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Background/purpose: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan., Methods: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR)., Results: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 10 3 /uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353., Conclusion: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objectives: Blood-brain barrier (BBB) disruption is a critical pathological process involved in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterized the profile of five cell adhesion molecules in patients with NMOSD., Methods: We measured levels of cell adhesion molecules, including ICAM-1, ICAM-2, VCAM-1, PECAM-1, and NCAM-1, in the serum of 28 patients with NMOSD, 24 patients with multiple sclerosis (MS), and 25 healthy controls (HCs)., Results: ICAM-2 levels (median: 394.8 ng/mL) were increased in patients with NMOSD compared with MS (267.1 ng/mL, P = 0.005) and HCs (257.4 ng/mL, P = 0.007), and VCAM-1 and ICAM-1 levels were higher in patients with NMOSD (641.9 ng/mL and 212.7 ng/mL, respectively) compared with HCs (465 ng/mL [P = 0.013] and 141.8 ng/mL [P = 0.002], respectively). However, serum PECAM-1 levels were lower in patients with NMOSD (89.62 ng/mL) compared with MS (106.9 ng/mL, P = 0.015) and HCs (107.2 ng/mL, P = 0.007). Receiver operating characteristic curve analysis revealed that PECAM-1 (area under the curve (AUC): 0.729) and ICAM-2 (AUC: 0.747) had adequate abilities to distinguish NMOSD from MS, and VCAM-1 (AUC: 0.719), PECAM-1 (area under the curve: 0.743), ICAM-1 (AUC: 0.778), and ICAM-2 (AUC: 0.749) exhibited potential to differentiate NMOSD and HCs. Serum levels of PECAM-1 also demonstrated a negative correlation with Kurtzke Expanded Disability Status Scale scores in patients with NMOSD., Interpretation: Our results reveal possible BBB breakdown signals specifically observed in NMOSD and highlight the potential role of cell adhesion molecules as biomarkers of this disease., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: CIS to MS conversion rates vary depending on population cohorts, initial manifestations, and durations of follow-up., Objective: To investigate conversion rate of patients from CIS to MS and the prognostic significance of demographic and clinical variables in Taiwanese population., Design: Nationwide, prospective, multi-centric, observational study from November 2008 to November 2014 with 4 years follow-up., Setting: Multi-centre setting at 5 institutions in Taiwan., Participants: 152 patients having single clinical event potentially suggestive of MS in last 2 years were enrolled as consecutive sample. 33 patients were lost to follow-up and 16 patients did not complete the study.103 patients completed the study., Intervention(s) (for Clinical Trials) or Exposure(s) (for Observational Studies): Natural progression from first episode of CIS to MS or NMO was observed., Main Outcome(s) and Measure(s): Variables analysed were 'proportion of patients converting to MS or NMO after first episode of CIS', 'duration between first episode of neurological event and diagnosis of MS', 'status of anti-AQP4 IgG' and 'length of longest contiguous spinal cord lesion in MS patients'. Association between baseline characteristics and progression to MS from CIS was analyzed using multiple logistic regression. Multivariate time dependent effect of baseline characteristics on progression to MS was plotted., Results: 14.5% patients with CIS converted to MS after 1.1 ± 1.0 years with greater predisposition (18.8%) in those having syndromes referable to the cerebral hemispheres. Conversion rate from ON to MS was 9.7%. 90.9% patients had mild disease course. 46.7% patients had abnormal MRIs at baseline, with 0.6±0.5 contrast enhanced lesions. 'Below normal BMI' and 'MRI lesion load (≥ 4 lesions)' were identified as risk indicators for the development of MS. Amongst the patients who developed NMO as diagnosed by modern criteria, 80% were positive for anti-AQP4 IgG antibody., Conclusions and Relevance: 'Below normal BMI' and 'number of demyelinating lesions (≥4)' are significant predictors of conversion from CIS to MS. A low conversion rate to MS in Taiwanese CIS patients and majority of them having a mild course and minimal disability suggest the roles of geographic, genetic and ethnic factors., Trial Registration: Non-trial observational study., Competing Interests: One author, Dr. Li-Chieh Huang is a salaried employee of Merck Biopharma, Taiwan. The study was funded with a research grant by Merck Biopharma, Taiwan. The funding organization had no role in study design; collection, analysis, and interpretation of data; writing of the paper; and/or decision to submit for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the central nervous system with different pathogenesis, brain lesion patterns, and treatment strategies. However, it is still difficult to distinguish these two disease entities by neuroimaging studies. Herein, we attempt to differentiate NMOSD from MS by comparing brain lesion patterns on magnetic resonance imaging (MRI)., Methods: The medical records and cranial MRI studies of patients with NMOSD diagnosed according to the 2006 Wingerchuk criteria and the presence of anti-aquaporin 4 (anti-AQP4) antibodies, and patients with MS diagnosed according to the Poser criteria, were retrospectively reviewed., Results: Twenty-five NMOSD and 29 MS patients were recruited. The NMOSD patients became wheelchair dependent earlier than MS patients (log rank test; P = 0.036). Linear ependymal (28% vs. 0%, P = 0.003) and punctate lesions (64% vs. 28%, P = 0.013) were more frequently seen in NMOSD patients. Ten NMOSD patients (40%) had brain lesions that did not meet the Matthews criteria (MS were separated from NMOSD by the presence of at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion or a Dawson finger-type lesion). The different image patterns of NMOSD didn't correlate with the clinical prognosis. However, NMOSD patients with more (≧10) brain lesions at onset became wheelchair dependence earlier than those with fewer (<10) brain lesions (log rank test; P < 0.001)., Conclusions: The diagnostic sensitivity of NMOSD criteria can be increased to 56% by combining the presence of linear ependymal lesions with unmet the Matthews criteria. The prognoses of NMOSD and MS are different. A specific imaging marker, the linear ependymal lesion, was present in some NMOSD patients. The diagnosis of NMOSD can be improved by following the evolution of this imaging feature when anti-AQP4 antibody test results are not available.

Background: Neuromyelitis optica (NMO), which was previously considered a variant of multiple sclerosis (MS), is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. It has been shown that the level of haptoglobin in cerebrospinal fluid (CSF) is elevated in NMO. However, it is uncertain whether this change is specific to NMO, or is also seen in MS and other neurological diseases., Methods: We used an enzyme-linked immunosorbent assay (ELISA) to measure the haptoglobin levels in the CSF and serum in 25 NMO, 16 MS, and 15 Alzheimer's disease (AD) patients and 22 controls., Results: The CSF haptoglobin concentration of the NMO patients (0.309±0.074mg/dl, P<0.001) was significantly higher than that of MS patients (0.081±0.016mg/dl) and AD patients (0.058±0.011mg/dl), and the controls (0.060±0.009mg/dl), whereas the serum haptoglobin and albumin concentrations in the serum and CSF did not differ significantly across groups. NMO patients (0.59±0.15, P=0.001) demonstrated a higher haptoglobin index than MS patients (0.13±0.01), AD patients (0.12±0.03), and the controls (0.17±0.04). Furthermore, the haptoglobin concentration and haptoglobin index in the CSF correlated significantly with the expanded disability scale score (EDSS) in NMO patients., Conclusions: The high CSF haptoglobin concentration in NMO may be explained by increased intrathecal haptoglobin synthesis. The correlation between CSF haptoglobin concentration/haptoglobin index and EDSS highlights the potential of haptoglobin as a biomarker of NMO., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Motor and somatosensory evoked potentials (MEPs and SSEPs) are sensitive tools for detecting subclinical lesions, assessing disease severity, and determining the prognosis for outcomes of patients with inflammatory neurological diseases such as multiple sclerosis. However, their roles in neuromyelitis optica (NMO), a severe inflammatory neurological disease that predominantly involves optic nerves and spinal cord, have not yet been clarified. Methods and Findings: Clinical symptoms and examination findings at relapses of 30 NMO patients were retrospectively reviewed. Abnormal MEPs were observed in 69.2% of patients. Patients with abnormal motor central conduction time (CCT) of the lower limbs had higher Kurtzke Expanded Disability Status Scale (EDSS) scores than those with normal responses (P = 0.027). Abnormal SSEPs were found in 69.0% of patients. Patients with abnormal lower limb sensory CCT had higher EDSS scores than those with normal responses (P = 0.019). In 28 patients followed up more than 6 months, only one of 11 patients (9.1%) with normal SSEPs of the lower limbs had new relapses within 6 months, whereas 8 of 17 patients (47.1%, P = 0.049) with abnormal SSEPs of the lower limbs had new relapses. Conclusions: These results indicate MEPs and SSEPs of the lower limbs are good indicators for the disability status at relapses of NMO. Lower limb SSEPs may be a good tool for reflecting the frequency of relapses of NMO. [ABSTRACT FROM AUTHOR]

Abstract: Prostaglandin D2 synthase (PGDS) is the most abundant brain protein in cerebrospinal fluid (CSF) and is tied closely with inflammatory processes. This study investigated whether CSF PGDS levels in patients with acute inflammatory demyelinating polyneuropathy (AIDP) are altered. The results suggest that PGDS concentration is significantly increased in the CSF of AIDP patients compared with the control patients (p <0.05) due to a blood-CSF barrier dysfunction, whereas the intrathecal synthesis of PGDS, reflected by the CSF PGDS/albumin ratio, is significantly decreased in AIDP compared with the control group (p <0.05). The changes of CSF PGDS/albumin ratio are only observed in AIDP patients, but not in Miller Fisher Syndrome (MFS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or multiple sclerosis (MS) patients. [Copyright &y& Elsevier]