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing. METHODS: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation. RESULTS: 19 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 17/19 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 79%. Copy number variation profiles were generated for all cases and matched EPIC results in 18/19 (95%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations. CONCLUSION: Methylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing.

Surgical options of chiasmatic hypothalamic glioma-a relevant part of therapy in an interdisciplinary approach for tumor control.

OBJECTIVE: The extent of resection of pediatric low-grade glioma mostly improves progression-free survival. In chiasmatic hypothalamic glioma (CHG), complete resections are limited due to the relevantly high risk of associated neurological and endocrinological deficits. Still, surgery might have its role in the framework of a multidisciplinary team (MDT) approach. We report our retrospective experience from two centers on surgical options and their impact on long-term outcomes. METHODS: Medical records of surgically treated pediatric CHG patients between 2004 and 2022 were analyzed. Patient characteristics, surgical interventions, histology, and non-surgical therapy were retrieved together with outcome measures such as visual acuity, endocrine function, and survival. RESULTS: A total of 63 patients (33 female, NF-1, n = 8) were included. Age at first diagnosis was 4.6 years (range 0.2-16.9) and cohort follow-up was 108 ± 72 months. Twenty patients were surgically treated with a biopsy and 43 patients with debulking at a median age of 6.5 years (range 0.16-16.9). Patients received a median of 2 tumor surgeries (range 1-5). Cyst drainage was accomplished in 15 patients, and 27 patients had ventriculoperitoneal shunt implantation. Non-surgical therapy was given in 69.8%. At the end of follow-up, 74.6% of patients had stable disease. The cohort had a median Karnofsky score of 90 (range 0-100). Four patients died. Hormone substitution was necessary in 30.2%, and visual acuity was impaired in 66% of patients. CONCLUSION: Pediatric CHG is a chronic disease due to overall high survival with multiple progressions. Surgical therapy remains a key treatment option offering biopsy, limited tumor-debulking, cyst fenestration, and hydrocephalus management in the framework of MDT decision-making. Team experience contributes to reducing possible deficits in this challenging cohort.

Navigated bedside implantation of external ventricular drains with mobile health guidance: technical note and case series.

PURPOSE: External ventricular drain (EVD) implantation is one of the fundamental procedures of emergency neurosurgery usually performed freehand at bedside or in the operating room using anatomical landmarks. However, this technique is frequently associated with malpositioning leading to complications or dysfunction. Here, we describe a novel navigated bedside EVD insertion technique, which is evaluated in a clinical case series with the aim of safety, accuracy, and efficiency in neurosurgical emergency settings. METHODS: From 2021 to 2022, a mobile health-assisted navigation instrument (Thomale Guide, Christoph Miethke, Potsdam, Germany) was used alongside a battery-powered single-use drill (Phasor Health, Houston, USA) for bedside EVD placement in representative neurosurgical pathologies in emergency situations requiring ventricular cerebrospinal fluid (CSF) relief and intracranial pressure (ICP) monitoring. RESULTS: In all 12 patients (8 female and 4 male), navigated bedside EVDs were placed around the foramen of Monro at the first ventriculostomy attempt. The most frequent indication was aneurysmal subarachnoid hemorrhage. Mean operating time was 25.8 ± 15.0 min. None of the EVDs had to be revised due to malpositioning or dysfunction. Two EVDs were converted into a ventriculoperitoneal shunt. Drainage volume was 41.3 ± 37.1 ml per day in mean. Mean length of stay of an EVD was 6.25 ± 2.8 days. Complications included one postoperative subdural hematoma and cerebrospinal fluid infection, respectively. CONCLUSION: Combining a mobile health-assisted navigation instrument with a battery-powered drill and an appropriate ventricular catheter may enable and enhance safety, accuracy, and efficiency in bedside EVD implantation in various pathologies of emergency neurosurgery without adding relevant efforts.

Neurosurgical morbidity in pediatric supratentorial midline low-grade glioma: Results from the German LGG studies.

Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Exactly 537 operations (230 resections, 167 biopsies, 140 nontumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed following 254/537 (47.3%) and medical morbidity following 97/537 (18.1%) patients with a 40.1% 30-day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age <3 years at operation, tumor volume ≥80 cm3 , presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor-related procedures and during the earlier study period between 1998 and 2006, while the neurosurgical approach, tumor location, NF1 status or previous nonsurgical treatment were not. Neurosurgery-associated morbidity was frequent in pediatric patients with SML-LGG undergoing surgery in the German LGG-studies. We identified patient- and institution-associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills.

The Supraorbital Eyebrow Approach in Pediatric Neurosurgery: Perspectives and Challenges of Frontal Keyhole Surgery.

OBJECT: Supraorbital craniotomy via an eyebrow incision provides minimally invasive cosmetically favorable access to both orbital and intracranial pathologies. We describe the indication, surgical technique, and clinical course using this surgical approach in a cohort of patients from a single pediatric neurosurgery unit. METHODS: In a retrospective analysis, we identified all surgical cases between January 2013 and April 2022 who underwent the supraorbital craniotomy via an eyebrow incision. Craniotomy was performed using piezosurgery ultrasonic bone incision. An interdisciplinary team of an orbital surgeon and a neurosurgeon performed the orbital surgeries. Clinical and surgical characteristics, perioperative data, possible complications, or redo surgeries as well as ophthalmologic status were assessed. RESULTS: Clinical data of 37 interventions (cases) in 30 patients (age: 8 ± 6.5 years) were analyzed. The supraorbital craniotomy established access to the cranial, lateral, and central portions of the orbit (n = 11) and ipsilateral fronto-medial portions of the skull base (n = 26). Thirty cases suffered from tumor disease with heterogeneous histopathologic diagnoses, and in 13 cases, adjuvant therapy was required. The mean duration of surgery was 163 ± 95 min, and the mean time of hospital stay was 6.0 ± 2.8 days. In two cases (5.4%), the following complications were observed. One infection treated by puncture and antibiotics and one revision surgery was necessary due to loosening of osteosynthesis material. Postoperative visual function was stable compared to preoperative status after all interventions. After a mean follow-up time of 26 ± 25.9 months for oncologic cases the long term outcome was complete remission in 13, stable disease in 14, progressive disease in 1 and death in 2 patients. CONCLUSION: The supraorbital eyebrow approach is feasible and safe in pediatric neurosurgical cases as a minimally invasive and cosmetic favorable technique and should be considered for intraorbital as well as ipsilateral intracranial lesions adjacent to the skull base. Interdisciplinary cooperation enables a broader spectrum of surgical options in orbital and complex, fronto-basal, skull base pathologies.

Maneuver protocol for outpatient telemetric intracranial pressure monitoring in hydrocephalus patients.

INTRODUCTION: Telemetric intracranial pressure measurement (tICPM) offers new opportunities to acquire objective information in shunted and non-shunted patients. The sensor reservoir (SR) provides tICPM modality at a decent sampling rate as an integrated component of the CSF shunt system. The aim of this study is to perform tICPM during a defined protocol of maneuvers in an outpatient setting as feasibility study including either shunt-dependent patients or candidates for possible shunt therapy. METHODS: A total of 17 patients received a SR and were investigated within a protocol of maneuver measurements involving different body postures (90°, 10°, 0°, and - 10°), breathing patterns (hypo- and hyperventilation), and mild venous congestion (Valsalva, Jugular vein compression), while the latter two were performed in lying postures (10° and 0°). The cohort included 11 shunted and 6 non-shunted (stand-alone-SR) patients. All measurements were evaluated using an ICP-analysis software (ICPicture, Miethke, Germany) looking at ICP changes and amplitude (AMP) characteristics. RESULTS: The shunted patient group consisted of 11 patients (median age: 15.8 years; range: 4-35.2 years) with either a primary shunt (n=9) and 2 patients received a shunt after stand-alone-SR tICPM. Six patients were enrolled with a stand-alone SR (median age 11.9 years, range 3.6-17.7 years). In the stand-alone SR group, maneuver related ICP and AMP changes were more sensitive compared to shunted patients. Postural maneuvers caused significant ICP changes in all body positions in both groups. The highest ICP values were seen during Valsalva maneuver, provoked by the patients themselves. In the stand-alone group, significant higher ICP values during hyperventilation were observed compared to shunted individuals. In shunted patients, a significant correlation between ICP and AMP was observed only during hyperventilation maneuver, while this correlation was additionally seen in Valsalva and jugular vein compression in stand-alone patients. CONCLUSION: SR-related tICPM is helpful to objectify diagnostic evaluation in patients with CSF dynamic disturbances. The defined protocol did result in a wide range of ICP changes with promising potential for effective outpatient tICPM investigation. Since the correlation of ICP and AMP was observed during mild venous congestion maneuvers it appears to be specifically helpful for the evaluation of intracranial compliance. Further investigations of maneuver-related tICPM in a larger population, including variable pathologies, are needed to further establish the protocol in the clinical practice.

[Pediatric Intracranial Ependymoma - Recommendations for First-Line Treatment from the German HIT-MED study group]. / Kinder und Jugendliche mit intrakraniellem Ependymom ­ Empfehlungen der HIT-MED-Studiengruppe der GPOH zur Erstlinientherapie.

Biological subtypes of ependymoma (EPN) have been introduced by the recent WHO classification and appear to have great impact on the clinical course, but have not yet found their way into clinical risk stratification. Further, the overall unfavorable prognosis underlines the fact that current therapeutic strategies need further evaluation for improvement. To date, there is no international consensus regarding first-line treatment for children with intracranial EPN. Extent of resection is known to be the most important clinical risk factor, leading to the consensus that consequent evaluation for re-surgery of postoperative residual tumor needs to have highest priority. Furthermore, efficacy of local irradiation is unquestioned and recommended for patients aged>1 year. In contrast, efficacy of chemotherapy is still under discussion. The European trial SIOP Ependymoma II aims at evaluating efficacy of different chemotherapy elements, leading to the recommendation to include German patients. The BIOMECA study, as biological accompanying study, aims at identifying new prognostic parameters. These results might help to develop targeted therapies for unfavorable biological subtypes. For patient who are not qualified for inclusion into the interventional strata, the HIT-MED Guidance 5.2 provides specific recommendations. This article is meant as an overview of national guidelines regarding diagnostics and treatment as well as of treatment according to the SIOP Ependymoma II trial protocol.

How to define CSF overdrainage: a systematic literature review.

PURPOSE: Overdrainage (OD) is one of the most frequent complications related to drainage of the cerebrospinal fluid (CSF). It is mostly associated with valve-bearing shunt systems but should probably be considered as a risk factor in any type of CSF diversion procedure. There is extreme variation in the reported incidence of OD due to the lack of consensus on defining criteria and an unclear perception of the pathophysiology. Hence, OD is probably underreported and underestimated. The objective of this paper was to establish a definition of OD, based on a systematic review of the literature. METHODS: A systematic search was conducted in MEDLNE and EMBASE. Studies providing a definition or a description of diagnostic findings related to OD in ventriculoperitoneal shunt treated hydrocephalus were included. Non-English titles, abstracts and manuscripts were excluded. Extracted descriptions were graded into five groups (class I-V studies) based on how precise the terminology used to describe OD was. Class I studies were included for further analysis and characteristics of OD were extracted. The quality of included descriptions was assessed by a clinical expert panel. RESULTS: A total of 1309 studies were screened, 190 were graded into groups, and 22, which provided specific definitions or descriptions of OD, were graded as class I studies. We extracted 32 different characteristics consistent with OD (e.g., clinical symptoms, radiological signs, and syndromes). CONCLUSION: There was an overall agreement that CSF overdrainage following implantation of a ventriculoperitoneal shunt in a mixed pediatric and adult population is characterized as a persistent condition with clinically manifestations as postural dependent headache, nausea, and vomiting and/or radiological signs of slim ventricles and/or subdural collections.

Tumor load rather than contrast enhancement is associated with the visual function of children and adolescents with optic pathway glioma - a retrospective Magnetic Resonance Imaging study.

INTRODUCTION: Optic pathway gliomas are often asymptomatic tumors occurring in children with neurofibromatosis type 1 (NF1 + OPG) or sporadically (spOPG). Treatment is usually prompted by visual loss and/or tumor progression on MRI. The aim of this study was to investigate the relationship between visual acuity (VA), tumor growth, and contrast enhancement to provide more distinct indications for the administration of gadolinium-based contrast agents. METHODS: Tumor load was retrospectively measured and enhancement semi-quantitatively scored on 298 MRIs of 35 patients (63% NF1 + OPG). Spearman rank correlation between tumor load and enhancement was calculated and a linear mixed model used to examine the influence of tumor load and enhancement on corresponding VA tests (LogMAR). RESULTS: The optic nerve width in NF1 + OPGs was strongly associated with VA (regression coefficient 0.75; confidence interval 0.61-0.88), but weakly with enhancement (0.06; -0.04-0.15). In spOPGs, tumor volume and optic nerve width were more relevant (0.31; -0.19-0.81 and 0.39; 0.05-0.73) than enhancement (0.09; -0.09-0.27). CONCLUSIONS: Tumor load measures may be more relevant for the surveillance of optic pathway gliomas than enhancement, given that VA is the relevant outcome parameter. Regular contrast administration should therefore be questioned in these patients.

Underestimating isolated bilateral hygroma as non-accidental head injury with dramatic consequences: a case presentation.

OBJECTIVE: Abusive head injury (AHI) in infancy is associated with significantly worse outcomes compared to accidental traumatic brain injury. The decision-making of the diagnosis of AHI is challenging especially if the clinical signs are not presenting as a multifactorial pattern. METHOD: We present a case of isolated bilateral hygroma in which this differential diagnosis of AHI was evaluated but primarily not seen as such leading subsequently to extensive secondary AHI with fatal brain injury. RESULTS: The case of an 8-week-old infant with apparently isolated bilateral hygroma without any external signs of abuse and no retinal hemorrhages was interpreted in causative correlation to the perinatal complex course of delivery. At a second readmission of the case, severe brain injury with bilateral cortical hypoxia, subarachnoid and subdural hemorrhages, and skull and extremity fractures led to severe disability of the affected infant. CONCLUSION: Any early suspicion of AHI with at least one factor possibly being associated with abusive trauma should be discussed in multidisciplinary team conferences to find the best strategy to protect the child. Beside clinical factors, social factors within the family household may additionally be evaluated to determine stress-related risk for traumatic child abuse. In general, prevention programs will be essential in future perspective.

In vitro testing of explanted shunt valves in hydrocephalic patients with suspected valve malfunction.

Diagnosis of symptomatic valve malfunction in hydrocephalic patients treated with VP-Shunt (VPS) might be difficult. Clinical symptoms such as headache or nausea are nonspecific, hence cerebrospinal fluid (CSF) over- or underdrainage can only be suspected but not proven. Knowledge concerning valve malfunction is still limited. We aim to provide data on the flow characteristics of explanted shunt valves in patients with suspected valve malfunction. An in vitro shunt laboratory setup was used to analyze the explanted valves under conditions similar to those in an implanted VPS. The differential pressure (DP) of the valve was adjusted stepwise to 20, 10, 6, and 4 cmH2O. The flow rate of the explanted and the regular flow rate of an identical reference valve were evaluated at the respective DPs. Twelve valves of different types (Codman CertasPlus valve n = 3, Miethke Shuntassistant valve n = 4, Codman Hakim programmable valve n = 3, DP component of Miethke proGAV 2.0 valve n = 2) from eight hydrocephalic patients (four male), in whom valve malfunction was assumed between 2016 and 2017, were replaced with a new valve. Four patients suffered from idiopathic normal pressure (iNPH), three patients from malresorptive and one patient from obstructive hydrocephalus. Post-hoc analysis revealed a significant difference (p < 0.001) of the flow rate between each explanted valve and their corresponding reference valve, at each DP. In all patients, significant alterations of flow rates were demonstrated, verifying a valve malfunction, which could not be objectified by the diagnostic tools used in the clinical routine. In cases with obscure clinical VPS insufficiency, valve deficiency should be considered.

Severe Traumatic Brain Injury in children-paradigm of decompressive craniectomy compared to a historic cohort.

PURPOSE: Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. Medical therapy remains limited, and decompressive craniectomy (DC) is an established rescue therapy in case of elevated intracranial pressure (ICP). Much discussion deals with clinical outcome after severe TBI treated with DC, while data on the pediatric population is rare. We report our experience of treating severe TBI in two different treatment setups at the same academic institution. METHODS: Forty-eight patients (≤ 16 years) were hospitalized with severe TBI (GCS ≤ 8 points) between 2008 and 2018 in a pediatric intensive care unit (ICU) at a specialized tertiary pediatric care center. Data on treatment, clinical status, and outcome was retrospectively analyzed. Outcome data included Glasgow Outcome Scale (GOS) at 3-, 12-, and 36-month follow-up. Data was compared to a historic cohort with 53 pediatric severe TBI patients treated at the same institution in a neurointensive care unit between 1996 and 2007. Ethical approval was granted (EA2/076/21). RESULTS: Between 2008 and 2018, 11 patients were treated with DC. Compared to the historic cohort, patients were younger and GCS was worse, while in-hospital mortality and clinical outcome remained similar. A trend towards more aggressive EVD placement and the internal paradigm change for treatment in a specialized pediatric ICU was observed. CONCLUSIONS: In children with severe TBI treated over two decades, clinical outcome was comparable and mostly favorable in two different treatment setups. Consequent therapy is warranted to maintain the positive potential for favorable outcome in children with severe TBI.

Importance of urodynamic evaluation of bladder function after secondary untethering in spina bifida patients: single center experience of 30 years.

INTRODUCTION: A TCS after primary closure of meningomyeloceles is a known complication of the spina bifida disease. Data on the outcome after SSCU surgery is heterogeneous and lacking standardization. Thus we aimed to find a reliable system for assessment of the bladder function before and after SSCU surgery and document postoperative outcome. METHODS: A retrospective study was performed on a cohort of patients with spina bifida diagnosis. In total, 130 patients underwent 182 SSCU surgeries, 56 of those met our inclusion criteria. A classification system, including two different methods, was used. The AC system used baseline pressure and detrusor over activity to define three levels of bladder dysfunction, the second method ranked the severity of bladder dysfunction by awarding points from 0 to 2 for bladder capacity, maximal detrusor pressure during autonomous contractions, leak point pressure and vesicoureteral reflux A high score is correlated with a severe bladder dysfunction. RESULTS: Gender distribution was equally (male: n = 29; 51.8%; female: n = 27; 48.2%). The median age at SSCU was 902 years (range 0.5-22.8 years). After SSCU, the stage improved in 11 patients (19.6%), worsened in 11 (19.6%) patients and remained the same in 34 patients (60.7%) after intervention (AC score). Non-worsening was observed in a total of 45 cases (80.4%) (p < 0.001). MHS score (n = 27, 48.2%) improved, remained unchanged (n = 12, 21.4%), 17 patients worsened (30.4%). Non-worsening in postoperative bladder functional outcome was demonstrated in 39 cases (69.6%) over all (p < 0.005). Regardless of whether bladder function is categorized by AC or MHS, postoperative outcome worsened significantly when SSCU was performed due to increasing deterioration in motor function alone (p < 0.05). Of the 24 cases with NOD as indication, 22 (91.7%) had an unchanged (n = 10; 41.7%) or improved (n = 12; 50.0%), meaning positive neuro-orthopedic outcome, only 2 (8.3%) deteriorated (p < 0.001). CONCLUSION: Our study presents reliable evaluation systems for bladder function in spina bifida patients. Since indications for SSCU surgery differ, it is important to know the possible effects on bladder function after this surgical procedure. Even a mild impairment of bladder function has a risk to deteriorate after SSCU surgery. Particularly interesting becomes this with regard to the fact that the prevalence of TCS might become more frequent with the rising numbers of prenatal closures of meningomyeloceles.

Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel-Lindau disease-related tumours.

AIMS: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. METHODS: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. RESULTS: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). CONCLUSION: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.

Neuroendoscopic surgery in neonates - indication and results over a 10-year practice.

PURPOSE: Neuroendoscopic procedures for treatment of term and preterm newborn infants, such as endoscopic lavage for posthemorrhagic hydrocephalus, are gaining popularity despite sparse data. This single-institution report compiles all neuroendoscopic surgical procedures performed in neonates during a 10-year period. METHODS: Charts and electronic records were reviewed of all consecutive newborns who underwent a neuroendoscopic procedure before reaching a postmenstrual age of 44 weeks between 09/2010 and 09/2020. Available documentation was reviewed regarding the performed neuroendoscopic procedure, course of disease, complications, and all re-operations throughout the first year of life. RESULTS: During the 10-year study period, 116 infants (median gestational age at birth: 29 1/7 weeks) underwent a total of 153 neuroendoscopic procedures (median postmenstrual age at surgery: 35 0/7 weeks). The most common indication at the time of the neuroendoscopic procedures (n = 153) was intraventricular hemorrhage (IVH, n = 119), intraventricular infection (n = 15), congenital malformation (n = 8), isolated 4th ventricle (n = 7), multiloculated hydrocephalus (n = 3), and tumor (n = 1). Thirty-eight of 116 children (32.8%) underwent 43 operative revisions after 153 neuroendoscopic procedure (28.1%). Observed complications requiring surgical revision were secondary infection (n = 11), CSF fistula (n = 9), shunt dysfunction (n = 8), failure of ETV (n = 6), among others. 72 children (62%) of 116 children required permanent CSF diversion via a shunt. The respective shunt rates per diagnosis were 47 of 80 (58.8%) for previously untreated IVH, 11 of 13 (84.6%) for intraventricular infection. Shunt survival rate for the first year of life was 74% for the whole cohort. CONCLUSION: The experience with this large cohort of neonates demonstrates the feasibility of neuroendoscopic technique for the treatment of posthemorrhagic or postinfectious hydrocephalus. Rate and type of complications after neuroendoscopic procedures were within the expected range. Assessing the potential long-term benefits of neuroendoscopic techniques has to await results of ongoing studies.

Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas.

PURPOSE: Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. METHODS: We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients' individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. RESULTS: Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. CONCLUSION: We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

Extended experience in parieto-occipital expansion surgery by meander technique-clinical and radiological evaluation.

INTRODUCTION: Brachycephaly and anterior and posterior plagiocephaly appear as an isolated entity or manifest in syndromic conditions. In severe cases, possible treatment options currently comprise either cranioplasty or osteogenetic distraction. The aim of this paper is to retrospectively review the perioperative course of a series of children treated by posterior meander expansion technique at our institution with focus on the course of postoperative intracranial volume and eventual tonsillar descent evolution. METHODS: Forty-two children received a posterior cranial vault remodeling by means of a posterior meander technique during a 7-year period. Hospital records were reviewed, and pre- and postoperative MRIs were analyzed for intracranial volume, cephalic and asymmetry index, and tonsillar position over time. RESULTS: Median age at surgery was 11.5 months (range 17 days-10 years). Nineteen children had a symmetrical cranial deformity, twenty-three an asymmetrical synostosis. Half of the cohort showed a syndromic condition. Transfusions were administered in the majority (92.2%) of the cases. A significant postoperative increase of intracranial volume was present from 1188.9 ± 370.4 cm3 to 1324.8 ± 352.9 cm3 (p < 0.001). The asymmetry index showed a significant improvement postoperatively: 0.86 ± 0.06 versus 0.91 ± 0.05 (p < 0.001), while the cephalic index showed a non-statistical change (0.91 ± 0.11 versus 0.88 ± 0.08). Tonsillar herniation, bilateral or homolateral, showed no significant changes at early control, while a nonsignificant amelioration of tonsillar descent was seen among children older than 12 months at late imaging follow-up. CONCLUSION: Among the osteoplastic techniques, the posterior meander technique offers several advantages, such as early mobilization of the child, less bony defects, absence of implants, and a small complication rate. However, further comparative studies among different surgical techniques are needed.

Reduced rates of infection after myelomeningocele closure associated with standard perioperative antibiotic treatment with ampicillin and gentamicin.

PURPOSE: Postnatal closure of a myelomeningocele (MMC) is a complex procedure with frequent complications following surgery. Bacterial colonization of the placode may cause infection and subsequent complications. The objectives of this study were to determine the preoperative bacterial colonization rates, to assess the antibiotic regimen, and to evaluate the overall postoperative infection rate. METHODS: All consecutive patients undergoing MMC closure in our hospital from January 2010 to January 2020 were evaluated. Epidemiological data, surgical data, complication characteristics, and microbiological results were documented. RESULTS: A total of 45 patients were evaluated; in 41 patients, a wound swab of the placode was performed directly before MMC closure (91%). All patients received a prophylactic antibiotic treatment for a mean of 5.6 ± 2.7 days around the performed MMC closure. In three patients with a wound swab (7.3%), a bacterial colonization could be detected-none of the patients developed a subsequent infection. Overall, 7 other patients developed an infection (15.6%), three local surgical site infections, and four shunt-related infections. After applying a standardized perioperative prophylactic antibiotic treatment with ampicillin and gentamicin, the infection rate was observed to be lower compared with that of a non-standardized treatment (6% vs. 45%; p = 0.019). CONCLUSIONS: In neonates who undergo MMC closure in the first 48 h after birth, the colonization rate of the placode was lower than previously reported. While the data presented cannot proof the benefit of a perioperative antibiotic prophylaxis, as compared with no prophylaxis, infection rates are low with a standardized antibiotic regime comprising ampicillin and gentamicin.

First experience with augmented reality neuronavigation in endoscopic assisted midline skull base pathologies in children.

INTRODUCTION: Endoscopic skull base approaches are broadly used in modern neurosurgery. The support of neuronavigation can help to effectively target the lesion avoiding complications. In children, endoscopic-assisted skull base surgery in combination with navigation systems becomes even more important because of the morphological variability and rare diseases affecting the sellar and parasellar regions. This paper aims to analyze our first experience on augmented reality navigation in endoscopic skull base surgery in a pediatric case series. PATIENTS AND METHODS: A retrospective review identified seventeen endoscopic-assisted endonasal or transoral procedures performed in an interdisciplinary setting in a period between October 2011 and May 2020. In all the cases, the surgical target was a lesion in the sellar or parasellar region. Clinical conditions, MRI appearance, intraoperative conditions, postoperative MRI, possible complications, and outcomes were analyzed. RESULTS: The mean age of our patients was 14.5 ± 2.4 years. The diagnosis varied, but craniopharyngiomas (31.2%) were mostly represented. AR navigation was experienced to be very helpful for effectively targeting the lesion and defining the intraoperative extension of the pathology. In 65% of the oncologic cases, a radical removal was proven in postoperative MRI. The mean follow-up was 89 ± 79 months. There were no deaths in our series. No long-term complications were registered; two cerebrospinal fluid (CSF) fistulas and a secondary abscess required further surgery. CONCLUSION: The implementation of augmented reality to endoscopic-assisted neuronavigated procedures within the skull base was feasible and did provide relevant information directly in the endoscopic field of view and was experienced to be useful in the pediatric cases, where anatomical variability and rarity of the pathologies make surgery more challenging.

Management of pineal region tumors in a pediatric case series.

Pineal region tumors commonly present with non-communicating hydrocephalus. These heterogeneous histological entities require different therapeutic regimens. We evaluated our surgical experience concerning procurance of a histological diagnosis, management of hydrocephalus, and choice of antitumoral treatment. We analyzed the efficacy of neuroendoscopic biopsy and endoscopic third ventriculocisternostomy (ETV) in patients with pineal region tumors between 2006 and 2019 in a single-center retrospective cross-sectional study with regard to diagnostic yield, hydrocephalus treatment, as well as impact on further antitumoral management. Out of 28 identified patients, 23 patients presented with untreated hydrocephalus and 25 without histological diagnosis. One patient underwent open biopsy, and 24 received a neuroendoscopic biopsy with concomitant hydrocephalus treatment if necessary. Eighteen primary ETVs, 2 secondary ETVs, and 2 ventriculoperitoneal shunts (VPSs) were performed. Endoscopic biopsy had a diagnostic yield of 95.8% (23/24) and complication rates of 12.5% (transient) and 4.2% (permanent), respectively. ETV for hydrocephalus management was successful in 89.5% (17/19) with a median follow-up of more than 3 years. Following histological diagnosis, 8 patients (28.6%) underwent primary resection of their tumor. Another 9 patients underwent later-stage resection after either adjuvant treatment (n = 5) or for progressive disease during observation (n = 4). Eventually, 20 patients received adjuvant treatment and 7 were observed after primary management. One patient was lost to follow-up. Heterogeneity of pineal region tumor requires histological confirmation. Primary biopsy of pineal lesions should precede surgical resection since less than a third of patients needed primary surgical resection according to the German pediatric brain tumor protocols. Interdisciplinary decision making upfront any treatment is warranted in order to adequately guide treatment.