Lessons learned from the COVID-19 pandemic: Improving initial investigations with the implementation of a COVID-19 blood request panel.

BACKGROUND: During the COVID-19 pandemic, the Hillingdon Hospitals NHS Foundation Trust produced trust guidelines for the initial blood investigation of COVID-19 inpatients. However, insufficient education meant inconsistent adherence to this guidance. OBJECTIVE: To examine whether the implementation of a COVID-19 blood request panel improves adherence to local trust guidelines. METHOD: Between March and April 2020, initial blood investigations performed for positive COVID-19 cases were compared to guidelines. Results were presented locally and a COVID-19 panel was added to the electronic system that provided prompts for appropriate investigations. A re-audit between May and June 2020 was conducted to assess adherence post-intervention. RESULTS: 383 patients were identified in the initial audit cohort and a sample of 20 patients were re-audited. Adherence to Full Blood Count, Urea and Electrolytes, C-reactive Protein and Liver Function Tests increased to 100% from 99.7% (p = 0.8), 99.2% (p = 0.69), 98.7% (p = 0.61), and 96.6% (p = 0.4) respectively. Coagulation screen adherence increased to 90% from 72.8% (p = 0.09). Appropriate requesting of D dimers increased to 50% from 19.9% (p = 0.001). Inappropriate troponin requesting decreased to 26.3% from 38.9% (p = 0.23). CONCLUSION: A user-friendly COVID-19 panel of investigations resulted in improved adherence to guidelines. Clear communication and education are essential to help alleviate uncertainty during a pandemic.

Presurgical accuracy of dipole clustering in MRI-negative pediatric patients with epilepsy: Validation against intracranial EEG and resection.

OBJECTIVE: To assess the utility of interictal magnetic and electric source imaging (MSI and ESI) using dipole clustering in magnetic resonance imaging (MRI)-negative patients with drug resistant epilepsy (DRE). METHODS: We localized spikes in low-density (LD-EEG) and high-density (HD-EEG) electroencephalography as well as magnetoencephalography (MEG) recordings using dipoles from 11 pediatric patients. We computed each dipole's level of clustering and used it to discriminate between clustered and scattered dipoles. For each dipole, we computed the distance from seizure onset zone (SOZ) and irritative zone (IZ) defined by intracranial EEG. Finally, we assessed whether dipoles proximity to resection was predictive of outcome. RESULTS: LD-EEG had lower clusterness compared to HD-EEG and MEG (p < 0.05). For all modalities, clustered dipoles showed higher proximity to SOZ and IZ than scattered (p < 0.001). Resection percentage was higher in optimal vs. suboptimal outcome patients (p < 0.001); their proximity to resection was correlated to outcome (p < 0.001). No difference in resection percentage was seen for scattered dipoles between groups. CONCLUSION: MSI and ESI dipole clustering helps to localize the SOZ and IZ and facilitate the prognostic assessment of MRI-negative patients with DRE. SIGNIFICANCE: Assessing the MSI and ESI clustering allows recognizing epileptogenic areas whose removal is associated with optimal outcome.

Source imaging of seizure onset predicts surgical outcome in pediatric epilepsy.

OBJECTIVE: To assess whether ictal electric source imaging (ESI) on low-density scalp EEG can approximate the seizure onset zone (SOZ) location and predict surgical outcome in children with refractory epilepsy undergoing surgery. METHODS: We examined 35 children with refractory epilepsy. We dichotomized surgical outcome into seizure- and non-seizure-free. We identified ictal onsets recorded with scalp and intracranial EEG and localized them using equivalent current dipoles and standardized low-resolution magnetic tomography (sLORETA). We estimated the localization accuracy of scalp EEG as distance of scalp dipoles from intracranial dipoles. We also calculated the distances of scalp dipoles from resection, as well as their resection percentage and compared between seizure-free and non-seizure-free patients. We built receiver operating characteristic curves to test whether resection percentage predicted outcome. RESULTS: Resection distance was lower in seizure-free patients for both dipoles (p = 0.006) and sLORETA (p = 0.04). Resection percentage predicted outcome with a sensitivity of 57.1% (95% CI, 34-78.2%), a specificity of 85.7% (95% CI, 57.2-98.2%) and an accuracy of 68.6% (95% CI, 50.7-83.5%) (p = 0.01). CONCLUSION: Ictal ESI performed on low-density scalp EEG can delineate the SOZ and predict outcome. SIGNIFICANCE: Such an application may increase the number of children who are referred for epilepsy surgery and improve their outcome.

Development, validation, and pilot MRI safety study of a high-resolution, open source, whole body pediatric numerical simulation model.

Numerical body models of children are used for designing medical devices, including but not limited to optical imaging, ultrasound, CT, EEG/MEG, and MRI. These models are used in many clinical and neuroscience research applications, such as radiation safety dosimetric studies and source localization. Although several such adult models have been reported, there are few reports of full-body pediatric models, and those described have several limitations. Some, for example, are either morphed from older children or do not have detailed segmentations. Here, we introduce a 29-month-old male whole-body native numerical model, "MARTIN", that includes 28 head and 86 body tissue compartments, segmented directly from the high spatial resolution MRI and CT images. An advanced auto-segmentation tool was used for the deep-brain structures, whereas 3D Slicer was used to segment the non-brain structures and to refine the segmentation for all of the tissue compartments. Our MARTIN model was developed and validated using three separate approaches, through an iterative process, as follows. First, the calculated volumes, weights, and dimensions of selected structures were adjusted and confirmed to be within 6% of the literature values for the 2-3-year-old age-range. Second, all structural segmentations were adjusted and confirmed by two experienced, sub-specialty certified neuro-radiologists, also through an interactive process. Third, an additional validation was performed with a Bloch simulator to create synthetic MR image from our MARTIN model and compare the image contrast of the resulting synthetic image with that of the original MRI data; this resulted in a "structural resemblance" index of 0.97. Finally, we used our model to perform pilot MRI safety simulations of an Active Implantable Medical Device (AIMD) using a commercially available software platform (Sim4Life), incorporating the latest International Standards Organization guidelines. This model will be made available on the Athinoula A. Martinos Center for Biomedical Imaging website.

The impact of the COVID-19 pandemic on final year medical students in the United Kingdom: a national survey.

BACKGROUND: The coronavirus disease (COVID-19) global pandemic has resulted in unprecedented public health measures. This has impacted the UK education sector with many universities halting campus-based teaching and examinations. The aim of this study is to identify the impact of COVID-19 on final year medical students' examinations and placements in the United Kingdom (UK) and how it might impact their confidence and preparedness going into their first year of foundation training. METHODS: A 10-item online survey was distributed to final year medical students across 33 UK medical schools. The survey was designed by combining dichotomous, multiple choice and likert response scale questions. Participants were asked about the effect that the COVID-19 global pandemic had on final year medical written exams, electives, assistantships and objective structured clinical examinations (OSCEs). The survey also explored the student's confidence and preparedness going into their first year of training under these new unprecedented circumstances. RESULTS: Four hundred forty students from 32 UK medical schools responded. 38.4% (n = 169) of respondents had their final OSCEs cancelled while 43.0% (n = 189) had already completed their final OSCEs before restrictions. 43.0% (n = 189) of assistantship placements were postponed while 77.3% (n = 340) had electives cancelled. The impact of COVID-19 on OSCEs, written examinations and student assistantships significantly affected students' preparedness (respectively p = 0.025, 0.008, 0.0005). In contrast, when measuring confidence, only changes to student assistantships had a significant effect (p = 0.0005). The majority of students feel that measures taken during this pandemic to amend their curricula was necessary. Respondents also agree that assisting in hospitals during the outbreak would be a valuable learning opportunity. CONCLUSIONS: The impact on medical student education has been significant, particularly affecting the transition from student to doctor. This study showed the disruptions to student assistantships had the biggest effect on students' confidence and preparedness. For those willing to assist in hospitals to join the front-line workforce, it is crucial to maintain their wellbeing with safeguards such as proper inductions, support and supervision.

Scalp ripples as prognostic biomarkers of epileptogenicity in pediatric surgery.

OBJECTIVE: To assess the ability of high-density Electroencephalography (HD-EEG) and magnetoencephalography (MEG) to localize interictal ripples, distinguish between ripples co-occurring with spikes (ripples-on-spike) and independent from spikes (ripples-alone), and evaluate their localizing value as biomarkers of epileptogenicity in children with medically refractory epilepsy. METHODS: We retrospectively studied 20 children who underwent epilepsy surgery. We identified ripples on HD-EEG and MEG data, localized their generators, and compared them with intracranial EEG (icEEG) ripples. When ripples and spikes co-occurred, we performed source imaging distinctly on the data above 80 Hz (to localize ripples) and below 70 Hz (to localize spikes). We assessed whether missed resection of ripple sources predicted poor outcome, separately for ripples-on-spikes and ripples-alone. Similarly, predictive value of spikes was calculated. RESULTS: We observed scalp ripples in 16 patients (10 good outcome). Ripple sources were highly concordant to the icEEG ripples (HD-EEG concordance: 79%; MEG: 83%). When ripples and spikes co-occurred, their sources were spatially distinct in 83-84% of the cases. Removing the sources of ripples-on-spikes predicted good outcome with 90% accuracy for HD-EEG (P = 0.008) and 86% for MEG (P = 0.044). Conversely, removing ripples-alone did not predict outcome. Resection of spike sources (generated at the same time as ripples) predicted good outcome for HD-EEG (P = 0.036; accuracy = 87%), while did not reach significance for MEG (P = 0.1; accuracy = 80%). INTERPRETATION: HD-EEG and MEG localize interictal ripples with high precision in children with refractory epilepsy. Scalp ripples-on-spikes are prognostic, noninvasive biomarkers of epileptogenicity, since removing their cortical generators predicts good outcome. Conversely, scalp ripples-alone are most likely generated by non-epileptogenic areas.

Ictal and interictal source imaging on intracranial EEG predicts epilepsy surgery outcome in children with focal cortical dysplasia.

OBJECTIVE: To localize the seizure onset zone (SOZ) and irritative zone (IZ) using electric source imaging (ESI) on intracranial EEG (iEEG) and assess their clinical value in predicting epilepsy surgery outcome in children with focal cortical dysplasia (FCD). METHODS: We analyzed iEEG data from 25 children with FCD-associated medically refractory epilepsy (MRE) who underwent surgery. We performed ESI on ictal onset to localize SOZ (ESI-SOZ) and on interictal discharges to localize IZ (ESI-IZ). We tested whether resection of ESI-SOZ and ESI-IZ predicted good surgical outcome (Engel 1). We further compared the prediction performance of ESI-SOZ and ESI-IZ to those of SOZ and IZ defined using conventional methods, i.e. by identifying iEEG-contacts showing ictal onsets (conventional-SOZ) or being the most interictally active (conventional-IZ). RESULTS: The proximity of ESI-SOZ (p = 0.043, odds-ratio = 3.9) and ESI-IZ (p = 0.011, odds-ratio = 7.04) to resection has higher effect on patients' outcome than proximity of conventional-SOZ (p = 0.17, odds-ratio = 1.7) and conventional-IZ (p = 0.038, odds-ratio = 2.6). Resection of ESI-SOZ and ESI-IZ presented higher discriminative power in predicting outcome (68% and 60%) than conventional-SOZ and conventional-IZ (48% and 53%). CONCLUSIONS: Localizing SOZ and IZ via ESI on iEEG offers higher predictive value compared to conventional-iEEG interpretation. SIGNIFICANCE: iEEG-ESI may help surgical planning and facilitate prognostic assessment of children with FCD-associated MRE.

Assessing the localization accuracy and clinical utility of electric and magnetic source imaging in children with epilepsy.

OBJECTIVE: To evaluate the accuracy and clinical utility of conventional 21-channel EEG (conv-EEG), 72-channel high-density EEG (HD-EEG) and 306-channel MEG in localizing interictal epileptiform discharges (IEDs). METHODS: Twenty-four children who underwent epilepsy surgery were studied. IEDs on conv-EEG, HD-EEG, MEG and intracranial EEG (iEEG) were localized using equivalent current dipoles and dynamical statistical parametric mapping (dSPM). We compared the localization error (ELoc) with respect to the ground-truth Irritative Zone (IZ), defined by iEEG sources, between non-invasive modalities and the distance from resection (Dres) between good- (Engel 1) and poor-outcomes. For each patient, we estimated the resection percentage of IED sources and tested whether it predicted outcome. RESULTS: MEG presented lower ELoc than HD-EEG and conv-EEG. For all modalities, Dres was shorter in good-outcome than poor-outcome patients, but only the resection percentage of the ground-truth IZ and MEG-IZ predicted surgical outcome. CONCLUSIONS: MEG localizes the IZ more accurately than conv-EEG and HD-EEG. MSI may help the presurgical evaluation in terms of patient's outcome prediction. The promising clinical value of ESI for both conv-EEG and HD-EEG prompts the use of higher-density EEG-systems to possibly achieve MEG performance. SIGNIFICANCE: Localizing the IZ non-invasively with MSI/ESI facilitates presurgical evaluation and surgical prognosis assessment.

Altered White Matter Connectivity Associated with Intergyral Brain Disorganization in Hemiplegic Cerebral Palsy.

Despite extensive literature showing damages in the sensorimotor projection fibers of children with hemiplegic cerebral palsy (HCP), little is known about how these damages affect the global brain network. In this study, we assess the relationship between the structural integrity of sensorimotor projection fibers and the integrity of intergyral association white matter connections in children with HCP. Diffusion tensor imaging was performed in 10 children with HCP and 16 typically developing children. We estimated the regional and global white-matter connectivity using a region-of-interest (ROI)-based approach and a whole-brain gyrus-based parcellation method. Using the ROI-based approach, we tracked the spinothalamic (STh), thalamocortical (ThC), corticospinal (CST), and sensorimotor U- (SMU) fibers. Using the whole-brain parcellation method, we tracked the short-, middle-, and long-range association fibers. We observed for the more affected hemisphere of children with HCP: (i) an increase in axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) for the STh and ThC fibers; (ii) a decrease in fractional anisotropy (FA) and an increase in MD and RD for the CST and SMU fibers; in (iii) a decrease in FA and an increase in AD, MD, and RD for the middle- and long-range association fibers; and (iv) an association between the integrity of sensorimotor projection and intergyral association fibers. Our findings indicate that altered structural integrity of the sensorimotor projection fibers disorganizes the intergyral association white matter connections among local and distant regions in children with HCP.

Magnetoencephalographic Spike Analysis in Patients With Focal Cortical Dysplasia: What Defines a "Dipole Cluster"?

BACKGROUND: The purpose of this study is to clarify the source distribution patterns of magnetoencephalographic spikes correlated with postsurgical seizure-free outcome in pediatric patients with focal cortical dysplasia. PATIENTS AND METHODS: Thirty-two patients with pathologically confirmed focal cortical dysplasia were divided into seizure-free and seizure-persistent groups according to their surgical outcomes based on Engel classification. In each patient, presurgical magnetoencephalography was reviewed. Dipole sources of magnetoencephalographic spikes were calculated according to a single dipole model. We obtained the following quantitative indices for evaluating dipole distribution: maximum distance over all pairs of dipoles, standard deviation of the distances between each dipole and the mean coordinate of all dipoles, average nearest neighbor distance, the rate of dipoles located within 10, 20, and 30 mm from the mean coordinate, and the rate of dipoles included in the resection. These indices were compared between the two patient groups. RESULTS: Average nearest neighbor distance was significantly smaller in the seizure-free group than in the seizure-persistent group (P = 0.008). The rates of dipoles located within 10, 20, and 30 mm from the mean coordinate were significantly higher in the seizure-free group (P = 0.001, 0.001, 0.005, respectively). The maximum distance, standard deviation, and resection rate of dipoles did not show a significant difference between the two groups. CONCLUSIONS: A spatially restricted dipole distribution of magnetoencephalographic spikes is correlated with postsurgical seizure-free outcomes in patients with focal cortical dysplasia. The distribution can be assessed by quantitative indices that are clinically useful in the presurgical evaluation of these patients.