Clinical and neuroanatomical predictors of cerebellar mutism syndrome

Abstract

Cerebellar mutism syndrome (CMS) is an important medical challenge in the management of pediatric posterior fossa brain tumors, because it occurs in a subset of children following tumor resection. A definitive clinical profile and neuroanatomical substrate associated with CMS remains unclear. We investigated the relationship between presurgical and clinical variables and the incidence of CMS, along with diffusion tensor imaging, to characterize the integrity of cerebello-thalamo-cerebral white matter pathways. Seventeen children with posterior fossa tumors and CMS, 34 children with posterior fossa tumors without CMS, and 28 healthy children were enrolled in this study. Bilateral cerebello-thalamo-cerebral pathways were delineated and segmented into anatomical regions. Mean integrity measures for each region were compared among children with CMS, children without CMS, and healthy children. Left-handedness, medulloblastoma histology, and larger tumor size distinguished between patients with CMS and patients without CMS (P < .04). Right cerebellar white matter within the cerebello-thalamo-cerebral pathway was compromised in children with CMS relative to children without CMS and healthy children (P < .02). We provide a potential schema for CMS risk among children treated for posterior fossa tumors. Left-handed children treated for medulloblastoma may be the most at risk for CMS, and unilateral, localized damage within the cerebello-thalamo-cerebral pathway at the level of the right cerebellum is implicated in the presentation of CMS. This disruption in communication between the right cerebellum and left frontal cortex may contribute to speech-language problems observed in children with CMS. Our findings may be relevant for surgical planning and speech-language therapy to mitigate symptoms of CMS.

Fig. 1.

A schematic of the C-T-C pathway. This bilateral C-T-C pathway originates in deep cerebellar nuclei, ascending through superior cerebellar peduncles, decussating in the rostral midbrain, and routing through ventrolateral thalamic nuclei into frontal cortex.

Fig. 2.

Presurgical and clinical predictors of CMS: the distribution of handedness and tumor pathology across patients with CMS and without CMS. Bars reflect within-group percentages. In terms of tumor pathology, “Other” signifies any other tumor type in our sample excluding medulloblastoma (eg, astrocytoma and ependymoma).

Fig. 3.

A sagittal view of the C-T-C pathway connecting right cerebellar hemispheric white matter with left frontal cortex via thalamus (in multicolor). The left frontal anatomical region of the C-T-C pathway falls within the red segmentation, the internal capsule/thalamus region of the pathway in the green segmentation, the midbrain/pons region of the pathway in the blue segmentation, and the cerebellar hemispheric white matter region of the pathway in yellow segmentation. Generated with MedINRIA.

Fig. 4.

A potential schema for CMS risk, based on our quantitative and qualitative observations of presurgical and clinical variables. According to this schema left-handed patients are highly likely to present with CMS (85%); this chance rises to 100% if the left-handed patient is treated for medulloblastoma. Based on our sample, right-handed patients have a 25% chance of presenting with CMS in general; this chance becomes 41% if the right-handed patient is diagnosed with medulloblastoma. Further, larger tumor size is associated with greater risk for CMS in right-handed patients. Tumor size was not found to be a factor for CMS risk in our sample of left-handed patients. Under the determination of pathology section, “Other Tumor Type” includes ependymoma and low-grade glioma/astrocytoma, among others.