Clinical Spectrum of Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G-Associated Disease in Korean Children

Background@#and Purpose: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOGantibody-positive demyelinating diseases in children. @*Methods@#This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. @*Results@#The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4–169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p= 0.011). @*Conclusions@#MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.

Erratum to: Elevated Serum Uric Acid in Benign Convulsions with Mild Gastroenteritis in Children

The Anti-Inflammatory Effect of Sulforaphane in Mice with Experimental Autoimmune Encephalomyelitis

BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.

Elevated Serum Uric Acid in Benign Convulsions with Mild Gastroenteritis in Children

BACKGROUND AND PURPOSE: To identify whether serum uric acid levels are significantly higher in patients with benign convulsion associated with mild gastroenteritis (CwG) than in patients with acute gastroenteritis. METHODS: This retrospective study compared the serum levels of uric acid between CwG, acute gastroenteritis, and febrile seizure after correcting for the varying degree of mild dehydration using serum HCO3⁻ levels. We also compared the serum uric acid levels between patients with CwG and febrile seizures in order to exclude the effect of seizures on uric acid. RESULTS: This study included 154 CwG patients (age range 0.73–3.19 years), 2,938 patients with acute gastroenteritis, and 154 patients with febrile seizure. The serum uric acid level was significantly higher in CwG patients than in patients with acute gastroenteritis [9.79±2.16 mg/dL vs. 6.04±2.3 mg/dL (mean±SD), p<0.001]. This difference was also significant after correcting for dehydration. The serum uric acid level was significantly higher in CwG patients than in dehydration-corrected acute gastroenteritis patients (9.79±2.16 mg/dL vs. 6.67±2.48 mg/dL, p<0.001). The serum uric acid level was not elevated in patients with febrile seizure. CONCLUSIONS: We have confirmed that serum uric acid is elevated in CwG patients even after correcting for their dehydration status, and that this was not a postictal phenomenon. Highly elevated serum uric acid in CwG could be a useful clinical indicator of CwG in patients with acute gastroenteritis.

A Case of a Child with Seizure caused by Organophosphate Poisoning / 대한소아신경학회지

Seizure is a temporary symptom or sign which is caused by an abnormal electrical stimulation of brain. Depending on whether a seizure has preceding factors or not, it can be further categorized into provoked and unprovoked seizure. In provoked seizure, it is important to find a cause for treatment. In this study, we would like to report a case of a 6 year-old male child with seizure caused by organophosphate poisoning. The patient's chief complaint was his decreased mental status accompanying seizure. Initially, status epilepticus was suspected but the response to anticonvulsants was not good, and resulted in prolonged respiratory failure. After 3 hours, the patient showed signs of cholinergic crisis. In response, atropine was administered and the condition improved. If respiratory failure or mental confusion persists even after cessation of seizure in status epilepticus, repetitive physical and neurological examinations should be carried out to find preceding factors. Even though the recent incidence of organophosphate poisoning has decreased, we would like to emphasize from our study that it should be considered as a preceding factor for seizure.

Effects of Anticonvulsant Monotherapy on Bone Mineral Density in Children / 대한소아신경학회지

PURPOSE: The use of anticonvulsants can cause side effects such as reduction of bone mineral density, requiring attention in growing children. The aim of our study is to investigate the effects of different anticonvulsants on bone mineral density in epileptic patients treated with monotherapy. METHODS: We retrospectively reviewed medical records of 60 subjects who visited the Pediatric Epilepsy Clinic of Bucheon St. Mary's Hospital from January 2013 to December 2017. Bone mineral density was measured with dual photon absorptiometry every 6 months. RESULTS: The number of patients treated with oxcarbazepine, valproate and levetiracetam was 31, 16 and 13, respectively. Reduction of bone mineral density was seen in 8 out of 31 patients (25.8%, P=0.10) treated with oxcarbazepine, 9 out of 16 patients treated with valproate (56.3%, P=0.04) and 4 out of 13 patients treated with levetiracetam (30.8%, P=0.50). CONCLUSION: There was a significant reduction of bone mineral density in patients treated with valproate compared to the other anticonvulsants in our study. We believe attention to bone mineral density is required in children treated with anticonvulsants.

Eosinophilic Granulomatosis with Polyangiitis Presented as Acute Polyneuropathy and Cerebral Vasculitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is an immune related systemic disease that is caused by vasculitis affecting multiple organ systems. It is characterized by asthma, fever, eosinophilia, cardiac problems, renal injury, and peripheral neuropathy. In this report, we describe a patient with EGPA with concurrent cerebral infarction and acute polyneuropathy mimicking a Guillain-Barre syndrome (GBS). A 46-year-old man presented with rapidly progressing gait disturbance, muscular weakness, and tingling sensation in all four limbs. A nerve conduction study revealed sensorimotor polyneuropathy in all four limbs, and a test of the cerebrospinal fluid showed an albumin-cytologic dissociation. In addition, brain magnetic resonance imaging (MRI) using fluid-attenuated inversion recovery and diffusion weighted MRI revealed high signal intensity lesions with gadolinium enhancement on T1-weighted MRI in the right caudate nucleus. After performing laboratory tests, paranasal sinus computed tomography, and a nasal smear, the patient was diagnosed with EGPA and treated with high dose glucocorticoid and oral cyclophosphamide. In conclusion, our findings indicate that a diagnosis of EGPA should be considered when a patient presents with rapidly progressing polyneuropathy mimicking a GBS along with unusual systemic symptoms or brain lesions.

Factors Associated with Favorable Outcome of Topiramate Migraine Prophylaxis in Pediatric Patients

BACKGROUND AND PURPOSE: There are few studies that have investigated predictive factors related to migraine prophylaxis of which produced inconsistent results. The aim of this study was to identify factors that can predict the treatment response to topiramate prophylaxis in pediatric patients with migraine. METHODS: One hundred and thirteen patients who were older than 7 years and received topiramate for at least 3 months were recruited from the Seoul National University Bundang Hospital outpatient clinic from 2005 to 2014. A positive response was defined as a reduction of more than 50% in the number of migraine episodes after topiramate treatment. Proposed predictive factors such as migraine characteristics including severity and frequency were assessed, as were other data on sex, disease duration, associated symptoms, family history, and impairment of daily activities. RESULTS: Seventy patients (61.9%) responded to prophylactic treatment with topiramate. Patients who experienced significant impairment in daily activities showed significant benefit from the treatment (p=0.004). Sex, the severity, frequency, and duration of migraine episodes, disease duration, treatment duration, age at onset, and associated symptoms were not significantly related to a response to topiramate treatment. CONCLUSIONS: Migraine characteristics and associated symptoms were not significantly related to a response to topiramate treatment. However, patients with significant impairment in daily activities showed significant benefit from the treatment, and so prophylactic topiramate treatment should be strongly encouraged in this patient group.

Efficacy and Tolerability of Valproic Acid Once Daily Dosing for Juvenile Myoclonic Epilepsy

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerability of extended-release valproic acid once daily dosing in juvenile myoclonic epilepsy (JME). METHODS: Medical records of patients who received valproic acid monotherapy for the treatment of JME were retrospectively reviewed. Their clinical information regarding age, gender, seizure types, underlying neurologic status, dosing regimen, response to treatment, and adverse events related to valproic acid, were analyzed. Seizure control, compliance, and adverse events rates were compared between the group of once daily dosing and the group of twice daily dosing. RESULTS: Twenty one patients (11 boys and 10 girls) were included in the study. Twelve patients were taking valproic acid extended-release once daily and nine patients were taking twice a day. More than 50% decrease in myoclonic seizure was achieved in all the patients in both groups. Generalized tonic-clonic seizure was controlled in all the patients who were taking once daily while 3 patients (36%, 3/8 patients) in twice daily group had breakthrough generalized tonic clonic seizures during the 2 year period of treatment. However, there were no statistically significant differences in seizure control, compliance, and adverse event rates between the two groups. CONCLUSION: This study demonstrated that valproic acid extended-release once daily dosing was as effective and tolerable as twice daily in the treatment of JME. Once daily dosing of valproic acid would be convenient which improve patient compliance and consequently bring better outcome in treatment of JME.

Electroencephalographic Features of Rasmussen's Encephalitis by Stage

PURPOSE: The purpose of this study was to describe the characteristic electroencephalographic features in Rasmussen's encephalitis by stage. METHODS: Patients diagnosed with Rasmussen's encephalitis at Seoul National University Children's Hospital were retrospectively assessed. We analyzed the background activities and epileptiform discharges from electroencephalography (EEG) findings to identify the characteristic EEG features by stage. RESULTS: Seven patients were included in the study. The mean age of first seizure onset was 6.7 years, and the mean duration of the prodromal phase was 21.4 months. During disease course, background activities, such as slow waves, were more prominent and diffuse, and contralateral slow waves were observed. In most patients, focal epileptiform discharges were observed during all stages without change. CONCLUSION: As Rasmussen's encephalitis progresses, background abnormalities in the affected hemisphere increased, and contralateral slow waves occurred. However, characteristic EEG findings that were distinguishable at each stage were not observed.

Effectiveness and Tolerability of Fosphenytoin for Pediatric Status Epilepticus

PURPOSE: The study was aimed to investigate the effectiveness and tolerability of intravenous fosphenytoin (fPHT) in the treatment of pediatric status epilepticus (SE). METHODS: Medical-records of patients who received intravenous (IV) fPHT for the treatment of SE were retrospectively reviewed and their clinical data were analyzed regarding age, gender, seizure types, underlying neurologic status, use of other anticonvulsants, loading dose, response and adverse events of IV fPHT. RESULTS: Twenty patients (12 boys and 8 girls) were included in the study. The mean age at administration of IV fPHT was 3.98 years (range 0-18.6 years). Of the 20 patients, 15 patients had no underlying neurological conditions, but five patients were on anticonvulsants. IV fPHT terminated the seizures in 15 of the 20 patients (75%). No adverse events occurred during or after the infusions. CONCLUSION: This study demonstrated that IV fPHT was as effective as phenytoin and was well-tolerated in the treatment of pediatric SE. IV fPHT can be considered as a substitute for phenytoin in the management of pediatric SE.

A Neonatal Form of Alexander Disease Presented with Intractable Seizures and Obstructive Hydrocephalus

Alexander disease is a rare degenerative leukodystrophy caused by dominant mutations in glial fibrillary acidic protein (GFAP). The neonatal form of Alexander disease may manifest as frequent and intractable seizures or obstructive hydrocephalus, with rapid progression leading to severe disability or death within two years. We report a case of a 50-day-old male who presented with intractable seizures and obstructive hydrocephalus. His initial magnetic resonance imaging (MRI) suggested a tumor-like lesion in the tectal area causing obstructive hydrocephalus. Despite endoscopic third ventriculostomy and multiple administrations of antiepileptic drugs, the patient experienced intractable seizures with rapid deterioration of his clinical status. After reviewing serial brain MRI scans, Alexander disease was suspected. Subsequently, we confirmed the de novo missense mutation in GFAP (c.1096T>C, Y366H). Although the onset was slightly delayed from the neonatal period (50 days old), we concluded that the overall clinical features were consistent with the neonatal form of Alexander disease. Furthermore, we also suspected that a Y366 residue might be closely linked to the neonatal form of Alexander disease based on a literature review.

Efficacy and Tolerability of Rufinamide for Intractable Generalized Epilepsies

PURPOSE: The purpose of the study was to evaluate the efficacy and safety of rufinamide for intractable generalized epilepsies. METHODS: Eighteen patients with intractable generalized epilepsies were included in the study. Their medical records were retrospectively reviewed. Rufinamide was administered as an add-on treatment for intractable epilepsies. The initial administered dose was 10 mg/kg/day, which was subsequently titrated up to 30-50 mg/kg/day. The effectiveness was assessed by comparing the frequency of seizures after the treatment. The difference in number of seizures during 4 weeks was compared before and after reaching the final dose. RESULTS: The study population consisted of 13 males and 5 females (mean age 13.6+/-6.2 years, range 3.3-29.2 years). The responder rate (> or =50% in seizure frequency) was 39% and the seizure free rate was 11%. Retention rate was 44% and the reasons for withdrawal was adverse events (6/18 patients, 33%), aggravation of seizures (4/18 patients, 22%), and ineffectiveness (2/18 patients, 11%). Adverse events included hyperactivity, somnolence, ataxia and polyhidrosis. Adverse events and seizure aggravation occurred even at the starting dose of rufinamide treatment. CONCLUSION: Rufinamide can be used as an efficacious and safe adjunctive anticonvulsant for patients with intractable generalized epilepsy.

A Family-based and Case-control Association Study of the Dopamine D5 Receptor Gene Polymorphism in Attention Deficit Hyperactivity Disorder / 신경정신의학

OBJECTIVES: Recent genetic studies have suggested a preferential transmission of the Dopamine D5 receptor gene (DRD5) 148bp marker allele. The aim of this study is to test the association between DRD5 and ADHD. METHODS: 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk test (HHRR). And also the ADHD children were compared with 212 age and gender matched normal controls. RESULTS: We found the evidence for an association of short alleles of DRD5 dinucleotide repeat polymorphism in both case control and family based studyies. Additionally, we observed some evidence for biased transmission of allele 152 bp and 144 bp. CONCLUSION: Our results lend credence to the notion that the relationship between ADHD and DRD5 is complex. The number of cases and informative transmissions in our study were small, therefore it would be premature to make any conclusions concerning the role of DRD5 in ADHD. Further work is needed to support these findings.

A Family-based and Case-control Association Study of the Dopamine D5 Receptor Gene Polymorphism in Attention Deficit Hyperactivity Disorder / 신경정신의학

OBJECTIVES: Recent genetic studies have suggested a preferential transmission of the Dopamine D5 receptor gene (DRD5) 148bp marker allele. The aim of this study is to test the association between DRD5 and ADHD. METHODS: 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk test (HHRR). And also the ADHD children were compared with 212 age and gender matched normal controls. RESULTS: We found the evidence for an association of short alleles of DRD5 dinucleotide repeat polymorphism in both case control and family based studyies. Additionally, we observed some evidence for biased transmission of allele 152 bp and 144 bp. CONCLUSION: Our results lend credence to the notion that the relationship between ADHD and DRD5 is complex. The number of cases and informative transmissions in our study were small, therefore it would be premature to make any conclusions concerning the role of DRD5 in ADHD. Further work is needed to support these findings.