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With the increased clinical interest in myelin-oligodendrocyte glycoprotein-antibody-associated disease (MOGAD), the international MOGAD panel's proposed criteria were recently released. To evaluate its diagnostic performance, the criteria were applied to a single-center cohort. Among the enrolled 100 patients, 93 fulfilled the criteria throughout the median 24 months of follow-up. All 36 patients with a clear-positive MOG-immunoglobulin G (IgG) satisfied the supporting features, except one who did not undergo magnetic resonance imaging (MRI) scan at disease onset. The criteria also contributed significantly to the confirmation of MOGAD in 57 of 64 patients without clear-positive MOG-IgG. When limited to the first attack, 51 of 61 patients (84%) satisfied the criteria, 4 of whom were initially negative for MOG-IgG. These results support the diagnostic utility of the International MOGAD Panel criteria. [ABSTRACT FROM AUTHOR]

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD. [ABSTRACT FROM AUTHOR]

In a large acute myelitis cohort, we aimed to determine whether brighter spotty lesions (BSLs)—using the refined terminology—on spinal magnetic resonance imaging (MRI) help distinguish aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) from myelin oligodendrocyte glycoprotein antibody disease (MOGAD). An experienced neuro-radiologist and two neurologists independently analyzed 133 spinal MRI scans (65 from MOGAD and 68 from AQP4-NMOSD) acquired within 1 month of attacks. BSLs were observed in 18 of 61 (30%) participants with AQP4-NMOSD, while none of 49 participants with MOGAD showed BSL (p < 0.001). BSL during the acute phase would be useful to differentiate AQP4-NMOSD from MOGAD. [ABSTRACT FROM AUTHOR]

The prevalence of cerebrospinal fluid–specific oligoclonal bands (CSF-OCBs) was reported to be low in Asian people with multiple sclerosis (pwMS) compared to that in Western pwMS. It is yet to be determined whether it is a genuine feature of Asian pwMS or a misapprehension owing to past mis-classification of MS-mimicking diseases as MS. We aimed to reappraise the prevalence of CSF-OCBs in Korean pwMS after carefully excluding other central nervous system-inflammatory demyelinating diseases since 2017. Among 88 subjects, 78 (88.6%) were positive for CSF-OCBs, which suggests the prevalence of CSF-OCBs is not different between Korean and Western pwMS. [ABSTRACT FROM AUTHOR]

Objectives: Likelihood of clinical events occurring within the same anatomical location in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) was retrospectively investigated. Methods: A total of 236 clinical events in 90 patients with MOGAD from nine referral hospitals were analyzed via logistic regression, and odds ratios (ORs) were calculated. Anatomical lesion location was divided into four groups; optic nerve, spinal cord, cerebral hemisphere, and brainstem/cerebellum. Results: At all locations, there was an increased likelihood of a second attack occurring at the same location as the initial event (cerebral hemisphere OR = 22.14, brainstem/cerebellum OR = 18.4, spinal cord OR = 9.1, and optic nerve OR = 7.8). There was an increased likelihood of a third attack occurring at the same location as the initial event in the optic nerve (OR = 14.9), cerebral hemisphere (OR = 11.7), and spinal cord (OR = 6.7). There were positive trends toward a third clinical event occurring at the same location as the first and/or second events if the event was in the optic nerve (OR = 13.5), cerebral hemisphere (OR = 6.9), or spinal cord (OR = 5.7). Conclusions: The current study suggests that clinical relapses of MOGAD during early stage tend to recur at the same anatomical locations in the central nervous system. [ABSTRACT FROM AUTHOR]

Objectives: Serum neurofilament light chain (sNfL) has been proposed a potential biomarker in multiple sclerosis (MS) based on mainly cross-sectional observations in Western population. To clarify clinical implication of sNfL, we longitudinally analysed sNfL levels at multiple time points in Korean MS patients undergoing alemtuzumab therapy. Methods: Between 2016 and 2018, 144 sera from 17 MS patients treated with alemtuzumab at National Cancer Centre and 35 sera from 35 age- and gender-matched healthy controls (HCs) were collected for a longitudinal study with a mean 21-month follow-up. The sera were measured for sNfL levels using single molecule array. Patients were classified into two groups: evidence of disease activity (EDA) or no evidence of disease activity (NEDA). Results: During alemtuzumab therapy, sNfL levels in EDA patients were significantly higher than those in NEDA patients and HCs (p < 0.001). In longitudinal analysis, the sNfL levels were consistently low in NEDA patients, while it consistently increased in radiologically and/or clinically active status in EDA patients. All sNfL levels in radiologically and/or clinically active status samples were higher than those in inactive status samples. Conclusion: These results suggest that sNfL is a promising monitoring biomarker for personalized therapeutics in MS patients. [ABSTRACT FROM AUTHOR]

Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell–mediated disease within 1 year of the first cycle of alemtuzumab. We raise awareness that severe B cell–mediated disease activation could develop, even after two cycles of alemtuzumab, in some vulnerable MS patients; therefore, individualized therapeutic strategies should be considered in clinical practice. We also propose that a novel regulatory B-cell subset may be a candidate for a predictive biomarker of disease activation in MS patients treated with alemtuzumab. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the validity of the revised 2017 McDonald criteria for multiple sclerosis (MS) compared with the 2010 McDonald criteria to predict conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). Methods: A total of 163 patients from seven referral hospitals in Korea, who experienced a first clinical event suggestive of MS between 2006 and 2017, were enrolled. Patients were stratified into two groups according to outcome at the last visit: CDMS converters who experienced a second clinical event and non-converters. Results: Of the 163 patients with a mean follow-up of 63 months, 60% converted to CDMS. The sensitivity, specificity, positive and negative predictive values and accuracy were, respectively, 88.8%, 43.1%, 70.2%, 71.8% and 70.6% for the 2017 McDonald criteria and 53.1%, 69.2%, 72.2%, 49.5% and 59.5% for the 2010 McDonald criteria. After exclusion of 82 patients who received disease-modifying agents before the second attack, the specificity of the 2017 and 2010 McDonald criteria increased to 85.0% and 95.0%, but sensitivity decreased to 83.6% and 47.5%, respectively. Conclusion: The 2017 McDonald criteria afforded higher sensitivity and accuracy but lower specificity compared with the 2010 McDonald criteria for prediction of conversion to CDMS in Korean CIS patients. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the utility of the recently described brain lesion distribution criteria to differentiate multiple sclerosis (MS) from aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein immunoglobulin G-associated encephalomyelitis (MOG-EM) at disease onset in an Asian cohort. Methods: A total of 214 patients who fulfilled the published criteria for MS, NMOSD, or MOG-EM and underwent brain magnetic resonance imaging (MRI) within 3 months of disease onset were enrolled. The brain lesion distribution criteria were defined as the presence of a lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe, or an S-shaped U-fiber lesion, or a Dawson's finger-type lesion. Results: Brain lesions were identified in the initial MRI scans of 166/214 patients. The distribution criteria were applied to these scans (MS (n = 94), NMOSD (n = 64), and MOG-EM (n = 8)). The sensitivity, specificity, and positive and negative predictive values of the criteria for MS versus NMOSD were 79.8%, 87.5%, 90.4%, and 74.7%, and for MS versus MOG-EM these were 79.8%, 100%, 100%, and 29.6%, respectively. Conclusion: These findings suggest that the brain lesion distribution criteria are helpful in distinguishing MS from NMOSD and MOG-EM in an Asian population, even at disease onset. [ABSTRACT FROM AUTHOR]

Background: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. Objective: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. Methods: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. Results: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). Conclusion: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments. [ABSTRACT FROM AUTHOR]

Objectives: We compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). Methods: Between 2006 and 2016, we enrolled 170 patients who had a first clinical event suggestive of multiple sclerosis (MS) from seven referral hospitals in Korea. Patients were classified into two groups based on the main outcome at the last follow-up: CDMS converters, who experienced a second attack, and non-converters. Results: Of 170 patients with mean follow-up duration of 54 months, 51% converted to CDMS. The sensitivity, specificity, accuracy, and positive and negative predictive values of 2010 McDonald criteria were 70.9%, 63.1%, 67.1%, 66.3%, and 67.9%, and those for 2016 MAGNIMS criteria were 88.4%, 46.4%, 67.7%, 62.8%, and 79.6%, respectively. When we excluded 80 patients who underwent disease-modifying therapy before the second clinical event, the specificity increased to 92.3% and 84.6%, but the sensitivity decreased to 58.8% and 82.4% for 2010 McDonald and 2016 MAGNIMS criteria, respectively. Conclusion: 2016 MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher sensitivity but lower specificity than 2010 McDonald criteria in predicting conversion to CDMS in CIS patients. [ABSTRACT FROM AUTHOR]

Background: Some patients with neuromyelitis optica spectrum disorders (NMOSD) present with spinal cord lesions extending fewer than three vertebral segments (short transverse myelitis, STM), hindering an early diagnosis. Objective: We investigated the frequency and imaging characteristics of STM lesions in patients presenting with myelitis as an initial manifestation of NMOSD. Methods: Patients seen at three referral hospitals in Korea between June 2005 and March 2015 who met the following inclusion criteria were recruited for review: seropositivity for aquaporin-4 antibody, initial presentation with myelitis and spinal cord magnetic resonance imaging (MRI) performed within 1 month of initial myelitis onset. Results: Of the 76 enrolled patients, 65 (85.5%) collectively had 69 longitudinally extensive transverse myelitis lesions, while the remaining 11 (14.5%) had a total of 15 STM lesions. Of the 15 STM lesions, 5 spanned 2.5 vertebral segments, 6 were continuous over two segments, 3 showed a length of 1.5 segments and 1 was confined to a single segment. On axial imaging, all of the STM lesions involved the central grey matter. Conclusion: These MRI findings suggested that STM does not preclude the possibility of an NMOSD diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the frequency and pattern of cognitive impairment (CI) between patients with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Methods: A total of 82 NMOSD patients, 58 MS patients, and 45 healthy controls (HCs) underwent a neuropsychological assessment. Results: CI was observed in 29% of NMOSD and 50% of MS patients (p < 0.001); CI was considered present if a patient scored lower than the fifth percentile compared with HCs in at least three domains. A lower frequency of CI was consistently found when CI was indicated by at least two failed tests (p < 0.001). MS patients performed worse than did NMOSD patients on verbal learning and verbal and visual memory tests. Levels of education and depression and the interval from disease onset to treatment were associated with a negative influence on cognition in patients with NMOSD. Conclusion: CI in patients with NMOSD may be not as common as in patients with MS. MS patients exhibited severe impairment, particularly on learning and memory tests, compared with NMOSD patients. Differential prevalence and patterns of CI between NMOSD and MS patients suggest that the two diseases have different mechanisms of brain injury. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are inflammatory autoimmune diseases of the central nervous system. We hypothesized that the degree of demyelination within lesions in MS and NMOSD would differ as the pathophysiology of the two diseases do. We used myelin water imaging to compare the myelin water fraction (MWF) in 106 periventricular white matter (PVWM) lesions in 27 MS patients and 51 PVWM lesions in 20 NMOSD patients. The MWF was significantly reduced in the MS compared with the NMOSD lesions, suggesting that myelin loss was more severe in MS than in NMOSD. [ABSTRACT FROM AUTHOR]

Background: There is still an unmet need for comparative analyses of available treatment options for neuromyelitis optica spectrum disorder (NMOSD). Objective: We aimed to compare the efficacies of the immunosuppressants most commonly prescribed for patients with NMOSD using multifaceted endpoints. Methods: We conducted a retrospective analysis of treatment outcomes in 138 NMOSD patients treated with azathioprine, mycophenolate mofetil (MMF), or rituximab. The primary outcome measures were the annualized relapse rate (ARR), annualized severe relapse rate, time to first relapse, and time to first severe relapse. Results: A comparison of any relapse among the groups revealed that the azathioprine had a significantly higher risk of relapse relative to the rituximab (hazard ratio: 1.82; 95% CI: 1.1–3.1; p=0.03). A comparison of severe relapse among the groups revealed that the hazard ratios of severe relapse for the azathioprine and MMF relative to the rituximab were 11.66 (95% CI: 2.6–52.3; p=0.001) and 5.96 (95% CI: 1.0–35.1; p=0.048), respectively. The times to first relapse and first severe relapse were also significantly different among the treatment groups Conclusions: The present study showed that reductions in the risks of relapse and severe relapse differed among patients who were initially treated with azathioprine, MMF, and rituximab. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding the association of aquaporin-4 (AQP4) antibody with longitudinally extensive transverse myelitis (LETM). Topics discussed include manifestation of autoimmune disease neuromyelitis optica (NMO), the measurement of cerebrospinal fluid and glial fibrillary acidic protein (GFAP), and investigation of astrocyte damage.

The article discusses a study which aimed at identifying the extent to which Korean adults wanted to exercise autonomy in the process of decision making with respect to end-of-life (EOL) treatment and determine the association of economic issues and family functioning with preferences for involvement in decision making about EOL treatment in Korean people. Topics discussed include findings that most Korean people wanted autonomy in the decision-making process about treatment at end-of-life.

We evaluated whether the location of the initial attack predicted the locations of subsequent events in neuromyelitis optica spectrum disorder (NMOSD). In the retrospective analysis from 164 patients with NMOSD, increased odds of a second attack occurring in the initial event location were seen in all locations (odds ratio [OR] brain: 16.00; brainstem: 4.42; optic nerve: 4.08; and spinal cord: 4.59), as was a positive linear trend when evaluating the number of previous events in the same location as the third event location (OR brain: 62.52; brainstem: 44.55; optic nerve: 6.48; and spinal cord: 2.98). This study suggests early clinical events of NMOSD tend to recur in the same anatomical location within the central nervous system (CNS). [ABSTRACT FROM AUTHOR]

The article presents a study which aims to give disability weights (DWs) for each of the ordinal Expanded Disability Status Scale (EDSS) levels which are used ordinal disability scale for multiple sclerosis (MS). The study conducted the person trade-off (PTO) procedure to trigger DWs for EDSS categories and used the modified Delphi process to achieve consensus among pace. Results showed that DWs supported that EDSS is an ordinal scale with highly variable intervals.

The article focuses on the research which shows the capability of brain magnetic resonance imaging (MRI) of helping the differentiation of multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorder (NMOSD). It states the difficulty to differentiate MS from NMOSD by fulfillment of the MRI criteria for MS on brain MRI. It mentions that the characteristics morphology and enhancement pattern of brain lesions are useful for diagnosis of MS and NMOSD.

We investigated the validity of the 2005 and 2010 McDonald magnetic resonance imaging (MRI) criteria for dissemination in space (DIS) to predict the conversion of clinically definite multiple sclerosis (CDMS) in 94 Korean patients with clinically isolated syndromes (CIS). The sensitivity, specificity, accuracy, positive and negative predictive values of the 2005, 2010 McDonald DIS criteria were comparable to those observed in the Caucasian population. This finding suggests that after careful exclusion of alternative explanations, particularly neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD), both the 2005 and 2010 McDonald DIS criteria are also useful to predict conversion to CDMS in Korean patients with CIS. [ABSTRACT FROM AUTHOR]

The article presents a study on the clinical attributes and consequences of multiple sclerosis (MS) in South Korea. It mentions that researches were conducted in Asia without proper differentiation of neuromyelitis optica (NMO) from the autoimmune disorder. It also notes that the exclusion of neuromyelitis optica spectrum disorder (NMOSD) indicated the pattern of MS similar to those in Western nations.

The article presents a study of the degree to which interferon beta (INF- β) exacerbates neuromyelitis optica (NMO) spectrum disorders (NMOSD). It assesses the annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) scores of patients before and after IFN- β treatment. Results showed INF- β treatment is not effective fore disease relapse prevention and significantly increases relapses.

Advances in the understanding of central nervous system aquarporin-4 autoimmunity have promoted the recognition of diverse clinical presentations beyond the traditional view of neuromyelitis optica. We describe a patient who developed hemiparesis caused by an extensive cerebral lesion as an initial manifestation of central nervous system aquarporin-4 autoimmunity. Although the patient had no history of optic neuritis or myelitis, not only was serum anti-aquarporin-4 antibody positive, but an imaging, treatment response and histopathological features also revealed characteristic findings suggestive of central nervous system aquarporin-4 autoimmunity. The present case highlights the importance of a comprehensive evaluation for anti-aquarporin-4 antibody even in patients presenting with isolated cerebral lesions. [ABSTRACT FROM AUTHOR]

Background: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO).Methods: To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4–Ab in 787 samples collected from 51 patients with definite or high-risk NMO.Results: AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations.Conclusions: We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity. [ABSTRACT FROM AUTHOR]

Background: Although brain abnormalities are being recognized more frequently in patients with neuromyelitis optica spectrum disorder (NMOSD), most brain lesions in previous reports have accompanied pre-existing NMOSD. Here, we describe clinical and imaging characteristics of patients with NMOSD who presented with brain symptoms as their first manifestation of the condition.Methods: Anti-aquaporin-4 antibody was measured using cell-based assays and/or enzyme-linked immunosorbent assay in the sera of 257 patients with inflammatory diseases of the central nervous system who attended the multiple sclerosis clinic of the National Cancer Center, Korea, between May 2005 and December 2009. Eighty-three were seropositive, and 15 of these who presented with brain symptoms were included in this study. We retrospectively reviewed these individuals’ clinical and radiological findings.Results: Patients with NMOSD were followed for a mean of 90 months. Median age at onset was 24 years (6–54 years) and there was a female preponderance (94%). The initial manifestation was classified into two groups according to clinical characteristics: encephalopathy mimicking acute disseminated encephalomyelitis or posterior reversible encephalopathy syndrome and characteristic brainstem symptoms such as intractable hiccup and vomiting. The majority of brain symptoms and lesions resolved. Intriguingly, eight patients (53%) experienced brain relapses that followed a similar pattern during the course of their disease.Conclusion: It is important to recognize that NMO or NMOSD can initially present with brain symptoms. [ABSTRACT FROM AUTHOR]