Purpose: Because of its super cial location in the dorsal regions of the scalp, the greater occipital nerve (GON) can be injured during neurosurgical procedures, resulting in post-operative pain and postural disturbances. The aim of this work is to specify the course of the GON and how its injuries can be avoided while performing posterior fossa approaches.Methods: This study was carried out at the department of anatomy in Bordeaux University. 4 specimens were dissected to study the GON course. Posterior fossa approaches (midline suboccipital, paramedian suboccipital, retrosigmoid and petrosal) were performed on 4 other specimens in order to assess potential risks of GON injuries.Results: The GON runs around the obliquus capitis inferior (100%), crosses the semispinalis capitis (100%) and the trapezius (75%) or its aponeurosis (25%). Direct GON injuries can be seen in paramedian suboccipital approaches. Stretching of the GON can occur in midline suboccipital and paramedian suboccipital approaches. We found no evidence of direct or indirect GON injury in retrosigmoid or petrosal approaches. Conclusion:Our study provides interesting data regarding the risk GON injury in posterior fossa approaches. Direct GON injuries in paramedian suboccipital approaches can be avoided with careful dissection. Placing retractors in contact with the periosteum and performing a minimal retraction may help to avoid excessive GON stretching in midline suboccipital and paramedian suboccipital approaches. Furthermore, incision for retrosigmoid approaches should be as lateral as possible and not too caudal. Finally, avoiding extreme patient positioning reduces the risk of GON stretching in all approaches.

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Background Diffuse Midline Glioma, H3K27M-mutant (DMG) is a rare, highly aggressive pediatric tumor affecting the brainstem, and is one of the deadliest cancers. Currently available treatment options such as chemotherapy and radiotherapy do only modestly prolong survival. In this pathology, H3K27 mutations deregulate Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2, which is therefore under investigation as a therapeutic target. Methods We used a chemical EZH2 inhibitor, GSK126, small interfering RNAs and a CRISPR/Cas9 knockout approaches in a series of DMG tumor cell lines to investigate metabolic treatment responses by proteomic analysis. A combination strategy was elaborated and studied in primary and established DMG cells, spheroid 3D cultures and in vivo in a chick chorio-allantoic membrane DMG assay and an orthotopic intracranial DMG mouse model. Results GSK126 shows significant (p<0.05-0.001) inhibitory effects in in vitro cell proliferation assays and induces apoptosis. Chemical targeting of EZH2 induced expression of proteins implicated in cholesterol metabolism. Low-dose GSK126 treatment together with statins revealed strong growth inhibition in combinatorial treatments, but not in single treatments, both in DMG cells in vitro, in DMG spheroid cultures and in chick and mouse in vivo models (p<0.05). All statistical tests were two-sided. Conclusions Our results reveal an unexpected GSK126-inducible sensitivity to cholesterol biosynthesis inhibitors in highly aggressive pediatric glioma that warrants further evaluation as treatment strategy. This combinatorial therapy should have few side effects because of the low doses used to achieve significant anti-tumor activity.

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