Hydrocephalus due to marked enlargement of spinal roots in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Hydrocephalus or papilledema has rarely been reported in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We report a 65-year-old woman with a 12-year history of CIDP presenting with progressive dementia, hallucination and deterioration of gait. RESULTS: Neurological examination revealed cognitive impairment, symmetric proximal and distal weakness with areflexia and muscle atrophy in the distal four limbs. The cerebrospinal fluid examination showed marked elevation of protein concentration. Magnetic resonance imaging revealed hydrocephalus and marked enlarged cervical and lumbar roots and plexus. The cervical cord and cauda equina were compressed by the swollen roots. A ventriculoperitoneal shunt resulted in reduction of the ventricles size along with improvement of her cognitive impairment. CONCLUSION: In our patient with CIDP, hydrocephalus was likely caused by hypertrophic nerve roots. Our findings suggest that CIDP patients with pronounced hypertrophic nerve roots require careful observation.

Evaluation of non-Gaussian model-based diffusion-weighted imaging in oral squamous cell carcinoma: comparison with tumour functional information derived from positron-emission tomography.

AIM: To evaluate and compare diffusion-weighted imaging (DWI) parameters derived from a non-Gaussian fitting model and positron-emission tomography (PET) parameters derived from 18F-fluoromisonidazole-PET (FMISO-PET) in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Primary sites were evaluated prospectively in 18 patients. DWI was performed using six b-values (0-2,500). Diffusion-related parameters of kurtosis value (K), the kurtosis-corrected diffusion coefficient (DK), diffusion heterogeneity (α), distributed diffusion coefficient (DDC), the slow diffusion coefficient (Dslow), and the apparent diffusion coefficient (ADC) were calculated from four diffusion-fitting models. Maximal standardised uptake values (SUVmax), mean standardised uptake values (SUVmean), and the tumour-to-muscle ration (TMR) of the SUV value were calculated for FMISO-PET. Spearman's correlation coefficient was used to evaluate the correlation between each non-Gaussian diffusion model parameters and PET parameter. RESULTS: There was moderate correlation between FMISO-PET SUVmax and Dslow (ρ=-0.45, p=0.06). In addition, there was good correlation between TMRmax and five non-Gaussian diffusion model parameters (K: ρ=0.65, p=0.004, DK: ρ=-0.72, p=0.0008, DDC: ρ=-0.75, p=0.0003, ADC: ρ=-0.74, p=0.0005, and Dslow: ρ= -0.65, p=0.003), and between TMRmean and five non-Gaussian model parameters (K: ρ=0.64, p=0.005, DK: ρ=-0.61, p=0.007, DDC: ρ=-0.63, p=0.005, ADC: ρ=-0.61, p=0.007, and Dslow: ρ=-0.56, p=0.015). CONCLUSION: Non-Gaussian diffusion model parameters can be related to tumour hypoxia.

Restless legs syndrome is associated with headache-related disabilities in patients with migraine: a prospective 7-year follow-up study.

BACKGROUND AND PURPOSE: No prospective study has evaluated the impact of restless legs syndrome (RLS) on clinical factors in patients with migraine. We planned a prospective study to assess the impact of RLS comorbid status on clinical factors in patients with migraine. METHODS: A total of 101 patients with migraine who were evaluated for RLS twice at 7-year intervals in a university hospital setting were included in this study. The RLS group was defined as positive for RLS at either baseline or follow-up and the non-RLS group was defined as negative for RLS at both baseline and follow-up. The Migraine Disability Assessment (MIDAS) questionnaire, Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale were administered to all patients. RESULTS: The RLS prevalence was 16.8% at baseline and 20.8% at follow-up. Compared with the non-RLS group (n = 27), the RLS group (n = 74) showed a significantly higher rate of smoking and higher MIDAS and BDI-II scores at 7-year follow-up. A significant reduction in MIDAS and BDI-II scores at 7-year follow-up compared with those at baseline was observed in the non-RLS group, but not in the RLS group. The non-RLS group showed a significantly lower MIDAS score at 7-year follow-up than the RLS group after adjusting for confounding variables such as age, gender, smoking status, Epworth Sleepiness Scale and PSQI scores using analysis of covariance. The persistent RLS group (n = 11) (positive for RLS at both baseline and follow-up) showed a significantly higher rate of smoking and increased MIDAS, BDI-II and PSQI scores compared with the non-RLS group (n = 74) at 7-year follow-up. CONCLUSION: Our prospective study showed that RLS had a significant impact on headache-related disability in patients with migraine.

A multiparametric MRI-based machine learning to distinguish between uterine sarcoma and benign leiomyoma: comparison with 18F-FDG PET/CT.

AIM: To compare the performance of machine learning using multiparametric magnetic resonance imaging (mp-MRI) and positron-emission tomography (PET) to distinguish between uterine sarcoma and leiomyoma. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and informed consent was waived. Sixty-seven consecutive patients with uterine sarcoma or leiomyoma who underwent pelvic 3 T MRI and PET were included. Of 67 patients, 11 had uterine sarcomas and 56 had leiomyomas. Seven different parameters were measured in the tumours, from T2-weighted, T1-weighted, contrast-enhanced, and diffusion-weighted MRI, and PET. The areas under the receiver operating characteristic curves (AUC) with a leave-one-out cross-validation were used to compare the diagnostic performances of the univariate and multivariate logistic regression (LR) model with those of two board-certified radiologists. RESULTS: The AUCs of the univariate models using MRI parameters (0.68-0.8) were inferior to that of the maximum standardised uptake value (SUVmax) of PET (0.85); however, the AUC of the multivariate LR model (0.92) was superior to that of SUVmax, and comparable to that of the board-certified radiologists (0.97 and 0.89). CONCLUSION: The diagnostic performance of the machine learning using mp-MRI was superior to PET and comparable to that of experienced radiologists.

A Polymorphism rs6726395 in Nrf2 Contributes to the Development of Emphysema-Associated Age in Smokers Without COPD.

INTRODUCTION: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. METHODS: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. RESULTS: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers. CONCLUSION: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.

Cerebrospinal fluid orexin-A levels in systemic lupus erythematosus patients presenting with excessive daytime sleepiness.

Objective Involvement of the hypothalamus is rare in patients with systemic lupus erythematosus (SLE). In this study, we measured cerebrospinal fluid (CSF) orexin-A levels in SLE patients with hypothalamic lesions to investigate whether the orexin system plays a role in SLE patients with hypothalamic lesions who present with excessive daytime sleepiness (EDS). Methods Orexin-A levels were measured in CSF from four patients with SLE who presented with hypothalamic lesions detected by MRI. Three patients underwent repeated CSF testing. All patients met the updated American College of Rheumatology revised criteria for SLE. Results Tests for serum anti-aquaporin-4 antibodies, CSF myelin basic protein and CSF oligoclonal bands were negative in all patients. All patients presented with EDS. Low to intermediate CSF orexin-A levels (92-180 pg/ml) were observed in three patients in the acute stage, two of whom (patients 1 and 2) underwent repeated testing and showed increased CSF orexin-A levels, reduced abnormal hypothalamic lesion intensities detected by MRI and EDS dissipation at follow-up. In contrast, CSF orexin-A levels were normal in one patient (patient 4) while in the acute stage and at follow-up, despite improvements in EDS and MRI findings. Patient 4 showed markedly increased CSF interleukin-6 levels (1130 pg/ml) and a slightly involved hypothalamus than the other patients. Conclusions Our findings suggest that the orexinergic system has a role in EDS in SLE patients with hypothalamic lesions. Furthermore, cytokine-mediated tissue damage might cause EDS without orexinergic involvement.

Integrating quantitative morphological and intratumoural textural characteristics in FDG-PET for the prediction of prognosis in pharynx squamous cell carcinoma patients.

AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Association analysis of the ACTN3 R577X polymorphism with passive muscle stiffness and muscle strain injury.

Passive muscle stiffness is considered to be a major factor affecting joint flexibility and is thought to relate to the occurrence of muscle strain injury. In skinned muscle fiber experiments, the R577X polymorphism of the α-actinin-3 gene (ACTN3) has been associated with passive muscle stiffness. Our primary purpose was to clarify whether the ACTN3 R577X polymorphism influences passive stiffness of human muscle in vivo. We also examined whether the ACTN3 R577X polymorphism is associated with the occurrence of hamstring strain injury. Seventy-six healthy young male subjects were genotyped for the ACTN3 R577X (rs1815739) polymorphism. Shear modulus (an index of stiffness) of each hamstring muscle (biceps femoris, semitendinosus, and semimembranosus) was assessed using ultrasound shear wave elastography, and history of hamstring strain injury was collected via a questionnaire. The muscle shear moduli of the semitendinosus and semimembranosus were significantly higher in R-allele (RR + RX genotype) carriers than in XX genotype carriers, whereas the shear modulus of the biceps femoris did not differ among the ACTN3 R577X genotypes. Frequency of past hamstring strain injury also did not differ between the 3 genotypes nor between the R-allele and XX genotype carriers. This study indicates that RR and RX genotypes of the ACTN3 R577X polymorphism (corresponding to the presence of α-actinin-3 in type II muscle fibers) are associated with increased passive muscle stiffness of the human hamstring in vivo. However, this altered mechanical property might not affect the risk of hamstring muscle strain injury.

Effects of hamstring stretching on passive muscle stiffness vary between hip flexion and knee extension maneuvers.

The purpose of this study was to examine whether the effects of hamstring stretching on the passive stiffness of each of the long head of the biceps femoris (BFl), semitendinosus (ST), and semimembranosus (SM) vary between passive knee extension and hip flexion stretching maneuvers. In 12 male subjects, before and after five sets of 90 s static stretching, passive lengthening measurements where knee or hip joint was passively rotated to the maximal range of motion (ROM) were performed. During the passive lengthening, shear modulus of each muscle was measured by ultrasound shear wave elastography. Both stretching maneuvers significantly increased maximal ROM and decreased passive torque at a given joint angle. Passive knee extension stretching maneuver significantly reduced shear modulus at a given knee joint angle in all of BFl, ST, and SM. In contrast, the stretching effect by passive hip flexion maneuver was significant only in ST and SM. The present findings indicate that the effects of hamstring stretching on individual passive muscles' stiffness vary between passive knee extension and hip flexion stretching maneuvers. In terms of reducing the muscle stiffness of BFl, stretching of the hamstring should be performed by passive knee extension rather than hip flexion.

Characterization of secondary ion emission processes of sub-MeV C60 ion impacts via analysis of statistical distributions of the emitted ion number.

We report probability distributions of the number of secondary ions (SIs) emitted by sub-MeV C60 ion impacts on an organic polymer target and the characterization of their emission processes through the analysis of the distributions. The probability distributions were obtained by analyzing experimental SI counting data obtained by a time-of-flight SI mass spectrometer combined with pulsed primary ion beams, using an analytical model developed to derive the distributions from the experimental data. A series of probability distribution functions was investigated for ion impacts of C60 with sub-MeV energies (0.12-0.54 MeV), which can provide sufficient SIs per impact to determine the functions. Their complicated and undefined SI emission processes were characterized based on the determined functions.

Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.

WHAT IS KNOWN AND OBJECTIVE: Midazolam (MDZ) is commonly used for sedating critically ill patients. The daily dose required for adequate sedation increases in increments over 100 h after administration. The objectives of this study were to characterize the MDZ pharmacokinetics in critically ill patients and to describe the phenomenon of increasing daily dose by means of population pharmacokinetic analysis. METHODS: Data were obtained from 30 patients treated in an intensive care unit. The patients received MDZ intravenously as a combination of bolus and continuous infusion. Serum MDZ concentration was assayed by high-performance liquid chromatography. Population pharmacokinetic analysis was performed using the NONMEM software package. The alteration of clearance unexplained by demographic factors and clinical laboratory data was described as an autoinduction of MDZ clearance using a semi-mechanistic pharmacokinetic-enzyme turnover model. RESULTS AND DISCUSSION: The final population pharmacokinetic model was a one-compartment model estimated by incorporating a semi-mechanistic pharmacokinetic-enzyme turnover model for clearance, taking autoinduction into account. A significant covariate for MDZ clearance was total bilirubin. An increase in total bilirubin indicated a reduction in MDZ clearance. From simulation using the population pharmacokinetic parameters obtained in this study, MDZ clearance increased 2·3 times compared with pre-induced clearance 100 h after the start of 12·5 mg/h continuous infusion. WHAT IS NEW AND CONCLUSION: Autoinduction and total bilirubin were significant predictors of the clearance of MDZ in this population. Step-by-step dosage adjustment using this population pharmacokinetic model may be useful for establishing a MDZ dosage regimen in critically ill patients.

Oscillatory behavior of vortex-lattice melting transition line in mesoscopic Bi_{2}Sr_{2}CaCu_{2}O_{8+y} superconductors.

The vortex-lattice melting transition of a limited number of vortices confined in mesoscopic square superconductors was studied by c-axis resistance measurements using stacks of intrinsic Josephson junctions in Bi_{2}Sr_{2}CaCu_{2}O_{8+y}. In contrast to the melting transition in bulk crystals, we have first found a clear oscillatory behavior in the field dependence of the melting temperature in small samples of 5-10 µm square. The periods of the oscillations roughly obey the regularity of the matching conditions of square vortex lattices surrounded by a square boundary and the melting temperatures are enhanced around the vortex number of i^{2} (where i is an integer). The results suggest that a confinement effect by the square boundary stabilizes square lattice structures which are realized around i^{2} vortex number even in competition with the favorable Abrikosov triangular lattice in the bulk.

Positron emission tomography-computed tomography can be useful in the early detection of metastases in primary mucinous carcinoma of the skin on the head and neck.

Primary mucinous carcinoma of the skin (PMCS) is a rare cutaneous malignant neoplasm; its regional node metastasis is also rare. Currently, positron emission tomography-computed tomography (PET-CT) is known to be a useful tool to search for early metastatic lesions in various carcinomas. However, PET-CT is not always specific for head and neck lesions because of physiological uptake in the brain, palatine tonsil, salivary gland, thyroid etc. Herein we present two cases of head and neck PMCS in which metastasis was diagnosed accurately by PET-CT. In these cases, nodal uptake of fluorodeoxy-d-glucose (FDG) histopathologically proved PMCS metastasis, verifying the utility of PET-CT in detail. A surgeon was involved in the verification to compare the histopathological manifestations with the imaging results. Histopathologically, two of 13 nodes were positive in case 1, and one of 41 nodes was positive in case 2. These positive nodes were completely in accordance with the FDG uptake findings with no false negative findings. In treating PMCS on head and neck lesions, PET-CT may be useful in the preoperative assessment when planning the extent of resection.

Evaluation of cutoff scores for the Parkinson's disease sleep scale-2.

BACKGROUND: The Parkinson's Disease Sleep Scale (PDSS)-2 is a recently developed tool for evaluating disease-related nocturnal disturbances in patients with Parkinson's disease (PD). However, its cutoff score has not been clinically assessed. We determined the optimal cutoff score of the Japanese version of the PDSS-2. METHODS: Patients with PD (n = 146) and controls (n = 100) completed the PDSS-2 and the Pittsburgh Sleep Quality Index (PSQI). Poor sleepers were defined as having global PSQI scores >5. Optimal cutoff scores for determining poor sleepers were assessed using the receiver operating characteristic curve. RESULTS: A PDSS-2 total score ≥ 14 exhibited 82.0% sensitivity and 70.6% specificity, whereas a PDSS-2 total score ≥ 15 provided 72.1% sensitivity and 72.9% specificity in distinguishing poor sleepers (PSQI score >5) from good sleepers (PSQI ≤ 5). Nocturnal disturbances were more frequently observed in patients with PD than in controls (PDSS-2 total score ≥ 14 or ≥ 15; 51.4% vs 20%; 45.9% vs 19%). Nocturnal disturbances were associated with higher Hoehn and Yahr stages and Unified Parkinson's Disease Rating Scale motor scores, impaired quality of life, daytime sleepiness, and depressive symptoms. CONCLUSION: We suggest that PDSS-2 total scores ≥ 15 are useful for detecting poor sleepers among patients with PD.

Impact of glucose fluctuation and monocyte subsets on coronary plaque rupture.

BACKGROUND AND AIMS: It remains unclear whether glycemic fluctuation can affect plaque rupture in acute myocardial infarction (AMI). Here we investigate the impact of glucose fluctuation on plaque rupture, as observed by optical coherence tomography (OCT), and monocyte subsets in patients with AMI. METHODS AND RESULTS: We studied 37 consecutive patients with AMI. All patients underwent OCT examination, which revealed 24 patients with plaque rupture and 13 patients without plaque rupture at the culprit site. Peripheral blood sampling was performed on admission. Three monocyte subsets (CD14(+)CD16(-), CD14(bright)CD16(+), and CD14(dim)CD16(+)) were assessed by flow cytometry. Glycemic variability, expressed as the mean amplitude of glycemic excursion (MAGE), was determined by a continuous glucose monitoring system 7 days after the onset of AMI. MAGE was significantly higher in the rupture patients than in the non-rupture patients (P=0.036). Levels of CD14(bright)CD16(+) monocytes from the rupture patients were significantly higher than those from the non-rupture patients (P=0.042). Of interest, levels of CD14(bright)CD16(+) monocytes correlated positively and significantly with MAGE (r=0.39, P=0.02). CONCLUSION: Dynamic glucose fluctuation may be associated with coronary plaque rupture, possibly through the preferential increase in CD14(bright)CD16(+) monocyte levels.

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence.

BACKGROUND: Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence. METHODS: Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed. RESULTS: The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71-83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30-18.8). CONCLUSION: CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.