Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Treatment developments and the unfolding of the quality of life discussion in childhood medulloblastoma: a review.

PURPOSE: To describe how the quality of life (QOL) discussion in childhood medulloblastoma (MB) relates to treatment developments, survival and sequelae from 1920 to 2014. METHODS: Articles containing "childhood medulloblastoma" and "quality of life" were identified in PubMed. Those containing phrases pertaining to psychological, emotional, behavioral or social adjustment in the title, abstract or keywords were selected. Inclusion of relevant older publications was assured by cross-checking references. RESULTS: 1920-1930s: suction, electro-surgery, kilovolt (KV) irradiation. Survival = months. Focus on operative mortality, symptoms and survival. 1940s: radiotherapy improved. 1950s: chemotherapy and intubation. Survival = years. Opinions oscillated between optimism/awareness of physical sequelae of radiotherapy. 1960s: magnified vision, ventriculo-peritoneal (VP) shunts, megavolt (MV) irradiation. Long-term survival shifted the attention towards neurological problems, disability and carcinogenesis of radiotherapy. 1970s: CT, microscope, bipolar coagulation, shunt filters, neuroanesthesia, chemotherapy trials and staging studies. Operative mortality decreased and many patients (re)entered school; emphasis on neuropsychological sequelae, IQ and academic performance. 1980s: magnetic resonance imaging (MRI), Cavitron ultrasonic aspiration (CUSA), laser surgery, hyper-fractionated radiotherapy (HFRT). Cerebellar mutism, psychological and social issues. 1990s: pediatric neurosurgery, proton beams, stem cell rescue. Reflections on QOL as such. 21st century: molecular genetics. Premature aging, patterns of decline, risk- and resilience factors. DISCUSSION: QOL is a critical outcome measure. Focus depends on survival and sequelae, determined after years of follow-up. Detailed measurements are limited by time, money and human resources, and self-reporting questionnaires represent a crude measure limited by subjectivity. Therapeutic improvements raise the question of QOL versus cure. QOL is a potential primary research endpoint; multicenter international studies are needed, as are web-based tools that work across cultures.

Cerebellar mutism: review of the literature.

PURPOSE: Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention. METHODS: We reviewed all peer-reviewed English publications on cerebellar mutism between the years of 1985 and 2009. The majority were found by searching for 'cerebellar mutism' and 'posterior fossa syndrome' in PubMed. Additional cases were identified by cross-checking reference lists. RESULTS: The overall incidence of postoperative cerebellar mutism is 11-29%, and patients with medulloblastomas and/or brainstem invasion are at a greater risk of developing it than those with other kinds of tumors and/or without brainstem invasion. Permanent sequelae in the form of both motor- and non-motor-related speech deficits are common, especially when the right cerebellar hemisphere is involved. The mutism is caused by bilateral pertubation of the dentate nuclei and their efferent pathways, which emphasizes the need to explore surgical methods that spare these structures. The pathophysiological mechanisms of delayed onset and resolution of cerebellar mutism are not clear, but axonal damage, edema, perfusional defects and metabolic disturbances may be involved. CONCLUSION: The incidence of cerebellar mutism is well documented in children with medulloblastoma, but precise figures for those with astrocytoma and ependymoma are lacking. Further anatomical, functional imaging and neuropsychological studies are needed to clarify the pathophysiological mechanisms in order to define preventive measures during surgery. Randomized, controlled trials of the effects of different medication and post-operative speech therapy are necessary for improving treatment.