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This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA (n = 37) and other non-inflammatory neurological diseases (ONDs; n = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.

The current study aimed to evaluate whether cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels are elevated in amyotrophic lateral sclerosis (ALS) and are effective in distinguishing ALS from cervical spondylotic myelopathy (CSM). We retrospectively evaluated 45 patients with ALS, 23 with CSM, and 28 controls who underwent analysis of CSF NSE levels. The control group comprised patients aged above 45 years who underwent lumbar puncture because of suspected neurological disorders that were ruled out after extensive investigations. CSF NSE levels were evaluated using the electro-chemiluminescent immunoassay. The ALS group had significantly higher CSF NSE levels than the CSM and control groups (P < 0.001 for both comparisons). The CSM and control groups did not significantly differ in terms of CSF NSE levels. A receiver-operating characteristic curve analysis was performed to assess the diagnostic value of CSF NSE levels in distinguishing ALS from CSM. The area under the curve for CSF NSE levels was 0.86. The optimal cutoff value was 17.7 ng/mL, with a specificity of 87% and a sensitivity of 80%. Hence, CSF NSE levels are elevated in ALS and are effective in distinguishing ALS from CSM.

The current study aimed to evaluate whether cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels are elevated in amyotrophic lateral sclerosis (ALS) and are effective in distinguishing ALS from cervical spondylotic myelopathy (CSM). We retrospectively evaluated 45 patients with ALS, 23 with CSM, 28 controls, and 10 with Parkinson’s disease (PD) who underwent analysis of CSF NSE levels. The control group comprised patients aged above 45 years who underwent lumbar puncture because of suspected neurological disorders that were ruled out after extensive investigations. CSF NSE levels were evaluated using the electro-chemiluminescent immunoassay. The ALS group had significantly higher CSF NSE levels than the CSM and control groups (P

Background Fulminant Guillain-Barré syndrome (GBS) is characterized clinically by rapid progression of severe symptoms, such as the absence of brainstem reflexes, complete tetraplegia and respiratory arrest. The clinical course of fulminant GBS remains unclear. Here, we report a patient with fulminant GBS, who showed severe weakness of the pharyngeal-cervical-branchial (PCB) area in the recovery phase. Case presentation A 38-year-old man rapidly developed fulminant GBS. In blood examination, he was positive for a broad range of anti-ganglioside antibodies, including anti-GQ1b, GT1a, GT1b, GD1a, GD1b and GD3 IgG antibodies. We performed immunosuppressive therapies using intravenous immunoglobulin and intravenous methylprednisolone. Although disturbance of consciousness and weakness of the distal upper and lower limbs improved gradually, weakness of the oropharynx, neck, and proximal upper limbs were resistant to these therapies. Anti-GT1a IgG antibodies remained persistently positive. Consequently, mechanical ventilation and tube feeding were required for 7 and 10 months, respectively. Two years later, weakness of the proximal upper limbs and mild respiratory dysfunction remained as sequelae. Conclusion Anti-GT1a IgG antibodies are known to be detected in patients with the PCB variant of GBS. In fulminant GBS, the persistent presence of anti-GT1a IgG antibodies may be associated with occurrence of severe PCB-like weakness in the recovery phase.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often causes peripheral nervous system impairments. However, little is known about subclinical involvements of the central nervous system in AAV. We investigated the frequency and progression of cerebral small vessel disease (SVD) in patients with AAV. This single-center, case–control study comprised 56 patients with myeloperoxidase (MPO)-ANCA-positive AAV. Cerebral SVD presenting periventricular and deep white matter hyperintensities was assessed using brain magnetic resonance imaging (MRI). Seventy-five patients with non-stroke-associated neurological diseases were employed as controls. At clinical diagnosis of MPO-ANCA-positive AAV, the frequency of periventricular hyperintensities in the AAV group was significantly higher than that in the control group (P = 0.014). Shinohara and Fazekas grades of periventricular hyperintensities in the AAV group were significantly higher than those in the control group (P = 0.019 and 0.020, respectively). In the AAV group, atherosclerosis-related factors, such as age and hypertension, were not associated with the Shinohara grades of periventricular hyperintensities, whereas serum CRP levels were significantly associated (odds ratio = 6.000, 95% confidence interval 1.648–21.840, P = 0.004). MRI changes were followed in 23 patients with AAV until 2 years after 6 months of diagnosis. Six of these patients worsened the grades of periventricular hyperintensities, while two of 27 in the control group worsened the grades (P = 0.013). Inflammatory events are associated with the occurrence of cerebral SVD before clinical diagnosis of MPO-ANCA-positive AAV. The patients may be continuously exposed to the risk of cerebral SVD after immunosuppressive therapy.

An 84-year-old woman developed blepharoptosis, diplopia, weakness of extremities, and dysphagia with elevation of serum CK levels after treatment with nivolumab against renal cell carcinoma. 3 Hz repetitive stimulation showed waning in the trapezius muscle, leading to the diagnosis of myasthenia gravis. Laboratory examination showed that anti-acetylcholine receptor antibody was negative. We performed IVIg and steroid therapy. However, her symptoms did not improve, and she died of respiratory failure, although serum CK levels ameliorated to the normal range. The results of autopsy showed atrophy of muscle fibers and massive infiltration of inflammatory cells in the endomysium of the iliopsoas muscle and diaphragm, indicating occurrence of myositis. Immunohistochemical analysis showed that CD8-positive T cells mainly infiltrates in the endomysium with a small number of CD4-potive T cells. Here, we report an autopsy case of nivolumab-induced myasthenia gravis and myositis.

Serum cytokine levels were comprehensively measured, and the association with cerebrovascular lesions on brain magnetic resonance imaging (MRI) in microscopic polyangiitis (MPA) patients was investigated. The initial serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly higher in the high-grade white matter hyperintensities (WMH) group than those in the low-grade WMH group. In multivariate analyses, high serum levels of GM-CSF were independently associated with high-grade WMH. The initial serum GM-CSF levels correlated positively with the Birmingham Vasculitis Activity Score and semi-quantitative scales of WMH. The initial serum GM-CSF levels were associated with the severity of WMH in MPA patients.

Introduction In myasthenia gravis (MG) therapy, achieving Myeasthenia Gravis Foundation of America minimal manifestation (MM) or better status is proposed as a desirable target. However, this level of control often is not achieved and clinical factors affecting prognosis remain unclear. Methods Participants were 104 consecutive patients with MG who visited Osaka Medical College Hospital. We retrospectively assessed the association of clinical and laboratory features at baseline with prognosis. Eighty patients who achieved MM or better status were classified as the good outcome group and the remaining 24 patients were classified as the poor outcome group. Results The rate of dysphagia at baseline was significantly higher in the poor outcome group than in the good outcome group (p = 0.002). The levels of serum total protein and albumin at baseline were both significantly lower in the poor outcome group than in the good outcome group (p = 0.036 and p = 0.014, respectively). Additionally, Controlling Nutritional Status scores at baseline were significantly higher in the poor outcome group than in the good outcome group (p = 0.043). Multivariate analysis using a Cox proportional hazards model showed that dysphagia (hazard ratio [HR], 6.92; 95% confidence interval [CI], 1.49-40.31) and hypoalbuminemia (HR, 2.57; 95% CI, 1.04-6.57) at baseline were risk factors that predicted prognosis. Discussion These findings suggest that dysphagia and hypoalbuminemia at baseline are associated with outcomes and are predictive risk factors for poorer outcomes in patients with MG.

Circular dichroism (CD), defined as the differential absorption of left- and right-handed circularly polarized light (CPL), is a useful spectroscopic technique for structural studies of biological systems composed of chiral molecules. The present study evaluated the effects of CPL on germination, hypocotyl elongation and biomass production of Arabidopsis and lettuce. Higher germination rates were observed when Arabidopsis and lettuce seedlings were irradiated with red right-handed CPL (R-CPL) than with red left-handed CPL (L-CPL). Hypocotyl elongation was effectively inhibited when Arabidopsis and lettuce seedlings were irradiated with red R-CPL than with red L-CPL. This difference was not observed when a phytochrome B (phyB) deficient mutant of Arabidopsis was irradiated, suggesting that inhibition of elongation by red R-CPL was mediated by phyB. White R-CPL induced greater biomass production by adult Arabidopsis plants, as determined by their fresh shoot weight, than white L-CPL. To determine the molecular basis of these CPL effects, CD spectra and the effect of CPL on the photoreaction of a sensory module of Arabidopsis phyB were measured. The red light-absorbing form of phyB showed a negative CD in the red light-absorbing region, consistent with the results of germination, inhibition of hypocotyl elongation and biomass production. L-CPL and R-CPL, however, did not differ in their ability to induce the interconversion of the red light-absorbing and far-red light-absorbing forms of phyB. These findings suggest that these CPL effects involve phyB, along with other photoreceptors and the photosynthetic process.

Purpose Many studies have found no notable long-term differences in functional outcomes between operative and conservative treatments for distal radius fractures (DRFs) in elderly patients. However, those studies have not considered hand dominance. The current study compared outcomes between both treatments in a dominant wrist–injured group (dominant group) and nondominant wrist–injured group (nondominant group). Methods A total of 101 patients aged 65 years and older who experienced displaced DRF requiring reduction and who were managed for over 3 months with either operative or conservative treatment were examined. The dominant group included 46 subjects (operative, n = 26; conservative, n = 20), and the nondominant group included 55 subjects (operative, n = 28; conservative, n = 27). All operative treatments were performed with volar locking plate fixation, and all conservative treatments were immobilized with a sugar-tong orthosis or forearm cast. Functional outcomes and radiographic assessments were compared 3 months after treatment. The primary outcome measure was the Quick–Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score; secondary outcomes were grip strength, range of motion, and Mayo wrist score. We also examined QuickDASH scores after at least 1 year. Results The QuickDASH score showed no significant differences between treatments by dominance at 3 months or more than a year. In the dominant group, operative treatment resulted in significant 7-kg greater grip strength at 3 months, whereas the nondominant group showed no significant differences in functional outcomes between treatments. Conclusions Although QuickDASH scores were similar at 3 months and 1 year between treatments regardless of hand dominance, surgery for dominant-side DRF resulted in better grip strength than conservative treatment at 3 months. Clinical relevance This study will help clarify potential outcomes differences between operative and conservative DRF treatment in patients aged over age 65 years.

Background It is not well defined whether Guillain–Barré syndrome (GBS) patients with elevated serum creatine kinase (CK) levels have characteristic clinical features and are related to the subgroups of GBS. Methods We retrospectively studied 51 consecutive patients with GBS, who visited our hospital, and compared clinical, laboratory and electrophysiological findings between patients with and without elevated CK levels. Results Of 51 patients, 14 patients (27%) showed an elevation of serum CK levels. When compared with patients with the normal CK levels, the ratios of male, antecedent infections, and anti-GM1 antibody positivity were significantly higher in patients with elevated CK levels. The ratios of hypoesthesia, cranial nerve involvement, and urinary retention were significantly less in patients with elevated CK levels. There were no significant differences in disability at peak between two groups. In the electrophysiological examination, sensory nerve abnormalities were not observed. Although some patients with elevated CK levels showed prolongation of distal motor latencies (DMLs) and increase of durations in the initial examination, development of the prolongation of DMLs and increase of durations was not observed in the follow-up examinations. The findings were consistent with acute motor axonal neuropathy (AMAN) with reversible conduction failure (RCF) but not acute inflammatory demyelinating polyneuropathy (AIDP). Conclusions The results suggest that the GBS patients with elevated CK levels represent not a group of AIDP but a group of AMAN with axonal degeneration or RCF even though the initial electrophysiological examination shows AIDP pattern.

We herein report the case of a 53-year-old man with cerebellar ataxia with anti-glutamic acid decarboxylase antibody (GAD-Ab) who mimicked Miller Fisher syndrome (MFS). He developed ophthalmoplegia, diplopia, and gait ataxia for one week. The serum and cerebrospinal fluid GAD-Ab titers were greatly increased, and the GAD-Ab index suggesting intrathecal antibody synthesis was elevated, while GQ1b-Ab was negative. After steroid pulse therapy and following prednisolone, his symptoms dramatically improved over the course of 11 months with the simultaneous decline of GAD-Ab titers. This case indicates that cerebellar ataxia with GAD-Ab can present with acute neurological findings mimicking MFS, and that steroid therapy has an excellent therapeutic effect.

Sodium secondary batteries are attracting considerably renewed interest as new battery systems owing to the high and uniform abundance and cost advantages of Na. However, their performance is still far from optimal as compared to the well-developed Li-ion technology. Herein, Na secondary batteries with unprecedented rate capability and a long life has been achieved by using a highly concentrated bis(fluorosulfonyl)amide anion (FSA – )-based ionic liquid electrolyte (3.3 mol dm −3 Na[FSA]) and a Na 2 FeP 2 O 7 positive electrode, in a targeted operating temperature range from room to intermediate. Nearly full discharge capacity is obtained at 4000 mA g −1 , and 79% of the capacity is retained at a discharge rate as high as 20000 mA g −1 at 363 K. Stable cycling (>300 cycles) with satisfactory coulombic efficiency (>99.5%) is found at an intermediate rate (100 mA g −1 ) over 298–363 K. A high-rate cycling test (1000 mA g −1 ) at 363 K reveals that the cell could retain 93% of its initial capacity after 1500 cycles.

The stability of [C2C1im][FSA] (C2C1im+: 1-ethyl-3-methylimidazolium; FSA–: bis(fluorosulfonyl)amide) and [C2C1im][TFSA] (TFSA–: bis(trifluoromethylsulfonyl)amide) ionic liquids against Na metal has been investigated in view of their application as electrolytes for Na secondary batteries. Cyclic voltammetry revealed that Na metal electrodeposition/dissolution reactions occur in Na[FSA]–[C2C1im][FSA], whereas these processes do not occur in Na[TFSA]–[C2C1im][TFSA]. Both visual and spectroscopic changes were observed for Na[TFSA]–[C2C1im][TFSA] after immersion of Na metal for 4 weeks, but no changes were observed for Na[FSA]–[C2C1im][FSA]. X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy indicated that there were differences in the thickness of the surface films on Na metal immersed in these ionic liquids. The presence of Na+ also affects the thickness of the surface film, and the nature of the surface films determines the difference in the stability of Na metal in these two ionic...

Ionic liquid electrolytes are widely studied to construct safe electrochemical devices owing to their unique properties such as low volatility, low flammability, and wide liquid-phase temperature range. Ionic liquids based on sulfonylamide anions (bis(fluorosulfonyl)amide anion (FSA-) have low melting point, low viscosity, and high ionic conductivitysome and are attractive as electrolytes in secondary batteries. The present study reports physical and electrochemical properties of FSA-based ionic liquid electrolytes for secondary betteries operating from room temperature to intermediate temperature. Intermediate operation of secondary batteries in is available in some circumstances such as an engine compartment of automobiles and is preferable to enhance both the ion transport and electrode reactions. The Na[FSA]-[C3C1pyrr][FSA] (C3C1pyrr+ = N-methyl-N-propylpyrrolidinium) and Na[FSA]-[C2C1im][FSA] (C2C1im+ = 1-ethyl-3-methylimidazolium) ionic liquid systems have wide liquid phase temperature ranges around room temperature and high ionic conductivities [1,2]. Immersion of Na metal in FSA- and TFSA-based ionic liquids clearly showed that FSA-based ionic liquids form stable film on Na metal to prevent futher reduction. Dendrite formation during Na metal electrodeposition is suppressed by increasing temperature. Excellent rate capability and cycle property were observed for the Na2FeP2O7 positive electrode in FSA-based ionic liquids at 363 K.[3] The origin of this performance will be discussed based on transport properties of Na+ by considering transport number and Na+fraction in these ionic liquids. Acknowledgements: This study was partly supported by Advanced Low Carbon Technology Research and Development Program (ALCA) of Japan Science and Technology Agency (JST) and Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) program “Elements Strategy Initiataive to Form Core Research Center”. References [1] K. Matsumoto, T. Hosokawa, T. Nohira, R. Hagiwara, A. Fukunaga, K. Numata, E. Itani, S. Sakai, K. Nitta, S. Inazawa, J. Power Sources, 2014, 265, 36-39 [2] K. Matsumoto, Y. Okamoto, T. Nohira, R. Hagiwara, J. Phys. Chem. C, 2015, 119, 7648-7655. [3] C. Chen, K. Matsumoto, T. Nohira, C. Ding, T. Yamamoto, R. Hagiwara, Electrochim. Acta, 2014, 133, 583-588.

Introduction: Patient-reported outcomes recently have been used to assess treatment outcomes. The Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) is a particularly convenient and useful tools. However, data on the normative values of Japanese population are lacking, so the present study was conducted to gather this information. Methods: We assessed 1098 volunteers over 18 years of age (363 men and 735 women, average 50 years old) who had not received upper limb treatment in a medical facility. These participants included our institution’s staff, their family members, and the participants in the group meetings held by institution’s staff. Their occupations were also examined. We divided occupations into nonmanual and manual labor. These factors of the participants were then analyzed to clarify which (if any) influenced the QuickDASH. Results: Valid answers were obtained from 961 subjects (87.5%). The median score was 2 (mean: 4.8) in the overall population, 0 (mean: 2.6) in men, and 2.5 (mean: 6.0) in women. The scores increased with age and were higher in women than in men. There were no significant differences by manual labor. Female sex and older age were identified as factors that influenced the QuickDASH score in the multiple regression analysis. There were high correlations among QuickDASH, work and sports/music scores. Conclusions: The present study provided QuickDASH scores for Japanese volunteers who had not received upper limb treatment in a medical facility. The scores were associated with older age and female sex. This study helps us to know the degree of potential upper limb impairment in the general population, and will help in populational strategies as primary and secondary preventive medicine for upper limb-related diseases.

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy.

Background Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein–Barr virus (EBV) infection. Case presentation A 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative. Conclusions This case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

Physical and electrochemical properties of the Na[FSA]–[C2C1im][FSA] (C2C1im+:1-ethyl-3-methylimidazolium and FSA−:bis(fluorosulfonyl)amide) ionic liquids have been investigated in view of their application as electrolytes for sodium secondary batteries operating in a wide temperature range. The Na[FSA]–[C2C1im][FSA] ionic liquids in the range of 0.0 ≤ x(Na[FSA]) ≤ 0.5 are in the liquid state at room temperature, where x(Na[FSA]) is the mole fraction of Na[FSA]. In the case of x(Na[FSA]) = 0.3, the ionic conductivity, viscosity, and electrochemical window at 298 K are 5.4 mS cm−1, 78 mPa s, and 5.1 V, respectively. Sodium metal deposition/dissolution test in the ionic liquid at x(Na[FSA]) = 0.3 resulted in average cycle efficiencies of 69% and 96% at 298 K and 363 K, respectively, at a current density of 1.0 mA cm−2.

Objective To evaluate the factors related to the choice of a tracheostomy and invasive ventilation in amyotrophic lateral sclerosis patients and to determine survival time after a tracheostomy at a single institute in Japan between 1990 and 2010. Methods Data for survival time until death or tracheostomy were obtained from 160 patients. Fifty-two patients (33%) underwent tracheostomy/mechanical ventilation. Results Tracheostomy and invasive ventilation prolonged median survival time (74 months), as did non-invasive ventilation (48 months) when compared to a non-ventilation-supported control group (32 months; p 65 years old significantly increased after 1999 (27%) compared to earlier years (10%, p = 0.002). Cox proportional modeling confirmed an age of ≤ 65 years as advantageous for long-term survival after a tracheostomy. In univariate logistic regression analysis, factors related to the decision to perform a tracheostomy included an age of ≤ 65 years, greater use of non-invasive ventilation, the presence of a spouse, interval and speed from disease onset to diagnosis/tracheostomy and preservation of motor function. In multivariate logistic regression analysis, age, shorter duration from disease onset until tracheostomy and the presence of a spouse were independently associated with the decision to perform a tracheostomy. Kaplan–Meier plots revealed longer survival times in patients who resided at home after a tracheostomy compared to patients who stayed at a hospital (p = 0.007). Conclusions Tracheostomy and invasive ventilation are frequently used in Japan. Various factors impact patients' decisions to have these procedures. This study identified factors related to the decision-making process and post-tracheostomy survival.

Eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids, is a neuroprotective lipid with anti-inflammatory properties. We investigated the possible therapeutic effect of EPA on experimental autoimmune encephalomyelitis (EAE). EAE mice were fed a diet with or without EPA. The clinical EAE scores of the EPA-fed mice were significantly lower than those of the non-EPA mice. In the EPA-treated mice, IFN-γ and IL-17 productions were remarkably inhibited and the expression levels of peroxisome proliferator-activated receptors were significantly enhanced in the CNS-infiltrating CD4T cells. Thus EPA shows promise as a potential new therapeutic agent against multiple sclerosis.

A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.

Osteochondroma of the carpal is rare. We found only 1 case of osteochondroma of the trapezium in the literature. We present a case of a 52-year-old woman with an osteochondroma of the left trapezium and trapeziometacarpal arthritis.

Aim: Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinson's disease (PD). This study examined hedonic tone in patients with PD using the Snaith–Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self-Rating Questionnaire for Depression (SRQ-D). Methods: This study examined 100 patients with PD and 111 age-matched controls (C2) recruited from 300 healthy subjects (C1) to compare the frequency of anhedonia and to clarify whether anhedonia in PD is associated with depression and anti-Parkinson medication. Results: Forty-six percent of PD patients revealed possible/probable depression and 10 patients (10%) with PD showed anhedonia as compared to 3.3% in C1 and 2.7% in C2. The reduction in hedonic tone was related to depression in PD. Among 10 PD patients with anhedonia, seven were in anhedonia with depression and three were in anhedonia without depression. There was no sex difference in anhedonia and depression. No patients treated with pramipexole showed anhedonia but also the highest proportion of normal hedonic tone was found in patients treated with pramipexole among PD patients. In analysis of each SHAPS item, no significant difference was seen on social interaction scores in contrast to the significant reduction of interest/pastimes and sensory experience and food/drink scores between PD patients and C1/C2. Conclusion: Anhedonia may overlap depressive syndrome but some PD patients without depression presented anhedonia. Pramipexole could maintain hedonic tone. The PD patients could enjoy attracting attention and wish to do things helpful for others. Geriatr Gerontol Int 2011; 11: 275–281.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.

Guillain–Barre syndrome (GBS) is an acute, post-infectious, inflammatory, autoimmune peripheral neuropathy with a highly diverse clinical course and outcome. We classified GBS on the basis of patients’ first nerve conduction and validated this system to be associated with outcome on the basis of electrophysiological characteristics during the acute phase of GBS. We retrospectively evaluated 40 GBS patients who underwent their first electrophysiological study within 14 days of onset and classified GBS into four patterns: (1) acute inflammatory demyelinating polyneuropathy (AIDP) pattern with sensory nerve conduction abnormalities (motor–sensory AIDP: MS-AIDP), (2) AIDP pattern without sensory nerve conduction abnormalities (motor AIDP: M-AIDP), (3) acute motor axonal neuropathy (AMAN) pattern, and (4) minor abnormalities pattern. We compared the clinical, electrophysiological, and laboratory findings between groups and determined subgroups associated with poor outcome. The MS-AIDP and AMAN patterns more frequently exhibited prolonged recovery compared with the M-AIDP and minor abnormalities patterns and were associated with prolonged recovery (specificity, 100 %; sensitivity, 73 %; P < 0.001). The period of inability to walk independently was significantly longer in the MS-AIDP and AMAN patterns than in the M-AIDP and minor abnormalities patterns (median 85 vs. 10 days; P < 0.001). In conclusion, our classification of GBS using a single nerve conduction study in the early phase of disease is associated with outcomes. This classification can be used to counsel individual patients and guide decision-making with respect to treatment.

Ceftriaxone is known to induce gallstones and intrabiliary debris as the adverse effects. Ceftriaxone-related cholelithiasis occurs mainly in children treated with a high dosage of ceftriaxone for severe infections and has been rarely reported in adults. Here we report two cases of bacterial meningitis, with cholelithiasis complication developed during ceftriaxone treatment. A 65 year old man and a 66 year old man were treated with long-term (3 weeks) administration of high-dose ceftriaxone (4 g/day) for bacterial meningitis. Both patients had renal dysfunction, which may have affected gallstone formation. In one patient, gallstones spontaneously disappeared after discontinuing ceftriaxone treatment. However, the other patient needed the drainage by endoscopic retrograde cholangiopancreatography. These events are associated with elevated doses of ceftriaxone and require particular attention in the elderly and patients with renal dysfunction.

Polystyrene-block-polyisoprene (PS-block-PI; high 3,4-structure) diblock copolymer was prepared by living anionic polymerization. For transfer into a reactive intermediate, the hydroxylation of the double bonds of PI block was achieved by hydroboration, followed by oxidation. Esterification of the hydroxy-derivative with stearoyl chloride or decanoyl chloride resulted in block-graft copolymers composed of PS (flexible chain)-grafted long alkane (stretched chains). After partial chloromethylation of PS block copolymer, photofunctional N,N-diethyldithiocarbamate (DC) groups were introduced into such pendant sites by reaction with the corresponding sodium salt. We studied the self-assemblies of photofunctional block-graft copolymers in a selective solvent, such as heptane, and constructed nanostructured polymers by crosslinking PS cores under UV irradiation. © 2001 Society of Chemical Industry

Polystyrene-block-poly(4-vinylpyridine) (PS-block-P4VP) (P4VP block, 36 mol%) was prepared by anionic polymerization. Three types of morphologies (sphere, cylinder and lamella) were controlled by changing the casting solvents. Subsequently, the cross-linking reaction of P4VP spherical, cylindrical or lamellar microdomains was carried out with the vapor of 1,4-dibromobutane in the solid state. The morphologies and solution properties of the cross-linked products were studied by electron microscopy, small-angle X-ray scattering and static and dynamic light scattering.

In networks with heavy WWW traffic, the disk I O performance can become a bottleneck for caching proxies. To solve this problem, we propose a memory-based architecture for WWW caching proxies. The features of the proposed architecture are (1) a cache contents control that retrieves only frequently accessed WWW pages, and (2) an automatic distribution mechanism that enables efficient cache space sharing among multiple caching proxies. A statistical analysis shows that our approach reduces the required cache space. It consumes only 1 10 the cache space of current typical proxies while retaining the same cache hit rate. The reduced cache space enables the use of fast DRAMs in the caching proxies, and solves the disk I O problem.

Background Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson’s disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements. Methods This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson’s disease. Results Deep vein thrombosis was detected in 23 patients (20%) with Parkinson’s disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson’s drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson’s disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson’s disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis. Conclusion Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson’s disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson’s disease.

Matrix metalloproteinase-9 (MMP-9) plays an important role in some neuroinflammatory diseases through the blood-brain barrier (BBB) disruption. To investigate the pathogenicity of MMP-9 in neuromyelitis optica (NMO), serum and CSF MMP-9 concentrations were measured in 13 NMO and 15 multiple sclerosis (MS) patients and 14 healthy controls, and correlated with clinical and laboratorial parameters. Serum MMP-9 concentrations were significantly higher in NMO than MS and controls, and correlated with EDSS score, CSF/serum albumin ratio, and CSF IL-8 concentrations. Our results indicate that MMP-9, promoted by elevated IL-8 activation, plays a crucial role in the pathogenesis of NMO through the BBB disruption.

Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinson's disease (PD). This study examined hedonic tone in patients with PD using the Snaith-Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self-Rating Questionnaire for Depression (SRQ-D).This study examined 100 patients with PD and 111 age-matched controls (C2) recruited from 300 healthy subjects (C1) to compare the frequency of anhedonia and to clarify whether anhedonia in PD is associated with depression and anti-Parkinson medication.Forty-six percent of PD patients revealed possible/probable depression and 10 patients (10%) with PD showed anhedonia as compared to 3.3% in C1 and 2.7% in C2. The reduction in hedonic tone was related to depression in PD. Among 10 PD patients with anhedonia, seven were in anhedonia with depression and three were in anhedonia without depression. There was no sex difference in anhedonia and depression. No patients treated with pramipexole showed anhedonia but also the highest proportion of normal hedonic tone was found in patients treated with pramipexole among PD patients. In analysis of each SHAPS item, no significant difference was seen on social interaction scores in contrast to the significant reduction of interest/pastimes and sensory experience and food/drink scores between PD patients and C1/C2.Anhedonia may overlap depressive syndrome but some PD patients without depression presented anhedonia. Pramipexole could maintain hedonic tone. The PD patients could enjoy attracting attention and wish to do things helpful for others.

Respiratory insufficiency is a problem that develops in nearly all people diagnosed with amyotrophic lateral sclerosis (ALS). A 46-year-old man with ALS, who had been in a bedridden state with tracheal ventilation support, complained of faintness and dyspnea. The airway pressure of the ventilator had increased, and bleeding from the trachea had occurred several times. A fiberoptic bronchoscopy showed granulation located on the anterior wall of the trachea and severe airway obstruction of the tracheostomy tube. Although a long tracheostomy tube had been intubated for the initial management of the tracheal granulation, a tumor on the posterior tracheal wall had relapsed and occluded the tracheal lumen. A self-expandable metallic airway stent was placed into the tracheal stenosis. After stenting, his symptoms of dyspnea and syncope imploved, and the increased airway pressure of the ventilator was normalized. We speculated that the tracheal granuloma had occurred due to a tracheal mucosal injury related to endotracheal suctioning. We should pay attention to complaints of dyspnea in ALS patients with tracheostomy and make a careful consideration to airway care including suction management.

Although Japanese encephalitis virus is mainly associated with encephalitis, it does cause other diseases. However, descriptions of symptomatic infections other than encephalitis are limited. In this study, cerebrospinal fluid (CSF) specimens from 21 patients with aseptic meningitis from July to October (in summer season) in each year from 1993 to 2005 were investigated for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified by nested polymerase chain reaction (PCR). Among the specimens, only one product had highest homology with Japanese encephalitis virus genotype III. The patient was a 34-year-old man who complained of headache and fever in July 1998. He was clinically diagnosed with aseptic meningitis, and the symptoms subsided spontaneously without specific treatment in several days. It is suggested that some cases of aseptic meningitis in summer could be caused by Japanese encephalitis virus.

To determine which of the three motor functions (bulbar, upper extremities, lower extremities) was normally preserved at the time that respiratory symptoms occurred in amyotrophic lateral sclerosis (ALS).Respiratory failure is the major cause of death in ALS. The course of the disease progression to the onset of subjective respiratory symptom can vary from patient to patient and the diversity of this progression in ALS patients is not well understood.The subjects were 120 Japanese patients with sporadic ALS who were followed-up at our hospital or for whom precise information was available regarding death or the time that the patient required tracheotomy or ventilation assistance. Symptoms started: in the upper limbs in 47 patients; in the lower limbs in 44 patients; in the bulbar region in 22 patients; as the combined type (two regions involved simultaneously on initial presentation) in 6 patients; and with respiratory symptoms in 1 patient.At the time of the appearance of respiratory symptoms, 43 patients (35.8%) had some normally preserved motor function. Significantly fewer patients with progressive bulbar palsy maintained one or more normal motor functions (14%) compared to patients whose disease started in the extremities (43%). Patients were divided into two groups depending on whether they had significant bulbar involvement at the time of the appearance of respiratory symptoms: 88 patients had significant bulbar involvement (B type), and 32 patients did not (R type). Based on the Kaplan-Meier survival curves, no significant difference in the median survival time was noted between the two groups (R type, 29.4 months vs. B type, 32.5 months; p = 0.06). We could not find any difference about clinical characteristics such as gender, onset age, initial site between R and B group. The motor functions that were preserved at the time of respiratory symptom onset included: bulbar function in 32 patients (26.7%); lower extremity function in 12 patients (10%); and upper extremity function in only 3 patients (2.5%). The use of mechanical ventilation in ALS patients with one or more preserved motor functions was significantly higher than in those without any normally preserved motor function (p = 0.03).From a low rate of upper extremity motor function preservation, respiratory function deterioration appears to be related to upper-limb involvement, likely due to a possible link to diaphragmatic function. Advanced directives should carefully address the use of mechanical ventilation in patients without bulbar symptoms.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.

A 69-year-old man with a recurrent ventricular tachycardia (VT) was admitted. The patient was diagnosed as myotonic dystrophy type 1 (DM1) and DNA analysis revealed 1,800 CTG-repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. Ultrasonic cardiogram (UCG), left ventriculogram (LVG) and magnetic resonance imaging (MRI) did not show any abnormal sign including fatty infiltration. But, endomyocardial biopsy obtained from ventricular outflow tract revealed severe fatty infiltration and interstitial fibrosis. Radiofrequency catheter ablation at the biopsy site could eliminate VT, so it was strongly suggested that the re-entry circuit was formed by focal fatty-fibrosis. Careful observation should be continued for a long period.

An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to1.0 x 10(9)/L were5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Background Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON. Methods Medical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse. Results All MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO. Conclusions NMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.