Post-operative pediatric cerebellar mutism syndrome and its association with hypertrophic olivary degeneration

Background: The dentato-thalamo-cortical (DTC) pathway is recognized as the anatomical substrate for postoperative pediatric cerebellar mutism (POPCMS), a well-recognized complication affecting up to 31% of children undergoing posterior fossa brain tumour resection. The proximal structures of the DTC pathway also form a segment of the Guillain and Mollaret triangle, a neural network which when disrupted causes hypertrophic olivary degeneration (HOD) of the inferior olivary nucleus (ION). We hypothesize that there is an association between the occurrence of POPCMS and HOD and aim to evaluate this on MR imaging using qualitative and quantitative analysis of the ION in children with and without POPCMS. Methods: In this retrospective study we qualitatively analysed the follow up MR imaging in 48 children who underwent posterior fossa tumour resection for presence of HOD. Quantitative analysis of the ION was possible in 28 children and was performed using semi-automated segmentation followed by feature extraction and feature selection techniques and relevance of the features to POPCMS were evaluated. The diagnosis of POPCMS was made independently based on clinical and nursing assessment notes. Results: There was significant association between POPCMS and bilateral HOD (P=0.002) but not unilateral HOD. Quantitative analysis showed that hyperintensity in the left ION was the most relevant feature in children with POPCMS. Conclusions: Bilateral HOD can serve as a reliable radiological indicator in establishing the diagnosis of POPCMS particularly in equivocal cases. The strong association of signal change due to HOD in the left ION suggests that injury to the right proximal efferent cerebellar pathway plays an important role in the causation of POPCMS. Keywords: Cerebellar mutism syndrome (CMS); hypertrophic olivary degeneration; posterior fossa syndrome (PFS); postoperative pediatric cerebellar mutism syndrom

Development and clinical acceptability of a pre-operative risk stratification tool of cerebellar mutism syndrome in children with posterior fossa tumour

Aims: Despite identification of numerous pre-operative cerebellar mutism syndrome (CMS) clinical and radiological predictors, a unifying pre-operative risk stratification model for use during surgical consent is currently lacking. The aims of the project are (1) to develop a simple, easy to implemented risk scoring scheme to flag patients at higher risk of post-operative CMS; and (2) to assess its clinical acceptability amongst medical professionals. Methods: The combined cohort consists of 89 patients from two major treatment centres (age: 2-23yrs, gender 28M,61F, MRI pathology estimate 36 medulloblastoma, 40 pilocytic astrocytoma, 12 ependymoma, 1 non-committal); 26 (29%) of whom developed post-operative CMS. Post-operative CMS status was ascertained from clinical notes and pre-operative MRI scans, blinded to CMS status, underwent structured evaluation for 21 tightly-defined candidate imaging risk markers based on prior literature. All variables were first screened based upon results from univariate analysis and C4.5 decision tree. Stepwise logistic regression was then used to develop the optimal model, and multiple logistic regression coefficients for the predictors were converted into risk scores. Results: Univariate analysis identified five significant risks and C4.5 decision tree identified six predictors. The final model (Table 1) has an accuracy of 88.8% (79/89), with a sensitivity of 96.2% (25/26) and specificity of 85.7% (54/63). Using risk score cut-offs 203 and 238 permit discrimination into low (38/89, predicted probability < 3%), intermediate (17/89, predicted probability 3–52%) and high-risk (34/89, predicted probability 52%), respectively (Figure 1). Three illustrative cases from these categories will be used to collect clinicians’ opinion on surgical treatment decision and the acceptability of using this risk stratification for decision making and surgical consenting process. A web-based voting app will be used. Conclusions: A risk stratification model for post-operative CMS could flag patients at increased risk pre-operatively and may influence strategies for surgical treatment of cerebellar tumours. Following future testing and prospective validation, this risk scoring scheme may be utilised during the surgical consenting process

Development of a pre-operative scoring system for predicting risk of post-operative paediatric cerebellar mutism syndrome

BACKGROUND: Despite previous identification of pre-operative clinical and radiological predictors of post-operative paediatric cerebellar mutism syndrome (CMS), a unifying pre-operative risk stratification model for use during surgical consent is currently lacking. The aim of the project is to develop a simple imaging-based pre-operative risk scoring scheme to stratify patients in terms of post-operative CMS risk. METHODS: Pre-operative radiological features were recorded for a retrospectively assembled cohort of 89 posterior fossa tumour patients from two major UK treatment centers (age 2-23yrs; gender 28 M, 61 F; diagnosis: 38 pilocytic astrocytoma, 32 medulloblastoma, 12 ependymoma, 1 high grade glioma, 1 pilomyxoid astrocytoma, 1 atypical teratoid rhabdoid tumour, 1 hemangioma, 1 neurilemmoma, 2 oligodendroglioma). Twenty-six (29%) developed post-operative CMS. Based upon results from univariate analysis and C4.5 decision tree, stepwise logistic regression was used to develop the optimal model and generate risk scores. RESULTS: Univariate analysis identified five significant risk factors and C4.5 decision tree analysis identified six predictors. Variables included in the final model are MRI primary location, bilateral middle cerebellar peduncle involvement (invasion and/or compression), dentate nucleus invasion and age at imaging >12.4 years. This model has an accuracy of 88.8% (79/89). Using risk score cut-off of 203 and 238, respectively, allowed discrimination into low (38/89, predicted CMS probability <3%), intermediate (17/89, predicted CMS probability 3-52%) and high-risk (34/89, predicted CMS probability ≥52%). CONCLUSIONS: A risk stratification model for post-operative paediatric CMS could flag patients at increased or reduced risk pre-operatively which may influence strategies for surgical treatment of cerebellar tumours. Following future testing and prospective validation, this risk scoring scheme will be proposed for use during the surgical consenting process

Development and clinical acceptability of a pre-operative risk stratification tool of cerebellar mutism syndrome in children with posterior fossa tumour

Aims: Despite identification of numerous pre-operative cerebellar mutism syndrome (CMS) clinical and radiological predictors, a unifying pre-operative risk stratification model for use during surgical consent is currently lacking. The aims of the project are (1) to develop a simple, easy to implemented risk scoring scheme to flag patients at higher risk of post-operative CMS; and (2) to assess its clinical acceptability amongst medical professionals. Methods: The combined cohort consists of 89 patients from two major treatment centres (age: 2-23yrs, gender 28M,61F, MRI pathology estimate 36 medulloblastoma, 40 pilocytic astrocytoma, 12 ependymoma, 1 non-committal); 26 (29%) of whom developed post-operative CMS. Post-operative CMS status was ascertained from clinical notes and pre-operative MRI scans, blinded to CMS status, underwent structured evaluation for 21 tightly-defined candidate imaging risk markers based on prior literature. All variables were first screened based upon results from univariate analysis and C4.5 decision tree. Stepwise logistic regression was then used to develop the optimal model, and multiple logistic regression coefficients for the predictors were converted into risk scores. Results: Univariate analysis identified five significant risks and C4.5 decision tree identified six predictors. The final model (Table 1) has an accuracy of 88.8% (79/89), with a sensitivity of 96.2% (25/26) and specificity of 85.7% (54/63). Using risk score cut-offs 203 and 238 permit discrimination into low (38/89, predicted probability < 3%), intermediate (17/89, predicted probability 3–52%) and high-risk (34/89, predicted probability 52%), respectively (Figure 1). Three illustrative cases from these categories will be used to collect clinicians’ opinion on surgical treatment decision and the acceptability of using this risk stratification for decision making and surgical consenting process. A web-based voting app will be used. Conclusions: A risk stratification model for post-operative CMS could flag patients at increased risk pre-operatively and may influence strategies for surgical treatment of cerebellar tumours. Following future testing and prospective validation, this risk scoring scheme may be utilised during the surgical consenting process

Post-operative pediatric cerebellar mutism syndrome and its association with hypertrophic olivary degeneration

Background: The dentato-thalamo-cortical (DTC) pathway is recognized as the anatomical substrate for postoperative pediatric cerebellar mutism (POPCMS), a well-recognized complication affecting up to 31% of children undergoing posterior fossa brain tumour resection. The proximal structures of the DTC pathway also form a segment of the Guillain and Mollaret triangle, a neural network which when disrupted causes hypertrophic olivary degeneration (HOD) of the inferior olivary nucleus (ION). We hypothesize that there is an association between the occurrence of POPCMS and HOD and aim to evaluate this on MR imaging using qualitative and quantitative analysis of the ION in children with and without POPCMS. Methods: In this retrospective study we qualitatively analysed the follow up MR imaging in 48 children who underwent posterior fossa tumour resection for presence of HOD. Quantitative analysis of the ION was possible in 28 children and was performed using semi-automated segmentation followed by feature extraction and feature selection techniques and relevance of the features to POPCMS were evaluated. The diagnosis of POPCMS was made independently based on clinical and nursing assessment notes. Results: There was significant association between POPCMS and bilateral HOD (P=0.002) but not unilateral HOD. Quantitative analysis showed that hyperintensity in the left ION was the most relevant feature in children with POPCMS. Conclusions: Bilateral HOD can serve as a reliable radiological indicator in establishing the diagnosis of POPCMS particularly in equivocal cases. The strong association of signal change due to HOD in the left ION suggests that injury to the right proximal efferent cerebellar pathway plays an important role in the causation of POPCMS