Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up. Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions. A new, proposed definition of “post-operative pediatric CMS” was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed. The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS.

Consensus paper on post-operative pediatric cerebellar mutism syndrome: the Iceland Delphi results.

Our aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved An umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised The following databases were searched: MEDLINE, EMBASE, Web of Science, CENTRAL, PsycINFO and CINAHL In addition, reference lists were screened We included reviews of the effects of MLT on any type of health-related outcome measure Altogether, 195 reviews met the inclusion criteria Most were of low methodological quality (mean -45, standard deviation 67) Of those, 164 did not pool the data and were synthesised narratively (qualitatively) whereas the remaining 31 used meta-analytic techniques and were synthesised quantitatively Seven meta-analyses were significant with P values less than 0001 under the random-effects model These pertained to sleep latency, pre-operative anxiety, prevention of agitation and risk of breast cancer There is an abundance of reviews evaluating the effects of exogenous and endogenous MLT on health In general, MLT has been shown to be associated with a wide variety of health outcomes in clinically and methodologically heterogeneous populations Many reviews stressed the need for more high-quality randomised clinical trials to reduce the existing uncertainties

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Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action.

Introduction
Cerebellar mutism (CM) is defined as a peculiar form of mutism that may complicate the surgical excision of posterior cranial fossa tumor. The incidence is variable in the literature, occurring in up to one third of cases in some series. Commonly occurring peculiar features of CM are delayed onset following surgery, limited duration, and spontaneous recovery usually associated with dysarthria.

Cerebellar mutism

The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman in 1998. Despite their clear depiction of the syndrome, it is our experience that the CCAS has not yet found solid ground as a disease entity in routine clinical practice. This made us question the dimension of the CCAS in cerebellar patients. We performed a systematic review of the literature according to the PRISMA guidelines, in order to answer the question whether patients with acquired isolated cerebellar lesions perform significantly worse on neuropsychological testing compared to healthy controls. Studies were selected based on the predefined eligibility criteria and quality assessment. The systematic search resulted in ten studies, mainly observational cohorts consecutively including adult patients with isolated cerebellar lesions. Patients were compared to healthy controls, and neuropsychological investigation was done within one year of diagnosis. Meta-analysis of the twelve tests that were done in two or more studies showed that cerebellar patients perform significantly worse on Phonemic Fluency, Semantic Fluency, Stroop Test (naming, reading and interference), Block Design test and WMS-R visual memory. Cerebellar patients have significant and relevant deficits in the visuospatial, language and executive function domain. This meta-analysis therefore emphasizes the importance of the cerebellar cognitive affective syndrome as described by Schmahmann and Sherman.

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The Cerebellar Cognitive Affective Syndrome-a Meta-analysis.

Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.

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Dentatorubrothalamic tract localization with postmortem MR diffusion tractography compared to histological 3D reconstruction

Cerebellar mutism is a serious neurosurgical complication after posterior fossa surgery, but the cause, incidence and outcome remain incompletely defined. The aim of this paper was to identify and review all reports of this phenomenon to better delineate and improve the evidence base. A systematic search and retrieval of databases was conducted using advanced search techniques. Review/outcomes criteria were developed, and study quality was determined. The retrieval identified 2,281 papers of which 96 were relevant, identifying 650 children with cerebellar mutism. Causative factors, clinical features and outcomes were reported variably; papers focussed on multiple areas, the majority reporting incidence in single or series of case studies with little or no analysis further than description. The complexity and variability of data reporting, likely contributing factors and outcomes make cerebellar mutism difficult to predict in incidence and the degree of impact that may ensue. A clear and accepted universal definition would help improve reporting, as would the application of agreed outcome measures. Clear and consistent reporting of surgical technique remains absent. Recommendations for practice are provided.

Cause and outcome of cerebellar mutism: evidence from a systematic review

This is the first UK multi-centre case-controlled study with follow-up in excess of 10 years to report the neurocognitive, academic and psychological outcomes of individuals diagnosed with a brain tumour in early childhood. Children enrolled into the UKCCSG CNS 9204 trial, diagnosed with intracranial ependymoma when aged ≤ 36 months old, who received a primary chemotherapy strategy to defer or avoid radiotherapy, were recruited. Outcomes of those who relapsed and subsequently received radiotherapy (n = 13) were compared to those enrolled who did not relapse (n = 16), age-matched controls—diagnosed with solid non-central nervous system (SN-CNS; n = 15) tumours or low-grade posterior fossa pilocytic astrocytoma (PFPA; n = 15), and normative data. Analyses compared nine neurocognitive outcomes as primary measures with quality of survival as secondary measures. Relapsed ependymoma participants performed significantly worse than their non-relapsed counterparts on measures of Full Scale IQ, Perceptual Reasoning, Word Reading and Numerical Operations. The relapsed ependymoma group performed significantly worse than SN-CNS controls on all primary measures, whereas non-relapsing participants only differed significantly from SN-CNS controls on measures of Processing Speed and General Memory. Relapsed ependymoma participants fared worse than all groups on measures of quality of survival. The relapsed irradiated ependymoma group demonstrated the most significantly impaired neurocognitive outcomes at long-term follow-up. Non-relapsing participants demonstrated better outcomes than those who relapsed. Results tentatively suggest avoiding radiotherapy helped preserve neurocognitive and learning outcomes of individuals diagnosed with ependymoma when aged ≤ 36 months old. Prospective neurocognitive surveillance is required. Recommendations for clinical and research practice are provided.

Neurocognitive, academic and functional outcomes in survivors of infant ependymoma (UKCCSG CNS 9204).

Objective: To retrieve and review all the relevant literature describing the administration of melatonin to treat impaired sleep in children following acquired brain injury (ABI). Methods: A systematic search and retrieval of the literature was conducted using advanced search techniques. The retrieval identified 589 papers, seven of which were relevant. Review/outcomes criteria were developed and study quality was determined. Results: There is paucity of high-quality evidence to support use of melatonin for sleep impairment post paediatric ABI. Variation in dosage, screening and outcome measures, data reporting and a lack of impairment delineation and treatment stratification were recurrent themes. Conclusion: Retrieved evidence for the effectiveness of melatonin for post paediatric ABI sleep impairment appears promising. There is a clear need for further study in this area to inform clinical and research practices. Recommendations are given.

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Rosa Reed-Berendt

Papers

Cause and outcome of cerebellar mutism: evidence from a systematic review

Neurocognitive, academic and functional outcomes in survivors of infant ependymoma (UKCCSG CNS 9204).

Effectiveness of melatonin for sleep impairment post paediatric acquired brain injury: Evidence from a systematic review