Case report: Frontotemporal dementia and amyotrophic lateral sclerosis caused by a missense variant (p.Arg89Trp) in the valosin-containing protein gene.

Frontotemporal dementia and/or amyotrophic lateral sclerosis 6, also known as amyotrophic lateral sclerosis 14, is an autosomal dominant, progressive neurodegenerative disorder caused by various mutations in the valosin-containing protein gene. In this report, we examined a 51-year-old female Japanese patient with frontotemporal dementia and amyotrophic lateral sclerosis. The patient began noticing gait disturbances at the age of 45 years. Neurological examination at the age of 46 years met the Awaji criteria for clinically probable amyotrophic lateral sclerosis. At the age of 49 years, she tended to have poor mood and an aversion to activity. Her symptoms gradually worsened. She required a wheelchair for transport and had difficulty communicating with others because of poor comprehension. She then began to frequently exhibit irritability. Eventually, she was admitted to the psychiatric hospital because uncontrollable violent behavior throughout the day. Longitudinal brain magnetic resonance imaging revealed progressive brain atrophy with temporal dominance, non-progressive cerebellar atrophy, and some non-specific white matter intensities. Brain single photon emission computed tomography showed hypoperfusion in the bilateral temporal lobes and cerebellar hemispheres. Clinical exome sequencing revealed the presence of a heterozygous nonsynonymous variant (NM_007126.5, c.265C>T; p.Arg89Trp) in the valosin-containing protein gene, which was absent in the 1000 Genomes Project, the Exome Aggregation Consortium Database, and the Genome Aggregation Database, and was predicted to be "damaging" by PolyPhen-2 and "deleterious" using SIFT with a Combined Annotation Dependent Depletion score of 35. We also confirmed the absence of this variant in 505 Japanese control subjects. Therefore, we concluded that the variant in the valosin-containing protein gene was responsible for the symptoms of this patient.

Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study.

In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. A total of 31 individuals aged 47-87 years were randomly assigned to receive either 5 g/day of fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups' blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (homeostasis model assessment ratio [HOMA-R]) than the placebo group. In addition, the percentage changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

OBJECTIVES: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC. DESIGN: The current study was a retrospective cross-sectional study. SETTING AND PARTICIPANTS: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture. MEASURES: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI. CONCLUSIONS AND IMPLICATIONS: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.

Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms.

Background We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31-91 years) without cerebro- or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial-ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0-8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low-density lipoprotein cholesterol. Conclusions The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low-density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low-density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.

Association of Creatinine-to-Cystatin C Ratio with Myosteatosis and Physical Performance in Older Adults: The Japan Shimanami Health Promoting Program.

OBJECTIVE: Sarcopenia is a risk factor for poor outcomes in older adults. Identification of plasma markers may facilitate screening of sarcopenia. We previously reported that creatinine-to-cystatin C ratio is a simple marker of muscle mass. To further assess the clinical relevance of the creatinine-to-cystatin C ratio, we investigated its association with myosteatosis and physical performance. DESIGN: Observational study. SETTING AND PARTICIPANTS: Cross-sectional analysis of the dataset obtained from a Japanese population consisting of 1468 older (≥60 years of age) community residents. METHODS: The mean attenuation values of the skeletal muscle calculated from computed tomography images of the midthigh were used as an index of myosteatosis, while the cross-sectional area of the muscle was used as a proxy for muscle mass. Physical performance was assessed by 1-leg standing time. RESULTS: Creatinine-to-cystatin C ratio was positively associated with the cross-sectional area of muscle fiber-rich muscles, while it showed an inverse association with fat-rich muscle areas, resulting in the positive association between creatinine-to-cystatin C ratio and the mean attenuation value of the skeletal muscle [creatinine-to-cystatin C ratio quartiles (Q), Q1: 47.4 ± 4.8, Q2: 48.9 ± 4.4, Q3: 49.8 ± 4.1, Q4: 50.9 ± 3.7, P < .001]. The results of the linear regression analysis adjusted for major covariates (including muscle cross-sectional area) identified creatinine-to-cystatin C ratio as an independent determinant of the mean attenuation value (Q1: reference, Q2: ß = 0.07, P = .019, Q3: ß = 0.11, P < .001, Q4: ß = 0.16, P < .001). Low creatinine-to-cystatin C ratio was independently associated with 1-leg standing time, although the association was attenuated substantially by adjusting for skeletal muscle cross-sectional area and mean attenuation value. CONCLUSION AND IMPLICATIONS: Creatinine-to-cystatin C ratio was associated with myosteatosis in older adults, independent of the muscle mass. Creatinine-to-cystatin C ratio may serve as a convenient marker of sarcopenia.

Unilateral lower limb atrophy associated with glomus tumors: a case report.

BACKGROUND: Glomus tumors are soft tissue neoplasms comprised of glomus cells, vasculature, and smooth muscle cells, which occur commonly in a single subungual area of the digits, and their main clinical features include severe paroxysmal pain, localized tenderness, and cold hypersensitivity. CASE PRESENTATION: A 47-year-old Japanese man had suffered from chronic progressive paroxysmal shooting pain in his right leg since childhood. He avoided putting weight on his right foot whenever he walked. The frequency of paroxysmal pain and the number of tender points both gradually increased with age, and his right leg gradually atrophied. Magnetic resonance imaging of the lower extremity demonstrated multiple gadolinium-enhanced nodules that corresponded with his tender points. Excisional biopsy relieved his pain and provided a histopathological diagnosis of glomus tumors. CONCLUSION: This case suggests that small glomus tumors located in deep tissue may cause disuse atrophy because of their long delay before diagnosis. Clinicians should consider the potential for glomus tumors when patients exhibit unilateral lower limb muscular atrophy with pain.

Casein Hydrolysate Containing Milk-Derived Peptides Reduces Facial Pigmentation Partly by Decreasing Advanced Glycation End Products in the Skin: A Randomized Double-Blind Placebo-Controlled Trial.

Casein hydrolysate has been shown to improve arterial stiffness as estimated by brachial-ankle pulse wave velocity (baPWV) in untreated hypertensive patients. Facial pigmentation is associated with atherosclerosis, both of which are supposed to be modulated by tissue accumulation of advanced glycation end products (AGEs). However, effects of casein hydrolysate on facial pigmentation and AGEs remain largely unknown. This randomized double-blind placebo-controlled trial evaluated whether and how casein hydrolysate improves facial pigmentation in 80 nonhypertensive Japanese patients. Study participants were randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation area, baPWV, and skin accumulation levels of AGEs were evaluated by Robo Skin Analyzer RSA50S II, volume-plethysmographic apparatus, and AGE Reader, respectively, at baseline and at the end of the intervention. Treatment with casein hydrolysate, but not placebo significantly reduced triglycerides and facial pigmentation area. There were significant differences of changes in triglycerides, facial pigmentation area, skin accumulation levels of AGEs, and baPWV between the two groups. Furthermore, changes in triglycerides and skin accumulation levels of AGEs were positively and independently associated with those in facial pigmentation area, whereas changes in baPWV were not. This study suggests that casein hydrolysate reduces facial pigmentation area in nonhypertensive participants partly by decreasing skin accumulation levels of AGEs. Clinical-Trials.gov ID: UMIN000027675.

Creatinine-to-cystatin C ratio as a marker of skeletal muscle mass in older adults: J-SHIPP study.

BACKGROUND: Sarcopenia increases mortality risk in older adults. Loss of skeletal muscle mass is a cardinal feature of sarcopenia. The creatinine-to-cystatin C ratio (CCR) has been suggested as a marker of muscle mass. The present study investigated the usefulness of CCR in discriminating the risk of low muscle mass and weak muscle strength in an elderly population. METHODS: The present cross-sectional study included 1,329 apparently healthy community residents aged 60 years or older. The cross-sectional area (CSA) of muscle in the mid-thigh was measured using computed tomography. Clinical data recorded at routine medical check-ups were obtained from each participant's medical record. RESULTS: Mean muscle CSA was 109 ± 24 cm2. CCR by quartiles according to sex was strongly associated with muscle CSA (Q1: 104 ± 22, Q2: 108 ± 24, Q3: 110 ± 23, and Q4: 114 ± 25 cm2, F = 10.38, P < 0.001). This association was independent of major covariates (Q1: reference, Q2: ß = 0.06, P < 0.001, Q3: ß = 0.10, P < 0.001, and Q4: ß = 0.17, P < 0.001) even in a sex-separated analysis. Although creatinine alone was independently associated with muscle CSA (F = 5.81, P < 0.001), the association was weaker than that of CCR, particularly in the individuals with renal functional decline. Also, CCR was associated with grip strength independently of muscle CSA. CONCLUSION: CCR was a simple marker of low muscle mass and weak muscle strength in older community-dwelling adults.

ELAPSS score for prediction of risk of growth of unruptured intracranial aneurysms.

OBJECTIVE: To develop a risk score that estimates 3-year and 5-year absolute risks for aneurysm growth. METHODS: From 10 cohorts of patients with unruptured intracranial aneurysms and follow-up imaging, we pooled individual data on sex, population, age, hypertension, history of subarachnoid hemorrhage, and aneurysm location, size, aspect ratio, and shape but not on smoking during follow-up and family history of intracranial aneurysms in 1,507 patients with 1,909 unruptured intracranial aneurysms and used aneurysm growth as outcome. With aneurysm-based multivariable Cox regression analysis, we determined predictors for aneurysm growth, which were presented as a risk score to calculate 3-year and 5-year risks for aneurysm growth by risk factor status. RESULTS: Aneurysm growth occurred in 257 patients (17%) and 267 aneurysms (14%) during 5,782 patient-years of follow-up. Predictors for aneurysm growth were earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, and shape of the aneurysm (ELAPSS). The 3-year growth risk ranged from <5% to >42% and the 5-year growth risk from <9% to >60%, depending on the risk factor status. CONCLUSIONS: The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study.

BACKGROUND: There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross-sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. METHODS: Two sarcopenic indices were measured: thigh muscle cross-sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel-type Dementia Assessment Scale, and brachial-ankle pulse wave velocity was measured as an index of arterial stiffness. RESULTS: Both sarcopenic indices were modestly but significantly associated with brachial-ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel-type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. CONCLUSIONS: Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association.

Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population.

Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and -358 (rs3219175) located in the human resistin gene (RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP -358 G>A, followed by rs1423096 C>T, SNP -420 C>G, and rs10401670 C>T (P = 5.39×10-47, 1.81×10-22, 2.09×10-16, and 9.25×10-15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3'-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP-420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population.

A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

Visit-to-visit variability in systolic blood pressure is a novel risk factor for the growth of intracranial aneurysms.

BACKGROUND: Although rupture of unruptured intracranial aneurysms (UIAs) is closely associated with UIA growth during follow-up, few studies have investigated how UIAs grow during observation. Hypertension appears to affect the formation of intracranial aneurysms. However, few studies have investigated the association of blood pressure variability with UIA growth. Visit-to-visit variability (VVV) in systolic blood pressure (SBP) is a newly defined concept which appears to be a good predictor of stroke. With this factor in mind, here we conducted a prospective analysis of the results of 2 years of observation of UIAs by magnetic resonance angiography (MRA) and sought to identify risk factors for UIA growth and rupture. METHODS: From December 2006 through June 2010, two hundred patients with 212 UIAs were followed for 2 years. Patient ages ranged from 31 to 91 years. Putative risk factors for the growth of UIAs were evaluated. Subjects were divided into two groups: a UIA growth group consisting of patients whose UIAs increased by 1 mm or more in size or who developed subarachnoid hemorrhage (SAH), and an unchanged group. Brachial blood pressure values were recorded at the time of diagnosis and during follow-up in the outpatient clinic. All blood pressure values were then averaged, and the VVV of SBP was defined as the standard deviation (SD) of a minimum of 5 blood pressure measurements at outpatient visits. RESULTS: UIA growth occurred in 20 patients and SAH occurred in 1 patient. Current smoking tended to be more prevalent in the UIA growth group (p < 0.01). Five of the 12 patients with multiple UIAs showed UIA growth within 2 years and multiplicity was a significant risk factor for UIA growth (p < 0.01). The mean baseline size in the UIA growth group was larger than that in the unchanged group (p = 0.01) and 7 of the 18 patients with large UIAs, categorized as having an initial diameter of 7 mm or more, had an increase in UIA size over the 2 years (p < 0.01). On multivariable logistic regression analysis, current smoking, multiplicity, and UIA size ≥7 mm were significant risk factors for UIA growth. Although no significant difference was seen between the UIA growth and unchanged groups in office SBP during the observation period, VVV in SBP was significantly higher in the UIA growth group than in the unchanged group, and it was significantly and independently associated with UIA growth. CONCLUSIONS: VVV in SBP is a novel risk factor for the growth of UIAs and may be a key factor for the prevention of UIA rupture. Future research is needed to confirm that SBP stability prevents UIA rupture.

[A case of myasthenia gravis with an invasive thymoma infiltrating the superior vena cava and right atrium and causing lung metastasis].

A 72-year-old woman was admitted to a local hospital with general fatigue, ptosis and dysarthria. Her anti-AchR antibody titer was high, so myasthenia gravis was diagnosed. She was given a cholinesterase inhibitor, but her symptoms did not improve. CT and MRI scans revealed a mass in the anterior mediastinum infiltrating the superior vena cava (SVC) and the right atrium (RA) . The diagnosis was an invasive thymoma extending into the SVC and the RA. Moreover, there was a mass in the right middle lobe of her lung, which was suspected to be the result of metastasis of the thymoma. She was transferred to our hospital for medication and surgery for the invasive thymoma. Urgent surgery was performed without preoperative therapy, because the tumor was nearly obstructing her tricuspid valve. An expanded thymomectomy and a right middle lobectomy were performed. As the tumor had infiltrated into the SVC, the SVC was replaced with an artificial graft. The clinicopathological diagnosis of thymoma (Masaoka Stage IVb) was given. The patient had a myasthenic crisis for several weeks after surgery, so her breathing was controlled by an artificial respirator. Her symptoms improved after treatment with steroids, tacrolimus and a cholinesterase inhibitor. Although major surgery was required to prevent tumor embolism, the patient survived. Careful observation is necessary to detect signs of relapse of invasive thymoma.

[Anti-aging dock].

Our anti-aging center (AAC) began providing health check-up services to local citizens in western Japan in February 2006, with the mission of promoting 'successful' aging through the employment of anti-aging check-ups, termed 'anti-aging dock' in Japan, using evidence-based 'anti-aging dock' strategies designed to diagnose atherosclerosis based on personal data. Clinical test items routinely received by most patients are as follows: 1) general physical measurement, 2) blood tests and urine analysis, 3) brain MRI/MRA, 4) carotid ultrasound imaging, 5) visceral fat area (VFA) estimation by abdominal CT, 6) brachial ankle pulse wave velocity (baPWV), 7) bone mineral density measurement, 8) stabilometer testing, 9) cognitive function testing, and 10) optional tests, including ambulatory blood pressure monitoring (ABPM). Data from patients providing written informed consent has been used for research. As of December, 2008, the total number of patients has exceeded 1,000. About 50 participants (5%) were found to have cerebral aneurysm, as diagnosed using 3.0 tesla MRI. Of these, 10 patients required surgery, 7 in our hospital and 3 in an affiliated hospital. About 5% of participants were evaluated as probably having dementia; in particular, three patients required treatment for Alzheimer disease. With regard to research, we have focused on the association between cerebral microbleeds and atherosclerotic disease, and the clinical implications of a high ankle-brachial index (ABI).

[Case of recurrent transverse myelitis and diplopia after meningomyeloradiculitis caused by Epstein-Barr virus].

A 60-year-old woman was admitted to our hospital because of pyrexia, headache, gait disturbance, and sensory disturbance in the lower part of the body four days after she received an epidural block for postherpetic neuralgia. Neurological tests revealed neck stiffness, flaccid paraparesis in the legs with absent deep tendon reflexes, and hyperesthesia below Th7. According to a cerebrospinal fluid examination, the protein concentration was 245 mg/dl and the cell count was 176/mm3. PCR analysis of the cerebrospinal fluid was positive for Epstein-Barr virus (EBV). Serological tests for EBV yielded mild increases of serum IgG antibodies against EBV nuclear antigen (EBNA) and IgG antibodies against EBV viral capsid antigen (VCA). In a spinal MRI, the inferior lumbar meninges showed gadolinium enhancement. Nerve conduction studies revealed a decreased F wave ratio in the bilateral tibial nerves. The patient was diagnosed with meningomyeloradiculitis caused by EBV. The symptoms improved after steroid pulse therapy, but relapses of transverse myelitis and diplopia due to disturbance of the bilateral abducent nerves and left trochlear nerve occurred 7, 12, 16, and 26 months after treatment. The relapses were sometimes accompanied by small fluctuations in cerebrospinal fluid protein concentration, cell count, or serum anti-EBV antibody titer. These findings suggest that the myelopathy and diplopia were induced by a secondary immune reaction after inflammation caused by EBV infection.

[Case of relapsing polychondritis followed by cognitive impairment].

A 64-year-old man developed cognitive impairment. A neurological examination showed hypereactive tendon reflex. A cerebrospinal fluid (CSF) examination showed a mild increase in both the number of mononuclear cells (14 cells/mm3) and the protein level (45 mg/dl). An electroencephalogram showed diffuse slow wave activity. Brain MR images revealed multifocal lesions in the limbic area and white matter regions. He was suspected to have autoimmune encephalitis and his symptoms improved after treated with methylprednisolone (1 g/day for 3 days). Despite this treatment, his mental disorders later relapsed. His condition improved after undergoing repeated treatment. Thereafter, he developed bacterial meningoencephalitis which had been caused by Listeria monocytogenes during the period of the internal administration of steroids. Antibiotics successfully cured his Listeria meningoencephalitis. He thereafter developed conjunctivitis, polyarthritis, hearing difficulties, dizziness and auricular chondritis. Based on these findings, we diagnosed the patient to have relapsing polychondritis (RP). It was thus conceivable that his cognitive impairment has been caused by CNS vasculitis associated with RP. RP therefore should be carefully taken into consideration and be included in the differential diagnosis as a possible cause for CNS vasculitis.

[Elements necessary for end-of-life care for terminal cancer patients and standardization of discharge planning].

AIM: Unitil now, most terminal cancer patients have received end-of-life care service in a hospital. How, recently, home health care services have received much attention instead of the hospital care. In this study, we investigated important factors affecting smooth transition to home health care from hospital care. METHODS: We examined the records of 66 deceased subjects with terminal cancers who received medical care by staff of home heath care agency "Yunomori Tnapopo clininc" were included in this study. METHODS: The categories evaluated were: 1) general condition, 2) breakdown of family caregivers, 3) rate of application for care insurance, 4) the percentage of cases with a discharge planning conference, 5) the time of death and, 6) frequency of visiting care in the first 1 week and the last 1 week. RESULTS: The 66 subjects consisted of 38 men (58%) and the average age of the group was 71.1 2.0. 1) Dementia was indicated in 20 (30%) patients and 23% of the patients were reliant on intravenous nutrition. Oxygen treatment was required for 45% of the patients. Some help for excretion was required by 70% of the patients. 2) 70% of a main care giver were woman and the average number of persons per household was 2.0. 3) 50% of the patients did not apply for care insurance. 4) Discharge planning conferences between the hospital and the clininc were held in only 21% of the case. 5) over 70% of the patients died outside duty hours (between 8AM and 6PM). 6) Although the average duration of stay at home was 62.5 days, 10% of the cases died or had to leave their home due to worsening condition during the first 2 weeks. Vsits by medical doctor in the last 1 week significantly increased in frequency compared to that in the last 1 week. (5.0 0.2 vs. 3.9 0.2, p<0.01). In addition, frequency of care visits by nurses increased significantly as well (3.2 0.2 vs. 2.4 0.2, p<0.01). Overall the number of care visits in the last 1 week was more than once a day. CONCLUSION: 1. A home-health care clinic which gives 24-hour care is necessary so that the patients receive end-of-life care as well as hospital care. 2. Earliest possible transfer to the home health care setting is needed so trhat the patients could have enough time to live in their hom with their family. On this account, it is most important to convene a conference co-organaized by the home health care adjusytment. In addition, the patients or their family need to apply to the munided office for care insurance. Medical staff should provide information and help them.