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To reduce the burden of caregivers and fulfill successful aging of family caregivers self, better supporting systems of caring elderly are requested. A questionnaire was mailed to each caregiver, who lives in Tokyo metropolitan. Quesions included burden of the caregivers and ADL of centenarians. Physical and psychological burden of caregivers is storongly affected by centenarian's ADL,cognitive level, and abnormal behaviors. Family caregivers of centenarians had a lower accumulated fatigue level and rated their health as very good to good, despite being older themselves and in spite of impoverished ADL of centenarians. Family caregivers of centenarians perceive their work not just duty or responsibility but worthwhile and satisfying. The care of centenarians might be possible model for successful caring.

We examined the medical records of Japanese centenarians to clarify whether centenarians lived free from diseases, what kinds of morbidity they had experienced, and how such morbidity affected their autonomy. Three hundreds and thirty five centenarians living in Tokyo area were enrolled in this study. Informed consent was obtained in written form from the centenarians or their proxies. Their medical records were questioned by questionnaire and/or interview. The levels of activities of daily living (ADL) and cognitive function were also assessed using Barthel Index and mini-mental state examination (MMSE), respectively. The levels of ADL and cognitive function were significantly lower in female centenarians. About one third of centenarians escaped from grave diseases. Among their present and previous diseases, cataract, coronary and valvular heart diseases, hypertension, and cerebrovascular diseases were frequently reported. The incidence of fracture was significantly high in female centenarians. Another remarkable finding was very low incidence of diabetes mellitus (DM). The levels of ADL and cognitive function of the centenarians with the history of fracture were lower, suggesting that fracture, irrespective of its location, affected their autonomy. In conclusion, one third of Japanese centenarians escape from severe diseases, DM is unfavorable for longevity, and prevention of fracture may improve autonomy in the oldest old.

It is reported that some personality traits in centenarians are different from those in younger controls. Recently polymorphism of dopamine receptor 4(D4DR) and serotonin transporter (5HTT) genes are shown to be related with novelty seeking and neurosis, respectively. It is not reported that polymorphism of these genes is associated with longevity. One hundred and forty five female centenarians living in Tokyo metropolitan area were enrolled in this study. As control group. 173 young females(average age 18.9 years old) were recruited. Polymorphism of D4DR in centenarians was not different from that in younger control and was not associated with the level of ADL and cognitive function of the centenarians. As for the polymorphism of 5HTT, frequency of 1 allele in centenarians was significantly higher than that in control. Centenarians with 1 allele have high level of ADL and serum albumin, compared with those with s allele. These data suggests that 5HTT polymorphism seems to be associated with longevity through behavioral and biological factors.

Background: A large-scale randomized trial of adjuvant interferon-α therapy for patients with osteosarcoma has been initiated as a joint protocol by the European and American Osteosarcoma Study Group. Because the expression of functional interferon-α/β receptor is necessary for interferon-α agents to interact with osteosarcoma cells, we examined the expression of interferon-α/β receptor in a series of osteosarcoma specimens.Methods: Forty patients with high-grade resectable osteosarcoma, from whom surgical specimens had been obtained at the time of biopsy, were included in this retrospective study. Biopsy specimens were immunohistochemically stained with anti-interferon-α/β receptor antibodies. Survival was estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis to determine the independent prognostic factors. Furthermore, we used Holm and Benjamini-Hochberg procedures to adjust for multiple comparisons in setting the level of significance. The median follow-up period was five years and two months (range, four to 195 months).Results: The expression of interferon-α/β receptor was positive in eighteen (45%) of the forty patients with high-grade osteosarcoma. American Joint Committee on Cancer surgical stage IIA, a good histologic response to chemotherapy, and expression of interferon-α/β receptor correlated significantly with better disease-free survival (p < 0.05). Multivariate analysis showed that interferon-α/β receptor expression alone retained its power to predict an improved prognosis (p = 0.042). There were no significant variables after corrections for multiple comparisons.Conclusions: Interferon-α/β receptor may be a useful marker for assessing tumor prognosis in patients with osteosarcoma and may play an important role in tumor progression. These findings are encouraging and support the ongoing clinical trials of adjuvant interferon-α therapy by the multinational Osteosarcoma Study Group. Our pilot study was based on a small sample size, and larger trials are needed to confirm this finding.Level Of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Abstract Background One of the major components of telomerase is the human telomerase reverse transcriptase (hTERT) as the catalytic protein. hTERT mRNA expression are reported to be associated with prognosis and tumor progression in several sarcomas. However, there is no clear understanding of the mechanisms of hTERT in human sarcomas. Recent studies have suggested that signals transmitted through p38 mitogen-activated protein kinase (MAPK) can increase or decrease hTERT transcription in human cells. The purpose of this study was to analyse the correlation between p38 MAPK and hTERT in sarcoma samples. Methods We investigated 36 soft tissue malignant fibrous histiocytomas (MFH), 24 liposarcomas (LS) and 9 bone MFH samples for hTERT and p38 MAPK expression. Quantitative detection of hTERT and p38 MAPK was performed by RT-PCR. Results There was a significant positive correlation between the values of hTERT and p38 MAPK in all samples (r = 0.445, p = 0.0001), soft tissue MFH (r = 0.352, p = 0.0352), LS (r = 0.704, p = 0.0001) and bone MFH samples (r = 0.802, p = 0.0093). Patients who had a higher than average expression of p38 MAPK had a significantly worse prognosis than other patients (p = 0.0036). Conclusions p38 MAPK may play a role in up-regulation of hTERT, and therefore, p38 MAPK may be a useful marker in the assessment of hTERT and patients' prognosis in sarcomas.

Background and Purpose: Slowly expanding lesions (SELs) have been proposed as novel MRI markers of chronic active lesions in multiple sclerosis (MS). However, the mechanism through which SELs affect brain volume loss in patients with MS remains unknown. Additionally, the prevalence and significance of SELs in Asian patients with MS remain unclear. This study aimed to investigate the association between SELs and no evidence of disease activity (NEDA)-3 status as well as brain volume loss in Japanese patients., Methods: A total of 99 patients with relapse-onset MS were retrospectively evaluated. SELs were identified on brain MRI based on local deformation when consecutive scans were registered longitudinally. We developed a logistic regression model and generalized linear mixed models (GLMMs) to evaluate the association between the number of SELs and disease activity and changes in brain volume., Results: During the observation period (2.0 ± 0.22 years), 35 patients developed at least one SEL. Multivariable logistic regression analysis showed that ≥2 SELs were associated with 0.2 times the risk of achieving a NEDA-3 status. GLMMs revealed that the number of SELs was negatively associated with volume changes in the cortex (p = .00169) and subcortical gray matter (p = .00964) after correction for multiple comparisons., Conclusion: SELs were identified in Japanese patients with MS during the 2-year observation period. The number of SELs is associated with disease activity and brain volume loss, suggesting that the number of SELs could be a biomarker of disease activity in MS., (© 2024 American Society of Neuroimaging.)

Progression independent of relapse activity (PIRA) is prevalent among Caucasian patients with relapsing and remitting multiple sclerosis (RRMS). However, there is limited knowledge regarding the characteristics of PIRA in Asian patients with RRMS. Therefore, we retrospectively analyzed the clinical and radiological progression of 95 Japanese patients with RRMS during a 2-year observation period. PIRA was observed in three patients who were characterized by young age, large T2 lesion volume, and great reduction in brain volume. Despite having highly active disease, fewer patients with PIRA (33.3%) were treated with high-efficacy drugs compared with those without disease activity (60.7%)., Competing Interests: Declaration of competing interest HY has received speaker honoraria from Biogen, Mitsubishi-Tanabe Pharma, Alexion Pharma Godo Kaisha, Chugai Pharma, and Novartis. YM has received speaker honoraria from Mitsubishi-Tanabe Pharma, Alexion Pharma Godo Kaisha, Chugai Pharma, and Novartis. MN has received speaker honoraria from Novartis Pharma, Biogen Japan, Mitsubishi Tanabe Pharma, Chugai Pharmaand Alexion Pharma Godo Kaisha. IN serves on the scientific advisory boards for Biogen Japan and Novartis Pharma and receives honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai, and has granted by the Japanese Ministry of Health, Labour, and Welfare Program Grant Number 23FC1009. TY has received personal fees from Mitsubishi Tanabe Pharma and Takeda, outside the submitted work; TY has a patent Takeda with royalties paid. The other authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD., Methods: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured., Results: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044)., Discussion: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.

Background: Neurodegenerative changes are observed in relapsing-remitting multiple sclerosis (RRMS) and are prominent in secondary progressive MS (SPMS). However, whether neurodegenerative changes accelerate and are altered after the transition into SPMS or in the presence of relapses remains uncertain., Methods: In this study, 73 patients with MS (seven with relapsing RRMS, 56 with relapse-free RRMS, and 10 with relapse-free SPMS) were evaluated for brain segmental volume changes over a 2-year follow-up period. Volume change was calculated using a within-subject unbiased longitudinal image analysis model., Results: The rates of brain volume change in the 11 brain regions evaluated were relatively similar among different brain regions. Moreover, they were similar among the relapsing RRMS, relapse-free RRMS, and SPMS groups, even after adjusting for age., Conclusions: The relatively constant brain segmental atrophy rate throughout the disease course, regardless of relapse episodes, suggests that RRMS and SPMS are continuous, uniform, and silent progressing brain atrophy diseases on a spectrum., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest to disclose for this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Exact causes and mechanisms regulating the onset and progression in many chronic diseases, including multiple sclerosis (MS), remain uncertain. Until now, the potential role of random process based on stochastic models in the temporal course of chronic diseases remains largely unevaluated. Therefore, the present study investigated the applicability of stochastic models for the onset and disease course of MS., Methods: Stochastic models with random temporal process in disease activity, underlying clinical relapse and/or subclinical brain atrophy, were developed. The models incorporated parameters regarding the distribution of temporal changes in disease activity and the drift constant., Results: By adjusting the parameters (temporal change dispersion and drift constant) and the threshold for the onset of disease, the stochastic disease progression models could reproduce various types of subsequent disease course, such as clinically isolated syndrome (monophasic), relapsing-remitting MS, primary-progressive MS, and secondary-progressive MS. Furthermore, the disease prevalence and distribution of onset age could be also reproduced with stochastic models by adjusting the parameters. The models could further explain why approximately half of the patients with relapsing-remitting MS will eventually experience a transition to secondary-progressive MS., Conclusion: Stochastic models with random temporal changes in disease activity could reproduce the characteristic onset age distribution and disease course forms in MS. Further studies by using real-world data to underscore the significance of random process in the occurrence and progression of MS are warranted., Competing Interests: Declaration of Competing Interest The author declares no conflict of interests to be disclosed for the present study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To determine which disease-modifying therapies should be used in patients with multiple sclerosis (MS), identifying patients at high and low risk for brain volume loss (BVL) is important. Although the BVL rate in MS is nearly constant from early to late disease onset, regardless of the disease stage, individual differences have been noted. Moreover, as disease duration increases, the risk of chronic progression increases, and brain atrophy becomes more noticeable. Therefore, measuring prognosis using a classification that considers BVL rate and disease duration is appropriate. We aimed to investigate the BVL in Japanese patients with MS., Methods: Herein, with an observational period of approximately 3.5 years, 82 Japanese patients with MS were included. The volumes and annualised volume changes (AVCs) of the grey matter (GM) and whole brain were evaluated using ico brain ms., Results: Whole-brain AVCs varied, especially among patients with a disease duration within approximately 16 years. Cluster analysis using two variables, disease duration and whole-brain AVC, identified the SM (short to middle duration and mild atrophy rates), SS (short to middle duration and severe atrophy rates), and L (long duration) groups. The optimal cut-off values for disease duration and whole-brain AVC to discriminate among the three groups were 15.8 years and -0.43%, respectively. Compared with the SM group, the SS group had higher Multiple Sclerosis Severity Scale (MSSS) and Expanded Disability Status Scale (EDSS) scores, lower information processing speed (IPS), higher lesion loads, higher whole-brain and GM volume loss, and higher GM atrophy rates. Moreover, among the 63 patients with MS included in the SM and SS groups, whole-brain AVCs were significantly correlated with the EDSS and MSSS scores and IPS., Conclusion: BVL rates vary, especially among Japanese patients with MS with short to middle disease duration, and BVL degree is associated with poor prognosis., Competing Interests: IN serves on scientific advisory boards for Biogen Japan and Novartis Pharma and receives honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. JF declares no conflicts of interest., (© 2024 The Authors.)

Background: A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established., Methods: To develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS-with either relapsing-remitting MS (86%) or secondary progressive MS (14%)-and 41 healthy controls were included in this longitudinal retrospective analysis over an observational period of approximately 3.5 years. Using a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis, we classified the pwMS into clusters., Results: At baseline and follow-up, pwMS were cross-sectionally classified into three major clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL. Among the patients included in Cluster 1 at baseline, approximately one-third of patients (12/52) transitioned into Cluster 2 at follow-up. The volumes of the corpus callosum, the thalamus, and the whole brain excluding the ventricles were significantly decreased in the transition group compared with the nontransition group and were found to be the most important predictors of transition., Conclusion: Decreased volumes of the corpus callosum and thalamus in the relatively early stage of MS may predict the development of BVL., Competing Interests: Declaration of Competing Interest IN is serving on scientific advisory boards for Biogen Japan and Novartis Pharma and is receiving honouraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. JF have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Enlargement of the choroid plexus (CP) is reported to associate with inflammatory activity and contribute to brain atrophy in patients with multiple sclerosis (pwMS). However, a recent study in healthy volunteers (HVTs) has suggested that CP enlargement can be attributed to ventriculomegaly., Objectives: To clarify the pathological significance of the enlargement of CP in multiple sclerosis (MS)., Methods: A total of 102 pwMS (89 with relapsing-remitting MS and 13 with secondary progressive MS) and 41 HVTs were cross-sectionally evaluated using brain volumetry. The CP volume was compared between disease groups and investigated for the relationships with other brain regional volumes., Results: CP volume was significantly larger in pwMS than in HVTs in the univariate analysis, but not in multivariable analysis. Meanwhile, the CP and lateral ventricle (LV) volumes were significantly correlated. CP enlargement was significantly associated with increased lesion load and cerebral white matter (WM) atrophy, even after adjusting for LV volume. In contrast, multivariable analyses revealed that LV enlargement, but not CP enlargement, was associated with total gray matter (GM) atrophy., Conclusion: CP enlargement was closely associated with LV enlargement. After adjusting for LV volume, CP enlargement in pwMS was associated with increased lesion load and WM atrophy but not GM atrophy., Competing Interests: Declaration of Competing Interest I. Nakashima serves on the scientific advisory boards for Biogen Japan and Novartis Pharma and receives honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. T. Akaishi and J. Fujimori have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Impaired cognitive processing speed is among the important higher brain dysfunctions in multiple sclerosis (MS). However, the exact structural mechanisms of the dysfunction remain uncertain. This study aimed to identify the brain regions associated with the impaired cognitive processing speed in MS by comparing the cognitive processing speed, measured using the Cognitive Processing Speed Test (CogEval) z-score, and brain regional volumetric data. Altogether, 80 patients with MS (64 with relapsing-remitting MS [RRMS] and 16 with secondary progressive MS [SPMS]) were enrolled. Consequently, CogEval z-scores were worse in patients with SPMS than in those with RRMS (p=0.001). In the univariate correlation analyses, significant correlations with CogEval z-score were suggested in the MS lesion volume (p<0.001; Spearman's rank correlation test) and atrophies in the cerebral cortex (p=0.031), cerebral white matter (p=0.013), corpus callosum (p=0.001), thalamus (p=0.001), and putamen (p<0.001). Multiple linear regression analysis revealed that putamen atrophy was significantly associated with CogEval z-score (p=0.038) independent of volume in other brain regions, while thalamic atrophy was not (p=0.79). Univariate correlation analyses were further performed in each of RRMS and SPMS. None of the evaluated volumetric data indicated a significant correlation with the CogEval z-score in RRMS. Meanwhile, atrophies in the cerebral white matter (p=0.008), corpus callosum (p=0.002), putamen (p=0.011), and pallidum (p=0.017) demonstrated significant correlations with CogEval z-score in SPMS. In summary, the putamen could be an important region of atrophy contributing to the impaired cognitive speed in MS, especially in the later disease stages after a transition to SPMS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Akaishi et al.)

To evaluate B-cell involvement in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 11 patients with CIDP, 8 patients with Guillain-Barré syndrome and 13 patients with idiopathic normal pressure hydrocephalus (iNPH) were studied. CSF cytokine and chemokine (IL-10, IL-15, TNF-α, TGF-β1, GM-CSF, BAFF, CXCL10, and CXCL13) levels were measured by ELISA. The CSF CXCL13 level was significantly higher in patients with CIDP than in those with iNPH. The CSF CXCL13 level was significantly higher in CIDP patients with higher annualized relapse rates and higher modified Rankin scale scores. The CSF CXCL13 level is elevated in CIDP, especially in those with higher disease activity., Competing Interests: Declaration of Competing Interest IN serves on the scientific advisory boards for Biogen Japan and Novartis Pharma and receives honouraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. RM, JF and YA have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Electrolyte disorders are among the important conditions negatively affecting the disease course of neuromyelitis optica spectrum disorder (NMOSD). Possible mechanisms may include renal tubular acidosis (RTA) accompanying Sjögren's syndrome (SS), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and central diabetes insipidus (DI). Currently, the overlap profiles between these conditions remain uncertain., Methods: This cross-sectional study collected data from the nationwide administrative Diagnosis Procedure Combination (DPC) database and evaluated the overlap profiles., Results: Among the 28,285,908 individuals from 1203 DPC-covered hospitals, 8477 had NMOSD, 174108 had SS, 4977 had RTA, 7640 had SIADH, and 24,789 had central DI. Of those with NMOSD, 986 (12%) had SS. The odds ratio (OR) for a diagnosis of NMOSD in those with SS compared with those without was 21 [95% confidence interval (CI), 20-23]. Overlap between NMOSD and SS was seen both in males (OR, 28 [95% CI, 23-33]) and females (OR, 16 [15-17]) and was more prominent in the younger population. Among patients with SS, the prevalence of RTA was lower in patients with NMOSD compared with those without NMOSD. Patients with NMOSD showed a higher prevalence of SIADH (OR, 11 [7.5-17]; p < 0.0001) and DI (OR, 3.7 [2.4-5.3]; p < 0.0001). Comorbid SS in NMOSD was associated with a higher prevalence of DI., Conclusions: Patients with NMOSD are likely to have SS, SIADH, and central DI. RTA in SS does not facilitate the overlap between NMOSD and SS. SS in NMOSD may predispose patients to DI., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A few case reports have described patients with myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelinating syndrome who presented with symptoms of aseptic meningitis. All such patients required immunotherapy. We report a patient with MOG-Ab-associated disorder (MOGAD) who presented with symptoms of aseptic meningitis and improved without treatment., Case: A 13-year-old girl presented with fever, headache, decreased appetite, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and magnetic resonance imaging (MRI) showed leptomeningeal enhancement. The patient was diagnosed with aseptic meningitis at admission. However, there were no signs of recovery 4 days after admission (i.e., 8 days after disease onset). Therefore, we performed extensive investigations to identify the cause of the underlying infection and inflammation. On day 14 after admission, the serum MOG-Ab test performed at admission came back positive (1:128) and she was diagnosed with MOGAD. She was discharged on day 18 after admission, because her symptoms, CSF pleocytosis, and MRI findings had improved. About 6 weeks after discharge, MRI revealed hyperintensity without gadolinium enhancement. However, her serum MOG-Ab test was negative. We did follow-ups for 11 months but found no new neurological symptoms., Discussion and Conclusion: To the best of our knowledge, this is the first ever report of a pediatric patient with MOGAD experiencing spontaneous remission with no demyelinating symptoms during an extended follow-up period., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p < 0.0001), monocyte count (p = 0.0191), MLR (p = 0.0320), and NLR (p = 0.0002) than those of MOGAD-matched volunteers (n = 130). The three demyelinating diseases showed similar levels of the total and differential WBC counts; however, MOGAD and MS showed different structures in the hierarchical clustering and distributions on a two-dimensional canonical plot using differential WBC counts from the other three groups. WBC count profiles were similar in patients with MOGAD and MS but differed from profiles in matched volunteers or patients with AQP4-NMOSD., (© 2023. The Author(s).)

Background: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted., Objective: We examined the epidemiology and clinical features of MOGAD in Japan., Methods: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurology, pediatric-neurology, and neuro-ophthalmology facilities throughout Japan., Results: In total, 887 patients were identified. The estimated number of total and newly diagnosed MOGAD patients was 1,695 [95% confidence interval (CI): 1483-1907] and 487 (95% CI: 414-560), respectively. The estimated prevalence and incidence were 1.34/100,000 (95% CI: 1.18-1.51) and 0.39/100,000 (95% CI: 0.32-0.44), respectively. The median age at onset was 28 years (range: 0-84 years). At onset, optic neuritis was present in approximately 40% of patients, irrespective of the onset age. Acute disseminated encephalomyelitis was more frequent in younger patients, whereas brainstem encephalitis, encephalitis, and myelitis were more frequent in elderly patients. Immunotherapy was highly effective., Conclusion: The prevalence and incidence rates of MOGAD in Japan are similar to those in other countries. Notable characteristics such as the preferential occurrence of acute disseminated encephalomyelitis in children exist; however, general characteristics including symptoms and treatment response are common irrespective of the onset age.

Objectives: Neurological disabilities, especially physical issues, can adversely affect the daily lives of people with multiple sclerosis (MS) and negatively impact their health-related quality of life (HRQOL). On the other hand, physical and psychiatric symptoms are variable in people with MS, and QOL can be influenced by cultural and educational background. This study aimed to evaluate the association of HRQOL with disabilities, fatigue, and depression in Japanese subjects with MS., Methods: Evaluation of HRQOL, fatigue, and depression was performed in 184 Japanese individuals with MS, using the Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II), respectively., Results: Multiple linear regression analysis demonstrated negative correlations of the Expanded Disability Status Scale (EDSS) with scores on the FAMS subscales of mobility, symptoms, thinking and fatigue, total FAMS, and additional concerns. The FSS score had negative correlations with mobility, symptoms, emotional well-being, thinking and fatigue, total FAMS, and additional concerns. There were negative correlations between BDI-II scores and all items of FAMS., Conclusions: HRQOL had relatively close correlations with disabilities and fatigue, and depression had an especially close relationship with HRQOL., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Chest discomfort is the representative symptom of dangerous coronary artery disease (CAD), but rarely occurs in patients with seizures. We treated a 74-year-old man with right mesial temporal lobe epilepsy and amygdala enlargement, who was initially suspected of CAD and underwent repeated cardiac angiography because of recurrent episodes of paroxysmal chest discomfort starting from 68 years old. He visited an epileptologist and underwent long-term video electroencephalography monitoring (LTVEM), which confirmed right temporal seizure onset during a habitual episodes of "chest discomfort," stereotyped movement of chest rubbing with the right hand, followed by impaired conscousness. Brain magnetic resonance imaging revealed right amygdala enlargement. The present case emphasizes the importance of the wide range of symptoms, such as chest discomfort, which may associated with epielpsy and result in a delayed diagnosis. LTVEM is useful for diagnosis of epilepsy with unusual seizure semiology by recording ictal EEG changes during chest discomfort., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Retinal atrophy in the chronic phase of optic neuritis (ON) in anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear., Methods: Patients with these diseases were repeatedly evaluated using optical coherence tomography (OCT) for the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) in the ON-involved eyes during relapse-free period after the first ON episode before relapse. Optic MRI with short tau inversion recovery (STIR) sequences was further evaluated retrospectively., Results: Twelve patients with MOGAD (20 eyes with ON-involvement) and 14 with AQP4-Ab-positive NMOSD (16 eyes with ON-involvement) were enrolled. The progression of retinal atrophy ≥12 months after onset was observed in AQP4-Ab-positive NMOSD, but was not apparent in MOGAD. A decrease in retinal thickness by the same amount results in more severe visual impairment in AQP4-Ab-positive NMOSD. On optic MRI, the residual STIR hyperintensity in the optic nerves remained in the chronic phase in almost all eyes with ON in both diseases. Optic nerve atrophy occurred in all evaluated ON-involved eyes in AQP4-Ab-positive NMOSD, while it was observed in half of ON-involved eyes in MOGAD., Conclusions: Progression of retinal atrophy in the chronic phase has been observed in patients with AQP4-Ab-positive NMOSD, while it remains uncertain in patients with MOGAD. The visual impairments upon similar levels of retinal atrophy would be worse in AQP4-Ab-positive NMOSD, possibly attributable in part to a higher incidence of optic nerve atrophy in this disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD)., Methods: In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments., Results: Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined., Conclusions: The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases., (© 2021. The Author(s).)

Background: Two-dimensional (2D) measures have been proposed as potential proxy measures for whole-brain volume in multiple sclerosis (MS); however, cut-off values that determine the degree of brain volume loss (BVL) have not been established. Since we had previously developed a system to categorize MS patients into clusters with significantly different degrees of BVL, we tried to identify cut-off values for 2D measurements that can discriminate MS patients on the basis of disease severity associated with brain atrophy., Methods: In this cross-sectional analysis, ninety-one consecutive Japanese MS patients-clinically isolated syndrome (5%), relapsing-remitting MS (78%) and progressive MS (17%)-were categorized into two clusters (CL1 and CL2) with a significantly different degree of BVL using the method described in our previous study. MS patients were also evaluated for 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), bicaudate ratio (BCR), and corpus callosum index (CCI). Thereafter, we performed receiver operating characteristic analysis to determine the cut-off values of the 2D measurements for categorizing the MS patients into two clusters., Results: We identified optimal cut-off values for each 2D measure with high specificity and sensitivity. The cut-off values for LVW, BCR, and CCI divided the MS patients into two subgroups, in which whole-brain and grey matter volume, EDSS, and processing speed were significantly different., Conclusion: LVW, BCR, and CCI with particular cut-off values are useful to discriminate MS patients with decreased brain volume, physical disability, and processing speed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Two-dimensional (2D) measures have been proposed as potential proxies for whole-brain volume in multiple sclerosis (MS)., Objective: To verify whether 2D measurements by routine MRI are useful in predicting brain volume or disability in MS., Methods: In this cross-sectional analysis, eighty-five consecutive Japanese MS patients-relapsing-remitting MS (81%) and progressive MS (19%)-underwent 1.5 Tesla T1-weighted 3D MRI examinations to measure whole-brain and grey matter volume. 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), brain width, bicaudate ratio, and corpus callosum index (CCI), were obtained from each scan. Correlations between 2D measurements and 3D measurements, the Expanded Disability Status Scale (EDSS), or processing speed were analysed., Results: The third and lateral ventricle widths were well-correlated with the whole-brain volume ( p  < 0.0001), grey matter volume ( p  < 0.0001), and EDSS scores ( p  = 0.0001, p  = .0004, respectively).The least squares regression model revealed that 78% of the variation in whole-brain volume could be explained using five explanatory variables, namely, LVW, CCI, age, sex, and disease duration. By contrast, the partial correlation coefficient excluding the effect of age showed that the CCI was significantly correlated with the EDSS and processing speed ( p  < 0.0001)., Conclusion: Ventricle width correlated well with brain volumes, while the CCI correlated well with age-independent (i.e. disease-induced) disability., Competing Interests: Declaration of conflicting interests: IN is serving on scientific advisory boards for Biogen Japan and Novartis Pharma and is receiving honouraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. JF and SA report no disclosure., (© The Author(s), 2022.)

Background: This study aimed to evaluate the association between cognitive impairment and health-related quality of life (HRQOL), fatigue, and depression in Japanese patients with multiple sclerosis (MS)., Methods: The Brief International Cognitive Assessment for MS (BICAMS) was performed in 184 Japanese patients with MS. The Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II) were used to evaluate HRQOL, fatigue, and depression, respectively., Results: Multiple linear regression analysis demonstrated positive correlations of the Symbol Digit Modalities Test (SDMT) with the scores on the FAMS subscales of mobility, symptoms, emotional well-being, and additional concerns and with the total FAMS score even after controlling for the Expanded Disability Status Scale score, age at examination, and duration of education. The SDMT score in the BICAMS battery had negative correlations with the BDI-II score, as revealed by multiple linear regression analysis. None of the three tests in the BICAMS had any correlation with the FSS score., Conclusion: The SDMT has a significant relationship with HRQOL and depression in Japanese patients with MS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Vaccine administration may be involved in the development of some central nervous system demyelinating diseases. The COVID-19 vaccine is being administered to the entire population, but to date, little association between vaccination and the risk of developing multiple sclerosis (MS) has been suggested, and only a few case reports have been published. Here, we present a 40-year-old woman who developed cervical myelitis after receiving the COVID-19 vaccine. Myelitis was considered the initial clinical manifestation of MS. Our case suggests a possible link between the vaccination and the clinical MS attack., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p < 0.0001), monocyte (p < 0.0001), basophil (p = 0.0027), and neutrophil (p < 0.0001) counts were higher in the MS group than in the HC group, whereas the lymphocyte and eosinophil counts did not differ. Adjustments for the smoking status and body mass index yielded the same results. The total and differential WBC counts of the patients with MS did not correlate with the counts of T2 hyperintense brain lesions or the levels of neurological disturbance. In summary, patients with MS showed elevated counts of total WBCs, monocytes, basophils, and neutrophils at the time of diagnosis. However, the clinical relevance of these biomarkers in the context of the development and progression of MS remains unclear., (© 2021. The Author(s).)

Introduction: Optic neuritis (ON) is a major phenotype of clinical attack related to demyelinating neurological diseases of the central nervous system, including multiple sclerosis (MS), anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). As the concept of MOGAD is relatively new, the long-term visual outcomes after ON in MOGAD remains unclear., Methods: To elucidate the long-term visual prognosis after ON in MOGAD, patients with MOGAD whose visual acuity were regularly followed for more than 5 years from the onset of ON were enrolled. Best-corrected visual acuity (BCVA) at nadir in the acute phase and at 1 and 5 years from onset was evaluated. The data from patients with MOGAD were compared with those from patients with MS or anti-AQP4-positive NMOSD., Results: Twenty-three patients (31 ON-involved eyes) with MOGAD, 20 patients (24 ON-involved eyes) with MS, and 22 patients (24 ON-involved eyes) with anti-AQP4-positive NMOSD were evaluated. All BCVA at nadir, 1 year, and 5 years from the onset of ON were much worse in anti-AQP4-positive NMOSD than in MS (p = 0.0024) and MOGAD (p = 0.0014) patients. In MOGAD and anti-AQP4-positive NMOSD, the serum disease-specific antibody titer was not associated with the subsequent visual prognosis. Visual acuity had almost fully recovered spontaneously or shortly after initiating acute treatment in 22 of the 23 patients with MOGAD-ON. The administration of high-dose intravenous steroid therapy further facilitated early recovery of visual acuity. Meanwhile, a small fraction of patients with extensive optic nerve lesions involving the chiasma irreversibly experienced severe visual impairment despite appropriate acute treatment., Conclusion: Although a small fraction of patients with MOGAD who presented with extensive optic nerve lesions experienced irreversible severe visual impairment, the long-term visual outcomes after 5 years from ON in patients with MOGAD were generally as good as that in patients with MS and much better than that in patients with anti-AQP4-positive NMOSD., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To evaluate the degree of neuroaxonal injury in Japanese multiple sclerosis (MS) patients using serum neurofilament light (sNfL) and to investigate the relationship of sNFL with the degree of brain volume., Methods: sNfL levels in 82 consecutive Japanese MS patients in remission were cross-sectionally evaluated using a single molecule array assay. Within this sample, cross-sectional volumetric brain MRI data was evaluated in 80 patients, and longitudinal data was evaluated in 63 patients., Results: MS patients (female/male = 61/21), including those with relapsing-remitting MS (82%), secondary progressive MS (17%), and primary progressive MS (1%), were studied. The mean age of the patients was 41.2 ± 8.7 years, and 77 of the MS patients (94%) were treated with disease-modifying therapy (DMT). Their median sNfL level was 7.985 (IQR, 5.959-10.9), and their sNfL levels were significantly correlated with their grey matter volume and their age. A standard least squares regression model revealed that approximately 57% of the variation in grey matter volume could be explained by a regression equation using three explanatory variables: sNfL concentration, age, and sex. Moreover, the sNfL level multiplied by disease duration was significantly correlated with the Expanded Disability Status Scale (EDSS) scores and whole and grey matter volumes., Conclusion: Although neuroaxonal injury appeared to be mild in our Japanese MS patients, their sNfL levels significantly reflected grey matter volume. Moreover, when multiplied by the disease duration, sNfL can reflect disability and brain volume., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To elucidate the differences in the source and in the level of intrathecal synthesis between anti-aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)., Methods: Thirty-eight patients with MOG-IgG-associated disease and 36 with AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients., Results: Eleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG-positive cases and 43.8% of AQP4-IgG-positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability., Conclusions: Intrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG-associated disease and AQP4-IgG-positive NMOSD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)