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Archives of plastic surgery. 05/2013; 40(3):277-80.
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ABSTRACT: BACKGROUND AND PURPOSE: Recently published, evidence-based guidelines should alter the management of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). However, the newest recommendations for ALS/MND therapy are not reflected in actual clinical practice. We sought to evaluate the current status of the diagnosis and management of ALS in Korea. METHODS: The Korean ALS/MND research group was organized in 2010, involving more than 50 neurologists from neuromuscular centers in Korea. Participating centers collected data from April to September 2010 on the diagnosis and management of patients with ALS. Data forms from the ALS patient care database, which is a component of the ALS clinical assessment, research, and education program (http://www.outcomes-umassmed.org/ALS/), were modified and used for data collection. RESULTS: In total, 373 sporadic ALS cases from 35 centers were enrolled. The demographic features and clinical findings were similar to those in previous reports from other countries. The mean age at onset was 50-60 years, and a slight male predominance was observed. The enrolled patients predominantly showed focal onset of cervical or lumbosacral symptoms. Only about one-half of the indicated patients (31.4%) received a physician's recommendation for a parenteral gastrostomy, and 18.1% underwent the procedure. Noninvasive ventilation was recommended in 23% of patients, but applied in only 9.5% of them. Tracheostomy was performed in 12.7% of patients. CONCLUSIONS: The demographic and clinical features of the diagnosis and management of ALS in Korea are similar to those reported in other countries; however, supportive management, as recommended in evidence-based guidelines, are not yet widely recommended or performed for patients with ALS in Korea.
Journal of Clinical Neurology 12/2012; 8(4):293-300. · 1.69 Impact Factor
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ABSTRACT: Glycogen synthase kinase-3β (GSK-3β) activity plays a central role in motor neuron degeneration. We hypothesized that GSK-3β inhibitor would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS).
A total of 40 transgenic mice harboring the human G93A mutated SOD1 gene and 14 wild type mice were used following confirmation of their genotype. The 40 transgenic mice were divided into 2 groups; ALS transgenic mice_control and ALS transgenic mice_GSK-3β inhibitor treatment. The clinical status, rotarod test and survival of the transgenic ALS mice and wild-type mice were evaluated. Additionally, motor neuron counting, GSK-3β activity and extrinsic apoptotic signals in spinal cord were also investigated.
The treatment with GSK-3β inhibitor showed excellent motor ability and delay of the symptom onset and survival in the ALS transgenic mice. However, after clinical symptoms developed, the neuroprotective effect of GSK-3β inhibitor was not significant. And the biochemical results revealed the weakly increased extrinsic apoptotic signals in the ALS transgenic mice by GSK-3β inhibitor treatment.
The present study suggests that GSK-3β inhibitor would be a novel promising therapeutic strategy in ALS; however neuroprotective effect of GSK-3β inhibitor may be reduced via extrinsic apoptosis or non-neuronal patho-mechanism in late-stage of disease.
Journal of the neurological sciences 06/2012; 320(1-2):1-5. · 2.32 Impact Factor
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ABSTRACT: Mutations in mitofusin-2 (MFN2) are the most common cause of axonal Charcot-Marie-Tooth (CMT) neuropathy. Herein, we report a novel double mutation in cis (c.[474+4A>G; 668T>A]) in a Korean family with late-onset autosomal dominant mild axonal CMT. Transcriptional analysis demonstrated aberrant splicing with exon 5 skipping and premature termination of translation before the missense mutation in exon 7. Interestingly, the aberrant splicing was incomplete, with some of the primary transcripts being spliced correctly and expressing the downstream missense mutation. The pathogenic relevance of the missense mutation would not be appreciated without the leaky aberrant splicing and the insensitivity of MFN2 to haploinsufficiency.
Neurogenetics 04/2012; 13(3):275-80. · 3.35 Impact Factor
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ABSTRACT: To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.
Journal of Korean medical science 02/2012; 27(2):200-6. · 0.84 Impact Factor
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ABSTRACT: Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy.
We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies.
Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy.
Journal of Clinical Neurology 12/2011; 7(4):233-6. · 1.69 Impact Factor
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ABSTRACT: This study was performed to investigate the asymmetry of motor unit number estimate (MUNE) and its longitudinal course in patients with amyotrophic lateral sclerosis. A modified statistical MUNE was performed at the hypothenar muscles bilaterally in a total of 135 patients, and 18 of these patients underwent a follow-up study. The degree of asymmetry varied considerably among those patients whose average MUNE of both sides was moderately reduced, whereas it tended to be low in those whose average MUNE was either severely reduced or close to normal. The rate of motor unit loss was also asymmetric, and two distinct patterns were identified. In patients whose MUNE was greater than 30 in both sides (n = 7), the rate of motor unit loss tended to be greater in the initially more affected side compared with the contralateral one, yielding the so-called lead phenomenon. In contrast, the other patients (n = 11) tended to show the opposite pattern of "catch-up," that is, MUNE declined faster in the initially less affected side compared with the contralateral one. This study shows that not only the MUNE but also the rate of motor unit loss are frequently asymmetric in amyotrophic lateral sclerosis patients.
Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 09/2011; 28(5):528-32. · 1.47 Impact Factor
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ABSTRACT: Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibody (MuSK-MG) is often associated with prominent facial and bulbar muscle atrophy. It remains unclear whether the muscle atrophy is a consequence of long-term corticosteroid treatment, or of the disease process per se. Herein, we report a steroid-naive patient with MuSK-MG who presented with severe weakness and marked atrophy of the facial and tongue muscles.
Journal of Clinical Neuroscience 09/2011; 18(9):1274-5. · 1.25 Impact Factor
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ABSTRACT: Glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase also known as tau protein kinase I, has been implicated in the pathogenic conditions of Alzheimer's disease. Many investigators have focused on GSK-3 inhibitor as a therapeutic drug. In this study, we established a cell-based assay for the screening of novel GSK-3β inhibitors. For this purpose, four-repeat tau cDNAs were stably expressed in human embryonic kidney 293 (HEK293) cells (HEK293-Tau). The proliferation of HEK293-Tau cells was no different from that of HEK293 cells, as measured by the bromodeoxyuridine enzyme-linked immunosorbent assay (BrdU ELISA). The concentration-dependent reduction of tau phosphorylation by GSK-3 inhibitors, LiCl, Chir98023, and SB415286, was examined by immunoblot analysis and Tau ELISA (in situ ELISA). Highly consistent data were obtained, suggesting that this novel ELISA method is highly reproducible. Using this ELISA strategy, we isolated a few candidate compounds, including compounds 114 and 149, from several hundreds of synthetic agents and demonstrated that such candidates protect nerve growth factor-differentiated PC12 cells against amyloid-β-induced cell death. These data indicate that this Tau ELISA method in HEK293-Tau cells may be a suitable cell-based assay system to screen for GSK-3β inhibitors.
Assay and Drug Development Technologies 05/2011; 9(5):503-13. · 1.73 Impact Factor
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ABSTRACT: Differentiating neuromyelitis optica (NMO) from multiple sclerosis (MS) is a real challenge in the clinical field. In the past, NMO (not MS), was inferred when abnormality was not detected in the brain magnetic resonance imaging (MRI). Recently, some studies have reported abnormalities in the brain MRIs of NMO, but only few among the Asian population. The aim of this study was to evaluate the frequency of brain MRI among Korean NMO patients and characterize findings that might be helpful to distinguish NMO from MS.
Medical records, NMO-IgG, and brain MRI of 17 patients diagnosed with NMO by the revised diagnostic criteria of Wingerchuk et al. (2006) [6] from 2008 to 2010, were reviewed.
11 out of 17 patients (64.7%) had abnormal MRI findings. More than two lesions were detected in most patients. The majority of patients with brain MRI abnormality showed nonspecific (5 patients) or atypical (6 patients) findings. Cerebral white matter was most frequently involved (58.8%). 3 patients (17.6%) involved corpus callosum, 4 (23.5%) with internal capsule, 2 (11.8%) with cerebellum, and 3 (17.6%) with brainstem. There were 5 (29.4%) patients who met the Paty et al. criteria (1988) [15] and 3 patients (35.3%) who met the multiple sclerosis (MS) spatial distribution diagnostic criteria of Barkhof et al. (1997) [14] in their brain MRI.
Brain abnormalities have been frequently found among Korean NMO patients and the frequencies have been reported to be higher than that of Caucasians. Current MS spatial distribution criteria, such as Paty et al. (1988) [15] or Barkhof et al. (1997) [14], are not sufficient to discriminate NMO from MS in brain MRI findings. Our results will provide valuable information that would be useful in establishing future revising criteria for NMO.
Journal of the neurological sciences 03/2011; 302(1-2):43-8. · 2.32 Impact Factor
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ABSTRACT: Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time.
The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity.
Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity.
The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 03/2011; 38(2):242-6. · 0.97 Impact Factor
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ABSTRACT: The pathophysiology of axonal Guillain-Barré syndrome (GBS) is not simple axonal degeneration, but includes reversible conduction failure. Acute motor axonal neuropathy (AMAN) and acute motor conduction block (CB) neuropathy are the two subtypes of pure motor axonal GBS, but their nosologic boundary is still in debate. We investigated clinical and electrophysiological features of 21 consecutive patients with GBS in Korea. Analysis was focused on the presence of CB at intermediate nerve segments (iCB) in pure motor GBS, and its serial changes during the acute phase of disease. Pure motor GBS was common (81%), and iCB was observed in 12 patients with pure motor GBS. Clinical features of pure motor GBS with iCB were distinct from sensorimotor GBS, but similar to pure motor GBS without iCB, characterized by frequent preceding diarrhea, uncommon cranial nerve palsy, and fast recovery. The iCB was not restricted to common entrapment sites, and the distal segments were also commonly involved in the nerves with iCB. The temporal course of iCB was marked by a rapid and often disproportionate increase of proximal and distal amplitudes without remyelinating slow components. Clinical and electrophysiological features of pure motor GBS in patients with iCB suggest that acute motor CB neuropathy may constitute a spectrum of axonal GBS, sharing a common pathomechanism with AMAN.
Journal of the Peripheral Nervous System 03/2011; 16(1):37-46. · 2.80 Impact Factor
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ABSTRACT: The motor unit number index (MUNIX) refers to an electrophysiologic technique that measures the approximate number of motor units using the surface electromyographic interference pattern (SIP) recorded during voluntary contraction. This study was done to assess the reproducibility of MUNIX performed on hypothenar muscles in 62 normal controls and 22 amyotrophic lateral sclerosis (ALS) patients. Inter- and intraoperator correlation coefficients for MUNIX were 0.74 and 0.86, respectively, in normal controls, and 0.95 and 0.93, respectively, in ALS patients (P < 0.01 in all). Inter- and intraoperator coefficients of variation for MUNIX measurements were 17.5% and 15.3%, respectively, in normal controls, and 23.7% and 24.0%, respectively, in ALS patients. This study shows a good correlation for MUNIX between intra- and interoperator results in both normal controls and ALS patients. The test-retest variability seems to be greater in ALS patients compared with normal controls, but this will need to be confirmed in future studies. Sources of variability should be identified and corrected for clinical use.
Muscle & Nerve 11/2010; 42(5):808-13. · 2.37 Impact Factor
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ABSTRACT: We investigated the availability of motor unit number estimation (MUNE) as a quantitative method to assess the severity and clinical progression of amyotrophic lateral sclerosis (ALS). The 143 ALS patients were evaluated by statistical MUNE and the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). By using mean values of MUNE according to disease duration, regression equation between mean MUNE and disease duration was presented as a formula. The individual MUNE ratio was calculated by dividing individual MUNE value by mean MUNE value. All patients were classified into 2 groups (MUNE ratio <1 vs. MUNE ratio >or=1) according to the MUNE ratio. Comparison between the 2 groups revealed that the patients in MUNE ratio <1 group or MUNE ratio >or=1 group were respectively assigned to rapid progression or slow progression. We recommended informative mean values of MUNE and best regression equation in ALS patients according to disease duration. These values allow us to evaluate the severity and rapidity of progression in ALS.
Journal of Korean medical science 09/2010; 25(9):1359-63. · 0.84 Impact Factor
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ABSTRACT: Longitudinally extensive transverse myelitis (LETM) is a syndrome with extensive spinal cord lesions spanning three or more vertebral segments on spinal cord MRI. Although many reports have indicated that LETM is a characteristic feature of neuoromyelitis optica (NMO) in Western countries, the clinical characteristics and risk for development of NMO in Korean patients with LETM is not clear. We retrospectively investigated the clinical, laboratory, radiological features, and prognosis of Korean patients with a first-ever episode of idiopathic LETM. Patients were classified into four subgroups, depending on their clinical course: monophasic LETM, recurrent LETM, NMO, and classic multiple sclerosis (MS). We compared various clinical, laboratory, and radiological features between groups. Of 20 patients with first-ever LETM, 15 (75%) were men, and 13 (65%) experienced clinical relapse over a mean follow-up period of 58 months. Three of 20 patients (two with NMO, one with recurrent myelitis) were seropositive for anti-AQP4 antibodies. The predominance of men in the monophasic and recurrent LETM groups compared to the NMO group was remarkable. In conclusion, Korean patients with LETM are predominantly male and have low seropositivity for anti-AQP4 antibody, which distinguishes them from LETM patients in Western countries. Patients with LETM and seropositivity for anti-AQP4 antibody have a high risk of relapse. The male predominance and the relatively low seropositive rate for anti-AQP4 suggests that rather than being a limited form of NMO, recurrent LETM is a new clinical entity in Koreans.
Journal of Neurology 06/2010; 257(6):920-5. · 3.47 Impact Factor
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ABSTRACT: Hereditary spastic paraplegia (HSP) is a group of genetically heterogenous neurodegenerative disorders characterized by progressive spasticity and weakness of both lower extremities. Herein, we report a novel splicing mutation (c.870+3A>G) in SPG4 in a Korean family with an autosomal dominant-inherited pure HSP. The mutation is located in intron 5, and results in a deletion of the 188bp-sized exon 5. It is likely that the exon 5 deletion leads to spastin dysfunction and cause the typical symptoms and signs of patients.
Journal of the neurological sciences 11/2009; 290(1-2):186-9. · 2.32 Impact Factor
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ABSTRACT: Reports on sleep in multiple system atrophy (MSA) are rare and many confounding variables affect the results. Among them, obstructive sleep apnea and periodic limb movements during sleep are very common. We conducted this study to see the changes of sleep parameters originating from MSA itself without confounders.
We compared polysomnographic variables of 15 MSA patients and 15 age-, gender-, apnea-hypopnea index-, and periodic limb movements index-matched controls. We also applied cyclic alternating pattern scoring in 7 MSA patients and 7 controls.
Total sleep time and sleep efficiency are decreased in MSA. Wake after sleep onset, sleep onset latency, and stage 2 latency are prolonged. There is no difference in the proportion of slow wave sleep and rapid eye movement sleep between MSA patients and the controls. Cyclic alternating pattern scoring shows no difference, either.
MSA itself does not affect the macro- and microstructures of sleep. However, patients with MSA sleep less and it cannot be explained by obstructive sleep apnea and periodic limb movements during sleep.
The Neurologist 10/2009; 15(5):274-6. · 1.26 Impact Factor
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ABSTRACT: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is one of the most common complicated forms of autosomal recessive hereditary spastic paraplegia (HSP). Mutation in SPG11 gene, which is mapped to chromosome 15q21, was recently found to be a major cause of this variant form of HSP. The aim of this study is to investigate SPG11 mutations and clinical manifestations in two Korean families with HSP-TCC. Direct sequencing of the 40 coding exons and boundaries of exon-intron in SPG11 gene, and descriptions of clinical findings in two nonconsanguineous families with HSP-TCC are presented. Three novel and one known compound heterozygous mutations were found in two affected families, which were not found in controls, including one deletion in exon (c.5410_5411delTG), two insertions (c.1834_1835InsT and c.2163_2164InsT), and one missense mutation (c.3291+1G>T). Both of our patients had impairments in frontal lobe functions. We present the first SPG11 mutations in Korean families, three of which are novel. SPG11 mutation should be suspected in Korean patients having HSP with TCC and executive dysfunction.
Journal of Neurology 06/2009; 256(10):1714-8. · 3.47 Impact Factor
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ABSTRACT: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly inherited muscular disorder, which is characterized by weakness of facial, shoulder and hip girdle, humeral, and anterior distal leg muscles. The FSHD gene has been mapped to 4q35 and a deletion of integral copies of a 3.3-kb DNA repeat motif named D4Z4 was known to be the genetic background of the disorder. Although FSHD is the second most common muscular dystrophy in adulthood, there were few reports on the genetically confirmed patients in Korea. Recently, we experienced four Korean patients with clinical features resembling FSHD. In order to confirm the diagnosis, conventional Southern blot (SB) analysis by using double digestion with EcoRI and BlnI and hybridization with p13E-11 probe was performed in three patients and newly developed long polymerase chain reaction (PCR) method was used for one patient because genomic DNA was not enough for conventional SB for this patient. All patients were demonstrated to have shortened D4Z4 repeats that were consistent with FSHD. Therefore, we could confirm the diagnosis of FSHD in four Korean patients and appropriate genetic counseling was done for the patients and their families. It is of note that long-PCR method could be a good alternative for conventional SB when D4Z4 repeats were less than 5.
Journal of Korean Medical Science 01/2009; 23(6):959-63. · 0.99 Impact Factor
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ABSTRACT: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant muscular dystrophy caused by expansion of cytosine-thymine-guanine (CTG) trinucleotide repeats in the myotonic dystrophy protein kinase (DMPK) gene. The clinical features of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations. The aim of this study was to characterize the molecular and clinical spectra of DM1 in Koreans.
The CTG repeats of 283 Korean individuals were tested by PCR fragment analysis and Southern blot. The following characteristics were assessed retrospectively: spectrum of CTG expansions, clinical findings, genotype-phenotype correlation, anticipation, and genetic instability.
One-hundred twenty-four patients were confirmed as DM1 by molecular tests, and the CTG expansions ranged from 50 to 2,770 repeats (median 480 repeats). The most frequent clinical features were myotonia, muscular weakness, and family history. Patients with muscular weakness or dysfunction of the central nervous system harbored larger CTG expansions than those without each symptom (P<0.05). The age of onset was inversely correlated with the size of the CTG expansion (gamma=-0.422, P<0.001). The instability of CTG expansion representing as the maximum difference between sibships was observed from 50 to 700 repeats in nine families. Clinical anticipation and the increase in CTG repeat were significantly higher in maternally transmitted alleles (P=0.002).
Molecular genetic tests are not only essential for diagnosis, but also helpful for suggesting the spectrum and relationship between genotype and phenotype in Korean DM1 patients.
The Korean Journal of Laboratory Medicine 12/2008; 28(6):483-92. · 0.63 Impact Factor
