Jong-Hee Chae

Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy

Mutations in the calpain 3 gene have been proven to be responsible for limb-girdle muscular dystrophy (LGMD) type 2A. To determine the incidence and genotypes of the calpain 3 (p94) gene mutations in Japanese LGMD patients, we sequenced the gene in 80 patients with clinical characteristics of autosomal recessive or sporadic LGMD. We identified 13 distinct pathogenic mutations in 21 patients (26%), including seven missense mutations, four splice-site mutations and two insertions in which six were novel mutations. Among the 21 patients, 15 (71%) had three types of the common missense (G233V, R461C, D707G) and one insertion (1795-1796insA) mutation. The patients had slowly progressive muscle weakness with age of onset of the disease varying from 6 to 52 years, averaging 20.9. The most striking pathologic findings were the presence of lobulated fibers in 14 patients, especially in the advanced stages. Differing from Duchenne and Becker muscular dystrophy, opaque (hypercontracted) fibers were very rarely seen. These findings may be helpful in establishing diagnostic screening strategies in Japanese LGMD patients.

Childhood ocular myasthenia gravis

PURPOSE To investigate the clinical manifestations and ocular findings in children with ocular myasthenia gravis (MG) that rarely have been reported in the literature. DESIGN Retrospective, noncomparative case series. PARTICIPANTS Twenty-four consecutive patients less than 15 years of age with ocular MG treated between June 1988 and July 2001. METHODS The medical records of 6 boys and 18 girls with ocular MG were reviewed retrospectively. MAIN OUTCOME MEASURES Alternate prism cover and uncover test, examination of ductions and versions, and visual acuity. RESULTS Mean age at onset was 38 months. Ptosis was found in 23 patients (96%), strabismus in 21 patients (88%), and amblyopia in 5 patients (21%). Exotropia combined with vertical heterotropia was the most frequent type of strabismus. Ductions were limited in 17 patients (71%), among whom supraduction or infraduction limitations were most frequently observed. Contrary to previous reports, medial rectus underaction was less common than lateral rectus underaction. Manifestations of strabismus and limitation of duction were variable and changed frequently during the follow-up period. The combined use of prednisone and pyridostigmine was found to be the predominant form of maintenance therapy, and ptosis was more responsive to drug therapy than limited ocular motility. CONCLUSIONS Children with ocular MG were found to have a high incidence of ptosis (96%) and exotropia and vertical hyperdeviation. Limitation on adduction was less common than that on abduction. First reported incidence of amblyopia (21%) and a relative nonresponsiveness of the limitation of eye movement to treatment were also noted.

Longitudinal analyses of the surgical outcomes of pediatric epilepsy patients with focal cortical dysplasia.

OBJECT The long-term surgical outcome of pediatric patients with epilepsy accompanied by focal cortical dysplasia (FCD) is not clear. The authors report on the long-term surgical outcomes of children with FCD, based on longitudinal analyses. METHODS The authors retrospectively analyzed the records of 41 children who underwent epilepsy surgery for pathologically proven FCD. Twenty of these patients were male and 21 were female. The median age at surgery was 9 years (range 1-17 years). RESULTS The actuarial seizure-free rates were 49, 44, and 33% in the 1st, 2nd, and 5th years after surgery, respectively. There was no seizure recurrence after 3 years. Three patients with initial failure of seizure control experienced late remission of seizures (the so-called running-down phenomenon). Eventually, 19 patients (46%) were seizure free at their last follow-up visit. Absence of a lesion on MR imaging and incomplete resection were significantly associated with seizure-control failure. Concordance of presurgical evaluation data was a marginally significant variable for seizure control in patients with lesional epilepsy. Three patients with seizure-control failure became seizure free as a result of the running-down phenomenon. The actuarial rate of antiepileptic drug discontinuation was 91% in the 5th year in the seizure-free patients. CONCLUSIONS The seizure-free rate after surgery in children with FCD was 49% in the 1st year; however, it declined thereafter. The running-down phenomenon could be an important mechanism of seizure alleviation for patients with FCD during long-term follow-up. Because a complete resection of FCD has a strong prognostic implication for seizure control, a better method to define the extent of FCD is required to assist with resection, especially in nonlesional epilepsy.

Relapsing demyelinating CNS disease in a Korean pediatric population: Multiple sclerosis versus neuromyelitis optica

Background and Objective:Our objective was to characterize the clinical and radiologic features of Korean pediatric patients with relapsing central nervous system (CNS) demyelination disease. Methods:Twenty-one patients with relapsing CNS demyelinating events were classified as having multiple sclerosis (MS, 18 patients) or neuromyelitis optica (NMO, three patients) according to the international consensus definitions. Retrospective analysis of clinical and radiologic features was conducted. Anti-aquaporin-4 antibody (AQP4 Ab) test was performed in six patients (including three NMO patients) who showed selective involvement of optic nerve and spinal cord. Results: Median age at the initial episode in patients with MS was 7.0 years (range, 4.4–13.6 years). Three of 18 MS patients (3/18, 17%) showed selective involvement of the optic nerve and spinal cord during the clinical course. Five patients (31%) at the initial episode and nine patients (50%) at relapse met the McDonald magnetic resonance imaging criteria for dissemination in space. Oligoclonal bands detected with a silver staining method were positive in only one patient of 16 patients tested. Two NMO patients positive for AQP4 Ab showed frequent relapses and early disabilities that were unresponsive to interferon treatment. Conclusions:We conclude that Korean pediatric patients with relapsing CNS demyelination disease were characterized by preferential involvement of the optic nerve or spinal cord. The AQP4 Ab test seems to be useful for predicting clinical courses in the setting of heterogeneous opticospinal presentations.

Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation

Background and Purpose:  The purpose of this study was to evaluate the mutation status of PANK2 among Korean patients with pantothenate kinase‐associated neurodegeneration (PKAN) and to document the outcome of pallidal deep brain stimulation (DBS).

Clinical and EEG risk factors for subsequent epilepsy in patients with complex febrile seizures

PURPOSE To identify the risk factors for subsequent epilepsy in patients with complex febrile seizures from a single-center retrospective cohort. METHODS The medical records of 1091 patients discharged with a diagnosis of febrile seizures from the Seoul National University Bundang Hospital from February 2004 to October 2009 were reviewed. One hundred eighty-three patients (107 boys and 76 girls) with complex febrile seizures who showed normal neurocognitive development were included in the analysis. Clinical characteristics, including features of complex febrile seizure, initial interictal electroencephalographic findings, and subsequent epilepsy, were reviewed and the odds ratio of subsequent epilepsy was estimated. The mean follow-up duration for subsequent epilepsy was 6.1 years (range, 2.5-8.0 years). RESULTS Complex febrile seizures were observed in 22.6% of all patients with febrile seizures. Among 183 patients with complex febrile seizures, 22 patients (12.0%) developed subsequent epilepsy. Prolonged (>10 min) seizure (p=0.031; odds ratio, 3.04; 95% confidence interval, 1.11-8.32) or the presence of multiple seizures for 24 h (p=0.032; odds ratio, 3.63; 95% confidence interval, 1.12-11.8) was significantly more frequent in patients with subsequent epilepsy, whereas the presence of focal seizure was not significantly different. Epileptiform discharges (focal in all cases) were significantly more frequent in patients with subsequent epilepsy (50% vs. 13%, p=0.002), with an odds ratio of 5.15 (95% confidence interval, 1.84-14.5). CONCLUSION The presence of epileptiform discharges is a significant risk factor for subsequent epilepsy in patients with complex febrile seizures. Electroencephalography should be considered in all patients with complex febrile seizures especially those who had multiple or prolonged seizures.

Mutational analysis of TSC1 and TSC2 in Korean patients with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction and dermatological abnormalities. TSC is caused by mutations affecting either of the tumor-suppressor genes TSC1 and TSC2. At least 495 mutations of TSC1 and TSC2 have been reported. Twenty-two males and 22 females who were diagnosed with TSC at the Seoul National University Childrens Hospital between 1982 and 2002 were enrolled in the study. Forty-four patients were from different families and included nine familial cases and 35 sporadic cases. Denaturing high performance liquid chromatography and DNA sequencing analysis of TSC1 and TSC2 revealed 13 types of mutations (30%). One novel mutation of TSC1 and nine novel mutations of TSC2 were identified. The TSC1 mutation and one of the nine TSC2 mutations were missense mutations and seven of the nine TSC2 mutations caused truncation of proteins. One novel single nucleotide substitution was identified at the consensus splicing donor site of exon 39 (c.5,069-1G>A). This mutation is predicted to cause a splicing error. Of the TSC2 mutation loci, the correlation with cardiac rhabdomyoma was more significant when the mutation was in the C-terminal part of tuberin than the N-terminal part. This is the first extensive mutational analysis of TSC1 and TSC2 in Korean TSC patients.

Paroxysmal nonepileptic events in pediatric patients confirmed by long-term video-EEG monitoring — Single tertiary center review of 143 patients

The purpose of the study was to evaluate the clinical characteristics of paroxysmal nonepileptic events (PNEs) in pediatric patients. Reports of 1108 patients who underwent long-term video-EEG monitoring at Seoul National University Childrens Hospital were reviewed retrospectively. One hundred forty-three (12.9%) patients were diagnosed as having PNEs. The most common type of PNE was staring. Staring, tonic posturing, sleep myoclonus, and sleep-related disorders were more common in patients younger than 6 years old. Psychogenic nonepileptic seizure was the most common PNE in patients older than 6 years. Patients who were younger than 6 years old showed shorter disease duration and more varied types of PNEs when compared to older patients (6 years old or older). Presence of epilepsy was not significantly related to clinical difference in PNEs. In patients with developmental delay, staring and tonic posture were significantly more frequent than patients without developmental delay. Thirty-two patients without concurrent epilepsy were misdiagnosed with epilepsy, and AEDs were discontinued after the correct diagnosis of PNEs. Whenever the diagnosis of paroxysmal abnormal behavior is uncertain, correct diagnosis should be made using long-term video-EEG monitoring, especially in younger pediatric patients and patients with developmental delay.

Selective preconcentration and online collection of charged molecules using ion concentration polarization

A multilayer micro/nanofluidic device was presented for the selective preconcentration and online collection of charged molecules with different physicochemical properties based on ion concentration polarization phenomena. With a balance of electroosmotic drag force and electrophoretic force on the molecules, a sample mixture of sulforhodamine B and Alexa Fluor 488 could be highly preconcentrated and separated simultaneously. A repeated microchamber structure was employed to capture each dye at a desirable position. For subsequent on-chip or off-chip application, pneumatic microvalves were integrated and selectively collected the target dyes with cyclic valve operations. Using the integrated system, Alexa Fluor 488 was solely collected (with a separation resolution of 1.75) out of the mixture at a 30-fold preconcentration ratio. This integrated device would be a key component for lab on a chip applications.

Long-term effectiveness of ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy

PURPOSE We performed this study to evaluate the long-term efficacy and tolerability of ethosuximide (ESX), valproic acid (VPA), and lamotrigine (LTG) as initial monotherapies for patients with newly diagnosed childhood absence epilepsy. METHODS We retrospectively reviewed the medical records of 128 patients (45 boys and 83 girls) diagnosed with childhood absence epilepsy at the Seoul National University Hospital. The diagnosis was based on the criteria proposed by Panayiotopoulos in 2005. We measured the seizure-free rate and the retention rate observed during 2 years of treatment. Follow-up electroencephalography (EEG), any reported adverse events, and reasons for antiepileptic drug (AED) discontinuation were reviewed. RESULTS The seizure-free rate of ESX (84%) was significantly higher than that of VPA (62%) and LTG (53%) at 3 months. The seizure-free rate of ESX (90%) was significantly higher than that of LTG (63%) at 6 months. After 9 months, there was no significant difference in seizure-free rate among the three groups. There were no significant differences among the three groups in terms of normalization of EEG at 12 months (ESX, 77%; VPA, 83%; and LTG, 64%), retention rate throughout the whole treatment period, and adverse-event rates (ESX, 25%; VPA, 29%; and LTG, 14%). CONCLUSION This study suggests that ESX, VPA, and LTG are equally effective in the long-term treatment of newly diagnosed CAE patients. However, the onset of efficacy was faster for ESX compared with VPA or LTG. Efficacy, tolerability, and adverse event profiles should be carefully considered when selecting AEDs to treat individual patients with CAE.