Akihiko Morita

Polymorphism of the C-Reactive Protein (CRP) Gene Is Related to Serum CRP Level and Arterial Pulse Wave Velocity in Healthy Elderly Japanese

The objective of this study was to clarify relationships between the C-reactive protein (CRP) gene and both the serum level of CRP and arterial pulse wave velocity (PWV), using haplotype analysis of healthy elderly Japanese. Five single-nucleotide polymorphisms (SNPs) of the human CRP gene (rs1341665, rs3091244, rs1800947, rs1130864 and rs1205) were used to genotype 315 healthy elderly Japanese subjects (mean age, 77.9±4.1 years; male/female ratio, 0.96). Linkage disequilibrium was analyzed for the five SNPs. The frequency of each haplotype and diplotype was estimated using the expectation/maximization (EM) algorithm. There were statistically significant associations between the CRP level and two CRP genotypes; the p value for the T allele of rs3091244 (CT+AT+TT vs. CC+CA+AA) was 0.002 (95% confidential interval [CI], 2.1–24), and the p value for the T allele of rs1130864 (TT+TC vs. CC) was 0.002 (95% CI, 2.1–24). The only genotype that was significantly associated with arterial PWV was the C allele of rs1800947, with a p value of 0.039. The haplotype was constructed using rs1341665, rs3091244 and rs1800947, in that order. There was a significant association between the CRP level and the T-T-G haplotype, with a p value of 0.002 (95% CI, 2.1–24). There was a significant association between arterial PWV and the C-C-C haplotype, with a p value of 0.039. We concluded that rs3091244, rs1130864 and the T-T-G haplotype are genetic markers for elevated basal CRP levels. rs1800947 and the C-C-C haplotype appear to be susceptibility markers for atherosclerosis, but this requires confirmation.

Comparison of quantitative EEGs between Parkinson disease and age-adjusted normal controls.

Summary: Quantitative EEG (qEEG) findings in Parkinson disease (PD) have been reported in only five previous studies. In these studies, the sample size was small and the distribution of qEEG changes was not estimated. This is the first qEEG evaluation not only employing multiple logistic regression analysis but also estimating the distribution of qEEG changes. The subjects comprised 45 PD patients without remarkable dementia and 40 age-adjusted normal controls. The lack of ischemic lesions in all subjects was confirmed by MRI. Absolute power values were measured for four frequency bands from delta to beta. The electrodes were divided into six, viz. frontal pole, frontal, central, parietal, temporal, and occipital locations. We calculated the spectral ratio, i.e., the sum of the power values in the alpha and beta waves divided by the sum of the values in the slow waves. The dependent variable was either PD or normal control; the independent variables were the spectral ratios, age, sex, and Mini-Mental State Examination score. The significant predictive variables in PD were the spectral ratios at all electrode locations except for the frontal pole (frontal location: P = 0.025, other locations: P < 0.01). PD presented diffuse slowing in the qEEG when compared with age-adjusted normal controls.

Nested polymerase chain reaction for assessing the clinical course of tuberculous meningitis

The authors examined the usefulness of nested PCR (N-PCR) to detect Mycobacterium tuberculosis (MTB) DNA in CSF for assessing the clinical course of tuberculous meningitis (TBM). N-PCR successfully detected MTB DNA in all nine CSF samples from patients with suspected TBM. During anti-tuberculosis treatments, N-PCR results converted from positive to negative, correlating with the improvement of the patient’s clinical condition.

Prognostic value of cerebrospinal fluid cytokine changes in herpes simplex virus encephalitis

A recent trial suggested that corticosteroid was beneficial in herpes simplex virus encephalitis (HSVE), but that precise role remains unclear. We assessed the differences of cerebrospinal fluid (CSF) cytokine changes between different outcomes and between patients with and without corticosteroid administration at the acute stage of HSVE. Interleukin (IL)-1beta, IL-2, IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor-alpha were measured in 56 serial CSFs taken from 20 adult HSVE patients. Their outcomes were poor in 7 and good in 13 patients, and corticosteroid was administered in 10. The differences in the initial and maximum cytokine values were assessed among the different outcomes. The decline rate of cytokine values between the initial and second CSF samples was also assessed between patients with and without corticosteroid. The initial IFN-gamma and maximum IL-6 with a poor outcome were higher than those with a good outcome (p=0.019 for IFN-gamma and p=0.013 for IL-6). The decline rate of IL-6 in patients with corticosteroid was higher than that without corticosteroid (p=0.034). The initial IFN-gamma and maximum IL-6 CSF values represented prognostic biomarkers in HSVE. One pharmacological mechanism related to corticosteroid in HSVE is apparently inhibition of pro-inflammatory cytokines such as IL-6.

Fatigue in Japanese patients with Parkinson's disease: a study using Parkinson fatigue scale.

The objective of this multicenter cross‐sectional study was to determine the prevalence of fatigue and factors contributing to it in a large sample of Japanese patients with Parkinsons disease (PD). We used the 16‐item Parkinson Fatigue Scale (PFS‐16), which was designed to assess fatigue exclusively associated with PD. We carried out this study using PFS‐16, the Unified Parkinsons Disease Rating Scale, Zungs Self‐Rating Depression Scale, Parkinsons Disease Sleep Scale (PDSS), and the PD quality of life (QOL) scale (PDQ‐39) by interview using questionnaires and physical examination by neurologists in 361 nondemented PD patients. Fatigue (an average PFS score of 3.3 or greater) was revealed in 151 patients (41.8%). Multiple logistic regression analysis indicated that the significant independent variables related to the presence of fatigue were the scores of PDSS and PDQ‐39. Depression score was not a significant contributing factor. Our study revealed that the prevalence of fatigue in Japanese PD patients is as high as that in Western countries, and that fatigue is a relatively independent symptom, although sleep disturbance may be associated with fatigue. Since fatigue is significantly related to QOL reduction, therapeutic interventions including treatment of sleep disturbance are important.

Quantitative EEG analysis of executive dysfunction in Parkinson disease.

Quantitative EEG evaluation in Parkinson disease (PD) reveals diffuse slowing. This is the first quantitative EEG evaluation of the differences between PD with and without executive dysfunction (ExD). The subjects were 32 PD patients without remarkable dementia. The lack of ischemic lesions was confirmed by magnetic resonance imaging. ExD was defined as <70 points on the age-controlled standardized score of the Behavioral Assessment of the Dysexecutive Syndrome. Absolute power was measured for four frequency bands from delta to beta. Electrodes were placed at frontal pole, frontal, central, parietal, occipital, and temporal locations. Spectral ratio was calculated as the sum of power values for alpha and beta waves divided by the sum of values for the slow waves. In multiple logistic regression analysis of each electrode location, the dependent variable was ExD or not, and the independent variables were spectral ratio, age, and Unified Parkinson Disease Rating Scale. The only significant predictor of ExD was spectral ratio at the frontal pole (P = 0.031) and frontal (P = 0.048) locations. PD with ExD exhibited an increase in slow wave activity and a decrease in alpha and fast wave activities in these locations. These findings indicated that the ExD in PD was caused by frontal dysfunction.

Executive dysfunction using behavioral assessment of the dysexecutive syndrome in Parkinson's disease†

The objective of this study was to evaluate the executive dysfunction (ExD) in Parkinsons disease (PD) using the Behavioral Assessment of the Dysexecutive Syndrome (BADS), which provides a wide‐range assessment of ExD. The BADS and the Unified Parkinsons Disease Rating Scale (UPDRS) were investigated in 63 nondemented PD patients who revealed scores of ≥24 points on the Mini‐Mental State Examination based on the DSM‐IV. Multiple logistic regression analysis was performed to evaluate the predisposing factors to ExD, which was defined as <70 points on the age‐controlled standardized score. The total score on the UPDRS was a significant independent predisposing factor to ExD. Among the various parts of the UPDRS, part II was the significant factor for ExD. The profile scores of all subtests on the BADS in patients with ExD were significantly lower than those of patients without ExD. All profile scores decreased with severity of PD, but the changes among these scores differed. ExD in nondemented PD predisposed to a greater severity of PD, particularly as regards the activity of daily living impairment. Nondemented PD revealed wide‐range components of ExD. All components of ExD were impaired with severity of PD, but the patterns of each component exhibited variety.

The Relationship Between Slowing Eegs and the Progression of Parkinson’s Disease

The previous association study confirmed that diffuse slowing of EEGs was present in Parkinson’s disease (PD), demonstrated with the use of the quantitative EEG technique. This study was the first to assess the relationship between progression of PD and quantitative EEG. A total of 106 patients with PD with a mean Hoehn-Yahr stage of 2.73 were serially enrolled. Lack of ischemic lesions was confirmed in all patients by magnetic resonance imaging. Absolute power values were measured for four frequency bands from delta to beta. The electrodes were divided among six locations: frontal pole, frontal, central, parietal, temporal, and occipital locations. Spectral ratio was calculated as the sum of power values for the alpha and beta waves divided by the sum values for the slow waves. The relationship between the progression of PD and spectral ratio was assessed by the Jonckheere-Terpstra trend test. At all electrode locations, spectral ratio significantly decreased with progression of Hoehn-Yahr stage (frontal pole, P = 0.007; frontal, P = 0.005; central, P = 0.031; parietal, P = 0.017; temporal, P = 0.005; occipital, P = 0.010). This shows that the slowing of EEGs became more obvious with PD progression.

Relationship between the thromboxane A2 receptor gene and susceptibility to cerebral infarction.

The risk of cerebral infarction (CI) in an individual is dependent on the interplay between genetic risk factors and environmental influences. Binding of thromboxane A2 (TXA2) to its receptor (TP) modulates thrombosis/hemostasis and plays a significant role in the pathogenesis of CI. The aim of the present study was to investigate the relationship between human TP gene single nucleotide polymorphisms (SNPs) and haplotypes and CI in a Japanese population. A genetic association study was performed in 194 CI patients and 365 non-CI subjects by specifically characterizing 6 SNPs in the human TP gene (rs2271875, rs768963, rs2238634, rs11085026, rs4523 and rs4806942). Analysis demonstrated that there were significant differences in the overall distribution of genotypes and dominant or recessive models of rs2271875 and rs768963 between the CI and the non-CI groups. Multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with CI (p=0.029), even after adjusting for confounding factors (odds ratio: 2.41). Further, the C-T-C haplotype of rs768963-rs2238634-rs4806942 was significantly more frequent in the CI group (23.0%) than in the non-CI group (17.7%). These results suggest that specific SNPs and haplotypes may have utility as genetic markers for the risk of CI and that TP or a neighboring gene is associated with the increased susceptibility to CI.

Relationship between slowing of the EEG and cognitive impairment in Parkinson disease.

Summary A previous study using the quantitative EEG technique confirmed that diffuse slowing of the EEG is present in Parkinson disease. The present study was the first to assess the relationship between cognitive impairment and quantitative EEG in Parkinson disease. A total of 100 patients with Parkinson disease with a mean Hoehn–Yahr stage of 2.68 were serially enrolled. Cognitive impairment was assessed using the Mini-Mental State Examination. Lack of ischemic lesions was confirmed in all the patients by MRI. Absolute power values were measured for four frequency bands from &dgr; to &bgr;. The electrodes were divided among six locations as follows: frontal pole and frontal, central, parietal, temporal, and occipital locations. Spectral ratio was calculated as the sum of power values for the &agr;- and &bgr;-waves divided by the sum of values for slow waves. The relationship between Mini-Mental State Examination score and spectral ratio was assessed by the Jonckheere–Terpstra trend test. At all electrode locations, spectral ratio significantly decreased with a decline in Mini-Mental State Examination score (frontal pole, P = 0.017; frontal, P = 0.028; central, P = 0.019; parietal, P = 0.004; temporal, P = 0.002; occipital, P = 0.006). The rate of patients with Parkinson disease with slowing of the EEG was more frequent with serious cognitive impairment.