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Background: No previous study has examined the effect of dual-task training using changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) as an outcome. Objective: This study aimed to examine the effects of simultaneous dual-task training of exercise and cognitive tasks on rCBF using SPECT in older adults with amnestic mild cognitive impairment (aMCI). Methods: In this non-randomized control trial, 40 older adults with aMCI participated from May 2016 to April 2018. Outpatients in the intervention group (n = 22) underwent 24 sessions (12 months) of dual-task training twice a month for 60 mins per session. Participants in the control group (n = 18) continued to have regular outpatient visits. The primary outcome was rCBF at baseline and after 12 months, which was compared in each group using the two-sample t-test. The secondary outcomes were the rate of reversion and conversion from aMCI after 12 months. Results: Of the 22 participants in the intervention group, six dropped out; therefore, 16 were included in the analysis. The intervention group showed more significant increases in rCBF in multiple regions, including the bilateral frontal lobes, compared with the control group. However, the rates of reversion or conversion from mild cognitive impairment (MCI) were not significantly different. Conclusions: Dual-task training for older adults with aMCI increased rCBF in the frontal gyrus but did not promote reversion from MCI to normal cognition. Future intervention studies, such as follow-up examinations after the intervention, are warranted to consider long-term prognosis.

Background Homeless persons are those who carry out their activities of daily living in city parks and other facilities. Little is known about homeless patients with lung cancer in Japan. Therefore, we characterized the clinical features and outcomes of homeless people in metropolitan Tokyo. Methods Between January 2014 and August 2018, 2,068 homeless patients were admitted to the homeless patient care unit at Tokyo Saiseikai Central Hospital. Of these, 13 patients were treated for primary lung cancer. We retrospectively analyzed the patients' clinical characteristics, including their age, gender, treatment, and outcome, obtained from the hospital's electronic medical records. Results A total of 13 patients were treated for lung cancer. The median age was 66.2 (range, 51-77) years old. Twelve patients (92.3%) were smokers. All of the patients were men and had advanced lung cancer. Of these, four patients had adenocarcinoma, four had squamous carcinoma, and four had other histologies. Ten patients received chemotherapy, and 3 received chemoradiotherapy (carboplatin, n=8; cisplatin, n=2, immune check point inhibitor, n=2; other, n=1). Of the patients on first-line treatment, 58% discontinued treatment, with 71% doing so willfully. The median overall survival was 7.5 (1-44) months. During the study, nine patients died in the hospital, and four were lost to follow up. Conclusion It is difficult for homeless patients to continue chemotherapy, and they often quit therapy willfully. Therefore, it is necessary to develop an education and health insurance support system to ensure treatment continuity in a good social environment.

Several outbreaks of trench fever caused by Bartonella quintana, occurred in soldiers during World Wars I and II. Although the number of trench fever cases has been decreasing worldwide, the disease has been reported among the homeless population in both developing and developed countries. The current prevalence of B. quintana infection in Japan is unclear. We collected blood and body louse (Pediculus humanus humanus) samples from homeless inpatients who had body lice at the time of emergency hospitalization in Tokyo from January 2013 to March 2015. Patients were tested for B. quintana infections using culture method, polymerase chain reaction, and indirect immunofluorescence assay (IFA). Among the 29 patients tested, the presence of Bartonella spp. was confirmed by genomic sequencing of DNA extracted from the samples from 2 patients (blood culture performed for 13 out of 15 patients), and from body louse samples of 20 patients (69%). Immunoglobulin G against B. quintana was detected in 10 patients (34.5%) at a cut-off titer of 1:256 in IFA. B. quintana infection was detected in samples obtained between 2013 and 2015 in Tokyo and needs to be on the list of differential diagnoses performed for febrile homeless individuals.

Introduction: The regional cerebral blood flow (rCBF) distribution can affect brain functioning, leading to amnestic mild cognitive impairment (aMCI) and mild Alzheimer disease (AD). This study aimed to clarify the detailed characteristics of rCBF distribution in patients with mild AD and aMCI. Methods: This cross-sectional study from April 2015 to March 2018 included 103 older adults (mean age 78.9 years; 60% females), out of a total of 302 adults, and categorized them into 3 groups according to cognitive symptoms. The normal control (NC), aMCI, and mild AD groups included 20, 50, and 33 participants, respectively. The primary outcome was rCBF, which was compared among the 3 groups using a 2-sample t test without correction for multiple comparisons. Results: In the aMCI group, the rCBF decreased in the bilateral parietal and left frontal association cortex and the bilateral premotor cortex (p < 0.01) but increased in the bilateral cerebellum (p < 0.01). In the mild AD group, the rCBF decreased in the bilateral parietal and occipital association cortex, the bilateral premotor cortex, the left temporal and frontal association cortex, and the left limbic lobe (p < 0.01). Conversely, the rCBF increased in some parts of the cerebellum, the bilateral frontal and temporal association cortex, the left occipital association cortex, and the right premotor cortex (p < 0.01). Conclusion: Based on the analysis of the values obtained, it was inferred that the rCBF undergoes reduction and elevation in aMCI and AD patients.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a hemizygous mutation of the ABCD1 gene. Patients with ALD show progressive central nervous system demyelination and primary adrenal insufficiency. In Japan, most reported ALD cases were childhood-onset, and only one case of an adult patient with Addison's disease form of ALD has ever been reported. Herein, we present a case of a 29-year-old man with Addison's disease form of ALD. The patient had anorexia, weight loss, and skin pigmentation from 18 years of age. At first visit, his weight had decreased by 12 kg from 57 kg when he was 15 years old. Endocrinological examination showed low serum cortisol (1.2 μg/dL) with high plasma ACTH (4,750 pg/mL), and abdominal computed tomography showed normal adrenal glands. Very-long-chain fatty acid (VLCFA) levels were elevated, and the ABCD1 mutation, p.Gly116Arg, was identified in hemizygous state. He had no significant neurological findings on physical examination and no white matter lesions on brain magnetic resonance imaging (MRI). He was diagnosed with ALD presenting as Addison's disease, and glucocorticoid replacement therapy was initiated. Four years after the diagnosis, he still did not show any neurological findings and any white matter lesions on brain MRI. Evaluating VLCFA levels for ALD diagnosis is important in young adult men with idiopathic primary adrenal insufficiency as well as in children. Early diagnosis enables more rational approaches including the early detection of neurological complications and might improve the prognosis of patients.

Immunotherapy using immune checkpoint inhibitors (ICIs) has improved the prognosis of many cancers, including lung cancer. The mechanisms of development of immune-related adverse events (irAEs) after treatment with ICIs are not completely understood. Because ICIs can exacerbate opportunistic infections by altering immune conditions, potential opportunistic infections such as those caused by Epstein–Barr virus (EBV) may be involved in the development of irAEs. However, there is a lack of clinical findings that indicate the relationship between irAEs and potential opportunistic infections. Herein, we present the case of a 67-year-old man with advanced lung adenocarcinoma who developed encephalitis after the third cycle of pembrolizumab administration. Polymerase chain reaction using cerebrospinal fluid and blood samples revealed positive results for EBV. An autopsy examination revealed lymphocyte infiltration in the area surrounding the EBV-infected cells in the brain. Our case suggests that immune reconstitution occurred after the administration of ICIs, followed by an enhanced immune response to EBV that resulted in fatal encephalitis. Additional findings regarding the interaction between irAEs and opportunistic infections should be acquired to confirm this speculation.

We herein report a 70-year-old man with recurrent multiple cerebral infarctions under warfarin therapy who was finally diagnosed with Trousseau's syndrome resulting from advanced bladder cancer. A histological examination of the mesenteric lymph nodes revealed metastasis of micropapillary urothelial cancer with positive mucin markers CA125 and MUC1. Blood examinations also indicated elevated tumor markers, such as CA19-9 and CA125. To our knowledge, this is the first report of Trousseau's syndrome in a patient with bladder micropapillary urothelial cancer in which mucin involvement was clearly proven by histological and serological examinations.

Several outbreaks of trench fever caused by Bartonella quintana occurred in soldiers during World Wars I and II. Although trench fever cases have been decreasing worldwide, the disease was reported among the homeless population in developing and developed countries. The current prevalence of B. quintana infection in Japan is unclear. Blood and body louse (Pediculus humanus humanus) samples were obtained from homeless inpatients with body lice during emergency hospitalization in Tokyo from January 2013 to March 2015. Patients were tested for B. quintana infections using the culture method, polymerase chain reaction, and indirect immunofluorescence assay (IFA). Among the 29 patients tested, the presence of Bartonella spp. was confirmed by genomic sequencing of DNA extracted from two samples from blood culture performed for 15 out of 29 patients and from body louse samples of 20 patients (69%). Immunoglobulin G against B. quintana was detected in 10 patients (34.5%) at a cut-off titer of 1:256 in IFA. B. quintana infection was detected in samples obtained between 2013 and 2015 in Tokyo and needs to be on the list of differential diagnoses performed for febrile homeless individuals.

Highlights • HvKP caused breakthrough and persistent bacteremia on an immunocompetent patient. • This is the first reported case of spondylitis due to HvKP. • A combination of CTRX and GM might be recommended for HvKP bacteremia., Herein, we report a case of breakthrough and persistent bacteremia due to serotype K1 Klebsiella pneumoniae in an immunocompetent 53- year-old man. He was diagnosed with pyogenic spondylitis owing to back pain and based on magnetic resonance imaging findings. On admission, several imaging studies were taken to search for other abscesses and infective endocarditis; however, there were no significant findings. Additionally, blood cultures were negative. Upon treatment with intravenous ampicillin/sulbactam, the patient’s symptoms improved. However, eleven days after admission, the patient experienced a fever and worsening back pain. Blood cultures were taken again, and K. pneumoniae was detected, which showed sensitivity to ampicillin/sulbactam. Fourteen days after admission, K. pneumoniae was detected again, suggesting breakthrough and persistent bacteremia with K. pneumoniae. The source of the K. pneumoniae infection was unknown. The antimicrobial regimen was changed to a combination of ceftriaxone and gentamicin. Sixty days after admission, the patient was discharged without any sequelae. The isolated K. pneumoniae strains were found to carry rmpA and were confirmed as serotype K1; thus, detected hypervirulent K. pneumoniae (HvKP). HvKP is an increasingly recognized pathotype of K. pneumoniae characterized clinically by its ability to cause organ- or life-threatening infections in healthy persons. To the best of our knowledge, our case is the first report of spondylitis due to confirmed HvKP. Moreover, HvKP caused breakthrough and persistent bacteremia on an immunocompetent patient.

Background: Patients undergoing anticoagulation therapy often experience intracerebral hemorrhages (ICHs), and warfarin in particular is known to increase hematoma expansion in ICHs, which results in a poor outcome. Recent studies reported that, in comparison with warfarin, direct oral anticoagulants (DOACs) cause fewer ICHs with better functional outcome. However, since it is still unknown whether DOACs are associated with a smaller hematoma volume of ICHs, we aimed to compare the volume, hematoma expansion, and outcomes associated with ICHs treated with DOACs and warfarin. Methods: We performed a prospective multicenter cross-sectional study. The subjects included patients with acute ICHs who received either DOACs or warfarin. We evaluated the clinical characteristics, and measured initial and follow-up ICH volumes. The volume of ICHs and hematoma expansion were compared between the DOAC and warfarin groups. Mortality and modified Rankin score at discharge were evaluated as outcomes. Results: There were 18 patients in the DOAC group and 71 in the warfarin group. The baseline characteristics were similar between the 2 groups. Initial median hematoma volume of ICHs in the DOAC group was significantly lower than that in the warfarin group (6.2 vs. 24.2 mL, respectively; p = 0.04). In cases involving follow-up computed tomography scanning, the median hematoma volume of ICHs at follow-up was lower in the DOAC group than in the warfarin group (initial: DOACs 4.4 vs. warfarin 13.5 mL; follow-up: 5.0 vs. 18.4 mL, respectively; p = 0.05). Further, the hematoma in ICHs associated with DOACs did not expand. Although the mortality of ICHs associated with DOACs (11%) was lower than that associated with warfarin (24%), this difference was not statistically significant. The univariate analysis showed that the anticoagulant type (DOACs vs. warfarin) and sex (male vs. female) were associated with ICH volume. The multivariable linear regression showed that the use of DOACs (compared to warfarin; β: –0.23, p = 0.03) and female sex (compared to male; β: –0.25, p = 0.02) were associated with a small hematoma volume. Conclusions: Based on the results of the present study, in terms of the risks associated with ICHs, the use of DOACs appears to be safer than warfarin for anticoagulation therapy. Further studies are required to validate these findings.

TIAを含めた虚血性脳血管障害で入院後,発症30日以降経過観察された296例(平均観察期間780.8日)の脳血管障害再発は48例(脳梗塞42例,脳出血6例)であった.累積再発率は1年8.5%,2年14.1%,3年20.0%,4年26.1%であった.臨床病型別では再発率に差は認めなかった.高血圧,脳血管障害の既往,経過観察中拡張期血圧が75mmHg以下あるいは86mmHg以上,抗血小板薬非内服,抗凝固薬内服,HbAlc6.2%以上で再発が多かった.再発臨床病型は入院時と同じ臨床病型が多かった.脳出血で再発した6例中6例全例で高血圧があり,5例では入院時臨床病型がラクナ梗塞,2例で脳出血の既往,5例で抗血栓薬内服が認められた.

CVM has been applied to measure the value of non-market goods including natural environment. It has been known that measuring values by CVM tends to involve a number of biases. Consequently the NOAA's guidelines were proposed for measuring values without biases by CVM. However, the validity of the guidelines has not been clearly tested. In the present study, we replicated the CVM survey designed according to the guidelines by Kuriyama et al. for measuring values of natural environment in Yakushima-Island, and analyzed cognitive decision making processes based on a verbal-protocol method. The analysis indicated that it is not easy at all to measure value without any biases by CVM designed according to the NOAA's guidelines.

記憶障害で発症し経過中に多幸的言動が見られた右尾状核頭部出血の一例を経験した.症例は54歳男性, 記憶障害を主訴として来院した.神経学的には著明な短期記憶の障害, 失見当識を認める以外は明らかな所見はなかった.頭部CTで右尾状核頭部出搬を認めた.入院中に多幸的な言動も見られ, 記憶障害の軽快と共にこれらの症状も軽快した.123I-SPECTで右側頭葉内側に集積の低下が見られ, 記憶障害, 多幸的言動の出現に尾状核頭部自体の障害, 尾状核と側頭葉の問のdiaschisis様の機序の関与が考えられた.

Objectives We have often observed silent subcortical brain lesions on CT or MRI in first-ever ischemic stroke, but there is little published information on the relationship of these lesions to stroke subtypes. Here, we describe the incidence of MRI-detected silent subcortical brain lesions, including infarctions and white matter lesions, in a series of patients with first-ever ischemic stroke classified according to stroke subtypes. We also discuss the pathogenesis of these silent subcortical lesions. Patients We evaluated 171 patients with acute first-ever ischemic stroke. Methods The subjects were divided into three groups: lacunar, atherothrombotic and cardioembolic infarction groups. We evaluated silent subcortical brain infarction (SSBI), enlargement of perivascular space (EPS), and other white-matter lesions using MRI. Results Hypertension was observed in 67.6% of lacunar infarction, 57.1% of atherosclerotic infarction, and 54.1% of cardioembolic infarction. SSBI was more frequently observed in lacunar infarction than the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 81.5% vs. 44.4% vs. 42.1%, p=0.006). High-grade EPS (grade 2 or higher) was also observed more frequently in lacunar infarction than in the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 63.3% vs. 24.2% vs. 0%, p

Purpose and methods To investigate the association between social environment and aging of the brain, we studied P300 event-related evoked potentials in 95 normal elderly subjects living in different social environments. The subjects were divided into two groups: 22 healthy people living in old-age homes (average age 76.5 +/- 5.6 years, average Hasegawa Dementia Scale-Revised 27.4 +/- 2.5), and 93 healthy people living in their own homes (average age 74.1 +/- 5.4 years, average Hasegawa Dementia Scale-Revised 28.3 +/- 2.3). Target and Novelty P300 were recorded by using an auditory oddball paradigm. There were no differences in risk factors for strokes or in findings on magnetic resonance imaging between the two groups. Results Cognitive function (Okabe's Score and Koh's Block Design Test) were lower in those living in an old-age home than in those living in their own homes. Both target and novelty N100 examinations showed no significant differences in amplitude or latencies between the two groups. However, P300 latencies were larger among those living in an old-age home than among those living in their own homes; P300 amplitudes in the two groups were similar. Those living in an old-age home also had greater age-associated declines in function, as shown by longer latencies in target P300 than in novelty P300. Conclusion Social-environmental factors are closely associated with the aging of the brain.

Background and Purpose The pathogenesis of periventricular hyperintensity (PVH) is still uncertain. We investigated the relationship between PVH and risk factors for cerebrovascular diseases, especially extracranial carotid artery stenosis (ECAS). Methods We studied PVH and ECAS in 323 subjects between 1991 and 1994. Using 1.5-T MRI scan images, we measured PVH quantitatively at eight points and evaluated cerebral infarction. Duplex carotid sonography was performed on the carotid arteries bilaterally and used to divide the severity of ECAS into five grades. Risk factors for cerebrovascular diseases and atherosclerotic complications were assessed from the clinical history. Results Age was significantly correlated with the size of frontal and whole PVH ( P P P P Conclusions PVH correlated with age, hypertension, and past history of cerebrovascular disease but not with ECAS. PVH was significantly more severe in lacunar infarction and infarction of the deep border zone. These results suggest that small-vessel disease may underlie the pathogenesis and development of PVH.