Abstract
BackgroundChildhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors.MethodsDKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof.ResultsThe mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 – 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P < 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions.ConclusionOur study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.
Highlights
Intracranial germ cell tumors (GCT), while rare in the West, are more common in Asia accounting for up to 15% of primary intracranial tumors in Asian children
We have previously demonstrated that fractional anisotropy (FA), a diffusion metric commonly obtained from diffusion tensor imaging (DTI), correlated with the cognitive outcomes of medulloblastoma survivors [12, 13]
We have successfully demonstrated using diffusional kurtosis imaging that there were extensive microstructural changes in the grey and white matter of intracranial GCT survivors with a history of cranial irradiation when compared to healthy controls
Summary
Intracranial germ cell tumors (GCT), while rare in the West, are more common in Asia accounting for up to 15% of primary intracranial tumors in Asian children. Because of the high survival rates of childhood intracranial GCT, there is growing concern over the long-term neurocognitive outcomes. Damage to the basal ganglia and deep brain nuclei can lead to cognitive impairment as well as loss of motor control [5]. Majority of basal ganglia germinomas with poor neurocognitive outcomes were associated with early cerebral atrophy [6]. It is conceivable that the cognitive and functional impairments in intracranial GCT survivors are likely due to both grey and white matter damage. Childhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors
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