Abnormal Electroencephalogram Research Articles

Molecular Mechanisms of Epileptic Encephalopathy Caused by KCNMA1 Loss-of-Function Mutations.

The gene kcnma1 encodes the α-subunit of high-conductance calcium- and voltage-dependent K+ (BK) potassium channel. With the development of generation gene sequencing technology, many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. Here, we performed a genetic screen of 26 patients with febrile seizures and identified a novel mutation of KCNMA1 (E155Q). Electrophysiological characterization of different KCNMA1 mutants in HEK 293T cells, the previously-reported R458T and E884K variants (not yet determined), as well as the newly-found E155Q variant, revealed that the current density amplitude of all the above variants was significantly smaller than that of the wild-type (WT) channel. All the above variants caused a positive shift of the I-V curve and played a role through the loss-of-function (LOF) mechanism. Moreover, the β4 subunit slowed down the activation of the E155Q mutant. Then, we used kcnma1 knockout (BK KO) mice as the overall animal model of LOF mutants. It was found that BK KO mice had spontaneous epilepsy, motor impairment, autophagic dysfunction, abnormal electroencephalogram (EEG) signals, as well as possible anxiety and cognitive impairment. In addition, we performed transcriptomic analysis on the hippocampus and cortex of BK KO and WT mice. We identified many differentially expressed genes (DEGs). Eight dysregulated genes [i.e., (Gfap and Grm3 associated with astrocyte activation) (Alpl and Nlrp10 associated with neuroinflammation) (Efna5 and Reln associated with epilepsy) (Cdkn1a and Nr4a1 associated with autophagy)] were validated by RT-PCR, which showed a high concordance with transcriptomic analysis. Calcium imaging results suggested that BK might regulate the autophagy pathway from TRPML1. In conclusion, our study indicated that newly-found point E155Q resulted in a novel loss-of-function variant and the dysregulation of gene expression, especially astrocyte activation, neuroinflammation and autophagy, might be the molecular mechanism of BK-LOF meditated epilepsy.

A case of Landau-Kleffner syndrome with SLC26A4-related hearing impairment

BackgroundLandau-Kleffner syndrome (LKS) is an acquired aphasia and electroencephalogram (EEG) abnormalities mainly in temporoparietal areas. SLC26A4 mutations can cause hearing loss associated with enlarged vestibular aqueduct (EVA).Case presentationsWe report a case of LKS in a 5-year-old boy with non-syndromic EVA due to homozygous mutations of c.919-2A>G (IVS7-2A>G) in SLC26A4. He had normal language development before 2 years old. At the age of 2.5 years, he was admitted to the hospital due to remarkable language delay, and diagnosed with hearing loss with EVA. The seizures started at 4.4 years of age and EEG recording showed electrical status epilepticus during sleep (ESES) with a posterior-temporal predominance. He received cochlear implantation in the right ear at 4.7 years of age, which improved his hearing and language skills. The nocturnal focal motor seizures recurred at 4.9 years of age. Then a remarkable inability to respond to calls and reduction in spontaneous speech were noticed. He was treated with methylprednisolone at 5 years old, which controlled the seizures, suppressed ESES, and remarkably improved the language ability. The absence of seizures maintained until the last follow-up at 5.3 years of age, with further improvements in EEG recording and language ability.ConclusionsThe co-existence of LKS and hearing loss caused by SLC26A4 mutations increases the difficulty of LKS diagnosis, especially in the presence of hearing loss and impaired language skills. EEG discharges predominantly in temporoparietal areas, the occurrence of ESES, and language improvement after antiepileptic medications are potential indicators for LKS diagnosis.

Evaluation of graphene-derived bone scaffold exposure to the calvarial bone_in-vitro and in-vivo studies

Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.

Risk factors of epilepsy in children with complex febrile seizures: A retrospective cohort study.

Febrile seizures are the most common seizures in children. Children with complex febrile seizures have a higher risk of subsequent epilepsy compared with children with simple febrile seizures. Multiple risks factors for epilepsy, including focal status epilepticus, family history of epilepsy, neurodevelopmental abnormalities and abnormal electroencephalogram findings, have been found with inconsistent results. The aim of this study is to identify risk factors for developing epilepsy in children with complex febrile seizures. The study included 248 children aged 3-72-months, diagnosed with complex febrile seizures at Chiang Mai University Hospital. Demographic data, seizure characteristics, electroencephalogram and neuroimaging findings were identified, and assessed to establish whether they were risk factors for subsequent epilepsy. Fifty-five patients (22.1%) had subsequent epilepsy. Using Cox regression-survival analysis, factors associated with epilepsy were prolonged seizures >15 min (P = 0.006; Hazard Ratio (HR): 2.475; 95% Confidence Interval (CI): 1.294-4.735), developmental delay (P = 0.019; HR: 4.476; 95% CI: 2.280-15.646), epileptiform discharges on electroencephalogram (P = 0.023; HR: 1.391; 95%CI: 1.174-1.876), and abnormal neuroimaging (computed tomography or magnetic resonance imaging; P = 0.028; HR: 1.355; 95% CI: 1.034-1.776). Age at onset, peak febrile temperature, duration between the onset of fever and the occurrence of seizure, recurrent seizures within 24 h, focal seizures, abnormal neurological exams and family history of febrile seizure or epilepsy were not associated with increased risk of subsequent epilepsy in this study. Risk factors associated with increased risk of epilepsy in children with complex febrile seizures are prolonged seizures or febrile status epilepticus, developmental delay, electroencephalogram epileptiform discharges, and abnormal neuroimaging. Their presence would merit close clinical monitoring.

The frequency of abnormal electroencephalography for detecting acute ischemic stroke

Introduction. Cerebrovascular accident is defined as rapidly developing symptoms or signs of focal and global loss of cerebral function lasting for 24 hours or more with no apparent cause other than that of vascular origin. Stroke is the fifth leading cause of death in the United States and it is one of the most disabling cause of neurological disorders. The attack of cerebrovascular accident begins abruptly, the focal neurologic deficit either fully evolved at the onset or it progress over minutes to hours or within days. Electroencephalogram (EEG) is used to detect electrical activity in the brain for various neurologic disorders like epilepsy, encephalopathy, prion diseases (CJD), Alzheimer disease and also stroke. Objective. To determine the frequency of abnormal EEG for detecting acute ischemic stroke. Methods. This was a cross sectional study conducted at Department of Medicine, Dow University of Health Sciences Karachi OJHA Campus, Dow International Medical College (DIMC), and Duration of study was 06 month from 1st October 2020 to 30th March 2021. Non-probability consecutive sampling technique was used. A total of 460 patients of acute ischemic stroke were included in this study. Patients were diagnosed on the basis of CT scan brain or diffusion weighted imaging. Within 24 hours the EEG was done in all admitted patients. The potentials recorded by EEG were cumulated excitatory and inhibitory postsynaptic potentials in neuronal dendrites, usually in most superficial regions of cerebral cortex. All data was entered and analyzed using SPSS v25.0. Data were stratified for age, gender, BMI and duration of stroke to address the effect modifiers. Post-stratification, Chi-square test was used by taking p-value ≤0.05 as significant. Results. 460 patients were selected for this study. Mean age was 40.04±9.1 years. Among cases, there were 276 (60%) males and 184 (40%) females. 235 patients (51.08%) had abnormal EEG. By stratification of abnormal EEG, it was found that duration of acute stroke had significant effect having abnormal EEG (p = 0.000001). Conclusions. The role of complexity of abnormal Electro Encephalogram is useful following acute ischemic stroke. The various parameters of EEG help to evaluate the large ischemic stroke.

GABRB3 mutation as a cause of Ohtahara syndrome: A case report

Ohtahara syndrome (OS) is a rare early infantile epileptic encephalopathy that is characterized by an abnormal electroencephalogram (EEG) and intractable seizures. The patient of this reported case is a 4-month-old male infant delivered by cesarean section with an uneventful antenatal and neonatal period. At 2 months of age, he developed seizures that were refractory to anticonvulsants. Prolonged video EEG showed a characteristic suppression-burst pattern. We report an infant OS associated with heterozygous mutation in the GABRB3 gene.

To Study the Electroencephalogram Changes in Children with Acute Encephalitis

Aim: To study the electroencephalogram changes in children with acute encephalitis. Study design: Cross-sectional study. Place and duration of study: The cases were admitted from OPD and emergency over duration of 10 months from May2009 to March 2010 in Children Hospital PIMS, Islamabad. Method: Patients with Cerebral Palsy, Degenerative Brain disease, Cerebral Malaria and Meningitis were excluded. Written informed consent was taken from parents /guardians. All patients, from both genders, age varying from 4 months to 12 years, fitting the criteria of Acute Encephalitis according to ICD 9 & 10 were included in the study, which were 56 in total. All cases had Lumbar puncture and Cerebro Spinal Fluid examination. The findings of pleocytosis (WBC count more than5 u/l), protein and sugar were recorded. EEG (Electroencecephlogram) was done in 52 patients, frequencies and percentages were calculated of the findings. Results: The mean age was 4. 6 years, (varying from 4 months to 12 years) with a standard deviation of 3. 2. From a total of fifty six patients, 38(68%) were males and 18(32%) females. All cases presented with fever (100%). Cerebro Spinal Fluid examination, showed Pleocytosis in 30(54%) while 46(46%) had normal cell count. Cerebro Spinal Fluid protein content was normal in 45(80%) and increased in 11(20%). Cerebro Spinal Fluid sugar was normal in 50(89%) and 6(11%) had low. Electroencephalogram was done in fifty-two patients out of which 30(58%) were normal, 22(42%) were abnormal. Intermittent slowing was found in 17(77%) and 5(23%) cases had focal discharges along with intermittent slowing, out of which three were unilateral temporo-frontal discharges, two cases had other focal discharges on EEG. Conclusion: In patients with Acute Encephalitis, slowing of the rhythm was the most frequent abnormal Electroencephalogram finding, followed by focal discharges in children admitted in Children’s Hospital PIMS, Islamabad. Keywords: Acute Encephalitis, Electroencephalogram (electro encephalogram), Cerebro Spinal Fluid Pleocytosis, Fever

Phenotypes in Children With SYNGAP1 Encephalopathy in China.

Objective: We aimed to explore the associated clinical phenotype and the natural history of patients with SYNGAP1 gene variations during early childhood and to identify their genotype–phenotype correlations.Methods: This study used a cohort of 13 patients with epilepsy and developmental disorder due to SYNGAP1 mutations, namely, 7 patients from Shenzhen Children’s Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied.Results: A total of 13 children with SYNGAP1 gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed.Conclusion: The most common age of disease onset in SYNGAP1 gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype–phenotype correlation.Trial registration: Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).

Neonatal Group B Streptococcal Meningitis: Predictors for Poor Neurologic Outcome at 18 Months

To find early predictors for poor neurodevelopmental outcome after neonatal group B streptococcal meningitis. We retrospectively analyzed clinical characteristics of 23 patients with neonatal group B streptococcal meningitis and their neurodevelopmental outcome at 18 months. Available group B Streptococcus strains were serotyped and their genomes characterized. We found several differences between patients with early- (n = 5) and late-onset (n = 18) disease. Nine children had neurologic abnormalities at 18 months and 4 had epilepsy, all of them after late-onset disease. Most important risk factors for poor outcome were impaired consciousness at admission, hemodynamic instability, seizures, or abnormal electroencephalogram during the acute illness and abnormal neurologic and ophthalmologic examination at the end of treatment, whereas abnormalities in laboratory and imaging studies were not predictive. Hypervirulent serotype III, multilocus sequence type 17 group B Streptococcus was the predominant pathogen. Neurodevelopmental impairment after neonatal group B streptococcal meningitis is likelier in those with clinical and neurophysiological features indicating worse disease severity.

Sex-Specific ADHD-like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice.

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5−/−) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5−/− mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5−/− mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5−/− mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5−/− mice. Together, St3gal5−/− mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.

Electroencephalogram Abnormalities and Epilepsy in Autism Spectrum Disorders: Clinical and Electroencephalogram Findings

AbstractIt has been known for several decades that epilepsy and autism spectrum disorders (ASD) are related to each other. Epilepsy frequently accompanies ASD. The purpose of this study was to investigate relationship between clinical and electroencephalogram (EEG) findings in ASD patients and to identify EEG characteristics that may create a disposition to epilepsy in ASD by examining differences in clinical and EEG findings between patients diagnosed with ASD without epilepsy and ASD with epilepsy. A total of 102 patients aged 2 to 18 years and diagnosed with ASD based on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria between January 2017 and June 2019 were included in the study. Patients were assigned into two groups: (1) ASD with epilepsy and (2) ASD without epilepsy. Clinical findings were retrieved from patients' files, and EEG findings from first EEG records in the EEG laboratory at the time of diagnosis. EEG findings were defined as central, parietal, frontal, temporal, or generalized, depending on the location of rhythmic discharges. The incidence of epilepsy in our ASD patients was 33.7% and that of febrile convulsion was 4%. Generalized motor seizures were the most common seizure type. Epileptic discharges most commonly derived from the central and frontal regions. These abnormalities, especially frontal and central rhythmic discharges, may represent a precursor for the development of epilepsy in ASD patients.

Reiterating the role of corpus callosum in generalization of interictal and ictal epileptiform discharges: a case report with post-callosotomy intracranial electroencephalography in Lennox–Gastaut syndrome

Lennox–Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by delayed mental development and intractable multiple seizure types, predominantly tonic. Drop attacks are the commonest and the most disabling type of seizures. Resective surgery is often not possible in LGS as the electroencephalogram (EEG) abnormalities are usually multifocal and generalized, and magnetic resonance image is often either normal or multilesional. We report a case of LGS with bilateral parieto-occipital gliosis where EEG before and after callosotomy demonstrated synchronized bilateral interictal epileptiform discharges and ictal discharges becoming desynchronized and running down. This phenomenon emphasizes the role of the corpus callosum in secondary bilateral synchrony.

Exposure of particulate matter (PM10) induces neurodevelopmental toxicity in zebrafish embryos

Particulate matter with 10 μm or less in diameter (PM10) exposure is a major threat to health and environment around the world. Even though a number of clinical and experimental studies have focused on the cardiopulmonary effects of PM10, its impact on neurovascular development and the underlying toxicity is relatively less studied. The present study is therefore undertaken to evaluate the potential toxic effects of PM10 on neurodevelopment and the associated gene expression profiles in the zebrafish embryo/larvae. During 2017–2018, PM10 samples (24 h sampling, 180 sampling days) were collected in an urban downtown site of Jinan, Shandong province, China. To delineate the potential toxic effects of PM10 during neurodevelopment, zebrafish embryos/larvae were exposed to different concentrations viz., 25, 50, 100, 200, and 400 μg/mL of PM10 solution for 24–120 h post-fertilization (hpf) and the effects on the mortality, morphology, swimming behavior, electroencephalogram discharges, growth of dopaminergic neurons, neurovasculature development and gene expression profiles of dopaminergic and neurodevelopment-related genes using qRT-PCR were studied.A significant increase in the mortality rate and morphological abnormalities were observed in 200 μg/mL of the PM10 treated group at 120 hpf. High concentrations (≥100 μg/mL) of PM10 exposure reduced locomotor behavior, caused abnormal electroencephalogram discharges, degeneration of dopaminergic neurons, inhibition of neurovascular development, cerebral hemorrhage, and significant changes in the expression pattern of genes involved in dopaminergic pathway and neurodevelopment such as (th1, dat, drd1, drd2a, drd3, drd4b, syn2a, gap43, α1-tubulin, gfap, map2, elavl3, eno2, neurog1, sox2, shha, and mbp). Taken together, all these parameters collectively imply developmental neurotoxicity and dysfunction of the dopaminergic neurons which provides the first evidence of PM10-induced neurodevelopmental toxicity in the zebrafish embryo/larvae.

KCTD7-related progressive myoclonic epilepsy: report of three Indian families and review of literature.

Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM# 611726) is a rare autosomal recessive condition associated with pathogenic variants in KCTD7, which encodes the BR-C,ttk and bab/pox virus and zinc finger domain-containing KCTD7 protein. We report four individuals from three Indian families presenting with an initial period of normal development, progressive myoclonic seizures followed by neuroregression and an abnormal electroencephalogram. We identified two novel missense variants, c.458G>C p.(Arg153Pro) and c.205C>G p.(Leu69Val) and one known disease-causing variant, c.280C>T p.(Arg94Trp) in KCTD7 by exome sequencing. We review the literature of 67 individuals with variants in KCTD7. Our study expands the molecular spectrum of KCTD7-related progressive myoclonic epilepsy.

Identification of Novel UBE3A Mutation Causing Angelman Syndrome

The Angelman Syndrome (AS) is neurodevelopmental disease associated with maternal disruption of the UBE3A gene and is mainly characterized by global developmental delay, sever mental retardation with absence of speech, seizures, dysmorphic facial features, and distinct behavioral profile. In this study a pedigree with one affected member with neurodevelopmental disease who was a result of an unconsanguineous marriage were investigated by Whole Exome Sequencing (WES). DNA was extracted from whole blood and library was prepared using Agilent V6 capturing system. WES was performed on Illumina HiSeq 4000 platform. Genome Analysis Toolkit (GATK) was used for variant calling. Classification of selected variants was done based on ACMG guideline for variant interpretation 2015. WES revealed that the proband has previously unreported nonsense variant (c.2459T>G) in UBE3A gene that causes the substitution of Leu (TTA) with stop codon (TGA), confirming the diagnosis of Angelman syndrome. The patient had delayed motor development, speech impairment, an attention deficit, and an abnormal electroencephalogram (EEG), but no seizures by the age of 2 years. This study emphasis the role of WES in the early diagnosis and better management for AS patient.

Discordant electroencephalogram epileptiform activity and hemispherectomy in children with refractory epilepsy and encephaloclastic lesions: a case series.

This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was in the neonatal period in three children, at 17 months in two, and at 5 years in one. Their ictal and interictal electroencephalogram (EEG) abnormalities showed paradoxical lateralization to the incorrect/'normal' hemisphere or showed bilateral abnormalities. After cautious discussion regarding the discordant electroclinical profile and implications for outcome, they proceeded to a functional hemispherectomy (between ages 4-11y) with good outcomes (at 1-10y follow-up). Their clinical details, EEG findings, electrocorticography, neuroimaging, and histology are reported. Possible surgical candidacy should be evaluated early in children with refractory epilepsy, even those with complex profiles and discordant data from the different investigations. Contralateral or bilateral EEG abnormalities should not preclude consideration of hemispherectomy in children with refractory epilepsy, hemiparesis, and uniclastic lesions.

Clinical Characteristics of H1N1 Influenza A-Associated Mild Encephalopathy with Reversible Splenial Lesion: 4 Pediatric Cases.

Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.

CNKSR2-related neurodevelopmental and epilepsy disorder: a cohort of 13 new families and literature review indicating a predominance of loss of function pathogenic variants

BackgroundPathogenic variants in connector enhancer of kinase suppressor of Ras-2 (CNKSR2) located on the X chromosome (Xp22.12) lead to a disorder characterized by developmental delay and a characteristic seizure phenotype. To date, 20 affected males representing 13 different pathogenic variants have been published.Case presentationWe identified an 8-year-old male with seizures, abnormal electroencephalogram (EEG) with epileptiform abnormalities in the right hemisphere, and developmental delay with notable loss of speech following seizure onset. Additional concerns include multiple nighttime awakenings, hyperactivity, and autism spectrum disorder. Genetic testing identified a de novo pathogenic nonsense variant in CNKSR2.Through an active family support group, an additional 12 males are described, each harboring a different CNKSR2 variant. The clinical presentation and natural history consistently show early developmental delay, sleep disturbances, and seizure onset in childhood that is initially intractable but later becomes better controlled. Virtually all of the pathogenic variants are predicted to be loss of function, including genomic deletions, nonsense variants, splice site mutations, and small insertions or deletions.ConclusionsThis expanded knowledge, combined with functional studies and work with animal models currently underway, will enable a better understanding and improved ability to care for individuals with CNKSR2-related neurodevelopmental and epilepsy disorder.

Distinct changes of brain cortical thickness relate to post-treatment outcomes in children with epilepsy

PurposeIn the current study, we examined the potential of neuroanatomic measures to cluster patients into different subgroups and established their clinical relevance to post-treatment outcomes. MethodsWe included seventy-two children with epilepsy (aged 14–195 months) who were treated with anti-seizure medication alone and 39 healthy participants (aged 36–60 months). High-resolution T1-weighted imaging was performed for all participants, and brain cortical thickness measurements were obtained for 68 cortical regions for each of them. Amongst the patients, data-driven hierarchical cluster analysis was performed using the selected cortical thickness measures as features. The average thickness measures in each of the 68 brain regions were then compared between patient subgroups and healthy controls. ResultsTwo distinct patient subgroups were identified but were not related to the clinical types. Patients within subgroup 1 (n = 56) had a significantly higher rate of recurrent seizure than those in subgroup 2 (n = 16) (41.1% vs. 14.3%, p<0.05), while the follow-up time or medication did not differ between them. This finding was further confirmed by a recent follow-up through phone calls. The demographic variables, rate of electroencephalogram abnormalities, or sleep problems did not significantly differ between patient subgroups. Compared with healthy controls, patients in subgroup 1 showed significantly increased cortical thickness in the neocortex, whereas patients in subgroup 2 only showed regional cortical thinning in the right superior temporal gyrus. ConclusionThese findings suggest the potential existence of distinct subgroups of children with epilepsy that were especially relevant to the differential patterns of post-treatment outcomes, with regional cortical thinning in the temporal regions relative to controls predicting lower risk of recurrent seizure.

Risk of seizure recurrence after a first unprovoked seizure in childhood

ObjectiveThe aim of this study was to assess the risk of recurrence after a first unprovoked seizure in childhood and to explore the correlation between the first and second seizures in recurrent patients. MethodsIn a prospective study, we included 467 children aged 1 month to 16 years, who were attended to between November 1, 2008 and October 31, 2016 following a first seizure. Children who had been started on treatment with antiepileptic drugs were excluded. Recurrence rates were calculated using Kaplan–Meier survival analyses. Univariate and multivariate analyses for recurrence risk were performed using the Cox proportional hazards model. The kappa coefficient of correlation for categorical data was calculated. ResultsRecurrences occurred in 280 children (60.0%), of which 75 (26.8%) occurred in the first month, 184 (65.7%) within 6 months, and 256 (91.4%) within 2 years. None of the patients had new neurologic sequelae after their first or second seizure. The estimates of seizure recurrence risk were 39.5%, 48.1%, 55.1%, 60.8%, 61.8% and 61.8% at 0.5, 1, 2, 5, 8, and 10 years after the first seizure, respectively. Multivariate analysis showed that abnormal electroencephalogram and neuroimaging findings significantly increased the risk of recurrence. First and second seizures were significantly associated with state of arousal, status epilepticus, and multiple seizures in recurrent patients. ConclusionOver half of untreated children had recurrence after a first unprovoked seizure, but prognosis was good overall.