Clinical Usefulness of a Cell-based Assay for Detecting Myelin Oligodendrocyte Glycoprotein Antibodies in Central Nervous System Inflammatory Disorders

Background@#The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients’ clinical characteristics. @*Methods@#We established the CBA using HEK 293 cells transiently overexpressing fulllength human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD). @*Results@#Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ = 0.883, P < 0.001); two patients (2/166, 1.2%) were only positive in our in-house CBA, and the CBA scores of the two laboratories correlated well (r = 0.663, P < 0.001). The commercial MOG-Ab CBA kit showed one falsenegative and three false-positive results. The clinical presentation at disease onset differed between MOGAD and NMOSD; ON was the most frequent manifestation in MOGAD, and transverse myelitis was most frequent in NMOSD. @*Conclusions@#The in-house CBA for MOG-Abs demonstrated reliable results and can potentially be used to evaluate CNS inflammatory disorders. A comprehensive, long-term study with a large patient population would clarify the clinical significance of MOG-Abs.

Results of a Survey on Diagnostic Procedures and Treatment Choices for Neuromyelitis Optica Spectrum Disorder in Korea: Beyond the Context of Current Clinical Guidelines

Background@#and Purpose Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system (CNS). We investigated the medical behaviors of experts in Korea when they are diagnosing and treating NMOSD. @*Methods@#An anonymous questionnaire on the diagnosis and treatment of NMOSD was distributed to experts in CNS demyelinating diseases. @*Results@#Most respondents used the 2015 diagnostic criteria for NMOSD and applied a cerebrospinal fluid examination, magnetic resonance imaging (MRI) of the brain and spine, and anti-aquaporin-4 antibody testing to all suspected cases of NMOSD. All respondents prescribed steroid pulse therapy as an first-line therapy in the acute phase of NMOSD, and 67% prescribed azathioprine for maintenance therapy in NMOSD. However, details regarding monitoring, the tapering period of oral steroids, second-line therapy use in refractory cases, management during pregnancy, and schedule of follow-up MRI differed according to the circumstances of individual patients. We analyzed the differences in response rates between two groups of respondents according to the annual number of NMOSD patients that they treated.The group that had been treating ≥10 NMOSD patients annually preferred rituximab more often as the second-line therapy (p=0.011) and had more experience with rituximab treatment (p=0.015) compared with the group that had been treating <10 NMOSD patients. @*Conclusions@#This study has revealed that NMOSD experts in Korea principally follow the available treatment guidelines. However, the differences in specific clinical practices applied to uncertain cases that have been revealed will need to be investigated further in order to formulate suitable recommendations.

Case Reports of Acute Transverse Myelitis Associated With mRNA Vaccine for COVID-19

Acute transverse myelitis (ATM) has been reported as rare complication of vaccination. Herein, we report 2 cases of ATM after the administration of an mRNA vaccine for coronavirus disease 2019 (COVID-19). The first one is an 81-year-old man who received the BNT162b2 vaccine. He presented with bilateral hand weakness. Spine magnetic resonance imaging (MRI) showed high signal intensity from the C1 to C3 vertebrae. The second is a 23-year-old woman who received the BNT162b2 vaccine and experienced tingling in her legs. Spine MRI showed a high signal intensity lesion at the conus medullaris. These patients were treated with intravenous methylprednisolone and their symptoms improved slightly. Careful follow-up is needed to identify adverse events after the administration of mRNA vaccines for COVID-19.

A Case of Glycogen Storage Disease Type V with Rhabdomyolysis after COVID-19 Vaccination / 대한신경근육질환학회지

Glycogen storage disease (GSD) type V, also known as McArdle’s disease, is an autosomal recessive genetic disease caused by a mutation of the PYGM gene related to the synthesis of the myophosphorylase enzyme. Here, we presented the case of an 83-year-old woman who was admitted for progressively worsening weakness of her legs due to rhabdomyolysis after a COVID-19 vaccination. In the muscle biopsy, myopathy with subsarcolemmal glycogen accumulation was revealed and she was diagnosed with a mild form of GSD type V. Although COVID-19 vaccines are generally safe and encouraged for everyone, adverse events following COVID-19 vaccinations are increasing. We should pay attention to the side effects of COVID-19 vaccination including rhabdomyolysis.

Prevalence and Incidence of Neuromyelitis Optica Spectrum Disorderin Korea: Population Based Study

Background@#Although neuromyelitis optica spectrum disorder (NMOSD) is known to be a rare disease, its prevalence and incidence have not yet been studied in Korea. We performed a population-based study to examine the prevalence and incidence of NMOSD in Korea using data from the Korean National Health Insurance (NHI) claims database. @*Methods@#Data from 2013 to 2017 were obtained, with a washout period set as 2013 and 2014. The prevalence and incidence of NMOSD in 2016 and 2017 were calculated using population census data. Subjects were divided into 5 groups at 15-year intervals, depending on the age at which the diagnostic code was entered. The relative risk (RR) for each age group was compared with the oldest (≥ 60 years) age group. @*Results@#The overall prevalence was estimated to be 3.36 and 3.56 per 100,000 individuals, with an incidence of 0.41 and 0.65 per 100,000 individuals-year in 2016 and 2017, respectively. The mean age was 43.08 (standard deviation, 14.56) years, and the ratio of male to females was 1:4.7. The incidence was higher in female individuals aged between 30 and 59 years (RR, 2.8–3.05; P < 0.05). @*Conclusion@#Nationwide prevalence of NMOSD in Korea was 3.36 and 3.56/100,000 and its incidence was 0.41 and 0.65/100,000-year in 2016 and 2017 respectively.

Estrogenic Activity of Sanguiin H-6 through Activation of Estrogen Receptor α Coactivator-binding Site

A popular approach for the study of estrogen receptor α inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt ERα and coactivator interaction with an ERα antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At 100 µg/mL, R. coreanus extract significantly stimulated cell proliferation (574.57 ± 8.56%). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the ERα coactivator-binding site in molecular docking analysis, with a binding energy of

A Case of Frey's Syndrome Diagnosed and Followed Up Using the Quantitative Sudomotor Axon Reflex Test

No abstract available.

Author Correction: Single CD271 marker isolates mesenchymal stem cells from human dental pulp / 国际口腔科学杂志·英文版

In the original version of this Article, Figure 1c was inadvertently assembled with a duplicate of Figure 1b. The correct image for Figure 1c, shown below, has been added in the HTML and PDF versions of the Article. This does not affect the conclusions of the study. We sincerely apologize for any inconvenience this may have caused our readers.

Late-onset non-thymomatous myasthenia gravis: Comparison with early-onset and very late-onset myasthenia gravis

Objective: To identify the clinical characteristics of patients with myasthenia gravis (MG) according to age at onset. Methods: We retrospectively recruited 227 non-thymomatous MG patients with adult onset who had been followed up for more than one year. The patients were classified based on the age of symptom onset as “early-onset MG” (EOMG,18–50 years; N=135), “late-onset MG” (LOMG, 50–64 years; N=53), and “very late-onset MG” (VLOMG, 65 years; N=39). Clinical features and serological findings were compared between these groups. Results: LOMG patients showed more frequent ocular MG (55%) and less frequent thymic hyperplasia (9%) compared to EOMG patients (31% and 38%; p=0.006 and p<0.001, respectively), and no female preponderance compared to VLOMG patients (female, 49% vs.77%; p=0.014). However, there were no significant differences between VLOMG and EOMG patients, except for more frequent thymic hyperplasia (p<0.001) in EOMG patients. When analyzing female patients only, less frequent secondary generalization (10%) were additionally found in LOMG patients, compared to EOMG (47%, p= 0.008) and VLOMG (59%, p=0.004) patients. Anti-acetylcholine receptor antibody (HR, 5.48; 95% CI, 1.73–17.37; p=0.004) was independently associated with secondary generalization in female EOMG patients. Conclusion: Our study suggests that LOMG patients, especially female, were characterized by frequent ocular MG and less frequent secondary generalization, distinguished from EOMG and VLOMG patients. Further large epidemiologic studies in Korea are needed to determine the characteristics of MG patients according to the age at onset and gender.

Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers / 国际口腔科学杂志·英文版

Mesenchymal stem cell (MSC)-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations: CD51/CD140α, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells (DMSCs) from heterogeneous periodontal ligament cells (PDLCs). Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51(+)/CD140α(+), 0.8% were CD271(+), and 2.4% were STRO-1(+)/CD146(+). Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271(+) DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

Two Cases of Lipoatrophy after Local Corticosteroid Injection / 대한임상신경생리학회지

The adverse effects of systemic steroid medications are well known, whereas those of local steroid injections are unclear even to clinicians. We report two cases of localized lipoatrophy and depigmentation following local steroid injection. Although the incidence of soft tissue atrophy after local steroid injection is rare, it will increase in proportion to the frequency of the procedure. All clinicians, even those who do not perform steroid injections, should be aware of the occurrence of this cosmetically disturbing adverse effect.

Single CD271 marker isolates mesenchymal stem cells from human dental pulp / 国际口腔科学杂志·英文版

Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow (BMSCs), adult MSCs are isolated from craniofacial tissues including dental pulp tissues (DPs) using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cells (DMSCs). In this study, we used different combinations of surface markers (CD51/CD140α, CD271, and STRO-1/CD146) to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells (DPCs) obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51(+)/CD140α(+), 10.6% were CD271(+), and 0.3% were STRO-1(+)/CD146(+). Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271(+) DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271(+) DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.

Intravenous administration of EGB 761 and 90-day functional outcome in patients with acute ischemic stroke

Background & Objective: EGB 761 is a standardized natural extract used to treat impaired cerebral perfusion and nutrition (cerebrovascular insufficiency) in Korea. Although several animal studies have been conducted, few studies have investigated the clinical effects of EGB 761 in acute stroke. This study assessed the clinical benefit of intravenous EGB 761 in patients with acute ischemic stroke. Methods: This retrospective study examined a prospectively collected stroke database. We evaluated 232 patients with acute ischemic stroke within 48 hours of symptom onset. All patients were treated with antiplatelet or anticoagulation agents. We compared baseline characteristics between the EGB 761-treated and non-treated groups. The functional outcome measure was the modified Rankin Scale (mRS) score 90 days after stroke onset. Results: Of the 232 patients, 170 received EGB 761 during the first 3 days after arrival in the emergency department. We found no significant differences in baseline characteristics between the groups, with the exception of atrial fibrillation (p=0.032). After adjusting for baseline factors, intravenous administration of EGB 761 was associated with an improved 90-day functional outcome (mRS ≤2) compared with the control group (odds ratio, 2.56; p<0.05). Conclusions: Our results showed a clinical benefit of intravenous EGB 761 in patients with acute ischemic stroke

A case of delayed radiation-induced lumbosacral radiculoplexopathy after 30 years

Lumbosacral radiculoplexopathy in colon cancer treatment is a very rare but serious complication after radiation. We report here a 66-year-old man with slowly progressive lower limb weakness which arose 30 years after local radiation treatment for colon cancer. Electrophysiological studies revealed signs of denervation confined to the lower limbs. Other causes were excluded by clinical presentation, serological, cerebrospinal fluid and imaging studies. This case shows that delayed radiation-induced lumbosacral radiculoplexopathy can occur 30 years after the initial treatment.

Association between carotid intima-media thickness and Ankle-Brachial Index in patients with ischemic stroke / 동물의과학연구지

BACKGROUND AND PURPOSE: The Ankle-Brachial Index (ABI) is the ratio of blood pressure in the lower legs to that in the arms. The intima-media thickness (IMT) of extracranial carotid arteries determined by B-mode ultrasound is a measurable index of the presence of atherosclerosis. A low ABI and a high carotid IMT are independently related to increased risk of cardiovascular events. This study examined the association between carotid IMT and ABI in patients with ischemic stroke. MATERIALS AND METHODS: Retrospectively, 116 hospitalized patients with ischemic stroke were recruited. Using a pulse wave velocity ABI device along with carotid duplex sonography, we measured carotid IMT and ABI and investigated the correlation between average values. RESULTS: There was a significant difference in carotid IMT between the normal and abnormal ABI groups (P=0.0262). The group with an abnormal ABI was more than five times as likely to have increased carotid IMT as the group with a normal ABI (age, sex-adjusted OR 5.67 (95% CI 1.85~17.38)). The ABI and carotid IMT showed a weak inverse linear correlation in patients with ischemic stroke (correlation coefficient -0.378 after adjusting for age and sex). CONCLUSION: Our study suggests that an abnormal ABI is associated with a high carotid IMT in patients with ischemic stroke.

Retraction: Maternal and lifestyle effect on bone mineral density in Korean children and adolescents aged 8-19 / 한국영양학회지

It has come to my attention that the manuscript below contains an accidental mistake in writing the institution that approved the IRB approval.

Maternal and lifestyle effect on bone mineral density in Korean children and adolescents aged 8-19

Higher bone mineral density (BMD) at a young age, calcium intake, and exercise are important for prevention of osteoporosis later in life. We examined familial effects of BMD between mothers and children and adolescents aged 8-19 in Cheonan, Korea and the relationships between BMD and lifestyle parameters, including: food and nutrient intake and exercise. For daughters and sons, significant differences in BMD were observed at the three bone sites (total femur, femur neck, and lumbar spine) according to age, gender, body mass index, exercise, and milk consumption, compared to the reference value for each classification category. Mean differences in children's BMD were observed according to maternal BMD. Energy and calcium intake were lower in both children and mothers in comparison to the estimated daily energy requirement; however, their protein intake was much greater than the daily recommended intake. After adjusting for age and gender and for mother's age, body mass index, and total calorie intake, results of the food frequency test showed an association of a higher intake of meat, meat products, milk and milk products with greater BMD of total femur, femur neck, and lumbar spine of children. In addition, exercise was positively associated with higher BMD. Regression analysis showed a positive association of BMD with age, male gender, exercise, and mother's BMD. In conclusion, after adjustment for environmental parameters, maternal BMD had a positive influence on BMD in daughters and sons. This finding suggests that parents need to check their BMD in order to determine whether their children are at increased risk of low BMD.

Dumping Syndrome in an Adult Patient Receiving Gastrostomy Feeding With Persistent Vegetative State

No abstract available.

Dlx3 and Dlx5 Inhibit Adipogenic Differentiation of Human Dental Pulp Stem Cells

Dlx3 and Dlx5 are homeobox domain proteins and are well-known regulators of osteoblastic differentiation. Since possible reciprocal relationships between osteogenic and adipogenic differentiation in mesenchymal stem cells exist, we examined the regulatory role of Dlx3 and Dlx5 on adipogenic differentiation using human dental pulp stem cells. Over-expression of Dlx3 and Dlx5 stimulated osteogenic differentiation but inhibited adipogenic differentiation of human dental pulp stem cells. Dlx3 and Dlx5 suppressed the expression of adipogenic marker genes such as C/EBPalpha, PPARgamma, aP2 and lipoprotein lipase. Adipogenic stimuli suppressed the mRNA levels of Dlx3 and Dlx5, whereas osteogenic stimuli enhanced the expression of Dlx3 and Dlx5 in 3T3-L1 preadipocytes. These results suggest that Dlx3 and Dlx5 exert a stimulatory effect on osteogenic differentiation of stem cells through the inhibition of adipogenic differentiation as well as direct stimulation.

TNFalpha Increases the Expression of beta2 Adrenergic Receptors in Osteoblasts

Tumor necrosis factor alpha (TNFalpha) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that beta2 adrenergic receptor (beta2AR) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether TNFalpha modulates betaAR expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by TNFalpha. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of betaAR, beta2 and beta3AR were found in our analysis to be upregulated by TNFalpha. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in TNFalpha-primed C2C12 cells, indicating that TNFalpha enhances beta2AR signaling in osteoblasts. TNFalpha was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a beta2AR antagonist, attenuated this TNFalpha suppression of osteogenic differentiation. TNFalpha increased the expression of receptor activator of NF-kappaB ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that TNFalpha increases beta2AR expression in osteoblasts and that a blockade of beta2AR attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by TNFalpha. These findings imply that a crosstalk between TNFalpha and beta2AR signaling pathways might occur in osteoblasts to modulate their function.