Infant high grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histological review, methylation profiling, custom panel and genome/exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an 'intrinsic' spectrum of disease specific to the infant population. These included those with targetable MAP-kinase alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n=31), NTRK1/2/3 (n=21), ROS1 (n=9) and MET (n=4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly supports the concept that infant gliomas require a change in diagnostic practice and management.

OBJECTIVEDuring the last 3 decades, robotic technology has rapidly spread across several surgical fields due to the continuous evolution of its versatility, stability, dexterity, and haptic properties. Neurosurgery pioneered the development of robotics, with the aim of improving the quality of several procedures requiring a high degree of accuracy and safety. Moreover, robot-guided approaches are of special interest in pediatric patients, who often have altered anatomy and challenging relationships between the diseased and eloquent structures. Nevertheless, the use of robots has been rarely reported in children. In this work, the authors describe their experience using the ROSA device (Robotized Stereotactic Assistant) in the neurosurgical management of a pediatric population.METHODSBetween 2011 and 2016, 116 children underwent ROSA-assisted procedures for a variety of diseases (epilepsy, brain tumors, intra- or extraventricular and tumor cysts, obstructive hydrocephalus, and movement and behavioral disorders). Each patient received accurate preoperative planning of optimal trajectories, intraoperative frameless registration, surgical treatment using specific instruments held by the robotic arm, and postoperative CT or MR imaging.RESULTSThe authors performed 128 consecutive surgeries, including implantation of 386 electrodes for stereo-electroencephalography (36 procedures), neuroendoscopy (42 procedures), stereotactic biopsy (26 procedures), pallidotomy (12 procedures), shunt placement (6 procedures), deep brain stimulation procedures (3 procedures), and stereotactic cyst aspiration (3 procedures). For each procedure, the authors analyzed and discussed accuracy, timing, and complications.CONCLUSIONSTo the best their knowledge, the authors present the largest reported series of pediatric neurosurgical cases assisted by robotic support. The ROSA system provided improved safety and feasibility of minimally invasive approaches, thus optimizing the surgical result, while minimizing postoperative morbidity.

BackgroundGanglioglioma (GG) and pilocytic astrocytoma (PA) represent the most frequent low-grade gliomas (LGG) occurring in paediatric age. LGGs not amenable of complete resection (CR) represent a challenging subgroup where traditional treatments often fail. Activation of the MAP Kinase (MAPK) pathway caused by the BRAFV600E mutation or the KIAA1549-BRAF fusion has been reported in pediatric GG and PA, respectively.Case presentationWe report on a case of BRAFV600E mutated cervicomedullary GG treated with standard chemotherapy and surgery. After multiple relapse, BRAF status was analyzed by immunohistochemistry and sequencing showing a BRAFV600E mutation. Treatment with Vemurafenib as single agent was started. For the first time, a radiological and clinical response was obtained after 3 months of treatment and sustained after 6 months.ConclusionOur experience underline the importance of understanding the driver molecular alterations of LGG and suggests a role for Vemurafenib in the treatment of pediatric GG not amenable of complete surgical resection.