Impact of transcranial magnetic stimulation on motor function in children with acquired brain injury: a scoping review protocol.

BACKGROUND: Children with severe acquired brain injury (ABI) require early and effective neurorehabilitation provision to promote a good long-term functional outcome. Transcranial magnetic stimulation (TMS) has been used to improve motor skills for children with cerebral palsy but there is limited material supporting its use in children with ABI who have a motor disorder. OBJECTIVE: To systematically answer what the TMS intervention effects are on motor function in children with ABI as reported in the literature. METHODS AND ANALYSIS: This scoping review will follow Arksey and O'MaIIey's scoping review methodological framework. A comprehensive computerised bibliographic databases search will be performed in MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine, BNI, Ovid Emcare, PsyclNFO, Physiotherapy Evidence Database, Cochrane Central Register using keywords related to TMS and children with ABI.Studies that examine the effect of TMS intervention on motor function as either a primary or secondary objective will be included for this review. Study design and publication detail, participant demographic details, type and severity of ABI and other clinical information, TMS procedure, associated therapy intervention, comparator/control parameters and the outcome measure used data will be gathered.The International Classification of Functioning, Disability and Health for Children and Youth framework will be used to report the TMS effect in children with ABI. A narrative synthesis of the findings describing the therapeutic effects of TMS intervention, limitations and adverse effects will be synthesised and reported. This review will help to summarise the existing knowledge base and to guide further research areas. This review outcome may help to evolve therapists' role to next-generation technology-based neurorehabilitation programmes. ETHICS AND DISSEMINATION: No ethical approval is required for this review as we will be collecting data from previously published studies. We will present the findings at scientific conferences and publish in a peer-review journal.

MEG detection of high frequency oscillations and intracranial-EEG validation in pediatric epilepsy surgery.

OBJECTIVE: To assess the feasibility of automatically detecting high frequency oscillations (HFOs) in magnetoencephalography (MEG) recordings in a group of ten paediatric epilepsy surgery patients who had undergone intracranial electroencephalography (iEEG). METHODS: A beamforming source-analysis method was used to construct virtual sensors and an automatic algorithm was applied to detect HFOs (80-250 Hz). We evaluated the concordance of MEG findings with the sources of iEEG HFOs, the clinically defined seizure onset zone (SOZ), the location of resected brain structures, and with post-operative outcome. RESULTS: In 8/9 patients there was good concordance between the sources of MEG HFOs and iEEG HFOs and the SOZ. Significantly more HFOs were detected in iEEG relative to MEG t(71) = 2.85, p < .05. There was good concordance between sources of MEG HFOs and the resected area in patients with good and poor outcome, however HFOs were also detected outside of the resected area in patients with poor outcome. CONCLUSION: Our findings demonstrate the feasibility of automatically detecting HFOs non-invasively in MEG recordings in paediatric patients, and confirm compatibility of results with invasive recordings. SIGNIFICANCE: This approach provides support for the non-invasive detection of HFOs to aid surgical planning and potentially reduce the need for invasive monitoring, which is pertinent to paediatric patients.

Pediatric stereo-electroencephalography: effects of robot assistance and other variables on seizure outcome and complications.

OBJECTIVE: The safety of stereo-electroencephalography (SEEG) has been investigated; however, most studies have not differentiated pediatric and adult populations, which have different anatomy and physiology. The purpose of this study was to assess SEEG safety in the pediatric setting, focusing on surgical complications and the identification of patient and surgical risk factors, if any. The authors also aimed to determine whether robot assistance in SEEG was associated with a change in practice, surgical parameters, and clinical outcomes. METHODS: The authors retrospectively studied all SEEG cases performed in their department from December 2014 to March 2020. They analyzed both demographic and surgical variables and noted the types of surgery-related complications and their management. They also studied the clinical outcomes of a subset of the patients in relation to robot-assisted and non-robot-assisted SEEG. RESULTS: Sixty-three children had undergone 64 SEEG procedures. Girls were on average 3 years younger than the boys (mean age 11.1 vs 14.1 years, p < 0.01). The overall complication rate was 6.3%, and the complication rate for patients with left-sided electrodes was higher than that for patients with right-sided electrodes (11.1% vs 3.3%), although the difference between the two groups was not statistically significant. The duration of recording was positively correlated to the number of implanted electrodes (r = 0.296, p < 0.05). Robot assistance was associated with a higher number of implanted electrodes (mean 12.6 vs 7.6 electrodes, p < 0.0001). Robot-assisted implantations were more accurate, with a mean error of 1.51 mm at the target compared to 2.98 mm in nonrobot implantations (p < 0.001). Clinical outcomes were assessed in the first 32 patients treated (16 in the nonrobot group and 16 in the robot group), 23 of whom proceeded to further resective surgery. The children who had undergone robot-assisted SEEG had better eventual seizure control following subsequent epilepsy surgery. Of the children who had undergone resective epilepsy surgery, 42% (5/12) in the nonrobot group and 82% (9/11) in the robot group obtained an Engel class IA outcome at 1 year (χ2 = 3.885, p = 0.049). Based on Kaplan-Meier survival analysis, the robot group had a higher seizure-free rate than the nonrobot group at 30 months postoperation (7/11 vs 2/12, p = 0.063). Two complications, whose causes were attributed to the implantation and head-bandaging steps, required surgical intervention. All complications were either transient or reversible. CONCLUSIONS: This is the largest single-center, exclusively pediatric SEEG series that includes robot assistance so far. SEEG complications are uncommon and usually transient or treatable. Robot assistance enabled implantation of more electrodes and improved epilepsy surgery outcomes, as compared to those in the non-robot-assisted cases.

Reliability in the assessment of paediatric somatosensory evoked potentials post cardiac arrest.

OBJECTIVE: To measure inter- and intra-rater agreement in the interpretation of cortical somatosensory evoked potential (SSEP) components following paediatric cardiac arrest (CA) in multi-professional neurophysiology teams. METHODS: Thirteen professionals blinded to patient outcome interpreted 96 SSEPs in paediatric patients 24-/48-/72-hours following CA. Of these, 34 were duplicates used to assess intra-rater agreement. Consistent interpretations (absent/present/indeterminate) between scientists (who record/identify SSEP components) and neurophysiologists (who provide prognostic SSEP interpretation) were expressed as percentages. Rates of agreement were calculated using Fleiss' kappa coefficient (K). RESULTS: Unanimous agreement between professionals was present in 40% (95%CI: 28-54%) of the interpreted SSEPs, with a K value of 0.62 (95%CI: 0.55-0.70) based on average agreement. Agreement was similar between neurophysiologists (K = 0.67; 95%CI: 0.57-0.77) and scientists (K = 0.62; 95%CI: 0.54-0.70) but lower in patients < 2 years old (K = 0.23; 95%CI: 0.14-0.33) and in those with poor outcome (K = 0.21; 95%CI: 0.07-0.35). No SSEP was unanimously interpreted as absent and 92% (95%CI: 89-95%) of duplicate SSEPs were interpreted consistently. CONCLUSION: Despite substantial agreement when interpreting prognostic SSEPs, this was significantly lower in children with poor outcome and of younger age. SIGNIFICANCE: Clinicians using SSEPs in the intensive care unit should be aware of the inter-rater variability when interpreting SSEPs as absent.

The Prognostic Value of Somatosensory Evoked Potentials in Children After Cardiac Arrest: The SEPIA Study.

PURPOSE: Absent cortical somatosensory evoked potentials (SSEPs) reliably predict poor neurologic outcome in adults after cardiac arrest (CA). However, there is less evidence to support this in children. In addition, targeted temperature management, test timing, and a lack of blinding may affect test accuracy. METHODS: A single-center, prospective cohort study of pediatric (aged 24 hours to 15 years) patients in which prognostic value of SSEPs were assessed 24, 48, and 72 hours after CA. Targeted temperature management (33-34°C for 24 hours) followed by gradual rewarming to 37°C was used. Somatosensory evoked potentials were graded as present, absent, or indeterminate, and results were blinded to clinicians. Neurologic outcome was graded as "good" (score 1-3) or "poor" (4-6) using the Pediatric Cerebral Performance Category scale 30 days after CA and blinded to SSEP interpreter. RESULTS: Twelve patients (median age, 12 months; interquartile range, 2-150; 92% male) had SSEPs interpreted as absent (6/12) or present (6/12) <72 hours after CA. Outcome was good in 7 of 12 patients (58%) and poor in 5 of 12 patients (42%). Absent SSEPs predicted poor outcome with 88% specificity (95% confidence interval, 53% to 98%). One patient with an absent SSEP had good outcome (Pediatric Cerebral Performance Category 3), and all patients with present SSEPs had good outcome (specificity 100%; 95% confidence interval, 51% to 100%). Absence or presence of SSEP was consistent across 24-hour (temperature = 34°C), 48-hour (t = 36°C), and 72-hour (t = 36°C) recordings after CA. CONCLUSIONS: Results support SSEP utility when predicting favorable outcome; however, predictions resulting in withdrawal of life support should be made with caution and never in isolation because in this very small sample there was a false prediction of unfavorable outcome. Further prospective, blinded studies are needed and encouraged.

Mapping language networks and their association with verbal abilities in paediatric epilepsy using MEG and graph analysis.

Recent theoretical models of language have emphasised the importance of integration within distributed networks during language processing. This is particularly relevant to young patients with epilepsy, as the topology of the functional network and its dynamics may be altered by the disease, resulting in reorganisation of functional language networks. Thus, understanding connectivity within the language network in patients with epilepsy could provide valuable insights into healthy and pathological brain function, particularly when combined with clinical correlates. The objective of this study was to investigate interactions within the language network in a paediatric population of epilepsy patients using measures of MEG phase synchronisation and graph-theoretical analysis, and to examine their association with language abilities. Task dependent increases in connectivity were observed in fronto-temporal networks during verb generation across a group of 22 paediatric patients (9 males and 13 females; mean age 14 years). Differences in network connectivity were observed between patients with typical and atypical language representation and between patients with good and poor language abilities. In addition, node centrality in left frontal and temporal regions was significantly associated with language abilities, where patients with good language abilities had significantly higher node centrality within inferior frontal and superior temporal regions of the left hemisphere, compared to patients with poor language abilities. Our study is one of the first to apply task-based measures of MEG network synchronisation in paediatric epilepsy, and we propose that these measures of functional connectivity and node centrality could be used as tools to identify critical regions of the language network prior to epilepsy surgery.

Implementation and Early Evaluation of a Quantitative Electroencephalography Program for Seizure Detection in the PICU.

OBJECTIVES: To describe implementation and early evaluation of using quantitative electroencephalography for electrographic seizure detection by PICU clinician staff. DESIGN: Prospective observational study of electrographic seizure detection by PICU clinicians in patients monitored with quantitative electroencephalography. Quantitative electroencephalography program implementation included a continuous education and training package. Continuous quantitative electroencephalography monitoring consisted of two-channel amplitude-integrated electroencephalography, color density spectral array, and raw-electroencephalography. SETTING: PICU. PATIENTS: Children less than 18 years old admitted to the PICU during the 14-month study period and deemed at risk of electrographic seizure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Real time electrographic seizure detection by a PICU team was analyzed for diagnostic accuracy and promptness, against electrographic seizure identification by a trained neurophysiologist, retrospectively reading the same quantitative electroencephalography and blinded to patient details. One-hundred one of 1,510 consecutive admissions (6.7%) during the study period underwent quantitative electroencephalography monitoring. Status epilepticus (35%) and suspected hypoxic-ischemic injury (32%) were the most common indications for quantitative electroencephalography. Electrographic seizure was diagnosed by the neurophysiologist in 12% (n = 12) of the cohort. PICU clinicians correctly diagnosed all 12 patients (100% sensitivity and negative predictive value). An additional eleven patients had a false-positive diagnosis of electrographic seizure (false-positive rate = 52% [31-73%]) leading to a specificity of 88% (79-94%). Median time to detect seizures was 25 minutes (5-218 min). Delayed recognition of electrographic seizure (> 1 hr from onset) occurred in five patients (5/12, 42%). CONCLUSIONS: Early evaluation of quantitative electroencephalography program to detect electrographic seizure by PICU clinicians suggested good sensitivity for electrographic seizure detection. However, the high false-positive rate is a challenge. Ongoing work is needed to reduce the false positive diagnoses and avoid electrographic seizure detection delays. A comprehensive training program and regular refresher updates for clinical staff are key components of the program.

MEG Assessment of Expressive Language in Children Evaluated for Epilepsy Surgery.

Establishing language dominance is an important step in the presurgical evaluation of patients with refractory epilepsy. In the absence of a universally accepted gold-standard non-invasive method to determine language dominance in the preoperative assessment, a range of tools and methodologies have recently received attention. When applied to pediatric age, many of the proposed methods, such as functional magnetic resonance imaging (fMRI), may present some challenges due to the time-varying effects of epileptogenic lesions and of on-going seizures on maturational phenomena. Magnetoencephalography (MEG) has the advantage of being insensitive to the distortive effects of anatomical lesions on brain microvasculature and to differences in the metabolism or vascularization of the developing brain and also provides a less intimidating recording environment for younger children. In this study we investigated the reliability of lateralized synchronous cortical activation during a verb generation task in a group of 28 children (10 males and 18 females, mean age 12 years) with refractory epilepsy who were evaluated for epilepsy surgery. The verb generation task was associated with significant decreases in beta oscillatory power (13-30 Hz) in frontal and temporal lobes. The MEG data were compared with other available presurgical non-invasive data including cortical stimulation, neuropsychological and fMRI data on language lateralization where available. We found that the lateralization of MEG beta power reduction was concordant with language dominance determined by one or more different assessment methods (i.e. cortical stimulation mapping, neuropsychological, fMRI or post-operative data) in 89% of patients. Our data suggest that qualitative hemispheric differences in task-related changes of spectral power could offer a promising insight into the contribution of dominant and non-dominant hemispheres in language processing and may help to characterize the specialization and lateralization of language processes in children.

Consensus-based guidelines for Video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK.

PURPOSE: Paediatric Epilepsy surgery in the UK has recently been centralised in order to improve expertise and quality of service available to children. Video EEG monitoring or telemetry is a highly specialised and a crucial component of the pre-surgical evaluation. Although many Epilepsy Monitoring Units work to certain standards, there is no national or international guideline for paediatric video telemetry. METHODS: Due to lack of evidence we used a modified Delphi process utilizing the clinical and academic expertise of the clinical neurophysiology sub-specialty group of Children's Epilepsy Surgical Service (CESS) centres in England and Wales. This process consisted of the following stages I: Identification of the consensus working group, II: Identification of key areas for guidelines, III: Consensus practice points and IV: Final review. Statements that gained consensus (median score of either 4 or 5 using a five-point Likerttype scale) were included in the guideline. RESULTS: Two rounds of feedback and amendments were undertaken. The consensus guidelines includes the following topics: referral pathways, neurophysiological equipment standards, standards of recording techniques, with specific emphasis on safety of video EEG monitoring both with and without drug withdrawal, a protocol for testing patient's behaviours, data storage and guidelines for writing factual reports and conclusions. All statements developed received a median score of 5 and were adopted by the group. CONCLUSION: Using a modified Delphi process we were able to develop universally-accepted video EEG guidelines for the UK CESS. Although these recommendations have been specifically developed for the pre-surgical evaluation of children with epilepsy, it is assumed that most components are transferable to any paediatric video EEG monitoring setting.