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The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Previous quantitative MRI studies have established important imaging markers of epilepsy-related pathology, including features sensitive to hippocampal cell loss and reactive astrogliosis. Here, we review the case of a female with pediatric drug-resistant epilepsy. Throughout her course of treatment, she had seven MRI investigations at several centers; the first three did not follow optimized epilepsy imaging protocols whereas the remaining four adhered to HARNESS-MRI protocols ( har monized n euroimaging of e pilepsy s tructural s equences). Visual inspection of a set of HARNESS-MR images revealed conspicuous left hippocampal hyperintensity which may have been initially overlooked on non-optimized MR images. Quantitative analysis of these multimodal imaging data along hippocampal subfields provided clear evidence of hippocampal sclerosis, with increased atrophy, increased mean diffusivity, increased T2-FLAIR signal, and lower qT1 values observed in the anterior portions of the left, compared to the right hippocampus. The patient underwent a left anterior temporal lobectomy with amygdalohippocampectomy at age 16 years. Histopathology of the resected specimen also confirmed hippocampal sclerosis with widespread gliosis and focal neuronal loss in the hippocampal subfields overlapping with regions of multimodal quantitative alterations. The patient remains seizure-free one year after surgery. Collectively, this case highlights the need for optimized data acquisition protocols early in the treatment of epilepsy and supports quantitative analysis of MRI contrasts to enhance personalized diagnosis and prognosis of drug-resistant patients with epilepsy.

IntroductionVagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy.Methods and analysisIn this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and video electroencephalography as part of the standard clinical workup for VNS. Neuroimaging data including resting-state functional MRI, diffusion-tensor imaging and magnetoencephalography will be collected before surgery. MR-based measures will also be repeated 12 months after implantation. Outcomes of VNS, including seizure control and health-related quality of life of both patient and primary caregiver, will be prospectively measured up to 2 years postoperatively. All data will be collected electronically using Research Electronic Data Capture.Ethics and disseminationThis study was approved by the Hospital for Sick Children Research Ethics Board (REB number 1000061744). All participants, or substitute decision-makers, will provide informed consent prior to be enrolled in the study. Institutional Research Ethics Board approval will be obtained from each additional participating site prior to inclusion. This study is funded through a Canadian Institutes of Health Research grant (PJT-159561) and an investigator-initiated funding grant from LivaNova USA (Houston, TX; FF01803B IIR).

Background and ObjectiveTo test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD).MethodsWe used clinically acquired 3-dimensional (3D) T1-weighted and 3D fluid-attenuated inversion recovery MRI of 148 patients (median age 23 years [range 2–55 years]; 47% female) with histologically verified FCD at 9 centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed MRI-negative in 51% of patients, in whom intracranial EEG determined the focus. For risk stratification, the CNN incorporated bayesian uncertainty estimation as a measure of confidence. To evaluate performance, detection maps were compared to expert FCD manual labels. Sensitivity was tested in an independent cohort of 23 cases with FCD (13 ± 10 years). Applying the algorithm to 42 healthy controls and 89 controls with temporal lobe epilepsy disease tested specificity.ResultsOverall sensitivity was 93% (137 of 148 FCD detected) using a leave-one-site-out cross-validation, with an average of 6 false positives per patient. Sensitivity in MRI-negative FCD was 85%. In 73% of patients, the FCD was among the clusters with the highest confidence; in half, it ranked the highest. Sensitivity in the independent cohort was 83% (19 of 23; average of 5 false positives per patient). Specificity was 89% in healthy and disease controls.DiscussionThis first multicenter-validated deep learning detection algorithm yields the highest sensitivity to date in MRI-negative FCD. By pairing predictions with risk stratification, this classifier may assist clinicians in adjusting hypotheses relative to other tests, increasing diagnostic confidence. Moreover, generalizability across age and MRI hardware makes this approach ideal for presurgical evaluation of MRI-negative epilepsy.Classification of EvidenceThis study provides Class III evidence that deep learning on multimodal MRI accurately identifies FCD in patients with epilepsy initially diagnosed as MRI negative.

During the COVID-19 pandemic, the Division of Neurology at BC Children’s Hospital rapidly transitioned to almost exclusively virtual health. In April 2020, 96% of outpatient visits were done virtually (64%) or by telephone, and only 4.2% were in-person. Total clinic visit numbers were unchanged compared to previous months. Neurologists reported high satisfaction with the virtual history and overall assessment, while the physical examination was less reliable. Additional in-person visits were rarely required. Rapid, sustained adoption of virtual health is possible in a pediatric neurology setting, providing reliable care that is comparable to in-person consultations when physical distancing is necessary.

The adult functional connectome is well characterized by a macroscale spatial gradient of connectivity traversing from unimodal toward higher-order transmodal cortices that recapitulates known principles of hierarchical organization and myelination patterns. Despite an emerging literature assessing connectome properties in neonates, the presence of connectome gradients and particularly their correspondence to microstructure remains largely unknown. We derived connectome gradients using unsupervised techniques applied to functional connectivity data from 40 term-born neonates. A series of cortex-wide analysis examined associations to magnetic resonance imaging-derived morphological parameters (cortical thickness, sulcal depth, curvature), measures of tissue microstructure (intracortical T1w/T2w intensity, superficial white matter diffusion parameters), and subcortico-cortical functional connectivity. Our findings indicate that the primary neonatal connectome gradient runs between sensorimotor and visual anchors and captures specific associations to cortical and superficial white matter microstructure as well as thalamo-cortical connectivity. A second gradient indicated an anterior-to-posterior asymmetry in macroscale connectivity alongside an immature differentiation between unimodal and transmodal areas, indicating a connectome-level circuitry en route to an adult-like organization. Our findings reveal an important coordination of structural and functional interactions in the neonatal connectome across spatial scales. Observed associations were replicable across individual neonates, suggesting consistency and generalizability.

Objective Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Although it is commonly related to hippocampal pathology, increasing evidence suggests structural changes beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood. Methods We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging (MRI) analyses. All patients had histologically verified hippocampal sclerosis and underwent postoperative imaging to outline the extent of their surgical resection. Our analysis leveraged a novel resting-state functional MRI framework that parameterizes functional connectivity distance, consolidating topological and physical properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and utility for surgical outcome prediction was assessed using machine learning techniques. Results Compared to controls, TLE patients showed connectivity distance reductions in temporoinsular and prefrontal networks, indicating topological segregation of functional networks. Testing for morphological and microstructural associations, we observed that functional connectivity contractions occurred independently from TLE-related cortical atrophy but were mediated by microstructural changes in the underlying white matter. Following our imaging study, all patients underwent an anterior temporal lobectomy as a treatment of their seizures, and postsurgical seizure outcome was determined at a follow-up at least 1 year after surgery. Using a regularized supervised machine learning paradigm with fivefold cross-validation, we demonstrated that patient-specific functional anomalies predicted postsurgical seizure outcome with 76 ± 4% accuracy, outperforming classifiers operating on clinical and structural imaging features. Significance Our findings suggest connectivity distance contractions as a macroscale substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance toward epileptogenesis in affected networks and that may assist in patient-specific surgical prognostication.

Objective Temporal lobe epilepsy (TLE) is classically associated with hippocampal pathology, and increasingly with structural changes beyond the mesiotemporal lobe. Functional anomalies, their link to cortical morphology and microstructure, and their utility in surgical prognosis, however, remain less well understood. Methods We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal 3T MRI. All patients had histologically-verified hippocampal sclerosis and underwent postoperative imaging to establish the extent of surgical resection. Our analysis leveraged a novel resting-state fMRI framework that parameterizes functional connectivity distance, consolidating functional and geometric properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and associations to post-surgical seizure outcome were examined using machine learning techniques. Results Compared to controls, TLE showed connectivity distance reductions in temporo-insular and dorsomedial prefrontal networks, with the former being more marked ipsilateral to the focus. Findings were driven by contractions in long-distance connections together with an excess in short-range connections, suggesting topological segregation of functional networks. Parallel structural profiling indicated that functional connectivity distance reductions in TLE were independent of atrophy but mediated by microstructural changes in the underlying white matter. Patients with persistent seizures showed anomalies a distinct network signature which predicted seizure outcome with 75±4% accuracy (using 5-fold cross-validation). Conclusions Our findings suggest connectivity distance contractions as a pathoconnectomic substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance towards epileptogenesis in affected networks.

I.AbstractAging is characterised by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesise, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n=102, age range = 30-89 years) with MRI and Aβ PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface-based morphological and metabolic mapping, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced towards higher-order transmodal regions. Age-related atrophy was greater towards the posterior end of the hippocampal long-axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioural measures of fluid intelligence and episodic memory in a topography-specific manner. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyse and conceptualize brain-based biomarkers of aging.

Background Status epilepticus (SE) is a common pediatric neurological emergency that requires timely treatment to minimize morbidity and mortality, yet administration of rescue medications is often delayed and underdosed. Seizure action plans (SAPs) outline the steps that should be taken by parents and caregivers in case of SE in order to optimize patient outcomes. Our study determined the uptake of SAPs in a pediatric population with epilepsy and assessed parental interest in a SAP mobile application. Methods A survey was distributed to parents of patients with epilepsy aged 1 month to 19 years at British Columbia Children’s Hospital. Following chart review, univariate and multivariate analyses were performed to identify variables that predict whether patients have SAPs. A systematic search of available mobile applications for epilepsy management was conducted. Results Of 192 participants, 62% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82% of patients with SAPs. 83% of parents were interested in a SAP mobile application. There are currently 40 mobile applications available for epilepsy management, but only 15% of respondents reported using them. Conclusions There is a need to increase the percentage of patients with epilepsy with SAPs, particularly in those at greater risk of SE. Most parents would find a SAP mobile application valuable in their child’s epilepsy management. There is a gap between the high parental interest in mobile applications for epilepsy management and their current use of such applications.

Background: Status epilepticus (SE) is the most common pediatric neurological emergency. Timely treatment is crucial, yet administration of rescue medications is often delayed and under-dosed. We aim to improve SE management by ensuring that every child at risk of SE in our province has an individualized seizure action plan (SAP) outlining the steps that should be taken during SE. Methods: A survey was distributed to parents of epilepsy patients aged 1 month to 19 years. Primary outcome was percentage of patients with SAPs. Secondary outcome was parental interest in a SAP mobile application. Following chart review, univariate and multivariate analysis was performed to identify variables that predict whether patients have SAPs. Results: Of 192 participants, 61.5% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of having a SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82.2% of patients with SAPs. 83.3% of parents were interested in a SAP mobile application. Conclusions: This is one of the first studies to examine SAP prevalence in a pediatric epilepsy population. There is a need to increase the percentage of epilepsy patients with SAPs. Most parents would find a SAP mobile application valuable in their child’s management.

To describe the novel finding of epileptic spasms arising from a cingulate lesion.We describe two children presenting with epileptic spasms who had lesions of the cingulate gyrus on MRI.In both patients, the lesions involved the midcingulate cortex. Seizures were characterized by prominent motor manifestations and resembled spasms. Both patients had a complete resolution of seizures after resection of their cingulate lesions.Cingulate seizures can present with a variety of behaviors including complex motor manifestations, vocalizations, and autonomic changes. Lesions in the midcingulate cortex can also produce epileptic spasms.

Purpose The objective of this retrospective study was to identify clinical and EEG features in children with occipital epilepsy that predict MR imaging abnormalities and seizure outcome. Methods Patients with clinical and/or EEG features indicating occipital lobe involvement were identified from the epilepsy database at a tertiary children’s hospital. The clinical and EEG features were analyzed to identify the most important predictors of abnormal MR imaging and seizure outcome. Results Sixty-six patients were identified: 21 had symptomatic epilepsy with abnormal MR imaging; 12 patients had probable symptomatic epilepsy based on an abnormal neurological exam; 33 patients had normal neurological development, normal neurological examination and normal neuroimaging. Twenty-two of these 33 patients satisfied criteria for idiopathic occipital syndromes: Panayiotopoulos syndrome (9 patients), Gastaut type idiopathic childhood occipital epilepsy (12 patients) and idiopathic photosensitive occipital epilepsy (1 patient). Eleven patients could not be classified. Early age of seizure onset and an abnormal neurological examination were significant predictors of abnormal MR imaging. None of the variables examined were strong predictors of seizure outcome. Conclusion Early age of seizure onset and an abnormal neurological examination are the best predictors of abnormal MR imaging in children with epilepsy with occipital features.

Refractory, convulsive status epilepticus has significant mortality and morbidity. Urgent resective surgery may be of benefit in selected cases where medical therapies have failed. At our institution, from January 1992 until December 2005, urgent resective surgery was performed in three children with medically refractory convulsive status epilepticus. The etiologies were microdysgenesis, focal cortical dysplasia, and bilateral Rasmussen's syndrome and cortical dysplasia. In two cases, surgery resulted in termination of status epilepticus. In all three cases, surgery permitted discontinuation of high-dose suppression therapy and allowed the patient to leave the intensive care unit, either by terminating status epilepticus or by providing important histopathological information about the nature of the underlying disease and prognosis.

Status epilepticus remains a life-threatening condition that afflicts both adults and children which although occurs in patients with epilepsy, often presents as new-onset seizure activity also. Refractory status epilepticus poses a management challenge for neurological and neurosurgical teams. Subdural grid electrodes were used to record cortical discharges and guide tumor resection involving eloquent cortex and multiple subpial transections in a 48-year-old man with left hemiparesis in status epilepticus. He had been refractory to multiple medical therapies in persistent epilepsia partialis continua for a prolonged period. As an alternative to higher-dose suppressive medical therapy, the patient elected to proceed with subdural grid mapping after seizure semiology (“negative” scalp electroencephalogram) localized the seizure focus to the right hemisphere, motor cortex. Following tumor removal, multiple subpial transections were subsequently performed over large areas of the motor and sensory strips and successfully resolved the status epilepticus. The patient made an excellent recovery, became seizure free, had improved left-sided strength and was discharged home shortly after. This case illustrates a potentially life-saving technique for the treatment of refractory status epilepticus. Multiple subpial transections and other neurosurgical intervention should be considered for patients with status epilepticus. When localization with surface electrodes is poor, especially in eloquent cortex, subdural grid recording can be used to direct focal resection and/or multiple subpial transections to minimize neurological deficits. A review and summary of previously published neurosurgery cases for status epilepticus is discussed.