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Disrupted development and integrity of frontal white matter in patients treated for pediatric medulloblastoma
John O Glass1, Robert J Ogg1, Jung W Hyun1
1Departments of Diagnostic Imaging, Biostatistics, Psychology, and Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.
Background:
Treatment of pediatric medulloblastoma is associated with known neurocognitive deficits that we hypothesize are caused by microstructural damage to frontal white matter (WM).
Methods:
Longitudinal MRI examinations were collected from baseline (after surgery but before therapy) to 36 months in 146 patients and at 3 time points in 72 controls. Regional analyses of frontal WM volume and diffusion tensor imaging metrics were performed and verified with tract-based spatial statistics. Age-adjusted, linear mixed-effects models were used to compare patient and control images and to associate imaging changes with Woodcock-Johnson Tests of Cognitive Abilities.
Results:
At baseline, WM volumes in patients were similar to those in controls; fractional anisotropy (FA) was lower bilaterally (P < 0.001) and was associated with decreased Processing Speed (P = 0.014) and Broad Attention (P = 0.025) performance at 36 months. During follow-up, WM volumes increased in controls but decreased in patients (P < 0.001) bilaterally. Smaller WM volumes in patients at 36 months were associated with concurrent decreased Working Memory (P = 0.026) performance.
Conclusions:
Lower FA in patients with pediatric medulloblastoma compared with age-similar controls indicated that patients suffer substantial acute microstructural damage to supratentorial frontal WM following surgery but before radiation therapy or chemotherapy. Additionally, this damage to the frontal WM was associated with decreased cognitive performance in executive function 36 months later. This early damage also likely contributed to posttherapeutic failure of age-appropriate WM development and to the known association between decreased WM volumes and decreased cognitive performance.
Insights
Pediatric medulloblastoma patients show early frontal white matter (WM) damage after surgery, impacting cognitive functions like processing speed and attention long-term. This damage also hinders normal WM development.
Area of Science:
- Neuroscience
- Radiology
- Pediatric Oncology
Background:
- Pediatric medulloblastoma treatment can lead to neurocognitive deficits.
- These deficits are hypothesized to stem from microstructural damage to frontal white matter (WM).
Purpose of the Study:
- To investigate microstructural changes in frontal white matter (WM) in pediatric medulloblastoma patients.
- To correlate these WM changes with cognitive performance over 36 months.
Main Methods:
- Longitudinal MRI scans were collected from 146 patients and 72 controls.
- Regional analyses of WM volume and diffusion tensor imaging (DTI) metrics were performed.
- Linear mixed-effects models assessed imaging changes and cognitive performance (Woodcock-Johnson Tests).
Main Results:
- Patients had lower fractional anisotropy (FA) in frontal WM at baseline, linked to later deficits in Processing Speed and Broad Attention.
- WM volumes decreased in patients but increased in controls during follow-up.
- Reduced WM volumes at 36 months correlated with impaired Working Memory.
Conclusions:
- Pediatric medulloblastoma patients experience acute frontal WM microstructural damage post-surgery, before adjuvant therapy.
- This early damage is associated with long-term executive function deficits.
- Early WM damage likely impairs post-therapeutic WM development and contributes to cognitive decline.
