A Japanese Family of Spinocerebellar Ataxia Type 21: Clinical and Neuropathological Studies.

Spinocerebellar ataxia type 21 (SCA21) is a rare subtype of autosomal dominant cerebellar ataxias, which was first identified in a French family and has been reported almost exclusively in French ancestry so far. We here report the first Japanese family with SCA21, in which all affected members examined carried a heterozygous c.509C > T:p.Pro170Leu variant in TMEM240. Their clinical features were summarized as a slowly progressive ataxia of young-adult onset (5-48 years) associated with various degree of psychomotor retardation or cognitive impairment. The MR images revealed atrophy in the cerebellum, but not in the cerebrum or brainstem. These clinical findings were consistent with those in the original French families with SCA21. Neuropathological findings in one autopsied patient showed a prominent decrease of cerebellar Purkinje cells, but no specific abnormalities outside the cerebellum.

Sepsis Caused by Newly Identified Capnocytophaga canis Following Cat Bites: C. canis Is the Third Candidate along with C. canimorsus and C. cynodegmi Causing Zoonotic Infection.

Sepsis caused by a Capnocytophaga canis infection has only been rarely reported. A 67-year-old female with a past medical history of splenectomy was admitted to our hospital with fever and general malaise. She had been bitten by a cat. She showed disseminated intravascular coagulation and multi-organ failure because of severe sepsis. On blood culture, characteristic gram-negative fusiform rods were detected; therefore, a Capnocytophaga species infection was suspected. A nucleotide sequence analysis revealed the species to be C. canis, which was newly identified in 2016. C. canis may have low virulence in humans; however, C. canis with oxidase activity may cause severe zoonotic infection.

Corrigendum to "Optimal Hemoglobin A1c Levels for Screening of Diabetes and Prediabetes in the Japanese Population".

[This corrects the article DOI: 10.1155/2015/932057.].

Optimal Hemoglobin A1c Levels for Screening of Diabetes and Prediabetes in the Japanese Population.

The aim of this study was to evaluate the utility of hemoglobin A1c (HbA1c) to identify individuals with diabetes and prediabetes in the Japanese population. A total of 1372 individuals without known diabetes were selected for this study. A 75 g oral glucose tolerance test (OGTT) was used to diagnose diabetes and prediabetes. The ability of HbA1c to detect diabetes and prediabetes was investigated using receiver operating characteristic (ROC) analysis. The kappa (κ) coefficient was used to test the agreement between HbA1c categorization and OGTT-based diagnosis. ROC analysis demonstrated that HbA1c was a good test to identify diabetes and prediabetes, with areas under the curve of 0.918 and 0.714, respectively. Optimal HbA1c cutoffs for diagnosing diabetes and prediabetes were 6.0% (sensitivity 83.7%, specificity 87.6%) and 5.7% (sensitivity 60.6%, specificity 72.1%), respectively, although the cutoff for prediabetes showed low accuracy (67.6%) and a high false-negative rate (39.4%). Agreement between HbA1c categorization and OGTT-based diagnosis was low in diabetes (κ = 0.399) and prediabetes (κ = 0.324). In Japanese subjects, the HbA1c cutoff of 6.0% had appropriate sensitivity and specificity for diabetes screening, whereas the cutoff of 5.7% had modest sensitivity and specificity in identifying prediabetes. Thus, HbA1c may be inadequate as a screening tool for prediabetes.

The relation between CA 19-9 level and early-phase insulin secretion in normoglycemic and prediabetic subjects.

BACKGROUND: Carbohydrate antigen (CA) 19-9 is used as a clinical tumor marker of pancreatic cancer; recent studies report that CA 19-9 is also associated with changes in blood glucose levels. The aim of the present study was to investigate the relationship between serum CA 19-9 levels and early-phase insulin secretion in nondiabetic individuals. METHODS: We enrolled 269 normoglycemic participants and 172 prediabetic participants who had undergone the 75-g oral glucose tolerance test during their annual health examination. Insulin secretion was estimated using the disposition index (DI) [(Δinsulin(0-30 min)/Δglucose(0-30 min) × (1/HOMA-IR)], which is an adjusted measure of relationship between ß-cell sensitivity and insulin sensitivity. RESULTS: Serum CA 19-9 level was significantly higher in the prediabetic participants than in the normoglycemic participants. Simple linear regression analysis showed a negative correlation between CA 19-9 levels and DI for all participants and prediabetic participants (r = -0.126, p = 0.009, and r = -0.189, p = 0.002, respectively). However, in the normoglycemic participants, CA 19-9 levels did not correlate with DI. For all participants, and prediabetic subjects, multivariate linear regression analysis revealed that serum CA 19-9 levels were one of the independent predictors of DI (adjusted ß = -0.098, p = 0.025, and adjusted ß = -0.177, p = 0.004, respectively). CONCLUSIONS: Serum CA 19-9 levels significantly correlate with early-phase insulin secretion in the prediabetic individuals. Our results indicate that CA 19-9 may be involved in the endocrine function of pancreas.

Predominant cerebellar phenotype in spastic paraplegia 7 (SPG7).

We report a Japanese family with spastic paraplegia 7 (SPG7) that carries a deleterious homozygous p.R398X mutation in SPG7. The patients showed a predominant cerebellar ataxia phenotype. SPG7 is quite rare in Japan, but it should be included in the differential diagnosis for hereditary spastic-ataxic syndromes, even if the cerebellar signs are much more pronounced than the pyramidal tract signs.

Impact of serum triglyceride and high density lipoprotein cholesterol levels on early-phase insulin secretion in normoglycemic and prediabetic subjects.

BACKGROUND: Increased triglycerides (TGs) and decreased high density lipoprotein cholesterol (HDL-C) levels are established as diabetic risks for nondiabetic subjects. The aim of this study was to investigate the relationship among TG, HDL-C, TG/HDL-C ratio, and early-phase insulin secretion in normoglycemic and prediabetic subjects. METHODS: We evaluated 663 Japanese subjects who underwent the 75-g oral glucose tolerance test. On the basis of these results, the subjects were divided into four groups: those with normal glucose tolerance (NGT; n=341), isolated impaired fasting glucose (i-IFG; n=211), isolated impaired glucose tolerance (i-IGT; n=71), and combined IFG and IGT (IFG+IGT; n=40). Insulin secretion was estimated by the insulinogenic index (IGI) (Δinsulin/Δglucose [30 to 0 minutes]) and disposition index (DI) (IGI/homeostasis model assessment of insulin resistance). RESULTS: In prediabetic subjects (i-IFG, i-IGT, and IFG+IGT), linear regression analyses revealed that IGI and DI were positively correlated with HDL-C levels. Moreover, in subjects with i-IGT and (IFG+IGT), but not with i-IFG, the indices of insulin secretion were negatively correlated with the log-transformed TG and TG/HDL-C ratio. In both the subjects with i-IGT, multivariate linear regression analyses revealed that DI was positively correlated with HDL-C and negatively with log-transformed TG and TG/HDL-C ratio. On the other hand, in subjects with NGT, there was no association between insulin secretion and lipid profiles. CONCLUSION: These results revealed that serum TG and HDL-C levels have different impacts on early-phase insulin secretion on the basis of their glucose tolerance status.

Correlation between mean platelet volume and blood glucose levels after oral glucose loading in normoglycemic and prediabetic Japanese subjects.

AIMS/INTRODUCTION: Mean platelet volume (MPV) reflects platelet activity, and high MPV is associated with thrombogenic activation and increased cardiovascular disease risk. Although a positive correlation between MPV and fasting plasma glucose (FPG) levels has been reported, the correlation between MPV and postprandial glucose levels remains unclear. The purpose of the present study was to evaluate the correlation between MPV and postprandial glucose levels in prediabetic and normoglycemic participants. MATERIALS AND METHODS: We evaluated 1,080 Japanese participants who underwent the 75-g oral glucose tolerance test (OGTT). Based on these results, the participants were divided into three groups: normal glucose tolerance group (NGT; n = 582), impaired fasting glucose group (IFG; n = 205) and impaired glucose tolerance group (IGT; n = 252). The relationship between MPV, FPG, and postchallenge glucose levels after 1 h (1 h-PG) and 2 h (2 h-PG) were analyzed. RESULTS: Bivariate correlation analyses showed a significant positive correlation between MPV and both FPG and 1 h-PG levels in the NGT group, as well as between MPV and 2 h-PG, total cholesterol, and low-density lipoprotein cholesterol in the IGT group. In contrast, no significant correlation was observed between MPV and postchallenge glucose levels in the IFG group. Multiple correlation analyses showed that FPG levels significantly correlated with MPV in the NGT and IGT groups. In addition, 1 h-PG and 2 h-PG levels correlated with MPV in the NTG and IGT groups, respectively. CONCLUSIONS: These results suggest a possible mechanism by which subjects with postprandial hyperglycemia might be at increased cardiovascular risk.

Serum triglyceride levels correlated with the rate of change in insulin secretion over two years in prediabetic subjects.

BACKGROUND/AIMS: Increased triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C) levels are considered risk factors for diabetes among prediabetic subjects. In this study, we retrospectively investigated the relationship between lipid profiles and the rate of change in early-phase insulin secretion in prediabetic subjects. METHODS: To evaluate insulin secretion, 50 prediabetic subjects underwent a 75-gram oral glucose tolerance test at the beginning of the study (baseline), and they were reexamined after a 2-year interval. The results were expressed as insulinogenic index (IGI) and disposition index (DI). RESULTS: The lipid profiles and indices of insulin secretion had not significantly changed over 2 years. However, Pearson's correlation analyses indicated that the rate of change in IGI and DI was negatively correlated with log-transformed baseline TG level, but not with baseline HDL-C level. Multiple linear regression analysis confirmed that the rate of change in IGI and DI was negatively correlated with the log-transformed baseline TG level (ß = -0.38, p = 0.006, and ß = -0.39, p = 0.006, respectively). CONCLUSIONS: Baseline TG level of prediabetic subjects appeared to be associated with rate of change in IGI and DI over a 2-year period, indicating that TG levels among prediabetic subjects should be carefully monitored.

Correlation between serum lipids and 1-hour postload plasma glucose levels in normoglycemic individuals.

BACKGROUND: One-hour plasma glucose (1-h PG) level of ≥ 155 mg/dL during an oral glucose tolerance test (OGTT) predicts the development of type 2 diabetes mellitus among individuals with normal glucose tolerance (NGT). In addition, high triglyceride (TG) and low high-density lipoprotein-cholesterol (HDL-C) levels are risks factors for development of diabetes mellitus in the future. OBJECTIVE: To examine the association between 1-h PG levels and serum lipid profiles in individuals with NGT. METHODS: We enrolled 736 individuals with NGT who underwent a 75-g OGTT. They were divided into 2 groups, those with 1-h PG levels < 155 mg/dL (n = 543) and those with 1-h PG levels ≥ 155 mg/dL (n = 193). Multivariate linear regression analyses were performed to assess correlations between 1-h PG levels and lipid profiles. RESULTS: The multiple linear regression analyses showed that 1-h PG levels negatively correlated with HDL-C in individuals with NGT who had 1-h PG levels ≥ 155 mg/dL as well as those with 1-h PG levels < 155 mg/dL (ß = -0.137, P = .001 and ß = -0.214, P = .003, respectively). In addition, 1-h PG levels positively correlated with log-transformed TG/HDL-C ratio in both groups (ß = 0.098, P = .032 and ß = 0.152, P = .035, respectively). Moreover, even after adjusting for confounding parameters, TG was higher and HDL-C was lower in individuals with NGT who had 1-h PG levels ≥ 155 mg/dL compared with those who had 1-h PG levels < 155 mg/dL. CONCLUSION: HDL-C levels and TG/HDL-C ratios closely correlate with 1-h PG levels in individuals with NGT.

Gender differences in the relationship between serum uric acid and mean platelet volume in a Japanese general population.

Mean platelet volume (MPV) can reflect platelet activity. Furthermore, high MPV is associated with thrombogenic activation and increased risk of cardiovascular disease. MPV of subjects with hypertension, hyperglycemia, or hyperlipidemia is higher compared with that of normal subjects. In contrast, the relationship between MPV and uric acid (UA) is poorly understood. The present study aims to evaluate the relationship between MPV and serum UA levels in both genders. We retrospectively studied 2104 Japanese subjects (1221 males, 883 females) undergoing general health examinations. Age, gender, body mass index (BMI), blood pressure (BP), smoking habits, alcohol intake, lipid profiles, fasting plasma glucose (FPG), high-sensitivity C-reactive protein, serum UA levels and MPV were evaluated. On the basis of the serum UA levels, the subjects were categorized into the following tertiles: 1st (Q1), 2nd (Q2), and 3rd (Q3). In males, a univariate analysis revealed that age, FPG and systolic and diastolic BP were significantly associated with MPV; in addition to these parameters, in females, UA and LDL-cholesterol correlate with MPV. Furthermore, in females, a stepwise linear regression analysis showed a significant positive correlation between UA and MPV (ß=0.059, p=0.008). MPV in females increased gradually based on the serum UA tertile, despite adjusting for confounding variables (Q1, Q2, and Q3 values were 9.88 ± 0.70, 9.95 ± 0.73, and 10.00 ± 0.77 fL, respectively; p<0.039). The serum UA levels were found to be a key determinant of MPV in females.

Correlation between mean platelet volume and fasting plasma glucose levels in prediabetic and normoglycemic individuals.

BACKGROUND: Prediabetes is an independent risk factor for cardiovascular diseases. Mean platelet volume (MPV) can reflect platelet activity, and high MPV is associated with thrombogenic activation and an increased risk of cardiovascular disease. In diabetic patients, MPV is higher when compared with normal subjects. However, the relationship between MPV and prediabetes is poorly understood. The purpose of the present study was to compare MPV in prediabetic and normoglycemic subjects, and to evaluate the relationship between MPV and fasting plasma glucose (FPG) levels in these two groups. METHODS: We retrospectively studied 1876 Japanese subjects who had undergone health checks at Iida Municipal Hospital. Age, sex, body mass index (BMI), blood pressure, medical history, smoking habits, alcohol intake, lipid profiles, FPG levels, and MPV were evaluated. Subjects were categorized into four groups according to FPG: Q1 (70 mg/dL ≤ FPG < 90 mg/dL, n = 467), Q2 (90 mg/dL ≤ FPG < 95 mg/dl, n = 457), Q3 (95 mg/dL ≤ FPG < 100 mg/dL, n = 442), and Q4 (100 mg/dL ≤ FPG < 126 mg/dL, n = 512). Q1, Q2, and Q3 were defined as normal FPG groups and Q4 was defined as prediabetic group. RESULTS: The MPV increased with the increasing FPG levels, in the following order: Q1 (9.89 ± 0.68 fl), Q2 (9.97 ± 0.69 fl), Q3 (10.02 ± 0.72 fl), and Q4 (10.12 ± 0.69 fl). After adjusting for the confounding parameters, MPV of the prediabetic group was higher than that in other groups (P < 0.001 for Q4 vs. Q1 and Q2, and P < 0.05 for Q4 vs. Q3). MPV in the high-normal glucose group (Q3) was significantly higher than in the low-normal glucose group (Q1). MPV was independently and positively associated with FPG, not only in prediabetic subjects but also in normal FPG subjects (ß = 0.020 and ß = 0.006, respectively). CONCLUSIONS: MPV in patients with prediabetes was higher than that in normal subjects, and was positively associated with FPG levels in prediabetic and normal subjects.

Coexistence of familial transthyretin amyloidosis ATTR Val30Met and spinocerebellar ataxia type 1 in a Japanese family--a follow-up autopsy report.

Three brothers in a family with Val30Met transthyretin (TTR) amyloid polyneuropathy (FAP) in Iiyama, Japan were studied pathologically. In this family, affected members have been reported to show typical clinical features of FAP, and some have been documented to exhibit symptoms and signs of central nervous system (CNS) involvement consisting of cerebellar ataxia and pyramidal tract signs. After the original description, this family was regarded as a unique phenotype of this form of FAP; however, subsequent molecular genetic studies revealed that some patients and asymptomatic members in the family had Val30Met TTR and/or spinocerebellar ataxia type 1 (SCA1) gene mutations. In this study, pathological examination of two patients with both FAP and CNS symptoms showed (1) TTR-immunoreactive leptomeningeal and cerebrovascular amyloid deposition compatible with Val30Met TTR FAP, and (2) neuronal loss and gliosis mainly in the Purkinje cell layer, spinocerebellar system, olivo-ponto-cerebellar system, dentato-rubral system, gracile nuclei, cuneate nuclei, and various nuclei of cranial nerves, accompanied by anti-expanded polyglutamine tract antibody positive neuronal intranuclear inclusions, all of which were compatible with the pathological findings of SCA1. On the other hand, the remaining patient with FAP symptoms only showed the former pathological finding alone. The present study demonstrates, at the pathological level, that Val30Met TTR FAP and SCA1 coexist in the same family members, and that the CNS dysfunction seen in the patients in this family is ascribable to SCA1 pathology but not to CNS amyloidosis.

Withdrawal of levodopa and other risk factors for malignant syndrome in Parkinson's disease.

A symptom complex identical to neuroleptic malignant syndrome (MS) is known to develop in patients with idiopathic Parkinson's disease (PD) or other forms of parkinsonism on long-term treatment with anti-parkinsonian drugs. In order to clarify the risk factors for parkinsonian MS, the authors retrospectively reviewed charts of consecutive inpatients with PD in the neurological departments at the three hospitals and found 16 episodes of parkinsonian MS in 14 patients. A survey of health status preceding MS disclosed that deterioration of parkinsonian symptoms alone may induce MS, while association of major risk factors, i.e. rapid discontinuation of anti-parkinsonian drugs, dehydration or infection may precipitate or exacerbate MS. Cerebral vascular disorders, mechanical brain injury or physiological stress could be other risk factors leading to MS.