Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study.

BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.

Risk of depression and anxiety in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD). OBJECTIVES: MS/NMOSD cohorts were collected from Korean National Health Insurance Service, using the International Classification of Diseases-10th and information on Rare Intractable Disease program. Patients who were younger than 20 years, had a previous depression/anxiety, or died in the index year were excluded. METHODS: Hazard ratios (HRs) of depression/anxiety in pwMS and pwNMOSD from controls matched 1:5 for age, sex, hypertension, diabetes, and dyslipidemia were calculated using Cox regressions with a 1-year lag period and estimated over time. RESULTS: During a mean follow-up of 4.1 years, adjusted hazard ratios (aHR) for depression were 3.25 (95% confidence interval (CI) = 2.59-4.07) in MS and 2.17 (1.70-2.76) in NMOSD, and aHRs for anxiety were 1.83 (1.49-2.23) in MS and 1.56 (1.26-1.91) in NMOSD. The risks of anxiety/depression did not differ between MS and NMOSD and were highest in the second year after diagnosis of MS/NMOSD. The relative risk of depression was higher in younger pwMS/pwNMOSD, and the relative risk of anxiety was higher in pwMS who was male, had low income, or lived in a non-urban area. CONCLUSION: The risk of depression and anxiety was increased in pwMS/pwNMOSD.

The risk of type 2 diabetes mellitus in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study.

BACKGROUND AND OBJECTIVES: An association has been suggested between premorbid type 2 diabetes mellitus (T2DM) and the risk of multiple sclerosis (MS). However, little is known about the risk of developing T2DM in MS and neuromyelitis optica spectrum disorder (NMOSD). This study aimed to determine the T2DM risk in patients with MS and NMSOD. METHODS: The Korean National Health Insurance Service database was analyzed, and 1,801 and 1,721 adults with MS and NMOSD, respectively, who were free of T2DM between January 2010 and December 2017, were included. Matched controls were selected based on age, sex, and the presence of hypertension and dyslipidemia. RESULTS: The risk of developing T2DM was 1.54 times higher in NMOSD than in the controls (adjusted hazard ratio [aHR], 95 % confidence interval [CI] = 1.20-1.96). However, increased T2DM risk was not observed in MS (aHR = 1.13, 95 % CI = 0.91-1.42). The T2DM risk in patients with NMOSD was higher in those who received steroid treatment (aHR = 1.77, 95 % CI = 1.36-2.30) but not in those who did not (aHR = 0.59, 95 % CI = 0.24-1.43, p for interaction = 0.02). DISCUSSION: T2DM risk was increased in NMOSD but not in MS. Administering steroid treatment to patients with NMOSD may increase their T2DM risk.

Evaluation of SARS-CoV-2 Vaccine-Induced Antibody Responses in Patients with Neuroimmunological Disorders: A Real-World Experience.

This study evaluates the antibody responses to SARS-CoV-2 vaccines in patients with neuroimmunological disorders (pwNID) who are receiving immunomodulating treatments, compared to healthy individuals. It included 25 pwNID with conditions such as optic neuritis, neuromyelitis optica spectrum disorder, multiple sclerosis, myasthenia gravis, and polymyositis, as well as 56 healthy controls. All participants had completed their full SARS-CoV-2 vaccination schedule, and their blood samples were collected within six months of their last dose. The concentration of anti-SARS-CoV-2 IgG antibodies was measured using an enzyme-linked immunosorbent assay. The results showed that pwNID had significantly lower antibody titers (58.4 ± 49.2 RU/mL) compared to healthy individuals (81.7 ± 47.3 RU/mL). This disparity persisted even after adjusting for age and the interval between the final vaccination and sample collection. A notable correlation was found between the use of immunomodulating treatments and reduced antibody levels, whereas mRNA vaccines were linked to higher antibody concentrations. The conclusion of this study is that immunomodulating treatments may reduce the effectiveness of SARS-CoV-2 vaccines in pwNID. This insight is crucial for healthcare providers in designing vaccination strategies and managing treatment plans for pwNID on immunomodulating therapies, highlighting the need for personalized approaches in this subgroup.

Clinical Features of Autoimmune Nodopathy With Anti-Neurofascin-155 Antibodies in South Koreans.

BACKGROUND AND PURPOSE: Anti-neurofascin-155 (NF155) antibody is one of the autoantibodies associated with autoimmune nodopathy. We aimed to determine the clinical features of South Korean patients with anti-NF155-antibody-positive autoimmune nodopathy. METHODS: The sera of 68 patients who fulfilled the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) were tested for anti-NF155 antibodies using a cell-based assay (CBA) and enzyme-linked immunosorbent assay (ELISA). The anti-NF155-positive sera were also assayed for NF155 immunoglobulin G (IgG) subclasses, and for anti-NF186 and NF140 antibodies. The clinical features of the patients were reviewed retrospectively. RESULTS: Among the 68 patients, 6 (8.8%) were positive for anti-NF155 antibodies in both the CBA and ELISA. One of those six patients was also positive for anti-NF186 and anti-NF140 antibodies. IgG4 was the predominant subclass in four patients. The mean age at onset was 32.2 years. All six positive patients presented with progressive sensory ataxia. Five patients treated using corticosteroids presented a partial or no response. All six patients were treated using intravenous immunoglobulin (IVIg). Among them, five exhibited a partial or poor response and the other exhibited a good response. All three patients treated using rituximab showed a good response. CONCLUSIONS: The clinical characteristics of the patients were consistent with those in previous studies. Anti-NF155 antibody assay is necessary for diagnosing autoimmune nodopathy and its appropriate treatment, especially in young patients with CIDP who present with sensory ataxia and poor therapeutic responses to corticosteroids and IVIg.

Serum neurofilament and glial fibrillary acidic protein in idiopathic and seropositive transverse myelitis.

BACKGROUND: Serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect the disease activity and disability in central nervous system (CNS) demyelinating diseases. However, the clinical significance of NfL and GFAP in idiopathic transverse myelitis (iTM), an inflammatory spinal cord disease with unknown underlying causes, remains unclear. This study aimed to investigate NfL and GFAP levels in iTM and their association with the clinical parameters compared with those in TM with disease-specific antibodies such as anti-aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies (sTM). METHODS: We collected serum and clinical data of 365 patients with CNS inflammatory diseases from 12 hospitals. The serum NfL and GFAP levels were measured in patients with iTM (n = 37) and sTM (n = 39) using ultrasensitive single-molecule array assays. Regression analysis was performed to investigate the associations between serum levels of NfL and GFAP and the clinical parameters such as higher EDSS scores (EDSS ≥ 4.0). RESULTS: Mean NfL levels were not significantly different between iTM (50.29 pg/ml) and sTM (63.18 pg/ml) (p = 0.824). GFAP levels were significantly lower in iTM (112.34 pg/ml) than in sTM (3814.20 pg/ml) (p = 0.006). NfL levels correlated with expanded disability status scale (EDSS) scores in sTM (p = 0.001) but not in iTM (p = 0.824). Disease duration also correlated with higher EDSS scores in sTM (p = 0.017). CONCLUSION: NfL levels and disease duration correlated with EDSS scores in sTM, and GFAP levels could be a promising biomarker to differentiate iTM from sTM.

Clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease according to their epitopes.

Background: The detection of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Ab) is essential for the diagnosis of MOG-Ab-associated disease (MOGAD). The clinical implications of different epitopes recognized by MOG-Ab are largely unknown. In this study, we established an in-house cell-based immunoassay for detecting MOG-Ab epitopes and examined the clinical characteristics of patients with MOG-Ab according to their epitopes. Methods: We conducted a retrospective review of patients with MOG-Ab-associated disease (MOGAD) in our single center registry, and collected serum samples from enrolled patients. Human MOG variants were generated to detect epitopes recognized by MOG-Ab. The differences in clinical characteristics according to the presence of reactivity to MOG Proline42 (P42) were evaluated. Results: Fifty five patients with MOGAD were enrolled. Optic neuritis was the most common presenting syndrome. The P42 position of MOG was a major epitope of MOG-Ab. The patients with a monophasic clinical course and childhood-onset patients were only observed in the group that showed reactivity to the P42 epitope. Conclusion: We developed an in-house cell-based immunoassay to analyze the epitopes of MOG-Ab. The P42 position of MOG is the primary target of MOG-Ab in Korean patients with MOGAD. Further studies are needed to determine the predictive value of MOG-Ab and its epitopes.

Differentiation between multiple sclerosis and neuromyelitis optica spectrum disorder using a deep learning model.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the central nervous system (CNS) with similar characteristics. The differential diagnosis between MS and NMOSD is critical for initiating early effective therapy. In this study, we developed a deep learning model to differentiate between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using brain magnetic resonance imaging (MRI) data. The model was based on a modified ResNet18 convolution neural network trained with 5-channel images created by selecting five 2D slices of 3D FLAIR images. The accuracy of the model was 76.1%, with a sensitivity of 77.3% and a specificity of 74.8%. Positive and negative predictive values were 76.9% and 78.6%, respectively, with an area under the curve of 0.85. Application of Grad-CAM to the model revealed that white matter lesions were the major classifier. This compact model may aid in the differential diagnosis of MS and NMOSD in clinical practice.

Novel index, neutrophil percentage (%) is a useful marker for disease activity in MOG antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS autoimmune disease affecting the brain, spinal cord, and optic nerve. The neutrophil-to-lymphocyte ratio (NLR) is related to autoimmune disease activity. However, the clinical implication of index ratios such as the NLR is unclear in patients with MOGAD. OBJECTIVES: We investigated the relationship between index ratios such as the NLR and disease activity and disability to discover the index that best correlates with an attack in MOGAD. METHODS: Using a CNS demyelinating disease cohort, we reviewed 39 patients with MOGAD (age 37.4 ± 12.0 years; F:M = 20:19) who had 390 blood samples available for cell count analysis. We calculated the NLR, eosinophil-to-lymphocyte-ratio (ELR), platelet-to-lymphocyte-ratio (PLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and neutrophil percentage (N%) [neutrophil count (/mm3) / WBC (/mm3) x 100 (%)]. We investigated the associations between each index ratio and disease activity and disability using the receiver operating characteristic (ROC) curve, machine learning program (kNN algorithm), and generalized estimating equations (GEE) analysis. RESULTS: In patients with MOGAD, the NLR, PLR, and N% were higher and ELR was lower during an attack than in remission (all p<0.001). The areas under the ROC curve for the NLR, ELR, PLR, and N% were 0.68, 0.69, 0.61, and 0.68, respectively, with the highest sensitivity of 76.0% in the ELR and the highest specificity of 76.3% in the N%. The classification accuracy scores of the kNN machine learning algorithm were 71% for the NLR, 62% for the ELR, 63% for the PLR, and 72% for the N%. In the GEE analysis of attack samples, both the NLR and treatment-naive had positive associations with the Expanded Disability Status Scale (EDSS) score (ß=0.137, p = 0.008 and ß=1.142, p = 0.003, respectively), and the PLR was negatively associated with the EDSS score (ß=-0.004, p = 0.022). DISCUSSION: Our study suggests that the novel index, neutrophil% is the simplest and the most useful marker to differentiate between attack and remission and shows comparable reliability with NLR in MOGAD. Moreover, the NLR and PLR could be used as supportive biomarkers for disease disability during an attack in patients with MOGAD.

Identifying important factors for successful surgery in patients with lateral temporal lobe epilepsy.

OBJECTIVE: Lateral temporal lobe epilepsy (LTLE) has been diagnosed in only a small number of patients; therefore, its surgical outcome is not as well-known as that of mesial temporal lobe epilepsy. We aimed to evaluate the long-term (5 years) and short-term (2 years) surgical outcomes and identify possible prognostic factors in patients with LTLE. METHODS: This retrospective cohort study was conducted between January 1995 and December 2018 among patients who underwent resective surgery in a university-affiliated hospital. Patients were classified as LTLE if ictal onset zone was in lateral temporal area. Surgical outcomes were evaluated at 2 and 5 years. We subdivided based on outcomes and compared clinical and neuroimaging data including cortical thickness between two groups. RESULTS: Sixty-four patients were included in the study. The mean follow-up duration after the surgery was 8.4 years. Five years after surgery, 45 of the 63 (71.4%) patients achieved seizure freedom. Clinically and statistically significant prognostic factors for postsurgical outcomes were the duration of epilepsy before surgery and focal cortical dysplasia on postoperative histopathology at the 5-year follow-up. Optimal cut-off point for epilepsy duration was eight years after the seizure onset (odds ratio 4.375, p-value = 0.0214). Furthermore, we propose a model for predicting seizure outcomes 5 years after surgery using the receiver operating characteristic curve and nomogram (area under the curve = 0.733; 95% confidence interval, 0.588-0.879). Cortical thinning was observed in ipsilateral cingulate gyrus and contralateral parietal lobe in poor surgical group compared to good surgical group (p-value < 0.01, uncorrected). CONCLUSIONS: The identified predictors of unfavorable surgical outcomes may help in selecting optimal candidates and identifying the optimal timing for surgery among patients with LTLE. Additionally, cortical thinning was more extensive in the poor surgical group.

Safety and Temporal Pattern of the Lymphocyte Count During Fingolimod Therapy in Patients With Multiple Sclerosis: Real-World Korean Experience.

BACKGROUND AND PURPOSE: Fingolimod (FTY) inhibits lymphocyte egress from lymphoid organs to cause lymphopenia, but the clinical implications of FTY-induced lymphopenia are not fully understood. We aimed to determine the frequency and severity of lymphopenia during FTY treatment among Korean patients with multiple sclerosis (MS), and its association with infections. METHODS: We retrospectively reviewed the medical records of patients with MS treated using FTY from 12 referral centers in South Korea between March 2013 and June 2021. Patients were classified according to their nadir absolute lymphocyte count (ALC) during treatment: grade 1, 800-999/µL; grade 2, 500-799/µL; grade 3, 200-499/µL; and grade 4, <200/µL. RESULTS: FTY treatment was administered to 69 patients with a median duration of 18 months (range=1-169 months), with 11 patients being treated for ≥7 years. During FTY treatment, mean ALCs were reduced after the first month (653.0±268.9/µL, mean±standard deviation) (p<0.0001) and remained low during treatment lasting up to 84 months. During follow-up, 41 (59.4%) and 7 (10.1%) patients developed grade-3 and grade-4 lymphopenia, respectively. No significant difference was found in age at FTY initiation, sex, baseline ALC, body mass index, or prior disease-modifying treatment between patients with and without grade-4 lymphopenia. Infections were observed in 11 (15.9%) patients, and the frequencies of patients with and without grade-4 lymphopenia were similar. CONCLUSIONS: FTY treatment induced grade-4 lymphopenia in 10% of South Korean patients with MS, but did not appear to be associated with an increased infection risk.

Validity and reliability of Korean version of Modified Fatigue Impact Scale (MFIS) for Korean patients with multiple sclerosis.

BACKGROUND: To determine the validity and reliability of the Korean version of the Modified Fatigue Impact Scale (MFIS-K) questionnaire for patients with multiple sclerosis (MS). METHODS: We prospectively enrolled 52 patients with MS and 102 healthy controls. Subjects were asked to complete the Korean version of Fatigue Severity Scale (FSS) and MFIS-K. To evaluate sleep quality, depression, pain, and quality of life, patients completed the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Scale II (BDI), the Brief Pain Inventory (BPI), and the Short Form 36 Health Survey (SF-36). RESULTS: It was demonstrated that MFIS-K has appropriate construct validity with distinctive 3 factors (cognitive, physical, and psychosocial). The criterion validity was also confirmed with the total score and the factor scores of the patients with MS, which were all significantly higher than those of healthy controls. Convergent validity of the MFIS-K was verified with the correlations with Fatigue Severity Scale (FSS) and other concurrent measures of sleep disturbances, depression, pain, and limitations in activities due to health problems. Furthermore, the internal consistency, temporal stability, and score consistency of the MFIS-K turned out acceptable. DISCUSSION: Our results indicate that the Korean version of MFIS is a valid and reliable scale to assess fatigue in the Korean MS population.

Prevalence and predictive factors of nocturia in patients with obstructive sleep apnea syndrome: A retrospective cross-sectional study.

OBJECTIVES: Many patients with obstructive sleep apnea syndrome (OSAS) have nocturia. However, the predictive index of nocturia in patients with OSAS is currently not well known. We aimed to investigate the prevalence of nocturia in patients with OSAS and determine the factors that could predict nocturia in these patients. METHODS: In this retrospective cross-sectional study, we enrolled 1,264 untreated patients with OSAS (Apnea-Hypopnea Index, AHI ≥5/h on polysomnography [PSG]) from January 2017 to January 2020. Participants completed the Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleepiness Scale. Participants were divided by sex and then subdivided into nocturia and non-nocturia groups according to the following question, "Do you go to the bathroom two times or more during your sleep?" Participants' characteristics and underlying disease were investigated, and all information, including PSG data, was compared between the two groups using the t-test or chi-square test. RESULTS: Overall, 35.2% (337/958) of male participants with OSAS and 59.8% (183/306) of female participants with OSAS had nocturia. The nocturia group was older; scored higher on the BDI-II, PSQI, and ISI; and had more underlying disease in both sexes. There was no difference in the AHI between the two groups among both sexes, but the hypoxia-related PSG parameters and sleep quality parameters, such as higher 90% oxygen desaturation index (90% ODI), lesser N3 sleep, and higher wakefulness after sleep onset, were worse among male participants with OSAS in the nocturia group than in the non-nocturia group. In multivariate logistic analysis, 90% ODI was an independent risk factor associated with nocturia in male participants with OSAS. CONCLUSIONS: Considerable number of patients with OSAS had nocturia and poor sleep quality. Nocturia should be evaluated in male OSAS patients with severe hypoxia observed during sleep.

Disrupted structural network of inferomedial temporal regions in relapsing-remitting multiple sclerosis compared with neuromyelitis optica spectrum disorder.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two representative chronic inflammatory demyelinating disorders of the central nervous system. We aimed to determine and compare the alterations of white matter (WM) connectivity between MS, NMOSD, and healthy controls (HC). This study included 68 patients with relapsing-remitting MS, 50 with NMOSD, and 26 HC. A network-based statistics method was used to assess disrupted patterns in WM networks. Topological characteristics of the three groups were compared and their associations with clinical parameters were examined. WM network analysis indicated that the MS and NMOSD groups had lower total strength, clustering coefficient, global efficiency, and local efficiency and had longer characteristic path length than HC, but there were no differences between the MS and NMOSD groups. At the nodal level, the MS group had more brain regions with altered network topologies than did the NMOSD group when compared with the HC group. Network alterations were correlated with Expanded Disability Status Scale score and disease duration in both MS and NMOSD groups. Two distinct subnetworks that characterized the disease groups were also identified. When compared with NMOSD, the most discriminative connectivity changes in MS were located between the thalamus, hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and inferior and superior temporal gyri. In conclusion, MS patients had greater network dysfunction compared to NMOSD and altered short connections within the thalamus and inferomedial temporal regions were relatively spared in NMOSD compared with MS.