Matthew C.H.J. Morrall

Parental and physician beliefs regarding the provision and content of written sudden unexpected death in epilepsy (SUDEP) information

Purpose:  The 2007 UK National Institute for Health and Clinical Excellence (NICE) guidelines for epilepsy recommend disclosing the risk of sudden unexpected death in epilepsy (SUDEP) to patients. This recommendation is not undertaken routinely, and considerable variation in individual physician practice exists. Literature indicates wariness of causing distress and anxiety, particularly to children/young people and their families through disclosing a nonpreventable risk. There has been no systematic pediatric study examining parent/guardian information needs and beliefs for risk of SUDEP and its impact on seizure management. It is important to first address these concerns before routinely imparting SUDEP information to parents following NICE recommendations.

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

PurposeCerebellar 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.MethodsA systematic search and retrieval of databases was conducted using advanced search techniques. Review/outcomes criteria were developed, and study quality was determined.ResultsThe 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.ConclusionsThe 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.

The use of stimulant medication to improve neurocognitive and learning outcomes in children diagnosed with brain tumours: A systematic review

PURPOSE Impaired attention is reported in children following treatment for brain tumours (BT). Attention problems impact on information processing and encoding, ultimately leading to academic under-performance. Having been successfully used to manage attention-deficit/hyperactivity disorder (ADHD), stimulants such as methylphenidate (MPH) have been investigated as a beneficial treatment for survivors of childhood BT. In order to develop appropriate strategies to manage late neurocognitive effects, the results of such trials should be evaluated to identify those children most likely to benefit from stimulants. DESIGN An advanced search was performed across twelve electronic databases for the selection of relevant randomised controlled trials with at least one active stimulant-treated arm. Abstracts were screened for eligibility and data on study design and results were extracted. RESULTS Of the 5446 records identified, 11 full text articles were assessed for eligibility and seven included in qualitative synthesis. Of the seven papers there were four original trials. Short term outcomes for MPH on objective direct measures of attention and parent/teacher ratings of behaviour were favourable. Observations of side effects indicate that MPH is generally well tolerated. Heterogeneity of study design and outcome measures precluded meta-analysis. CONCLUSION Despite yielding only a small number of trials with limited sample size, studies investigating the use of stimulant medication in survivors of childhood BT have provided promising outcomes. Current evidence indicates males, older age when treated, and higher baseline intelligence quotient (IQ) were predictive of greater responsiveness to MPH. While encouraging, additional research using a standardised protocol of outcome measures would be beneficial in identifying those likely to benefit from stimulant use. Further, the available data have yet to establish clear evidence for the effectiveness of MPH being translated into improvements on standardised measures of academic achievement.

Question 3 Should stimulants be administered to manage diffi culties with attention, hyperactivity and impulsivity following paediatric acquired brain injury?

An 11-year-old boy is struck by a car and sustains an acquired brain injury (ABI). He is admitted with a Glasgow Coma Scale score of 6/15. Cranial imaging reveals evidence of diffuse injury. Approximately 12 months later following discharge, the patient is seen for a planned review. The patient and his family report poor attention with hyperactive and impulsive behaviours. The school has reported to parents that there has been a change in his ability to concentrate at school and he is being disruptive in class. This represents a clear departure from the patients preinjury behaviour. Parental and school management of this concerning conduct is structured and consistent. You have heard that stimulant medication may be of benefit in managing difficulties with attention, hyperactivity and impulsivity (attention deficit hyperactivity disorder (ADHD) type behaviours) following an ABI. For children with an acquired brain injury [patient], does the administration of stimulant medication [intervention] help address inattention, impulsivity and hyperactivity [outcomes]? ### Secondary sources The Cochrane Library (including Cochrane Reviews, Database of Abstracts of Review of Effects and Clinical Trials) was searched. ### Primary sources Using a combination of subject headings and keyword terms, an advanced search was conducted of AMED (1985–present), BIOSIS Previews (1969–present), CAB Abstracts (1910–present), EMBASE (1947–present), Medline (1950–present), PsycINFO (1806–present), CINAHL (1981–present), Google Scholar, Global Health (1973–present) and Conference Papers Index for conference proceedings (1982–present). ### Search terms Search terms (designed for Medline and tailored accordingly for other sources) were: (exp Brain Injuries/OR Brain Neoplasms/ OR brain adj2 injur* …

The effectiveness and safety of proton beam radiation therapy in children with malignant central nervous system (CNS) tumours: protocol for a systematic review

BackgroundThe aim of this study is to use a systematic review framework to identify and synthesise the evidence on the use of proton beam therapy (PBT) for the treatment of children with CNS tumours and where possible compare this to the use of photon radiotherapy (RT).MethodsStandard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Twelve electronic databases have been searched, and further citation, hand searching and reference checking will be employed. Studies assessing the effects of PBT used either alone or as part of a multimodality treatment regimen in children with CNS tumours will be included. Relevant economic evaluations will also be identified. The outcomes are survival (overall, progression-free, event-free, disease-free), local and regional control rates, short- and long-term adverse events, functional status measures and quality of survival. Two reviewers will independently screen and select studies for inclusion in the review. All interventional study designs will be eligible for inclusion in the review. However, initial scoping searches indicate the evidence base is likely to be limited to case series studies, with no studies of a higher quality being identified. Quality assessment will be undertaken using pre-specified criteria and tailored to study design if applicable. Studies will be combined using a narrative synthesis, with differences in results between studies highlighted and discussed in relation to the patient population, intervention and study quality. Where appropriate, if no studies of a comparative design are identified, outcomes will be compared against a range of estimates from the literature for similar populations and treatment regimens from the best available evidence from studies that include the use of advanced conventional photon therapy.DiscussionThe evidence base for the use of PBT in children with CNS tumours is likely to be relatively sparse, highly heterogeneous and potentially of a low quality with small sample sizes. Furthermore, selection and publication biases may limit the internal and external validity of studies. However, any tentative results from the review on potential treatment effects can be used to plan better quality research studies that are of a design appropriate for outcome comparison with conventional therapy.Systematic review registrationPROSPERO CRD42015029583

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

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.

Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging

PURPOSE A review of all published evidence for mapping eloquent (motor, language and memory) cortex using advanced functional neuroimaging (functional magnetic resonance imaging [fMRI] and magnetoencephalography [MEG]) for paediatric epilepsy surgery candidates has not been conducted previously. Research in this area has predominantly been in adult populations and applicability of these techniques to paediatric populations is less established. METHODS A review was performed using an advanced systematic search and retrieval of all published papers examining the use of functional neuroimaging for paediatric epilepsy surgery candidates. RESULTS Of the 2724 papers retrieved, 34 met the inclusion criteria. Total paediatric participants identified were 353 with an age range of 5 months-19 years. Sample sizes and comparisons with alternative investigations to validate techniques are small and variable paradigms are used. Sensitivity 0.72 (95% CI 0.52-0.86) and specificity 0.60 (95% CI 0.35-0.92) values with a Positive Predictive Value of 74% (95% CI 61-87) and a Negative Predictive Value of 65% (95% CI 52-78) for fMRI language lateralisation with validation, were obtained. Retrieved studies indicate evidence that both fMRI and MEG are able to provide information lateralising and localising motor and language functions. CONCLUSIONS A striking finding of the review is the paucity of studies (n=34) focusing on the paediatric epilepsy surgery population. For children, it remains unclear which language and memory paradigms produce optimal activation and how these should be quantified in a statistically robust manner. Consensus needs to be achieved for statistical analyses and the uniformity and yield of language, motor and memory paradigms. Larger scale studies are required to produce patient series data which clinicians may refer to interpret results objectively. If functional imaging techniques are to be the viable alternative for pre-surgical mapping of eloquent cortex for children, paradigms and analyses demonstrating concordance with independent measures must be developed.

Question 3 Should carbamazepine be administered to manage agitation and aggressive behaviour following paediatric acquired brain injury

A 14-year-old boy sustains a brain injury and is admitted with a Glasgow Coma Scale score of 3/15. Imaging reveals evidence of diffuse injury. Approximately 12 months later, the patient is seen for a planned review in an outpatient clinic. Full reintegration into school has occurred and clear cognitive and physical improvements are evident. Despite this, the patient and his family explain that unprovoked episodes of agitation, aggression and emotional lability occur. These have not lessened in frequency and represent a clear departure from the patients preinjury behaviour. Parental and school management of this concerning conduct is structured and consistent. You have heard that carbamazepine (CBZ) may be of value in managing post-injury agitation and aggression. For children with an acquired brain injury [patient] does the administration of carbamazepine [intervention] reduce agitation and aggressive behaviour [outcome]? ### Primary sources An advanced search of AMED, CINAHL, EMBASE, MEDLINE, psychINFO and Google Scholar was completed. All databases were searched from 1980 to the present (February 2010) except AMED, which was searched from 1985 to the present. ### Secondary sources Cochrane Library (including Cochrane Reviews, Database of Abstracts of Review of Effects (DARE) and Clinical Trials and BestBETS) were searched using the terms ‘brain injury’ and ‘aggress*’ and ‘paediat*’ or ‘child*’ in the ‘Search All Text’ fields: no relevant results were found. ### Search terms Search terms included: ((traumatic adj2 …

A Novel Functional Magnetic Resonance Imaging Paradigm for the Preoperative Assessment of Auditory Perception in a Musician Undergoing Temporal Lobe Surgery

BACKGROUND Presurgical evaluation for temporal lobe epilepsy routinely assesses speech and memory lateralization and anatomic localization of the motor and visual areas but not baseline musical processing. This is paramount in a musician. Although validated tools exist to assess musical ability, there are no reported functional magnetic resonance imaging (fMRI) paradigms to assess musical processing. We examined the utility of a novel fMRI paradigm in an 18-year-old left-handed pianist who underwent surgery for a left temporal low-grade ganglioglioma. METHODS Preoperative evaluation consisted of neuropsychological evaluation, T1-weighted and T2-weighted magnetic resonance imaging, and fMRI. Auditory blood oxygen level-dependent fMRI was performed using a dedicated auditory scanning sequence. Three separate auditory investigations were conducted: listening to, humming, and thinking about a musical piece. RESULTS All auditory fMRI paradigms activated the primary auditory cortex with varying degrees of auditory lateralization. Thinking about the piece additionally activated the primary visual cortices (bilaterally) and right dorsolateral prefrontal cortex. Humming demonstrated left-sided predominance of auditory cortex activation with activity observed in close proximity to the tumor. CONCLUSIONS This study demonstrated an fMRI paradigm for evaluating musical processing that could form part of preoperative assessment for patients undergoing temporal lobe surgery for epilepsy.

Neuropsychological outcomes following paediatric temporal lobe surgery for epilepsies: Evidence from a systematic review

OBJECTIVE The systematic review aimed to assess the neuropsychological outcomes of temporal lobe resections for epilepsy in children. Additional objectives included determining whether earlier age at surgery leads to better neuropsychological outcomes; the relationships between and predictors of these outcomes. METHODS Using advanced search terms, a systematic review of electronic databases was conducted, comprising MEDLINE, Embase, PsycINFO, Global Health, Web of Science and CINAHL. Included studies reported on outcome following neurosurgical treatment for epilepsy. Specifically, studies were included if they reported neuropsychological outcomes and were concerned only with temporal lobe resection. RESULTS 73 studies met inclusion criteria. For reported neuropsychological outcomes, the majority of participants remained stable after surgery; some declined and some improved. There was some evidence for increased material-specific memory deficits after temporal lobe surgery based on resection side, and more positive cognitive outcome for those with lower pre-surgical ability level. SIGNIFICANCE Retrieved evidence highlights the need for improvements to quality of methodology and reporting. Appropriately designed prospective multicentre trials should be conducted with adequate follow-up for long-term outcomes to be measured. Core outcome measures should be agreed between centres. This would permit higher quality evidence so that clinicians, young people and their families may make better informed decisions about whether or not to proceed with surgery and likely post-operative profile.