The Early Response to Dietary Therapy can Predict the Late Outcome in Children with Intractable Epilepsy

Background@#and Purpose Dietary therapy (DT), including the ketogenic diet (KD), is one of the nonpharmacological treatment options for patient with drug-resistant epilepsy. However, maintaining DT in patients without seizure reduction is very difficult, so it is critical for clinicians to decide when to stop this intervention. @*Methods@#We retrospectively analyzed early clinical and laboratory findings and the clinical characteristics of children who received DT. The maintenance of DT and the clinical seizure frequency were assessed at 1, 3, 6, 12, and 24 months after KD initiation. Responders were defined as patients showing an overall reduction in seizure frequency of >50% relative to the baseline. @*Results@#We included 67 patients who received DT, but only 23 (34.3%) of these patients remained on DT at 6 months. Only 1 (5%) of the 20 responders at 1 month became a nonresponder at 6 months. The response rate at 6 months was significantly higher among patients under 2 years of age (15/17, 88.2%) than older patients (2/6, 33.3%; p=0.021). Moreover, the 6-month responders were significantly younger (29.4±38.6 months, mean±SD) than the nonresponders (98.9±84.6 months, p=0.012) at the initiation of the diet. A high blood β-hydroxybutyrate (BHB) level at 1 month predicted a good DT response at 6 months. @*Conclusions@#Most 1-month responders maintained their response on DT for up to 6 months.The blood BHB level at 1 month was significantly correlated with the 6-month seizure outcome.Confirming clinical and laboratory biomarkers for the efficacy of DT requires further studies with larger cohorts.

Altered Structural Network in Newly Onset Childhood Absence Epilepsy

Background@#and Purpose: Recent quantitative neuroimaging studies of childhood absence epilepsy (CAE) have identified various structural abnormalities that might be involved in the onset of absence seizure and associated cognitive and behavioral functions. However, the neuroanatomical alterations specific to CAE remain unclear, and so this study investigated the regional alterations of brain structures associated with newly diagnosed CAE. @*Methods@#Surface and volumetric magnetic resonance imaging data of patients with newly diagnosed CAE (n=18) and age-matched healthy controls (n=18) were analyzed using FreeSurfer software. A group comparison using analysis of covariance was performed with significance criteria of p<0.05 andp<0.01 in global and regional analyses, respectively. @*Results@#Compared with control subjects, the patients with CAE had smaller total and regional volumes of cortical gray-matter (GM) in the right rostral middle frontal, right lateral orbitofrontal, and left rostral middle frontal regions, as well as in the right precentral, right superior, middle, left middle, and inferior temporal gyri. The cortex in the right posterior cingulate gyrus and left medial occipital region was significantly thicker in patients with CAE than in controls. @*Conclusions@#Patients with CAE showed a reduced bilateral frontotemporal cortical GM volume and an increased posterior medial cortical thickness, which are associated with the default mode network. These structural changes can be suggested as the neural basis of the absence seizures and neuropsychiatric comorbidities in CAE.

Treatment of Children and Adolescents with Epilepsy with Atomoxetine

Objective@#The objective of this study was to assess the effectiveness and safety of atomoxetine in Korean children and adolescents with epilepsy. @*Methods@#We retrospectively reviewed the electronic medical records of 105 children and adolescents with epilepsy treated with atomoxetine. Effectiveness was measured with the Clinical Global Impressions-Severity (CGI-S) and/or Clinical Global Impressions-Improvement (CGI-I) scales at baseline, and after 4 and 12 weeks. We defined response to atomoxetine as a CGI-I score less than three at week 12. Safety was evaluated at each visit, based on clinical assessment by a child and adolescent psychiatrist and reports from participants or their caregivers. @*Results@#In total participants (n=105), 33 (31.4%) showed a response to treatment: a significant decrease in CGI-S scale score was observed over 12 weeks of atomoxetine treatment. The most common adverse event (AE) was decreased appetite (n=16, 15.2%), and life-threatening AEs were not observed. Seizure aggravation due to atomoxetine was observed in 7.6% (n=8) of total participants, and one of them discontinued atomoxetine. @*Conclusion@#Our results provide preliminary evidence of the effectiveness and safety of atomoxetine in children and adolescents with epilepsy.

Psychological Impact of Quarantine on Caregivers at a Children's Hospital for Contact with Case of COVID-19

Quarantine often provokes negative psychological consequences. Thus, we aimed to identify the psychological and behavioral responses and stressors of caregivers quarantined with young patients after a close contact to a coronavirus disease 2019 case at a children's hospital. More than 90% of the caregivers reported feelings of worry and nervousness, while some of them reported suicidal ideations (4.2%), and/or homicidal ideations (1.4%). Fear of infection of the patient (91.7%) and/or oneself (86.1%) were most frequently reported stressors. A multidisciplinary team including infection control team, pediatrician, psychiatrist, nursing staff and legal department provided supplies and services to reduce caregiver's psychological distress. Psychotropic medication was needed in five (6.9%), one of whom was admitted to the psychiatry department due to suicidality. Quarantine at a children's hospital makes notable psychological impacts on the caregivers and a multidisciplinary approach is required.

Clinical Implications of Ketosis in Children with Benign Convulsions with Mild Gastroenteritis

A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years / 소아과

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.

Efficacy and Tolerability of Low-Dose Perampanel in Patients with Childhood-Onset Intractable Epilepsy / 대한소아신경학회지

PURPOSE@#The aim of this study was to evaluate the efficacy and tolerability of perampanel as adjunctive therapy in childhood-onset refractory epilepsy.@*METHODS@#We retrospectively reviewed the medical records of 110 patients who were treated with perampanel in Asan Medical Center children's hospital. Two patients with poor compliance were excluded and 108 patients were enrolled. The clinical characteristics were reviewed, and the total seizure frequency before and after the add-on of perampanel was analyzed.@*RESULTS@#The mean age of the patients (64 males) was 20.2 years (range, 10.5 to 35.6). The mean maintenance dose was 4.8 mg/day (2 to 10 mg). Eight patients (7.4%) achieved seizure freedom and 35 (32.4%) achieved a seizure reduction of ≥50%. Among them, three patients achieved seizure freedom with only 2 mg/day of perampanel. There was no significant difference in sex, age at seizure onset, duration of epilepsy, use of concomitant enzyme-inducing antiepileptic drugs, number of concomitant antiepileptic drugs, and adverse events between responders and non-responders. The retention rate was up to 68.0% in the first year and 59.5% in the second year of the study. Thirty-four patients (31.5%) reported adverse events: violence, somnolence, dizziness, drooling, weight gain, insomnia, and vomiting. There was no contributing factor for the adverse events, including sex, age, and the number of concomitant antiepileptic drugs and enzyme-inducing antiepileptic drugs when comparing the adverse event present group with the adverse event absent group.@*CONCLUSION@#Low-dose perampanel showed reasonable efficacy and tolerability in patients with refractory childhood-onset epilepsy. Further validation with pharmacokinetic studies is needed.

Two Cases of Hirayama Disease in a Pediatric Clinic / 대한소아신경학회지

We report two pediatric cases with Hirayama disease—a 16-year-old boy with a left wrist drop and a 14-year-old-boy with weakness and muscle atrophy of right hand. Motor nerve conduction study revealed decreased motor nerve action potential amplitudes in the ulnar nerve and radial nerve of the affected hands. The former patient showed normal magnetic resonance imaging (MRI) of the cervical spine, but the latter showed mild, asymmetric thinning of the anterior spinal cord at levels C5 to C7. Following active rehabilitation and avoidance of neck flexion, no further progression of neurological findings was noticed. These clinical findings were typical of Hirayama disease. We show that timely and accurate diagnosis for Hirayama disease is possible with awareness of disease history, careful physical examination, and the use of neurophysiological studies and MRI studies.

Identification of two novel Duchenne muscular dystrophies mutations in patients with Becker muscular dystrophy

Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. BMD is a milder form with a later onset. Patients with BMD tend to survive much longer than those with DMD. The differentiation between DMD and BMD is important in the genetic counseling of affected patients and their families. Since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on muscle biopsy findings with other clinical findings. Here we describe two Korean patients with BMD confirmed by muscle biopsy and genetic testing. Two novel exonic deletions in the DMD gene were identified.

Genotype-Phenotype Correlation of SMN1 and NAIP Deletions in Korean Patients with Spinal Muscular Atrophy

BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Most SMA patients have a homozygous deletion in survival of motor neuron 1 (SMN1) gene, and neuronal apoptosis inhibitory protein (NAIP) gene is considered a phenotype modifier. We investigated the genotype-phenotype correlation of SMN1 and NAIP deletions in Korean SMA patients. METHODS: Thirty-three patients (12 males and 21 females) treated at the Asan Medical Center between 1999 and 2013 were analyzed retrospectively. The polymerase chain reaction (PCR), restriction-fragment-length polymorphism analysis, and multiplex PCR were used to detect deletions in SMN1 (exons 7 and 8) and NAIP (exons 4 and 5). We reviewed clinical presentations and outcomes and categorized the patients into three clinical types. NAIP deletion-driven differences between the two genotypes were analyzed. RESULTS: Deletion analysis identified homozygous deletions of SMN1 exons 7 and 8 in 30 patients (90.9%). Among these, compared with patients without an NAIP deletion, those with an NAIP deletion showed a significantly lower age at symptom onset (1.9±1.7 months vs. 18.4±20.4 months, mean±SD; p=0.007), more frequent type 1 phenotype (6/6 vs. 8/24, p=0.005), and worse outcomes, with early death or a requirement for ventilator support (4/4 vs. 2/12, p=0.008). CONCLUSIONS: Homozygous deletion in SMN1 and a concurrent NAIP deletion were associated with an early onset, severe hypotonia, and worse outcome in SMA patients. Deletion analysis of NAIP and SMN1 can help to accurately predict prognostic outcomes in SMA.

Analysis of Parenting Stress, Coping and the Quality of Life for the Mother of Children Suffering from Epilepsy

PURPOSE: The purpose of this study was to identify factors affecting the parenting stress, coping and the quality of life for the mother of children suffering from epilepsy. METHODS: Research subjects were 176 mothers of a child between 0 to 12 years old, who visited pediatric neurology department at a general hospital in Seoul. The data were collected between October 1, 2015 and October 20, 2015. The questionnaire was composed of a total of 75 questions: 36 questions on parenting stress, 13 questions on coping ability, and 26 questions on quality of life. The collected data were analyzed by Cronbach's α, percentage, mean, frequency, standard deviation, ANOVA, Pearson's correlations, t-test, Scheffe post hoc test, and Hierarchical regression analysis using SPSS WIN 22.0 program. RESULTS: 1) The mean scores of the parenting stress, coping ability and quality of life were 2.47±0.68, 3.83±1.29, 3.23±0.60. 2) The subjects showed significant differences in parenting stress depending on their occupation, monthly income, age of the child, the child's age at the time of epilepsy diagnosis, frequency of the child's seizure, the child's developmental delay, and the child's exposure to other disease and brain damage among general characteristics of the subjects. 3) Correlation analysis resulted in negative correlation between the parenting stress and quality of life, and positive correlation between coping ability and quality of life. 4) Regression analysis found that parenting stress and coping are the factors affecting quality of life. Finally, the model containing both parenting stress and coping explained 52.41% of variation in quality of life, and parenting stress had the highest influence. CONCLUSION: nursing intervention and educational program should be developed to improve the quality of life in the mother of children with epilepsy. Furthermore, governmental support is required to help with reducing parenting stress to better the quality of life for the mother.

Analysis of Parenting Stress, Coping and the Quality of Life for the Mother of Children Suffering from Epilepsy

PURPOSE: The purpose of this study was to identify factors affecting the parenting stress, coping and the quality of life for the mother of children suffering from epilepsy. METHODS: Research subjects were 176 mothers of a child between 0 to 12 years old, who visited pediatric neurology department at a general hospital in Seoul. The data were collected between October 1, 2015 and October 20, 2015. The questionnaire was composed of a total of 75 questions: 36 questions on parenting stress, 13 questions on coping ability, and 26 questions on quality of life. The collected data were analyzed by Cronbach's α, percentage, mean, frequency, standard deviation, ANOVA, Pearson's correlations, t-test, Scheffe post hoc test, and Hierarchical regression analysis using SPSS WIN 22.0 program. RESULTS: 1) The mean scores of the parenting stress, coping ability and quality of life were 2.47±0.68, 3.83±1.29, 3.23±0.60. 2) The subjects showed significant differences in parenting stress depending on their occupation, monthly income, age of the child, the child's age at the time of epilepsy diagnosis, frequency of the child's seizure, the child's developmental delay, and the child's exposure to other disease and brain damage among general characteristics of the subjects. 3) Correlation analysis resulted in negative correlation between the parenting stress and quality of life, and positive correlation between coping ability and quality of life. 4) Regression analysis found that parenting stress and coping are the factors affecting quality of life. Finally, the model containing both parenting stress and coping explained 52.41% of variation in quality of life, and parenting stress had the highest influence. CONCLUSION: nursing intervention and educational program should be developed to improve the quality of life in the mother of children with epilepsy. Furthermore, governmental support is required to help with reducing parenting stress to better the quality of life for the mother.

Rufinamide in Patients with Childhood Onset Intractable Epilepsy

PURPOSE: This study is aimed to evaluate the effectiveness and tolerability of rufinamide as add-on therapy in patients with intractable epilepsies. METHODS: We retrospectively reviewed the medical records of 70 patients treated with rufinamide in Asan Medical Center, children's hospital. Two cases with incomplete medical records were excluded and total sixty-eight cases were enrolled. Rufinamide was added on the existing antiepileptic drugs and the total seizure frequency at pre-medication, 3 months and 12 months were examined. RESULTS: The mean age of 68 patients (43 male) was 10.5 yrs (range, 1-24 yrs). At 3 months after rufinamide initiation, 5 patients achieved freedom from seizures and 28 (41.2%) achieved a ≥50% seizure reduction. At 12 months, 7 patients achieved seizure freedom and 29 (42.6%) achieved ≥50% seizure reduction. The retention rate was hold up to 75.0% at 3 months and 66.2% at 12 months of study. Total 29 patients reported adverse events in order of seizure aggravation, somnolence, insomnia, common cold, nausea and vomiting. CONCLUSION: In this study, rufinamide is effective and tolerable in patients with other intractable epilepsy of childhood onset as well as the patients with LGS. Further research is required to define the efficacy of rufinamide in intractable epilepsy other than LGS.

Clinical Characteristics of Transplant-associated Encephalopathy in Children

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

A young child of anti-NMDA receptor encephalitis presenting with epilepsia partialis continua: the first pediatric case in Korea / 소아과

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis, recently recognized as a form of paraneoplastic encephalitis, is characterized by a prodromal phase of unspecific illness with fever that resembles a viral disease. The prodromal phase is followed by seizures, disturbed consciousness, psychiatric features, prominent abnormal movements, and autonomic imbalance. Here, we report a case of anti-NMDAR encephalitis with initial symptoms of epilepsia partialis continua in the absence of tumor. Briefly, a 3-year-old girl was admitted to the hospital due to right-sided, complex partial seizures without preceding febrile illness. The seizures evolved into epilepsia partialis continua and were accompanied by epileptiform discharges from the left frontal area. Three weeks after admission, the patient's seizures were reduced with antiepileptic drugs; however, she developed sleep disturbances, cognitive decline, noticeable oro-lingual-facial dyskinesia, and choreoathetoid movements. Anti-NMDAR encephalitis was confirmed by positive detection of NMDAR antibodies in the patient's serum and cerebrospinal fluid, and her condition slowly improved with immunoglobulin, methylprednisolone, and rituximab. At present, the patient is no longer taking multiple antiepileptic or antihypertensive drugs. Moreover, the patient showed gradual improvement of motor and cognitive function. This case serves as an example that a diagnosis of anti-NMDAR encephalitis should be considered when children with uncontrolled seizures develop dyskinesias without evidence of malignant tumor. In these cases, aggressive immunotherapies are needed to improve the outcome of anti-NMDAR encephalitis.

A rare case of dysembryoplastic neuroepithelial tumor combined with encephalocraniocutaneous lipomatosis and intractable seizures / 소아과

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome that affects ectomesodermal tissues (skin, eyes, adipose tissue, and brain). The neurologic manifestations associated with ECCL are various including seizures. However, ECCL patients very rarely develop brain tumors that originate from the neuroepithelium. This is the first described case of ECCL in combination with dysembryoplastic neuroepithelial tumor (DNET) that presented with intractable seizures. A 7-year-old girl was admitted to our center because of ECCL and associated uncontrolled seizures. She was born with right anophthalmia and lipomatosis in the right temporal area and endured right temporal lipoma excision at 3 years of age. Seizures began when she was 3 years old, but did not respond to multiple antiepileptic drugs. Brain magnetic resonance (MR) imaging performed at 8 and 10 years of age revealed an interval increase of multifocal hyperintense lesions in the basal ganglia, thalamus, cerebellum, periventricular white matter, and, especially, the right temporal area. A nodular mass near the right hippocampus demonstrated the absence of N-acetylaspartate decrease on brain MR spectroscopy and mildly increased methionine uptake on brain positron emission tomography, suggesting low-grade tumor. Twenty-four-hour video electroencephalographic monitoring also indicated seizures originating from the right temporal area. Right temporal lobectomy was performed without complications, and the nodular lesion was pathologically identified as DNET. The patient has been seizure-free for 14 months since surgery. Although ECCL-associated brain tumors are very rare, careful follow-up imaging and surgical resection is recommended for patients with intractable seizures.

Megalencephaly-capillary malformation-polymicrogyria syndrome: the first case report in Korea / 소아과

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP), previously known as macrocephaly-cutis marmorata telangiectatica congenita and macrocephaly-capillary malformation syndrome, is a rare multiple-malformation syndrome that is characterized by progressive megalencephaly, capillary malformations of the midline face and body, or distal limb anomalies such as syndactyly. Herein, we report a female infant case that satisfies the recently proposed criteria of MCAP and describe the distinctive neuroradiological and morphological features. We have also reviewed recently published reports and the diagnostic criteria proposed by various authors in order to facilitate the clinical diagnosis of these children in pediatric neurology clinics.

Epilepsy and Other Neuropsychiatric Manifestations in Children and Adolescents with 22q11.2 Deletion Syndrome

BACKGROUND AND PURPOSE: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome. Epilepsy and other neuropsychiatric (NP) manifestations of this genetic syndrome are not uncommon, but they are also not well-understood. We sought to identify the characteristics of epilepsy and other associated NP manifestations in patients with 22q11.2DS. METHODS: We retrospectively analyzed the medical records of 145 child and adolescent patients (72 males and 73 females) with genetically diagnosed 22q11.2DS. The clinical data included seizures, growth chart, psychological reports, development characteristics, school performance, other clinical manifestations, and laboratory findings. RESULTS: Of the 145 patients with 22q11.2DS, 22 (15.2%) had epileptic seizures, 15 (10.3%) had developmental delay, and 5 (3.4%) had a psychiatric illness. Twelve patients with epilepsy were classified as genetic epilepsy whereas the remaining were classified as structural, including three with malformations of cortical development. Patients with epilepsy were more likely to display developmental delay (odds ratio=3.98; 95% confidence interval=1.5-10.5; p=0.005), and developmental delay was more common in patients with structural epilepsy than in those with genetic epilepsy. CONCLUSIONS: Patients with 22q11.2DS have a high risk of epilepsy, which in these cases is closely related to other NP manifestations. This implies that this specific genetic locus is critically linked to neurodevelopment and epileptogenesis.

Two cases of TSC2/PKD1 contiguous gene deletion syndrome

Tuberous sclerosis complex (TSC, MIM#191100) is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of TSC1 encoding hamartin or TSC2 encoding tuberin and characterized by seizure, mental retardation, and multiple hamartomas or benign tumors in the skin, brain, retina, heart, kidney, and lungs. The TSC2 gene on chromosome 16p13.3 lies adjacent to the PKD1 gene which is responsible for autosomal dominant polycystic kidney disease (MIM#173900). The TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1 CGDS, MIM#600273) is caused by deletion of both TSC2 and PKD1 gene. We recently experienced a 15 month-old boy and a 26 month-old girl with TSC2/PKD1 CGDS confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis. They showed not only typical neurologic manifestations of TSC such as epilepsy, subependymal nodules, and subcortical tubers, but also polycystic kidney disease. The contiguous gene syndrome involving PKD1 and TSC2 should be suspected in children with enlarged polycystic kidneys and TSC. MLPA analysis is a useful method for the genetic confirmation of TSC2/PKD1 CGDS.

Erratum to: Epilepsy and Other Neuropsychiatric Manifestations in Children and Adolescents with 22q11.2 Deletion Syndrome

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