Original Research: Clinical Significance of a Unique Pediatric EEG Configuration: Bi-Frontal Spikes With Simultaneous Bi-Occipital Positivity.

Introduction: Frontal-predominant epileptiform discharges (EDs) include generalized spike-wave (GSW) and frontal spikes (FS). However, negative bi-frontal ED with simultaneous occipital positivity (BFOD) are rare, leading to questions regarding physiological generators. Methods: To determine the clinical significance of BFOD, electroclinical features of children with BFOD (n = 40) were compared to control patients with GSW (n = 102) and FS (n = 100). Results: Results are presented in the following order: BFOD, GSW, and FS. Epilepsy was prevalent among the groups: 95.0%, 90.2%, and 77.0%, respectively. The median age of seizure-onset did not significantly differ between groups: 3.00, 4.00, and 2.25 years, respectively. Regarding EEG background features, the BFOD group had more disorganized sleep architecture than other groups, P < .005. There was a significant difference in the proportion of developmental delay (DD) between the groups (P < .005). BFOD had much higher odds of DD compared to GSW and FS groups: odds ratio (OR) (confidence interval [CI]) 19.44 [5.64, 64.05] and 3.98 [1.16, 13.34]. Furthermore, BFOD had much higher odds of severe DD compared to GSW and FS groups: 9.60 [2.75, 33.45] and 2.73 [1.03, 7.27]. A Gross Motor Function Classification System (GMFCS) score of ≥ 4 was more prevalent in BFOD (22.5%), than GSW (0%) and FS groups (9%). On neuroimaging, BFOD had more structural (P < .005) and multilobar structural (P < .05) abnormalities than control groups. Conclusion: Children with BFOD had particularly severe significant DD, considerable motor deficit (GMFCS ≥ 4), and brain structural abnormalities, often multilobar. This suggests BFOD is a marker of severe underlying brain dysfunction and not benign when encountered on routine EEG review.

The impact of anti-seizure medications on psychiatric disorders among children with epilepsy: Both a challenge and an opportunity?

Psychiatric disorders are common co-existing conditions in children with epilepsy and can precede or follow epilepsy onset. Therefore, when selecting anti-seizure medications (ASMs) for children with epilepsy, in addition to seizure control, careful consideration of behavioral and psychotropic effects (BPEs) is critical, as they can have a negative impact on ASM adherence and quality of life. The goal in supporting children with epilepsy is an individualized approach to maximize seizure control and minimize negative BPEs. A previous history of a psychiatric disorder is the most significant risk factor for negative BPEs. Therefore, systematic screening for psychiatric symptoms can guide ASM selection and prompt intervention as needed. Besides familiarity with different ASM profiles, awareness of risk factors for negative BPEs including rapid dose titrations and weaning schedules, polypharmacy, high ASM doses, and drug interactions are important. In children with co-existing psychiatric disorders, ASMs with mood stabilizing, behavior regulating or anxiolytic properties may be preferred choices. Overall, a comprehensive and coordinated approach, with family psychoeducation and a mutual understanding of clinical aspects between the disciplines of neurology and psychiatry will enable better outcomes in children with epilepsy. Further pediatric "real-world" studies will expand knowledge of BPEs and potential risk factors. For some children, timely epilepsy surgery or precision therapies targeting a pathological defect may reduce the ASM burden in a child's life and subsequent BPEs. The ability to predict an individual child's susceptibility to negative BPEs with valid biomarkers may become available in the near future with advances in pharmacogenomics and technology.

Les troubles psychiatriques sont des états commun coexistants chez les enfants souffrant d'épilepsie et ils peuvent précéder ou suivre le début de l'épilepsie. Par conséquent, lorsqu'on choisit des médicaments anticonvulsivants (MAC) pour des enfants souffrant d'épilepsie, outre le contrôle des convulsions, il faut prendre sérieusement en considération les effets comportementaux et psychotropes (ECP) car ils peuvent avoir un effet négatif sur l'adhésion aux MAC et à la qualité de vie. Soutenir les enfants souffrant d'épilepsie a pour but une approche individualisée afin de maximiser le contrôle des convulsions et de minimiser les ECP négatifs. Des antécédents d'un trouble psychiatrique constituent le facteur de risque le plus significatif des ECP négatifs. Donc le dépistage systématique des symptômes psychiatriques peut guider la sélection des MAC et provoquer une intervention au besoin. Autre que la familiarité avec différents profils de MAC, la connaissance de facteurs de risque d'ECP négatifs englobe les titrages de dose rapides, et les calendriers de sevrage, la polypharmacie, les doses élevées de MAC, et les interactions des médicaments, tous importants. Chez les enfants souffrant de troubles psychiatriques coexistants, les MAC qui stabilisent l'humeur, régulent le comportement ou ont des propriétés anxiolytiques peuvent être préférés. Généralement, une approche détaillée et coordonnée avec la psychoéducation familiale et une compréhension mutuelle des aspects cliniques entre les disciplines de la neurologie et de la psychiatrie permettront de meilleurs résultats chez les enfants souffrant d'épilepsie. D'autres études psychiatriques « en situation réelle ¼ accroîtront les connaissances des ECP et les facteurs de risque potentiels. Chez certains enfants, une chirurgie de l'épilepsie en temps opportun ou des thérapies de précision ciblant un défaut pathologique peuvent réduire le fardeau des MAC dans la vie de l'enfant et les ECP subséquents. La capacité de prédire la susceptibilité individuelle d'un enfant aux ECP négatifs par des biomarqueurs valides peut être disponible dans un avenir rapproché grâce aux progrès de la pharmacogénomique et de la technologie.

Outcome of Absence Epilepsy With Onset at 8-11 Years of Age: Watershed Ages When Syndromes Overlap.

Introduction: Absence seizures occur in various epilepsy syndromes, including childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. When children present with absence seizures at ages when syndromes overlap, initial syndrome designation is not always possible, making early prognostication challenging. For these children, the study objective is to determine clinical and initial electroencephalograph (EEG) findings to predict the development of generalized tonic-clonic seizures, which is a factor that affects outcome. Methods: Children with new-onset absence seizures between 8 and 11 years of age with at least 5 years of follow-up data were studied through the review of medical records and initial EEG tracings. Results: Ninety-eight patients were included in the study. The median age of absence seizure onset was 9 years (interquartile range [IQR] = 8.00, 10.00) and follow-up was 15 years (IQR = 13.00, 18.00). Forty-six percent developed generalized tonic-clonic seizures and 20% developed myoclonic seizures. On multiple regression analysis, a history of myoclonic seizures, anxiety, as well as bifrontal slowing and mild background slowing on initial EEG (P < .05) were associated with generalized tonic-clonic seizures. Although not statistically significant, a shorter duration of shortest EEG burst on baseline EEG was also associated with generalized tonic-clonic seizures. Conclusion: On initial EEG, bifrontal and background slowing and myoclonic seizures and anxiety are associated with developing generalized tonic-clonic seizures, which is of prognostic significance when early syndrome designation is difficult.

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

BACKGROUND AND OBJECTIVES: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. METHODS: We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details. RESULTS: We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death. DISCUSSION: We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.

School performance in children at the time of new-onset seizures and at long-term follow-up: A retrospective cohort study.

OBJECTIVE: School-performance difficulties (SPD) are common in children with epilepsy. The objectives of this study were to determine if the rate of SPD in children with seizures change from seizure-onset to follow-up and differ from children with psychiatric disorders. METHODS: School-aged children who required an initial electroencephalography (EEG) test in 2016 were reviewed and separated into two groups based on the presence or absence of seizures. Developmental delay and SPD were compared between groups at initial assessment and SPD was assessed after 2-4 years of follow-up. Analysis was also performed on a sub-set of patients with psychiatric disorders. RESULTS: At baseline, the rate of SPD was similar between the seizure (n = 146) and non-seizure (n = 332) groups [26% vs. 27%]. At follow-up, the seizure (n = 119) group had a significantly higher rate of SPD than the non-seizure (n = 215) group (54% vs. 43%). There was no difference in the rate of SPD between the seizure (n = 119) and psychiatric (n = 69) groups at baseline (31% vs. 43%) or follow-up (54% vs. 55%). CONCLUSION: Over time, children with recurrent seizures experience more SPD than children without seizures, but similar SPD to children with psychiatric disorders.

Resilience of adolescents and teenagers with self-limited and genetic-generalized epilepsy during the COVID-19 pandemic.

INTRODUCTION: The study-objective was to determine the emotional impact of the COVID-19 pandemic on children with self-limited and genetic-generalized epilepsy. METHODS: Patients completed the Children's Depression Inventory-2 (CDI-2) and Multidimensional Anxiety Scale for Children 2nd Edition (MASC-2) questionnaires before and during the pandemic. Via tele-visits, a pandemic-lifestyle survey and Obsession with COVID-19 Scale (OCS) was administered. RESULTS: Fifty subjects with a mean (SD) age of 14.44 (2.97) years and 4.85 (2.97) years of epilepsy were included. Overall, mood (62%), anxiety (61%), sleep (68%) and seizure frequency (88%) were unchanged/improved during the pandemic. There was no significant difference in pre-COVID-19 and during COVID-19 CDI-2 and MASC-2 total T-scores. In 24% with a worsening CDI-2 total T-score, associations included higher total OCS score (p = 0.001), poor sleep (p = 0.013) and pre-existing psychiatric history (p = 0.0450). In 28% with a worsening MASC-2 total T-score, associations included less exercise during the pandemic (p = 0.028) and lower maternal education history (p = 0.022). On OCS, 6% were in the dysfunctional range. CONCLUSIONS: This cohort demonstrated emotional resilience during the COVID-19 pandemic. However, screening is important, as a subgroup experienced disruptive changes, possibly related to modifiable factors, such as sleep and exercise. LAY SUMMARY: To determine the impact of the COVID-19 pandemic on children with epilepsy (CWE), 50 CWE completed a pandemic-lifestyle survey. Questionnaires for anxiety and depression completed before and during the COVID-19 pandemic were also compared. Overall, there was no worsening of seizures, anxiety, or depression during the pandemic. During the pandemic, 24% had more depressive symptoms (associations: poor sleep and psychiatric history) and 28% had more anxiety (associations: less exercise and lower maternal education).This cohort showed emotional resilience during the COVID-19 pandemic. Regular screening is important, as some CWE experienced disruptive changes, related to modifiable-factors, such as sleep and exercise.

Children With Trisomy 21 and Lennox-Gastaut Syndrome With Predominant Myoclonic Seizures.

INTRODUCTION: Lennox-Gastaut syndrome is a severe form of pediatric epilepsy that is classically defined by a triad of drug-resistant seizures, including atonic, tonic, and atypical absence seizures; slow spike-and-wave discharges and paroxysmal fast activity on electroencephalography (EEG); and cognitive and behavioral dysfunction. In the vast majority, Lennox-Gastaut syndrome develops in patients with an identified etiology, including genetic or structural brain abnormalities. Long-term prognosis is generally poor with progressive intellectual deterioration and persistent seizures. At present, there are few reported cases of Lennox-Gastaut syndrome and trisomy 21 in the literature. To further delineate the spectrum of epilepsy in trisomy 21, we reviewed children with trisomy 21 and Lennox-Gastaut syndrome at one center over 28 years. METHODS: This is a retrospective case series. At our institution, all EEG results are entered into a database, which was queried for patients with trisomy 21 from 1992 to 2019. Pertinent electroclinical data was obtained from medical records. RESULTS: Of 63 patients with trisomy 21 and epilepsy, 6 (10%) had Lennox-Gastaut syndrome and were included in the study. Four of the 6 patients were male and 5 of 6 had neuroimaging, which was normal. Follow-up ranged from 3 to 20 years. Notably, 5 of 6 had predominant myoclonic seizures throughout the course of their epilepsy, associated with generalized spike-wave discharges, <100 milliseconds. CONCLUSION: We observed myoclonic seizures to be a predominant seizure type in patients with trisomy 21, suggestive that trisomy 21 patients may have a unique pattern of Lennox-Gastaut syndrome.

Pediatric Occipital Spikes at a Single Center Over 26 Years and the Significance of Tangential Dipole.

BACKGROUND: Pediatric occipital epileptiform discharges occur in various clinical settings, including self-limited and treatment-resistant epilepsies. The study objective is to determine electro-clinical predictors for prognosis in children with occipital epileptiform discharges. METHODS: 205 patients with occipital epileptiform discharges were classified into seizure groups: self-limited occipital (SLO) (n = 57), including Panayiotopoulos and Gastaut syndrome; non-self-limited occipital (non-SLO) (n = 98), including various seizure etiologies; genetic-generalized (n = 18); febrile (n = 5); and no-seizure (n = 27) groups. Electro-clinical features of the SLO and non-SLO were compared, as this is of most clinical relevance. RESULTS: The median age of seizure onset was 3 years (range: 0-19). Occipital epileptiform discharges with frontal/central positivity were present in both groups, but more common in the SLO than non-SLO groups; 21/57 (36.8%) and 19/98 (19.4%), respectively (P < .022). However, when occipital epileptiform discharges with tangential dipoles (P < .048) were accompanied by abnormal ictal eye movements (P < .037), they were predictive of SLO epilepsy. CONCLUSIONS: In our cohort, occipital epileptiform discharges with tangential dipole detected by visual analysis and abnormal ictal eye movements were predictive of SLO epilepsy.

Infantile Spasms and Trisomy 21: Unfavorable Outcomes with First-line Vigabatrin Therapy.

INTRODUCTION: Among children with infantile spasms (ISs), those with trisomy 21 (T21) and those with normal development at onset and no identifiable etiology (previously referred to as "idiopathic") are expected to have relatively favorable outcomes. The study objective is to determine if differences exist in treatment response, relapse, and subsequent epilepsy between these two groups when vigabatrin is used as first-line treatment. METHODS: In this retrospective study, patients were classified into the following groups and clinical features were compared: T21 (n = 24) and IS with normal development at onset and no identified etiology (n = 40; control group). RESULTS: There was no significant difference in the age of IS onset, sex distribution, or treatment lag between the groups. The T21 compared to the control group required a higher mean number of anti-seizure therapies (3.6 vs. 1.9, p < 0.001), had more relapses [10 (42%) vs. 4 (10%), p < 0.005)], and had higher risk of subsequent epilepsy [11 (46%) vs. 8 (20%), p < 0.003]. Relapses were often delayed in the T21 group, with a mean of 8 months after IS cessation. CONCLUSION: Our results differ from most studies using steroids as first-line treatment where the groups were shown to have similar treatment response and T21 patients had a low risk of relapse and subsequent epilepsy. Therefore, our results suggest that vigabatrin as first-line treatment in T21 with IS may be less favorable than steroids.

Hypnagogic Frontal EEG Bursts in Children: Epileptic or Not?

PURPOSE: Various EEG patterns emerge in drowsiness. Intermittent bilateral midfrontal slowing (BFS) and hypnogogic frontal predominant sharply contoured waveforms (HFSC), maximal at (Fz, F3-4, and Fp1-2), are often encountered. These do not meet the criteria for epileptiform discharges. The study objective was to determine the clinical significance of BFS and HFSC. METHODS: Clinical information of children with BFS (n = 49) and HFSC (n = 99) was compared with control subjects with generalized spike-wave (GSW) discharges (n = 102) and normal EEGs (n = 100). RESULTS: HFSC was present in younger children (mean age was 3.5 ± 3.6 years), whereas BFS was present in older children (mean 12.9 ± 4.8 years). Seizures occurred in the normal EEG, BFS, HFSC, and GSW groups, respectively, as follows: 22 (22%), 15 (31%), 42 (43%), and 100 (98%) patients, whereas epilepsy occurred in 17 (17%), 10 (20%), 35 (35%), and 95 (93%) patients. The GSW group had more seizures and epilepsy than the other groups (P < 0.001), but the HFSC group also had more seizures (P < 0.001) and epilepsy (P < 0.003) than the normal EEG group. Seizures and neurodevelopmental and psychiatric comorbidities were similar between the BFS and normal EEG groups. Notably, the HFSC group had more developmental delay than the normal EEG group [33 (33%) versus 18 (18%), P < 0.009] but were similar to the GSW group 22 (22%). CONCLUSIONS: Bilateral midfrontal slowing and HFSC have had unclear significance. Our results suggest that HFSC may be a marker of increased risk of seizure, epilepsy, and developmental delay as compared to children with normal EEGs and has similar risk of developmental delay to those with GSW.

Two Patients With KCNT1-Related Epilepsy Responding to Phenobarbital and Potassium Bromide.

KCNT1 encodes a sodium-activated potassium channel highly expressed in the brain, regulating hyperpolarization following repetitive firing. Mutations in KCNT1 were originally implicated in autosomal-dominant nocturnal frontal lobe epilepsy and epilepsy of infancy with migrating focal seizures. It is now known that there is variability in phenotypic expression and incomplete penetrance. We describe 2 patients with KCNT1-related epilepsy, one with epilepsy of infancy with migrating focal seizures and one with multifocal epilepsy. As most patients with KCNT1 variants have treatment-resistant epilepsy, drugs that specifically target the KCNT1 channel have been of great interest. Quinidine, a broad-spectrum potassium channel blocker, has shown promise; however, clinical trial results have been variable. Our patient with epilepsy of infancy with migrating focal seizures did not respond to a trial of quinidine at 6 weeks of age-one of the earliest reported quinidine trials in the literature for KCNT1-related epilepsy. This indicates that timing of treatment and response may not be related. Both patients responded to high-dose phenobarbital. The patient with epilepsy of infancy with migrating focal seizures also had a significant reduction in seizures with potassium bromide (KBr). Our data suggest that alternative therapies to quinidine should be considered as a therapeutic option for patients with KCNT1-related epilepsy. Although improved seizure control led to parent-reported improvements in neurodevelopment, it is unknown if phenobarbital and KBr impact the overall developmental trajectory of patients with KCNT1-related epilepsy. Further multicenter longitudinal studies are required.

Clinical Significance of Incidental Rolandic Spikes in Children With Absence Epilepsy.

PURPOSE: Absence epilepsy and benign epilepsy of childhood with central temporal spikes are common childhood epilepsy syndromes. Although 3-Hz generalized spike-wave discharges are almost always associated with absence seizures, rolandic spikes can be present in individuals without rolandic seizures. The co-occurrence of 3-Hz generalized spike-wave and rolandic spikes is very rare. Our objective was to compare clinical features of patients with absence epilepsy with and without rolandic spikes, to determine if the additional feature of rolandic spikes has any clinical significance. METHODS: Clinical information of 17 children with absence epilepsy and rolandic spikes was compared to an age-matched control group of 90 children with absence epilepsy. RESULTS: Although most patients had excellent seizure control at follow-up, epilepsy comorbidities (cognitive and emotional problems) were observed. Comparing study vs control groups, there was no difference with anxiety (2 [11.8%] vs 8 [9%]), behavioral issues (4 [23.5%] vs 10 [11%]), mood disorders (0 vs 2 [2%]), and attention-deficit hyperactivity disorder (4 [24%] vs 10 [11%]). Significant differences were also observed: more global-developmental (5 [29%] vs 5 [6%], P < .009) and expressive-language (4 [24%] vs 5 [6%], P < .034) delay and more difficulties with school performance (11 [65%] vs 32 [36%], P < .025), especially with language-related tasks (6 [35%] vs 5 [6%], P < .001). CONCLUSION: Our results confirm the presence of additional epilepsy comorbidities in patients with absence epilepsy when rolandic spikes are present. Rolandic spikes in patients with absence epilepsy may be a marker of additional cognitive challenges that physicians should be aware of.

Co-existence of Rolandic and 3 Hz Spike-Wave Discharges on EEG in Children with Epilepsy.

OBJECTIVE: Benign epilepsy of childhood with central temporal spikes (BECTS) and absence epilepsy are common epilepsy syndromes in children with similar age of onset and favorable prognosis. However, the co-existence of the electrocardiogram (EEG) findings of rolandic spike and 3 Hz generalized spike-wave (GSW) discharges is extremely rare, with few cases reported in the literature. Our objective was to characterize the EEG findings of these syndromes in children in our center and review the electro-clinical features. METHODS: All EEGs at BC Children's Hospital are entered in a database, which include EEG findings and clinical data. Patients with both centro-temporal spikes and 3 Hz GSW discharges were identified from the database and clinical data were reviewed. RESULTS: Among the 43,061 patients in the database from 1992 to 2017, 1426 with isolated rolandic discharges and 528 patients with isolated 3 Hz GSW discharges were identified, and 20 (0.05%) patients had both findings: 3/20 had BECTS, and subsequently developed childhood absence epilepsy and 17/20 had no seizures characteristic for BECTS. At follow-up, 17 (85%) were seizure-free, 1 (5%) had rare, and 2 (10%) had frequent seizures. CONCLUSIONS: This is the largest reported group of patients to our knowledge with the co-existence of rolandic and 3 Hz GSW discharges on EEGs in one institution, not drug-induced. As the presence of both findings is extremely rare, distinct pathophysiological mechanisms are likely. The majority had excellent seizure control at follow-up, similar to what would be expected for each type of epilepsy alone.

OBJECTIF: L'épilepsie bénigne de l'enfance à pointes centro-temporales (ou épilepsie rolandique bénigne [ERB]) et l'absence épileptique sont des syndromes épileptiques communs chez des enfants dont le pronostic est favorable et dont l'apparition des premiers symptômes s'est produite à un âge similaire. Cependant, la coexistence, lors d'EEG, de résultats montrant des décharges rolandiques et des décharges à pointes-ondes continues de 3 Hz demeure extrêmement rare, peu de cas ayant été signalés dans la littérature scientifique. Notre objectif a donc consisté à décrire les résultats d'EEG liés à ces syndromes dans le cas d'enfants fréquentant notre établissement et à examiner leurs caractéristiques électro-cliniques. MÉTHODES: En plus de certaines données cliniques, tous les résultats d'EEG réalisés au BC Children's Hospital sont saisis dans une base de données. Tant les jeunes patients donnant à voir des décharges à pointes centro-temporales que ceux atteints de décharges à pointes-ondes continues de 3 Hz ont été identifiés à partir de cette base de données. Leurs données cliniques ont été ensuite passées en revue. RÉSULTATS: Sur un total de 43 061 jeunes patients présents dans la base de données de 1992 à 2017, nous en avons identifié 1426 avec des décharges rolandiques isolées et 528 avec des décharges isolées à pointes-ondes de 3 Hz. À noter que seulement vingt d'entre eux, soit 0,05 %, étaient concernés par ces deux types de décharge. À cet égard, 3 sur 20 étaient atteints d'ERB et ont développé ultérieurement un syndrome d'absence épileptique; chez les 17 autres, aucune convulsion caractéristique de l'ERB n'a été observée. Lors d'un suivi, 17 (85 %) d'entre eux n'avaient plus de crises convulsives tandis que 1 (5 %) avait exceptionnellement des crises et 2 (10 %), des crises fréquentes. CONCLUSIONS: À notre connaissance, il s'agit là du plus vaste groupe déclaré de patients donnant à voir, lors d'EGG menés au sein d'un seul établissement, une coexistence entre des décharges rolandiques et des décharges à pointes-ondes de 3 Hz, et ce, sans qu'elles n'aient été causées par des médicaments. Considérant que la présence de ces deux phénomènes est particulièrement inhabituelle, le rôle de divers mécanismes pathophysiologiques est fort probable. Fait à souligner, la majorité de ces patients ont pu montrer, au moment de leur suivi, une excellente maîtrise de leurs crises convulsives, maîtrise semblable à celle à laquelle on pourrait s'attendre pour chaque type d'épilepsie pris individuellement.

Predictive Value of Midline Spikes on Pediatric EEG for Seizure and Developmental Outcome.

PURPOSE: Midline spikes are epileptiform discharges localized to the midsagittal regions of the brain. Isolated midline spikes are rare, but more common in children. Our objective was to determine whether midline spikes are predictive of seizure characteristics and neurodevelopment. METHODS: EEGs and clinical information of 123 children with isolated midline spikes, and EEG follow-up within 12 to 24 months, were reviewed and compared with controls. RESULTS: Most children with midline spikes had seizures (91%), with an equal predisposition to focal or generalized seizure semiology. There was no difference between the midline spike and control groups in terms of neonatal complications, seizure characteristics (type, frequency, and etiology), and neurologic examination findings. In patients with abnormal neuro-maging, deep gray or white matter abnormalities were more frequent in the midline group (41% vs. 13%, P = 0.02). The midline group had a higher risk of development delay (DD) than controls (43% vs. 29%, odds ratio: 1.8, 95% CI [1.1-3.2], P = 0.03). A higher risk of DD was also noted in the midline group in those aged less than 4 years (52% vs. 26%, odds ratio: 3.1, 95% CI [1.0-9.2], P = 0.04) and in those without seizures (40% vs. 17%, odds ratio: 3.16, 95% CI [1.1-8.8], P = 0.03). CONCLUSIONS: This is the largest reported group of patients with midline spikes. Midline spikes have a strong association with seizures and DD. Our data suggest that midline spikes result from heterogeneous etiologies, are more common in young children, and are not benign.

Lack of response to quinidine in KCNT1-related neonatal epilepsy.

OBJECTIVE: To evaluate the clinical efficacy and safety of quinidine in patients with KCNT1-related epilepsy of infancy with migrating focal seizures (EIMFS) in the infantile period and to compare with the effect of quinidine on mutant channels in vitro. METHODS: We identified 4 patients with EIMFS with onset in the neonatal period, pathogenic variants in the KCNT1 gene, and lack of response to AEDs. Patients were prospectively enrolled, treated with quinidine, and monitored according to a predefined protocol. Electroclinical, neuroimaging, and genetic data were reviewed. Two patients had novel variants in the KCNT1 gene that were modeled in Xenopus oocytes with channel properties characterized using electrophysiology recordings. RESULTS: Three of four patients were treated with quinidine early in their disease course, prior to 6 months of age. No significant side effects were noted with quinidine therapy. In addition, there were no significant changes in electroencephalography (EEG)-confirmed seizure burden during therapy, and patients had near hourly seizures before, during, and after treatment. Two patients had previously reported gain-of-function mutations, which demonstrated sensitivity to high levels of quinidine in the oocyte assay. Two patients with novel variants, showed characteristic gain-of-function and were thus predicted to be pathogenic. Of interest, these variants were essentially insensitive to high levels of quinidine. SIGNIFICANCE: Patients had no reported benefit to quinidine therapy despite age at treatment initiation. Pharmacogenetic results in oocytes were consistent with clinical treatment failure in 2 patients, suggesting that single-dose pharmacologic assessment may be helpful in predicting which patients are exceedingly unlikely to achieve benefit with quinidine. In the 2 patients who had a lack of therapeutic benefit despite sensitivity to high concentrations of quinidine with in vitro oocyte assay, it is likely that the achievable exposure levels in the brain were too low to cause significant in vivo channel blockade.

Clinical Experience With Perampanel for Refractory Pediatric Epilepsy in One Canadian Center.

Perampanel (PER) is a new antiseizure medication that inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors. It is important for physicians to be aware of the efficacy and tolerability of new drugs in the postmarketing phase. We performed a retrospective review of our experience with perampanel at BC Children's Hospital. Twenty-four pediatric patients prescribed perampanel from 2014 to 2016 were identified. Fifteen (63%) discontinued perampanel, and 10 (42%) had greater than 50% reduction in seizures. Twelve (50%) had behavioral and 8 (33%) had nonbehavioral adverse events. One-third experienced serious adverse events. One patient experienced oculogyric crisis, which is not previously reported with perampanel. Adverse events were not dose related and were reversible. Possible risk factors for behavioral adverse events include a history of behavioral problems with other antiseizure medications and preexisting behavioral comorbidities. It is important to counsel patients about the potential for serious adverse events, particularly behavioral, when prescribing perampanel.

Intelligence quotient is not affected by epilepsy surgery in childhood.

Epilepsy surgery is known to help children with intractable seizures. The effect of epilepsy surgery itself on cognition in childhood is less well studied. We report our experience at the University of Alberta Hospital on the effects of epilepsy surgery on cognition. All children undergoing epilepsy surgery at the Comprehensive Epilepsy Program from 1990-2005 were examined. Sixty-seven patients received both preoperative and postoperative neuropsychologic evaluations. We compared verbal, performance, and full scale intelligent quotients and the Child Behavioral Checklist preoperatively and postoperatively. Forty-eight patients demonstrated excellent surgical outcomes, with significant reductions in disabling seizures. Overall, no significant change occurred in neuropsychologic parameters examined after surgery. Epilepsy surgery in childhood offers excellent surgical outcomes for seizure control, and does not adversely affect intelligence quotient.

Clinical presentation and diagnosis of tuberous sclerosis complex in infancy.

The age-dependent nature of the characteristic features of tuberous sclerosis complex has historically presented challenges for the diagnosis in infancy. Although the increasing availability of neuroimaging and genetic testing has facilitated the diagnosis in neonates and infants, there are few reports describing how tuberous sclerosis complex presents in this age group. We performed a retrospective review of children diagnosed with tuberous sclerosis complex during the first year of life, compiling their clinical features at presentation and diagnosis, seizure history, and imaging findings. We identified 41 infants diagnosed with tuberous sclerosis complex before age 1 year. Their age at initial presentation ranged from antenatal to 9 months of age. Twenty-three patients (56%) initially presented with a cardiac rhabdomyoma, of which 15 were identified antenatally. Fourteen patients (34%) initially presented with seizures, and 6 (15%) initially presented with hypomelanotic macules. Five infants (12%) had a family history of tuberous sclerosis complex. A definitive diagnosis of tuberous sclerosis complex was accomplished antenatally in 4 patients, whereas the rest were diagnosed at a median age of 2 months. All 41 patients underwent neuroimaging during infancy; 36 (88%) had radiographic evidence of cortical tubers, and 38 (93%) had subependymal nodules. Neuroimaging resulted in a definitive diagnosis of tuberous sclerosis complex in 95% of patients. The diagnosis of tuberous sclerosis complex in infancy is aided by a high index of suspicion and timely access to neuroimaging. Early diagnosis of tuberous sclerosis complex may be essential to the success of future therapies by providing a window of opportunity for their use.