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Background: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. Methods: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0–1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. Results: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24–20.6]; P =0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P =0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62–30.7]; P =0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. Conclusions: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: UMIN000006640.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has been widely used and highly effective for B-cell lymphoid malignancies. Immune-mediated adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in the acute phase and are monophasic after CAR T-cell therapy. However, late-onset inflammatory and neurological toxicities have not been well studied. We encountered a patient with recurrent late-onset inflammatory toxicities and progressive dysautonomia after CD19-directed CAR T-cell therapy. A 69-year-old man was treated with CD19-directed CAR T-cell therapy for transformed follicular lymphoma. Triphasic inflammation with stomatitis, cytopenia, and non-infectious pneumonia was first observed 7 months after CAR T-cell infusion. Progressive dysautonomia was also observed and eventually fatal. Residual CAR T cells, predominantly central memory CD4+ cells, were detectable in peripheral blood approximately one year after CAR T-cell infusion. The cytokine profile with the lack of tumor necrosis factor-α, interferon-γ, and interleukin-1β elevation in the peripheral blood and cerebrospinal fluid was inconsistent with that of typical CRS or ICANS. The persistence of central memory CD4+ CAR T cells might be associated with unique manifestations of late-onset immune-mediated adverse effects. More cases should be accumulated to elucidate the mechanism and establish the optimal management strategy of late-onset immune-mediated toxicities previously unrecognized.

Background: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disease progressively affecting cognitive and motor functions, most often caused by mutations in the colony-stimulating factor 1 receptor gene (CSF1R). / Aim: To elucidate the mechanism of disease progression, changes in white matter lesions and cortical cerebral blood flow (CBF) were evaluated in cases during various stages of the disease. ...

A 60-year-old man developed dyspnea without apparent limb weakness. He had cardiomyopathy in his 30s and was treated for chronic heart failure since 42. He was diagnosed as having four and a half LIM domains 1 (FHL1) mutation at 53 following the same diagnosis of his younger brother. He was first admitted to the cardiology department for possible worsening of chronic cardiac failure. Blood gas analysis showing respiratory acidosis prompted his treatment with a respirator. Neurological examination revealed that he had mild weakness limited to the shoulder girdle muscles and contracture at jaw, spine, elbows and ankles. Skeletal muscle CT showed truncal atrophy. He, as well as his younger brother, was diagnosed with FHL1 myopathy resulting in ventilation failure and was discharged after successful weaning from the respirator in the daytime. The present sibling cases are the first with FHL1 mutation to develop respiratory failure without limb weakness and suggest that FHL1 myopathy as a differentially diagnosis of hereditary myopathies with early respiratory failure.

A 70-year-old man presented with slow gait and a clumsy hand on the right side. Neurological examination revealed dystonia and ideomotor apraxia in the right hand. A mask-like face, rigidity in the right arm, and shuffling gait were noticed. Treatment with L-dopa had no effect. He was ......

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the “ATN” (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer’s disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aβ1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

We herein report a case of muscle biopsy-proven microscopic polyangiitis (MPA) in a patient with tuberculosis. The patient had developed a persistent fever after the initiation of treatment for tuberculosis and was positive for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). However, because conventional symptoms were lacking, determination of the biopsy site was difficult. Based on the findings of a biopsy of the biceps femoris, which confirmed small vessel vasculitis, the patient was diagnosed with MPA. The fever was alleviated by glucocorticoids. Tuberculosis and antituberculosis drugs can cause ANCA-associated vasculitis (AAV). A muscle biopsy is useful for the diagnosis of AAV.

Cerebral vessels are innervated by sympathetic and parasympathetic nerves, as well as the trigeminal nerve. Under physiological conditions, neural regulation contributes to coupling of cerebral blood flow (CBF) and metabolism and autoregulation of CBF against systemic blood pressure. It also plays a key role in vasodilatation distal to narrowed vascular lesions associated with atherosclerosis, hyperperfusion syndrome that occurs after vascular reconstruction in patients with chronic ischemic diseases, reversible cerebral vasoconstriction syndrome, and migraine. Moreover, cerebrovascular disease can cause autonomic dysfunction; frontal lobe and brain stem lesions are known to result in urinary incontinence, mydriasis, and Horner's syndrome.

While amyloid-β deposition in the cerebral cortex for Alzheimer's disease (AD) is often evaluated by amyloid positron emission tomography (PET), amyloid-β-related iron can be detected using phase difference enhanced (PADRE) imaging; however, no study has validated the association between PADRE imaging and amyloid PET. This study investigated whether the degree of hypointense areas on PADRE imaging correlated with the uptake of amyloid PET.PADRE imaging and amyloid PET were performed in 8 patients with AD and 10 age-matched normal controls. ROIs in the cuneus, precuneus, superior frontal gyrus (SFG), and superior temporal gyrus (STG) were automatically segmented. The degree of hypointense areas on PADRE imaging in each ROI was evaluated using 4-point scaling of visual assessment or volumetric semiquantitative assessment (the percentage of hypointense volume within each ROI). The mean standardized uptake value ratio (SUVR) of amyloid PET in each ROI was also calculated. The Spearman's correlation coefficient between the 4-point scale of PADRE imaging and SUVR of amyloid PET or between the semiquantitative hypointense volume percentage and SUVR in each ROI was evaluated.In the precuneus, a significant positive correlation was identified between the 4-point scale of PADRE imaging and SUVR of amyloid PET (Rs = 0.5; P = 0.034) in all subjects. In the cuneus, a significant positive correlation was identified between the semiquantitative volume percentage of PADRE imaging and SUVR of amyloid PET (Rs = 0.55; P = 0.02) in all subjects.Amyloid-β-enhancing PADRE imaging can be used to predict the SUVR of amyloid PET, especially in the cuneus and precuneus, and may have the potential to be used for diagnosing AD by detecting amyloid deposition.

Background: Clinical staging of Alzheimer disease (AD) may help develop novel treatment in the early stage. / Aim: We measured the accumulation of amyloid beta (Aβ) and tau with positron emission tomography (PET) in patients with AD to explore its utility for clinical staging. / Methods: Six patients with AD, two patients with mild cognitive impairment (MCI), and 12 healthy controls (HC) were studied. Aβ and tau accumulation was evaluated with [^11 C]PiB and [^11 C]PBB3, respectively....

Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with peripheral neuropathy, but reports of central nervous system involvement are quite rare. We herein report a patient with EGPA first identified as having hypereosinophilia who later developed asthma, eosinophilic otitis media, sinusitis, and hemorrhagic colitis. She subsequently developed hemiparesis. Head magnetic resonance imaging revealed multiple cerebral infarctions with subcortical and subarachnoid hemorrhaging colocalized at the bilateral border zone areas. She was diagnosed with EGPA-induced stroke and successfully treated with oral prednisolone. Inflammation in the small cerebral arteries in EGPA may induce bilateral border zone infarction with colocalizing subcortical and subarachnoid hemorrhaging.

Background: We previously reported that among cases clinically diagnosed with Alzheimer’s disease, the proportion of amyloid beta (Aβ) -negative case increases in the elderly population. Tauopathy including Argyrophilic Grain Disease (AGD) and Neurofibrillary Tangle-Predominant Dementia (NFTPD), may be the leading causes of such dementia. Objective: To evaluate the involvement of tau, we studied tau accumulation in Amyloid-Negative Dementia Cases in the Elderly (ANDE) with Positron Emission Tomography (PET). Methods: Seven cases with slowly progressive dementia who were older than 80 years and were negative for Aβ were studied. In one case, autopsy obtained 2 years after the PET examination revealed neurofibrillary tangles limited around the parahippocampal gyrus. Four cases showed strong laterality in magnetic resonance imaging atrophy (clinical AGD), while the other three cases had no significant laterality in atrophy (clinical NFTPD). Age-corrected PET data of healthy controls (HC; n = 12) were used as control. Tau accumulation was evaluated with [11C]PBB3-PET. Results: High accumulation was found in the lateral temporal cortex in ANDE. In autopsy case, scattered neurofibrillary tangles were found in the parahippocampal gyrus. In addition, there was a very high accumulation of PBB3 in the large area of bilateral parietal lobes, although no corresponding tau component was found in the autopsied case. Conclusion: Relatively high burden of tau deposition was commonly observed in the lateral temporal cortex and parietal cortex of ANDE, part of which may explain dementia in these subjects. [11C]PBB3 may be useful in detecting tauopathy in ANDE.

Background Good’s syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. Case presentation A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. Conclusions Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.

Disposition of amyloid β (Aβ) into the perivascular space of the cerebral cortex has been recently suggested as a major source of its clearance, and its disturbance may be involved in the pathogenesis of cerebral amyloid angiopathy and Alzheimer’s disease. Here, we explored the in vivo dynamics of Aβ in the perivascular space of anesthetized mice. Live images were obtained with two-photon microscopy through a closed cranial window. Either fluorescent-dye-labeled Aβ oligomers prepared freshly or Aβ fibrils after 6 days of incubation at 37 °C were placed over the cerebral cortex. Accumulation of Aβ was observed in the localized perivascular space of the penetrating arteries and veins. Transportation of the accumulated Aβ along the vessels was slow and associated with changes in shape. Aβ oligomers were transported smoothly and separately, whereas Aβ fibrils formed a mass and moved slowly. Parenchymal accumulation of Aβ oligomers, as well as Aβ fibrils along capillaries, increased gradually. In conclusion, we confirmed Aβ transportation between the cortical surface and the deeper parenchyma through the perivascular space that may be affected by the peptide polymerization. Facilitation of Aβ excretion through the system can be a key target in treating Alzheimer’s disease.

Mild cognitive impairment (MCI) can include the transition from a normal state to dementia. To explore biomarkers for the development of dementia, we performed an 18-month follow-up study in 28 patients with amnestic MCI. Amyloid deposition was examined using PiB PET, and cerebral blood flow (CBF) was examined using SPECT. Cognitive function was periodically assessed. The rate of conversion to dementia was higher in the PiB-positive/equivocal group (74%) than in the PiB-negative group (33%) (p = 0.041). Perfusion SPECT was performed in 16 patients. MCI patients with an AD-characteristic pattern of reduced CBF had a higher PiB-positive/equivocal rate (82%) than those with a non-AD pattern (20%) (p = 0.018), and patients with an AD pattern had a higher conversion rate (82%) than those with a non-AD pattern (40%) (p = 0.094). Clinically, all PiB-positive converters were diagnosed as having Alzheimer's disease (AD), whereas PiB-negative converters were thought to have some form of dementia other than AD. Amyloid PET is useful for predicting conversion to AD in MCI patients. A pattern analysis of perfusion SPECT findings might also be helpful for predicting conversion to AD, but with a lower specificity.

Globular glial tauopathy (GGT) is a 4-repeat (4R) tauopathy in which 4R tau accumulates to form globular glial inclusions (GGIs), predominantly in oligodendroglia. To date, little has been reported on iron deposits in patients with GGT. We report a case of GGT with iron deposits in a 78-year-old woman presenting with an 8-year history of slowly progressing limb weakness and cognitive decline. Susceptibility-weighted imaging revealed a low signal intensity in the right precentral gyrus, suggesting iron deposition. A clinical diagnosis of motor neuron disease with dementia was made 4 years after onset. At autopsy, gross pathological findings showed atrophy of the frontal and temporal lobes. A localized area of the precentral gyrus corresponding to the most severely affected limb showed the strongest atrophy, macroscopically, and displayed 4R tau-immunoreactive GGIs and microscopically many ferritin-immunoreactive neurons. We diagnosed this patient as having GGT. This is the first GGT case with iron deposition confirmed both radiologically and pathologically.

The dielectric function spectra of TlGaSe 2 crystal with quasi-two-dimensional layered structure were studied over the photon range 1.5–5.0 eV in the temperature range 80–400 K. The (100) and (001) surfaces were accessed by spectroscopic ellipsometry and the dielectric function was retrieved after conventional treatment of the ellipsometric data. Inter-band optical transitions associated with the obtained dielectric function were determined by using standard critical point analysis. Assignment of the transitions was done within the framework of the calculated electronic band structure. An abrupt temperature-induced change in energy of the retrieved critical points for inter-band optical transitions between the electronic states formed with participation of thallium orbitals was obtained at 104.5, 123.3 and 247.0 K. The last temperatures agree well with the temperature points of the subsequent structural phase transitions in TlGaSe 2 .

The originally published version of this article contained an error in Fig. 1 and Table 2. The correct figure and table of this article should have read as below. This has now been corrected in the PDF and HTML versions of the article. The authors apologize for any inconvenience caused.

We propose a rescoring method using words related to a query obtained by Web search and word vectors for spoken term detection (STD). In this paper, we assume that words associated with the topic in speech data and co-occurring with the query are called “words related to the query”, and that the related words appear multiple times in the speech data. To identify the words related to the query, we introduce distributed expression of words obtained by Word2vec [1] [2], and first convert each word in the word-recognition results of speech data into a word vector. Each word vector is then compared with a word vector of the query. Words related to the query are determined by calculating the degree of similarity between the two word vectors. However, a word vector of an out-of-vocabulary (OOV) query cannot be obtained in this manner, since OOV queries do not appear in word-recognition results. For such OOV queries, we perform a Web search using the query, whereupon texts including the query are extracted. Recognition results of the speech data and the extracted texts are then combined and used for training of Word2vec. In this manner, a word vector of the OOV query can be obtained. Distances to all candidates in the document, including words related to the query, are used advantageously. Experiments are conducted to evaluate the performance of the proposed method using open test collections of the NTCIR-10[3] and NTCIR-12[4] workshops. For retrieval accuracy, an improvement of 3.2 points in mean average precision was achieved using the proposed method.

Background We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. Methods and results We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. Conclusions We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Both amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with Alzheimer’s disease (AD). However, the constituents of these hallmarks, amyloid beta (Aβ) 40, Aβ42, and total Tau (t-Tau), have been detected in the blood of cognitively normal subjects by using an immunomagnetic reduction (IMR) assay. Whether these levels are age-dependent is not known, and their interrelation remains undefined. We determined the levels of these biomarkers in cognitively normal subjects of different age groups. A total of 391 cognitively normal subjects aged 23–91 were enrolled from hospitals in Asia, Europe, and North America. Healthy cognition was evaluated by NIA-AA guidelines to exclude subjects with mild cognitive impairment (MCI) and AD and by cognitive assessment using the Mini Mental State Examination and Clinical Dementia Rating (CDR). We examined the effect of age on plasma levels of Aβ40, Aβ42, and t-Tau and the relationship between these biomarkers during aging. Additionally, we explored age-related reference intervals for each biomarker. Plasma t-Tau and Aβ42 levels had modest but significant correlations with chronological age (r = 0.127, p = 0.0120 for t-Tau; r = −0.126, p = 0.0128 for Aβ42), ranging from ages 23 to 91. Significant positive correlations were detected between Aβ42 and t-Tau in the groups aged 50 years and older, with Rho values ranging from 0.249 to 0.474. Significant negative correlations were detected between Aβ40 and t-Tau from age 40 to 91 (r ranged from −0.293 to −0.582) and between Aβ40 and Aβ42 in the age groups of 30–39 (r = −0.562, p = 0.0235), 50–59 (r = −0.261, p = 0.0142), 60–69 (r = −0.303, p = 0.0004), and 80–91 (r = 0.459, p = 0.0083). We also provided age-related reference intervals for each biomarker. In this multicenter study, age had weak but significant effects on the levels of Aβ42 and t-Tau in plasma. However, the age group defined by decade revealed the emergence of a relationship between Aβ40, Aβ42, and t-Tau in the 6th and 7th decades. Validation of our findings in a large-scale and longitudinal study is warranted.

11 AbbreviationsBDI, Beck Depression Inventory; CFS, Chalder Fatigue Scale; EDSS, Expanded Disability Status Scale; HC, Health control subjects; MMSE, Mini-Mental State ExaminationMS, Multiple sclerosis; PASAT, Paced Auditory Serial Addition Test; QoL, Quality-of-lifeSD, Standard deviation; SDMT, Symbol Digit Modalities Test; VC, Visual cancellation;: Background: Depression and fatigue are debilitating symptoms in multiple sclerosis (MS), which affect cognitive function. This study investigated the association between depression and fatigue, and whether depression or fatigue influences cognition in MS patients. Methods: Twenty MS patients were included. The severity of fatigue was assessed using the Chalder Fatigue Scale (CFS), which classified CFS_Physical and CFS_Mental fatigue and MMSE. Depression was assessed using the Beck Depression Inventory (BDI). Attention deficit was evaluated using several tasks. The CFS scores, the BDI scores and performance during the attention tasks were compared between MS patients and healthy control subjects (HCs). Correlations between CFS sub-scores, BDI values, and participants’ attention performance were also investigated. Results: The total CFS, BDI, and MMSE scores were significantly worse in MS patients compared to HCs (p

A class of games for finding a leader among a group of candidates is studied in detail. This class covers games based on coin tossing and rock-paper-scissors as special cases and its complexity exhibits similar stochastic behaviors: either of logarithmic mean and bounded variance or of exponential mean and exponential variance. Many applications are also discussed.

Background The detection of amyloid β accumulation might be useful in confirming the diagnosis of Alzheimer's disease in clinically suspected cases. However, confirmation of the disease by a positron emission tomography scan is not always available. Aim We measured the cerebral blood flow in clinically suspected Alzheimer's disease cases, and compared the findings between amyloid-positive and -negative cases. Methods At the Osaka City University Hospital, patients with “probable or possible Alzheimer's disease” were enrolled. In addition, “healthy volunteers” with no subjective decline in cognitive function or in cognitive tests were evaluated as controls. A positron emission tomography scan with Pittsburgh compound B as a tracer was utilized to detect amyloid accumulation. Results In the healthy control cases aged >60 years, a positive rate of amyloid increased steeply with age. In contrast, an amyloid-positive rate decreased with age in the clinically suspected Alzheimer's disease cases aged >60 years. The Mini-Mental State Examination score was higher and the disease duration was longer in the amyloid-negative group than in the positive group, suggesting a slower progression of dementia in the amyloid-negative patients, though the tendency failed to reach the statistical significance. Cerebral blood flow decrease was classified into four patterns. Typical Alzheimer's disease patterns were found exclusively in the amyloid-positive group, whereas frontal dominant and temporal dominant were more frequently found in the amyloid-negative group. Conclusion Even in the era of amyloid imaging, cerebral blood flow measurement can help differentiate Alzheimer's disease from other diseases causing apparent Alzheimer's disease-type cognitive impairment.

Background In patients with multiple sclerosis (MS), development of hepatic injury has been sporadically reported after methylprednisolone (MP) pulse therapy. Some studies suggest autoimmune hepatitis, while other studies reported direct hepatotoxicity as a cause for hepatic injury. Here, we studied the pathological mechanism of such liver injury in patients with MS. Methods From 2005 to 2016, eight patients with MS developed liver injury after MP pulse therapy. Their average age was 38 years (range: 28–49 years, all female). Autoimmune antibodies were measured and a liver biopsy was performed in seven patients. Results Liver injury developed within two weeks in two patients and later (30–90 days after MP) in six patients. No hepatitis-related autoantibody or hepatitis virus were found. All cases were classified as hepatocellular injury and none as cholestatic or mixed. A liver biopsy in five cases revealed centrilobular necrosis with lobular infiltrates of inflammatory cells, suggesting drug-induced acute hepatitis. The biopsy findings in another case suggested a residual stage of acute hepatitis. Only one patient showed portal expansion with periportal fibrosis, suggesting autoimmune hepatitis. All patients recovered spontaneously or with only hepatoprotective drugs, although one patient with possible autoimmune hepatitis recovered slowly. Conclusion Liver injury develops usually later than two weeks after MP treatment. The prognosis is good in most cases and rarely autoimmune hepatitis may be involved.

We previously identified a novel mutation in amyloid precursor protein from a Japanese pedigree of familial Alzheimer’s disease, FAD (Osaka). Our previous positron emission tomography (PET) study revealed that amyloid β (Aβ) accumulation was negligible in two sister cases of this pedigree, indicating a possibility that this mutation induces dementia without forming senile plaques. To further explore the relationship between Aβ, tau and neurodegeneration, we performed tau and Aβ PET imaging in the proband of FAD (Osaka) and in patients with sporadic Alzheimer’s disease (SAD) and healthy controls (HCs). The FAD (Osaka) patient showed higher uptake of tau PET tracer in the frontal, lateral temporal, and parietal cortices, posterior cingulate gyrus and precuneus than the HCs (>2.5 SD) and in the lateral temporal and parietal cortices than the SAD patients (>2 SD). Most noticeably, heavy tau tracer accumulation in the cerebellum was found only in the FAD (Osaka) patient. Scatter plot analysis of the two tracers revealed that FAD (Osaka) exhibits a distinguishing pattern with a heavy tau burden and subtle Aβ accumulation in the cerebral cortex and cerebellum. These observations support our hypothesis that Aβ can induce tau accumulation and neuronal degeneration without forming senile plaques.

Creutzfeldt-Jakob disease (CJD) is a prion disease characterized by rapidly progressive dementia that is often followed by behavioral disturbances, ataxia, myoclonus, and akinetic mutism. The initial symptoms of CJD reportedly vary, but the onset is usually gradual. Here, we report a case of CJD with a sudden, stroke-like onset of right hemiparesis to alert readers that CJD can mimic a stroke during its early stage.

Background: Improving the quality of stroke care is an urgent issue worldwide. To facilitate the measurement of quality of stroke care in Japan, we aimed to develop the Close The Gap-Stroke initiative in the J-ASPECT Study. Methods and Results: Quality indicators (QIs) were developed by a multidisciplinary board between 2015 and 2017. The process involved a systematic review of domestic and international studies related to primary and comprehensive stroke care. Adherence rates for the defined QIs were calculated for 8,826 patients with acute ischemic stroke from 227 hospitals between 2013 to 2015. Seventeen and 12 measures were identified as QIs for primary and comprehensive stroke care (PSC and CSC), respectively. We analyzed adherence rates of all 17 QIs for PSC and 8 QIs for CSC related with acute ischemic stroke. We found NIHSS documentation (91.0 %), CT/MRI performed within 25min and 24hr (80.9 % and 99.1 %), evaluation of extracranial vascular imaging (90.4 %), treated in stroke unit (57.4 %), tPA administration (89.5 %), tPA performed within 1hr (37.4 %), early and discharge antithrombotics medication (75.1 % and 49.0 %), discharge anticoagulation for atrial fibrillation patients (76.2 %), discharge statin medication (32.7 %), discharge antihypertensive agents (54.3 %), deep vein thrombosis prophylaxis (34.5 %), early rehabilitation (57.0 %), dysphagia screening (76.6 %), smoking cessation (59.8 %) and stroke education (71.4 %) for primary stroke care; and median time to multimodal CT or MR brain and vascular imaging (33 min), proper endovascular recanalization (81.7 %), tPA before endovascular recanalization (65.7 %), TICI grade 2b/3 after endovascular recanalization (73.0 %), median time of door to puncture (105 min), symptomatic intracranial hemorrhage after thrombolytic or endovascular therapy (7.45 %), 90 days mRS documentation after thrombolytic or endovascular therapy (60.8 %), occurrence of complication within 24 hours of diagnostic neuroangiography (7.27 %) for comprehensive stroke care. Conclusion: This is a promising first step to measure the QIs related to primary and comprehensive stroke care at a national level in Japan.

Purpose: Cerebral amyloid angiopathy (CAA) is a disease with deposition of amyloid beta protein to meninges or intracerebral vessel walls. CAA is known as a cause of cerebral hemorrhage or subarachnoid hemorrhage occurring most frequently in the occipital lobe. CAA is usually accompanied with Alzheimer's disease, which shows specific pattern of amyloid accumulation. In this study we evaluated the distribution of the amyloid deposition in CAA patients using PIB-PET. Methods: Five patients, 3 males and 2 females, who developed cerebral hemorrhage or subarachnoid hemorrhage and clinically diagnosed as CAA were evaluated. Age of the patients was 28 - 74 years old. To detect amyloid accumulation, we injected 250-350mBq or 400-500mBq of [11C]PiB, followed by 60 minutes or 70 minutes dynamic scan using Eminence B PET camera (Shimadzu Corporation). Results: PIB accumulation was detected predominantly in the frontal lobe, parietal lobe, and lateral temporal lobe, but much less in the occipital lobe. The distribution of PIB accumulation was mostly similar to that in patients with Alzheimer disease. Little accumulation in the occipital lobe may reflect apparent effects of intracerebral hemorrhage. Conclusion: In most CAA patients, the examination by PIB-PET fails to detect amyloid deposition in the vessel walls of the occipital lobes. Instead, it more frequently reflect intracerebral amyloid deposition of accompanying Alzheimer's disease.

PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14 (PARK14). In addition, very recently, PLA2G6 mutations have been reported to represent a phenotype of hereditary spastic paraplegia (HSP). In this study, we screened 383 HSP families to clarify the frequency of PLA2G6 mutations in the Japan Spastic Paraplegia Research Consortium, and revealed the clinical characteristics of HSP with PLA2G6 mutations. We found three families with compound heterozygous mutations of the PLA2G6 gene, c.517 C T/c.1634A G, c.662 T C/c.991 G T, and c.1187-2 A G/c.1933C T, and one family with a homozygous mutation of the PLA2G6 gene, c.1904G A/c.1904G A. All three families with compound heterozygous mutations presented a uniform phenotype of a complicated form of HSP with infantile/child-onset spastic paraplegia, cerebellar ataxia, and mental retardation. On the other hand, the family with a homozygous mutation presented a late-onset complicated form of HSP with parkinsonism. This study may extend the clinical and genetic findings for PLAN.

We report the case of a 42-year-old female with neurosarcoidosis who was hospitalized in year 2017 for gait disturbance. In 2011, she suddenly had vertigo that lasted for a few days. In 2013, she noticed left hemiplegia. A brain MRI revealed an acute infarction on the right side of the upper pons extending longitudinally from the ventral surface. In 2017, she again had left lower limb paralysis. A Brain MRI showed another infarction on the right side of the mid-pons. Hydrocephalus and brainstem atrophy were also noted. The patient was referred to our hospital. Upon neurological examination, she presented with down beat nystagmus, muscle weakness on the left side, and a broad-based spastic gait. CSF findings included an increased number of cells and protein levels with decreased glucose levels. A contrast-enhanced MRI revealed basilar meningitis causing hydrocephalus. A contrast CT scan revealed inguinal lymph node swelling, and scintigram found gallium accumulation. We diagnosed sarcoidosis via a lymph node biopsy. We speculate that chronic basilar meningitis obstructed the patient's branching penetrating arteries inducing infarction together with obstruction of the spinal fluid flow causing hydrocephalus and cerebral atrophy.

Objective Control of red blood cell velocity in capillaries is essential to meet local neuronal metabolic requirements, although changes of capillary diameter are limited. To further understand the microcirculatory response during cortical spreading depression, we analyzed the spatiotemporal changes of red blood cell velocity in intraparenchymal capillaries. Methods In urethane-anesthetized Tie2-green fluorescent protein transgenic mice, the velocity of fluorescence-labeled red blood cells flowing in capillaries in layer I of the cerebral cortex was automatically measured with our Matlab domain software (KEIO-IS2) in sequential images obtained with a high-speed camera laser-scanning confocal fluorescence microscope system. Results Cortical spreading depression repeatedly increased the red blood cell velocity prior to arterial constriction/dilation. During the first cortical spreading depression, red blood cell velocity significantly decreased, and sluggishly moving or retrograde-moving red blood cells were observed, concomitantly with marked arterial constriction. The velocity subsequently returned to around the basal level, while oligemia after cortical spreading depression with slight vasoconstriction remained. After several passages of cortical spreading depression, hypercapnia-induced increase of red blood cell velocity, regional cerebral blood flow and arterial diameter were all significantly reduced, and the correlations among them became extremely weak. Conclusions Taken together with our previous findings, these simultaneous measurements of red blood cell velocity in multiple capillaries, arterial diameter and regional cerebral blood flow support the idea that red blood cell flow might be altered independently, at least in part, from arterial regulation, that neuro-capillary coupling plays a role in rapidly meeting local neural demand.

Pulmonary arteriovenous fistula (PAVF), a vessel malformation connecting the pulmonary circulation to the systemic circulation while bypassing the pulmonary capillaries, can cause paradoxical cerebral infarction. It is often associated with hereditary hemorrhagic telangiectasia (HHT), a genetic disease characterized by multiple dermal, mucosal, and visceral telangiectasia causing recurrent bleeding. Paradoxical cerebral embolism caused by PAVF without HHT is rare. Here, we report a patient with isolated PAVF who experienced an ischemic stroke caused by a paradoxical embolism from deep venous thrombosis; the patient was successfully treated with recombinant tissue plasminogen activator. She presented with a decrease in arterial oxygen saturation to 91%, and lung disease was suspected. A PAVF was subsequently found in the right S6 region using contrast computed tomography. Interventional radiologists successfully occluded the shunt using 6 microcoils. PAVF should be considered when determining the pathogenesis of cerebral ischemia in patients with hypoxia, which can be the only symptom of PAVF.

Background Despite the common practice of surgery and antiplatelet therapy for the prevention of recurrent stroke in patients with moyamoya disease, the benefit of these treatments is controversial. We analyzed the stroke recurrence rate in the Registry Study of Research Committee on Moyamoya Disease in Japan funded by the Health, Labor and Welfare Ministry of Japan. Methods An annual follow-up study of the registered cases was continued for 10 years. The rate of recurrent stroke, including cerebral infarction and hemorrhage but not transient ischemic attack and seizure, was evaluated with Kaplan–Meier analysis. Results The proportion of childhood-onset cases decreased in recently registered cases (within 10 years, n = 541) compared to remote cases (>10 years, n = 735). Among types at disease onset in adult-onset cases, intracerebral hemorrhage decreased recently. In recent cases, the rate of subsequent cerebral hemorrhage was much higher in the hemorrhagic group (10.9 ± 3.3%/5 years) than in the ischemic group (2.0 ± .9%/5 years). The recurrence rate of cerebral infarction was lower in the surgery group (1.8 ± .9%/5 years) than in the nonsurgery group (3.8 ± 2.2%/5 years). In the adult-onset ischemic group, the proportion of surgically treated patients increased and their recurrence rate was lower than that of nonsurgery patients. In the ischemic group, the rate of cerebral infarction was not significantly different between the antiplatelet subgroup and the non-antiplatelet subgroup, whereas the rate of cerebral hemorrhage was higher in the non-antiplatelet subgroup than in the antiplatelet subgroup. Conclusions Our results suggest revascularization surgery may suppress recurrent ischemic attacks in patients with moyamoya disease.

We reconstruct the published year of each cuneiform tablet of the Nuzi society in ancient Mesopotamia. The tablets are on land transaction, marriage, loan, slavery contracts, etc. The number of tablets seems to increase by logistic growth. It may show the dynamics of concentration of lands or other properties into few powerful families in a period of about sixty years and most of them are in about thirty years. We reconstruct family trees and social networks of Nuzi and estimate the published years of cuneiform tablets consistently with the trees and networks, formulating least squares problems with linear inequality constraints.

We consider sequential random packing of integral translate of cubes $[0,N]^n$ into the torus $Z^n / 2NZ^n$. Two special cases are of special interest: (i) The case $N=2$ which corresponds to a discrete case of tilings (considered in \cite{cubetiling,book}) (ii) The case $N=\infty$ corresponds to a case of continuous tilings (considered in \cite{combincubepack,book}) Both cases correspond to some special combinatorial structure and we describe here new developments., Comment: 5 pages, conference paper

Much research has been conducted on spoken term detection. Query-by-example has also been an important topic in spoken term detection, which covers spoken queries. A previous study examined posteriorgrams, which are sequences of output probabilities generated by a deep neural network from speech queries and speech data. Although posteriorgram matching between a spoken query and speech data exhibits improved retrieval accuracy, the time required to search with a spoken query is long, even for a relatively small quantity of speech data. Reducing retrieval time is thus a crucial problem. In this paper, we propose two methods for reducing retrieval time in posteriorgram matching. One is to accelerate posteriorgram matching by transforming a posteriorgram to a bit matrix, and the other is to use a sparse vector method. The first method, "posteriorgram bit operation," transforms the posteriorgrams of both spoken queries and speech data to bit matrices. The second method retains a small number of elements, of which only a few are of high probability, in a posteriorgram. Because most of the elements in a sparse vector are 0, the thousands of output probabilities of the posteriorgram are reduced to only a small number of output probabilities. Evaluation experiments have been carried out using open test collections (Spoken-Doc tasks of NTCIR-10 workshops) [1,2], and the results have demonstrated the effectiveness of the proposed method.

A hemodynamic mechanism has long been assumed to play an important role in watershed infarction. In recent years, however, clinical evidence has indicated that an embolic mechanism is involved. The mechanism by which emboli are trapped preferentially in watershed areas remains unclear. In the present study, we developed a mouse embolus model using fluorescent microspheres with different diameters and evaluated the role of the microspheres' diameters in the generation of a watershed-patterned distribution. We injected fluorescent microspheres of four different diameters (i.e., 13, 24, 40, and 69 μm) into the internal carotid artery of C57BL/6 mice either (1) without ligation of the common carotid artery (normal perfusion pressure model: NPPM) or (2) with ligation of the common carotid artery (low perfusion pressure model: LPPM). Left common carotid artery ligation induced reductions in local cerebral blood flow in both the periphery and the core area of the left middle cerebral artery. A greater reduction in the border-zone area between the left anterior cerebral artery and the middle cerebral artery was also noted. After 24 h, the brains were removed and the distribution of the microspheres in the brain was evaluated using a fluorescence microscope. The 24-μm microspheres were distributed in the watershed area more frequently than the other microsphere sizes (P .05, ANOVA followed by Tukey's test). Meanwhile, the distribution rates were similar between the NPPM and LPPM models for all microsphere sizes. This study suggested that the distribution pattern of the microspheres was only affected by the microspheres' diameters.

To evaluate the aerodynamic instability for buildings considering their high-order oscillation mode and torsional oscillation mode on which it is difficult to perform the usual wind tunnel experiments, the fluid–structure interaction (FSI) analysis code combined with a multi-degree-of-freedom structure model and large-eddy simulation was developed. The calculation results obtained in this study and the results of wind tunnel tests conducted in a previous study using a building model (average breadth 0.14 ​m ​× ​length 0.28 ​m ​× ​height 1 ​m; scale: 1/600) with a multi-degree-of-freedom structure were compared. The comparison showed that the FSI analysis results were corresponded well with those of the wind tunnel tests; for each spectrum of response displacement (wind, along-wind, and torsional direction) at the top mass node, the frequency distribution and the peak frequency of the first and second oscillation modes were in good agreement with the calculation results and the wind tunnel test results. As for the amplitude of the top displacement of the building, the results for both the along- and across-wind directions showed good correspondence. For the torsional direction, the calculation results reproduced a torsional flutter oscillation with a slightly low wind level in comparison with that observed in the wind tunnel experiments.