Yasuo Terayama

Efficacy of low-dose FK506 in the treatment of Myasthenia gravis--a randomized pilot study.

To determine the efficacy of low-dose FK506 in the treatment of myasthenia gravis (MG), untreated de novo patients were randomly selected to receive treatment with (n = 18) or without (n = 16) FK506, and were evaluated for 1 year after treatment with limitation of daily dose of prednisolone. Low-dose FK506 reduced the duration of early-phase therapy in hospital (p < 0.05) and the need for combined therapy with plasmapheresis and high-dose intravenous methylprednisolone or high-dose intravenous methylprednisolone alone (p < 0.05). It also reduced the daily dose of prednisolone (p < 0.05) required to maintain minimal manifestations of MGFA postintervention status. None of the patients exhibited significant side effects up to 1 year after treatment. These findings suggest that low-dose FK506 is safe and efficacious for the treatment of de novo MG patients.

Changes in substantia nigra and locus coeruleus in patients with early-stage Parkinson's disease using neuromelanin-sensitive MR imaging

Neuromelanin-sensitive magnetic resonance imaging is able to visualize changes associated with neuronal loss in the substantia nigra pars compacta (SNc) and locus coeruleus (LC) in patients with Parkinsons disease (PD). However, the diagnostic accuracy of this technique in the early stages of PD remains unknown. Therefore, changes in the SNc and LC observed using neuromelanin imaging were evaluated in patients with early PD. The signal intensities of the lateral, central, and medial parts of the SNc and that of the LC were measured, and the contrast ratios (CRs) were calculated against the adjacent white matter structures. CRs in the lateral part of the SNc and in the LC were significantly reduced in the early PD group when compared with the controls. Sensitivities and specificities in discriminating early PD patients from healthy controls were 73% and 87% in lateral SNc and 82% and 90% in LC, respectively. Neuromelanin imaging can depict signal alterations in the lateral part of the SNc and in the LC in patients with PD, even in its early stage, and can discriminate between these patients and healthy individuals with high sensitivities and specificities.

Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population

BACKGROUND High C-reactive protein (CRP) levels have been reported to be associated with an increased risk of atherosclerotic cardiovascular events. The relationship of CRP levels to the risk of cerebrovascular events in the Japanese population, which has a lower prevalence of coronary artery disease and a lower CRP level than Western populations, has not been fully clarified. The present study examined the predictive value of serum high sensitivity CRP (hs-CRP) levels for future cerebrovascular events and mortality in the general Japanese population. METHODS The subjects for this community-based, prospective cohort study were recruited from the general population (n=7901, male only, mean age=64.0 years). Serum hs-CRP levels and cardiovascular risk factors were determined at baseline. The mean follow-up period was 2.7 years. After excluding subjects with a cardiovascular history, the relationships between hs-CRP levels and cerebrovascular events and mortality were assessed. RESULTS During follow-up, 130 participants had a first stroke (95 ischemic strokes), and 161 participants died. The hs-CRP tertile level was a significant predictor for a first ischemic stroke (3rd tertile, HR=1.77: 95% Cl, 1.04-3.03, compared with the 1st tertile), after adjustment for age and classical cardiovascular risk factors. Similar trends were observed for the prediction of all-cause mortality (3rd tertile, HR=2.26: 95% Cl, 1.49-3.42, compared with the 1st tertile). CONCLUSION CRP levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population, independently from traditional cardiovascular risk factors.

Differentiation of early-stage parkinsonisms using neuromelanin-sensitive magnetic resonance imaging.

PURPOSE The purpose of this study was to investigate whether the signal intensity of the substantia nigra pars compacta (SNc) and locus coeruleus (LC) on neuromelanin-sensitive magnetic resonance imaging (MRI) can discriminate early-stage parkinsonism disorders, for which differential diagnosis is generally difficult. METHODS Neuromelanin-sensitive MRI at 3 T was performed in 53 patients with early parkinsonism and 22 healthy controls. After an observation period of >1.5 year, the patients were clinically diagnosed with Parkinsons disease (PD; n = 30), multiple system atrophy with predominant parkinsonism (MSA-P; n = 10), or progressive supranuclear palsy syndrome (PSPS; n = 13). The signal intensity of the lateral, central, and medial parts of the SNc and the LC were measured and the contrast ratios (CR) against adjacent white-matter structures was calculated. RESULTS The CR of the lateral SNc was lower in the PD and MSA-P groups than in the PSPS and control groups (p = 0.0001-0.05). The CR of the LC was lower in the PD group than in the other groups (p = 0.0001-0.05). Sensitivity and specificity of the CRs for discriminating PD from MSA-P was 60% and 90%, respectively, those for PD/PSPS were 63-88% and 77-92%, respectively, and those for MSA-P/PSPS were 80% and 85%, respectively. These properties were comparable or better to MIBG scintigraphy. CONCLUSIONS Neuromelanin-sensitive MRI can depict differences in signal intensity of the lateral SNc and the LC among the parkinsonism disorders at their early stages.

Use of Neuromelanin-Sensitive MRI to Distinguish Schizophrenic and Depressive Patients and Healthy Individuals Based on Signal Alterations in the Substantia Nigra and Locus Ceruleus

BACKGROUND We investigated alterations in the substantia nigra pars compacta (SNc) and locus ceruleus (LC) in schizophrenic and depressive patients by using a neuromelanin-sensitive magnetic resonance imaging (MRI) technique that enables direct visualization of these nuclei and examined whether this technique could distinguish between these disorders and healthy subjects. METHODS Using a neuromelanin-sensitive T1-weighted MRI technique, we examined 20 schizophrenia patients, 18 depressive patients, and 34 healthy control subjects. The signal intensities of the areas corresponding to the SNc and LC were measured, and the contrast ratios (CR) to the adjacent white matter were calculated. RESULTS The CR of the SNc was significantly higher in schizophrenic patients (22.6 +/- 5.6) than in depressive patients (19.2 +/- 4.7) and healthy control subjects (19.6 +/- 3.8), whereas the CR of the LC in depressive patients (7.7 +/- 2.4) was significantly lower than that in healthy control subjects (11.0 +/- 3.9) and schizophrenic patients (10.0 +/- 3.1). Further, the difference in the CR between the SNc and LC was significantly greater in schizophrenic patients (12.6 +/- 6.7) than in control subjects (8.6 +/- 4.1). CONCLUSIONS Neuromelanin-sensitive MRI enables visualization of alterations in the SNc and LC that are observed in schizophrenia and depression.

Increased mitochondrial oxidative damage and oxidative DNA damage contributes to the neurodegenerative process in sporadic amyotrophic lateral sclerosis

To investigate the possibility that mitochondrial oxidative damage or oxidative DNA damage or both contribute to the neurodegenerative process of sporadic amyotrophic lateral sclerosis (sALS), this study used high-performance liquid chromatography with an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q10 (CoQ10) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 17 patients with sALS and 17 age-matched controls with no neurological diseases. The percentage of oxidized CoQ10 in the CSF of sALS patients was greater than that in the CSF of controls (p<0.002) and was negatively correlated with the duration of illness (ρ=−0.61, p<0.01). The concentration of 8-OHdG in the CSF of sALS patients was greater than that in the CSF of controls (p<0.005) and was positively correlated with the duration of illness (ρ=0.53, p<0.005). The percentage of oxidized CoQ10 was correlated with the concentrations of 8-OHdG in the CSF of sALS patients (ρ=−0.53, p<0.05). These results suggest that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of sporadic amyotrophic lateral sclerosis.

Effects of yokukansan on behavioral and psychological symptoms of vascular dementia: An open-label trial

Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia (BPSD). The present study was conducted to elucidate the efficacy of yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients (9 men and 4 women) who were diagnosed as having vascular dementia (VaD) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks. Their mean age was 71.2±6.5 years. The BPSD was evaluated using the Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini-Mental State Examination (MMSE), the activities of daily living was evaluated by Barthel index (BI) and Disability Assessment for Dementia (DAD), and the extrapyramidal signs were evaluated by United Parkinsons Disease Rating Scale (UPDRS). The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment, respectively. It was significantly improved after treatment (p<0.05). In the NPI-subcategories, there was a significant improvement in agitation and disinhibition after the treatment. There was no significant change in MMSE, BI, DAD or UPDRS before and after the treatment. There was no adverse effect during the treatment period. The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients.

Leukb‐Araiosis and Cerebral Hypoperfusion Compared in Elderly Normals and Alzheimer's Dementia

To elucidate the pathogenesis of leuko‐araiosis in patients with Alzheimers disease by utilizing CT densitometry of the brain and measurements of local perfusion in order to quantify the extent of leuko‐araiosis and local hypoperfusion compared with similar measurements made among age‐matched normal volunteers.

Increased mitochondrial oxidative damage in patients with sporadic amyotrophic lateral sclerosis

To investigate whether mitochondrial oxidative damage contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (sALS), we used high-performance liquid chromatography with an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q10 (CoQ10) in the cerebrospinal fluid (CSF) of 30 patients with sALS and 17 age-matched controls with no neurological diseases. The percentage of oxidized CoQ10 in the CSF of sALS patients were significantly greater than those in the CSF of controls (P<0.002) and were negatively correlated with duration of illness (rho=-0.64, P<0.001). These results suggest that mitochondrial oxidative damage contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis.

Detection of changes in cerebrospinal fluid space in idiopathic normal pressure hydrocephalus using voxel-based morphometry

IntroductionWe attempted to detect alterations in the cerebrospinal fluid (CSF) space in patients with idiopathic normal pressure hydrocephalus (iNPH) using voxel-based morphometry (VBM).MethodsWe obtained sagittal volume images of the entire head by three-dimensional T1-weighted magnetic resonance imaging and compared the regional distribution of CSF in 12 patients with iNPH, 14 patients with Alzheimer’s disease (AD), and 17 healthy individuals using VBM with automatically extracted CSF objects.ResultsVBM demonstrated significant widening at the lateral ventricles and Sylvian fissures and narrowing of the CSF space at the high convexity/midline areas in iNPH patients, compared to the AD patients and healthy controls (p < 0.05, after correction with a false-discovery rate). In addition, the ratio of the CSF volume in the lateral ventricle/Sylvian fissure area to that in the high convexity/midline area in iNPH patients (3.9 ± 1.2) was remarkably greater than that in AD patients (1.2 ± 0.3) and controls (0.9 ± 0.3; one-way ANOVA, p < 0.001; post hoc Tukey’s test, p < 0.001); we could discriminate iNPH patients from those in the other two groups without any overlap, when using a cutoff level of 1.9.ConclusionVBM using CSF objects can be used to delineate the characteristic alteration of the CSF space in iNPH patients, which has been evaluated by visual interpretation.