Toshiki Mizuno - Academia.edu (original) (raw)
Papers by Toshiki Mizuno
Journal of Alzheimer's Disease, Nov 28, 2017
Background: The anti-aging protein, ␣-Klotho, may be involved in cognitive decline and has potent... more Background: The anti-aging protein, ␣-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of ␣-Klotho in the brain has not been sufficiently investigated. Objective: Here, we investigated the association between ␣-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). Methods: Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood ␣-Klotho level were retrospectively investigated. Results: The ␣-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the ␣-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low ␣-Klotho level, the odds
Alzheimers & Dementia, Jul 1, 2010
Stroke, Feb 1, 2008
Background and Purpose-Symptomatic progression is frequently observed in lacunar infarcts. The ex... more Background and Purpose-Symptomatic progression is frequently observed in lacunar infarcts. The exact mechanisms of this phenomenon have not yet been clarified. Summary of Cases-We report 2 patients with lenticulostriate artery infarcts that presented with skip lesions that were restricted to gray matter. One of the patients subsequently developed symptomatic deterioration; the other experienced no further neurological events. Conclusions-A possible mechanism of differential vulnerability to ischemia of gray and white matter is considered. White matter may have a longer therapeutic time window for neuroprotective treatment than gray matter.
Autonomic Neuroscience: Basic and Clinical, Dec 1, 2005
The clinical significance of evaluating autonomic nervous system functions in the early stages of... more The clinical significance of evaluating autonomic nervous system functions in the early stages of olivopontocerebellar atrophy (OPCA) has been investigated in 13 OPCA outpatients (7 males and 6 females, mean age: 51.0 years). We have employed measurements of blood pressure, plasma norepinephrine (NE), CVR-R, low-frequency power/high-frequency power ratio (L/H), high-frequency power (HF) score and heart rate (HR) monitoring using Holter ECG recording for evaluation of CVR-R. We have also carried out urodynamic examinations, focusing on the possible existence of bladder dysfunction. Although no significant changes were noted between control and OPCA groups concerning HR, CVR-R, L/H, plasma levels of norepinephrine and systolic blood pressure, HF (high-frequency power) (ms 2), especially at night time, invariably showed a significant decline in OPCA groups. All OPCA patients who showed a decreased circadian HF also exhibited a tendency towards urinary bladder dysfunction. The present results appear to relate to disorder of the parasympathetic autonomic nervous system and neuromuscular dysfunction in the lower urinary tract. In conclusion, HRV (heart rate variability) analysis is a useful and safe tool and a keen predictor for evaluating functional states of autonomic nervous activity, especially in the early stages of OPCA. This study has also suggested the possible efficacy of urodynamic measurements in OPCA patients as an indicator of neuromuscular dysfunction in the lower urinary tract and of parasympathetic malfunction.
Journal of Interferon and Cytokine Research, Nov 1, 2009
The mechanism of the infl ammatory response in the vascular wall in atherothrombosis and during t... more The mechanism of the infl ammatory response in the vascular wall in atherothrombosis and during the progression of atherosclerosis has attracted attention. We focused on the potential usefulness of infl ammatory markers in chronic recurrent brain infarction, and analyzed the role of infl ammatory markers in atherosclerosis of the intracranial artery. The subjects were 2 groups of patients treated between 2004 and 2006: a group of outpatients with recurrent infarction (group RI), who developed atherothrombotic brain infarction twice; another group of outpatients with brain infarction without recurrence (group BI), who developed brain infarction once and remained free of recurrence for >1 year; and a group of control subjects with normal brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) (group C). Plasma samples were collected from each group of patients for the simultaneous measurement of 17 kinds of candidate infl ammatory markers, using a fl uorescent microbead array system, and the results were compared with head MRA fi ndings. The levels of high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) were signifi cantly higher in group RI patients than in groups C and BI. Subjects with a hsCRP level ≥0.3 and a MCP-1 level ≥200 in the serum have, respectively, a 1.92 and 2.98 relative risk to have a potential recurrent infarction. Regarding the relation of infl ammatory marker levels with MRA fi ndings, group RI showed signifi cantly higher levels of hsCRP at M1 lesions and MCP-1 at A1 and M1 lesions than group BI (P < 0.05). In conclusion, the MCP-1 level as well as hsCRP in the blood can be a potential predictive marker of recurrent thrombotic brain infarction, and may refl ect infl ammation that promotes intracranial large-artery atherosclerosis.
Archives of Gerontology and Geriatrics, 2013
Oral Diseases, Sep 1, 2015
Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus... more Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders. This article is protected by copyright. All rights reserved.
Journal of Clinical Neuromuscular Disease, Jun 1, 2014
We report a patient with adult-type Pompe disease treated with enzyme replacement therapy (ERT) f... more We report a patient with adult-type Pompe disease treated with enzyme replacement therapy (ERT) for 5.5 years. We evaluated pulmonary function and muscle strength using 6-minute walk test, manual muscle test, and dynamometer-based measurement. The long-term ERT resulted in a substantial improvement in the pulmonary function and a possible stabilization followed by mild deterioration in muscle power measured by dynamometer and 6-minute walk test. Our data may rationalize the long-term use of ERT for adult-type Pompe disease in terms of maintaining pulmonary function.
Clinical and Applied Thrombosis-Hemostasis, Aug 10, 2009
Background: Platelet-derived microparticles (PDMPs) have attracted attention as blood coagulation... more Background: Platelet-derived microparticles (PDMPs) have attracted attention as blood coagulationpromoting, endothelial cell-activating factors. The objective of this study was to determine the parameters associated with elevated PDMP levels and examine their relationship with atherosclerotic lesions of main intracranial and extracranial arteries. Participants and Methods: Participants included a control group (C) of 61 patients with no apparent cerebral vascular lesions and 110 patients with acute-phase cerebral infarction, consisting of a small-vessel occlusion group (S) of 34 patients, a large-artery atherosclerosis group (L) of 41 patients, a cardioembolism group (CE) of 20 patients, and a stroke of undetermined etiology group (U) of 15 patients. Platelet-derived microparticle levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of admission, and the patients were reclassified into group CP (control level PDMPs), consisting of 70 patients with control PDMP levels, and group HP (high PDMPs), consisting of 40 patients with elevated PDMP levels. All patients underwent cranial magnetic resonance (MR) and carotid ultrasound examinations. Results: Plateletderived microparticle levels were significantly higher in groups S and L than in group C (P < .01). Concomitant intima-media thickness (IMT; odds ratio [OR] ¼ 1.29, P < .05) and concomitant intracranial stenosis (OR ¼ 3.95, P < .01) were significantly correlated with elevated PDMP levels. Fibrinogen and high-sensitivity CRP levels were significantly higher in group HP than in group CP. Conclusion: Alterations in PDMP levels correlated with the presence of atherothrombotic lesions, and PDMP levels are expected to be useful as a clinical indicator, reflecting the presence of intracranial atherosclerotic lesions in the acute phase of cerebral infarction.
Journal of the Neurological Sciences, Oct 1, 2017
Objective: To investigate the relationship between apathy and regional cerebral blood flow (rCBF)... more Objective: To investigate the relationship between apathy and regional cerebral blood flow (rCBF) in mild cognitive impairment (MCI). Patients and Methods/Material and Methods: We performed neuropsychological tests, brain MRI and SPECT of amnestic MCI (n =32) and normal controls (NC) (n =5). We investigated the correlations of apathy score of Japanese version of the apathy scale reported by Starkstein et al. with Fazekas score and the neuropsychological tests, such as GDS-15, hamilton depression rating scale (HDRS), MMSE, FAB, WMS-R, TMT-A/B scores in each group by SPSS. The voxel-wise correlations of rCBF with apathy score were assessed in MCI using SPM8. Results: The mean scores of MCI/NC were 12.2/12.2 in apathy scale, 4.1/1.2 in GDS, 2.6/0 in HDRS, 1.2/1.6 in PVH and 0.8/1.2 in WMH. There was significant correlations of apathy score with age (r=0.53, p= 0.002), FAB (r =-0.52, p=0.003), TMT-B (r =0.48, p=0.007), GDS (r =0.49, p=0.006) and HDRS (r= 0.43, p=0.02) in MCI, whereas no correlations in NC. Regression analysis showed that there was a significant negative correlation of rCBF in the middle frontal gyrus, inferior frontal gyrus and anterior cingulate gyrus of right hemisphere and in the left inferior frontal gyrus with apathy score in MCI (p= 0.05, spatial extent threshold 50 voxels). Conclusion: Our results suggest that apathy are related to aging, depression and frontal lobe dysfunction, especially in the bilateral dorsolateral prefrontal and right anterior cingulate gyrus and that the pathogenesis of apathy might be associated with AD pathology, independently of white matter abnormalities in MCI.
Journal of Alzheimer's Disease, Feb 20, 2017
Background: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory e... more Background: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory effects and vasodilative and immunomodulatory actions that is widely distributed throughout the vascular system of the brain. Objective: To investigate mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline. Methods: The study participants were 288 patients (194 men, 94 women) who gave consent to participate in a 5-year longitudinal survey on arteriosclerosis from 2008 to 2013. The Fazekas classification system (Grade [G] 0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain magnetic resonance imaging (MRI). In addition, all participants were asked to undergo cognitive function tests regarding word/letter fluency, the results of which were assessed for correlations with MR-proADM levels. Results: MR-proADM levels significantly increased with DWML grade progression. The odds ratio for high MR-proADM levels was 3.08 (95% confidence interval: 1.49-5.17) in the groups graded G3 on brain MRI, suggesting that a high level of MR-proADM is an independent risk factor for DWMLs. A significant inverse correlation was observed between MR-proADM levels and cognitive test scores. MR-proADM levels were significantly increased in the G3 group in 2013 compared with 2008.
Autonomic Neuroscience: Basic and Clinical, Oct 1, 2009
HTLV-1 associated myelopathy (HAM) has been known to reveal various clinical manifestations of au... more HTLV-1 associated myelopathy (HAM) has been known to reveal various clinical manifestations of autonomic dysfunction; thus the focus of the present study was to investigate whether or not thoracic spinal cord injury frequently observed in HAM patients leads to cardiovascular autonomic dysfunction. The subjects consist of 18 patients in the chronic phase of HAM (group HAM) and 29 normal subjects (group C). They were examined for CVR-R and total heart rate. A power spectral analysis of R-R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Nominated HAM patients were evaluated by neurological examination using clinical indicators of HAM (EDSS, OMDS and FIM). To examine the degree of atrophy of the upper thoracic spinal cord, we performed individual MR (magnetic resonance) imaging of HAM spinal cords. Correlations between the above indicators and clinical indicators of HAM were examined. The L/H ratio was significantly lower in group HAM (1.67 ± 0.79) than in group C. Significant reduction in the L/H ratio was observed in 8 (88.9%) of 9 patients in group HAM with orthostatic hypotension. The L/H ratio was significantly low in HAM patients with thoracic cord atrophy, strongly suggesting that the coexistence of a thoracic cord lesion is associated with a reduction of cardiovascular sympathetic activity. In conclusion, cardiovascular autonomic dysfunction in HAM patients is mainly associated with cardiac sympathetic efferent abnormalities in the upper thoracic segments.
Neurological Research, Oct 1, 2010
Neuroradiology, May 12, 2009
Journal of the Neurological Sciences, Oct 1, 2017
Background: 123I-iomazenil (IMZ)-SPECT displays the distribution of the benzodiazepine receptor (... more Background: 123I-iomazenil (IMZ)-SPECT displays the distribution of the benzodiazepine receptor (BZR) in the late phase and cerebral blood flow (CBF) in the early phase.
Neuroradiology, Feb 18, 2021
Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on mag... more Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.
Journal of Alzheimer's Disease, Jul 19, 2022
Background: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a po... more Background: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a potential risk factor for further bleeding, while the association between CMBs and the first onset of intracerebral hemorrhage has not been well investigated. Purpose: To analyze the association between CMBs and the first onset of primary intracerebral hemorrhage (pICH). Material and Methods: Two hundred and two consecutive inpatients with ICH and 234 consecutive outpatients without ICH as control group were enrolled in this study. MR imaging including T2 Ã-GRE, T 1 W, T 2 W and fluid attenuated inversion recovery (FLAIR) sequences were performed to detect CMBs and other abnormalities. Prevalence, distribution, and grades of CMBs, as well as the location and size of the intracerebral hematoma were analyzed, respectively. Comparison was made between pICH and control group. Logistic analysis was performed to evaluate the association between CMBs and ICH. The correlation between hematoma size and CMBs grade/numbers was analyzed. Results: CMBs were detected in 140 patients in pICH (69.3%) group and 62 patients in control group (26.5%). The incidence of CMBs in pICH group was significantly higher than that in control group (P , 0.0001). As the logistic regression analysis results, CMBs was the risk factor associated with ICH, with modulation OR value of 8.363 (95% CI 5.210-13.421). The volume of ICH with CMBs was 12.57 + 17.23 mL, and the volume of ICH without CMBs was 17.77 + 26.97 mL. Negative correlation was demonstrated between CMBs number and ICH volume (r s ¼ 20.1769, P ¼ 0.0118), as well as between CMBs grade and hematoma volume (r s ¼ 20.1185, P ¼ 0.1557). Conclusion: CMBs may be an independent risk factor for the first onset of intracerebral hemorrhage.
Journal of Nutrition Health & Aging, Dec 6, 2012
To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we exa... more To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking. Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.
Gerontology, 2010
Background: Hyperhomocysteinemia is correlated with diseases and lifestyle habits. However, there... more Background: Hyperhomocysteinemia is correlated with diseases and lifestyle habits. However, there is no epidemiological evidence concerning the distribution and prevalence of hyperhomocysteinemia in a local community. Objective: The purpose of this study was to clarify the distribution and prevalence of hyperhomocysteinemia and the existence or nonexistence of familial clustering. Methods: The subjects were participants in the Basic Health Check Service 1999. We administered a questionnaire and obtained blood samples from 865 subjects (306 men, 559 women) who agreed to participate in our study. Results: Hyperhomocysteinemia was present in 52 men (17.0%) and 25 women (4.5%). Ten subjects who had hyperhomosysteinemia ha a family member who also had hyperhomocysteinemia. The odds ratio for hyperhomocysteinemia adjusted for age and sex was 4.77 (p < 0.01, 95% CI = 1.95–11.65). Conclusion: Hyperhomocysteinemia shows familial clustering. Men and elderly persons were more likely to have hyperhomocysteinemia.
Magnetic Resonance in Medical Sciences, 2015
Purpose: The brain produces intense heat as a result of cerebral metabolism and cerebral blood fl... more Purpose: The brain produces intense heat as a result of cerebral metabolism and cerebral blood flow, and the generated heat is removed mainly through circulation of the intracranial blood vessels and cerebrospinal fluid (CSF). Because magnetic resonance (MR) images are constructed from analysis of the spin of various molecules, the diffusion coefficient can be used as a parameter that reflects the temperature of water molecules. We used diffusion-weighted imaging (DWI)-based MR imaging to measure the temperature of the CSF around the lateral ventricles in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods: Our study included 33 cases of iNPH (Group N, mean age, 75.1 years) and 40 age-matched controls (Group C, mean age, 74.5 years). We calculated CSF temperature in the ventricular domain using the conversion formula to evaluate the feasibility of iNPH study. Results: The mean temperatures were significantly higher in Group N (37.6°C « 0.4°C) than Group C (36.7°C « 0.5°C; P < 0.01). The cutoff value of 37.2°C (more than the mean + 2 standard deviations [SD] of the values in Group C) showed sensitivity of 72.4% and specificity of 77.5% for distinguishing the 2 groups. We confirmed improved CSF temperature in the lateral ventricles in all patients examined both before and after shunting. Conclusions: Elevated ventricular temperatures in patients with iNPH (Group N) may represent a disturbance in heat balance. Our results showed that thermometry using DWIbased MR imaging can help in the noninvasive and consistent evaluation of CSF temperature and may thus provide a useful supplementary brain biomarker for iNPH.
Journal of Alzheimer's Disease, Nov 28, 2017
Background: The anti-aging protein, ␣-Klotho, may be involved in cognitive decline and has potent... more Background: The anti-aging protein, ␣-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of ␣-Klotho in the brain has not been sufficiently investigated. Objective: Here, we investigated the association between ␣-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). Methods: Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood ␣-Klotho level were retrospectively investigated. Results: The ␣-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the ␣-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low ␣-Klotho level, the odds
Alzheimers & Dementia, Jul 1, 2010
Stroke, Feb 1, 2008
Background and Purpose-Symptomatic progression is frequently observed in lacunar infarcts. The ex... more Background and Purpose-Symptomatic progression is frequently observed in lacunar infarcts. The exact mechanisms of this phenomenon have not yet been clarified. Summary of Cases-We report 2 patients with lenticulostriate artery infarcts that presented with skip lesions that were restricted to gray matter. One of the patients subsequently developed symptomatic deterioration; the other experienced no further neurological events. Conclusions-A possible mechanism of differential vulnerability to ischemia of gray and white matter is considered. White matter may have a longer therapeutic time window for neuroprotective treatment than gray matter.
Autonomic Neuroscience: Basic and Clinical, Dec 1, 2005
The clinical significance of evaluating autonomic nervous system functions in the early stages of... more The clinical significance of evaluating autonomic nervous system functions in the early stages of olivopontocerebellar atrophy (OPCA) has been investigated in 13 OPCA outpatients (7 males and 6 females, mean age: 51.0 years). We have employed measurements of blood pressure, plasma norepinephrine (NE), CVR-R, low-frequency power/high-frequency power ratio (L/H), high-frequency power (HF) score and heart rate (HR) monitoring using Holter ECG recording for evaluation of CVR-R. We have also carried out urodynamic examinations, focusing on the possible existence of bladder dysfunction. Although no significant changes were noted between control and OPCA groups concerning HR, CVR-R, L/H, plasma levels of norepinephrine and systolic blood pressure, HF (high-frequency power) (ms 2), especially at night time, invariably showed a significant decline in OPCA groups. All OPCA patients who showed a decreased circadian HF also exhibited a tendency towards urinary bladder dysfunction. The present results appear to relate to disorder of the parasympathetic autonomic nervous system and neuromuscular dysfunction in the lower urinary tract. In conclusion, HRV (heart rate variability) analysis is a useful and safe tool and a keen predictor for evaluating functional states of autonomic nervous activity, especially in the early stages of OPCA. This study has also suggested the possible efficacy of urodynamic measurements in OPCA patients as an indicator of neuromuscular dysfunction in the lower urinary tract and of parasympathetic malfunction.
Journal of Interferon and Cytokine Research, Nov 1, 2009
The mechanism of the infl ammatory response in the vascular wall in atherothrombosis and during t... more The mechanism of the infl ammatory response in the vascular wall in atherothrombosis and during the progression of atherosclerosis has attracted attention. We focused on the potential usefulness of infl ammatory markers in chronic recurrent brain infarction, and analyzed the role of infl ammatory markers in atherosclerosis of the intracranial artery. The subjects were 2 groups of patients treated between 2004 and 2006: a group of outpatients with recurrent infarction (group RI), who developed atherothrombotic brain infarction twice; another group of outpatients with brain infarction without recurrence (group BI), who developed brain infarction once and remained free of recurrence for >1 year; and a group of control subjects with normal brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) (group C). Plasma samples were collected from each group of patients for the simultaneous measurement of 17 kinds of candidate infl ammatory markers, using a fl uorescent microbead array system, and the results were compared with head MRA fi ndings. The levels of high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) were signifi cantly higher in group RI patients than in groups C and BI. Subjects with a hsCRP level ≥0.3 and a MCP-1 level ≥200 in the serum have, respectively, a 1.92 and 2.98 relative risk to have a potential recurrent infarction. Regarding the relation of infl ammatory marker levels with MRA fi ndings, group RI showed signifi cantly higher levels of hsCRP at M1 lesions and MCP-1 at A1 and M1 lesions than group BI (P < 0.05). In conclusion, the MCP-1 level as well as hsCRP in the blood can be a potential predictive marker of recurrent thrombotic brain infarction, and may refl ect infl ammation that promotes intracranial large-artery atherosclerosis.
Archives of Gerontology and Geriatrics, 2013
Oral Diseases, Sep 1, 2015
Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus... more Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders. This article is protected by copyright. All rights reserved.
Journal of Clinical Neuromuscular Disease, Jun 1, 2014
We report a patient with adult-type Pompe disease treated with enzyme replacement therapy (ERT) f... more We report a patient with adult-type Pompe disease treated with enzyme replacement therapy (ERT) for 5.5 years. We evaluated pulmonary function and muscle strength using 6-minute walk test, manual muscle test, and dynamometer-based measurement. The long-term ERT resulted in a substantial improvement in the pulmonary function and a possible stabilization followed by mild deterioration in muscle power measured by dynamometer and 6-minute walk test. Our data may rationalize the long-term use of ERT for adult-type Pompe disease in terms of maintaining pulmonary function.
Clinical and Applied Thrombosis-Hemostasis, Aug 10, 2009
Background: Platelet-derived microparticles (PDMPs) have attracted attention as blood coagulation... more Background: Platelet-derived microparticles (PDMPs) have attracted attention as blood coagulationpromoting, endothelial cell-activating factors. The objective of this study was to determine the parameters associated with elevated PDMP levels and examine their relationship with atherosclerotic lesions of main intracranial and extracranial arteries. Participants and Methods: Participants included a control group (C) of 61 patients with no apparent cerebral vascular lesions and 110 patients with acute-phase cerebral infarction, consisting of a small-vessel occlusion group (S) of 34 patients, a large-artery atherosclerosis group (L) of 41 patients, a cardioembolism group (CE) of 20 patients, and a stroke of undetermined etiology group (U) of 15 patients. Platelet-derived microparticle levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of admission, and the patients were reclassified into group CP (control level PDMPs), consisting of 70 patients with control PDMP levels, and group HP (high PDMPs), consisting of 40 patients with elevated PDMP levels. All patients underwent cranial magnetic resonance (MR) and carotid ultrasound examinations. Results: Plateletderived microparticle levels were significantly higher in groups S and L than in group C (P < .01). Concomitant intima-media thickness (IMT; odds ratio [OR] ¼ 1.29, P < .05) and concomitant intracranial stenosis (OR ¼ 3.95, P < .01) were significantly correlated with elevated PDMP levels. Fibrinogen and high-sensitivity CRP levels were significantly higher in group HP than in group CP. Conclusion: Alterations in PDMP levels correlated with the presence of atherothrombotic lesions, and PDMP levels are expected to be useful as a clinical indicator, reflecting the presence of intracranial atherosclerotic lesions in the acute phase of cerebral infarction.
Journal of the Neurological Sciences, Oct 1, 2017
Objective: To investigate the relationship between apathy and regional cerebral blood flow (rCBF)... more Objective: To investigate the relationship between apathy and regional cerebral blood flow (rCBF) in mild cognitive impairment (MCI). Patients and Methods/Material and Methods: We performed neuropsychological tests, brain MRI and SPECT of amnestic MCI (n =32) and normal controls (NC) (n =5). We investigated the correlations of apathy score of Japanese version of the apathy scale reported by Starkstein et al. with Fazekas score and the neuropsychological tests, such as GDS-15, hamilton depression rating scale (HDRS), MMSE, FAB, WMS-R, TMT-A/B scores in each group by SPSS. The voxel-wise correlations of rCBF with apathy score were assessed in MCI using SPM8. Results: The mean scores of MCI/NC were 12.2/12.2 in apathy scale, 4.1/1.2 in GDS, 2.6/0 in HDRS, 1.2/1.6 in PVH and 0.8/1.2 in WMH. There was significant correlations of apathy score with age (r=0.53, p= 0.002), FAB (r =-0.52, p=0.003), TMT-B (r =0.48, p=0.007), GDS (r =0.49, p=0.006) and HDRS (r= 0.43, p=0.02) in MCI, whereas no correlations in NC. Regression analysis showed that there was a significant negative correlation of rCBF in the middle frontal gyrus, inferior frontal gyrus and anterior cingulate gyrus of right hemisphere and in the left inferior frontal gyrus with apathy score in MCI (p= 0.05, spatial extent threshold 50 voxels). Conclusion: Our results suggest that apathy are related to aging, depression and frontal lobe dysfunction, especially in the bilateral dorsolateral prefrontal and right anterior cingulate gyrus and that the pathogenesis of apathy might be associated with AD pathology, independently of white matter abnormalities in MCI.
Journal of Alzheimer's Disease, Feb 20, 2017
Background: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory e... more Background: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory effects and vasodilative and immunomodulatory actions that is widely distributed throughout the vascular system of the brain. Objective: To investigate mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline. Methods: The study participants were 288 patients (194 men, 94 women) who gave consent to participate in a 5-year longitudinal survey on arteriosclerosis from 2008 to 2013. The Fazekas classification system (Grade [G] 0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain magnetic resonance imaging (MRI). In addition, all participants were asked to undergo cognitive function tests regarding word/letter fluency, the results of which were assessed for correlations with MR-proADM levels. Results: MR-proADM levels significantly increased with DWML grade progression. The odds ratio for high MR-proADM levels was 3.08 (95% confidence interval: 1.49-5.17) in the groups graded G3 on brain MRI, suggesting that a high level of MR-proADM is an independent risk factor for DWMLs. A significant inverse correlation was observed between MR-proADM levels and cognitive test scores. MR-proADM levels were significantly increased in the G3 group in 2013 compared with 2008.
Autonomic Neuroscience: Basic and Clinical, Oct 1, 2009
HTLV-1 associated myelopathy (HAM) has been known to reveal various clinical manifestations of au... more HTLV-1 associated myelopathy (HAM) has been known to reveal various clinical manifestations of autonomic dysfunction; thus the focus of the present study was to investigate whether or not thoracic spinal cord injury frequently observed in HAM patients leads to cardiovascular autonomic dysfunction. The subjects consist of 18 patients in the chronic phase of HAM (group HAM) and 29 normal subjects (group C). They were examined for CVR-R and total heart rate. A power spectral analysis of R-R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Nominated HAM patients were evaluated by neurological examination using clinical indicators of HAM (EDSS, OMDS and FIM). To examine the degree of atrophy of the upper thoracic spinal cord, we performed individual MR (magnetic resonance) imaging of HAM spinal cords. Correlations between the above indicators and clinical indicators of HAM were examined. The L/H ratio was significantly lower in group HAM (1.67 ± 0.79) than in group C. Significant reduction in the L/H ratio was observed in 8 (88.9%) of 9 patients in group HAM with orthostatic hypotension. The L/H ratio was significantly low in HAM patients with thoracic cord atrophy, strongly suggesting that the coexistence of a thoracic cord lesion is associated with a reduction of cardiovascular sympathetic activity. In conclusion, cardiovascular autonomic dysfunction in HAM patients is mainly associated with cardiac sympathetic efferent abnormalities in the upper thoracic segments.
Neurological Research, Oct 1, 2010
Neuroradiology, May 12, 2009
Journal of the Neurological Sciences, Oct 1, 2017
Background: 123I-iomazenil (IMZ)-SPECT displays the distribution of the benzodiazepine receptor (... more Background: 123I-iomazenil (IMZ)-SPECT displays the distribution of the benzodiazepine receptor (BZR) in the late phase and cerebral blood flow (CBF) in the early phase.
Neuroradiology, Feb 18, 2021
Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on mag... more Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.
Journal of Alzheimer's Disease, Jul 19, 2022
Background: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a po... more Background: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a potential risk factor for further bleeding, while the association between CMBs and the first onset of intracerebral hemorrhage has not been well investigated. Purpose: To analyze the association between CMBs and the first onset of primary intracerebral hemorrhage (pICH). Material and Methods: Two hundred and two consecutive inpatients with ICH and 234 consecutive outpatients without ICH as control group were enrolled in this study. MR imaging including T2 Ã-GRE, T 1 W, T 2 W and fluid attenuated inversion recovery (FLAIR) sequences were performed to detect CMBs and other abnormalities. Prevalence, distribution, and grades of CMBs, as well as the location and size of the intracerebral hematoma were analyzed, respectively. Comparison was made between pICH and control group. Logistic analysis was performed to evaluate the association between CMBs and ICH. The correlation between hematoma size and CMBs grade/numbers was analyzed. Results: CMBs were detected in 140 patients in pICH (69.3%) group and 62 patients in control group (26.5%). The incidence of CMBs in pICH group was significantly higher than that in control group (P , 0.0001). As the logistic regression analysis results, CMBs was the risk factor associated with ICH, with modulation OR value of 8.363 (95% CI 5.210-13.421). The volume of ICH with CMBs was 12.57 + 17.23 mL, and the volume of ICH without CMBs was 17.77 + 26.97 mL. Negative correlation was demonstrated between CMBs number and ICH volume (r s ¼ 20.1769, P ¼ 0.0118), as well as between CMBs grade and hematoma volume (r s ¼ 20.1185, P ¼ 0.1557). Conclusion: CMBs may be an independent risk factor for the first onset of intracerebral hemorrhage.
Journal of Nutrition Health & Aging, Dec 6, 2012
To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we exa... more To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking. Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.
Gerontology, 2010
Background: Hyperhomocysteinemia is correlated with diseases and lifestyle habits. However, there... more Background: Hyperhomocysteinemia is correlated with diseases and lifestyle habits. However, there is no epidemiological evidence concerning the distribution and prevalence of hyperhomocysteinemia in a local community. Objective: The purpose of this study was to clarify the distribution and prevalence of hyperhomocysteinemia and the existence or nonexistence of familial clustering. Methods: The subjects were participants in the Basic Health Check Service 1999. We administered a questionnaire and obtained blood samples from 865 subjects (306 men, 559 women) who agreed to participate in our study. Results: Hyperhomocysteinemia was present in 52 men (17.0%) and 25 women (4.5%). Ten subjects who had hyperhomosysteinemia ha a family member who also had hyperhomocysteinemia. The odds ratio for hyperhomocysteinemia adjusted for age and sex was 4.77 (p < 0.01, 95% CI = 1.95–11.65). Conclusion: Hyperhomocysteinemia shows familial clustering. Men and elderly persons were more likely to have hyperhomocysteinemia.
Magnetic Resonance in Medical Sciences, 2015
Purpose: The brain produces intense heat as a result of cerebral metabolism and cerebral blood fl... more Purpose: The brain produces intense heat as a result of cerebral metabolism and cerebral blood flow, and the generated heat is removed mainly through circulation of the intracranial blood vessels and cerebrospinal fluid (CSF). Because magnetic resonance (MR) images are constructed from analysis of the spin of various molecules, the diffusion coefficient can be used as a parameter that reflects the temperature of water molecules. We used diffusion-weighted imaging (DWI)-based MR imaging to measure the temperature of the CSF around the lateral ventricles in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods: Our study included 33 cases of iNPH (Group N, mean age, 75.1 years) and 40 age-matched controls (Group C, mean age, 74.5 years). We calculated CSF temperature in the ventricular domain using the conversion formula to evaluate the feasibility of iNPH study. Results: The mean temperatures were significantly higher in Group N (37.6°C « 0.4°C) than Group C (36.7°C « 0.5°C; P < 0.01). The cutoff value of 37.2°C (more than the mean + 2 standard deviations [SD] of the values in Group C) showed sensitivity of 72.4% and specificity of 77.5% for distinguishing the 2 groups. We confirmed improved CSF temperature in the lateral ventricles in all patients examined both before and after shunting. Conclusions: Elevated ventricular temperatures in patients with iNPH (Group N) may represent a disturbance in heat balance. Our results showed that thermometry using DWIbased MR imaging can help in the noninvasive and consistent evaluation of CSF temperature and may thus provide a useful supplementary brain biomarker for iNPH.