ESPE Abstracts

Background: Craniopharyngioma is a non-malignant, embryological brain tumour in the sellar and parasellar region. Hypothalamic damage is common and accompanied by development of obesity in at least 50% of cases. Mechanisms underlying hypothalamic obesity in craniopharyngioma patients however remain unclear and treatment options are invasive and limited. This feasibility study included a novel application of functional neuroimaging, an established method in obesity research, to childhood-onset craniopharyngioma.

Method: Young people with craniopharyngioma were recruited to the feasibility study. Full clinical characterisation was conducted using medical notes. Historical control participants were matched on sex and the closest BMI-SDS match to each patient with craniopharyngioma from a previous study with identical fMRI acquisition. Resting state functional magnetic resonance imaging (rs-fMRI) data (5 minutes) and a T1-weighted structural MPRAGE scan was acquired. Seed-based rs-fMRI analysis was conducted with hypothalamus as the seed region using FSL analysis software.

Results: Two of the eleven patients were unable to undergo MRI at 3T due to a ‘bioplate’ and suspected surgical clips. Neuroimaging data were acquired from nine patients (mean[s.d.] age=14.6[3.8]y; BMI-SDS=1.0[1.9]; 3F/6M) and nine controls (mean[s.d.] age=22.39[2.7]y; BMISDS=-0.6[0.9]; 3F/6M). In terms of surgery, three patients had debulking surgery, four had cyst aspiration and a ventricular access device inserted and three underwent transphenoidal resection. Paris grading of the tumours based on hypothalamic involvement post-surgery revealed six patients were grade 2, one patient was grade 1, and two were grade 0. In patients compared to controls, hypothalamic activity showed a stronger association with activity in occipital, parietal, cingulate cortices, and most notably, the insula which is a key region in the appetitive brain network. By contrast in controls, activity in the hypothalamus showed a stronger association with activity in the right cerebellum, bilateral brain stem, frontal and occipital cortices, and left thalamus.

Conclusion: These preliminary results suggest that craniopharyngioma or its treatment has widespread effects beyond the hypothalamus. Connectivity of the hypothalamus to other brain regions may be disrupted, including visual and appetitive areas. Disruptions within the appetitive brain network to regions such as the insula, frontal cortex, and cerebellum may contribute to the development of obesity in patients with craniopharyngioma. These findings demonstrate the utility of these measures in understanding hypothalamic obesity in craniopharyngioma. Further research in larger samples is warranted to understand the relationship between these functional brain changes with the extent of hypothalamic damage and development of obesity.