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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.
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Background@#and Purpose Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy– Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. @*Methods@#There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). @*Results@#The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. @*Conclusions@#These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.
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Purpose@#To examine the clinical characteristics, demographic features, and visual prognosis of idiopathic intracranial hypertension (IIH) in Korean patients. @*Methods@#We conducted a retrospective chart review of patients diagnosed with IIH who visited the Neuro-ophthalmology Clinic at Samsung Medical Center from September 2011 to January 2023. This analysis focused on demographic characteristics at onset, clinical manifestations, and visual outcomes at the last follow-up. @*Results@#Out of 34 patients, 20 met the modified Dandy criteria and 14 were presumed to have IIH. The mean age at onset was 32.97 ± 9.6 years with females comprising 85.3% (n = 29) of the sample. The average body mass index (BMI) was 29.15 ± 6.43, with 47.0% of patients (n = 16) classified as obese. The most frequent symptom was headache, reported by 85.3% (n = 29) of patients, followed by pulsatile tinnitus (64.7%, n = 22) and transient visual obscuration (TVO; 32.4%, n = 11). Treatment included observation for 3 patients (8.8%), acetazolamide therapy for 26 patients (76.5%), and ventriculo-peritoneal shunt (V-P shunt) for 2 patients (5.9%). Out of 23 patients with follow-up > 6 months, 87.0%, 8.7%, and 4.3% showed good, fair, and poor visual outcomes, respectively; optic nerve atrophy was observed in 19.6% (9 eyes). The initial peripapillary retinal nerve fiber layer (pRNFL) thickness measured by OCT was 143.56 ± 62.41 μm in the right eye and 139.3 ± 76.38 μm in the left which decreased to 97.39 ± 25.72 and 94.91 ± 19.32 μm, respectively by the last examination. @*Conclusions@#While the proportion of obese patients in this Korean cohort and the average BMI were lower than in western countries, both have increased relative to previous reports from Korea. Most patients experienced a benign course.
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Purpose@#To investigate the causes of isolated ocular motor nerve palsy in patients with a history of cancer. @*Methods@#The charts of 30 patients with cancer diagnosed with isolated acquired third, fourth, and sixth cranial nerve palsies from March 2013 to December 2021 were retrospectively reviewed. Sex, age of onset, underlying disease and causes of cranial nerve palsy were analyzed. @*Results@#Sixth cranial nerve palsy (n = 18, 60.0%) was the most common. Brain metastasis (n = 13, 43.3%) was the most common etiology, followed by microvascular causes (n = 11, 36.7%), radiation-induced neuropathy (n = 2, 6.7%), and undetermined (n = 4, 13.3%). Among the 13 patients with palsies due to brain metastasis, only one (7.7%) had been in complete remission for more than 1 year. Of the remaining 17 patients with other causes, seven (41.2%) had been in complete remission of a previously diagnosed cancer for more than 1 year. @*Conclusions@#In patients with a history of cancer, cranial nerve palsy due to brain metastasis was the most common cause, and it was more likely if the primary cancer had not been in remission for more than 1 year. Brain magnetic resonance imaging should be performed as soon as possible to confirm brain metastasis and a differential diagnosis including various other causes is also important.
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Background@#To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea. @*Methods@#This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION. @*Results@#The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43–77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1–41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/ disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit. @*Conclusion@#Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION.
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Background and Objectives@#Given the major changes in spread of COVID-19 and the contribution of technological innovation, the objective of the current study was to compare the educational needs of thyroid cancer patients between 2012 and 2020. @*Materials and Methods@#The subject of this study were 159 patients in 2012 and 149 patients in 2020 who underwent thyroid cancer surgery. Data were collected from September 2020 to December 2020. Their responses were compared with response for the 2012 survey. The survey contained 36 questions regarding demographics and 5 areas of educational needs (Treatment plan after discharge, Management of the symptom and the complication after surgery, Medication management, Postoperative wound and dietary management, Daily life). @*Results@#The most preferred teaching method for thyroid cancer surgery patients has changed from small group education to self-study with videos. The Internet accounted for the largest proportion of source of information and the preferred educator for the patient were doctors and nurses in both 2012 and 2020. ‘Current disease condition and surgical result’ was the highest ranked in both 2012 and 2020. @*Conclusion@#It is necessary to develop and utilize an educational method using video centered on medical team including doctors and nurses.
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Purpose@#To compare clinical outcomes of Korean patients with seropositive myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-related optic neuritis (ON) and those with neuromyelitis optica antibody (NMO-IgG)-related ON. @*Methods@#Medical records were analyzed retrospectively among patients diagnosed with ON from January 2018 to June 2020, who were positive for MOG-IgG or NMO-IgG on serological tests. Clinical manifestations and outcomes were collected and compared between the two groups. @*Results@#The study included 14 eyes of 10 MOG-IgG positive patients, and 38 eyes of 25 NMO-IgG positive patients. Final visual acuity differed significantly between the two groups (p = 0.002), and the proportion of patients with no light perception was higher in the NMO-ON group (11%) compared with the MOG-ON group (0%). The mean deviation value on visual field tests also showed a significant difference between NMO-ON and MOG-ON groups (-18.98 ± 12.36 dB versus -10.17 ± 10.03 dB, respectively; p = 0.018). The recurrence rate was 42% in the NMO-ON group and 79% in the MOG-ON group (p = 0.020). @*Conclusions@#The clinical outcomes of NMO-ON and MOG-ON patients differed significantly. MOG-ON patients were more likely to experience a relapse. Patients with NMO-ON were given a poor visual prognosis despite having a lower recurrence rate than those with MOG-ON.
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Purpose@#To compare clinical outcomes of Korean patients with seropositive myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-related optic neuritis (ON) and those with neuromyelitis optica antibody (NMO-IgG)-related ON. @*Methods@#Medical records were analyzed retrospectively among patients diagnosed with ON from January 2018 to June 2020, who were positive for MOG-IgG or NMO-IgG on serological tests. Clinical manifestations and outcomes were collected and compared between the two groups. @*Results@#The study included 14 eyes of 10 MOG-IgG positive patients, and 38 eyes of 25 NMO-IgG positive patients. Final visual acuity differed significantly between the two groups (p = 0.002), and the proportion of patients with no light perception was higher in the NMO-ON group (11%) compared with the MOG-ON group (0%). The mean deviation value on visual field tests also showed a significant difference between NMO-ON and MOG-ON groups (-18.98 ± 12.36 dB versus -10.17 ± 10.03 dB, respectively; p = 0.018). The recurrence rate was 42% in the NMO-ON group and 79% in the MOG-ON group (p = 0.020). @*Conclusions@#The clinical outcomes of NMO-ON and MOG-ON patients differed significantly. MOG-ON patients were more likely to experience a relapse. Patients with NMO-ON were given a poor visual prognosis despite having a lower recurrence rate than those with MOG-ON.
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Background and Objectives@#Many patients with thyroid cancer are participating in the online community. Thyroid cancer patients write and read a variety of posts in the online community, and there is a great deal of data generated in the digital environment. However, few studies have analyzed the online community of thyroid cancer patients. The purpose of this study is to analyze the online community to understand the interests and information seeking behavior of thyroid cancer patients. @*Materials and Methods@#Data were collected from August 2017 to September 2019 using statistics from an online community of thyroid cancer patients. The frequency analysis was performed by collecting the members’ gender, age, average usage time, time-of-day views, average monthly visits, device distribution, online community inflow query, query within online community, and content of a post with more than 1000 views per month. @*Results@#Analyzing the online community of thyroid cancer patients, women accounted for 80.4% of the total, and the age group of people in their 30s and 40s accounted for 77.5%. Online community subscribers averaged 0.7 visits a day using mobile, with the most frequent use time between 10pm and 12pm. Frequently used queries are medical staff names, surgery, recurrence and scar. Posts showed informational and emotional exchanges. @*Conclusion@#Patients with thyroid cancer have searched for a lot of information about surgery and recurrence. Analyzing the online community will help to understand the experience of thyroid cancer patients and contribute to the development of online community intervention.
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PURPOSE@#To investigate the clinical features of acute ophthalmoplegia associated with anti-GQ1b antibody in the Republic of Korea.@*METHODS@#From January 2011 to July 2018, we retrospectively reviewed the medical records of all patients who tested positive for anti-GQ1b antibody, and who had been concurrently diagnosed with acute ophthalmoplegia at a tertiary hospital in the Republic of Korea. Ophthalmic and neurological features were carefully reviewed. Laboratory results including ganglioside antibody panels and treatment outcomes were analyzed.@*RESULTS@#Thirty-three patients were enrolled in the study and 8 (24%) of them showed pure Miller-Fisher syndrome with all three cardinal symptoms of ophthalmoplegia, ataxia, and areflexia. One patient (3%) showed ophthalmoplegia, areflexia, and pharyngeal- cervical-brachial weakness without ataxia and 2 patients (6%) showed only ophthalmoplegia and pharyngeal-cervical- brachial weakness without ataxia and areflexia. Twenty-two patients (67%) showed only ophthalmoplegia without any other neurological symptom. Early immunosuppressant treatment was used to treat 17 patients, and observation only was conducted as the initial treatment for 16 patients (48.5%). Twenty-four patients (72.7%) showed improvement and 9 patients showed persistent strabismus and diplopia. The average duration until recovery was 2.52 ± 2.11 months.@*CONCLUSIONS@#The symptoms of acute ophthalmoplegia associated with anti-GQ1b antibody can manifest in various forms that overlap with clinical features of demyelinating neuropathy, so it is important to recognize such characteristics when treating acute ophthamoplegia.
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PURPOSE@#We investigated changes in postoperative refractive error after surgery to treat congenital ptosis and the clinical outcomes by surgical method.@*METHODS@#The study was retrospective and interventional. We enrolled 73 patients in whom 86 eyes exhibited visual axis-obscuring congenital ptosis. All patients were under 8 years of age, with refractive errors or amblyopia, and underwent maximal levator resection or frontalis sling surgery with fascia lata preservation from January 2008 to January 2018; the minimum follow-up time was 6 months. Visual and surgical outcomes were assessed by reviewing clinical photographs taken before and 1 year after surgery. Refractive error changes were measured at these times.@*RESULTS@#Maximal levator resection was performed on 42 of 86 eyes (48.8%) and frontalis sling surgery with preservation of the fascia lata on 44 eyes, 95.2% and 75.0% of patients, respectively, exhibited good or fair surgical outcomes. The preoperative mean astigmatisms of the ptotic and control eyes of those with unilateral disease did not differ significantly: −0.71 ± 0.85 D for ptotic eyes and −0.66 ± 0.97 D for control eyes. The mean astigmatism increased from −0.71 ± 0.85 D preoperatively to −1.27 ± 1.2 D postoperatively (p < 0.001). The postoperative MRD1 value correlated with the increase in postoperative astigmatism (p = 0.022, r = −0.261).@*CONCLUSIONS@#Maximal levator resection tended to afford better surgical outcomes than frontalis sling surgery with preservation of the fascia lata in patients with congenital ptosis. Patients in whom the postoperative eyelid position was good tended to exhibit higher refractive errors. Careful examination and treatment are recommended to ensure good visual outcomes.
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PURPOSE@#To report the long-term surgical outcomes of a muscle union procedure in patients with paralytic strabismus.@*METHODS@#We retrospectively reviewed the medical records of 20 patients who underwent muscle union procedure for paralytic strabismus from September 2010 to March 2018. We analyzed the clinical results before and at the final visit after surgery. We also compared the outcomes of the first year after surgery between patients with sixth cranial nerve palsy, with third cranial nerve palsy and with medial rectus muscle rupture after endoscopic sinus surgery.@*RESULTS@#The mean follow-up duration was 42 ± 20 months (12–79 months). The mean age at surgery was 40 ± 19 years (7–65 years). Eleven patients underwent surgery for sixth cranial nerve palsy, six patients underwent surgery for third cranial nerve palsy, and three patients underwent surgery for medial rectus rupture after endoscopic sinus surgery. The mean horizontal deviation at the primary eye position was 58 ± 19 prism diopters before surgery and decreased to 14 ± 17 prism diopters at the final visit. The success rate at the last visit was 60%. The mean horizontal deviation at postoperative 1 year was 4 ± 9 prism diopters in the sixth nerve palsy group and 26 ± 16 prism diopters in the third nerve palsy group (p = 0.002). The success rate was 91% in the sixth nerve palsy group and 33% in the third nerve palsy group at postoperative 1 year (p = 0.017). There were no complications during surgery or anterior segment ischemia for any of the patients.@*CONCLUSIONS@#A muscle union procedure had good long-term surgical outcomes in patients with paralytic strabismus, especially in patients with sixth cranial nerve palsy. However, in the case of third cranial nerve palsy or rupture of the medial rectus muscle, the effects were limited.
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PURPOSE: To describe the clinical characteristics and course of optic neuritis (ON) and its association with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) in Korea. METHODS: In this retrospective case series, 125 eyes of 91 Korean patients with ON were included. The medical documents of adult patients with ON were retrospectively reviewed. Patients were assigned into idiopathic ON, NMOSD, and MS groups according to the presence of an association with NMOSD or MS for subgroup analysis. Clinical characteristics, disease course, and visual and systemic prognosis were analyzed. RESULTS: During the mean follow-up of 3.7 years, 73 patients were diagnosed as idiopathic ON, 14 patients were diagnosed as NMOSD, and four patients developed definite MS. At the final visit, there were 13 (13%) eyes out of 100 eyes with idiopathic ON, nine (43%) eyes out of 21 eyes with NMOSD, and one (25%) eye out of four eyes with MS had a severe visual loss of 20 / 200 or less. The mean Expanded Disability Status Scale was 3.1 ± 1.5 in NMOSD and 1.8 ± 1.5 in the MS group at the final visit. In the NMOSD group, 50% of patients showed severe visual loss in at least one eye or were unable to ambulate without assistance at the final visit (5.3 ± 4.4 years after the initial episode of ON). CONCLUSIONS: Fourteen percent of patients showed positive results for NMO-immunoglobulin G test and 50% of patients with NMOSD showed a severe visual loss in at least one eye or were unable to ambulate without assistance. The proportion of MS was relatively low in Korean ON patients.
Subject(s)
Adult , Humans , Follow-Up Studies , Korea , Multiple Sclerosis , Neuromyelitis Optica , Optic Neuritis , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND AND OBJECTIVES: Most thyroid cancers progress slowly, have high survival rates, and have good prognosis. Therefore, the management of patients with thyroid cancer should be viewed from a long-term perspective, taking into account a return to normal social life. Cancer patients have a higher risk of unemployment than the general population, and so unemployment can be an economic problem for thyroid cancer patients. However, there have been few studies on factors affecting return to work in thyroid cancer patients. The purpose of this study is to investigate occupational changes and the period of leave of absence for patients with thyroid cancer and to identify factors that affect the return to work after surgery.MATERIALS AND METHODS: A total of 427 questionnaires of thyroid cancer patients were used for the analysis. The occupational changes and sick leave periods were analyzed according to general characteristics, disease-related characteristics, and side effects.RESULTS: The factors related to occupational change and leave of absence in thyroid cancer patients were sex and type of occupation. Women had more occupational changes and longer leave of absence than men, office workers had the least change in occupation, and professional workers had a longer period of sick leave. Fatigue was the primary side effect that affected the leave of absence.CONCLUSION: Occupation is very important in the life of a thyroid cancer patient. Informing the patient of possible complications and planning proper leave of absence will help the patient return to work and improve the quality of life.
Subject(s)
Female , Humans , Male , Fatigue , Occupations , Prognosis , Quality of Life , Return to Work , Sick Leave , Survival Rate , Thyroid Gland , Thyroid Neoplasms , UnemploymentABSTRACT
Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.
Subject(s)
Animals , Mice , Adipokines , Adipose Tissue, Brown , Caloric Restriction , Diet, High-Fat , Inflammation , Lipocalins , Macrophages , Mice, Obese , Mitochondrial Dynamics , Neutrophils , Obesity , Oxidative Stress , PhenotypeABSTRACT
Korean women doctors have expanded their activities globally in various fields within the international community. This study conducted face-to-face interviews or e-mail surveys of representatives among internationally active women doctors with experience in working with the Medical Women's International Association and the World Health Organization. Conveying the activities of these senior women doctors will be valuable to the younger generation of doctors who are interested in international health and who aspire to become potential leaders in the international health care scene in the future.
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Korean women doctors have expanded their activities globally in various fields within the international community. This study conducted face-to-face interviews or e-mail surveys of representatives among internationally active women doctors with experience in working with the Medical Women's International Association and the World Health Organization. Conveying the activities of these senior women doctors will be valuable to the younger generation of doctors who are interested in international health and who aspire to become potential leaders in the international health care scene in the future.
Subject(s)
Female , Humans , Delivery of Health Care , Electronic Mail , Korea , World Health OrganizationABSTRACT
PURPOSE: The purpose of this study was to demonstrate whether the pattern of optic nerve enhancement in magnetic resonance imaging (MRI) can help to differentiate between idiopathic optic neuritis (ON), neuromyelitis optica (NMO), and multiple sclerosis (MS) in unilateral ON. METHODS: An MRI of the brain and orbits was obtained in patients with acute unilateral ON. Patients with ON were divided into three groups: NMO, MS, and idiopathic ON. The length and location of the abnormal optic nerve enhancement were compared for ON eyes with and without NMO or MS. The correlation between the pattern of optic nerve enhancement and the outcome of visual function was analyzed. RESULTS: Of the 36 patients with ON who underwent an MRI within 2 weeks of the onset, 19 were diagnosed with idiopathic ON, 9 with NMO, and 8 with MS. Enhancement of the optic nerve occurred in 21 patients (58.3%) and was limited to the orbital segment in 12 patients. Neither the length nor the location of the optic nerve enhancement was significantly correlated with visual functions other than contrast sensitivity or the diagnosis of idiopathic ON, MS, or NMO. Patients with greater extent of optic nerve sheath enhancement and more posterior segment involvement showed higher contrast sensitivity. CONCLUSIONS: Our data revealed that the pattern of optic nerve enhancement was not associated with diagnosis of idiopathic ON, NMO, or MS in Korean patients with unilateral ON. We believe further studies that include different ethnic groups will lead to a more definitive answer on this subject.
Subject(s)
Humans , Brain , Contrast Sensitivity , Diagnosis , Ethnicity , Magnetic Resonance Imaging , Multiple Sclerosis , Neuromyelitis Optica , Optic Nerve , Optic Neuritis , OrbitABSTRACT
In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic I(NMDA) in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate I(NMDA) facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg2+ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in I(holding) (I(GLU)) at a holding potential (V(holding)) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive I(GLU) was observed even in normal aCSF at V(holding) of -40 mV or -20 mV. I(GLU) was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in I(holding) (I(AMPA)) in SON MNCs. Pretreatment with AP5 attenuated I(AMPA) amplitudes to ~60% of the control levels in low-Mg2+ aCSF, but not in normal aCSF at V(holding) of -70 mV. I(AMPA) attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced I(AMPA) attenuation in SON MNCs. Finally, chronic dehydration did not affect I(AMPA) attenuation by AP5 in the neurons. These results suggest that tonic I(NMDA), mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.
Subject(s)
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid , Brain , Cerebrospinal Fluid , Dehydration , Glutamic Acid , Memantine , N-Methylaspartate , Neurons , Receptors, AMPA , Receptors, N-Methyl-D-Aspartate , Supraoptic Nucleus , Synaptic TransmissionABSTRACT
Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-kappaB (NF-kappaB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-kappaB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.