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Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.3 (AARS2_v001):c.1145C>A and NM_020745.3 (AARS2_v001):c.2255+1G>A was identified. Neither of the mutations has been previously reported, and this is the first report of alanyl-transfer RNA synthetase 2 mutation in Asia. We anticipate that further studies of the molecular basis of leukodystrophy will provide insight into its pathogenesis and hopefully lead to sophisticated diagnostic and treatment strategies.

ObjectiveTo clarify functional alterations of follicular helper T cells (Tfh) in myasthenia gravis (MG) because Tfh play important roles in helping B cells generate antibody-producing cells.MethodsA total of 24 immunotherapy-naive patients with anti–acetylcholine receptor (AchR) antibody–positive MG and 18 age-matched healthy subjects (HS) were enrolled. Samples from 6 patients were available for posttreatment analysis. Subsets of circulating Tfh (cTfh) and B cells were identified by flow cytometry analysis of surface molecules. Cytokine production by isolated cTfh subsets from 5 patients with MG and 5 HS was measured in vitro. Analysis was performed to examine the correlation between the frequency of cTfh subsets and that of plasmablasts and between cTfh subsets and the quantitative MG score.ResultscTfh increased with elevated expression of inducible T-cell costimulator (ICOS) in patients with MG. cTfh shifted to Th2 and Th17 over Th1 in MG. ICOShighcTfh produced significantly higher levels of interleukin (IL)-21, IL-4, and IL-17A than ICOSlow cTfh only in patients with MG. The frequency of cTfh within CD4 T cells was more closely associated with disease severity than the serum anti-AchR antibody titer and frequency of plasmablasts within B cells. Abnormalities of cTfh were improved after immunotherapy in parallel with clinical improvement.ConclusionsAlternation of cTfh is a key feature in the development of MG and may become a biomarker for disease severity and therapeutic efficacy.Classification of EvidenceThis study provides Class II evidence that the level of cTfh is associated with disease severity in patients with MG.

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01-1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00-1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01-11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.

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Background: Multiple sclerosis (MS) is a relapsing, inflammatory, and demyelinating disease of central nervous system showing marked clinical heterogeneity. Many factors might influence the choice of relapse prevention drug, and treatment response varies among patients. Despite the enlargement of disease-modifying drugs for MS (MS-DMDs), some patients have been treated with corticosteroid and/or immunosuppressant (CS/IS).Objective: To clarify the radiological and laboratory features of MS treated with CS/IS for relapse prevention.Methods: Clinical records including radiological and laboratory findings, and drugs used for relapse prevention were reviewed retrospectively.Results: Out of 92 consecutive MS patients, 25 (27%) were treated with CS/IS. The followings were observed less frequently in patients treated with CS/IS than in those with MS-DMDs: three or more periventricular lesions, ovoid lesions, subcortical lesions, typical contrast-enhancing lesions, negative for serum autoantibodies, and positive for oligoclonal bands in the cerebrospinal fluid. Multiple logistic regression analysis revealed that the absence of typical contrast-enhancing lesions and positivity for serum autoantibodies were independent factors associated with CS/IS prescription (odds ratio 25.027 and 14.537, respectively).Conclusion: In this cohort of Japanese patients clinically diagnosed with MS, radiological and serological findings atypical of MS were observed more frequently in patients treated with CS/IS than in those with MS-DMDs as a part of MS therapy. The absence of contrast-enhancing lesions typical of MS and positivity for serum autoantibodies were independent factors strongly associated with CS/IS use.

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