Transorbital point-of-care ultrasound versus fundoscopic papilledema to support treatment indication for potentially elevated intracranial pressure in children.

PURPOSE: To compare transorbital point-of-care ultrasound techniques -optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE)- with fundoscopic papilledema to detect potentially raised intracranial pressure (ICP) with treatment indication in children. METHODS: In a prospective study, 72 symptomatic children were included, 50 with later proven disease associated with raised ICP (e.g. pseudotumour cerebri, brain tumour, hydrocephalus) and 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array transducer. This was compared to fundoscopic optic disc findings (existence of papilledema) and, in 28 cases, invasively measured ICP values. RESULTS: The sensitivity and specificity of a cut-off value of US-ONSD (5.73 mm) to detect treatment indication for diseases associated with increased ICP was 92% and 86.4%, respectively, compared to US-ODE (0.43 mm) with sensitivity: 72%, specificity: 77.3%. Fundoscopic papilledema had a sensitivity of 46% and a specificity of 100% in this context. Repeatability and observer-reliability of US-ODE examination was eminent (Cronbach's α = 0.978-0.989). Papilledema was detected fundoscopically only when US-ODE was > 0.67 mm; a US-ODE > 0.43 mm had a positive predictive value of 90% for potentially increased ICP. CONCLUSION: In our cohort, transorbital point-of-care US-ONSD and US-ODE detected potentially elevated ICP requiring treatment in children more reliably than fundoscopy. US-ONSD and US-ODE indicated the decrease in ICP after treatment earlier and more reliably than fundoscopy. The established cut-off values for US-ONSD and US-ODE and a newly developed US-based grading of ODE can be used as an ideal first-line screening tool to detect or exclude conditions with potentially elevated ICP in children.

Role of surgery in the treatment of pediatric low-grade glioma with various degrees of brain stem involvement.

OBJECTIVE: Posterior fossa pediatric low-grade glioma involving the brainstem and cerebellar peduncles (BS-pLGG) are a subgroup with higher risks at surgery. We retrospectively analyzed the role of surgery in the interdisciplinary armamentarium of treatment options in our institutional series of BS-pLGG with various degrees of brainstem involvement. MATERIAL AND METHODS: We analyzed data of 52 children with BS-pLGG after surgical intervention for clinical/molecular characteristics, neurological outcome, factors influencing recurrence/progression pattern, and tumor volumetric analysis of exclusively surgically treated patients to calculate tumor growth velocity (TGV). Tumors were stratified according to primary tumor origin in four groups: (1) cerebellar peduncle, (2) 4th ventricle, (3) pons, (4) medulla oblongata. RESULTS: The mean FU was 6.44 years. Overall survival was 98%. The mean PFS was 34.07 months. Two patients had biopsies only. Fifty-two percent of patients underwent remission or remained in stable disease (SD) after initial surgery. Patients with progression underwent further 23 resections, 15 chemotherapies, 4 targeted treatments, and 2 proton radiations. TGV decreased after the 2nd surgery compared to TGV after the 1st surgery (p < 0.05). The resection rates were significantly higher in Groups 1 and 2 and lowest in medulla oblongata tumors (Group 4) (p < 0.05). More extended resections were achieved in tumors with KIAA1549::BRAF fusion (p = 0.021), which mostly occurred in favorable locations (Groups 1 and 2). Thirty-one patients showed postoperatively new neurological deficits. A total of 27/31 improved within 12 months. At the end of FU, 6% had moderate deficits, 52% had mild deficits not affecting activities, and 36% had none. Fifty percent of patients were free of disease or showed remission, 38% were in SD, and 10% showed progression. CONCLUSION: The first surgical intervention in BS-pLGG can control disease alone in overall 50% of cases, with rates differing greatly according to location (Groups 1 > 2 > 3 > 4), with acceptable low morbidity. The second look surgery is warranted except in medullary tumors. With multimodality treatments almost 90% of patients can obtain remission or stable disease after > 5 years of follow-up. An integrated multimodal and multidisciplinary approach aiming at minimal safe residual disease, combining surgery, chemo-, targeted therapy, and, as an exception, radiation therapy, is mandatory.

Role of intraoperative ultrasound and MRI to aid grade of resection of pediatric low-grade gliomas: accumulated experience from 4 centers.

PURPOSE: Pediatric low-grade gliomas (pLGG) are the most common brain tumors in children and achieving complete resection (CR) in pLGG is the most important prognostic factor. There are multiple intraoperative tools to optimize the extent of resection (EOR). This article investigates and discusses the role of intraoperative ultrasound (iUS) and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of pLGG. METHODS: The tumor registries at Tuebingen, Rome and Pretoria were searched for pLGG with the use of iUS and data on EOR. The tumor registries at Liverpool and Tuebingen were searched for pLGG with the use of iMRI where preoperative CR was the surgical intent. Different iUS and iMRI machines were used in the 4 centers. RESULTS: We included 111 operations which used iUS and 182 operations using iMRI. Both modalities facilitated intended CR in hemispheric supra- and infratentorial location in almost all cases. In more deep-seated tumor location like supratentorial midline tumors, iMRI has advantages over iUS to visualize residual tumor. Functional limitations limiting CR arising from eloquent involved or neighboring brain tissue apply to both modalities in the same way. In the long-term follow-up, both iUS and iMRI show that achieving a complete resection on intraoperative imaging significantly lowers recurrence of disease (chi-square test, p < 0.01). CONCLUSION: iUS and iMRI have specific pros and cons, but both have been proven to improve achieving CR in pLGG. Due to advances in image quality, cost- and time-efficiency, and efforts to improve the user interface, iUS has emerged as the most accessible surgical adjunct to date to aid and guide tumor resection. Since the EOR has the most important effect on long-term outcome and disease control of pLGG in most locations, we strongly recommend taking all possible efforts to use iUS in any surgery, independent of intended resection extent and iMRI if locally available.

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.

The effect of intraoperative cerebral oxygen desaturations on postoperative cerebral oxygen metabolism in neonates and infants a pilot study.

INTRODUCTION: Cerebral oxygen desaturation during pediatric surgery has been associated with adverse perioperative outcomes. The aim of this pilot study was to analyze the frequency and severity of intraoperative cerebral oxygen desaturations and their impact on postoperative cerebral oxygen metabolism in neonates and infants undergoing pediatric surgery. METHODS: In a prospective pilot study, intra- and postoperative regional cerebral oxygen saturation and blood flow were measured noninvasively using a device combining laser Doppler flowmetry and white-light-spectrometry. Thirty-seven consecutive neonates and infants undergoing noncardiac surgery under general anesthesia for more than 30 min and necessity for invasive arterial blood pressure monitoring were included. Patients with pre-known congenital structural heart disease or cerebral disease were excluded. Continuously brain monitor recording was started in sedated patients before induction of anesthesia (preoperative baseline) and was completed 1 h postoperatively in the PICU in sedated, intubated, and mechanically ventilated states at the PICU (postoperative state). Baseline and postoperative state for cerebral fractional tissue oxygen extraction and approximated cerebral metabolic rate of oxygen were calculated. RESULTS: Seventeen (46%) of the 37 studied neonates and infants suffered from intraoperative periods of regional cerebral oxygen desaturation below 20% of the baseline (event group). Severity of cerebral desaturations was median 4.0%min/h [range 0.1-58.7; interquartile range [IQR] 0.99-21.29]. In the event group, the duration of surgery was significantly longer (median 135 min [range 11-260; IQR 113.5-167.0] vs median 46.5 min [range 11-180; IQR 30.5-159.3]; difference of -62.94; 95% confidence interval [CI] -105.17 to -20.71; p = .021). In the event group, cerebral fractional tissue oxygen extraction (median 0.41 [range 0.20-0.55; IQR 0.26-0.44] vs. median 0.27 [range 0.11-0.41; IQR 0.20-0.31]; difference of -0.11; 95% CI -0.17 to -0.05; p = .001) and approximated cerebral metabolic rate of oxygen (median 6.15 arbitrary unit [range 2.69-12.07; IQR 5.12-7.21] vs. median 4.14 arbitrary unit [range 1.78-7.86; IQR 3.82-6.31]; difference of -1.76; 95% CI -3.03 to -0.49; p = .009) were significantly higher and the cerebral regional oxygen saturation (median 58.99% [range 44.87-79.1; IQR 54.26-72.61] vs median 70.94% [range 57.9-86.13; IQR 67.07-76.59]; difference of 10.01; 95% CI 4.13-15.90; p = .002) significantly lower after surgery compared to the nonevent group. DISCUSSION: The increase of approximated cerebral metabolic rate of oxygen could indicate an elevated oxidative energy metabolism in the "stressed" brain, due to repair processes. The increased cerebral fractional tissue oxygen extraction fits with the decreased NIRS cerebral oxygenation. Our data suggest that an increase in cerebral oxygen metabolism was the cause. CONCLUSION: Cerebral oxygen desaturation during major surgery in neonates and infants is associated with early postoperative increased cerebral oxygen extraction and possibly increased cerebral oxygen metabolism.

Ultrasound-guided initial diagnosis and follow-up of pediatric idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension in children often presents with non-specific symptoms found in conditions such as hydrocephalus. For definite diagnosis, invasive intracranial pressure measurement is usually required. Ultrasound (US) of the optic nerve sheath diameter provides a non-invasive method to assess intracranial pressure. Transtemporal US allows imaging of the third ventricle and thus assessment for hydrocephalus. OBJECTIVE: To investigate whether the combination of US optic nerve sheath and third ventricle diameter can be used as a screening tool in pediatric idiopathic intracranial hypertension to indicate elevated intracranial pressure and exclude hydrocephalus as an underlying pathology. Further, to analyze whether both parameters can be used to monitor treatment outcome. MATERIALS AND METHODS: We prospectively included 36 children with idiopathic intracranial hypertension and 32 controls. Using a 12-Mhz linear transducer and a 1-4-Mhz phased-array transducer, respectively, optic nerve sheath and third ventricle diameters were determined initially and during the course of treatment. RESULTS: In patients, the mean optic nerve sheath diameter was significantly larger (6.45±0.65 mm, controls: 4.96±0.32 mm) and the mean third ventricle diameter (1.69±0.65 mm, controls: 2.99±1.31 mm) was significantly smaller compared to the control group, P<0.001. Optimal cut-off values were 5.55 mm for the optic nerve sheath and 1.83 mm for the third ventricle diameter. CONCLUSIONS: The combined use of US optic nerve sheath and third ventricle diameter is an ideal non-invasive screening tool in pediatric idiopathic intracranial hypertension to indicate elevated intracranial pressure while ruling out hydrocephalus. Treatment can effectively be monitored by repeated US, which also reliably indicates relapse.

Evaluating the safety of perioperative dexamethasone treatment: A retrospective analysis of a single center pediatric low-grade glioma cohort.

In addition to surgical management, corticosteroids have proven to be beneficial in the management of acute symptoms related to CNS tumors, and have been widely used for many decades, with dexamethasone (DM) representing the most commonly used agent. However, lately published in vitro data possibly indicates a DM-induced suppression of oncogene-induced senescence (OIS) in a preclinical pediatric low-grade glioma (pLGG) model, which, alongside data associating perioperative DM treatment with reduced event-free survival in adult glioma, raises questions concerning the safety of DM treatment in pLGG. A total of 172 patients with pLGG were retrospectively analyzed concerning the impact of perioperative DM application on postoperative short- and long-term tumor growth velocity and progression-free survival (PFS). Three-dimensional volumetric analyses of sequential MRI follow-up examinations were used for assessment of tumor growth behavior. Mean follow-up period accounted for 60.1 months. Sixty-five patients (45%) were perioperatively treated with DM in commonly used doses. Five-year PFS accounted for 93% following gross-total resection (GTR) and 57% post incomplete resection (IR). Comparison of short- and long-term postoperative tumor growth rates in patients with vs without perioperative DM application showed no significant difference (short-term: 0.022 vs 0.023 cm3 /month, respectively; long-term: 0.019 vs 0.023 cm3 /month, respectively). Comparison of PFS post IR (5-year-PFS: 65% vs 55%, respectively; 10-year-PFS: 52% vs 53%, respectively) and GTR (5- and 10-years-PFS: 91% vs 92%, respectively) likewise showed similarity. This data emphasizes the safety of perioperative DM application in pLGG, adding further evidence for decision making and requested future guidelines.

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.

Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18% (n = 7) and 11% (n = 4) of the recurrences (n = 38) as compared to 7% (n = 3) and 0% (n = 0) in the primary tumors (n = 44), respectively. Similar to the observations made by DNA methylation profiling, RNA sequencing of our cohort revealed AT/RT primary tumors and matched recurrences clustering closely together. However, a number of genes showed significantly altered expression in AT/RT-SHH recurrences. Many of them are known tumor driving growth factors, involved in embryonal development and tumorigenesis, or are cell-cycle-associated. Overall, our work identifies subtle molecular changes that occur in the course of the disease and that may help define novel therapeutic targets for AT/RT recurrences.

Generation of patient-derived pediatric pilocytic astrocytoma in-vitro models using SV40 large T: evaluation of a modeling workflow.

PURPOSE: Although pediatric low-grade gliomas (pLGG) are the most common pediatric brain tumors, patient-derived cell lines reflecting pLGG biology in culture are scarce. This also applies to the most common pLGG subtype pilocytic astrocytoma (PA). Conventional cell culture approaches adapted from higher-grade tumors fail in PA due to oncogene-induced senescence (OIS) driving tumor cells into arrest. Here, we describe a PA modeling workflow using the Simian Virus large T antigen (SV40-TAg) to circumvent OIS. METHODS: 18 pLGG tissue samples (17 (94%) histological and/or molecular diagnosis PA) were mechanically dissociated. Tumor cell positive-selection using A2B5 was perfomed in 8/18 (44%) cases. All primary cell suspensions were seeded in Neural Stem Cell Medium (NSM) and Astrocyte Basal Medium (ABM). Resulting short-term cultures were infected with SV40-TAg lentivirus. Detection of tumor specific alterations (BRAF-duplication and BRAF V600E-mutation) by digital droplet PCR (ddPCR) at defined time points allowed for determination of tumor cell fraction (TCF) and evaluation of the workflow. DNA-methylation profiling and gene-panel sequencing were used for molecular profiling of primary samples. RESULTS: Primary cell suspensions had a mean TCF of 55% (+/- 23% (SD)). No sample in NSM (0/18) and ten samples in ABM (10/18) were successfully transduced. Three of these ten (30%) converted into long-term pLGG cell lines (TCF 100%), while TCF declined to 0% (outgrowth of microenvironmental cells) in 7/10 (70%) cultures. Young patient age was associated with successful model establishment. CONCLUSION: A subset of primary PA cultures can be converted into long-term cell lines using SV40-TAg depending on sample intrinsic (patient age) and extrinsic workflow-related (e.g. type of medium, successful transduction) parameters. Careful monitoring of sample-intrinsic and extrinsic factors optimizes the process.

Chronic Pleural Effusion in Ventriculoperitoneal Shunt due to Diaphragmatic CSF Fistula: Report of a Case Treated by Endoscopic Choroid Plexus Coagulation and Literature Review.

INTRODUCTION: Chronic pleural cerebrospinal fluid (CSF) effusion is a rare complication after ventriculoperitoneal (VP) shunt insertion and only 18 cases in children and adults have been described so far without catheter dislocation to the intrathoracic cavity. CASE PRESENTATION: We report on a 4-year-old girl with a complex history of underlying neurogenetic disorder, a hypoxic-ischemic encephalopathy after influenza A infection with septic shock and severe acute respiratory distress syndrome, followed by meningitis at the age of 10 months. In consequence, she developed a severe cerebral atrophy and post-meningitic hydrocephalus requiring placement of a VP shunt. At age 4, she was admitted with community-acquired mycoplasma pneumonia and developed increasing pleural effusions leading to severe respiratory distress and requiring continuous chest tube drainage (up to 1,000-1,400 mL/day) that could not be weaned. ß trace protein, in CSF present at concentrations >6 mg/L, was found in the pleural fluid at low concentrations of 2.7 mg/L. An abdomino-thoracic CSF fistula was finally proven by single photon emission computerized tomography combined with low-dose computer tomography. After shunt externalization, the pleural effusion stopped and the chest tube was removed. CSF production rate remains high above 500 mL/24 h. An atrial CSF shunt could not be placed, since a hemodynamically relevant atrial septum defect with frail circulatory balance would not have tolerated the large CSF volumes. Therefore, she underwent a total bilateral endoscopic choroid plexus laser coagulation (CPC) within the lateral ventricles via bi-occipital burr holes. Postoperatively CSF production rate went close to 0 mL and after external ventricular drain removal no signs and symptoms of hydrocephalus developed during a follow-up of now 2.5 years. CONCLUSION: In summary, pleural effusions in patients with VP shunt can rarely be caused by an abdomino-thoracic fistula, with non-elevated ß-trace protein in the pleural fluid. The majority of reported cases in literature were treated by ventriculoatrial shunt. This is the 2nd reported case, which has been successfully treated by radical CPC alone including the temporal horn choroid plexus, making the child shunt independent.

[Surgical procedures for treatment of spasticity]. / Chirurgische Verfahren zur Therapie von Spastik.

BACKGROUND: The causes of spasticity are various and include cerebral palsy, spinal cord injury, stroke, multiple sclerosis or other congenital or acquired lesions of the central nervous system (CNS). While there is often a partial functional component, spasticity also results in varying degrees of impairment of the quality of life. OBJECTIVE: A review of surgical treatment options for spasticity. MATERIAL AND METHODS: A systematic PubMed review of the literature on epidemiology and treatment options with a focus on neurosurgical interventions for spasticity and developments in the last 20 years as well as inclusion of still valid older landmark papers was carried out. Illustration of indications, technique, follow-up, and possible pitfalls of the different methods for the surgical treatment of spasticity. RESULTS: Depending on the affected region, the number of muscle groups, and the extent of spasticity, focal (selective peripheral neurotomy, nerve transfer), regional (selective dorsal rhizotomy), or generalized (baclofen pump) procedures can be performed. The indications are usually established by an interdisciplinary team. Conservative (physiotherapy, oral medications) and focally invasive (botulinum toxin injections) methods should be performed in advance. In cases of insufficient response to treatment or only short-term relief, surgical methods can be evaluated. These are usually preceded by test phases with, for example, trial injections. CONCLUSION: Surgical methods are a useful adjunct in cases of insufficient response to conservative treatment in children and adults with spasticity.

[Interdisciplinary networks in diseases of peripheral nerves-Exemplified by the Tübingen nerve team]. / Interdisziplinäre Netzwerke bei Erkrankungen der peripheren Nerven ­ am Beispiel des Tübinger Nerve Teams.

BACKGROUND: Nerve damage can be autoimmune inflammatory, metabolic or traumatic, among others, and can be difficult to differentiate. OBJECTIVE: What are the advantages of interdisciplinary networks and how do they work? MATERIAL AND METHOD: Field report with case presentation from the University Hospital Tübingen in cooperation with the BG Accident Clinic Tübingen. CONCLUSION: Interdisciplinary networks improve the care of our patients and also serve as regular multidisciplinary continuing education.

[Secondary surgical procedures following motor nerve injuries]. / Sekundäre operative Verfahren bei Verletzungen motorischer Nerven.

BACKGROUND: The functional deficits that develop after a peripheral nerve injury mean a considerable reduction in the quality of life for the affected patients. However, interventions on the injured nerve are not always possible or effective. In this case, secondary procedures, e.g. tendon transfers, are a feasible option for functional reconstruction. OBJECTIVES: An overview of the most common secondary surgical procedures for functional reconstruction after peripheral nerve injuries. METHODS: Presentation and discussion of the most common secondary surgical procedures with emphasis on tendon transfers. Illustration of the primary functions that need to be reconstructed depending on the respective nerve lesion. RESULTS: The basic principle of secondary surgical procedures after nerve injuries is the transposition of a healthy tendomuscular unit to replace a lost function following a loss of muscle or tendon or if an intervention on the nerve is not promising. For example, by transferring flexor forearm muscles, wrist, finger and thumb extension can be reconstructed after radial nerve injury. By transposing the tibialis posterior muscle, dorsiflexion in the talocrural joint can be restored to enable the affected patient to walk safely without an orthosis. CONCLUSIONS: Secondary surgical procedures are a valuable option for functional reconstruction after nerve injury.

Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery, genetics, and localization.

INTRODUCTION: Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT). Functional preservation and pain relief are the major goals in treating these tumors. METHODS: This retrospective observational study investigates the clinical and functional outcome of 205 operated peripheral (n = 148, 72%) and intraspinal (n = 57, 28%) schwannomas in 85 patients (53 NF2, 32 SWNT) treated at our department between 2006 and 2017. Associated factors such as genetics, age, and location were evaluated. RESULTS: Persisting drug-resistant pain was the most common symptom (84%, n = 173) and indication for surgery (54%, n = 110). Improvement in pain intensity was postoperatively seen in 81%. Peripheral nerve schwannomas exhibited worse pain intensity preoperatively compared to intraspinal lesions (p = 0.017 NF2, p = 0.029 SWNT). More total resections could be achieved in 93% of SWNT vs. 82% of NF2-associated tumors, p = 0.030). NF2 patients with intraspinal lesions were more neurologically affected (p < 0.05). Perioperative comparison of both tumor syndromes showed more neurological deficits (p = 0.027), and less pain (p = 0.024) in NF2-associated tumors. Mosaic NF2 patients had worse pain levels before surgery, and SWNT patients had a worse neurological function and more pain compared to non-mosaic or non-mutated cases. CONCLUSIONS: Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity. The influence of mutations needs to be further investigated in larger cohorts.

Resection extent and BRAF V600E mutation status determine postoperative tumor growth velocity in pediatric low-grade glioma: results from a single-center cohort analysis.

PURPOSE: Despite excellent long-term overall survival rates, pediatric low-grade gliomas (pLGG) show high variety of clinical behavior regarding progress or senescence post incomplete resection (IR). This study retrospectively analyzes tumor growth velocity (TGV) of pLGG before surgery and after IR to investigate the impact of surgical extent, tumor location and molecular BRAF status on postoperative residual tumor growth behavior. METHODS: Of a total of 172 patients with pLGG receiving surgical treatment, 107 underwent IR (66%). Fifty-three vs 94 patients could be included in the pre- and post-operative cohort, respectively, and were observed over a mean follow-up time of 40.2 vs 60.1 months. Sequential three-dimensional MRI-based tumor volumetry of a total of 407 MRI scans was performed to calculate pre- and postoperative TGV. RESULTS: Mean preoperative TGV of 0.264 cm3/month showed significant deceleration of tumor growth to 0.085 cm3/month, 0.024 cm3/month and -0.016 cm3/month after 1st, 2nd, and 3rd IR, respectively (p < 0.001). Results remained significant after excluding patients undergoing (neo)adjuvant treatment. Resection extent showed correlation with postoperative reduction of TGV (R = 0.97, p < 0.001). ROC analysis identified a residual cut-off tumor volume > 2.03 cm3 associated with a higher risk of progress post IR (sensitivity 78,6%, specificity 76.3%, AUC 0.88). Postoperative TGV of BRAF V600E-mutant LGG was significantly higher than of BRAF wild-type LGG (0.123 cm3/month vs. 0.016 cm3/month, p = 0.047). CONCLUSION: This data suggests that extensive surgical resection may impact pediatric LGG growth kinetics post incomplete resection by inducing a significant deceleration of tumor growth. BRAF-V600E mutation may be a risk factor for higher postoperative TGV.

Protocol for the multicentre prospective paediatric craniectomy and cranioplasty registry (pedCCR) under the auspices of the European Society for Paediatric Neurosurgery (ESPN).

PURPOSE: In the paediatric age group, the overall degree of evidence regarding decompressive craniectomy (DC) and cranioplasty is low, whereas in adults, randomised controlled trials and prospective multicentre registries are available. To improve the evidence-based treatment of children, a consensus was reached to establish a prospective registry under the auspices of the European Society for Pediatric Neurosurgery (ESPN). METHODS: This international multicentre prospective registry is aimed at collecting information on the indication, timing, technique and outcome of DC and cranioplasty in children. The registry will enrol patients ≤ 16 years of age at the time of surgery, irrespective of the underlying medical condition. The study design comprises four obligatory entry points as a core dataset, with an unlimited number of further follow-up entry points to allow documentation until adolescence or adulthood. Study centres should commit to complete data entry and long-term follow-up. RESULTS: Data collection will be performed via a web-based portal (homepage: www.pedccr.com ) in a central anonymised database after local ethics board approval. An ESPN steering committee will monitor the project's progress, coordinate analyses of data and presentation of results at conferences and in publications on behalf of the study group. CONCLUSION: The registry aims to define predictors for optimal medical care and patient-centred treatment outcomes. The ultimate goal of the registry is to generate results that are so relevant to be directly transferred into clinical practice to enhance treatment protocols.

Monitoring of cerebrovascular pressure reactivity in children may predict neurologic outcome after hypoxic-ischemic brain injury.

OBJECTIVES: Impaired cerebral blood flow is a first-line reason of ischemic-hypoxic brain injury in children. The principal goal of intensive care management is to detect and prevent further cerebral blood flow deficits. This can be achieved by actively managing cerebral perfusion pressure (CPP) using input from cerebrovascular autoregulation (CAR). The main objective of the current study was to investigate CAR after cardiac arrest in children. METHODS: Nineteen consecutive children younger than 18 years after cardiopulmonary resuscitation, in whom intracranial pressure (ICP) was continuously measured, were included. Blood pressure and ICP were continuously monitored via ICM + software and actively managed using the pressure reactivity index (PRx) to achieve and maintain an optimal CPP. Outcome was scored using the extended Glasgow outcome scale (eGOS) at discharge and 6 months. RESULTS: Eight children died in hospital. At 6 months, further 4 children had an unfavorable (eGOS1-4) and 7 a favorable (eGOS5-8) outcome. Over the entire monitoring period, we found an elevated ICP (24.5 vs 7.4 mmHg), a lower CPP (50.3 vs 66.2 mmHg) and a higher PRx (0.24 vs - 0.01), indicating impaired CAR, in patients with unfavorable outcome. The dose of impaired autoregulation was significantly higher in unfavorable outcome (54.6 vs 29.3%). Analyzing only the first 72 h after cardiac arrest, ICP ≥ 10 mmHg and PRx > 0.2 correlated to unfavorable outcome. CONCLUSIONS: Significant doses of impaired CAR within 72 h after resuscitation are associated with unfavorable outcome. The inability to restore autoregulation despite active attempts to do so as well as an elevated ICP may serve as a bad prognostic sign indicating a severe initial hypoxic-ischemic brain injury.

Identifying the optimal blood pressure for cerebral autoregulation in infants after cardiac surgery by monitoring cerebrovascular reactivity-A pilot study.

BACKGROUND: Advances in the treatment of pediatric congenital heart disease have increased survival rates. Despite efforts to prevent neurological injury, many patients suffer from impaired neurodevelopmental outcomes. Compromised cerebral autoregulation can increase the risk of brain injury following pediatric cardiac surgery with cardiopulmonary bypass. Monitoring autoregulation and maintaining adequate cerebral blood flow can help prevent neurological injury. AIMS: Our objective was to evaluate autoregulation parameters and to define the optimal blood pressure as well as the lower and upper blood pressure limits of autoregulation. METHODS: Autoregulation was monitored prospectively in 36 infants after cardiopulmonary bypass surgery for congenital heart defects between January and December 2019. Autoregulation indices were calculated by correlating invasive arterial blood pressure, cortical oxygen saturation, and relative tissue hemoglobin levels with near-infrared spectroscopy parameters. RESULTS: The mean patient age was 4.1 ± 2.8 months, and the mean patient weight was 5.2 ± 1.8 kg. Optimal mean arterial pressure could be identified in 88.9% of patients via the hemoglobin volume index and in 91.7% of patients via the cerebral oxygenation index, and a lower limit of autoregulation could be found in 66.7% and 63.9% of patients, respectively. No significant changes in autoregulation indices at the beginning or end of the monitoring period were observed. In 76.5% ± 11.1% and 83.8% ± 9.9% of the 8 and 16 h monitoring times, respectively, the mean blood pressure was inside the range of intact autoregulation (below in 21.5% ± 25.4% and 11.3% ± 16.5% and above in 8.7% ± 10.4% and 6.0% ± 11.0%, respectively). The mean optimal blood pressure was 57.4 ± 8.7 mmHg and 58.2 ± 7.9 mmHg and the mean lower limit of autoregulation was 48.8 ± 8.3 mmHg and 45.5 ± 6.7 mmHg when generated via the hemoglobin volume index and cerebral oxygenation index, respectively. CONCLUSIONS: Postoperative noninvasive autoregulation monitoring after cardiac surgery in children can be reliably and safely performed using the hemoglobin volume index and cerebral oxygenation index and provides robust data. This monitoring can be used to identify individual hemodynamic targets to optimize autoregulation, which differs from those recommended in the literature. Further evaluation of this subject is needed.

Rediscovery of the transcerebellar approach: improving the risk-benefit ratio in robot-assisted brainstem biopsies.

OBJECTIVE: Conventional frame-based stereotaxy through a transfrontal approach (TFA) is the gold standard in brainstem biopsies. Because of the high surgical morbidity and limited impact on therapy, brainstem biopsies are controversial. The introduction of robot-assisted stereotaxy potentially improves the risk-benefit ratio by simplifying a transcerebellar approach (TCA). The aim of this single-center cohort study was to evaluate the risk-benefit ratio of transcerebellar brainstem biopsies performed by 2 different robotic systems. In addition to standard quality indicators, a special focus was set on trajectory selection for reducing surgical morbidity. METHODS: This study included 25 pediatric (n = 7) and adult (n = 18) patients who underwent 26 robot-assisted biopsies via a TCA. The diagnostic yield, complication rate, trajectory characteristics (i.e., length, anatomical entry, and target-point location), and skin-to-skin (STS) time were evaluated. Transcerebellar and hypothetical transfrontal trajectories were reconstructed and transferred into a common MR space for further comparison with anatomical atlases. RESULTS: Robot-assisted, transcerebellar biopsies demonstrated a high diagnostic yield (96.2%) while exerting no surgical mortality and no permanent morbidity in both pediatric and adult patients. Only 3.8% of cases involved a transient neurological deterioration. Transcerebellar trajectories had a length of 48.4 ± 7.3 mm using a wide stereotactic corridor via crus I or II of the cerebellum and the middle cerebellar peduncle. The mean STS time was 49.5 ± 23.7 minutes and differed significantly between the robotic systems (p = 0.017). The TFA was characterized by longer trajectories (107.4 ± 11.8 mm, p < 0.001) and affected multiple eloquent structures. Transfrontal target points were located significantly more medial (-3.4 ± 7.2 mm, p = 0.042) and anterior (-3.9 ± 8.4 mm, p = 0.048) in comparison with the transcerebellar trajectories. CONCLUSIONS: Robot-assisted, transcerebellar stereotaxy can improve the risk-benefit ratio of brainstem biopsies by avoiding the restrictions of a TFA and conventional frame-based stereotaxy. Profound registration and anatomical-functional trajectory selection were essential to reduce mortality and morbidity.