Surgical outcomes in children with drug-resistant epilepsy and hippocampal sclerosis.

BACKGROUND: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. OBJECTIVE: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. METHODS: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. RESULTS: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. CONCLUSIONS: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.

Stimulation-Induced Seizures in Children Undergoing Stereo-EEG Evaluation.

PURPOSE: This study reports our center's initial experience with the use of low-frequency stimulation in provoking stimulation-induced seizures (SIS) in children with drug-resistant epilepsy undergoing stereo-EEG evaluations. METHODS: This retrospective study enrolled children aged 2 to 18 years with drug-resistant focal epilepsy who underwent stereo-EEG evaluation and extraoperative direct electrical cortical stimulation to elicit seizures. The low-frequency stimulation parameters consisted of biphasic square waveforms at frequency of 1 Hz, pulse width 1 millisecond, current 1 to 3 mA, and train duration of 20 seconds. Various epilepsy-related, imaging, neurophysiology, and surgery-related variables were collected and summarized. RESULTS: Fourteen children (mean age 13 years; 57.1% girls) were included, 10 of whom had unilateral stereo-EEG coverage. Cortical stimulation for provoking seizures was performed after a median of 5 days after electrode implantation. The median number of electrode-contacts stimulated per patient was 42. Four patients (28.6%) experienced habitual SIS (all extratemporal). The etiology in three patients was focal cortical dysplasia. Interictal high-frequency oscillations at electrode-contacts provoking SIS were observed in three cases (75%). Two of these individuals (50%) had class 1 International League Against Epilepsy seizure outcome at last follow-up, after the resection of the brain regions generating SIS. CONCLUSIONS: Low-frequency (1-Hz) stimulation could provoke habitual SIS in nearly one-fourth of children with focal epilepsy undergoing stereo-EEG monitoring. This study provides a limited pediatric experience with the low-frequency cortical stimulation and SIS.

KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature.

OBJECTIVE: KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort. METHODS: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized. RESULTS: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years). SIGNIFICANCE: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.

A Video is Worth a Thousand Words: The Use of Home Videos in Pediatric Neurology.

The use of home video recordings (HVRs) may aid in the diagnosis of neurological disorders. However, this practice remains underutilized. Through an anonymous survey, we sought to understand the perspectives of healthcare providers regarding the sharing of HVRs alongside referrals for responsive and economical pediatric neurology care. This was timely given COVID-19 has worsened wait times for diagnosis and consequently treatment. Most providers agree that sharing of HVRs improves patient care (93.1%: 67/73) and prevents both additional investigations (67%: 49/73) and hospital admissions (68.5%: 50/73). However, a minority of providers (21.9 %: 16/73) currently share HVRs alongside their referrals.

Contralateral hippocampal sclerosis following functional hemispherectomy in children: A report of three cases.

PURPOSE: Hippocampal Sclerosis (HS) may co-exist with temporal or extratemporal lesions (dual pathology) in children and is usually ipsilateral to the radiological lesion. Here were report three cases with extensive hemispheric cortical malformation and drug resistant epilepsy who had persistent seizures after functional hemispherectomy (FH) and developed contralateral HS after the surgery. METHODS: This retrospective study enrolled children who underwent FH and developed contralateral HS after surgery. Their clinical, EEG, radiological and pathological data were reviewed and summarized. RESULTS: Ninety-five children underwent FH during the study period; Three cases (3.2%) were eligible. They all had unilateral extensive hemispheric cortical malformation who underwent FH between 3 and 5 months of age with no clinical, EEG or radiological suggestion for involvement of contralateral hemisphere prior to FH. All three patients had persisting seizures after FH. Contralateral HS was detected between 2.2 to 3.7 years after FH in all three cases. Two of the patients showed pathogenic variants in GATOR1 pathway genes. CONCLUSIONS: The genesis of contralateral HS in the reported patients remains unexplained. The presence and distribution of "second-hit" somatic mutations may play an important role in governing the seizure outcomes of epilepsy surgery in patients with apparently unilateral malformations of cortical development.

Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

Epilepsy surgery outcomes in patients with GATOR1 gene complex variants: Report of new cases and review of literature.

AIM: To report seizure outcomes in children with GATOR1 gene complex disorders who underwent epilepsy surgery and perform a systematic literature search to study the available evidence. METHODS: The records of children with pathogenic/likely pathogenic variants in GATOR1 gene complex who underwent epilepsy surgery were reviewed. Clinical, radiological, neurophysiological, and histological data were extracted/summarized. The systematic review included all case series/reports and observational studies reporting on children or adults with genetic (germline or somatic) variants in the GATOR1 complex genes (DEPDC5, NPRL2, NPRL3) with focal epilepsy with/without focal cortical dysplasia who underwent epilepsy surgery; seizure outcomes were analyzed. RESULTS: Eight children with pathogenic/likely pathogenic variants in GATOR1 complex genes were included. All had drug-resistant epilepsy. Six children had significant neurodevelopmental delay. Epilepsy surgery was performed in all; clinical seizure freedom was noted in 4 children (50%). Systematic literature search identified 17 eligible articles; additional 30 cases with patient-level data were studied. Lesional MRI brain was seen in 80% cases. The pooled rate of seizure freedom following surgery was 60%; FCD IIa was the most encountered pathology. INTERPRETATION: Epilepsy surgery may be effective in some children with GATOR1 complex gene variants. Seizure outcomes may be compromised by extensive epileptogenic zones.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (ß ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (ß ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (ß ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021.

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Epilepsy disrupts hippocampal phase precision and impairs working memory.

OBJECTIVE: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. METHODS: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. RESULTS: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03). SIGNIFICANCE: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

Interictal discharges delay target-directed eye movements and impair attentional set-shifting in children with epilepsy.

OBJECTIVE: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy. METHODS: Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization-related epilepsy performed an attentional set-shifting task while tandem intracranial electroencephalographic signals and eye-tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial-by-trial basis. Hierarchical mixed-effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs. RESULTS: Hierarchical mixed-effects modeling revealed that both the presence of an IED (ß ± SE = 72.74 ± 24.21 ms, p = .003) and the frequency of epileptiform events (ß ± SE = 67.54 ± 17.30 ms, p < .001) were associated with prolonged RT on the attentional set-shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p = .017). SIGNIFICANCE: The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target-directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior.

Leveraging electronic patient diaries in SUDEP risk evaluation.

OBJECTIVE: Our aim was to describe the risk factors known to be related to sudden unexpected death in epilepsy (SUDEP) that can be extracted from patients that utilizes an online seizure diary tool (SeizureTracker™). METHOD: We conducted a descriptive analysis of SeizureTracker™ users across factors relevant to SUDEP risk. We also compared our app-using cohort to published SUDEP case-control studies. RESULTS: We report across seven risk factors from 30,813 users of SeizureTracker™ who had a median length of time using the app of 5.69 years (range from 1 month to 15 years). We found that they are at greater risk for SUDEP than groups from published studies (p < .00001) based on the risk factor of generalized tonic-clonic seizures. SIGNIFICANCE: We demonstrated that the population using the SeizureTracker™ tool can be a valuable population for expanding investigation of SUDEP risk factors and is a first step towards establishing a large sample with a method to ascertain data prospectively that might be critical to developing a SUDEP risk algorithm.

Connectomic Profiles and Cognitive Trajectories After Epilepsy Surgery in Children.

BACKGROUND AND OBJECTIVES: Neurocognitive outcomes after surgery for temporal lobe epilepsy in childhood are variable. Postoperative changes are not directly predicted by seizure freedom, and associations between epilepsy, neuropsychological function, and developing neural networks are poorly understood. Here, we leveraged whole-brain connectomic profiling in magnetoencephalography (MEG) to retrospectively study associations between brain connectivity and neuropsychological function in children with temporal lobe epilepsy undergoing resective surgery. METHODS: Clinical and MEG data were retrospectively analyzed for children who underwent temporal lobe epilepsy surgery at the Hospital for Sick Children from 2000 to 2021. Resting-state connectomes were constructed from neuromagnetic oscillations via the weighted-phase lag index. Using a partial least-squares (PLS) approach, we assessed multidimensional associations between patient connectomes, neuropsychological scores, and clinical covariates. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A total of 133 medical records were reviewed, and 5 PLS analyses were performed. Each PLS analysis probed a particular neuropsychological domain and the associations between its baseline and postoperative scores and the connectomic data. In each PLS analysis, a significant latent variable was identified, representing a specific percentage of the variance in the data and relating neural networks to clinical covariates, which included changes in rote verbal memory (n = 41, p = 0.01, σ2 = 0.38), narrative/verbal memory (n = 57, p = 0.00, σ2 = 0.52), visual memory (n = 51, p = 0.00, σ2 = 0.43), working memory (n = 44, p = 0.00, σ2 = 0.52), and overall intellectual function (n = 59, p = 0.00, σ2 = 0.55). Children with more diffuse, bilateral intrinsic connectivity across several frequency bands showed lower scores on all neuropsychological assessments but demonstrated a greater propensity for gains after resective surgery. DISCUSSION: Here, we report that connectomes characterized by diffuse connectivity, reminiscent of developmentally immature networks, are associated with lower preoperative cognition and postoperative cognitive improvement. These findings provide a potential means to understand neurocognitive function in children with temporal lobe epilepsy and expected changes postoperatively.

Ketonuria and Seizure Control in the Medium Chain Triglyceride and Classic Ketogenic Diets.

We hypothesized that children receiving medium-chain triglyceride ketogenic diet (MCTKD) experience similar seizure reduction despite lower ketosis compared with classic ketogenic diet (CKD). Children initiating CKD or MCTKD were enrolled in a prospective observational study. Forty-five children completed 6 months of KD (n = 17 MCTKD, n = 28 CKD). The proportion achieving ≥50% seizure reduction was 71% CKD group and 59% MCTKD group; ≥90% reduction was 32% and 36% in CKD and MCTKD groups, respectively. CKD had higher urine ketones (≥8 mmol/L: 79% vs. 36%, p = 0.005). Children receiving MCTKD experience similar seizure control to CKD despite lower urine ketone measures.

Caractéristiques des hospitalisations au Canada d'enfants ayant contracté une infection aiguë par le SRAS-CoV-2 en 2020.

CONTEXTE: Les facteurs de risque de complications graves de l'infection par le SRAS-CoV-2 n'ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. MÉTHODES: Nous avons procédé à une étude prospective nationale en utilisant l'infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d'enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés. RÉSULTATS: Sur les 264 hospitalisations d'enfants ayant contracté le SRAS-CoV-2 au cours de la période de l'étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d'autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d'une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d'une forme d'assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d'obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l'exclusion de l'asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19. INTERPRÉTATION: Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l'obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue.

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020.

BACKGROUND: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. METHODS: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. RESULTS: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. INTERPRETATION: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

Cognitive outcome in children with infantile spasms using a standardized treatment protocol. A five-year longitudinal study.

AIM: To evaluate the long-term developmental trajectory of children with infantile spasms (IS) and identify the clinical protective and risk factors associated with their cognitive outcome. METHODS: We analyzed the five-year follow-up results of 41 children (13 female) from the previously published cohort (n = 68) recruited in a multicenter randomized controlled trial for 2-years, examining the effect of an adjunctive therapy (Flunarizine) on standardized IS treatment. The children were subsequently monitored in an open-label study for additional 3 years.  The Vineland Adaptive Behavior Scale, second edition, and either the Stanford-Binet Intelligence Scale, Fifth Edition (SB5) or the Bayley Scales of Infant Development, second edition (BSID-II) were used as cognitive outcome measures. RESULTS: Etiology was the strongest predictor of outcome. Children with no identified etiology (NIE) showed a progressive improvement of cognitive functions, mostly occurring between 2 and 5 years post-diagnosis.  Conversely, symptomatic etiology was predictive of poorer cognitive outcome. Developmental delay, other seizure types (before and after IS diagnosis), and persistent electroencephalographic abnormalities following treatment were predictive of poor cognitive outcome. INTERPRETATION: Given the 5-year cognitive improvement, children with IS should undergo a developmental assessment before school entry. Factors influencing their cognitive outcome emphasize the importance of thorough investigation and evidence-based treatment.

Why child neurologists talk about SUDEP: Results from two cross-sectional surveys.

Objective: To characterize SUDEP discussion practices of child neurologists approximately 6 and 12 months after publication of the American Academy of Neurology SUDEP Clinical Practice Guideline and explore factors associated with discussion practice. Methods: Child Neurology Society members (~2450) were electronically surveyed in November 2017 and May 2018 regarding their practice of discussing SUDEP with patients with epilepsy or their caregivers. Multivariable proportional odds ordinal logistic regression evaluated factors associated with discussing SUDEP with a greater proportion of epilepsy patients/caregivers. Reasons for changing practice were described. Results: Among the 369 child neurologist respondents, 36% reported discussing SUDEP with at least half of their epilepsy patients/caregivers including 12% who discuss with all or almost all (>90%) of their epilepsy patients/families. Those who discussed SUDEP with an increased proportion of their patients were more likely to agree that they knew enough to talk about SUDEP, agree that healthcare providers have an ethical obligation to discuss SUDEP, and disagree that there is not enough time to talk about SUDEP. Those who agreed SUDEP could provoke excessive anxiety or worry were less likely to discuss SUDEP with an increased proportion of their patients. Reading the SUDEP Clinical Practice Guideline was a frequently cited reason among respondents who reported a recent change in discussion practice. Significance: Most child neurologists do not follow the current SUDEP Clinical Practice Guideline regarding SUDEP discussion. Feeling sufficiently knowledgeable and ethically obligated to discuss SUDEP were associated with increased discussion practice, suggesting an educational intervention may be effective at increasing SUDEP discussion rates.

Neutropenia in Children Treated With Ketogenic Diet Therapy.

OBJECTIVES: The objectives were to investigate the relationship between ketogenic diet therapy and neutropenia in children with epilepsy. METHODS: A retrospective chart review of children who initiated ketogenic diet at the Hospital for Sick Children between January 1, 2000, and May 1, 2018 was performed. Factors associated with the development of neutropenia during ketogenic diet therapy were evaluated and the relationship between development of a significant or suspected infection and neutrophil count was analyzed. RESULTS: One hundred two children met inclusion criteria and were followed on the diet for up to 24 months. Thirteen of 102 (13%) children were neutropenic at diet initiation. In the remaining 89 children, 27 developed neutropenia. Developing neutropenia was significantly associated with the ketogenic diet at 6 (13%), 12 (23%), and 24 (25%) months follow-up. Developing neutropenia was associated with higher urinary ketones (OR = 4.26, 95% CI: 1.27, 14.15) and longer duration of ketogenic diet therapy (OR = 3.29, 95% CI: 1.42, 7.96). There was no significant association between development of a clinically significant infection and neutropenia. CONCLUSION: Ketogenic diet therapy is associated with neutropenia in children with epilepsy, however, it does not have a significant clinical impact. Concern regarding neutropenia should not discourage the use of the ketogenic diet in children.

Autopsy-reported cause of death in a population-based cohort of sudden unexpected death in epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a diagnosis of exclusion; the definition includes individuals with epilepsy who die suddenly without an identifiable toxicological or anatomical cause of death. Limited data suggest underidentification of SUDEP as the cause of death on death certificates. Here, we evaluate the autopsy-reported cause of death in a population-based cohort of SUDEP cases. METHODS: Case summaries of forensic autopsies conducted in Ontario, Canada between January 2014 and June 2016 were retrospectively screened using a language processing script for decedents with a history of epilepsy or seizures. After manual review for potential SUDEP cases, two neurologists independently examined the autopsy reports and classified deaths by Nashef criteria. Demographic characteristics and consideration by the forensic pathologist of the role of epilepsy, seizure, and SUDEP in death were summarized. RESULTS: One hundred and eight Definite, 34 Definite Plus, and 22 Possible SUDEP cases were identified. Seventy-five percent of Definite/Definite Plus SUDEP cases identified by the neurologists were attributed to SUDEP, epilepsy, or seizure disorder in the autopsy report. There was a significant association between the proportion of cases listed in the autopsy report as SUDEP, epilepsy, or seizure disorder and neurologists' SUDEP classification (86% of Definite, 38% of Definite Plus, 0% of Possible). Age was significantly associated with SUDEP classification; Definite cases were younger than Definite Plus, which were younger than Possible SUDEP cases. SIGNIFICANCE: Most SUDEP cases identified by neurologists were classified concordantly by forensic pathologists in Ontario, Canada; however, concordance decreased with increased case complexity. Although the role of epilepsy/seizures was considered in most Definite/Definite Plus cases, this study highlights the need for autopsy report review of potential SUDEP cases in research studies and assessments of the public health burden of SUDEP. The relationship between age and SUDEP classification has important public health implications; SUDEP incidence may be underappreciated in older adults.