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Precise detection of brain regions harboring heightened electrical activity plays a central role in the understanding and treatment of diseases such as epilepsy. Superparamagnetic iron oxide nanoparticles (SPIONs) react to magnetic fields by aggregating and represent interesting candidates as new sensors for neuronal magnetic activity. We hypothesized that SPIONs in aqueous solution close to active brain tissue would aggregate proportionally to neuronal activity. We tested this hypothesis using an in vitro model of rat brain slice with different levels of activity. Aggregation was assessed with dynamic light scattering (DLS) and magnetic resonance imaging (MRI). We found that increasing brain slice activity was associated with higher levels of aggregation as measured by DLS and MRI, suggesting that the magnetic fields from neuronal tissue could induce aggregation in nearby SPIONs in solution. MRI signal change induced by SPIONs aggregation could serve as a powerful new tool for detection of brain electrical activity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Children with complex congenital heart disease (CHD) experience high incidence of perioperative seizures. Population-based studies also report high epilepsy co-morbidity in CHD. Given the increasing survival of patients with CHD and the interference of seizures and epilepsy with the long-term outcomes, characterizing them in this population is of high relevance. This study investigated the incidence and risk factors of perioperative clinical seizures (CS) and epilepsy in a prospective cohort of children with complex CHD who underwent cardiac surgery., Methods: We included 128 consecutive children with CHD, followed for at least two years at the neurocardiac clinic of Montreal's Sainte-Justine University Hospital Center. We collected perinatal, surgical, critical care and clinical follow-up information and performed logistic regression to reveal risk factors of CS and epilepsy., Results: Ten patients (7.8%) experienced perioperative CS. Four of them (40%) developed epilepsy. The incidence of epilepsy was therefore 3.1%. Higher surgical complexity scores, delayed sternal closure, extracorporeal membrane oxygenation (ECMO) use, longer intensive care and hospital stay were associated with CS. ECMO use and hospital stay were also associated with epilepsy. Nine (90%) patients with CS had brain injuries: five strokes, one white matter and three hypoxic-ischemic injury (HII). All patients with HII developed epilepsy, which became intractable in one of them., Conclusion: Our study reports high incidence, surgical risk factors and brain injury patterns underlying CS and epilepsy in CHD. Further studies are needed to investigate how epilepsy interferes with neurodevelopment and quality of life in CHD., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming., Methods: We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events., Results: Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence., Conclusion: This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate how rewarming impacts the evolution of EEG background in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH)., Methods: We recruited a retrospective cohort of 15 consecutive newborns with moderate (9) and severe (6) HIE monitored with a continuous EEG during TH and at least 12h after its end. EEG background was analyzed using conventional visual and quantitative EEG analysis methods including EEG discontinuity, absolute and relative spectral magnitudes. One patient with seizures on rewarming was excluded from analyses., Results: Visual and quantitative analyses demonstrated significant changes in EEG background from pre- to post-rewarming, characterized by an increased EEG discontinuity, more pronounced in newborns with severe compared to moderate HIE. Neonates with moderate HIE also had an increase in the relative magnitude of slower delta and a decrease in higher frequency theta and alpha waves with rewarming., Conclusions: Rewarming affects EEG background in HIE newborns undergoing TH, which may represent a transient adaptive response or reflect an evolving brain injury., Significance: EEG background impairment induced by rewarming may represent a biomarker of evolving encephalopathy in HIE newborns undergoing TH and underscores the importance of continuously monitoring the brain health in critically ill neonates., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Little is known about the genetics of nonsyndromic intellectual disability (NSID). Recently, we reported de novo truncating mutations in the SYNGAP1 gene of 3 of 94 NSID cases, suggesting that its disruption represents a common cause of autosomal dominant NSID., Methods: To further explore the involvement of SYNGAP1 in NSID, we sequenced its exons and intronic boundaries in 60 additional sporadic cases of NSID, including 30 patients with autism spectrum disorders (ASD) and 9 with epilepsy, and in 380 control individuals., Results: We identified de novo out-of-frame deletions in two patients with NSID and mild generalized epilepsy (c.2677delC/p.Q893RfsX184 and c.321&#95;324delGAAG/p. K108VfsX25) and a de novo splicing mutation (c.2294 + 1G>A), which results in the creation of a premature stop codon, in a patient with NSID and autism. No splicing or truncating mutations were found in control subjects., Conclusions: We provide evidence that truncating mutations in SYNGAP1 are common in NSID and can be also associated with autism., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

We investigated the development of the magnitude and phase alignment of steady-state visual evoked potentials induced by 5 Hz intermittent photic stimulation in 46 children (3 to 16 years) and 8 adults, as a function of age. We found that, over the occipital region, magnitude values were the highest in 8-11-year old children, but decreased with age over all other cerebral regions. Phase alignment values increased with age over the occipital, parietal and frontal cerebral regions. We interpret these findings in terms of the development of functional interactions between different cortical areas involved in the processing of visual stimuli., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Aims: Valproic acid (VPA) is reported to be effective for the control of absence seizures in 75% of children. The aim of this study was to determine the clinical and socio-demographic factors associated with VPA response in newly diagnosed childhood absence epilepsy (CAE) and to determine if these factors also influence the chances of achieving long-term seizure freedom., Methods: Medical charts of 180 children with CAE were retrospectively reviewed. Clinical, electroencephalographic and imaging findings were recorded to correlate with complete VPA response and long-term epilepsy outcome. Factors associated with non-responsiveness were identified individually and in a multivariable logistic regression analysis., Results: Treatment was successful in 112 (58.3%) children. More children that were non-responsive to VPA experienced generalized tonic clonic seizures (GTCS) (33.8% vs. 13.4% for responders; p=0.001) and 52.9% had a pre-treatment seizure frequency greater than 10/day (vs. 27.0% for responders; p<0.001). Finally, responders were older at time of diagnosis versus non-responders (p=0.001). Absence of long-term seizure freedom was linked to the presence of GTCS, the absence of initial response and the need for multiple AEDs to control seizures., Interpretation: Our results suggest that clinical phenotypes are associated with reduced response rates to VPA. This should be taken into account when counselling families of children with newly diagnosed absence epilepsy.

Purpose: The goals of this study are to evaluate the efficacy and tolerability of levetiracetam (LEV) as add-on therapy in children with refractory epilepsies and to determine the value of LEV blood level monitoring in this population., Methods: Sixty-nine children (39 males and 30 females) treated with LEV between 2006 and 2007 were selected. Their medical files were reviewed for LEV efficacy and tolerability. In a subgroup of children currently taking LEV, plasma concentrations were determined by high performance liquid chromatography by ultraviolet detection (HPLC-UV) method and correlated with the given dose per kilo as well as clinical response., Results: Fifty-one patients (74%) had a more than 50% reduction in seizure frequency with 16 patients (23%) becoming seizure free on LEV. Eighteen (26%) patients had a less than 50% reduction in seizure frequency. Adverse events due to LEV ranged from mild to moderate in only 18 patients (26%). The most frequently observed were drowsiness, behavioral difficulties, increase in seizure frequency and headaches. The majority (60.5%) of the responders received doses between 10 and 50mg/kg/day and had a plasma concentration (PC) between 5 and 40microg/ml. However, we found no clear correlation between PC and efficacy., Conclusion: Levetiracetam given twice a day in children with refractory epilepsy reduces seizure frequency in all types of epilepsy. In children, LEV is a broad spectrum anticonvulsant with a favourable safety profile.

Purpose: The goal of this retrospective study is to review the causes of infantile spasms and to correlate aetiology with outcome., Methods: All children diagnosed with infantile spasms between 1990 and 2003 at our institution were included. Charts were reviewed for the presence or absence of a defined aetiology/association, response to treatment, long-term epileptic and cognitive outcome., Results: 80 out of 95 children are included in this review. 50 children (63%) had symptomatic spasms with disorders of cortical development being the most frequent cause followed by neonatal injury and tuberous sclerosis. Symptomatic children with developmental brain lesions responded at a rate of 54% to vigabatrin versus 62% for ACTH/prednisone, while other symptomatic aetiologies 83% responded to vigabatrin versus 63% for ACTH/prednisone. Cryptogenic spasms responded at a similar rate to both drugs. Other than children with cryptogenic spasms, very few went on to develop normally. Our results are however biased by on average more than 30 days of delay to diagnosis. None of our children developed Lennox-Gastaut syndrome but a number developed severe epilepsy with multifocal spikes., Discussion: The aetiology and prognosis of infantile spasms is evolving. To improve outcome, we need to reduce the delay to diagnosis and develop prospective double-blind randomized clinical trials looking at not only the epileptic outcome but also cognitive outcome of these children.

Near-infrared spectroscopy (NIRS) is a novel imaging technique of potential value in the pre-surgical investigation of patients with refractory epilepsy. We recorded simultaneously electrophysiology (EEG; Compumedics, USA) and near-infrared spectroscopy (NIRS; ISS, USA) to examine the localization of the ictal onset zone and assess language lateralization in a young epileptic boy (L.H., 10 years) as part of his pre-surgical evaluation. L.H. underwent a prolonged EEG-NIRS recording while electro-clinical and electrical seizures were recorded. Results were compared to those obtained with other pre-surgical techniques (SPECT, FDG-PET, EEG-fMRI and EEG-MEG) and showed good concordance for ictal onset zone localization. A second NIRS session without EEG was carried out in order to investigate language lateralization. For this purpose, the patient performed a categorical verbal-fluency task during NIRS recordings. Results showed left-hemisphere dominance for language function in this young boy. This case report illustrates that multi-channel EEG-NIRS has the potential to contribute favourably to pre-surgical investigation in young patients.