Background: Low Grade Gliomas(LGG) account for about 50% of childhood brain tumors. Elevated citrate levels have previously been shown to be markers for aggressive behavior in LGGs and the H3K27M and G34R/V mutations have emerged as molecular drivers for pediatric high-grade gliomas(HGG). Procedure: We retrospectively analyzed data from 25 patients with midline gliomas to determine whether citrate levels measured through magnetic resonance spectroscopy(MRS) were associated with histone mutations identified by immunohistochemistry. Results: Median age was 6 years (range:0-16 years) with 13 males and 12 females. Most of the patients 14(56%) had a LGG with the most common locations being the thalamus 13(52%) and brainstem 7(28%). The majority had undergone a biopsy 16(65%) or a partial resection 8(32%). Gross total resection was achieved in only one patient(4%). The majority of the patients received adjuvant chemotherapy and/or radiotherapy. Median citrate levels trended higher in patients with HGG compared to those with LGG (1.49vs0.93mmol/kg, p-value=0.16) and in patients with the H3K27M mutation compared to those without (2.30vs0.80mmol/kg, p-value 0.26). Histological grading (LGGvsHGG) (OR: 3.96, 95% confidence interval (CI):1.32-11.94), H3K27M mutation (OR:3.77, 95% CI:1.05-13.61), and age (OR:1.12, 95%CI:1.00-1.25) were significant adverse prognostic factors in univariate analysis but only the histological grading remained significant in multivariate analysis. Conclusion: We determined that H3K27M mutations and elevated citrate levels were adverse prognostic factors in both patients with LGG and HGG. Exploring the relation between these two markers in larger studies could lead to a noninvasive way of predicting high risk behavior prior to biopsy.

Data for visual acuity (VA) after treatment of neurofibromatosis type 1-associated optic pathway gliomas (NF1-OPGs) is limited. We retrospectively collected VA, converted to logMAR, before and after targeted therapy with everolimus for NF1-OPG, and compared to radiologic outcomes (14/18 with NF1-OPG, 25 eyes [3 without quantifiable vision]). Upon completion of treatment, VA was stable in 19 eyes, improved in 4 eyes, and worse in 2 eyes; visual and radiologic outcome were discordant. In summary, the majority of children with NF1-OPG exhibited stabilization of their VA after everolimus treatment. A larger, prospective study will help delineate visual outcomes after targeted therapy.