A descriptive study of Parkinson disease and atypical parkinsonisms in the Annuals of the Pathological Autopsy Cases in Japan.

Although many entities have been established within the broad spectrum of Parkinson disease (PD) and atypical parkinsonisms, they are often difficult to differentiate. To clarify the current clinical diagnostic conditions and problems in PD and atypical parkinsonisms, we analyzed volumes of the Annuals of the Pathological Autopsy Cases in Japan. Among 130 105 autopsies conducted from 2007 to 2016 throughout Japan, patients were included in the study if they had been either clinically or pathologically diagnosed with PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD). Autopsy rates were 6.4% for clinically diagnosed PD, 34.1% for MSA, 16.3% for PSP, and 17.4% for CBD. The specificities and sensitivities of clinical diagnoses were 88.0% and 82.0% for PD, 95.2% and 86.0% for MSA, 82.7% and 73.2% for PSP, and 55.4% and 57.7% for CBD, respectively. Clinical diagnoses had relatively high accuracy, but low autopsy rates are of concern. Many patients with rarer disorders were clinically misdiagnosed with PD, a more common disorder. Autopsy rates, irrespective of specific disorders, should be increased to detect rare diseases. Increasing autopsy rates will increase the available clinical information regarding pathologically confirmed patients and contribute to more accurate clinical diagnoses.

Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions.

Although several studies have demonstrated correlation between white matter hyperintensities (WMH) and impairment of executive functions, the underlying anatomical-functional relationships are not fully understood. The present study sought to investigate the correlations between the volume of WMH and medial temporal lobe atrophy (MTA) using quantitative magnetic resonance image (MRI) and a variety of executive function assessments. A total of 91 patients ranging in age from 58 to 90 years with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or early phase AD were recruited from the outpatient clinic at the Department of Neurology of Nagoya City University Hospital. We administered neuropsychological batteries evaluating verbal memory, orientation, spatial ability, sustained attention, and a variety of executive functions, including verbal fluency, flexibility, inhibition, and working memory. Quantitative MRI analyses were performed using Dr. View/Linux software and a voxel-based specific regional analysis system. Significant correlations were observed between WMH, as well as MTA, and some executive function scores. Regression analysis revealed that MTA was the strongest predictor of flexibility and verbal fluency. These findings provide new insight into the relationship between quantitative MRI analyses and various types of executive dysfunction in elderly people with MCI due to AD and/or early phase AD. When cognitive function is examined in elderly patients with MCI due to AD or early phase AD, it is important to consider the involvement of WMH and MTA, which is indicative of AD pathology in cognitive dysfunction, particularly executive function.

Impaired Motor Skill Acquisition Using Mirror Visual Feedback Improved by Transcranial Direct Current Stimulation (tDCS) in Patients With Parkinson's Disease.

Recent non-invasive brain stimulation techniques in combination with motor training can enhance neuroplasticity and learning. It is reasonable to assume that such neuroplasticity-based interventions constitute a useful rehabilitative tool for patients with Parkinson's Disease (PD). Regarding motor skill training, many kinds of tasks that do not involve real motor movements have been applied to PD patients. The purpose of this study is to elucidate whether motor skill training using mirror visual feedback (MVF) is useful to patients with PD in order to improve untrained hand performance dependent on the time course of training; and whether MVF combined with anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) causes an additional effect based on increased motor cortical excitability. Eighteen right-handed patients with PD in the off-medication state and 10 age-matched healthy subjects (HS) performed four sessions of right-hand ball rotation using MVF (intervention) on two separate days, 1 week apart (day 1 and day 2). HS subjects received only sham stimulation. The intervention included four sessions of motor-skill training using MVF for 20 min comprised of four sets of training for 30 s each. PD patients were randomly divided into two intervention groups without or with anodal tDCS over the right M1 contralateral to the untrained hand. As the behavior evaluation, the number of ball rotations of the left hand was counted before (pre) and immediately after (post) intervention on both days (pre day 1, post day 1, pre day 2, and post day 2). Motor evoked potential (MEP), input-output function, and cortical silent period were recorded to evaluate the motor cortical excitatory and inhibitory system in M1 pre day 1 and post day 2. The number of ball rotations of the left hand and the facilitation of MEP by intervention were significantly impaired in patients with PD compared to HS. In contrast, if anodal tDCS was applied to right M1 of patients with PD, the number of ball rotations in accordance with I-O function at 150% intensity was significantly increased after day 1 and retained until day 2. This finding may help provide a new strategy for neurorehabilitation improving task-specific motor memory without real motor movements in PD.

Integrated mental health care in a multidisciplinary maternal and child health service in the community: the findings from the Suzaka trial.

BACKGROUND: Perinatal mental health problems such as mood disorders are common. We propose a new multidisciplinary health service intervention program providing continuous support to women and their children from the start of pregnancy till after childbirth. The aim of this study was to examine the effects of the program with respect to making women's mental health better in the postpartum period and improving the state of care for women and their children in the perinatal period. METHODS: We performed a controlled study to investigate the effectiveness of the program in Suzaka City, Japan. The women's mental health status was assessed using the Edinburgh Postnatal Depression Scale (EPDS) 3 months postpartum. Of 349 women, 210 were allocated to the intervention group and 139 to the control group. From April 2014 to March 2015, the number of the pregnant women who were followed-up by the multidisciplinary meeting in the intervention and control groups were 60 and 4, respectively. In the same period, the number of the pregnant women who were identified as requiring intensive care were 21 and 2, respectively. RESULTS: The total EPDS score, which was the primary outcome of the present study, differed significantly between the intervention and control groups (Mean [SD] = 2.74 (2.89) and 4.58 [2.62], respectively; p < 0.001). The number of the women receiving counseling from a public health nurse (5.3% in intervention group, 0.7% in control group, p = 0.02), attending maternal seminars (attendant ratio: 46% whereas 16%, p = 0.01), and receiving home visits by public health nurses (home visit ratio: 93.8% whereas 82.6%, p < 0.001) was significantly higher in the intervention group compared to the control group. CONCLUSIONS: The present study indicates that continuum support provided by integrated mental health care through a multidisciplinary maternal and child health service in the community can make women's mental health better in the postpartum period and help women and their children receive more health services from public health nurses. TRIAL REGISTRATION: Name of registry: Research for the effectiveness of a multi-professional health service intervention program of continuum supports for mother and child which starts for pregnancy periods to enhance maternal mental health. UMIN Clinical Trials Registry number: UMIN000032424 . Registration date: April 29th, 2018. Registration timing: retrospective.

Establishing a New Screening System for Mild Cognitive Impairment and Alzheimer's Disease with Mental Rotation Tasks that Evaluate Visuospatial Function.

BACKGROUND: The mental rotation task is well-known for the assessment of visuospatial function; however, it has not been used for screening of dementia patients. OBJECTIVE: The aim of this study was to create a simple screening test for patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by focusing on non-amnestic symptoms. METHODS: Age-matched healthy controls (age 75.3±6.8), patients with MCI (76.5±5.5), and AD (78.2±5.0) participated in this study. They carried out mental rotation tasks targeting geometric graphics or alphabetical characters with three rotating angles (0°, 90°, and 180°) and indicated the correct answer. Response accuracy and reaction time were recorded along with their eye movements using an eye tracker. To quantify their visual processing strategy, the run count ratio (RC ratio) was calculated by dividing the mean number of fixations in incorrect answers by that in correct answers. RESULTS: AD patients showed lower accuracy and longer reaction time than controls. They also showed a significantly greater number of fixation and smaller saccade amplitude than controls, while fixation duration did not differ significantly. The RC ratio was higher for AD, followed by MCI and control groups. By setting the cut-off value to 0.47 in the 180° rotating angle task, we could differentiate MCI patients from controls with a probability of 80.0%. CONCLUSIONS: We established a new screening system for dementia patients by evaluating visuospatial function. The RC ratio during a mental rotation task is useful for discriminating MCI patients from controls.

[Replacement therapy of adrenal insufficiency].

The adrenal cortex produces three principal categories of steroid hormones that regulate a wide variety of physiologic process from fetal to adult. Three steroid hormones are glucocorticoids (principally cortisol), mineralocorticoids (principally aldosterone) and adrenal androgens. Glucocorticoids are named for their carbohydrate mobilizing activity but are ubiquitous physiologic regulators influencing a wide variety of bodily functions. In case of deficiency of endogenous adrenal cortex steroid hormones, glucocorticoid replacement therapy is employed. There are two pathologic forms in steroid hormones deficiency, one is "the primary" that is adrenal failure and the other is "the secondary" that is pituitary failure. Symptoms and treatments are different between the two forms and onset (acute or chronic).

Augmentation of antitumor immune responses by multiple intratumoral inoculations of replication-conditional HSV and interleukin-12.

Intratumoral inoculation with a herpes simplex virus (HSV) mutant, G207, as an in situ cancer vaccine has been shown to inhibit tumor growth by inducing tumor-specific immune responses. Here, as a step toward the clinical application of this therapeutic approach, we evaluated different protocols for enhancing the antitumor effect. First, in a bilaterally established tumor model with CT26 colon carcinoma, we demonstrated that multiple intratumoral inoculations with G207 induced a greater antitumor effect on both the inoculated and distant tumors than did 1 or 2 inoculations. Second, to boost this antitumor effect, we developed 2 strategies: multiple in situ cancer vaccines with G207 in combination with systemic administration of recombinant interleukin-12 (rIL-12) (G207/systemic rIL-12) or local administration of rIL-12 (G207/local rIL-12). The antitumor effects in both the inoculated and distant tumors by the combined treatments were significantly greater than by either G207 or rIL-12 treatment alone. G207/systemic rIL-12 and G207/local rIL-12 mediated the complete regression of both the inoculated and distant tumors in 67% and 79% of the animals, respectively. These results indicate that multiple intratumoral inoculations of G207 and systemic or local rIL-12 administration work synergistically to facilitate tumor regression and that this combination of treatments may have potential for treating cancer metastasis.