Staged neurosurgical approach for giant and progressive neonatal arachnoid cysts: a case series and review of the literature.

OBJECTIVES: Prenatally diagnosed complex arachnoid cysts are very rare. While the true prenatal incidence is still unknown, they account for approximately 1% of intracranial masses in newborns. They rarely exhibit rapid growth or cause obstructive hydrocephalus, but if they increase to such a dimension during pregnancy, the ideal management is not well established. We present our detailed perinatal experience, covering prenatal diagnosis, a compassionate delivery process, and neonatal stabilization. Finally, a thorough postnatal neurosurgical intervention was performed. Initially, our focus was on the gradual reduction of cyst size as a primary effort, followed by subsequent definitive surgical treatment. METHODS: This case series shows the treatment course of three fetuses with antenatally diagnosed large arachnoid cysts. We present pre- and postnatal management and imaging, as well as the surgical treatment plan and the available clinical course during follow-up. RESULTS: Two girls and one boy were included in the current review. All three cases presented with prenatally diagnosed complex arachnoid cysts that increased in size during pregnancy. The mean gestational age at delivery was 35 weeks (range 32 to 37 weeks), and all patients were delivered by a caesarian section. Increasing head circumference and compression of brain structures were indications for delivery, as they are associated with a high risk of excess intracranial pressures and CSF diapedesis, as well as traumatic delivery and maternal complications. All cysts were supratentorial in location; one expanded into the posterior fossa, and one was a multicompartment cyst. All children underwent an initial surgical procedure within the first days of life. To relieve cyst pressure and achieve a reduction in head circumference, an ultrasound-guided or endoscopic-assisted internal shunt with drainage of the cyst to the ventricles or subdural/subarachnoid space was inserted. Definite surgical therapy consisted of cyst marsupialization and/or cysto-peritoneal shunt implantation. All children survived without severe neurodevelopmental impairments. CONCLUSION: With the cases presented, we demonstrate that the slow reduction of immense cyst size as an initial procedure until optimal requirements for final surgical treatment were achieved has proven to be optimal for neurological outcome. Special emphasis has to be taken on the delicate nature of premature newborn babies, and surgical steps have to be thoroughly considered within the interdisciplinary team.

Controversies in the Treatment of Arachnoid Cysts with Special Emphasis on Temporal Arachnoid Cysts.

Intracranial arachnoid cysts (ACs) are benign lesions. The incidence in children is 2.6%. ACs are often diagnosed incidentally. Because of the broad use of CT and MR imaging, the frequency of AC diagnosis has increased. In addition, prenatal diagnosis of ACs is becoming more common. This places clinicians in a difficult situation with regard to the optimal treatment, since the presenting symptoms are often vague and operative management includes not negligible risks. It is generally accepted that conservative management is indicated in cases with small and asymptomatic cysts. In contrast, patients with definite signs of raised intracranial pressure should be treated. There are however clinical situations in whom the decision about the preferred treatment is difficult to make. Unspecific symptoms such as headaches and neurocognitive or attention deficits can be challenging to evaluate, whether they are related to the presence of the AC or not. The treatment techniques intent to establish a communication between the cyst and the normal cerebrospinal spaces or consist of a diversion of the cyst fluid by a shunt system. Which surgical method (open craniotomy for cyst fenestration, endoscopic fenestration, or shunting) is preferred differs between neurosurgical centers or the pediatric neurosurgeon in charge. Each treatment option has a unique profile of advantages and disadvantages which should be considered when discussing treatment with the patients or their caregivers.

Compare and contrast: pediatric cancer versus adult malignancies.

Cancer is a leading cause of death in both adults and children, but in terms of absolute numbers, pediatric cancer is a relatively rare disease. The rarity of pediatric cancer is consistent with our current understanding of how adult malignancies form, emphasizing the view of cancer as a genetic disease caused by the accumulation and selection of unrepaired mutations over time. However, considering those children who develop cancer merely as stochastically "unlucky" does not fully explain the underlying aetiology, which is distinct from that observed in adults. Here, we discuss the differences in cancer genetics, distribution, and microenvironment between adult and pediatric cancers and argue that pediatric tumours need to be seen as a distinct subset with their own distinct therapeutic challenges. While in adults, the benefit of any treatment should outweigh mostly short-term complications, potential long-term effects have a much stronger impact in children. In addition, clinical trials must cope with low participant numbers when evaluating novel treatment strategies, which need to address the specific requirements of children.

Development and assessment of competency-based neurotrauma course curriculum for international neurosurgery residents and neurosurgeons.

OBJECTIVE: Traumatic brain injuries (TBIs) are a significant disease burden worldwide. It is imperative to improve neurosurgeons' training during and after their medical residency with appropriate neurotrauma competencies. Unfortunately, the development of these competencies during neurosurgeons' careers and in daily practice is very heterogeneous. This article aimed to describe the development and evaluation of a competency-based international course curriculum designed to address a broad spectrum of needs for taking care of patients with neurotrauma with basic and advanced interventions in different scenarios around the world. METHODS: A committee of 5 academic neurosurgeons was involved in the task of building this course curriculum. The process started with the identification of the problems to be addressed and the subsequent performance needed. After this, competencies were defined. In the final phase, educational activities were designed to achieve the intended learning outcomes. In the end, the entire process resulted in competency and outcomes-based education strategy, including a definition of all learning activities and learning outcomes (curriculum), that can be integrated with a faculty development process, including training. Further development was completed by 4 additional academic neurosurgeons supported by a curriculum developer specialist and a project manager. After the development of the course curriculum, template programs were developed with core and optional content defined for implementation and evaluation. RESULTS: The content of the course curriculum is divided into essentials and advanced concepts and interventions in neurotrauma care. A mixed sample of 1583 neurosurgeons and neurosurgery residents attending 36 continuing medical education activities in 30 different cities around the world evaluated the course. The average satisfaction was 97%. The average usefulness score was 4.2, according to the Likert scale. CONCLUSIONS: An international competency-based course curriculum is an option for creating a well-accepted neurotrauma educational process designed to address a broad spectrum of needs that a neurotrauma practitioner faces during the basic and advanced care of patients in different regions of the world. This process may also be applied to other areas of the neurosurgical knowledge spectrum. Moreover, this process allows worldwide standardization of knowledge requirements and competencies, such that training may be better benchmarked between countries regardless of their income level.

Accuracy of oscillometric noninvasive blood pressure compared with intra-arterial blood pressure in infants and small children during neurosurgical procedures: An observational study.

BACKGROUND: General anaesthesia in children results in a significant decrease of arterial pressure. Hypotension in neonates and infants reduces cerebral perfusion; therefore, an accurate arterial pressure measurement is of utmost importance. Although arterial pressure measured via an arterial catheter is considered to be the gold standard, in most children undergoing anaesthesia, arterial pressure is monitored by an upper arm cuff using an oscillometric technique. Data on the accuracy of these devices in such young patients are rare. OBJECTIVE: The aim of this study was to assess the accuracy of oscillometric blood pressure measurement compared with intra-arterial measurement. DESIGN: An observational comparison study. SETTING: A single-centre study, conducted in a German university hospital from November 2015 to January 2018. PATIENTS: Twenty-five children of 2 years old or less (median age 6 [IQR, 5 to 11]) months undergoing neurosurgical procedures requiring invasive arterial pressure determination. MAIN OUTCOME MEASURES: Arterial pressure was measured invasively and also oscillometrically by an upper arm cuff every 10 min. Simultaneously measured pairs of mean arterial pressures were analysed by the Bland-Altman method; the correlation coefficient, percentage error and concordance were calculated. RESULTS: Data from 21 children were analysed. Mean, (standard deviation) and [range] of invasive and noninvasive mean arterial pressures were 54 (8) [30 to 94] and 57 (8) [40 to 108] mmHg, respectively. The overall bias between invasive and noninvasive arterial pressure was -3 (7) mmHg, with 95% limits of agreement from -17 to +10 mmHg. The correlation coefficient, percentage error and concordance were 0.65, 25% and 0.77, respectively. For hypotensive invasive arterial pressure values below 45 mmHg, the mean bias (invasive arterial pressure - noninvasive arterial pressure) was -9 (5) mmHg. CONCLUSION: Arterial pressure derived by the oscillometric device showed acceptable levels of agreement. However, during hypotension, a clinically relevant overestimation of arterial pressure occurred when measured by an upper arm cuff.

Falsely low values of oxygen saturation measured by pulse oximetry in a boy treated with Chinese herb tea.

An 8-year-old boy suffering from progressive glioblastoma was scheduled for neurosurgery. Prior to induction of anaesthesia pulse oximetry measured 64 % saturation of oxygen (SpO2). Arterial blood gas analysis revealed normal oxygen saturation and normal oxygen partial pressure. After having ruled out technical problems of pulse oximetry the neurosurgical procedure was halted. Meticulous examination of the child's history and medication did not explain a possible interaction of drugs with pulse oximetry. A Chinese herb tea had been given to the child, but was then stopped on the day of admission. The surgical procedure took place the next day without any complications. During the subsequent inpatient stay, repeated blood gas analyses showed normal oxygenation, but pulse oximetry measured initially SpO2 values of 64 %, gradually increasing over 7 days up to 91 % by the time of discharge from hospital. Blood samples were taken and analysed. Absorption spectroscopy from the patient's blood showed an uncommon absorption maximum at 684 nm besides the normal maxima. The normalisation of SpO2 values after stopping Chinese herb tea administration leads to the conclusion that one of its ingredients caused the distorted pulse oximetry measurement.

Anomia produced by direct cortical stimulation of the pre-supplementary motor area in a patient undergoing preoperative language mapping.

There is sparse data on the analysis of supplementary motor area in language function using direct cortical stimulation of the supplementary motor area. Here, we report a patient who experienced isolated anomia during stimulation of the anterior supplementary motor area and discuss the role of the supplementary motor area in speech production. The role of the pre-supplementary motor· area in word selection, observed in fMRI studies, can be confirmed by direct cortical stimulation.

Use of intrathecal baclofen in children and adolescents: interdisciplinary consensus table 2013.

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.

Neurodevelopmental and esthetic results in children after surgical correction of metopic suture synostosis: a single institutional experience.

INTRODUCTION: Metopic suture synostosis leading to trigonocephaly is considered the second most frequent type of craniosynostosis. Besides esthetic results, we present 25 consecutive pediatric cases operated upon metopic suture synostosis with a focus on the child's motor, speech, and neurocognitive development. METHODS: Twenty-five children (aged 6 to 33 months; median 9.2 months) with trigonocephaly were operated upon between 2002 and 2012 with fronto-orbital advancement including frontal bone cranioplasty and fronto-orbital bandeau remodeling. Neurodevelopmental deficits were evaluated by a standardized questionnaire including gross motor function, manual coordination, speech, and cognitive function performed by independent pediatric/developmental neurologists before surgery and at 6 and 12 months of time interval postoperatively. RESULTS: Twenty-one (84 %) boys and four (16 %) girls were included in this study. Mean follow-up period was 33 ± 28 months. Outcome analysis for esthetic results showed a high degree of satisfaction by the parents and treating physicians in 23 cases (92 %). Preoperative evaluation revealed neurodevelopmental deficits in 10 children (40 %; six mild, four moderate degree). Twelve children (48 %) were proven to have a normal preoperative neuropediatric development. Mild or moderate developmental restraints were no longer apparent in 6/13, improved but still apparent in 3/13, and stable in 4/13, 6 months after cranial vault reconstruction. At 12 months of follow-up, deficits were no longer present in 9/13 and improved in 4/13. Apart from this cohort, two children were diagnosed with a syndromic form, and one child had a fetal valproate syndrome. In these three children, neurodevelopmental deficits were more pronounced. Neurocognitive progress was obvious, but was comparably slower, and major deficits were still apparent at last follow-up. All children with proven mild/moderate/severe deficits received intensive physiotherapy, logopedic, or neurobehavioral support. CONCLUSIONS: As shown in a single-center observation, surgical correction of metopic suture synostosis not only refines esthetic appearance but also might improve neurodevelopmental outcome if deficits are apparent, even in syndromic forms of the deformity under additional physiotherapy, logopedic, or neurobehavioral support.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. METHODS: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. RESULTS: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

The Potential Role of the Extracellular Matrix Glycoprotein Reelin in Glioblastoma Biology.

Glioblastoma, the most common and lethal primary adult brain tumor, cannot be successfully removed surgically due to its highly invasive nature. Therapeutically, approaches must be aimed at a systemic brain disease and not merely at a tumor located within the brain, unless a successful containment strategy can be found. Reelin, an extracellular matrix glycoprotein, plays an important role in neuronal migration and serves here as a natural stop signal. Interestingly, the expression of reelin is negatively associated with tumor grade and, within glioblastoma, correlates with increased overall survival. To further elucidate a potential biological reason for these findings, we looked at the cellular behavior of glioblastoma cell lines grown on a pure fibronectin matrix or a matrix with reelin inserts. While reelin had no significant effects on cellular metabolism, proliferation, or resistance to chemotherapeutic agents, it did significantly affect the cells' interaction with fibronectin. Both matrix attachment and detachment were modulated by reelin, and thus, the invasion and motility of cells interacting with a reelin-containing matrix were altered. The data presented in this work strongly suggest that reelin might be a potential modulator of underlying molecular mechanisms that contribute to glioblastoma invasion.

Dynamic regulation of P-glycoprotein in human brain capillaries.

Considering its role as a major blood-brain barrier gatekeeper, the dynamic regulation of the efflux transporter P-glycoprotein is of considerable functional relevance. In particular, disease-associated alterations in transport function might affect central nervous system drug efficacy. Thus, targeting regulatory signaling cascades might render a basis for novel therapeutic approaches. Using capillaries freshly prepared from patient tissue resected during epilepsy surgery, we demonstrate dynamic regulation of P-glycoprotein in human brain capillaries. Glutamate proved to up-regulate P-glycoprotein efflux transport in a significant manner via endothelial NMDA receptors. Both inhibition of cyclooxygenase-2 and antagonism at the glycine-binding site of the NMDA receptor prevented the glutamate-mediated induction of P-glycoprotein transport function in human capillaries. In conclusion, the data argue against species differences in the signaling factors increasing endothelial P-glycoprotein transport function in response to glutamate exposure. Targeting of cyclooxygenase-2 and of the NMDA receptor glycine-binding site was confirmed as an efficacious approach to control P-glycoprotein function. The findings might render a basis for translational development of add-on approaches to improve brain penetration and efficacy of drugs.

Proper cerebellar development requires expression of ß1-integrin in Bergmann glia, but not in granule neurons.

ß1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of ß1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of ß1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of ß1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of ß1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of ß1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a ß1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that ß1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of ß1-integrin in glia that is crucial for the proper development of the cerebellar cortex.

IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival.

BACKGROUND: The favorable prognostic impact of mutations in the IDH1 gene is well documented for malignant gliomas; its influence on World Health Organization (WHO) grade II astrocytomas, however, is still under debate. METHODS: A previously published database of 127 predominantly surgically treated patients harboring WHO grade II astrocytomas was revisited. Patients were screened for TP53 mutations (sequencing analysis), IDH1 mutations (pyrosequencing), and MGMT promoter methylation (methylation-specific polymerase chain reaction and bisulfite sequencing). Endpoints were overall survival, progression-free survival (PFS), time to malignant transformation, and postrecurrence survival. Radiotherapy was usually withheld until tumor progression/malignant transformation occurred. RESULTS: IDH1 mutations, TP53 mutations, and methylated MGMT promoters were seen in 78.1%, 51.2%, and 80.0% of the analyzed tumors, respectively. IDH1 mutations, which were significantly associated with TP53 mutations and/or MGMT promoter methylation (P < .001), resulted in shortened PFS (median, 47 vs 84 months; P = .004); postrecurrence survival, however, was significantly increased in those patients undergoing malignant transformation (median, 49 vs 13.5 months; P = .006). Overall survival was not affected by IDH1. A similar pattern of influence was seen for MGMT promoter methylation. Methylated tumors did significantly worse (better) in terms of PFS (postrecurrence survival); a low number of unmethylated tumors, however, limited the power of this analysis. Conversely, TP53 mutations were stringently associated with a worse prognosis throughout the course of the disease. CONCLUSIONS: IDH1 mutations are associated with a Janus headlike phenomenon; unfavorable prognostic influence on PFS turns into favorable impact on postrecurrence survival. A similar pattern of influence might exist for MGMT methylation.

Microsurgical outlet restoration in isolated fourth ventricular hydrocephalus: a single-institutional experience.

PURPOSE: Isolated fourth ventricles as a consequence of shunted posthemorrhagic hydrocephalus can cause significant brainstem compression and subsequent clinical deficits in children. Several treatment options have been described. We report the clinical and radiological outcome after microsurgical fenestration of fourth ventricular outlet foramen via a suboccipital approach. METHODS: In nine patients (age, 9 to 87 months; median age, 21 months), microsurgical reopening of formerly occluded outlet foramen of the fourth ventricle was performed under electrophysiological monitoring. Pre- and postoperative clinical outcome as well as radiological results are reported. RESULTS: Mean follow-up for all children was 25 months. Three children older than 3 years were less significantly involved, the remaining six showed tremendous long tract signs and lower cranial nerve deficits. All children exhibited a remarkable improvement of their preexisting neurological deficits post-surgery. Despite successful fenestration, one child required additional internal drainage of fourth ventricle to the lateral ventricles due to malabsorption. Median diameters of the fourth ventricle changed markedly after surgery with anterior-posterior (a.p.) extension from 3.8 to 2.9 cm, lateral extension from 4.2 to 2.8 cm (p = 0.018), and craniocaudal extension from 5.8 to 4.7 cm, respectively. Also, the pontine a.p. diameter increased significantly from 0.8 to 1.5 cm (p = 0.022). CONCLUSION: The clinical and radiological outcomes after microsurgical fenestration in children with an isolated fourth ventricle are very promising. This treatment modality is a safe and effective shunt-free option when electrophysiological monitoring and thorough preoperative neuroradiological work-up are applied.

Bcl-XL but Not Bcl-2 Is a Potential Target in Medulloblastoma Therapy.

Medulloblastoma (MB) is the most common solid tumour in children and, despite current treatment with a rather aggressive combination therapy, accounts for 10% of all deaths associated with paediatric cancer. Breaking the tumour cells' intrinsic resistance to therapy-induced cell death should lead to less aggressive and more effective treatment options. In other tumour entities, this has been achieved by modulating the balance between the various pro- and anti-apoptotic members of the Bcl-2 family with small molecule inhibitors. To evaluate the therapeutic benefits of ABT-199 (Venetoclax), a Bcl-2 inhibitor, and ABT-263 (Navitoclax), a dual Bcl-XL/Bcl-2 inhibitor, increasingly more relevant model systems were investigated. Starting from established MB cell lines, progressing to primary patient-derived material and finally an experimental tumour system imbedded in an organic environment were chosen. Assessment of the metabolic activity (a surrogate readout for population viability), the induction of DNA fragmentation (apoptosis) and changes in cell number (the combined effect of alterations in proliferation and cell death induction) revealed that ABT-263, but not ABT-199, is a promising candidate for combination therapy, synergizing with cell death-inducing stimuli. Interestingly, in the experimental tumour setting, the sensitizing effect of ABT-263 seems to be predominantly mediated via an anti-proliferative and not a pro-apoptotic effect, opening a future line of investigation. Our data show that modulation of specific members of the Bcl-2 family might be a promising therapeutic addition for the treatment of MB.

Children with tethered cord syndrome of different etiology benefit from microsurgery-a single institution experience.

PURPOSE: The term "tethered cord syndrome" (TCS) illustrates, according to the literature, both a separate diagnosis, as well as a combination of symptoms in the context of dysraphic conditions. The common denominator is the increased tension and abnormal stretching of the spinal cord, caused by tissue attachments that limit its movement in the spinal canal. In light of the fact that no real data exists regarding the management of these patients, the purpose of this single institutional study is to underscore management strategies and discuss the results, pitfalls, and the treatment of pediatric patients with tethered cord syndrome. METHODS AND RESULTS: The clinical outcome in 20 pediatric patients was studied retrospectively. Ten children with closed spinal dysraphism, nine with tethering after postpartum myelomeningocele repair, and one child with an infected open dermal sinus were included. A total of 22 detethering procedures were performed. The most common symptoms prior to surgery were muscle weakness and urinary dysfunction, followed by foot deformities and pain. Of all symptoms, pain responded most favorably to surgical treatment. There was improvement in 11 out of 15 patients with preoperative motor deficits, while that was the case in 11 out of 16 patients with urinary dysfunction. CONCLUSIONS: In view of the lack of evidence regarding the treatment of children with tethered cord syndrome, the best way to aim for a favorable outcome is correct indication for surgical intervention, combined with the implementation of technical advancements, such as intraoperative neurophysiological monitoring and ultrasound.

Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature.

Intracranial penetration during attempted nasotracheal intubation is a potentially devastating complication, which should be carefully evaluated and the risk should be addressed in neonatal resuscitation trainings.

ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression.

The purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in high and low c-myc-expressing medulloblastoma cells. Our data show that treatment with the imipridone ONC201/TIC10 leads to a significant inihibitory effect on the cellular viability of different medulloblastoma cells independent of c-myc expression. This effect is enhanced by glucose starvation. While ONC201/TIC10 decreases the oxidative consumption rates in D458 (c-myc high) and DAOY (c-myc low) cells extracellular acidification rates experienced an increase in D458 and a decrease in DAOY cells. Combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose led to a synergistic inhibitory effect on the cellular viability of medulloblastoma cells including spheroid models. In conclusion, our data suggest that ONC201/TIC10 has a profound anti-proliferative activity against medulloblastoma cells independent of c-myc expression. Metabolic targeting of medulloblastoma cells by ONC201/TIC10 can be significantly enhanced by an additional treatment with the glycolysis inhibitor 2-Deoxyglucose. Further investigations are warranted.