Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome

Abstract

Aims Cerebellar mutism syndrome occurs in 25% of children following resection of posterior fossa tumours. Characterised by mutism, emotional lability and cerebellar motor signs, the syndrome is usually reversible over weeks to months. Its pathophysiology remains unclear, but evidence from diffusion MRI studies has implicated damage to the superior cerebellar peduncles in the development of this condition. The objective of this study was to describe the application of automated tractography of the cerebellar peduncles to provide a high-resolution spatiotemporal profile of diffusion MRI changes in cerebellar mutism syndrome. Method A retrospective case-control study was performed at Lucille Packard Children’s Hospital, Stanford University. Thirty children with midline medulloblastoma (mean age ± standard deviation 8.8 ± 3.8 years) underwent volumetric T1-weighted and diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, were included as age- and sex-matched controls. Cerebellar mutism syndrome status was determined by contemporaneous casenote review. Automated Fibre Quantification was used to segment each subject’s cerebellar peduncles (Figure 1), and fractional anisotropy was computed at 30 nodes along each tract. A non-parametric permutation-based method was used to generate a critical cluster size and p-value for by-node ANOVA group comparisons. Z-scores for patients’ fractional anisotropy at each node were calculated based on values from controls’ corresponding nodes; these were analysed using mixed ANOVA with post-hoc false discovery rate-corrected pairwise t-tests. Results 13 patients developed cerebellar mutism syndrome. Automated fibre segmentation successfully identified the cerebellar peduncles in the majority of participants, but was more robust at follow-up timepoints (78.7% vs. 44.7% pre-operatively). Fractional anisotropy was significantly lower in the distal regions of the left superior cerebellar peduncle pre-operatively (p=0.0137) in patients compared to controls, although patients could not be distinguished pre-operatively with respect to cerebellar mutism syndrome status (Figure 2). Post-operative reductions in fractional anisotropy in children with cerebellar mutism syndrome were highly specific to the distal left superior cerebellar peduncle, and were most pronounced at follow-up timepoints (p=0.006; Figure 3). There were no significant differences in other cerebellar peduncles, either in along-tract fractional anisotropy or Z-scores, with respect to cerebellar mutism syndrome status. Conclusion A novel application of an automated tool to extract diffusion MRI data along the length of the cerebellar peduncles is described in a longitudinal retrospective cohort of paediatric medulloblastoma. Changes in fractional anisotropy in the cerebellar peduncles following tumour resection are described in a heretofore unprecedented level of spatiotemporal detail. In particular, children with post-operative cerebellar mutism syndrome show changes in the distal regions of the left superior cerebellar peduncle, and these changes persist up to a year post-operatively. These findings will have direct clinical implications for neurosurgeons performing resection of midline paediatric posterior fossa tumours.

A presurgical voxel-wise predictive model for cerebellar mutism syndrome in children with posterior fossa tumors

“…Here we further found that the right superior cerebellar peduncle was especially involved in CMS as more massive voxels localized in the right side. However, this is inconsistent with another study, which indicated that the left superior cerebellar peduncle was associated with CMS ( Toescu et al, 2022 ). The laterality of superior cerebellar peduncles associated with CMS still needs to be studied further.…”

“…Controversy remains regarding the laterality of superior cerebellar peduncle (SCP) damage in CMS occurrence. Previous diffusion-weighted studies have detected significant fractional anisotropy (FA) reduction in bilateral superior peduncles in CMS cases compared with non-CMS cases ( Albazron et al, 2019 , Avula et al, 2015 , McEvoy et al, 2016 , Morris et al, 2009 ), while others found only unilateral (right or left) impairment in SCP is associated with CMS ( Law et al, 2012 , Toescu et al, 2022 , Vedantam et al, 2019 ), with fiber pathway damage lasting for a long time ( McEvoy et al, 2016 ). Besides, no difference was detected in MCP bilaterally or unilaterally ( Vedantam et al, 2019 ).…”

Investigating lesion location in relation to cerebellar mutism following pediatric tumor resection

“…[2][3][4][5][6][7][8] This constellation of symptoms is commonly referred to as cerebellar mutism syndrome (CMS), 9 posterior fossa syndrome, or cerebellar cognitive affective syndrome +/-cerebellar mutism; we will use the term CMS for this paper. The duration and severity of this syndrome is variable, but importantly, patients who develop CMS typically have worse long-term cognitive outcomes, 5,[10][11][12][13] highlighting the importance of this syndrome as a potential harbinger of long-term impairment.…”