Postoperative Cerebellar Mutism Syndrome Research Articles

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.

Catatonia associated with pediatric postoperative cerebellar mutism syndrome

Catatonia associated with pediatric postoperative cerebellar mutism syndrome

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.

Characterising the Long-Term Language Impairments of Children Following Cerebellar Tumour Surgery by Extracting Psycholinguistic Properties from Spontaneous Language.

Following cerebellar tumour surgery, children may suffer impairments of spontaneous language. Yet, the language processing deficits underlying these impairments are poorly understood. This study is the first to try to identify these deficits for four levels of language processing in cerebellar tumour survivors. The spontaneous language of twelve patients who underwent cerebellar tumour surgery (age range 3-24years) was compared against his or her controls using individual case statistics. A distinction was made between patients who experienced postoperative cerebellar mutism syndrome (pCMS) and those who did not. Time since surgery ranged between 11months and 12;3years. In order to identify the impaired language processing levels at each processing level (i.e., lexical, semantic, phonological and/or morphosyntactic) nouns and verbs produced in the spontaneous language samples were rated for psycholinguistic variables (e.g., concreteness). Standard spontaneous language measures (e.g., type-token ratio) were calculated as well. First, inter-individual heterogeneity was observed in the spontaneous language outcomes in both groups. Nine out of twelve patients showed language processing deficits three of whom were diagnosed with pCMS. Results implied impairments across all levels of language processing. In the pCMS-group, the impairments observed were predominantly morphosyntactic and semantic, but the variability in nature of the spontaneous language impairments was larger in the non-pCMS-group. Patients treated with cerebellar tumour surgery may show long-term spontaneous language impairments irrespective of a previous pCMS diagnosis. Individualised and comprehensive postoperative language assessments seem necessary, given the inter-individual heterogeneity in the language outcomes.

Postoperative MRI features of cerebellar mutism syndrome: a retrospective cohort study.

In this study, the authors aimed to investigate the relationship between postoperative MRI features and cerebellar mutism syndrome. A retrospective cohort of patients who underwent tumor resection from July 2013 to March 2021 for midline posterior fossa tumors was investigated. All patients were followed up at least once. Clinical data were extracted from medical records and follow-up databases. Two neuroradiologists independently reviewed preoperative and postoperative MRI. Univariable and multivariable analyses were performed to compare the postoperative cerebellar mutism syndrome (pCMS) and non-pCMS groups. Correlation analysis was performed using the Spearman correlation coefficient analysis. Of 124 patients, 47 (37.9%) developed pCMS. The median follow-up duration was 45.73 (Q1: 33.4, Q3: 64.0) months. The median duration of mutism was 45 days. The median tumor size was 48.8 (Q1: 42.1, Q3: 56.8) mm. In the univariable analysis, abnormal T2-weighted signal of the left dentate nucleus (DN) (74.5% in the pCMS group vs 36.4% in the non-pCMS group, p < 0.001), right DN (83.0% vs 40.3%, p < 0.001), left superior cerebellar peduncle (SCP) (74.5% vs 27.3%, p < 0.001), right SCP (63.8% vs 23.4%, p < 0.001), left middle cerebellar peduncle (MCP) (51.1% vs 26.0%, p = 0.008), and right MCP (61.7% vs 26.0%, p < 0.001); male sex (83.0% vs 45.5%, p < 0.001); vermis 3 impairment (49.4% vs 19.1%, p = 0.002); solid tumor (91.5% vs 72.7%, p = 0.022); and hydrocephalus (72.3% vs 45.5%, p = 0.006) were more frequent in the pCMS group than in the non-pCMS group. Multivariable logistic analysis showed that male sex (adjusted OR 4.08, p = 0.010) and the cerebro-cerebellar circuit score of T2-weighted images (adjusted OR 2.15, p < 0.001) were independent risk factors for pCMS. The cerebro-cerebellar circuit score positively correlated with the duration of mutism. In Cox regression analysis, the cerebro-cerebellar integrated circuit injury score of T2 (adjusted HR 0.790, 95% CI 0.637-0.980; p = 0.032) and injury of vermis 3 (adjusted HR 3.005, 95% CI 1.197-7.547; p = 0.019) were independently associated with the duration of mutism. Male sex and cerebro-cerebellar circuit damage are independent risk factors for pCMS. The cerebro-cerebellar circuit score indicates the duration of mutism.

Factors predicting “postoperative cerebellar mutism syndrome’’ after posterior fossa tumor excision in pediatric patients

Abstract Background: Central tumor location, brain stem involvement, and medulloblastoma have been implicated as risk factors for pediatric postoperative cerebellar mutism syndrome (pCMS) by most researchers. However, conflicting results have been reported for surgical factors, such as the extent of excision, surgical approach, and the need for cerebrospinal fluid diversion. The role of emergency or elective surgery is also not well established. Aim: To assess the role of surgical factors as a risk for pCMS. The secondary variables assessed include patient profile, histopathology, radiological features, and the effect of pCMS on patient survival. Materials and Methods: Overall, 162 consecutively operated patients with posterior fossa tumor (PFT) from July 2012 to March 2020, younger than 16 years of age, were included in the study. The study population was divided into two cohorts: the pCMS group and the non-pCMS group for statistical analysis. A P-value of less than 0.05 was considered statistically significant. Results: In the sample size of 162 patients, 129 patients were included for analysis. There were 11 patients in the pCMS group. Emergency surgery was found to be a significant risk for pCMS (P = 0.021). There was a trend toward statistical significance for the need for preoperative cerebrospinal fluid diversion. The extent of resection and surgical approach were not found to be statistically significant factors. Central tumor location and contrast enhancement were significant radiological risk factors (P &lt; 0.05). Conclusion: Aggressive tumor resection causing iatrogenic injury to the cerebellar circuitry and the brain stem is the most important risk factor for pCMS. Patients with pCMS have adverse survival outcomes.

Fastigial nuclei surgical damage and focal midbrain disruption implicate PAG survival circuits in cerebellar mutism syndrome.

Pediatric postoperative cerebellar mutism syndrome (CMS) is a rare but well-known complication of medulloblastoma (Mb) resection with devastating effects on expressive language, mobility, cognition, and emotional regulation that diminishes quality of life for many Mb survivors. The specific anatomical and neuronal basis of CMS remains obscure. We address this issue by identifying patterns of surgical damage and secondary axonal degeneration in Mb survivors with CMS. Children with Mb deemed high risk for CMS based on intraventricular location of the tumor had T1 images analyzed for location(s) of surgical damage using a specially developed algorithm. We used three complementary methods of spatial analysis to identify surgical damage linked to CMS diagnosis. Magnetization transfer ratio (MTR) images were analyzed for evidence of demyelination in anatomic regions downstream of the cerebellum, indicating neuronal dysfunction. Spatial analyses highlighted damage to the fastigial nuclei and their associated cerebellar cortices as the strongest predictors of CMS. CMS-related MTR decrease was greatest in the ventral periaqueductal gray (PAG) area and highly consistent in the left red nucleus. Our evidence points to disruption of output from the fastigial nuclei as a likely causal trigger for CMS. We propose that core CMS symptoms result from a disruption in the triggering of survival behaviors regulated by the PAG, including the gating of vocalization and volitional movement. The fastigial nuclei provide the densest output to the PAG from the cerebellum, thus sparing these structures may provide a greater likelihood of CMS prevention.

MEDB-29. Application of Rotterdam Post-Operative Cerebellar Mutism Syndrome Prediction Model to Patients Operated for Medulloblastoma in a Single Institution

BACKGROUND: Post-operative cerebellar mutism syndrome (CMS) develops in up to 30% of children. The Rotterdam model (RM) predicts a 66% risk of CMS in patients with a score ≥100. However, our findings suggested that surgical experience contributes to CMS risk. The aim of this study was to retrospectively apply the RM and report incidence of CMS in high-risk patients from our institution. METHODS: Participants had to have first tumor resection at our institution and be enrolled on SJMB12 protocol (NCT01878617). All participants got structured serial neurologic evaluations. CMS, when present, was categorized into type 1 (complete mutism) and type 2 (paucity of speech with an inability to string 3-word sentence). Rotterdam score is calculated based on pre-operative imaging parameters and study neurologist (RBK) obtained it while blinded to CMS status. RESULTS: Of the 40 (14 female, 26 male) study participants, 4 (10%) had CMS (3 CMS1, 1 CMS2). Median age at tumor resection was 11.7 years (range 3.5-17.8). Tumor location was midline in 30 (75%), right lateral 6 (15%) and left lateral 4 (10%). Median Evans index was 0.3 (0.2-0.4) and 34 (85%) were ≥0.3 (indicative of hydrocephalus); 5 participants needed ventricular shunt. Median tumor volume was 50 cm3 (2-180.6). Gross total resection was achieved in 35 (87.5%), near total in 4 (10%) and subtotal in 1. Twelve tumors were SHH, 7 WNT, and 29 NWNS. Median RM score was 90 (25 – 145). Eighteen participants had a score of ≥100 and 16.7% of these (n=3) had CMS. Scores for the 4 with CMS were 85, 125, 145 and 145. CONCLUSION: At our institution, the incidence of CMS in those that had RM of ≥100 was much lower than reported risk of 66%. This data supports our hypothesis that neurosurgical experience remains a significant risk factor in the development of CMS.

SURG-17. Impact of introduction of sagittal dimensions to predictive model of post-operative cerebellar mutism (CMS): A report of the Nottingham CMS Workshop

Abstract BACKGROUND: The Nottingham-Liverpool risk stratification tool for predicting post-operative cerebellar mutism syndrome (CMS) requires further refinement. Previous smaller studies identified tumours arising in cerebellar hemispheres (CH+ve) as very low risk and proposed that larger sagittal dimensions may be associated with a higher CMS risk. METHODS: An international multi-centre workshop assembled clinical, imaging and surgical data from 242 posterior fossa tumour patients from 9 centres (age 2-23.8, mean 8.23 years; histology 122 medulloblastoma, 75 pilocytic astrocytoma, 25 ependymoma, 18 other tumour types, 2 not known). Post-operative CMS developed in 0/66 CH+ve and 40/176 CH-ve patients (23%, range 13-33%) and. Tumour measurements in the sagittal plane were incorporated into the predictive model. RESULTS: In CH-ve tumours, CMS was associated higher D-Sag (CMS+ve 3.91±1.08 vs CMS-ve 3.01±1.56 cm p=0.001), d-Sag (CMS+ve 0.63±0.27 vs CMS-ve 0.44±0.31 cm p=0.001) and D-Sag*d-Sag (CMS+ve 2.60±1.36 vs CMS-ve 1.65±1.45 cm2 p=0.001). The Rotterdam model identified CMS rates for CH-ve tumours for low, intermediate and high risk groups as: 4% (2/45), 20% (16/79) and 42% (22/52), respectively. CONCLUSIONS: Incorporating D-sag and d-Sag estimates of tumour size, proposed, and adopted by the Beijing and Rotterdam groups, respectively, enhanced the objectivity and supports the model’s CMS predictive capacity for the purposes of consent and future trials. Higher CMS risk, associated with larger sagittal dimensions, may account for variability in CMS rates between cohorts and, as a new finding, may have broader clinical implications around the timing of diagnosis.

Structural damage burden and hypertrophic olivary degeneration in pediatric postoperative cerebellar mutism syndrome

Cerebellar mutism syndrome (CMS) occurs in one out of four children after posterior fossa tumor surgery, with open questions regarding risk factors, pathophysiology, and prevention strategies. Because of similarities between several cerebellar syndromes, a common pathophysiology with damage to the dentato-thalamo-cortical and dentato-rubro-olivary pathways has been proposed. Hypertrophic olivary degeneration (HOD) is an imaging correlate of cerebellar injury observed for instance in stroke patients. Aim of this study was to investigate whether the occurrence and severity of CMS correlates with the extent of damage to the relevant anatomical structures and whether HOD is a time-dependent postoperative neuroimaging correlate of CMS. We performed a retrospective single center study of CMS patients compared with matched non-CMS controls. CMS occurred in 10 children (13% of the overall cohort) with a median age of 8 years. Dentate nucleus (DN) injury significantly correlated with CMS, and superior cerebellar peduncle (SCP) injury was associated by tendency. HOD was observed as a dynamic neuroimaging phenomenon in the postoperative course and its presence significantly correlated with CMS and DN injury. Children who later developed HOD had an earlier onset and tended to have longer persistence of CMS. These findings can guide surgical measures to protect the DN and SCP during posterior fossa tumor resections and to avoid a high damage burden (i.e., bilateral damage). Development of intraoperative neuromonitoring of the cerebellar efferent pathways as well as improved preoperative risk stratification could help to establish a patient-specific strategy with optimal balance between degree of resection and functional integrity.

Risk factors for postoperative cerebellar mutism syndrome in pediatric patients: a systematic review and meta-analysis.

A review article assessing all the risk factors reported in the literature for postoperative cerebellar mutism syndrome (pCMS) among children remains absent. The authors sought to perform a systematic review and meta-analysis to evaluate this issue. PubMed, Embase, and Web of Science were queried to systematically extract potential references. The articles relating to pCMS were required to be written in the English language, involve pediatric patients (≤ 18 years of age), and provide extractable data, which included a comparison group of patients who did not develop pCMS. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Data were pooled using RevMan 5.4, and publication bias was assessed by visual inspection for funnel plot asymmetry. The study protocol was registered through PROSPERO (ID: CRD42021256177). Overall, 28 studies involving 2276 patients were included. Statistically significant risk factors identified from univariate analysis were brainstem invasion (OR 4.28, 95% CI 2.23-8.23; p < 0.0001), fourth ventricle invasion (OR 12.84, 95% CI 4.29-38.44; p < 0.00001), superior cerebellar peduncle invasion (OR 6.77, 95% CI 2.35-19.48; p = 0.0004), diagnosis of medulloblastoma (OR 3.26, 95% CI 1.93-5.52; p < 0.0001), medulloblastoma > 50 mm (OR 8.85, 95% CI 1.30-60.16; p = 0.03), left-handedness (OR 6.57, 95% CI 1.25-34.44; p = 0.03), and a vermis incision (OR 5.44, 95% CI 2.09-14.16; p = 0.0005). On the other hand, a tumor located in the cerebellar hemisphere (OR 0.23, 95% CI 0.06-0.92; p = 0.04), cerebellar hemisphere compression (OR 0.23, 95% CI 0.11-0.45; p < 0.0001), and intraoperative imaging (OR 0.36, 95% CI 0.18-0.72; p = 0.004) reduced the risk of pCMS. This study provides the largest and most reliable review of risk factors associated with pCMS. Although some risk factors may be dependent on one another, the data may be used by surgeons to better identify patients at risk for pCMS and for intervention planning.

Individual cerebrocerebellar functional network analysis decoding symptomatologic dynamics of postoperative cerebellar mutism syndrome.

IntroductionPostoperative cerebellar mutism syndrome (pCMS) consists of three types of symptoms (motoric, linguistic, and neurobehavioral) in patients with posterior fossa pathologies. The evolutional mechanism of this high cognitive syndromic complex from cerebellar origin remains unconfirmed. Previous studies analyzing CMS patients mostly focused on the association between structural abnormalities that occur during CMS, of which proximal efferent cerebellar pathway (pECP) injury appears to be the most common pathogenesis. However, structural imaging may not be sensitive enough to determine the dynamic course of CMS, since the symptomatology is primarily an output of cerebral operation.MethodWe took a network approach in a child during her course of development and recovery of the pCMS. On the other hand, a network neuroscience approach using a mathematical model to extract information from functional imaging to generate interregional connectivity provides abundant evidence that the cerebellum is influential in modulating cerebral functions.ResultThis study applied a network approach to children with pCMS. An individual cerebrocerebellar functional network analysis using graph theory was then performed to determine the network dynamics during CMS. Cross-validation of clinical neurophysiology and functional neuroscience suggested the critical role of the pECP within CMS from the network analysis.ConclusionThe employed approach was therefore useful in determining the complex clinical symptoms using individual functional network analysis, which bridges the gap between structural neuroimaging and clinical neurophysiology.

Perioperative risk factors for long-term intelligence in children with postoperative cerebellar mutism syndrome after medulloblastoma surgery.

Approximately 7%-50% of children with medulloblastoma (MB) develop postoperative cerebellar mutism syndrome (pCMS). pCMS has a short-term negative impact on intelligence, but effects on long-term outcomes are contradictory. The aim of this study was to assess long-term effects of pCMS in MB patients on aspects of intelligence quotient (IQ) and its perioperative risk factors. In this single-center retrospective cohort study, 31 children were included (14 pCMS). Perioperative risk factors included brainstem invasion, vermis incision, hydrocephalus, tumor size, severity of pCMS, neurological symptoms, mean body temperature (BT) on days 1-4 post surgery, and age at resection. Age-appropriate Wechsler Intelligence tests were assessed at least 2years after tumor resection. Mean interval between tumor resection and neuropsychological evaluation was 3.9years in pCMS and 4years and 11months in the no-pCMS group. No significant differences in IQ scores were found between groups. The pCMS group had a clinically relevant difference of 10 points when compared to age norms on verbal IQ (VIQ). Bilateral pyramidal and swallowing problems were risk factors for lower performance. In the overall group, tumor size, younger age at surgery, and raised mean BT were negatively correlated with aspects of IQ. We found a clinically significant reduction of VIQ in the pCMS patient group. pCMS patients with a larger tumor size, younger age at surgery, a higher mean BT in the first days after surgery, bilateral pyramidal symptoms, and swallowing problems 10days post surgery are more at risk for VIQ deficits at long-term.

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.

QOL-13. NEUROCOGNITIVE OUTCOMES ACCORDING TO RISK-ADAPTED TREATMENT REGIMENS FOR CHILDREN OLDER THAN 4 WITH MEDULLOBLASTOMA AND POSTERIOR FOSSA EPENDYMOMA – RESULTS OF THE HIT2000 TRIAL

OBJECTIVESReduced neuropsychological outcomes are a major concern in pediatric patients with malignant brain tumors. We aimed to estimate decline in cognitive function according to treatment regimens.METHODSCross-sectional analysis of cognitive functions tested with the Neuropsychological Basic Diagnostic tool (NBD) in 279 patients >4 years at diagnosis (median: 8.66; range: 4.01–18.98) with medulloblastoma (n=110, 23.7–25.0Gy CSI; n=131, >30Gy CSI) or posterior fossa ependymoma (n=38 local radiotherapy) who participated in the HIT-2000 trial. Multivariable regression analysis was conducted to adjust for postoperative cerebellar mutism syndrome, preoperative hydrocephalus, postoperative shunt placement, the interval between diagnosis and assessment, sex and age.RESULTSMean time from diagnosis to assessment was 5.1 years. Increasing CSI-dose was significantly associated with a deterioration in performance of most subtests, particularly in areas of fluid intelligence (mean z-values per test for no CSI/23.4Gy/>30Gy respectively: matrix reasoning:-0.40/-0.52/-0.98, p<.001), short-term memory (number recall: -0.07/-0.58/-0.64, p=.002), visuo-spatial skills (visual-motor integration:-0.49/-0.68/-1.12, p<.001) and fine motor skills (dominant-hand:-1.09/-1.80/-2.12, p=.008; non-dominant-hand:-1.47/-2.59/-2.82, p=.003; bimanual coordination:-1.33/-2.68/-2.76, p=.001). These differences were retained after adjustment for confounding variables. Within medulloblastoma patients treated with >30Gy CSI, selective attention, but no other function was reduced in patients treated with pre-radiotherapy chemotherapy including intraventricular MTX (selective attention (with chemotherapy/without chemotherapy mean z-values: -0.66/0.00, p=.006)). Patients with SHH-activated medulloblastoma did significantly better than WNT or Group3/Group4 medulloblastoma patients in fluid intelligence and fine motor skills.CONCLUSIONCSI dose among other highly relevant factors had significant effects on neuropsychological outcome. Pre-radiotherapy intraventricular MTX had only minor effects. Patients with SHH-activated medulloblastomas showed a more favorable outcome when compared to patients in the other subgroups.

Living with the cerebellar mutism syndrome: long-term challenges of the diagnosis.

After posterior fossa tumour surgery, up to 39% of children experience postoperative cerebellar mutism syndrome (CMS) characterized by mutism and other motor and cognitive impairments. There is a lack of knowledge on the patient-reported challenges and long-term needs. Consequently, no specific recommendations exist for rehabilitative and supportive interventions for patients with CMS. The aims of this study were to explore the patients' experiences related to the sequelae of CMS, to identify challenges and needs regarding support and rehabilitation in the period of growing from child to adult and to add perspectives for future developments of supportive care and rehabilitative guidelines. Ten semi-structured interviews were conducted with young adults diagnosed with CMS as children. A thematic analysis identified four themes describing challenges impacting aspects of the participants' lives. Four main themes were identified and highlight the rehabilitative need for focus on verbal and non-verbal communication skills in addition to the physical impairments. We found that brain tumour survivors with CMS can benefit from social and educational rehabilitation, straightforward and truthful information, support in structuring their everyday lives and increased public knowledge of CMS. Children with CMS face a variety of challenges affecting many aspects of their everyday lives. They should be entitled to the elements of a current rehabilitation initiative for childhood cancer to support patients' social disability and educational decline. Finally, we identified a need for an official information publication.

POSTERIOR FOSSA MENINGIOMA WITH CEREBELLAR MASS EFFECT PRESENTING AS DECLINE IN COGNITIVE FUNCTION AND IMPAIRED AFFECTIVE MODULATION: REVIEW OF THE CEREBELLAR COGNITIVE AFFECTIVE SYNDROME

POSTERIOR FOSSA MENINGIOMA WITH CEREBELLAR MASS EFFECT PRESENTING AS DECLINE IN COGNITIVE FUNCTION AND IMPAIRED AFFECTIVE MODULATION: REVIEW OF THE CEREBELLAR COGNITIVE AFFECTIVE SYNDROME

Preoperative prediction of postoperative cerebellar mutism syndrome. Validation of existing MRI models and proposal of the new Rotterdam pCMS prediction model

PurposePostoperative cerebellar mutism syndrome (pCMS) is a complication that may occur after pediatric fossa posterior tumor surgery. Liu et al. developed an MRI-based prediction model to estimate pCMS risk preoperatively. The goal of this study was to validate the model of Liu et al. and if validation was not as sensitive in our group as previously described to develop an easy to use, reliable, and sensitive preoperative risk prediction model for pCMS.MethodsIn this study, 121children with a fossa posterior tumor who underwent surgery at ErasmusMC/Sophia Children’s Hospital, the Netherlands between 2004 and 2018 could be included. Twenty-six percent of them developed pCMS. Preoperative MRI were scored using the Liu et al. model.ResultsThe Liu et al. model reached an accuracy of 78%, a sensitivity of 58%, and a specificity of 84% in our cohort. In a new risk model some of the variables of Liu et al. were included as well as some of the recently described preoperative MRI characteristics in pCMS patients by Zhang et al. The new model reached an accuracy of 87%, a sensitivity of 97%, and a specificity of 84% in our patient group.ConclusionBecause the Liu et al. model did not provide an as accurate risk prediction in our cohort as was expected, we created a new risk prediction model that reached high model accuracy in our cohort that could assist neurosurgeons in determining their surgical tactics and help prepare high risk patients and their parents for this severe complication.

Fully-Automated Identification of Imaging Biomarkers for Post-Operative Cerebellar Mutism Syndrome Using Longitudinal Paediatric MRI

Post-operative cerebellar mutism syndrome (POPCMS) in children is a post- surgical complication which occurs following the resection of tumors within the brain stem and cerebellum. High resolution brain magnetic resonance (MR) images acquired at multiple time points across a patient’s treatment allow the quantification of localized changes caused by the progression of this syndrome. However, MR images are not necessarily acquired at regular intervals throughout treatment and are often not volumetric. This restricts the analysis to 2D space and causes difficulty in intra- and inter-subject comparison. To address these challenges, we have developed an automated image processing and analysis pipeline. Multi-slice 2D MR image slices are interpolated in space and time to produce a 4D volumetric MR image dataset providing a longitudinal representation of the cerebellum and brain stem at specific time points across treatment. The deformations within the brain over time are represented using a novel metric known as the Jacobian of deformations determinant. This metric, together with the changing grey-level intensity of areas within the brain over time, are analyzed using machine learning techniques in order to identify biomarkers that correspond with the development of POPCMS following tumor resection. This study makes use of a fully automated approach which is not hypothesis-driven. As a result, we were able to automatically detect six potential biomarkers that are related to the development of POPCMS following tumor resection in the posterior fossa.