Assessing evidence quality in research reporting neurocognitive outcomes following paediatric temporal lobe surgery for epilepsy.

PURPOSE: RCTs are the gold standard in determining intervention efficacy with journal impact factor assumed to index research quality. Flint et al's (2017) systematic review examined neurocognitive outcomes following paediatric temporal lobe epilepsy surgery. Retrieved evidence was restricted to non-RCTs, which pose greater risk of bias and thus diminish research quality. The current study evaluated risk of bias in sources retrieved by Flint et al. and explored whether impact factor related to research quality within this selected field. METHODS: Methodological and reporting bias was evaluated using categories of bias specified by Cochrane. The relationship between the identified number of biases and journal impact factors of retrieved sources was examined. RESULTS: All studies carried substantial risk for bias. Methodology bias included low sample size (76.71%; 56/73), risk of confounding cognitive outcomes due to failure to report pre-surgery neurocognitive data (21.92%; 16/73) and to determine whether patients were prescribed antiepileptic drugs at follow-up (53.42%; 39/73). Reporting bias included overstating claims based on findings (53.42%; 39/73), failure to report individual patient characteristics (66%; 33/50) and omitting the nature of surgical interventions (15.07%; 11/73). The number of sources of common bias within studies was not associated significantly with journal impact factor (p = .878). CONCLUSION: This evaluation highlights risk of bias when sources are predominantly uncontrolled non-RCTs and provides evidence that journal impact factor is not a reliable indicator of quality within this field. Authors should limit bias in their methods and reporting of results, to ensure the highest quality evidence possible is used to inform treatment decisions and prognosis.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

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.

Improving access to pediatric neurorehabilitation for patients with moderate and severe head injuries.

INTRODUCTION: The majority of severely injured children in England have a significant head injury and will be seen in Major Trauma Centers (MTCs). The period following brain injury represents an opportunity to influence recovery of neurological function. The study sought to determine whether children who had sustained a head injury were referred for neurorehabilitation. METHOD: The study was conducted over one year at one center. Children sustaining a moderate or severe head injury were identified and compared to those referred for neurorehabilitation. RESULTS: A total of 41 patients were identified; 16/41 (39%) were referred for neurorehabilitation. Group comparison revealed significant associations between referral status and age (X2(3) = 8.35, p = 0.039), injury mechanism (X2(1) = 8.12, p = 0.017), injury severity (X2(1) = 21.3, p < 0.000), and imaging findings (X2(1) = 11.71, p = 0.001). DISCUSSION: Data reveal concerns for access to neurorehabilitation. Improved access to neurorehabilitation permitting long-term follow-up is required. The establishment of MTCs provides an opportunity to enact this.

Interventions for managing weight change following paediatric acquired brain injury: a systematic review.

OBJECTIVE: To systematically review literature reporting interventions for weight change following paediatric acquired brain injury (ABI). METHOD: A systematic search of the literature was conducted using advanced search techniques. The retrieval identified 1562 papers, of which 30 were relevant. The total number of paediatric participants was 759. RESULTS: There is a paucity of higher quality evidence to support the use of weight change interventions following paediatric ABI. Substantial variation in screening, outcome measures, intervention, and reporting were demonstrated. Some support was found for the use of hypothalamic-sparing surgery as a method to prevent obesity following craniopharyngioma resection. INTERPRETATION: There is a need for further study in this area to inform clinical and research practice; recommendations are given.

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

PURPOSE: 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. METHODS: A systematic search and retrieval of databases was conducted using advanced search techniques. Review/outcomes criteria were developed, and study quality was determined. RESULTS: 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. CONCLUSIONS: 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.

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.

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.

Clinical reasoning and investigations for resective surgery for medically refractory epilepsies in children.

The article presents results of a UK survey of pediatric neurologists' views regarding resective surgery for medically refractory epilepsies in children. In contrast to surveys with adult neurologists, the findings indicate that delays to surgery in the pediatric field are not likely to be due to clinicians' views. There is, however, variability in clinicians' opinions as to what constitutes medically refractory epilepsy, variability in the factors reported as necessary for surgery eligibility, and uncertainty as to how these concepts should be defined. The survey highlights the need for elucidation of the epilepsy surgery process for pediatric patients, clear communication between epilepsy surgery centers and referring neurologists, and dissemination of consensus guidelines relating to the criteria for both medically refractory epilepsy and surgery eligibility.

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. METHODS: Two questionnaire surveys: a questionnaire examining the provision by pediatric neurologists of SUDEP information, and questionnaires examining parental beliefs and implications at two time points regarding SUDEP information provided in a leaflet. Participants were included in the study if their child had an established diagnosis of epilepsy. Factors for exclusion were single unprovoked seizure, absence seizures, patients in remission, and active discontinuation of treatment. RESULTS: The majority (74%) of pediatric neurologists provided SUDEP information only to a select group of children with epilepsy and were uncertain about the effect such information would have upon the parent and child. Conversely, 91% of parents expected the pediatric neurologist to provide SUDEP risk information. The provision of this information did not have a significant immediate and longer-term negative impact. DISCUSSION: The majority of parents wanted to know about SUDEP and its associated risks. Whenever possible, SUDEP information should be given by the physician accompanied by an information leaflet.