OBJECTIVE:Genetic testing is now included in the diagnostic assessment of childhood onset epilepsies. We evaluated the yield of a targeted next generation sequencing (TNGS) panel dedicated to pediatric epilepsies. METHODS:We tested by TNGS panel 1000 consecutive patients presenting with childhood onset epilepsies and including mainly patients with early onset epilepsies (under 2 years, 61%). RESULTS:Causal variants were identified in 31% of patients, spanning 78 different genes. Patients with benign familial neonatal/infantile epilepsy (BFN/IS) exhibited the highest rate of positive findings (82%). Developmental and epileptic encephalopathies (DEEs) had a global diagnostic yield of 37%, with epilepsy of infancy with migrating focal seizures (EIMFSI) and Dravet syndrome (DS) presenting the highest yield in this group (78%) and early infantile DEE (EIDEE) laying next with a yield of 43%. The lowest rates of genetic diagnosis were observed in infantile epileptic spasms syndrome (IESS, 17%), epilepsy with myoclonic-atonic seizures (EMAtS, 19%), and DEE-SWAS (14%). Patients with GEFS+ had a yield of 16%. Among patients with developmental encephalopathies and refractory seizures with onset after 2 years, TNGS yielded a 33% diagnostic rate. Atypical absences yielded 16%, focal epilepsy yielded 18%, and generalized epilepsies with refractory seizures yielded 13%. These groups exhibited a high genetic heterogeneity. SIGNIFICANCE:TNGS is an effective first-step genetic screening in patients with high diagnostic yields (BFN/IS, EIMFS, DS, EIDEE) and for epilepsy syndromes associated with one or a few major genes (BFN/IS, EIMFS, DS, GEFS+, DEE-SWAS). Whole exome or genome sequencing (WES/WGS) should be considered as a second step in these groups with a probably relevant Mendelian inheritance. WES/WGS could be proposed as first-tier analysis in patients with IESS, EMAtS, generalized or focal epilepsies refractory to ASMs, and developmental encephalopathies with seizure onset after 2 years. However, the lower diagnostic yield obtained in these groups may suggest a complex inheritance. PLAIN LANGUAGE SUMMARY:This study emphasizes the importance of accurately identifying different types of epilepsy and epilepsy syndromes to improve genetic testing strategies. We suggest that a targeted gene panel can be a good first step for some genetic conditions, such as benign familial neonatal/infantile epilepsy, Dravet syndrome, and epilepsy of infancy with migrating focal seizures.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the TPP1 gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical TPP1 variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle-term treatment benefit for patients with CLN2.

Periodic discharges are a rare peculiar electroencephalogram pattern, occasionally associated with motor or other clinical manifestations, usually observed in critically ill patients. Their underlying pathophysiology remains poorly understood. Epileptic spasms in clusters and periodic discharges with motor manifestations share similar electroencephalogram pattern and some aetiologies of unfavourable prognosis such as subacute sclerosing panencephalitis or herpes encephalitis. Arterial spin labelling magnetic resonance imaging identifies localizing ictal and inter-ictal changes in neurovascular coupling, therefore assumed able to reveal concerned cerebral structures. Here, we retrospectively analysed ictal and inter-ictal arterial spin labelling magnetic resonance imaging in patients aged 6 months to 15 years (median 3 years 4 months) with periodic discharges including epileptic spasms, and compared these findings with those of patients with drug-resistant focal epilepsy who never presented periodic discharges nor epileptic spasms as well as to those of age-matched healthy controls. Ictal electroencephalogram was recorded either simultaneously with arterial spin labelling magnetic resonance imaging or during the close time lapse of patients' periodic discharges, whereas inter-ictal examinations were performed during the patients' active epilepsy but without seizures during the arterial spin labelling magnetic resonance imaging. Ictal arterial spin labelling magnetic resonance imaging was acquired in five patients with periodic discharges [subacute sclerosing panencephalitis (1), stroke-like events (3), West syndrome with cortical malformation (1), two of them also had inter-ictal arterial spin labelling magnetic resonance imaging]. Inter-ictal group included patients with drug-resistant epileptic spasms of various aetiologies (14) and structural drug-resistant focal epilepsy (8). Cortex, striatum and thalamus were segmented and divided in six functional subregions: prefrontal, motor (rostral, caudal), parietal, occipital and temporal. Rest cerebral blood flow values, absolute and relative to whole brain, were compared with those of age-matched controls for each subregion. Main findings were diffuse striatal as well as cortical motor cerebral blood flow increase during ictal examinations in generalized periodic discharges with motor manifestations (subacute sclerosing panencephalitis) and focal cerebral blood flow increase in corresponding cortical-striatal-thalamic subdivisions in lateralized periodic discharges with or without motor manifestations (stroke-like events and asymmetrical epileptic spasms) with straight topographical correlation with the electroencephalogram focus. For inter-ictal examinations, patients with epileptic spasms disclosed cerebral blood flow changes in corresponding cortical-striatal-thalamic subdivisions (absolute-cerebral blood flow decrease and relative-cerebral blood flow increase), more frequently when compared with the group of drug-resistant focal epilepsies, and not related to Vigabatrin treatment. Our results suggest that corresponding cortical-striatal-thalamic circuits are involved in periodic discharges with and without motor manifestations, including epileptic spasms, opening new insights in their pathophysiology and new therapeutical perspectives. Based on these findings, we propose a model for the generation of periodic discharges and of epileptic spasms combining existing pathophysiological models of cortical-striatal-thalamic network dynamics. Eisermann et al. report from arterial spin labelling magnetic resonance imaging studies in children that cortico-striatal-thalamic circuits are involved in periodic electroencephalogram discharges and epileptic spasms and propose a model for their generation by combining existing pathophysiological models of cortico-striatal-thalamic network dynamics.

BACKGROUND AND OBJECTIVES: When seizure onset affects a whole hemisphere, hemispheric disconnections are efficient and safe procedures. However, both lateral peri-insular hemispherotomy and vertical paramedian hemispherotomy approaches report a failure rate around 20%, which can be explained by residual connections giving rise to persistent seizures. In this study, we present the interhemispheric vertical hemispherotomy (IVH), a technical variation of the vertical paramedian hemispherotomy approach, that aims to increase seizure control avoiding residual connections while exposing the corpus callosum. METHODS: This is a retrospective study of IVH in two centers, with analysis of clinical and MRI data and outcomes. A detailed description of the technique is provided with a video. RESULTS: IVH was performed in 39 children. The mean age at surgery was 7.2 years, and etiologies were as follows: malformations of cortical development (n = 14), Rasmussen's encephalitis (n = 10), stroke (n = 10), post-traumatic (3), and Sturge-Weber Syndrome (2). Hemispheric disconnection was complete on postoperative MRI in 34 cases. There was no mortality, hydrocephalus occurred in one case, and subdural collection occurred in four cases. A second surgery was performed in four cases because of seizure relapse (n = 3) and/or incomplete disconnection on MRI (n = 4). With a mean follow-up of 3.2 years, International League Against Epilepsy class I epilepsy outcome was obtained for 37/39 patients. CONCLUSION: IVH is a safe and effective variation of the vertical approaches for hemispheric disconnection. It allows a good exposure and anatomic control of the corpus callosum, which is a frequent site of incomplete disconnection. IVH may be limited by the thalamic volume and the ventricular size, notably in hemimegalencephaly cases.

BACKGROUND: Focal cortical dysplasia (FCD) causes drug-resistant epilepsy in children that can be cured surgically, but the lesions are often unseen by imaging. OBJECTIVE: To assess the efficiency of arterial spin labeling (ASL), voxel-based-morphometry (VBM), fMRI electroencephalography (EEG), resting-state regional homogeneity (ReHo), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their combination in detecting pediatric FCD. METHODS: We prospectively included 10 children for whom FCD was localized by surgical resection. They underwent 3T MR acquisition with concurrent EEG, including ASL perfusion, resting-state BOLD fMRI (allowing the processing of EEG-fMRI and ReHo), 3D T1-weighted images processed using VBM, and FDG PET-CT coregistered with MRI. Detection was assessed visually and by comparison with healthy controls (for ASL and VBM). RESULTS: Eight children had normal MRI, and 2 had asymmetric sulci. Using MR techniques, FCD was accurately detected by ASL for 6/10, VBM for 5/10, EEG-fMRI for 5/8 (excluding 2 with uninterpretable results), and ReHo for 4/10 patients. The combination of ASL, VBM, and ReHo allowed correct FCD detection for 9/10 patients. FDG PET alone showed higher accuracy than the other techniques (7/9), and its combination with VBM allowed correct FCD detection for 8/9 patients. The detection efficiency was better for patients with asymmetric sulci (2/2 for all techniques), but advanced MR techniques and PET were useful for MR-negative patients (7/8). CONCLUSION: A combination of multiple imaging techniques, including PET, ASL, and VBM analysis of T1-weighted images, is effective in detecting subtle FCD in children.

BACKGROUND:Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions.METHODS:We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas.RESULTS:We included 7 patients (range: 3-15 years) and 6 aged-matched controls (range: 6-17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF.CONCLUSION:Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening.

Background: One of the worst complications of surgery for spinal deformity is postoperative neurological deficit. Multimodal intraoperative neuromonitoring (IONM) can be used to detect impending neurological injuries. This study aimed to analyze IONM in non-idiopathic scoliosis using a minimally invasive fusionless surgical technique. Methods: This retrospective, single-center study was performed from 2014 to 2018. Patients with non-idiopathic scoliosis who underwent a minimally invasive fusionless procedure and had at least 2 years of follow-up were included. IONM was performed using a neurophysiological monitoring work station with somatosensory evoked potentials (SSEP) and neurogenic mixed evoked potentials (NMEP). Results: A total of 290 patients were enrolled. The mean age at surgery was 12.9 +/- 3 years. The main etiology was central nervous system (CNS) disorders (n=139, 48%). Overall, 35 alerts (11%) in the SSEP and 10 (7%) in the NMEP occurred. There were two neurological deficits with total recovery after 6 months. There were no false negatives in either SSEP or NMEP, although there was one false positive in SSEP and two false positives for NMEP in the group without signal recovery. There was no significant relationship between the incidence of SSEP or NMEP loss and age, body mass index (BMI), number of rods used, upper instrumented vertebrae (p=0.36), lower instrumented vertebrae, or type of surgery. A preoperative greater Cobb angle was associated with a significantly higher risk of NMEP loss (p=0.02). In CNS patients, a higher BMI was associated with a statistically significant risk of NMEP loss (p=0.004). The use of a traction table was associated with a higher risk of signal loss (p=0.0005). Conclusion: A preoperative higher Cobb angle and degree of correction were associated with a significant risk of NMEP loss. In CNS scoliosis, a higher BMI was associated with a significant risk of NMEP loss. The use of a traction table was associated with a higher risk of signal loss. (c) 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). Methods: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5m.oto 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis. Results: Seventy video-EEGs were analyzed (1-16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15(8m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7m.o to 12 y.o, median 15m).Epilepsy: 6 Westsyndrome (WS) (2intdup15, 4idic15);4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-bandrapid-rhythms (RR):present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age. Conclusion: WS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay. This study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.

OBJECTIVE:To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants.METHODS:Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient.RESULTS:We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures.CONCLUSIONS:Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort.SIGNIFICANCE:Combining these clinical and electroencephalographic features could help guide genetic diagnosis.

Objective: We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). Methods: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.o to 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis. Results: Seventy video-EEGs were analyzed (1-16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15 (8 m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7 m.o to 12 y. o, median 15 m). Epilepsy: 6 West syndrome (WS) (2intdup15, 4idic15); 4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-band rapid-rhythms (RR): present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age. Conclusion: WS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay. Significance: This study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Epileptic myoclonus (EM) is reported in many paediatric epilepsies from neonatal period to adolescence. Myoclonus can be the only seizure type or may occur among others, independently or in combination as a single ictal event. We report two children presenting with absences associated with myoclonus, predominating on one side, in a setting of two different types of absence seizures and two different electro-clinical syndromes. Patients were explored with long-duration video-EEG coupled to surface EMG polygraphy. EEG was visually analysed and complemented by jerk-locked back-averaging. Two types of seizure, encompassing myoclonus and absence, were identified: myoclonic absences in the context of epilepsy with myoclonic absences and atypical absences with atonic component (negative myoclonus) in the context of encephalopathy related to status epilepticus during slow sleep (ESES). In the latter case, rhythmic upper limb jerking, mimicking positive myoclonus, corresponded to recovery of muscular tone after each negative myoclonus. Due to the rhythmic recovery of muscle tone, subsequent rhythmic negative myoclonus may exhibit a similar clinical picture to that of rhythmic positive myoclonus. Video-EEG recording coupled to EMG polygraphy is essential in order to precisely characterize motor manifestations during seizures with myoclonus [Published with video sequences].

The first and most important step in establishing diagnosis of epilepsy consists of careful history taking from patients and witnesses. The clinical evaluation of the event will lead the indication for further diagnostic tests including e.g. EEG and MRI. Hence, identifying the paroxysmal event as epileptic or non-epileptic is the very first step in the diagnostic process. Paroxysmal events pose a clinical challenge, as these are unpredictable and do not usually occur in the doctor's office. History taking, hunting for witness reports and home-video recordings are the main tools to conclude whether a paroxysmal event is a seizure or not. In this review, we describe the most common differential diagnoses of epileptic seizures, including syncope, psychogenic non-epileptic seizures, as well as a variety of paroxysmal conditions and behaviours of all age groups. Misdiagnosis of non-epileptic events as epilepsy may not only defer the correct diagnosis and treatment but also poses additional risk by prescribing antiepileptic drugs unnecessarily. Moreover, missing the diagnosis of epilepsy implies risk of additional seizures and therefore possibly injuries, sudden death in people with epilepsy, or status epilepticus. Studies have shown that patient and witness accounts are unreliable in a high percentage of cases. Therefore, the core competency of doctors and medical professionals assessing paroxysmal events is knowledge of the clinical features that help define the different aetiologies, thus empowering them to establish the most accurate appraisal of an event. [Published with video sequences].

OBJECTIVE:To quantify whole-brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres.METHODS:Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a perithalamic section. Regional cerebral blood flow and fMRI network connectivity assessed the functional integrity of both hemispheres after surgery. The level of consciousness was tested by means of a support vector machine classifier which compared the intrinsic organization of the dissected hemispheres with those of patients suffering from disorders of consciousness.RESULTS:After hemispherotomy, both patients showed typical daily functionality. We found no interhemispheric transfer of functional connectivity in either patient as predicted by the operation. The healthy left hemispheres displayed focal blood hyperperfusion in motor and limbic areas, with preserved network-level organization. Unexpectedly, the disconnected right hemispheres showed sustained network organization despite low regional cerebral blood flow. Subcortically, functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. One patient further showed unusual ipsilateral right cerebello-cortical connectivity, which was explained by the mediation of the vascular system. The healthy left hemisphere had higher probability to be classified as in a minimally conscious state compared to the isolated right hemisphere.SIGNIFICANCE:Complete hemispherotomy leads to a lateralized whole-brain organization, with the remaining hemisphere claiming most of the brain's energetic reserves supported by subcortical structures. Our results further underline the contribution of nonneuronal vascular signals on contralateral connectivity, shedding light on the nature of network organization in the isolated tissue. The disconnected hemisphere is characterized by a level of consciousness which is necessary but insufficient for conscious processing, paving the way for more specific inquiries about its role in awareness in the absence of behavioral output.

Purpose: We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. Methods: We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. Results: We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/ 10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p=.044 and p=.610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p=.052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p=.037), duration of coma (p=.043), and mortality during the neonatal period (p=.020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. Conclusion: UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

Seizures caused by beta-lactam antibiotics are relatively rare. However, they represent a clinically significant phenomenon and have been widely reported in all age groups. Here we describe two infants presenting subtle multifocal seizures with a migrating aspect on EEG during beta-lactam antibiotic treatment with agents from the carbapenem group (meropenem) and the cephalosporin group (ceftazidime).

EEG changes during the perinatal period, infancy, childhood, and adolescence are concomitant with brain growth, myelination, expanding connectivity, and overall maturation, which are particularly fast during the first year of life. EEG aspects of early brain development are accessible in preterm during the third trimester of gestational age, and they evolve to full-term, infancy, and childhood EEG patterns. Each of these age periods shares specific EEG features that reach gross adult outlines in the first year. Interpreting EEG needs therefore a deep knowledge of pathological and normal EEG patterns with their variants belonging to each age range. Recording EEG during these periods also requires adapting the recording techniques to the specific age in order to obtain interpretable records. This chapter describes normal EEG features and variants, characteristic patterns of development, and some patterns that are unusual for age, from the neonatal period to adolescence.

Objective To report new sporadic cases and 1 family with epilepsy of infancy with migrating focal seizures (EIMFSs) due to KCNT1 gain-of-function and to assess therapies' efficacy including quinidine. Methods We reviewed the clinical, EEG, and molecular data of 17 new patients with EIMFS and KCNT1 mutations, in collaboration with the network of the French reference center for rare epilepsies. Results The mean seizure onset age was 1 month (range: 1 hour to 4 months), and all children had focal motor seizures with autonomic signs and migrating ictal pattern on EEG. Three children also had infantile spasms and hypsarrhythmia. The identified KCNT1 variants clustered as “hot spots” on the C-terminal domain, and all mutations occurred de novo except the p.R398Q mutation inherited from the father with nocturnal frontal lobe epilepsy, present in 2 paternal uncles, one being asymptomatic and the other with single tonic-clonic seizure. In 1 patient with EIMFS, we identified the p.R1106Q mutation associated with Brugada syndrome and saw no abnormality in cardiac rhythm. Quinidine was well tolerated when administered to 2 and 4-year-old patients but did not reduce seizure frequency. Conclusions The majority of the KCNT1 mutations appear to cluster in hot spots essential for the channel activity. A same mutation can be linked to a spectrum of conditions ranging from EMFSI to asymptomatic carrier, even in the same family. None of the antiepileptic therapies displayed clinical efficacy, including quinidine in 2 patients.

Teaching competency in the diagnosis and clinical management of epilepsy is of utmost importance for the ILAE. To achieve this mission, the Task Force for Epilepsy Education (EpiEd) developed a competency-based curriculum for epileptology, covering the spectrum of skills and knowledge for best medical practice. The curriculum encompasses seven domains, 42 competencies, and 124 learning objectives, divided into three levels: entry (Level 1), proficiency (Level 2), and advanced proficiency (Level 3). A survey of the currently existing ILAE-endorsed teaching activities identified a significant gap in education of basic knowledge of epileptology (Level 1). To bridge this gap, a web-based educational tool is being developed. A virtual campus will be constructed around the curriculum, integrating the various educational activities of the ILAE. This paper describes the development of the curriculum and future tasks necessary to achieve the educational goal of the ILAE.

Hemispherotomy is a treatment for drug-resistant epilepsy with the whole hemisphere involved in seizure onset. As recovery mechanisms are still debated, we characterize functional reorganization with multimodal MRI in two children operated on the right hemisphere (RH). We found that interhemispheric functional connectivity was abolished in both patients. The healthy left hemispheres (LH) displayed focal hyperperfusion in motor and limbic areas, and preserved network-level organization. The disconnected RHs were hypoperfused despite sustained network-level organization. Functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. The classification probability of the RH corresponding to a minimally conscious state was smaller than for the LH. We conclude that after hemispherotomy, neurological rehabilitation is sustained by cortical disinhibition and reinforcement of connectivity driven by subcortical structures in the remaining hemisphere. Our results highlight the effect of vascularization on functional connectivity and raise inquiries about the conscious state of the isolated hemisphere.