A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas

SIMPLE SUMMARY: Serious, poorly understood health issues affect young children with optic pathway tumours. We studied the risk of developing life-limiting hormonal, metabolic, and neurobehavioural disorders by tumour position, recurrence, and treatment, in those diagnosed under 3 years. We found the highest risk for future complex health issues in those presenting with failure to thrive, under one year of age, and/or a tumour involving a deep midbrain area called the hypothalamus. Time, repeated tumour growth, and salvage therapies (radiotherapy, surgery) contributed. We highlight the need for a better understanding of tumour-induced midbrain injury and for neurobehavioural and hormonal support to inform rehabilitation in the growing years, during and beyond cure, to optimise quality of life for these survivors and their families. This might inform oncology treatment strategies and determine new areas for support and collaborative neuroscience research in this high survival group. ABSTRACT: Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies.