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.

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.

Management of moderate/severe paediatric traumatic brain injury (mspTBI) varies across Europe. The decline in case numbers perceived in many regions raises concerns about maintaining high-quality, sustainable care. This study aimed to examine the organization of mspTBI management in Europe, focusing on expertise availability, guideline adherence, neuromonitoring use, and clinician's confidence in care delivery through a survey. A 34-question survey was distributed to European neurosurgical and intensive care communities. Only hospitals treating children with mspTBI were included. Centres were stratified by their catchment population size and their access to dedicated expertise. Seventy-six institutions from 23 countries responded. Most centres reported a mspTBI case load of less than 20 children per year. Access to paediatric anesthesiology was significantly associated with centre size (p = 0.001), while access to paediatric neurosurgery, intensive or neurointensive care was not. Most centres (96 %) reported adherence to (inter)national guidelines. Intracranial pressure (78.7 %) and transcranial Doppler (70.7 %) were the most frequently available/used neuromonitoring modalities. Confidence in managing mspTBI was significantly higher in centres with paediatric neurosurgeons and, for older children, paediatric neuro-intensivists. This first European survey examining organizational management of mspTBI reveals a low overall caseload and uneven access to paediatric expertise. Confidence in managing mspTBI correlates with availability of paediatric subspecialists. Guidelines are widely applied, independent of expert availability, but are alone insufficient to ensure treatment confidence. This finding underscores the need for improved guidelines and better access to paediatric neurotrauma expertise.