Recurrence of clinical events at the same anatomical location in patients with MOG antibody-associated disease.

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.

Comparison of MOG and AQP4 antibody seroprevalence in Korean adults with inflammatory demyelinating CNS diseases.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

Evaluation of brain lesion distribution criteria at disease onset in differentiating MS from NMOSD and MOG-IgG-associated encephalomyelitis.

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.

Restoration of regulatory B cell deficiency following alemtuzumab therapy in patients with relapsing multiple sclerosis.

BACKGROUND: Regulatory B cells (Bregs), which protect from autoimmunity, are deficient in multiple sclerosis (MS). Novel regulatory B cell subsets CD19+CD24hiCD38hi cells and CD19+PD-L1hi cells, with disparate regulatory mechanisms have been defined. Alemtuzumab provides a long-lasting suppression of disease activity in MS. In contrast to its documented efficacy, alemtuzumab's mechanism of action is not fully understood and information about the composition of repopulating B cell pool is scarce. AIM: To characterize repopulated B cell subsets and elucidate alemtuzumab's mechanism of action in B cell perspective. METHODS: The frequency and the absolute number of Bregs were studied in peripheral blood mononuclear cells (PBMC) of 37 MS patients and 11 healthy controls (HC). Longitudinal analysis of the frequency and the absolute number of Bregs in PBMC of 11 MS patients was evaluated, before and at 6, 9, and 12 months post alemtuzumab. RESULTS: We found deficiency of CD19+CD24hiCD38hi cells during relapse compared to remission and HC (relapse vs remission: p = 0.0006, relapse vs HC: p = 0.0004). CD19+PD-L1hi cells were deficient during relapse than remission and HC (relapse vs remission: p = 0.0113, relapse vs HC: p = 0.0007). Following alemtuzumab, the distribution of B cells shifts towards naïve phenotype and Breg deficiency is restored. The frequency of CD19+CD24hiCD38hi cells was significantly increased at 6 M and 9 M compared to 0 M (6 M vs 0 M: p = 0.0004, 9 M vs 0 M: p = 0.0079). At 9 M, the frequency of CD19+CD24hiCD38hi cells started to decrease and by 12 M the frequency was reduced compared to 6 M, although it was significantly higher than baseline level (12 M vs 0 M: p = 0.0257). The absolute number was significantly increased at 6 M and 9 M post-alemtuzumab (6 M vs 0 M: p = 0.0063, 9 M vs 0 M: p = 0.02). The frequency of CD19+PD-L1hi cells significantly increased until 12 M (6 M vs 0 M: p = 0.0004, 12 M vs 0 M: p = 0.0036). The frequency of CD19+PD-L1hi cells at 12 M was significantly higher than 9 M (p = 0.0311). We further pinpoint that CD19+CD24hiCD38hi cells were deficient at severe relapses following alemtuzumab infusion and restored during recovery. CONCLUSIONS: Our results highlight the preferential reconstitution of Bregs as a possible mechanism of action of alemtuzumab and CD19+CD24hiCD38hi cells as a potential biomarker for disease activity.

Clinical Implication of Corrective Saccades in the Video Head Impulse Test for the Diagnosis of Posterior Inferior Cerebellar Artery Infarction.

Objective: In the present study, we characterized the vestibulo-ocular reflex (VOR) gain and properties of corrective saccades (CS) in patients with posterior inferior cerebellar artery (PICA) stroke and determined the best parameter to differentiate PICA stroke from benign peripheral vestibular neuritis (VN). In particular, we studied CS amplitude and asymmetry in video head impulse tests (vHITs) to discriminate these two less-studied disease conditions. Methods: The vHITs were performed within 1 week from symptom onset in patients with PICA stroke (n = 17), patients with VN (n = 17), and healthy subjects (HS, n = 17). Results: PICA stroke patients had bilaterally reduced VOR gains in the horizontal semicircular canal (HC) and the posterior semicircular canal (PC) compared with HSs. When compared with VN patients, PICA stroke patients showed preserved gains in the HC and anterior semicircular canal (AC) bilaterally (i.e., symmetric VOR gain). Similar to VOR gain, smaller but bilaterally symmetric CS in the HC and AC were observed in PICA stroke patients compared with VN patients; the mean amplitude of CS for the ipsilesional HC was reduced (p < 0.001, Mann-Whitney U-test), but the mean amplitude of CS for the contralesional HC was increased (p < 0.03, Mann-Whitney U-test) in PICA stroke compared with VN. The receiver operating characteristic (ROC) curve showed that CS amplitude asymmetry (CSs) and VOR gain asymmetry (Gs) of HC are excellent parameters to distinguish PICA stroke from VN. Conclusion: In the current study, we quantitatively investigated the VOR gain and CS using vHITs for three semicircular canals in PICA stroke and VN patients. In addition to VOR gain, quantitative assessments of CS using vHITs can provide sensitive and objective parameters to distinguish between peripheral and central vestibulopathies.

Value of Area Postrema Syndrome in Differentiating Adults With AQP4 vs. MOG Antibodies.

Objectives: To compare the frequency of area postrema syndrome (APS) in adults with anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods: APS is defined as acute or subacute, single or combined, episodic or constant nausea, vomiting, or hiccups, persisting for at least 48 h, which cannot be attributed to any other etiology. The presence of APS was investigated in 274 adults with AQP4 antibodies and 107 adults with MOG antibodies from 10 hospitals. Results: The study population comprised Korean adults (≥18 years). At the time of disease onset, 14.9% (41/274) adults with AQP4 antibodies had APS, while none of the participants with MOG antibodies developed APS (p < 0.001). During the course of the disease, 17.2% (47/274) adults with AQP4 antibodies had APS in contrast to 1.9% (2/107) adults with MOG antibodies with APS (p < 0.001). Conclusions: APS, one of the core clinical characteristics of individuals with AQP4 antibodies, is an extremely rare manifestation in Korean adults with MOG antibodies.

Real-World Effectiveness of Disease-Modifying Therapies in Korean Patients with Relapsing Multiple Sclerosis.

BACKGROUND AND PURPOSE: This study assessed the long-term outcomes of disease-modifying therapies (DMTs) in Korean multiple sclerosis (MS) patients treated in real-world clinical settings in Korea. METHODS: We retrospectively evaluated the medical records of 160 patients with an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS who were treated for at least 2 years. A status of 3 for no evidence of disease activity (NEDA3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging (MRI) evaluations. RESULTS: Patients who were initially treated with interferon ß (n=152), glatiramer acetate (n=6), or teriflunomide (n=2) were included. The mean disease duration was 8.2 years. Compared to pretreatment, annualized relapse rates were significantly reduced after treatment [from 1.0±0.8 to 0.2±0.4 (mean±standard deviation), p<0.001]. At the follow-up, 79 patients (49%) had changed their treatment regimen due to lack of efficacy (33%), side effects (14%), or other reasons (2%). Disability progression was observed in 18% of the patients over a mean treatment duration of 5.7 years. After 2 years, NEDA3 was observed in 38% of the patients. Loss of NEDA3 at 2 years was associated with long-term disability progression [odds ratio (OR)=17.975, p=0.003]. Poor response to first-line treatment was independently associated with a delay in treatment from disease onset (OR=1.238, p=0.049) and 10 or more brain lesions in the initial MRI (OR=3.648, p=0.047). CONCLUSIONS: This study has provided real-world evidence that DMTs are effective in reducing disease activity and disability progression in Korean MS patients.

Therapeutic Outcome of Alemtuzumab in Korean Patients with Multiple Sclerosis: 2-Year Follow-Up.

BACKGROUND AND PURPOSE: Alemtuzumab has shown high efficacy in clinical trials that primarily involved Western multiple sclerosis (MS) patients. To evaluate the therapeutic outcome of alemtuzumab in Korean patients with MS. METHODS: This study enrolled 23 consecutive patients who were treated with alemtuzumab from 2015 to 2018. Efficacy was evaluated using the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), and radiological activity. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of the EDSS score, and no radiological activity. The safety profiles were also assessed. RESULTS: The mean age was 36 years and 16 of the patients were female. Seventeen and 12 of 23 patients were followed up for 1 year and 2 years, respectively. The ARR was markedly reduced from 1.52 during the 1-year period preceding alemtuzumab administration to 0.21 after initiating alemtuzumab (p<0.001). During the first and second years after initiating alemtuzumab, EDSS worsening was observed in 3 (18%) and 0 (0%) patients, respectively, and radiological activity was exhibited in 9 (53%) and 4 (33%). NEDA was observed in 6 (35%) patients during the first year and in 8 (67%) patients during the second year. Intriguingly, one patient experienced 2 severe clinical exacerbations, which occurred at 10 months after the first and 10 months after the second infusion of alemtuzumab. Nineteen of the 23 patients exhibited infusion-associated reactions and 3 patients exhibited herpes zoster infection. Thyroid dysfunction occurred in two patients at 18 and 20 months after initiating alemtuzumab. CONCLUSIONS: Consistent with observations in Western populations, alemtuzumab therapy in Korean MS patients led to marked reductions of disease activity without unexpected safety issues.

Changing patterns of multiple sclerosis in Korea: Toward a more baseline MRI lesions and intrathecal humoral immune responses.

BACKGROUND: The environmental risks of multiple sclerosis (MS), including adolescent obesity and vitamin D deficiency, are increasing in Korea. We aimed to determine whether the patterns and/or severity of MS in Korea can change according to the year of birth or disease onset. METHODS: Two hundred and sixty-six patients with adult-onset MS, including 164 with an available baseline magnetic resonance imaging (MRI), were retrospectively included from 17 nationwide referral hospitals in Korea. The demographics, MRI T2 lesion burden at disease onset, cerebrospinal fluid markers, and prognosis were assessed. RESULTS: The birth year, time from disease onset to first MRI, and female sex were associated with a higher number of baseline MRI T2 lesions. The birth year was also associated with the presence of oligoclonal band in the cerebrospinal fluid and high immunoglobin G index. An increased female/male ratio was observed among those with a more recent year of birth and/or disease onset. CONCLUSIONS: In Korea, the disease pattern of adult-onset MS may be changing toward a more baseline T2 MRI lesions, intrathecal humoral immune responses, and also higher female ratio.

Simultaneous recording of cervical and ocular vestibular-evoked myogenic potentials.

OBJECTIVE: To increase clinical application of vestibular-evoked myogenic potentials (VEMPs) by reducing the testing time by evaluating whether a simultaneous recording of ocular and cervical VEMPs can be achieved without a loss in diagnostic sensitivity and specificity. METHODS: Simultaneous recording of ocular and cervical VEMPs on each side during monaural stimulation, bilateral simultaneous recording of ocular VEMPs and cervical VEMPs during binaural stimulation, and conventional sequential recording of ocular and cervical VEMPs on each side using air-conducted sound (500 Hz, 5-millisecond tone burst) were compared in 40 healthy participants (HPs) and 20 patients with acute vestibular neuritis. RESULTS: Either simultaneous recording during monaural and binaural stimulation effectively reduced the recording time by ≈55% of that for conventional sequential recordings in both the HP and patient groups. The simultaneous recording with monaural stimulation resulted in latencies and thresholds of both VEMPs and the amplitude of cervical VEMPs similar to those found during the conventional recordings but larger ocular VEMP amplitudes (156%) in both groups. In contrast, compared to the conventional recording, simultaneous recording of each VEMP during binaural stimulation showed reduced amplitudes (31%) and increased thresholds for cervical VEMPs in both groups. CONCLUSIONS: The results of simultaneous recording of cervical and ocular VEMPs during monaural stimulation were comparable to those obtained from the conventional recording while reducing the time to record both VEMPs on each side. CLINICALTRIALSGOV IDENTIFIER: NCT03049683.

Racial differences in neuromyelitis optica spectrum disorder.

OBJECTIVE: We aimed to evaluate racial differences in the clinical features of neuromyelitis optica spectrum disorder. METHODS: This retrospective review included 603 patients (304 Asian, 207 Caucasian, and 92 Afro-American/Afro-European), who were seropositive for anti-aquaporin-4 antibody, from 6 centers in Denmark, Germany, South Korea, United Kingdom, United States, and Thailand. RESULTS: Median disease duration at last follow-up was 8 years (range 0.3-38.4 years). Asian and Afro-American/Afro-European patients had a younger onset age than Caucasian patients (mean 36, 33, and 44 years, respectively; p < 0.001). During the disease course, Caucasian patients (23%) had a lower incidence of brain/brainstem involvement than Asian (42%) and Afro-American/Afro-European patients (38%) (p < 0.001). Severe attacks (visual acuity ≤0.1 in at least one eye or Expanded Disability Status Scale score ≥6.0 at nadir) at onset occurred more frequently in Afro-American/Afro-European (58%) than in Asian (46%) and Caucasian (38%) patients (p = 0.005). In the multivariable analysis, older age at onset, higher number of attacks before and after immunosuppressive treatment, but not race, were independent predictors of severe motor disabilities at last follow-up. CONCLUSION: A review of a large international cohort revealed that race affected the clinical phenotype, age at onset, and severity of attacks, but the overall outcome was most dependent on early and effective immunosuppressive treatment.

Neutralizing Antibodies Against Interferon-Beta in Korean Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-ß) can develop neutralizing antibodies (NAbs) against IFN-ß that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-ß in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-ß for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-ß-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-ß-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-ß-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-ß.

Intermittent Theta Slowings in Contralateral Side of Weakness after Sleep Deprivation on Spot EEG in Sporadic Hemiplegic Migraine.

Hemiplegic migraine (HM) is an uncommon type of migraine which is classified into sporadic and familial subtype. The noticed electroencephalogram (EEG) findings during HM attack are diffuse slowing contralateral to the weakened limb, but are usually normal in asymptomatic states. A 52-year-old woman who suffered from headache accompanying right arm weakness and aphasic symptoms admitted to our hospital. She underwent total five times of EEG including 2 times before admission. Only the last EEG exam after 24 hours of sleep deprivation (SD) showed intermittent slowing and higher amplitude of positive occipital sharp transients (POSTs) on the left parieto-occipital area. Here, we report a case with HM who revealed abnormal EEG findings after SD, which was not observed in the routine EEG study without SD.

Electron microscopy study of novel Pt nanowires synthesized in the spaces of silica mesoporous materials.

Structures of Pt-nanowires, synthesized in channels of silica mesoporous materials MCM-41, SBA-15 and MCM-48, were investigated by transmission electron microscopy. One dimensional (1D) Pt-nanowires were formed inside the channels of the MCM-41, and were single crystals with a length of several tens to several hundreds nanometers and a diameter of ca. 3 nm pt-nanowires synthesized in SBA-15 formed a new 3D-network following 3D-pore geometry of SBA-15; that is, the main 1D-channels are interconnected to each other through randomly distributed tunnels. These Pt-nanowires showed a well single crystalline. MCM-48 has two non-intersecting chiral channels, and Pt-networks were mostly formed in one of the two channels. Therefore the networks were also chiral; however, the chirality of Pt-networks remained to be determined. It was shown that all Pt-nanowires were formed following the channel geometries of silica mesoporous materials used.