A Neuro-metabolic Syndrome that Needs to Be Discovered: A Child with Late Onset Asparagine Synthetase Deficiency

Asparagine synthetase (ASNS) deficiency is a rare inborn error of metabolism caused by a defect in ASNS—a gene encoding asparagine synthetase. It has mainly been described as a neurological phenotype manifesting as severe developmental delay, congenital microcephaly, spasticity, and refractory seizures; it is not associated with any specific dysmorphisms. ASNS deficiency leads to the inability to synthesize a nonessential amino acid in the brain, this explains why the symptoms are primarily neurological. The accumulation of aspartate/glutamate causes increased neuronal apoptosis leading to brain atrophy and increased neuronal excitability leading to seizures. Asparagine levels in plasma and cerebrospinal fluid are not reliable biomarkers for this disorder, therefore diagnosis is mainly obtained by molecular genetics. This disorder is associated with a poor prognosis and there is no treatment except supportive therapy. Prenatal diagnosis is possible. We report a case of a later onset form, c.146G > A (p.Arg49Gln) variant in the ASNS gene detected by molecular analysis using next-generation sequencing; the patient's clinical presentation included microcephaly, regression of developmental milestones, epilepsy, and hyperthermia.

Successful Use of Inhalational Anesthesia and Electroconvulsive Therapy in a Child with New Onset Prolonged Super-Refractory Status Epilepticus

The treatment of super-refractory status epilepticus (SRSE) and prolonged SRSE rests on urgent seizure control to minimize excitotoxic cerebral damage, other forms of neurologic damage, and multiple medical complications. To date no randomized controlled trials or clear-cut guidelines are available for the management of SRSE. We reported the case of a 10-year-old previously healthy male child patient who presented with a febrile illness and new onset prolonged SRSE that became refractory to multiple antiseizure medications (ASMs). Coma induction with anesthetic agents, 14 ASMs, ketogenic diet, immunotherapy failed to completely control the SRSE in our patient. On day 22, clinical and electroencephalographic seizure control was achieved with isoflurane inhalation anesthesia, which was continued for 3 weeks but was unable to be weaned. From day 57 onwards, electroconvulsive therapy was administered (total 14 sessions that resulted in complete control of seizures). He was discharged on the 80th day.

Patient Characteristics Associated with Seizure Freedom after Vagus Nerve Stimulation in Pediatric Intractable Epilepsy: An Analysis of “Super-Responders”

Clinical responses to vagus nerve stimulation (VNS) therapy for intractable epilepsy can be unpredictable, and factors that predict response to therapy are elusive. Minority of children undergoing VNS achieve seizure freedom. The current study aimed to characterize this exceptional patient population, defined as “super-responders” (SRs). Retrospective data were collected from 150 children who underwent VNS at a single pediatric institution. The patients' mean age at VNS device implantation was 12.0 years (range, 3.09–17.9 years). Ten SRs (6.7%) were identified who achieved and maintained seizure freedom for longer than 1 year following implantation. The interval between epilepsy onset and VNS device implantation was significantly shorter in SRs than in the other children (mean epilepsy duration 5.72 vs. 8.44 years, respectively; p = 0.032). SRs also had a significantly shorter proportion of life with epilepsy compared with the other children (mean ratio of epilepsy duration to age at implantation 0.52 vs. 0.71, respectively; p = 0.023). SRs reported their seizure freedom relatively early (six patients within 6 months and all patients within 12 months after implantation) at relatively low device settings (mean output current 0.81 mA at their last follow-up). Compared with conventional models, responsive VNS models with autostimulation features did not increase the ratio of SRs. No other clinical or imaging characteristic difference between SRs and the other children was found in this cohort. The current study showed a significant association between shorter epilepsy duration and shorter proportion of life with epilepsy and seizure freedom after VNS.

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

It 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.

Clinical Predictive Factors of Pathological EEG in Children with Febrile Seizures and Their Association with Subsequent Epileptic Seizures

The objective of this study was to identify clinical parameters predicting either a pathological EEG or a subsequent epileptic seizure (SES), based on the relation between paroxysmal EEG abnormalities and clinical features in children who presented at least one febrile seizure (FS). We collected data of children who presented to our department during the period 2013 to 2018 for EEG recording as part of their febrile seizure assessment. Only children aged between 1 month to 5 years were included. Both the clinical and EEG data were retrospectively collected and statistically studied. We performed a detailed analysis of the EEG recordings. SES was identified for patients with sufficient follow-up. A total of 120 children were included in the study, of whom 48% had EEG abnormalities. Psychomotor retardation (p = 0.002), completion of an EEG within 7 days of the last FS (p = 0.046), and late age (> 3 years) of the first FS onset (p = 0.021) were significantly associated with a pathological EEG. In multivariate analysis, performing early EEG (< 7 days from the last FS) (odds ratio [OR]: 2.35; p = 0.043; confidence interval [CI]: 1.028–5.375) and psychomotor retardation (OR: 4.19; p = 0.008; CI: 1.46–12) were independent predictors of a pathological EEG. Of 120 patients, 45 had a follow-up. However, only 10 (22.22%) had SES. Children with SES tended more to have a psychomotor delay, compared with children without SES (50% vs. 14.28%, p = 0.029). Moreover, the percentage of initial abnormal EEG in patients with SES was significantly higher than those without SES (70% vs. 34.28%, p = 0.05). Even though some FS characteristics predict EEG abnormalities, they are not always associated with SES. We highlight the importance of performing an EEG in the group of children who had both FS and psychomotor retardation. This is most likely the group at the highest risk of developing epilepsy.

Assessment of Parental Quality of Life in Febrile Seizures Using Pediatric Quality of Live Inventory Parental Report

Febrile seizure (FS) is the most common convulsive disorder in children with FS prevalence in Indonesia reaching 2 to 4% in 2008. Although this entity has a good prognosis, it often brings panic, fear, and anxiety to the parents. This seemingly benign condition might lead to changes in family structures resulting in adverse effects on the family's daily lives and affect their overall quality of life (QoL). This study evaluates the QoL of parents whose children have FS. A cross-sectional study done in 47 parents whose children had a FS between ages 1 and 4 years from January 2020 to May 2020 and who were evaluated at the Siloam General Hospital, Lippo Village. Parents were asked to fill in Pediatric Quality of Life Questionnaire parent proxy. Data normality was analyzed using the Shapiro–Wilk's test and the significant impact of parents' QoL using the chi-square and independent t-tests. From a total of 47 parents, 30 (63.8%) parents had children with simple FS and 17 (36.2%) parents had children with complex FS. Parents whose children were in the age group of 1 year to 1 year 11 months had the best mean score of 79.64 (12.17) compared with other age groups. In the subset of 3 to 4 years old, the daily activities domain was significantly affected (p-value = 0.3). Parents with a lower educational level had a higher mean score of 76.53 (14.42) than parents who had a higher educational level, with a total mean of 79.88 (11.85), particularly with the highest mean score of 100 in the communication domain. The occurrence of FSs in children affected their parents' QoL in almost all domains in the Pediatric Quality of Life Inventory questionnaire.

Quantitative Electroencephalogram in Pediatric Intensive Care Unit in Three Different Clinical Scenarios

Although clinical judgement and sedation scales are primarily used in intensive care units (ICUs) to manage sedation, adjunctive data are needed to direct therapy with sedative and hypnotic agents to prevent side effects and long-term sequelae. In this report, we describe three cases where we used quantitative electroencephalogram (qEEG) data in a pediatric ICU (PICU); to manage these specific clinical situations and to identify the limitations of the qEEG data, two patients were admitted for post–cardiac arrest care and the third was admitted for status epilepticus. In post–cardiac arrest patients, qEEG was mainly used for monitoring depth of sedation and drug titration. Unnecessary use of high-drug doses was prevented, and monitoring also helped to guide clinical intervention for the management of seizure activity. In the patient with status epilepticus, qEEG data on burst suppression and depth of sedation were used. In this report, we describe three different cases where we used qEEG data in a PICU, to give insight on the use of data in specific clinical situations and to describe the limitations of the qEEG data monitoring system.

Electrical Status Epilepticus during Sleep and Evaluating the Electroencephalogram

Electrical status epilepticus during sleep (ESES) is an age-related, self-limited epileptic encephalopathy characterized by heterogeneous clinical manifestations and a specific electroencephalographic pattern of continuous spikes and waves during slow sleep. The etiology of ESES is not completely clear, although structural brain lesions, abnormal immunological markers, and genetic mutations have been associated with the syndrome. ESES was first described in 1971 and since then, the diagnostic criteria have changed multiple times. Additionally, inconsistency between authors in how to record and evaluate the electroencephalogram also leads to variability between studies. These inconsistencies hamper objectivity, comparison, and generalization. Because of this, one of the first priorities of physicians treating this condition should be defining the parameters of this disease so that cooperative building can occur.

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) encodes a protein that is highly expressed in neurons and has been shown to regulate neurite outgrowth as well as synapse formation and synaptic transmission. Clinically, mutations in or deletions of IL1RAPL1 have been associated with a spectrum of neurological dysfunction including autism spectrum disorder and nonsyndromic X-linked developmental delay/intellectual disability of varying severity. Nearly all reported cases are in males; in the few reported cases involving females, the clinical presentation was mild or the deletion was identified in phenotypically normal carriers in accordance with X-linked inheritance. Using genome-wide microarray analysis, we identified a novel de novo 373 kb interstitial deletion of the X chromosome (Xp21.1-p21.2) that includes exons 4 to 6 of the IL1RAPL1 gene in an 8-year-old girl with severe intellectual disability and behavioral disorder with a history of developmental regression. Overnight continuous video electroencephalography revealed electrical status epilepticus in sleep (ESES). This case expands the clinical genetic spectrum of IL1RAPL1-related neurodevelopmental disorders and highlights a new genetic association of ESES.

Factors Predicting the Recurrence of Febrile Seizure in Siloam General Hospital: A Descriptive Analysis

Febrile seizure (FS) is one of the most common pediatric neurologic disorders, affecting 2 to 5% of children between 6 months and 5 years. In 2008 to 2010, almost half of children with FS in Indonesia experienced recurrences. Various factors have been related to potential predictors for FS recurrence. However, available data reported inconsistent results. Considering its high recurrence rate, this study aimed to determine and assess the factors predicting the recurrence of FS. A cross-sectional study was done in Siloam General Hospital, Lippo Village. The study period was from December 2018 to December 2019, and data were obtained through medical records. Out of 60 participants, 41.7% had recurrent FS. No administration of rectal diazepam before admission (odds ratio [OR] = 6.42; 95% confidence interval [CI]: 1.20–34.2, p = 0.027) was a predictive factor of recurrent FS, while female sex (OR = 0.23; 95% CI: 0.64–0.80, p = 0.025) and shorter duration of the first FS (OR = 0.21; 95% CI 0.06–0.69, p = 0.008) were protective factors of recurrent FS. Identification of factors predicting the recurrence of FS is a powerful tool for clinicians. This study showed that no administration of rectal diazepam before admission was correlated with the risk of FS recurrence, while shorter duration of FS and female sex were protective factors of recurrent FS.