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Aim People living with early-onset dementia (EOD) have specific social needs. Epidemiological studies are needed to obtain current information and provide appropriate service planning. This study aimed to clarify the current prevalence and subtype distribution of EOD, as well as the services frequently used by individuals with EOD. Methods A multisite, population-based, two-step study was conducted. Questionnaires were sent to 26 416 candidate facilities in 12 areas with a target population of 11 630 322 to inquire whether any individuals with EOD had sought services or stayed during the last 12 months (step 1). When "yes" responses were received, additional questionnaires were sent to the facilities both to complete and to distribute to the target individuals with EOD to obtain more detailed information, including the dementia subtype (step 2). Results In step 1, valid responses were obtained from 16 848 facilities (63.8%), and 4077 cases were identified. In step 2, detailed information was obtained for 1614 cases (39.6%) from the facilities and 530 cases (13.0%) from the individuals. The national EOD prevalence rate was estimated to be 50.9/100 000 population at risk (95% confidence interval: 43.9-57.9; age range, 18-64 years). The number of individuals with EOD was estimated to be 35 700 as of 2018. Alzheimer-type dementia (52.6%) was the most frequent subtype, followed by vascular dementia (17.1%), frontotemporal dementia (9.4%), dementia due to traumatic brain injury (4.2%), dementia with Lewy bodies/Parkinson's disease dementia (4.1%), and dementia due to alcohol-related disorders (2.8%). Individuals with EOD were most frequently identified at medical centers for dementia. Conclusion The prevalence rate estimated in this study was comparable to those in previous studies in Japan. However, the subtype distribution differed, with Alzheimer-type dementia being the most prominent. Based on the case identification frequencies, medical centers for dementia are expected to continue to function as the primary special health service by providing quality diagnosis and post-diagnostic support for individuals with EOD.

Objective/Background Older people with dementia often show behavioural and psychological symptoms of dementia such as agitation, aggression, and depression that affect their activities of daily living, and hence reduce the quality of life of their caregivers. The aim of this study was to investigate the effects of a new technological intervention—a parametric speaker, creating a narrow personal acoustic environment, which may reduce the manifestation of behavioural and psychological symptoms of dementia symptoms. Methods A parametric speaker was placed on the ceiling of a large day room, and personally selected pieces of music were provided in a narrow space just under the speaker during the intervention. Two older residents with behavioural and psychological symptoms of dementia participated in the experiment. Results Playing pieces of favorite music via the parametric speaker decreased their behavioural and psychological symptoms of dementia during the intervention. In addition, this intervention reduced the burden on caregivers. One of the advantages of using parametric speaker was being able to create a personal space in a common room. Conclusion We considered that the parametric speaker might be useful to reduce behavioural and psychological symptoms of dementia and the burden on caregivers, providing individualized rehabilitation for the improved quality of life of residents.

AIM The purpose of this study was to evaluate whether the clock drawing test (CDT) is useful to assess the cognitive function of community-dwelling elderly people. We evaluated the CDT as a tool to measure cognitive function by qualitative and quantitative analyses. METHODS A total of 14,949 community-dwelling elderly were invited by mail to undergo cognitive screening by CDT. Of these, 8,815 responded, of which 8,684 were eligible for enrollment. We were also able to determine the educational background of 7,404 of these. There were 3,525 men (age: 73.05±6.20 [mean±standard deviation] years old, duration of education: 11.40±2.81 years) and 3,879 women (73.67±6.66, 10.34±2.19) . The drawn clocks were evaluated using the Freedman method, and those clocks drawn with obvious errors such as no circle, numbers, or hands were recorded and analyzed. In addition, any vertical deviation from the center points was also evaluated. RESULTS The recorded percentages of the subjects who correctly completed the individual clock drawing test components varied. The mean total scores were 14.16±1.67 in men and 14.40±1.36 in women. The percentages of subjects with total scores of less than 13 were 16.09% in men and 11.7% in women. The percentage of subjects who made obvious errors was 3.24%, whose total points were significantly lower than those of the subjects who did not. Approximately half of all subjects showed vertical deviation from the center of the clock, and the percentage of upper deviation was greater than that of lower deviation. CONCLUSION CDT is useful to assess the cognitive function of community-dwelling elderly people, and it is also helpful to determine subjects with a potential risk of cognitive impairments.

We have developed a Robot Assisted Activity (RAA) program for recreational use in health care facilities for elderly people. The RAA program has been evaluated in such a facility to assess its usefulness. The program applies a standard classroom model, starting with homeroom and including lessons in the Japanese language, music, gymnastics, arithmetic, and other subjects. At the end of the program, there is a graduation ceremony. We use a video camera to record each scene. Each behavior and utterance of the participants is then analyzed. In addition, immediately upon completion of the RAA program, specialists conduct a Focus Group Interview (FGI) in which they collect comments, opinions, and requests from the participants. Ten elderly people participate in the program, two men and eight women (81.0±3.7 years old). All are residents at a health care facility in Aichi Prefecture, Japan. TheMMSE (MiniMental State Examination) score indicating the level of dementia is 24.1±3.0 points. Two participants are judged to be in a moderate stage of cognitive decline (21 points or less), six are in a mild stage (22-26 points), and the remaining two are normal. On the Geriatric Depression Scale (GDS), in which a score of 13.3±4.2 points indicates a state of depression, seven participants are judged to be depressive (11 points or more). The results of our study show that all participants have a favorable impression of the robot and nearly all have a positive opinion of the RAA program. This suggests that the program can be used for emotional and recreational therapy at health care facilities for the elderly. However, in spite of the overall success of the RAA program, we seldom observe interaction between participants and the robot.

AIM The number of group homes for elderly people with dementia has been increasing since the introduction of public long-term care insurance in Japan. The aim of this report is to clarify the differences in the end-of-life policy and practices among group homes managed by medical corporations and those run by social welfare corporations. METHODS A questionnaire for end-of-life care policy and practices was mailed to 1,535 group homes managed by medical corporations and 2,022 group homes managed by social welfare corporations. The questions related to the general characteristics of group homes, availability of admission to hospital, whether a doctor visits regularly or not, involvement in end-of-life care, experiences of previous end-of-life care, and provisions for anticipated end-of life care. RESULTS The response rates were 55.2% for medical corporations and 59.6% for public welfare corporations. Most group homes have one care unit. More than 50% of medical corporation-managed and more than 30% of social welfare corporation-managed group homes were involved with end-of-life care. Previous experiences with end-of-life care experienced in both types of group homes were reported to be 38.0% and 30.1%, respectively. The results of end-of-life care were evaluated positively in both types of group home. Group homes managed by medical corporations which also managed hospitals and group homes managed by social welfare corporations with regular visits of doctors showed a high percentage of cooperation with and previous experience of end-of-life care. CONCLUSIONS Cooperation between medical and care staffs in end-of-life care of the elderly with dementia in group homes is important. This report demonstrated that education about end-of-life care to the staffs of group home is necessary.

The aim of this study is to investigate the frequency, causes, and clinical characteristics of individuals with presenile dementia with an age of onset less than 65 years. A staged questionnaire survey was performed among all hospitals and clinics, all faculties of care and welfare services, and all local governmental offices in Aichi prefecture. The response rate of the primary survey was 62.3%, and that of the secondary survey was 90.1%. The number of people with presenile dementia after adjusting for duplicated subjects was 1,092 (569 men, 520 women and 3 of unknown gender). The average age was 60.7 +/- 7.1 (mean +/- SD) years, and age of onset was 55.1 +/- 7.8 years. Vascular dementia (VD) was the most frequent cause in men (42.2%), followed by Alzheimer's disease (AD: 24.8%), frontotemporal dementia (FTD: 4.6%) and Parkinson disease (PD: 3.8%). In women, AD was the most common (45.8%), followed by VD (25.4%), FTD (7.4%) and PD (3.4%). Overall, AD and VD were the most common causes of presenile dementia, followed by FTD and PD. The highest prevalence of presenile dementia was seen in the age range of 60- 64-years-old. This was true for both men and women.

In 38 patients with hypoparathyroidism, electrolytes, amino-terminal PTH(1--34) and carboxyl-terminal PTH in serum and urinary cyclic AMP were measured. Serum PTH(1--34) levels were low and C-PTH levels measured simultaneously in the same sera were low except one having a high level. In pseudohypoparathyroidism, serum C-PTH was elevated and in 1 of 2 patients serum PTH(1--34) was elevated. Urinary cyclic AMP was decreased in hypoparathyroidism and there was a positive correlation between urinary cyclic AMP and serum PTH in normal subjects and parathyroid dysfunctions. Responses of urinary cyclic AMP to PTH were better in hypoparathyroidism and less in primary hyperparathyroidism than normal subjects. These data suggest that measurements of serum PTH(1-34), C-PTH and urinary cyclic AMP are important in the diagnosis and pathophysiological classification of hypoparathyroidism.

Nine patients with multiple system atrophy (MSA) were studied based on MRI findings of cerebral hemispheric involvement. The age at onset was 56.4+/-8.6 (mean+/-S.D.) years, duration of illness at the first MRI study 2.1+/-1.1 years, duration of illness at the last study 9.7+/-2.6 years, and the follow-up duration 7.6+/-2.3 years. Controls were 85 neurologically intact persons (60.2+/-11.1 years age). In the MRI study, measurements of the ratio of each area to the intracranial area were performed for the cerebral hemisphere, frontal, temporal and parietal-occipital lobes. A significant progression of atrophy to under the normal limit was observed in the cerebrum, frontal and temporal lobes. Besides the typical pathological lesions in MSA, five autopsied patients revealed frontal lobe atrophy with mild gliosis, mild demyelination and glial cytoplasmic inclusions (GCIs). One of these patients showed remarkable frontal lobe atrophy with degenerative changes in the cerebral cortex. We observed the involvement of the cerebral hemisphere, especially the frontal lobe.

We analyzed the results of the clock drawing test (CDT) in patients with Alzheimer's disease (AD) by quantitative and qualitative methods to evaluate its significance for cognitive function screening. We administered the CDT and mini-mental state examination (MMSE) to a total of 156 AD patients, and CDT performance was scored quantitatively in accordance with the method by Freedman, while the CDT error types were qualitatively classified by Rouleau's method. We divided AD patients into three groups by their MMSE total score (A: 23 ≤, B: 18~22, C: ≤ 17). The mean total scores of CDT and MMSE in AD were 11.5 ± 3.4 and 19.8 ± 4.7, respectively, and the total CDT scores showed significant positive correlation with the total MMSE scores (r = 0.450). Fewer than 80% of subjects drew the clock correctly for 8 out of 15 sub-items, and fewer were able to correctly draw clock hands than could correctly draw numbers, contour or a center. In analysis of CDT qualitative error types, the most common error types were spatial and/or planning deficit (SPD) (28.2%), and conceptual deficit (CD) (23.7%), which suggested visuospatial impairments and semantic impairments play essential roles in AD patients' poor clock drawings. The frequency of CD and SPD error types significantly increased as severity of cognitive function worsened (p < 0.001, p < 0.05, respectively), and those of stimulus-bound response and perseveration had tendency to increase as severity of cognitive function. The present study suggests that CDT is a useful screening method not only for the impairment of cognitive function and the severity of cognitive dysfunction, but also for identification of specific cognitive function impairments in AD patients.

The autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. He showed slowly progressive spasticity, pseudobulbar palsy and character change, and died 32 months after the onset of symptoms. Autopsy revealed severe atrophy of the frontal and temporal lobes, remarkable neuronal loss and gliosis in the precentral gyrus, left temporal lobe pole and amygdala, mild degeneration of the Ammon's horn, degeneration of the corticospinal tract, and very mild involvement of the lower motor neurons. The anterior horn cells only occasionally demonstrated Bunina body by cystatin-C staining, and skein-like inclusions by ubiquitin staining. This is a peculiar case with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease predominantly affecting the upper motor neuron.

AIM The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. METHODS At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. RESULTS At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p

Slit-hyperintensity in the outer margin of the putamen on T2 weighted MRI was found in 17 out of 28 patients with clinically diagnosed multiple system atrophy. Thirteen of these 17 patients showed extrapyramidal signs. Five patients had only unilateral slit-hyperintensity; four of them had contralateral rigidity; and one had bradykinesia. Despite mild rigidity, one case showed no slit-hyperintensity. One of the 14 cases with parkinsonism showed no hyperintensity, and four of the 14 cases without parkinsonism showed hyperintensity. On the other hand, slit-hyperintensity was not seen in any of 25 patients with clinically diagnosed Parkinson's disease. Putaminal slit-hyperintensity is a useful MRI feature in the differential diagnosis between Parkinson's disease and multiple system atrophy predominantly affecting the extrapyramidal system.

We developed a robot-assisted activity (RAA) program using learning tasks with a communication robot. The purpose of this study was to examine the usefulness of this RAA program for elderly people. Subjects were four women (aged 81.5 ± 3.1 years old) living in a geriatric health services facility. The cognitive ability of the participants estimated by Mini-Mental Status Examination (MMSE) was 23 ± 2.8 points. The RAA program consisted of reading aloud a Japanese folk tale and arithmetic calculation including addition, subtraction, multiplication, and division. Participants were asked to perform the RAA program at least once daily for 1 month in their private room. The communication robot (Business Design Laboratory, Nagoya, Japan) could talk with humans and change its facial expression. The time required for the RAA program was approximately 20 min. A focus group interview (FGI) was held for all subjects after the intervention period. Subjects performed the RAA program 57 ± 33 times during the intervention period. The FGI identified positive opinions regarding the robot such as interest in it, attachment to it, and pleasure obtained through it.

AIM Hip fracture in elderly people is a major risk factor in the deterioration of activities of daily living (ADL). The aim of this study was to investigate the incidence of hip fractures and the neurological symptoms contributing to hip fracture in patients with subacute myelo-optic-neuropathy (SMON), a drug-induced neurological disease manifesting various symptoms. METHODS We investigated the incidence of hip fracture in 3,269 SMON patients with 24,187 medical check-ups from 1979 through 2007 by the SMON Research Committee in Japan. Neurological symptoms were evaluated in 80 patients who had undergone clinical examinations within 2 years before the fracture (hip-fracture group: age at examination = 75.7 ± 8.8 years (mean ± SD)), and the control group (160 SMON patients without a history of hip fracture; 76.5 ± 10.4) were matched for age, gender, and duration of illness. Incidence of hip fracture in SMON as well as severity of visual acuity, motor and sensory symptoms, and ADL were investigated. RESULTS A total 230 hip fractures occurred in 208 patients (6.4%) with a men-to-women ratio of 21 : 187. In comparison with the Japanese general population, SMON patients showed a statistically high incidence of hip fracture in the 50s and 60s age groups in women (p < 0.002 in both), and in those under 40 (p < 0.02) and in their 50s (p < 0.002) in men. In those with neurological symptoms related to gait, the percentage of subjects who could walk with crutches was significantly higher in the hip-fracture group (43.8%) than in the control group (28.1%) (p < 0.05). Analysis of the vibratory sensation revealed that the hip-fracture group showed a significantly higher percentage of severe impairment (51.9%) than the control group (32.0%) (p < 0.025). There were no significant differences in variance between the two groups in other clinical symptoms or ADL. CONCLUSIONS Impairment of vibration sense, a deep sensation, is more likely to be associated with falling and hip fracture than visual acuity or other neurological symptoms in SMON patients. Those persons with vibration sense disturbance, such as elderly or patients with neurological diseases, should be particularly cautious of falling.

Chronic illnesses are common among elderly people, and may considerably affect to their quality of life (QOL). We investigated the impact of chronic conditions on QOL among community-dwelling elderly people, and the stability of QOL over time.A total of 2,762 community-dwelling elderly persons (men: 47.0%, age 76.7±5.8 [mean±SD]) completed postal QOL questionnaires twice over 4 years. Chronic illnesses were selected from the following 9 conditions: cerebrovascular disease, hypertension, heart disease, cancer, diabetes mellitus, bone fracture, chronic digestive disease, chronic respiratory disease, and the diseases of joints or muscles. The QOL questionnaire was developed based on the QOL components proposed by Lawton, and consisted of 6 subscales: daily activity, health satisfaction, human support satisfaction, economic state satisfaction, symptoms of depression, and positive mental attitude. The subjects were divided into 3 groups regardless of the presence of chronic illnesses. QOL subscale scores were compared among the 3 groups, and fluctuations over 4 years were also evaluated.The baseline QOL scores showed significant differences among the 3 groups, especially regarding health satisfaction, but not in satisfaction with human support. There were significant differences among the 3 groups in fluctuations over 4 years in health satisfaction, daily activity, and positive mental attitude.Chronic illnesses have a negative impact on the QOL of elderly people, and also influence fluctuations in QOL over time. Degrees of impacts differed according to each QOL subscale. Therefore, evaluation of QOL in community-dwelling elderly needs multi-dimensional assessment.

It has become important for elderly to live better rather than to live longer. There have been many reports about quality of life (QOL) of the elderly, but we have no knowledge about the relation between the QOL and the cognitive function. We investigated the relationship between the QOL and the cognitive function among community-dwelling elderly.A total of 12,059 community-dwelling elderly were invited to join a cognitive screening study by telephone (TICS-J) combined with a mailed QOL questionnaire. Among them, 1,920 subjects (age 71.87+/-5.50 (mean+/-SD) years old, duration of education 11.08+/-2.61 years) who completed both TICS-J and QOL questionnaire were actually measured. TICS-J was administered by the previously reported method, and the QOL questionnaire was developed based on the component of QOL proposed by Lawton, and consisted of 6 subscales (daily activity, satisfaction with health, satisfaction with human support, satisfaction with economic state, symptoms of depression, and positive mental attitude). Correlations were analyzed among the scores of TICS-J, age, duration of education, and scores on each QOL subscale. Multiple linear regression analysis was conducted after QOL subscale scores, adjusting for gender, age, and duration of education, were entered as dependent variables.Four out of 6 subscales scores of QOL showed significant differences between men and women. All QOL subscale scores showed significant differences between the two groups in the TICS-J scores. Partial correlations were seen among TICS-J scores and each QOL subscale score. Multiple linear regression analysis revealed significant influence of cognitive function by TICS-J on QOL subscales scores.Cognitive function was considered to have more influence on QOL scores than gender or age. TICS-J and the QOL questionnaire in this study were useful to evaluate the outcome of welfare in community-dwelling elderly.

The purpose of this study was to evaluate whether the Telephone Interview for Cognitive Status in Japanese (TICS-J) is accepted among community-dwelling elderly, to examine the correlations among gender, age or the duration of education and the TICS-J, as well as to grasp the subjects with probable cognitive impairment.A total of 12,059 community-dwelling elderly were invited to join the cognitive screening by the TICS-J, among which 3,482 responded, of these we were actually able to measure 2,620 and found out the educational back ground of the 2,431. They counted 1,186 men (age 72.3+/-5.7 (mean+/-SD) years old, duration of education 11.4+/-2.9 years) and 1,245 women (72.4+/-5.8, 10.3+/-2.2). The TICS-J was administered according to the TICS manual. The TICS-J consisted of orientation concerning name, time and place, counting backward from 20 to 1, remembering a word list, 7 serial subtractions, naming of verbal descriptions, repetition, recent memory, praxis and opposites. The subjects were divided into two groups by the duration of education (less than 11 years, or 11 years or more), or four groups by age (65-69, 70-74, 75-79 and 80 years old or more).There were no significant differences of total TICS-J scores between men and women, 34.3+/-3.5 and 34.4+/-3.6, respectively. The mean total score of the high education group (35.3+/-3.0) was significantly higher than that of the low education group (33.3+/-3.8). Moreover, the averages of the total scores decreased according to age increase. The number of the subjects who showed the total TICS-J scores below the cut-off point of 33 was 564 (23.2%).There was no difference between men and women with the average total score of the TICS-J, however, there were correlations between ages and extent of education and their average total scores. The TICS-J is useful to assess the cognitive function of the community-dwelling elderly.

Background In recent years, the population of elderly people in Japan with dementia has increased. Detection of cognitive impairment in the early stages is important for adequate treatment, care, and prevention. Aim To investigate whether the reliability and validity of the instrument would carry over to a different population and language before using it for population-based epidemiological studies. Methods We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls (CTL) using the Telephone Interview for Cognitive Status (TICS) and developed the Japanese version of the TICS (TICS-J). We also evaluated combination of another telephone battery, the Category Fluency Test (CF). Results The sensitivity and specificity of the TICS-J to differentiate AD patients from CTL was 98.0% and 90.7%, respectively. Pearson's correlation coefficient for the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p

In recent years, population of elder people has increased in Japan, following augmentation of the number of people with dementia in Japan. Then it is important to detect cognitive impairment in early stage for adequate treatment, care and prevention. We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls using Telephone Interview for Cognitive Status (TICS), and developing Japanese version of the TICS (TICS-J). The sensitivity and the specificity of the TICS-J to differentiate AD patients from healthy controls was 98.0% and 90.7%, respectively. Pearson's correlation coefficiency between the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p0.001). On the receiver operating curves, the area under the curve for the TICS-J was 98.7% (95% CI: 97.5%-100%). These results indicate that TICS-J is sensitive and specific instrument for differentiating AD patients from healthy controls.

This report concerns a Japanese family with neuropathological findings consistent with amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Island of Guam. The proband was a 68-year-old woman with an 8-year history of parkinsonism which was followed by psychiatric symptoms and neurogenic amyotrophy 5 years after the onset. She had a family history of parkinsonism associated with dementia in all of her three siblings. They grew up in the Hobara village, a focus of amyotrophic lateral sclerosis in the Kii Peninsula of Japan in their childhood. Their parents were not consanguineous nor natives of the Kii Peninsula. The brain weight was 1040 g and there were mild frontal lobe atrophy, moderate atrophy of pes hippocampi, decoloration of the substantia nigra and locus coeruleus, and atrophy of the anterior root of the spinal cord. The microscopic examinations revealed degeneration of CA1 portion of the hippocampus to the parahippocampus gyrus, substantia nigra, locus coeruleus and spinal anterior horn with Bunina bodies. The spinal pyramidal tracts also mildly degenerated. Neurofibrillary tangles (NFT) were observed in the cerebral cortex, especially in the cortices from hippocampus to lateral occipitotemporal gyri, basal nucleus of Mynert, basal ganglia, thalamus, substantia nigra and widespread regions of the central nervous system through the brainstem to spinal cord including the nucleus of Onufrowitcz. In spite of a small amount of the senile plaques in the cerebral cortex and Lewy bodies in the substantia nigra and locus coeruleus, abundant NFT were distributed mainly in the third layer of the cerebral cortex, which is the characteristic feature of ALS/PDC. Thus, this was likely to be an ALS/PDC case outside the Guam Island. A tau mutation was not found on DNA analysis.

The autopsy findings of a multiple system atrophy (MSA) patient with remarkable frontal lobe atrophy are described. The patient was a 65-year-old woman with a 13-year history of untreatable parkinsonism, dysautonomia and progressive motor aphasia. The brain weight was 810 g, and there was remarkable atrophy of the cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum. Microscopic examination revealed a preserved cortical structure with laminar gliosis in the sixth layer of the precentral and superior frontal gyri of the frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal lobe. The second layer of the cortices of these regions were also revealed to be in a spongy state, and mild cell loss was seen in the fifth and six layers. The frontal lobe white matter showed a mild loss of myelinated fibers and axons, and mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the deep layer of the cortex in the regions mentioned above, and were more abundant in the white matter of the frontal and parietal lobes, callosal body, and internal, external and extreme capsules. There was severe degeneration in the olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of the brain. No Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or significant amounts of neurofibrillary tangles were detected. There were no vascular changes. Thus, this was a verified MSA patient with progressive aphasia and remarkable frontal lobe atrophy. We indicate a possible involvement of the cerebral lobes in MSA.

A young man with congenital mirror movements was studied by non-invasive magnetic stimulation. Radiological examination showed no craniocervical or pituitary abnormality except for mild atrophy of the right hippocampus. Magnetic stimulation of the motor cortex caused large amplitudes in the ipsilateral hand muscles, indicating the possibility of functional disorder in the motor pathways from the motor cortex to muscles in the upper extremities.

A young woman with slowly progressive muscular weakness and atrophy localized in both thighs is reported. Laboratory, electromyographic and histological findings suggested that the patient suffered from chronic myositis with a background of autoimmune disorder. Quadriceps myositis is a rare condition. The previously reported cases of this disease in the literature are reviewed.

Neuroleptic malignant syndrome (NMS) usually occurs during treatment with neuroleptic drugs, but a similar condition may occur after a sudden withdrawal of antiparkinsonian drugs or an imbalance of the monoaminergic systems in the brain. On the other hand, extrapyramidal symptoms and dysautonomia are common in multiple system atrophy, which is a disorder of the monoaminergic system, affecting dopamine, noradrenaline, and serotonin. Catecholaminergic agents are sometimes used to treat multiple system atrophy, and NMS-like conditions may also occur in patients with multiple system atrophy.1 2 We found six episodes of an NMS-like condition in three out of 14 patients with multiple system atrophy over a one year period (table). View this table: Description of patients Patient 1 was a 47 year old man who had been receiving antiparkinsonian drugs from the age of 45. Because the drugs did not cause much response, he needed an increasing dosage. On 12 October 1995, the daily dosage of bromocriptine was decreased from 26 mg to 8.6 mg and he was also given 6 mg trihexiphenidyl HCI. After four days, he developed myalgia, hallucination, hyperhidrosis, and severe bradykinesia. On 19 October his body temperature was 37.7°C. He had high serum creatine kinase (5264 IU (normal

A case of partial sphingomylinase deficiency with supranuclear vertical ophthalmoplegia, perceptive hearing loss and renal failure is reported. Extensive studies revealed sea-blue histiocytosis in bone marrow, delayed peripheral nerve conduction velocity, selective IgG and IgM deficiency, mild hepatosplenomegaly and testicular hypotrophy and retention. Although renal failure, perceptive deafness, immunoglobulin deficiency and testicular malformation are rare conditions in sphingomyelinase deficiency, this case mimicked to lipidosis reported by Neville. The association of congenital malformation and uremia might accentuate the symptoms.

A radioimmunoassay for human skeletal muscle myosin light chain 3 (MLC-3) was developed. The serum level of MLC-3 was evaluated in 143 patients suffering from neuromuscular diseases. Increased MLC-3 level was observed in muscular dystrophies. There were significant positive correlations between serum levels of MLC-3 and creatine kinase (CK) in Duchenne and limb-girdle type muscular dystrophy, but the regression lines were different. Patients with neurogenic amyotrophy, especially amyotrophic lateral sclerosis, also showed elevated MLC-3 levels with or without high CK, and the frequency of increase in MLC-3 was greater than that of CK. The results of the present study suggest that circulating MLC might be a useful marker for muscle breakdown not merely in myopathies but in neurogenic disorders.

To introduce a simple procedure and reliable diagnostic criteria for parathyroid hormone (PTH) infusion test, 128 patients with either pseudo- (PsH) or idiopathic hypoparathyroidism (IdH) and 25 normocalcemic controls were studied. Incremental responses of urinary cyclic AMP and phosphate to 20 micrograms (67 U) or 30 micrograms (100 U) of human PTH(1-34) were assessed by using simple parameters of urinary excretion rates of the two substances. The results are summarized as follows. (1) PTH dose-cyclic AMP response relation suggests that 100 U of PTH is more appropriate than 67 U as a standard test dose for adults. (2) By presenting the magnitude of cyclic AMP response as either net increase or fold increase during 1 h after 100 U of PTH infusion, we can differentiate PsH type I from others without overlap. (3) Differentiation between PsH and IdH or normocalcemic subjects by phosphaturic response is less clearcut than that made by cyclic AMP response whatever indices and criteria are used. Thus it seems difficult to diagnose PsH type II merely based on the discrepancy between cyclic AMP and phosphaturic responses to exogenous PTH. (4) The test results are essentially similar in the examinations performed before and during vitamin D therapy. However, when the magnitude of phosphaturic response is expressed as net increase during 2 h after PTH, it tends to be enhanced after vitamin D therapy in patients with PsH compared to the response before therapy.

29才,男性. 27才の時に肩甲部痛,背部・腰部痛とともに舌の右への偏位に気付いた.その後,胸部絞扼感,乾性咳嗽,下肢脱力感が出現したため,入院.胸部X線写真で多量の胸水と左肺に円形陰影を認めた.胸部CTで左後部胸腔内の腫瘤と判明した.胸水細胞診にて異型形質細胞を証明した.血清M成分は認めず血中IgA, IgG, IgM, IgE, IgDは全て低値であつたが,尿中にはκ型のBence Jones蛋白を認めた.髄液蛋白の著明増加も認めた.舌は右へ偏位し線維束攣縮を認めた.入院後数日にしてTh5以下の横断性脊髄障害を来した.入院2カ月後には項部硬直も出現し,腫瘤形成性形質細胞腫による横断性脊髄障害と髄膜癌腫症と考え,放射線治療,薬物治療を行なつたが,全経過14カ月で死亡した.剖検では肉眼的には脳硬膜・軟膜には肥厚や混濁を認めず,頭蓋底部にも異常を認めなかつた.脊髄はTh5のレベルで腫瘤により圧迫されており,その部分より下約10cmにわたつて脊髄は軟らかく細くなつていた.光顕的には髄膜癌腫症と腫瘤の脊髄への圧迫壊死が判明した.舌下神経麻痺を初発とする髄膜癌腫症はまれであり,また過去に腫瘤形成性形質細胞腫による髄膜癌腫症と横断性脊髄症状の報告はない.

A homologous radioimmunoassay specific for amino-terminal portion of human parathyroid hormone (PTH) was developed in order to study the clearance of biologically active species of the hormone in the circulation in man. Characterization of the assay system with synthetic analogues of human PTH(1-34) in dicated that the carboxyl-terminal region of human PTH (1-34) is an important recognition site.Plasma amino-terminal PTH levels were less than 0.3 ng/ml in all of 35 normal subjects. The levels were elevated above 0.3 ng/ml in 15 of 24 patients with primary hyperparathyroidism. In 5 patients in whom the levels were determined before and after parathyroidectomy, the elevated levels were all normalized within 60 minutes after the removal of adenomata. The disappearance of exogenous human PTH(1-34) was studied after intravenous administration in 1 7 patients with hypoparathyroidism. A graphical analysis of the data disclosed two major componentsof the disappearance curve with estimated half-disappearance time of 3 and 28 munites respectively, suggesting that multiple mechanisms are involved in the clearance of the peptide from the circulation. These results demonstrate usefulness of homologousradioimmunoassay for human PTH (1-34) in diagnosis and management of hyperparathyroidism, as well as in studying the clearance of amino-terminal portion of PTHwhich is known to represent biological activity.

The diurnal changes of serum myoglobin level and CK activity were investigated in 20 cases of Duchenne dystrophy and 6 normal males under ordinary circumstances in their daily lives. Changes of myoglobin levels were also checked in 25 cases of Duchenne carrier and 11 control females with muscular exercise by ergometer of 70 W for 3 min. In Duchenne dystrophy, the myoglobin level was rather low before waking up, then it abruptly increased thereafter and remained high until retiring. The fluctuation range of myoglobin was greater than that of CK. The myoglobin level of control males was extremely low compared with that in Duchenne dystrophy. In Duchenne carriers, although CK activity did not significantly change after the exercise, 5 of 11 known carriers showed an increased myoglobin level.

Tuberoinfundibular dopaminergic system (TIDA) together with anterior pituitary dopamine receptor was evaluated in 9 patients with Shy-Drager syndrome (SDS) through the responses of serum growth hormone (GH) and prolactin (PRL) to dopaminergic stimulation or dopamine receptor inhibition. A variety of abnormal responses of serum GH and/or PRL following the administration of these drugs suggests the TIDA involvement as well as the nigrostriatal system and moreover the different degeneration processes in each dopaminergic system in SDS.

We evaluated 16 Guamanian Chamorros with amyotrophic lateral sclerosis and 33 patients with parkinsonism-dementia for disturbances of calcium and vitamin D metabolism. The serum immunoreactive parathyroid hormone level was mildly elevated in 6 patients with amyotrophic lateral sclerosis and in 5 patients with parkinsonism-dementia. There were significant positive correlations between serum immunoreactive parathyroid levels and duration of illness in male patients with motor neuron disease, but not in female patients or in patients with parkinsonism-dementia. Intestinal absorption of calcium, as assessed by serum and urinary activity of calcium 47 following oral administration, was decreased in 2 patients with amyotrophic lateral sclerosis and in 4 patients with parkinsonism-dementia, all of whom had low levels of serum 1,25-dihydroxyvitamin D. Reductions in cortical bone mass were striking in patients with motor neuron disease. A significant negative correlation was found between the percentage of cortical area of the second metacarpal bone and muscle atrophy and weakness, and significant positive correlations were found between degree of immobility and ratio of urinary hydroxyproline to creatinine in patients with amyotrophic lateral sclerosis and parkinsonism-dementia. In general, abnormalities in calcium metabolism were subtle. Thus, if the demonstrated deposition of metals, particularly calcium and aluminum, in central nervous system tissues of Guamanians with these two conditions is a cause of the diseases and of the early appearance of neurofibrillary tangles in neurons, the accumulation has apparently occurred long before onset of symptoms, and detectable abnormalities of calcium and vitamin D metabolism may already have been corrected.

Evaluation of glutamate dehydrogenase (GDH) in 12 patients with olivopontocerebellar atrophy showed deficiency of the enzyme in the group as well as in each patient. The activity of total GDH was 77.7% of that in controls. We also demonstrated two components of this enzyme differentiated by their thermostabilities. The activity of the heat-labile component was remarkably reduced in patients although that of the heat-stable component showed the same magnitude as in controls. These data suggest that GDH deficiency is mainly caused by its heat-labile component deficiency, which might be related to the pathogenesis of this disease.

The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

Endocrine abnormalities in myotonic dystrophy (MyD) reflect some of the multi-systemic involvement resulting from this disorder. One of these, abnormal insulin secretion, is considered to be caused by receptor dysfunction. Bone abnormalities, cataract and calcium transport defect suggest the abnormal calcium metabolism in MyD. The calcium metabolism is chiefly regulated by parathyroid hormone (PTH). An interest in the similarity between MyD and pseudohypoparathyroidism, which is a disorder of PTH receptor dysfunction, encouraged the authors to evaluate renal PTH receptor function from the responses of urinary adenosine 3',5'-monophosphate (cAMP) and phosphate excretion after administration of human PTH(1-34). The responses of cAMP were high in 3 cases, low in one case, but normal in the 4 other cases. The phosphaturic responses were elevated in 3 cases, reduced in 3 cases, and normal in 2 other cases. Since these abnormal responses closely mimic those in hypoparathyroidism, there may also be renal PTH receptor dysfunction in some cases of MyD. The results of the present study suggest another peptide hormone receptor defect, similar to insulin, which supports the hypothesis of generalised receptor dysfunction in MyD.

We studied the regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one], a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Increased enzyme activity was specific for glucocorticoids; other steroid hormones were essentially without effect. The induction of glutamine synthetase was selective, in that glutaminase activity was not induced by dexamethasone treatment of L6 cells. Thus, glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.

A case of chronic polyneuropathy associated with ulcerative colitis was reported. The patient was 57-year-old man who developed sensory disturbances and muscle weakness in four extremities along with the digestive symptoms of ulcerative colitis. Neurological examination revealed that sensory impairment in all modalities, muscular atrophy and weakness in the distal portions of all extremities and decreased or absent muscle stretch reflexes. Laboratory data included sedimentation rate 119mm/hour, CRP 4+, increased IgG and IgM. Lumbar puncture revealed normal CSF pressures, increased protein and IgG content with almost normal cell count. Nerve conduction velocity was delayed dominantly in sensory nerves. Sural nerve biopsy demonstrated degeneration of myelin sheath and decreased number of large fibers. Teased nerve study showed shortened internodal distances with myelin ovoids. These data together with the clinical course of this patient suggested that this peripheral neuropathy might be resulted from the common pathogenesis for ulcerative colitis which is considered as autoimmune disease.