Cerebellar Mutism Syndrome Research Articles

Predicting cerebellar mutism syndrome in children using lesion map combined with clinical features.

This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

Catatonia associated with pediatric postoperative cerebellar mutism syndrome.

To ascertain the presence of catatonia in cases of pediatric postoperative cerebellar mutism syndrome (PPCMS). A systematic review of PPCMS case reports of patients aged 0-17 years with sufficient clinical information to extract catatonic phenomena was undertaken following PRISMA guidelines. Standardized catatonia rating scales were applied to selected cases retrospectively to ascertain whether diagnostic criteria for catatonia were met. A case known to the authors is also presented. Two hundred twenty-one suitable full-text articles were identified. Following screening and application of inclusion criteria, 51 articles were selected plus seven more from their references, reporting on 119 subjects. All cases met Bush and Francis (BF) diagnostic criteria for catatonia, 92.5% Pediatric Catatonia Rating Scale (PCRS), 52.9% ICD-11, and 44.5% DSM-5. All patients presented with mutism. The next most frequent signs were immobility/stupor (77.3%), withdrawal (35.3%), mannerisms (23.5%), and excitement/agitation (18.5%). Most cases presented with stuporous catatonia (75.6%). Catatonia most frequently occurred following resection of medulloblastoma (64.7%). Preoperative hydrocephalus occurred in 89 patients (74.8%). Catatonia was frequent in this PPCMS sample, with a predominant stuporous variant; it should be considered in patients with PPCMS and assessed with reliable and validated instruments for prompt diagnosis and management.

MDB-30. ZOLPIDEM, A PROMISING DRUG TO IMPROVE POSTOPERATIVE CEREBELLAR MUTISM SYNDROME (CMS): RETROSPECTIVE STUDY OF 19 PEDIATRIC PATIENTS WITH POSTERIOR FOSSA TUMORS

Abstract INTRODUCTION Postoperative Cerebellar Mutism Syndrome (CMS) affects up to 25% of patients undergoing surgeries for posterior fossa (PF) tumors. There is no established treatment for CMS, although zolpidem has become widespread after reporting remarkable responses in some cases. However, there is very limited scientific evidence, prompting us to document our experience with zolpidem. OBJECTIVES To evaluate the efficacy and safety of zolpidem in patients with postoperative CMS in PF tumors. METHODS Observational, descriptive, retrospective study conducted at our institution. Patients <21 years diagnosed with CMS following PF tumor surgery between 2011-2023 and treated with zolpidem were included. Demographic and clinical data, therapies, CMS scales, and outcomes were collected. RESULTS Nineteen patients met the criteria, 84% males, median age 8 years (range, 9 months-19 years), and median follow-up time 30 months (range, 2-126). Diagnoses included 58% medulloblastoma, 21% pilocytic astrocytoma, 10.5% ependymoma, 10.5% others. CMS mutism scale was rated mild, moderate and severe in 5%, 21% and 74%, respectively. Median zolpidem administration was 31 days (range, 2-241) and median maximum dose was 0.25 mg/kg/day (range, 0.10-0.90). Mutism scores improved in 37% (7/19), 53% (8/15) and 64% (9/14) of patients that received zolpidem for at least 48h, 7 and 14 days, respectively. Subjective improvement in communication and interaction was observed in 74% (14/19). Only three patients with mild somnolence and one with initial irritability and insomnia were reported. CONCLUSIONS To our knowledge, this is the largest study of patients treated with zolpidem for CMS. A considerable proportion of children improved their language abilities within the first 24-48h, but some patients may even benefit from more prolonged treatment. Most children showed an adequate tolerance with very few side effects. Further studies are urgently needed, preferably within a randomized clinical trial, to find the real efficacy, appropriate dosage, and duration of zolpidem.

NURS-06. MUSIC THERAPY: AN INTEGRAL PART OF REHABILITATION FOR CEREBELLAR MUTISM SYNDROME

Abstract BACKGROUND Cerebellar mutism syndrome (CMS) also known as posterior fossa syndrome (PFS), can occur in up to 25% of pediatric patients following surgical resection of posterior fossa brain tumors, particularly medulloblastoma. It is well recognized that intensive rehabilitation with physical therapy, occupational therapy and speech therapy are essential to recovery. Music therapy can be immensely helpful during rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. This case-based review aims at analyzing the available evidence to support our recommendation to include music therapy in the rehabilitation plan for all patients. METHODS We report on the case of a 4-year-old male with medulloblastoma and cerebellar mutism syndrome who began talking after just a few sessions with music therapy. We include an extensive review of the literature where multiple papers were found describing the positive effects of music therapy for management of neurologic diseases. RESULTS The pathophysiology of CMS is still poorly understood however, the most likely mechanism is injury along proximal components of the efferent cerebellar pathway. Intensive inpatient rehabilitation remains the standard of care. Music therapy uses and activates many different parts of the brain at the same time, promoting neuron repair and regeneration. Some of the advantages of music therapy are: it promotes plasticity in the brain and facilitates processing of sensory information and motor function; improves stress and helps patients adapt to stressful environments; facilitates more normative speech production for patients with dysarthria. CONCLUSIONS Despite efforts to identify preventative measures for CMS, it still occurs. Intensive rehabilitation remains the cornerstone of treatment. The case study as well as the review of the literature support our recommendation to include music therapy in the rehabilitation plan for patients with CMS. More studies are necessary to explore the therapeutic efficacy of music on patients with CMS.

QOL-50. THE ROLE OF TUMOR SIZE IN COGNITIVE FUNCTIONING AMONG SURVIVORS TREATED FOR MEDULLOBLASTOMA

Abstract BACKGROUND Medical and treatment variables, including presence of post-operative cerebellar mutism syndrome (CMS), shunt placement, craniospinal radiation, and total radiotherapy (RT) dose, have been evaluated as potential risk factors for adverse cognitive effects among pediatric patients diagnosed and treated for medulloblastoma. Larger brain tumor size is associated with increased risk of medical complications, but cognitive risk of larger tumor size remains unknown. METHODS Cognitive scores were examined for 40 participants diagnosed and treated for medulloblastoma. The age-appropriate Wechsler Intelligence Scale was administered at the start of RT and up to 10 years post-RT (M=4.96, SD=3.78). A total of 162 evaluations were examined across participants. Linear mixed models examined change in Wechsler Index scores over time since RT based on tumor size, which was dichotomized at the median diameter (small ≤4.6cm versus large >4.6cm), covarying for maternal education, total RT dose, and presence of CMS. RESULTS Patients (72.5% male) were diagnosed with medulloblastoma and began RT at a mean age of 8.89 years. Groups did not differ on demographic or medical variables with the exception of presence/absence of CMS, with a higher proportion of patients diagnosed with CMS having large-size tumors (40%) versus small-size tumors (5%). Tumor size did not predict change in IQ, working memory, or processing speed performance over time since RT after accounting for covariates. CMS was associated with significant decline in processing speed (p<.001) and IQ over time (p<.05); RT dose was associated with significant working memory and IQ decline (both p<.05); and maternal education was associated with decline in processing speed, working memory, and IQ (all p<.05). CONCLUSIONS While tumor size may be associated with treatment intensity and other medical risk factors, CMS and RT dose significantly increase cognitive risk, independent of tumor size. Lower socioeconomic status also increases cognitive risk post-RT, which may illuminate pathways for prevention and intervention efforts.

IMG-01. LONGITUDINAL SIGNAL CHANGES IN THE DENTATE AND INFERIOR OLIVARY NUCLEI IN PATIENTS WITH CEREBELLAR MUTISM SYNDROME

Abstract BACKGROUND Cerebellar mutism syndrome (CMS) is a complication of posterior fossa surgery with an acute impairment in speech, and long-term neurocognitive deficits. Lesion mapping studies suggest the cognitive symptoms are associated with dentatorubrolivary damage1. We hypothesize that CMS patients will demonstrate more longitudinal MRI signal abnormalities in the dentate and inferior olivary nuclei as compared to non-CMS patients. METHODS MRI brains on 40 pediatric medulloblastoma patients between 2013-2015 were retrospectively reviewed by a neuroradiologist blinded to the diagnosis at pre-operative and immediate, 6-month, 12 month and most recent post-operative time points. The dentate and inferior olivary nuclei were scored for restricted diffusion, T1 and T2 hypo-and hyperintensity. A linear regression with different scores on CMS status (YES vs NO) was applied, after adjusting for age. RESULTS In the dentate nuclei, there was significantly higher T2 hypointensity in the CMS group on immediate (difference is 0.4084, p=0.0467) and most recent (difference is 0.7190, p=0.0386) post-operative MRIs. The CMS group had significantly higher T1 hyperintensity on the 1-year (difference is 0.9254, p=0.0108) and most recent (difference is 1.3291, p<0.001) post-operative MRIs. In the inferior olivary nuclei, there was significantly higher T2 hyperintensity on the 6-month (difference is 0.71, p=0.0045) and 1-year (difference is 0.6356, p=0.0162) post-operative MRIs. CONCLUSION The immediate post-operative findings are suggestive of a hemorrhagic, rather than an ischemic process in the dentate nuclei. On long-term follow up, the signal changes in the dentate and the inferior olivary nuclei represent dystrophic mineralization and hypertrophic degeneration, due to inflammation and axonal degeneration within the dentatorubroolivary tract2

QOL-20. A REVIEW OF THE LITERATURE ON THE REHABILITATION OF PATIENTS WITH POSTERIOR FOSSA SYNDROME

Abstract BACKGROUND Posterior fossa syndrome (also recently described as pediatric postoperative cerebellar mutism syndrome) is a well described phenomenon, in which a patient develops a spectrum of speech and motor/coordination deficits generally in the acute stage after posterior fossa tumor resection. While most patients recover well, some patients evidence significant deficits years after diagnosis, and there is some evidence that minor long-term deficits may remain. While its frequency of occurrence is relatively low, and efforts have been made to identify strategies to decrease the rate of Posterior Fossa Syndrome, the fundamental interventions for functional optimization and rehabilitation of patients are still being discussed and researched. METHODS Along with reviewing the most up-to-date literature on the rehabilitation management of patients with posterior fossa syndrome, we will discuss current a survey based study designed by a group of representatives from the American Academy of Physical Medicine and Rehabilitation (AAPM&R) Pediatric Cancer Rehabilitation subcommittee, to better understand the standards of how the syndrome is managed by physiatrists in the US. This survey distributed via email, posting on an AAPM&R online community, as well as social media sites. RESULTS While literature is limited, there is evidence for the practice of therapy services, bracing, and in admission for acute inpatient rehabilitation to guide treatment for patients with posterior fossa syndrome. Results from the above survey study will be discussed, which preliminarily shows a consistent reliance on therapy services and a broader heterogeneity to frequency and treatment preferences among physicians in the US. CONCLUSION Posterior Fossa Syndrome can be a challenging and debilitating disorder for pediatric brain tumor patients. Further research into treatment options and outcomes is necessary to guide future management.

Features of the course of hydrocephalus in children after removal of a tumor of the posterior cranial fossa in the near and long term

The article presents the results of a study of the dynamics of the development of persistent hydrocephalus in children after surgical removal of a tumor of the posterior cranial fossa in the early and late postoperative period. The analysis of the incidence of neuropsychological syndromes: cerebellar cognitive-affective syndrome and cerebellar mutism syndrome in children of this group was carried out. Retrospective analysis included 30 patients under 18 years of age with a diagnosis tumor of the posterior cranial fossa complicated by occlusive hydrocephalus. All patients were operated on in the conditions of the Department of Neurosurgery for Children No. 7 of the Almazov National Medical Research Centre. As a result of the study, the risk groups for maintaining hydrocephalus after removal of the tumor of the posterior cranial fossa were determined, and the frequency of occurrence of neuropsychological syndromes in the postoperative period was determined.

Neuroanatomy of cerebellar mutism syndrome: the role of lesion location.

Approximately 25% of paediatric patients who undergo cerebellar tumour resection develop cerebellar mutism syndrome. Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with an increased risk of cerebellar mutism syndrome. Here, we tested whether these findings replicate in an independent cohort. We evaluated the relationship between lesion location and the development of cerebellar mutism syndrome in an observational study of 56 paediatric patients ranging from five months to 14 years of age who underwent cerebellar tumour resection. We hypothesized that individuals who developed cerebellar mutism syndrome after surgery, relative to those who did not, would have lesions that preferentially intersect with: (i) the cerebellar outflow pathway and (ii) a previously generated 'lesion-symptom map' of cerebellar mutism syndrome. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). We found supporting evidence for both hypotheses. Compared to patients who did not develop cerebellar mutism syndrome, patients with cerebellar mutism syndrome (n = 10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d = 0.73, P = 0.05), and the cerebellar mutism syndrome lesion-symptom map (Cohen's d = 1.1, P = 0.004). These results strengthen the association of lesion location with the risk of developing cerebellar mutism syndrome and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to paediatric cerebellar tumours.

Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa - Results of the HIT 2000 trial.

Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization and biology in pediatric survivors of a posterior fossa tumor. Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic (NBD) tool based on Cattell-Horn-Carroll's model for intelligence were analyzed. Cognitive performance 5.14 years (mean; range=1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had strong impact on most subtests. pCMS was associated with psychomotor abilities (β=-0.25 to -0.16) and processing speed (β=-0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β=-0.20) and short-term memory (β=-0.15), age with crystallized intelligence (β=0.15) and psychomotor abilities (β=-0.16 and β=-0.17). Scores for fluid intelligence (β=-0.23), short-term memory (β=-0.17) and visual processing (β=-0.25) declined, and scores for selective attention improved (β=0.29) with time after diagnosis. Dose of CSI was strongly associated with neurocognitive outcome. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI-dose and toxicity caused by other treatment modalities.

Cerebellar Mutism Syndrome and Dentato-Thalamo-Cortical Tract Disruption in Diffusion Tractography Following Surgery for Medulloblastoma.

Background Cerebellar mutism syndrome (CMS), a complication following medulloblastoma surgery, has been linked to dentato-thalamo-cortical tract (DTCT) injury; the association of the degree of DTCT injury with severity of CMS-related symptoms has not been investigated. Purpose To investigate the association between severity of CMS-related symptoms and degree and patterns of DTCT injury with use of diffusion tensor imaging (DTI), and if laterality of injury influences neurologic symptoms. Materials and Methods This retrospective case-control study used prospectively collected clinical and DTI data on patients with medulloblastoma enrolled in a clinical trial (between July 2016 and February 2020) and healthy controls (between April and November 2017), matched with the age range of the participants with medulloblastoma. CMS was divided into types 1 (CMS1) and 2 (CMS2). Multivariable logistic regression was used to investigate the relationship between CMS likelihood and DTCT injury. Results Overall, 82 participants with medulloblastoma (mean age, 11.0 years ± 5.2 [SD]; 53 male) and 35 healthy controls (mean age, 18.0 years ± 3.06; 18 female) were included. In participants with medulloblastoma, DTCT was absent bilaterally (AB), absent on the right side (AR), absent on the left side (AL), or present bilaterally (PB), while it was PB in all healthy controls. Odds of having CMS were associated with higher degree of DTCT damage (AB, odds ratio = 272.7 [95% CI: 269.68, 275.75; P < .001]; AR, odds ratio = 14.40 [95% CI: 2.84, 101.48; P < .001]; and AL, odds ratio = 8.55 [95% CI: 1.15, 74.14; P < .001). Left (coefficient = -0.07, χ2 = 12.4, P < .001) and right (coefficient = -0.15, χ2 = 33.82, P < .001) DTCT volumes were negatively associated with the odds of CMS. More participants with medulloblastoma with AB showed CMS1; unilateral DTCT absence prevailed in CMS2. Lower DTCT volumes correlated with more severe ataxia. Unilateral DTCT injury caused ipsilateral dysmetria; AB caused symmetric dysmetria. PB indicated better neurologic outcome. Conclusion The severity of CMS-associated mutism, ataxia, and dysmetria was associated with DTCT damage severity. DTCT damage patterns differed between CMS1 and CMS2. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dorigatti Soldatelli and Ertl-Wagner in this issue.

Diffusion Tensor Imaging May Help Diagnose Cerebellar Mutism Syndrome.

Diffusion Tensor Imaging May Help Diagnose Cerebellar Mutism Syndrome.

Proceedings of the first global meeting of the Posterior Fossa Society: state of the art in cerebellar mutism syndrome.

The Posterior Fossa Society, an international multidisciplinary group, hosted its first global meeting designed to share the current state of the evidence across the multidisciplinary elements of pediatric post-operative cerebellar mutism syndrome (pCMS). The agenda included keynote talks from world-leading speakers, compelling abstract presentations and engaging discussions led by members of the PFS special interest groups. This paper is a synopsis of the first global meeting, a 3-day program held in Liverpool, England, UK, in September 2022. Topics included nosology, patient and family experience, cerebellar modulation of cognition, and cerebellar cognitive affective syndrome. In addition, updates from large-scale studies were shared as well as abstracts across neuroradiology, neurosurgery, diagnosis/scoring, ataxia, and rehabilitation. Based on data-driven evidence and discussions, each special interest group created research priorities to target before the second global meeting, in the spring of 2024.

Secondary cerebro-cerebellar and intra-cerebellar dysfunction in cerebellar mutism syndrome.

Cerebellar mutism syndrome (CMS) is characterized by deficits of speech, movement, and affect that can occur following tumor removal from the posterior fossa. The role of cerebro-cerebellar tract injuries in the etiology of CMS remains unclear, with recent studies suggesting that cerebro-cerebellar dysfunction may be related to chronic, rather than transient, symptomatology. We measured functional connectivity between the cerebellar cortex and functional nodes throughout the brain using fMRI acquired after tumor removal but prior to adjuvant therapy in a cohort of 70 patients diagnosed with medulloblastoma. Surgical lesions were mapped to the infratentorial anatomy, and connectivity with cerebral cortex was tested for statistical dependence on extent of cerebellar outflow pathway injury. CMS diagnosis was associated with an increase in connectivity between the right cerebellar and left cerebral hemisphere, maximally between cerebellum and ventromedial prefrontal cortex (VM-PFC). Connectivity dependence on cerebellar outflow was significant for some speech nodes but not for VM-PFC, suggesting altered input to the cerebellum. Connectivity between posterior regions of cerebellar cortex and ipsilateral dentate nuclei was abnormal in CMS participants, maximally within the right cerebellar hemisphere. The functional abnormalities we identified are notably upstream of where causal surgical injury is thought to occur, indicating a secondary phenomenon. The VM-PFC is involved in several functions that may be relevant to the symptomatology of CMS, including emotional control and motor learning. We hypothesize that these abnormalities may reflect maladaptive learning within the cerebellum consequent to disordered motor and limbic function by the periaqueductal gray and other critical midbrain targets.

Evaluation of safety of fluoxetine for cerebellar mutism syndrome in children after posterior fossa surgery

BackgroundCerebellar mutism syndrome (CMS) occurs in 8–29 % of children undergoing posterior fossa tumor surgery. Its main symptoms are mutism and emotional lability. Although it is always transient, recovery time can be lengthy with long-term cognitive sequelae. There is no approved drug treatment for CMS, but some drugs are used in everyday medical practice. One of these is fluoxetine, which has been used for many years in our institution. The main objective of this study was to establish the safety profile of fluoxetine in this condition. Materials and methodsThe records of patients admitted to the pediatric intensive care unit after brain surgery at Angers University Hospital from 2010 to 2020 were reviewed. Children aged 2 years and older who underwent a posterior fossa tumor surgery and were diagnosed with CMS were included. Data on patient characteristics, prescription of fluoxetine treatment, side effects if any, and complete mutism duration were collected. ResultsAmong 246 patients admitted to the pediatric intensive care unit for brain surgery during the study period, 23 had CMS and eight were prescribed fluoxetine. No serious adverse event related to fluoxetine was reported. Complete mutism duration did not differ significantly between the fluoxetine group and the non-fluoxetine group(p = 0.22). However, the treatment was initiated after recovery from complete mutism in half of the treated patients. ConclusionThis study suggests a positive safety profile of fluoxetine used in postoperative CMS. It does not answer the question of whether the treatment is effective for this indication. A randomized controlled trial based on a syndrome severity scale should be conducted to provide a more reliable assessment of the efficacy and safety of fluoxetine.

REhabilitation Approaches in CHildren with cerebellar mutism syndrome (REACH): An international cross-disciplinary survey study.

Pediatric cerebellar mutism syndrome (pCMS) can occur following resection of a posterior fossa tumor and, although some symptoms are transient, many result in long-lasting neurological deficits. A multi-disciplinary rehabilitation approach is often used in cases of pCMS; however, there have been no clinical trials to determine gold standards in rehabilitation practice in this population, which remains a research priority. The purpose of this study was to identify and compare intervention practices used in pCMS throughout the disciplines of occupational and physical therapy, speech-language pathology, and neuropsychology across geographic regions. A 55-question e-survey was created by an international multidisciplinary research group made up of members of the Posterior Fossa Society and sent to rehabilitation professionals in pediatric neuro-oncology centers in the US, Canada, and Europe. Although some differences in the type of intervention used in pCMS were identified within each discipline, many of the targeted interventions including dose, frequency, and intensity were similar within disciplines across geographic regions. In addition, there were common themes identified across disciplines regarding challenges in the rehabilitation of this population. These results provide a foundation of current practices on which to build future intervention-based clinical trials.

Vestibular Testing and Impairments in Postoperative Pediatric Cerebellar Mutism Syndrome: A Case Series

BackgroundPostoperative pediatric cerebellar mutism syndrome (CMS) may occur following a process affecting the posterior cranial fossa. Recent evidence demonstrates disabling and potentially lasting motor components of this syndrome, including ataxia, hemiparesis, and oculomotor dysfunction. These impairments may contribute to vestibular deficits. MethodsThis case series contributes data to quantify vestibular dysfunction in postoperative CMS. The pair consisted of one female and one male. ResultsVestibular testing demonstrated both peripheral and central dysfunction. ConclusionsGiven these findings, a thorough vestibular assessment may be indicated as part of a comprehensive evaluation following a postoperative CMS diagnosis. Further research is needed to understand the pathophysiology, treatment, and long-term outcomes of postoperative pediatric CMS.

CTH Secondary to Paediatric Posterior Fossa Tumour and Post-operative Paediatric Cerebellar Mutism Syndrome: A Retrospective Study in a Tertiary Care Centre

CTH Secondary to Paediatric Posterior Fossa Tumour and Post-operative Paediatric Cerebellar Mutism Syndrome: A Retrospective Study in a Tertiary Care Centre

Postoperative cerebellar mutism syndrome is an acquired autism-like network disturbance.

Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumor surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates. In this study, we analyzed postoperative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and pediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n = 427). Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the pediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to the prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviors. Our findings indicate that CMS-associated lesions may result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children.

Application of the Rotterdam postoperative cerebellar mutism syndrome prediction model in patients undergoing surgery for medulloblastoma in a single institution.

Postoperative cerebellar mutism syndrome (CMS) develops in up to 40% of children with medulloblastoma. The Rotterdam model (RM) has been reported to predict a 66% risk of CMS in patients with a score of ≥ 100. The aim of this study was to retrospectively apply the RM to an independent cohort of patients with newly diagnosed medulloblastoma and study the applicability of the RM in predicting postoperative CMS. Participants had to have their first tumor resection at the authors' institution and be enrolled in the SJMB12 protocol (NCT01878617). All participants underwent structured serial neurological evaluations before and then periodically after completing radiation therapy. Imaging was reviewed by the study neurologist who was blinded to CMS status when reviewing the scans and retrospectively applied RM score to each participant. Forty participants were included (14 females and 26 males). Four (10%) patients had CMS. The median age at tumor resection was 11.7 years (range 3.5-17.8 years). Tumor location was midline in 30 (75%), right lateral in 6 (15%), and left lateral in 4 (10%). The median Evans index was 0.3 (range 0.2-0.4), and 34 (85%) patients had an Evans index ≥ 0.3. Five participants required a ventricular shunt. The median tumor volume was 51.97 cm3 (range 20.13-180.58 cm3). Gross-total resection was achieved in 35 (87.5%) patients, near-total resection in 4 (10%), and subtotal in 1. The median RM score was 90 (range 25-145). Eighteen participants had an RM score of ≥ 100, and of these 16.7% (n = 3) had CMS. Of the 22 patients with an RM score < 100, 1 child developed CMS (4.5%, CI 0.1%-22.8%); 3 of the 18 patients with an RM score ≥ 100 developed CMS (16.7%, CI 3.6%-41.4%). The observed rate of CMS in the cohort of children with an RM score ≥ 100 was significantly lower than the observed rate in the original RM cohort (66.7%, CI 51%-80.0%, p < 0.001). A greater risk of CMS in patients with an RM score ≥ 100 could not be confirmed (p = 0.31). At the authors' institution, the incidence of CMS in patients who had an RM ≥ 100 was significantly lower than the RM cohort. These findings raise questions regarding generalizability of RM; however, fewer cases of CMS and a relatively small cohort limit this conclusion.