Epilepsy education can help address a multitude of concerns encountered by families of children with seizures. The Mobile Epilepsy Education Package (MEEP) was developed, tested and integrated into practice in Turkey to manage epilepsy and increase treatment compliance. This study aims to develop English and French versions of MEEP, adapt it culturally, and evaluate its effectiveness. A two-group, single-center, randomized controlled intervention trial with 1:1 allocation ratio will be conducted in the Pediatric Neurology Clinic of the Montreal Children's Hospital. Seventy-two caregivers of children with epilepsy (intervention=36, control= 36), aged 1-17 years, will be recruited. Family Introduction Form, Epilepsy Information Scale for Parents and Parental Anxiety Scale for Seizures will be used to collect data at baseline and 3 weeks post-delivery of the 7-week intervention. The MEEP consists of 2 parts: educational content and a parental monitoring section. The control group will receive standard educational services. Primary outcomes are epilepsy knowledge and anxiety, which will be analyzed using multivariate analysis. The content of the MEEP and the questions of the epilepsy education package have been translated into English and French and transferred to the smartphone application. By the end of the study, the English and French versions of MEEP will have been rigorously tested, and ready for future testing and scalability evaluations in Canada. Together, a simple-to-use, easy-to-access and low-cost mobile application will have been created to address a critical gap in the provision of supports and resources for families managing a child with epilepsy in Canada.
Introduction: Rett syndrome (RS) is a neurodevelopmental disorder characterised by speech regression, loss of acquired voluntary hand skills, and stereotypic hand movements and gait abnormalities. IQSEC2 mutation is an Xlinked inherited gene that can cause X-linked semidominant disorders with different severity between males and females such as intellectual disability, epilepsy, autism, microcephaly,d stereotypic movement disorder etc. Material-Methods: Written informed consent was obtained from the patient and his guardian for the case report. Identity information was hidden due to patient privacy. Case Report: An 8-year-old male patient was followed for epilepsy and global developmental regression. In the medical history, neuromotor development was normal for the first 12 months, after which there was a loss of voluntary hand skills and a loss of language ability. Follow-up of the patient revealed gait impairment and Rett-like stereotypic hand movements. The brain MRI examination was normal. No abnormality was detected in the basic metabolic and genetic work up. IQSEC2 mutation was detected in the large epilepsy next-generation sequence analysis panel. Because of presence of all the main clinical criteria ,IQSEC2-related RS was diagnosed in the patient. Conclusion: RS is a clinical diagnosis, for which all the main criteria are required. IQSEC2 mutation should be considered in male patients presenting with clinical findings consistent with RS, and in whom common mutations such as MECP2, CDKL5, and FOXG1 are not detected.
Introduction: Febrile Infection-Related Epilepsy Syndrome [FIRES] is a rare, catastrophic epileptic syndrome that strikes previously healthy children, whose pathogenesis is unknown. It starts with a febrile illness and refractory seizures, but without evidence of an identifiable infectious encephalitis. Purpose: To study the course of illness and the outcomes in children with FIRES. Methods: This is a retrospective study conducted at a tertiary healthcare center in southern India between August 2014 and August 2022, which included all children diagnosed with FIRES. The demographic details, clinical manifestation, cerebrospinal fluid [CSF] analysis, neuroimaging findings, electroencephalography (EEG), treatment, and outcome were analyzed. Results: A male preponderance of 66% (12/18) was noted, with the median age of disease onset being 8.55 years. The onset of seizures following fever was noted at a median duration of 3 days. The median duration of hospitalization was 26 days. The average number of anti-seizure medications (ASMs) used was five. The CSF analysis was normal in 72% [13/18], pleocytosis seen in 16% [3/18], and elevated protein in 11% [2/18]. Neuroimaging was done in all children. Of the eighteen cases, 22% showed cerebral edema [4/18], while 5% [1/18] showed irregular hyperintensities, and 72% [13/18]were normal. The EEG was abnormal in all the cases, with multifocal epileptiform discharges being the commonest finding, seen in 77% [14/18]. The outcome was analyzed using a modified Rankin scale(mRS). Among those who survived, the score ranged from 1 to 3, with a median score of 2, reflecting mild disability. Fifty percent of the cases succumbed. The most common cause of death was septic shock, followed by arrhythmias. The surviving nine children underwent magnetic resonance imaging [MRI] during follow-up, and 66% [6/9] had abnormal neuroimaging findings, with cerebral atrophy being the commonest finding. Conclusion: FIRES is a highly fatal condition, occurring in previously normal children, more commonly boys. The condition requires multiple ASMs to halt the seizures. All the infective parameters, including CSF analysis, were normal. Fifty percent mortality and fifty percent morbidity was seen.
Significance Recognition of intracranial hemorrhage is challenging in children who require deep sedation to tolerate mechanical ventilation. The Correlate Of Injury to the Nervous System (COIN) index may enable real-time recognition of intracranial hemorrhage at bedside. Methods Retrospective analysis of electroencephalography (EEG) data from children with spontaneous intracranial hemorrhage while intubated and sedated in the pediatric intensive care unit. Patients were selected for having normal head imaging at time of EEG start and required demonstration of hemorrhage on repeat imaging following an uninterrupted period of EEG recording. Power spectrum data were analyzed to yield a COIN value and visualization for every 4 seconds of recording. EEG recordings were subdivided based on COIN-risk alarm states (low, medium, or high). Changes in COIN were compared with changes in commercially available quantitative EEG trending software. COIN values for each subdivision were compared within cases using the Wilcoxon Rank-Sum Test. Results Two children developed spontaneous intracranial hemorrhage while intubated. COIN shows transitions from low-to-medium (p<0.001) and medium-to-high-risk (p<0.001 in both cases) alarm states. Discrete transitions in COIN alarm state preceded clinical recognition of hemorrhage by several hours. COIN visualized focal power attenuation concordant with hemorrhage localization. In both cases, qualitative EEG was not reported to have focal abnormalities during the medium-risk alarm state. Conclusion COIN may assist in real-time recognition of intracranial hemorrhage in children at bedside. Further study and development are required for clinical implementation of COIN in several clinical settings where patients are at high risk of new or worsening intracranial hemorrhage.
Objective: To investigate the trends, usage, and outcomes of stereotactic electroencephalography (SEEG) usage relative to subdural electrode (SDE) usage in pediatric intractable epilepsy patients. Methods: The 2016-2019 National Inpatient Sample (NIS) was queried for pediatric patients with epilepsy using ICD-10 diagnostic codes. Patients who underwent percutaneous (SEEG) or open (SDE) insertion of intracranial electrodes within two days of hospital admission with their removal during the same admission were selected. Hospital and patient demographics, yearly trends, outcomes, and healthcare resource utilization were compared between patients receiving SEEG or SDE. Results: SEEG patients were less likely to be in the Q1 median income category (OR 0.481, p = 0.003) or of Hispanic ethnicity (OR 0.277, p < 0.001) than SDE patients. SEEG patients did not have significantly different total charges during their stay and were more likely to be discharged home (OR 5.091, p < 0.001). In 2016, 15.2% of 165 total patients undergoing intracranial monitoring received SEEG (OR 0.192, p < 0.001). Relative SEEG usage peaked at 59.6% of intracranial EEG surgeries in 2018 and was significantly greater than SDE usage in this year (OR 3.303, p < 0.001). Significance: Pediatric SEEG patients have shorter hospital stays and incur similar costs relative to SDE peers, and relative utilization of this technology expanded from 15.9% in 2016 to 59.4% in 2018. The ability for optimal localization of seizure foci while minimizing postoperative complications and neurologic deficits renders SEEG a compelling intracranial monitoring method for pediatric patients. This trend suggests growing preference for minimally invasive techniques in pediatric centers and reflects an evolving clinical confidence in SEEG.
Background: The coexistence of spinal muscular atrophy (SMA) with other diseases has been rarely described. We report a unique case with dual pathogenic gene mutations: SMN1 gene causing SMA and SLC13A5 gene causing citrate transporter deficiency induced epilepsy (EIEE 25, OMIM 615905). Case presentation: The girl presented with recurrent focal seizures with semiology of eyelid blinking, deviation of eyes and facial twitches, which started from the second day of her life. Interictal EEG showed bilateral multifocal and generalized discharges. Brain MRI revealed delayed myelination and generalized volume loss. PET scan showed diffuse cortical hypometabolism. She had refractory seizures, including two episodes of status epilepticus while being treated with various antiseizure medications. Genetic analysis revealed homozygous deletion of SLC13A5 gene at 17p13.1. At one year of age, progressive hypotonia, initially ascribed to seizures and antiseizure medications, appearance of tongue fasciculations and need for respiratory support, prompted testing for SMA. Mutation at SMN1 gene locus (5q11.2-13.2) was found and SMA type I diagnosis was established. EMG/NCV revealed a motor neuron disorder. She was started on nusinersen at the age of 2.5 years, once it became available. She was tracheostomized for Bi Pap support. At the age of 4.5 years, she had a cardiac arrest and passed away. Conclusion: This is a case report of co-existent mutations in the SMN1 and SCL13A5 genes with overlapping and diagnostically confusing features of progressive hypotonia. The constellation of these separate genetic entities constitutes a clinical phenotype that has not been reported previously.
Background: Epilepsy is the most common neurologic disorder affecting children in Nigeria. It is often associated with other neurologic comorbidities in addition to epileptic seizures, such as attention deficit hyperactivity disorder (ADHD) and cognitive, visual and hearing impairments, which can be unrecognized while focusing on the seizures. Methods: This cross-sectional study assessed the prevalence, pattern and predictors of neurologic comorbidities among 100 children with Epilepsy (CWE) attending the pediatric neurology clinic of Jos University Teaching Hospital, Jos, Nigeria, and age and sex-matched controls selected consecutively. Data were summarized using frequencies and proportions. Chi-square and Mann-Whitney U tests were used to test categorical values, while logistic regression was used to determine predictive factors for neurologic comorbidities. Results: The prevalence of neurologic comorbidities among CWE vs controls was 65% vs 15% (P<0.001). Factors associated with neurologic comorbidities in CWE include younger age at onset of epileptic seizures (P<0.003), severity of seizures (P<0.001), history of status epilepticus (P<0.044), background history of intracranial infections (P<0.029) and the use of combination antiepileptic drugs (P<0.001). Predictors of comorbidities in CWE were treatment with Sodium Valproate and polytherapy. Conclusion: Neurologic comorbidities are more frequent among CWE than controls; therefore, screening for neurologic comorbidities should be routine when assessing and managing CWE.
Hashimoto encephalopathy (HE) is a neuropsychiatric syndrome associated with positive thyroid antibodies (Ab). Its pathophysiology is still in debate and pediatric cases are considered rare. We present a case of an 11-year-old girl with new-onset refractory status epilepticus (NORSE) who presented a good initial response to corticosteroids but then required a second line of treatment with mycophenolate. In children presenting with NORSE of suspected autoimmune origin and no identification of autoimmune encephalitis traditional Ab, HE must be considered.
Lingual seizures (LS) mean isolated seizures of the tongue. They are uncommon, and only a few cases have been reported. Sensory, motor, and autonomic auras or focal manifestations have a localizing value in seizures. LS have been reported with and without focal pathology in the brain. LS must be differentiated from more common conditions, like lingual tremors/dyskinesias. We report a 4-year-and-8-month-old boy with LS.
Introduction Status epilepticus (SE) is a common neurological emergency in children. Recent guidelines suggest initiating treatment after 5 minutes of seizure activity. Objective This study analyzes the clinical, laboratory parameters, and treatment outcomes of children with SE to identify preventable risk factors. Materials and Methods Prospective observational study of 150 children. They were evaluated for relevant history, clinical features, laboratory investigations, treatment, course, and outcome. Results The risk factors that had an impact on outcome in children with SE were identified as red flag signs on initial pediatric advanced life support (PALS) assessment, malnutrition, abnormal head circumference and number of seizures before child presented to hospital. The strongest predictor of outcome was stable status of children on initial PALS assessment (odds ratio = 20.174 [1.117, 364.393], p = 0.042). Presence of abnormal head size was 86% less likely to have favorable outcome and if the child had lesser number of seizures before child presented to hospital (single), it was 3.7 times likely that it would yield a favorable outcome. Conclusion Aggressive treatment of seizures, identification of red flag signs on initial PALS assessment, identification and treatment of malnutrition, anemia, hypocalcemia, and sodium derangements, strengthening vaccination to prevent central nervous system infections, and early intervention for developmental delay, can all help to combat morbidity and mortality in children with SE.
Although explaining epilepsy is a separate source of stress for children with epilepsy and their parents, studies evaluating the disclosure of epilepsy by patients and their parents are insufficient. The aim of this study was to test the validity and reliability of the Turkish form of the “Epilepsy Disclosure Scale (EDS)—Youth and Parent Versions,” which measures the concealment/disclosure of epilepsy by youth patients with epilepsy and their parents. The population of the study consisted of 126 children who were diagnosed with epilepsy and who were between the ages of 8 to 18 and their parents (63 children and 63 parents) who applied to two hospitals pediatric neurology. Both scales consist of six items. When the scale was adapted, language, content, structural, and reliability analyses were conducted. The factor loads varied between 0.78 and 0.88 and contributed 71.99% to the total variance in the Youth Version. In the Parent Version, they varied between 0.79 and 0.88 and contributed 67.09% to the total variance. The Cronbach's α coefficients of the youth and parent versions of the scale were calculated as 0.92 in the youth version and 0.90 in the parent version. The Composite Reliability Index of the youth version was 0.94, and that of the parent version was 0.92. It was concluded that all statistical studies in the study were compatible with the original scale and that it could be applied to children with epilepsy between the ages of 8 to 18 and their parents in Turkish society.
Introduction GRIN1 encephalopathy is an emerging genetic entity due to de novo monoallelic or biallelic pathogenic variants in the GRIN1 gene that impair the function of the GluN1 subunit of the N-methyl-D-aspartate (NMDA) receptor. Here, we describe two patients with GRIN1 encephalopathy with an uncommon neuroradiological pattern. Cases Presentation Two boys presented with a neurodevelopmental disorder characterized by severe cognitive impairment, autistic features, hand stereotyped movements, self-injurious behavior, and hyperkinetic movements. They were nonverbal and did not acquire the ability to walk. Both developed epileptic encephalopathy with epileptic spasms. Magnetic resonance imaging of the brain showed bilateral hippocampal sclerosis in both, and one of them showed multiple cortical lesions with diffusion restriction. Two relevant missense variants in the GRIN1 gene were identified by a next-generation sequencing panel, one was novel (c.1927A > G-p.(Ile643Val)) and the other (c.2530C > T-p.(Arg844Cys)) was previously reported associated with GRIN1-neurodevelopmental disorder. Both variants are predicted to affect the normal function of the GluN1 subunit and were classified as likely pathogenic and pathogenic, respectively. Conclusion The association of severe cognitive impairment, autistic features with hand stereotypies, self-injurious behavior, and hyperkinetic movements in patients with epileptic encephalopathy are characteristic of GRIN1 encephalopathy. The hippocampal sclerosis and cortical lesions, similar to those found in NMDA autoimmune encephalitis, observed in these patients expand the neuroradiological features of this entity.
AbstractInfantile epilepsy syndromes' nomenclature has changed over time. The International League Against Epilepsy (ILAE) revised its 2021 classification and definition of epilepsy syndromes in neonates and infants, replacing the term “benign” with “self-limited,” and now identifies them as “self-limited infantile epilepsy” (SeLIE). SeLIE is characterized by seizures that begin during infancy and resolve spontaneously with normal developmental progress. The recognition of infantile seizures with favorable outcomes dates back more than 60 years, as noted by Fukuyama in Japan. Thirty years later, Watanabe et al reported benign focal seizures in infancy, with the majority of cases being nonfamilial. These seizures' self-limited nature during infancy has since been acknowledged in various countries, spanning diverse ethnic populations beyond Japan. Infants who undergo such seizures are now recognized as having self-limited nonfamilial infantile epilepsy (SeLNFIE). Initially, Vigevano et al detailed the familial variant in five infants, coining the term “benign familial infantile seizures” to characterize this condition, now known as self-limited familial infantile epilepsy (SeLFIE). SeLNFIE and SeLFIE may present similarly with the exception of a positive family history. After the initial description and classification of these syndromes (familial and nonfamilial) in the ILAE's 1989 Classification of Epilepsies and Epileptic Syndromes, several less frequently encountered related syndromes have been recognized. These conditions comprise a spectrum including SeLFIE with choreoathetosis and paroxysmal dyskinesia, now termed infantile convulsions with paroxysmal choreoathetosis syndrome (ICCA); self-limited focal epilepsy in infancy with midline spikes and waves during sleep (SeLIMSE); self-limited infantile seizures with mild gastroenteritis (SeLISwG); SeLFIE associated with familial hemiplegic migraine (FHM); and self-limited familial neonatal-infantile epilepsy (SeLFNIE). This review aims to document the prevalence of these SeLIEs, elucidate their unique characteristics, and underscore their self-limited nature.
Consanguineous marriages in India continue to give rise to a wide spectrum of recessively inherited disorders that require a broader base of knowledge. A 2-year-old boy presented with global development delay, persistent vomiting, drug refractory seizures, deafness, and central hypotonia. He had profound bilateral hearing loss, barium swallow showed severe reflux but magnetic resonance imaging brain was normal, leading to a diagnostic dilemma. A normal electromyogram with nerve conduction velocity ruled out disorders of muscle and nerve. Whole-exome sequencing showed salt and pepper development regression syndrome but phenotypically, he did not have the classic skin changes. He has shown mild improvement in cognition, mobility, and weight gain with citicoline, antireflux medications, antiseizure medications, and a protein diet. Accurate diagnosis based on cohort of symptoms and appropriate early intervention can help improve the quality of life in such children.
We analyzed the electroclinical features, molecular findings, treatment, disease course, and outcomes of patients with Dravet syndrome (DS) with positive genetic markers seen at a public hospital in Argentina. A retrospective study was conducted assessing the clinical records of 44 patients who met the diagnostic criteria for DS according to the 2022 classification of epilepsy of the International League Against Epilepsy seen at our center between March 2018 and June 2023. Of 44 patients, 35 (18 males and 17 females), in whom genetic studies yielded positive results, were included. Median age was 9 years (range 4 to 16 years), and the median time of follow-up was 10 years (range 3 to 14 years). The mean age at onset was 7 months. The first seizure was associated with febrile illness in all patients, and in 11 (31.4%), seizures were immediately preceded by either infectious disease or vaccination. Heterozygous pathogenic/likely pathogenic SCN1A variants were detected in 32 of the original 44 patients (73%), of which 47% were novel. Variants in other genes related to DS ( HCN1 , STXB1 , and SCN1B ) were identified in three patients. Cognitive delay and motor impairment were found to be more severe in patients that had multiple and drug-resistant seizures and in those who had the complete phenotype with myoclonic seizures. Novel SCN1A gene variants were identified in nearly half of the patients. The prognosis for cognitive development is unfavorable. Seizures are not well controlled with antiseizure medications and early treatment with ketogenic dietary therapy as well as cannabidiol should be considered.
An investigation by the publisher found a number of articles, including this one, published in Journal of Pediatric Epilepsy in Volume 11, Number 04, 95-96, in December 2022 (DOI: 10.1055/s-0042-1757159), with a number of concerns, including but not limited to undeclared conflicts of interest and manipulated peer review procedures. As a result, the publisher has retracted and removed this article.
Self-limited familial neonatal epilepsy is an autosomal dominant epileptic syndrome characterized by episodes of seizures occurring in the first days of life. Most patients have heterozygous mutations of KCNQ2 gene located on 20q13. A variety of clinical phenotypes have been associated with KCNQ2 mutations, making the prediction of this rare entity difficult. Herein, we report a rare KCNQ2 variant in two siblings with self-limited familial neonatal epilepsy. The siblings had tonic seizures accompanied by clonic jerks in the first few days after birth. Genetic analysis of the siblings revealed a heterozygous KCNQ2 variant: c.1589G > A; (p.Ser530Asn). The identical variant subsequently was identified in the mother. To our knowledge, this variant has not been previously reported in individuals with KCNQ2-related disease. This is the first report that reveals c.1589G > A variant of KCNQ2 gene as a pathogenic variant in two siblings.
Retraction An investigation by the publisher found a number of articles, including this one, published in Journal of Pediatric Epilepsy in Volume 12, Number 03, 89-90, in September 2023 (DOI: 10.1055/s-0043-1764149), with a number of concerns, including but not limited to undeclared conflicts of interest and manipulated peer review procedures. As a result, the publisher has retracted and removed this article.
Mutations in the PRRT2 gene lead to a spectrum of diseases with a common pathophysiology including self-limited (familial) infantile epilepsy and paroxysmal kinesigenic dyskinesia as well as other paroxysmal diseases involving movement and headache disorders. Atypical phenotypes, associated with episodic ataxia, epilepsy, hemiplegic migraine, developmental delay, and intellectual disability, have been reported in approximately 5% of the patients, which is probably an underestimation. Here, we present three patients with variable PRRT2 phenotypes in each patient. In the first two patients, the manifestations were characterized by episodes of nonepileptic paroxysms and focal seizures starting in the first years of life with good response to carbamazepine. One of them had no family history either of epilepsy or nonepileptic motor manifestations. The other patient simultaneously developed epileptic spasms. Neurodevelopment was normal in both. The third patient presented with early-onset focal epilepsy that was resistant to antiseizure medications and evolved to spike-wave activation in sleep associated with cognitive impairment and ataxia. In this patient, in addition to the mutation in the PRRT2 gene, a novel pathogenic SCN1A variant was identified. The distinct clinical presentations in the same patient observed in our cases confirm the broad spectrum of PRRT2 -associated diseases.
