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Anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease belongs to a new spectrum of disease entities that cause acute inflammatory demyelinating lesions in the central nervous system. MOG antibody-associated disease presents with several phenotypes including optic neuritis, myelitis, neuromyelitis optica spectrum disorder, brain stem encephalitis, acute disseminated encephalitis, and cortical encephalitis. For the diagnosis, brain magnetic resonance imaging (MRI) and cerebrospinal fluid studies are required to prove inflammatory demyelination apart from the identification of anti-MOG antibodies using cell-based assays. Immunotherapy is an effective treatment strategy to prevent relapse.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune neurological diseases of the central nervous system, which are characterized by the presence of serum anti-aquaporin-4 autoantibodies (AQP4-IgG). An association between Sjögren syndrome (SjS) and AQP4-IgG-positive NMOSD has been proposed, but the rate of coexistence has not been determined., Methods: In this study, 4,447 patients suspected of having NMOSD with acute neurological episodes were evaluated for the positivity of serum AQP4-IgG, serum SS-A/Ro antibody, and the presence of SjS-related symptoms (dry eye, dry mouth)., Results: Of the 4,447 patients, 1,651 were positive for serum AQP4-IgG, and the remaining 2,796 were negative. A significantly higher proportion of AQP4-IgG-positive patients were positive for serum anti-SSA/Ro antibody (26.3 vs. 4.5%; p < 0.0001) and anti-SSB/La antibody (7.2 vs. 1.2%; p < 0.0001) and had dry eye (9.1 vs .4.9%; p < 0.0001) and dry mouth symptoms (8.9 vs. 3.7%; p < 0.0001). More than 80% of the patients with SjS with acute neurological events such as myelitis or optic neuritis were AQP4-IgG positive. AQ4-IgG-positive patients with comorbid SjS showed a higher female rate (97.1 vs. 89.0%; p = 0.0062), a higher positivity rate for oligoclonal bands (15.4 vs. 7.5%; p = 0.029), and a higher relapse frequency (p = 0.027) than AQP4-IgG-positive patients without comorbid SjS., Conclusions: The prevalence of SjS is higher among AQP4-IgG-positive than AQP4-IgG-negative patients, with the potential prevalence of 10-20% at the diagnosis of AQP4-IgG-positive NMOSD. Comorbid SjS is more prevalent in females, and it has a higher relapse frequency among AQP4-IgG-positive patients.

Objective: The aim of this study was to report the possible association between minor trauma to the eyes and the subsequent occurrence of optic neuritis in patients with serum anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD)., Methods: Herein, we present three patients who developed acute optic neuritis with visual disturbances after accidental minor trauma to their eyes, without any fundus abnormality or orbital floor fractures present., Results: Two of the three patients had a preceding history of neurological disturbances compatible with NMOSD (e.g., myelitis, area postrema syndrome) before the occurrence of trauma. One patient was rapidly treated with steroid pulse therapy and plasmapheresis, and he fully recovered visual acuity. The other two, who were left untreated in the acute phase, had sequelae of severe visual disturbances in the affected eyes., Conclusions: These cases suggest possible association between minor trauma to the eyes and the subsequent occurrence of optic neuritis in patients with serum anti-AQP4 antibodies. Avoiding ocular trauma and early administration of steroid pulse therapy in response to optic neuritis after trauma are desired in such cases., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: To examine the patterns of cortical gray matter thickness in multiple sclerosis (MS) patients., Methods: Seventy-four MS patients-clinically isolated syndrome (4%), relapsing-remitting MS (79%), and progressive MS (17%)-and 21 healthy controls (HCs) underwent 1.5 Tesla T1-weighted 3D MRI examinations to measure brain cortical thickness in a total of 68 regions of interest. Using hierarchical cluster analysis with multivariate cortical thickness data, cortical thickness reduction patterns were cross-sectionally investigated in MS patients., Results: The MS patients were grouped into three major clusters (Clusters 1, 2, and 3). Most of the regional cortical thickness values were equivalent between the HCs and Cluster 1, but decreased in the order of Clusters 2 and 3. Only the thicknesses of the temporal lobe cortices (the bilateral superior and left middle temporal cortex, as well as the left fusiform cortex) were significantly different among Clusters 1, 2, and 3. In contrast, temporal pole thickness reduction was evident exclusively in Cluster 3, which was also characterized by increased lesion loads in the temporal pole and the adjacent juxtacortical white matter, dilatation of the inferior horn of the lateral ventricle, severe whole-brain volume reduction, and longer disease duration. Although cortical atrophy was significantly more common in the progressive phase, approximately half of the MS patients with the severe cortical atrophy pattern had relapsing-remitting disease., Conclusion: Cortical thickness reduction patterns in MS are mostly characterized by the degree of temporal lobe cortical atrophy, which may start in the relapsing-remitting phase. Among the temporal lobe cortices, the neurodegenerative change may accelerate in the temporal pole in the progressive phase., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune-related neurological disorder of the central nervous system. Most patients with NMOSD have serum anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). In addition to optic neuritis and myelitis, other insidious symptoms such as depressive state and chronic fatigue in NMOSD are gradually being recognized. Methods: To elucidate the impact of low- to medium-dose oral prednisolone (PSL) as a relapse prevention therapy for psychiatric disturbances and chronic fatigue in NMOSD, we evaluated clinical data from 39 patients with AQP4-IgG-positive NMOSD, along with the details of present and cumulative oral PSL dosage. Results: Thirty-six of the 39 patients were treated with low- to medium-dose oral PSL, and the mean and standard deviation of the present daily dose of oral PSL were 7.9 ± 4.0 mg/day. None of the patients were treated with a daily PSL dose of >15 mg. As a result, the disease duration and the untreated period before starting oral PSL showed weak to moderate correlations with the subsequent severities of psychiatric disturbance and fatigue level. Meanwhile, none of the other treatment-related variables evaluated, such as the present oral PSL daily dose, cumulative PSL dose, months of oral PSL administration, previous courses of steroid pulse therapy, and coadministered immunosuppressants, were correlated with these insidious symptoms. Conclusion: Our results suggest that the use of long-term low- to medium-dose oral PSL ≤15 mg daily for relapse prevention in AQP4-IgG-positive NMOSD would not aggravate the psychiatric and fatigue conditions. On the contrary, early initiation of oral PSL for relapse prevention, together with significantly decreased relapse rate, alleviated the subsequent depressive state and fatigue from the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Akaishi, Takahashi, Fujihara, Misu, Fujimori, Takai, Nishiyama, Abe, Ishii, Aoki and Nakashima.)

The progression pattern of neurological disability among patients with anti-myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) was evaluated. Neurological disability was evaluated annually for 408 person-years in 50 patients. More than 30% of the patients had clinical relapses in the first 5 years. Disability progression independent of relapse activity (PIRA) was not seen, whereas a stepwise disability progression was observed after clinical attacks in some instances. Disability worsening was more frequent after relapses than after the onset episode (p < 0.01). Similar to patients with anti-aquaporin-4 antibodies, attack-related stepwise disability progression without PIRA is typical in MOGAD, suggesting the importance of relapse prevention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To clarify the clinical and radiological features of adult onset anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated bilateral medial frontal cerebral cortical encephalitis (BFCCE). Methods: We systematically reviewed the literature for patients with anti-MOG antibody-associated BFCCE. Patients who were also positive for other encephalitis-related autoantibodies were excluded from the study. The frequency of several characteristic neurological symptoms and lesion distributions were analyzed. Results: We identified six patients with anti-MOG antibody-associated BFCCE. Among them, 6/6 had headache, 4/6 had fever, 3/6 had seizure, 2/6 had paraparesis, 2/6 had lethargy, and 2/6 had memory disturbance. CSF pleocytosis was observed in 5/6 patients, while CSF myelin basic protein was not elevated in any of the six patients. On brain MRI, 6/6 had bilateral medial frontal cortical lesions, 3/6 had corpus callosum lesions, and 3/6 had leptomeningeal enhancements. Most of the lesions were distributed in the territory of the anterior cerebral artery (ACA). Conclusion: Our results indicate that anti-MOG antibody-associated BFCCE presents with characteristic clinical symptoms and MRI findings, which might reflect lesion formation in the ACA territory., Competing Interests: IN is serving on scientific advisory boards for Biogen Japan and Novartis Pharma and is receiving honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SN declared a shared affiliation, with no collaboration, with the authors to the handling Editor., (Copyright © 2020 Fujimori, Nakamura, Yagihashi and Nakashima.)

This study aimed to determine the seasonal impact on the clinical onset of inflammatory neurological diseases of the central nervous system by analyzing the onset month with information on clinical manifestations in Japanese patients. As a result, patients with anti-aquaporin-4 antibodies (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD) showed spring-summer predominance of the clinical onset. Conversely, patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease showed autumn-winter predominance of the clinical onset. Both seasonal variations were irrespective of the clinical manifestation. Environmental factors with seasonal variation influence the development of neurological conditions related to AQP4-IgG and MOG-IgG., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The association between routine laboratory findings, including cerebrospinal fluid biomarkers, and neurological outcomes in patients with multiple sclerosis (MS) has not been fully elucidated. In this study, we evaluated blood and cerebrospinal fluid (CSF) analysis results at diagnosis and before treatment in patients with MS and assessed their correlations with neurological outcomes., Materials and Methods: In this study, 38 consecutive patients with MS (36 with relapsing-remitting MS and 2 with primary progressive MS) were recruited. Before treatment, all patients underwent routine CSF analysis at the time of diagnosis, including evaluation of albumin and immunoglobulin G (IgG) levels. The association between laboratory data and neurological outcomes was comprehensively evaluated. Subsequent neurological outcome was assessed by using the Expanded Disability Status Scale (EDSS) score at 1 year and 5 years after diagnosis and relapse frequency in the first year and in the first 5 years., Results: The IgG level in the CSF (rho = 0.46, p = 0.004), oligoclonal band count (rho = 0.61, p = 0.006), ratio of IgG and total protein in CSF (rho = 0.59, p < 0.0001), and ratio of IgG and albumin in CSF (rho = 0.67, p < 0.0001) showed moderate to strong correlations with the subsequent EDSS score 1 year after diagnosis. These variables still showed significant correlations with EDSS 5 years later. Albumin and lactate dehydrogenase levels in CSF did not correlate with the subsequent EDSS score. Relapse frequency did not correlate with any of the studied serum and CSF biomarkers., Conclusion: IgG levels in CSF at MS diagnosis are significantly correlated with the level of neurological disability independent of the relapse frequency. Markers of intrathecal IgG synthesis, such as the IgG index, are useful in estimating the present and subsequent clinical severity in patients with MS., Competing Interests: Declaration of Competing Interest The corresponding author declares that the manuscript has not been published previously that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. Tetsuya Akaishi 23th, June 2020., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Recent studies suggest that parameters of the corpus callosum (CC), such as the CC index (CCI) and fractional anisotropy (FA) of the CC, may be related to the degree of brain volume loss (BVL) in MS patients; however, cutoff values that determine the degree of BVL have not been set., Methods: Seventy-five MS patients and 21 healthy controls (HCs) underwent volumetric MRI examinations. MS patients were also evaluated for T2 lesion load, the CCI, and FA of the CC. Among the 75 MS patients, 20 had undergone cognitive assessments with the Symbol Digit Modalities Test (SDMT). After 75 MS patients were categorized into mild, moderate, or severe BVL subgroups according to our previous report, we performed receiver operating characteristic analysis to determine the cutoff values of CCI and FA, categorizing the MS patients into the three subgroups., Results: The volume of the CC was significantly reduced in MS patients compared to that in HCs. The CCI and FA were significantly associated with EDSS, disease duration, clinical phenotype, T2-lesion load, and whole brain volume. The FA was significantly correlated with the SDMT score. We identified optimal cutoff values for the CCI and FA of 0.32 (85% sensitivity, 92% specificity) and 0.39 (100% sensitivity, 92% specificity), respectively, which discriminated the severe BVL group from others, and 0.385 (84% sensitivity, 74% specificity) and 0.45 (81% sensitivity, 89% specificity), respectively, which discriminated the mild BVL group from others., Conclusion: The CCI and FA cutoff values may be useful for evaluating the degree of MS brain atrophy in clinical practice., Competing Interests: Declaration of Competing Interest KF serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, MedImmune, and Medical Review; serves as an editorial board member for Clinical and Experimental Neuroimmunology (2009 to present) and an advisory board member for the Sri Lanka Journal of Neurology; and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, and Genzyme Japan. MW reports speaker or consultancy fees from Bayer Healthcare, Biogen, Biologix, Celgene, Eisai, Genilac, Imcyse, Merck Serono, Novartis, Roche, and Sanofi Genzyme. IN is serving on scientific advisory boards for Biogen Japan and Novartis Pharma and is receiving honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. JF, KU, and CS report no disclosure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to elucidate the rapid impact of high-dose intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) on the eventual visual prognosis in patients with serum anti-aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) who had an attack of optic neuritis (ON). Methods: Data from 32 consecutive NMOSD patients (1 male and 31 female) with at least one ON attack, involving a total of 36 ON-involved eyes, were evaluated. The following variables at ON onset were evaluated: sex, age at the first ON episode, visual acuity at nadir, visual acuity after 1 year, duration from ON onset to treatment for an acute ON attack, cycles of high-dose intravenous methylprednisolone pulse therapy for the ON attack, and cycles of plasmapheresis for the ON attack. Among the 36 ON-involved eyes, 27 eyes were studied using orbital MRI with a short-T1 inversion recovery sequence and gadolinium-enhanced fat-suppressed T1 imaging before starting treatment in the acute phase. Results: In univariate analyses, a shorter duration from ON onset to the initiation of high-dose intravenous methylprednisolone pulse therapy favorably affected the eventual visual prognosis 1 year later (Spearman's rho = 0.50, p = 0.0018). The lesion length on orbital MRI was also correlated with the eventual visual prognosis (rho = 0.68, p < 0.0001). Meanwhile, the days to steroid pulse therapy and lesion length on orbital MRI did not show a significant correlation. These findings suggest that the rapidness of steroid pulse therapy administration affects the eventual visual prognosis independent of the severity of ON. In multivariate analysis, a shorter time from ON onset to the start of acute treatment ( p = 0.0004) and a younger age at onset ( p = 0.0071) were significantly associated with better visual outcomes. Conclusions: Rapid initiation of high-dose intravenous methylprednisolone pulse therapy is essential to preserve the eventual visual acuity in patients with serum AQP4-IgG-positive NMOSD. Once clinicians suspect acute ON with serum AQP4-IgG, swift administration of steroid pulse therapy before confirming the positivity of serum AQP4-IgG would be beneficial for preserving visual function., (Copyright © 2020 Akaishi, Takeshita, Himori, Takahashi, Misu, Ogawa, Kaneko, Fujimori, Abe, Ishii, Fujihara, Aoki, Nakazawa and Nakashima.)

The progressive patterns of neurological disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and the significance of clinical relapses to the progressions of neurological disability in these diseases have not been fully elucidated. In this study, to elucidate the impact of relapses to the progression of accumulated neurological disability and to identify the factors to affect the progression of neurological disability in MS and NMOSD, we followed 62 consecutive MS patients and 33 consecutive NMOSD patients for more than 5 years with the clinical symptoms, relapse occurrence, and Expanded Disability Status Scale (EDSS) in the chronic phase. All enrolled MS patients were confirmed to be negative for serum anti-myelin oligodendrocyte glycoprotein antibody. As a result, patients with NMOSD showed significantly severer neurological disability at 5 years from onset than MS patients. Progression in EDSS score was almost exclusively seen after clinical attacks in NMOSD, whereas progression could be observed apart from relapses in MS. Neurological disability did not change without attacks in NMOSD, whereas it sometimes spontaneously improved or deteriorated apart from relapses in MS (p < 0.001). In patients with MS, those with responsible lesions primarily in spinal cord were more likely to show such spontaneous improvement. In conclusion, clinical deterioration in NMOSD patients is irreversible and almost exclusively takes place at the timing of clinical attacks with stepwise accumulation of neurological disability. Meanwhile, changes in EDSS score can be seen apart from relapses in MS patients. Neurological disability in MS patients is partly reversible, and the patients with disease modifying drugs sometimes present spontaneous improvement of the neurological disability.

Unilateral cerebral cortical encephalitis (UCCE) with myelin oligodendrocyte glycoprotein (MOG)-antibody comprises a new spectrum of disease entities generally presenting seizures. Here, we report a case of a young adult with anti-MOG antibody-associated UCCE who only presented persistent left pulsatile headache. Neurological examination revealed no deficits. Brain MRI showed a fluid-attenuated inversion recovery hyperintense lesion along the swollen left cerebral cortex. The patient was positive for anti-MOG antibodies. We diagnosed him with anti-MOG antibody-associated UCCE. Immediately after the administration of high-dose IV methylprednisolone, the headache diminished. Anti-MOG antibody-associated UCCE is a new differential diagnosis in patients with unilateral chronic pulsatile headache., Competing Interests: Declaration of Competing Interest IN is serving on scientific advisory boards for Biogen Japan and Novartis Pharma and is receiving honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. JF, RO, TM, KJ, and YY report no disclosure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The recent development of a cell-based assay that can detect specific autoantibodies revealed the clinical features of diseases associated with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The anti-MOG antibody associated diseases may include inflammatory demyelinating central nervous system diseases such as neuromyelitis optica spectrum disorders, optic neuritis, myelitis, atypical multiple sclerosis, and encephalitis. Among them, anti-MOG antibody associated cortical encephalitis may develop seizure as one of the primary symptoms, present unique lateral or bilateral medial frontal cortical lesions on brain MRI FLAIR images. In acute phase, steroid pulse therapy and anti-epileptic drugs are required. In chronic phase, immunosuppressive drugs are often required to prevent relapses.

Objectives: Although whole and individual regional brain volume loss have been separately reported to correlate with disability in multiple sclerosis (MS), hierarchical cluster analyses of the whole and regional brain to find their pattern in MS are few., Methods: We cross-sectionally conducted high-resolution, T1-weighted volumetric MRI examinations in 75 MS patients and 21 healthy controls (HCs) to measure the volumes of whole brain and a total of 56 brain regions of interest. Using a hierarchical cluster analysis with multivariate imaging data, we classified the patients into clusters according to their brain-volume patterns. Principal component analysis was also applied. Clinical features and brain volumes were then compared among the MS clusters., Results: The MS patients were categorized into three major clusters (Clusters 1, 2, and 3) with increasing disability in that order. Principal component analysis also identified Clusters 1, 2 and 3. Whole brain volume and supratentorial regional brain volumes, including thalamus and corpus callosum, decreased severely in Cluster 3 and moderately in Cluster 2, while equally preserved in Cluster 1 and the HCs. Only the volumes of the ventral diencephalon and T1 white matter hypointensities significantly differed in Clusters 1, 2 and 3 and HCs. In contrast, the volumes of the cerebellar cortex and brainstem were significantly different between Clusters 3 and 1, whereas there were no significant differences between Clusters 1 and 2 and Clusters 2 and 3., Conclusion: We identified brain regions that exhibit different degree of atrophy in a background of global brain atrophy in MS.

Recently, we documented two Japanese cases of myelin-oligodendrocyte glycoprotein (MOG) antibody-associated relapsing encephalitis among patients who had been diagnosed with probable neuro-Behçet's disease (NBD). They presented partial systemic BD symptoms, brainstem lesions, and the human leukocyte antigen (HLA) B51 allele and responded well to steroid therapy. Our cases suggest that we need to differentiate anti-MOG antibody-associated encephalitis from probable NBD because both disorders can present with brainstem or cerebral lesions, CSF pleocytosis, and elevated levels of CSF IL-6 and respond to steroid treatment. Furthermore, oral ulceration, skin lesions, and HLA-B51 might be observed nonspecifically in patients with anti-MOG antibody-associated encephalitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract. We encountered an ENKTL patient who presented with generalized muscle weakness with eyelid swelling, diplopia, and facial edema. A muscle biopsy revealed lymphocytic infiltration without significant atypia; some lymphocytes formed granuloma-like structures. Although the initial response to steroids was encouraging, an ulcerative eruption appeared in the thigh, and a skin biopsy revealed lymphocytes with atypia. A re-analysis of the muscle biopsy with additional immunohistochemistry revealed neoplastic NK/T lymphocytes in the granulomatous structures. Our case highlights the significance of re-evaluating muscle biopsy specimens in cases of atypical myositis.

Background: The Brief International Cognitive Assessment for MS (BICAMS) is a practical battery for measuring cognitive function in multiple sclerosis (MS)., Objectives: We aimed to validate a Japanese version of the BICAMS in patients with MS and healthy controls., Methods: The Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-Second Edition (CVLT2) and the Brief Visuospatial Memory Test Revised (BVMTR) were administered to 156 patients with MS and 126 healthy controls (HCs). The BICAMS was re-administered in a subset of 27 MS patients and 30 HCs., Results: The mean (±SD) raw scores in the MS and HC groups were as follows: SDMT: MS 47.9 ± 14.0, HC 61.0 ± 9.5; CVLT2: MS 48.6 ± 12.6, HC 55.7 ± 10.5; BVMTR: MS 23.5 ± 8.4, HC 28.3 ± 5.4, respectively, and significant differences were found between the two groups on all tests ( p  < 0.0001). Cohen's d values were 1.07, 0.60, and 0.67 in SDMT, CVLT2, and BVMTR, respectively. The test-retest reliability coefficients for each test were as follows: SDMT: r  = 0.93; CVLT2: r  = 0.82; and BVMTR: r  = 0.77 ( p  < 0.0001)., Conclusions: This study provides results that support the reliability and validity of the BICAMS in Japan.

Background: Approximately 55% of patients with neuromyelitis optica spectrum disorder (NMOSD) show cognitive impairment as evaluated using the Rao Brief Repeatable Neuropsychological Battery (BRBN), but this frequency appears to be higher than the frequency of specific brain lesions in NMOSD., Objective: We studied whether cognitive impairment could be observed in NMOSD patients with no or minor non-specific brain lesions., Methods: We evaluated cognitive function in 12 NMOSD and 14 MS patients using the Wechsler Adult Intelligence Scale-III (WAIS-III), the Wechsler Memory Scale-Revised (WMS-R), and the BRBN. We judged as cognitively impaired patients whose scores were below the average by 2 standard deviations or greater in 2 or more cognitive domains., Results: Cognitive impairment was observed in 5 MS patients (35.7%) and in the only NMOSD patient (8.3%) with symptomatic brain lesions, but not in the other NMOSD patients who had no or minor non-specific brain lesions. Meanwhile, 5 NMOSD (41.7%) and 4 MS (28.6%) patients who had normal cognition according to the WAIS-III and WMS-R were assessed as cognitively impaired by the BRBN (which is not standardized for age)., Conclusions: Cognitive function in NMOSD patients with no or mild non-specific brain lesions was preserved according to the WAIS-III and WMS-R.

The two-step nucleation model for crystal nuclei formation explains several experimental and theoretical results better than the classical nucleation theory. We report here direct visualization of the two-step nucleation model for organic molecular crystallization. Evaporative crystallization from a solution of a dibenzoylmethane boron complex that displays mechanofluorochromism, a fluorescence color change induced by mechanical perturbation, was probed by fluorescence change. The dependence of fluorescence change on dispersion concentration of the complex in a polymer matrix was also investigated. We detected transitional emission from the amorphous cluster state prior to crystallization. This is the first demonstration of the two-step nucleation model based on fluorescence color changes.

Histones are intracellular proteins that are structural elements of nuclear chromatin and regulate gene transcription. However, the extracellular histones released in response to bacterial challenges have been identified as mediators contributing to endothelial dysfunction, organ failure, and death during sepsis. In the present study, the adsorption of histones as well as plasma proteins (α1-acid glycoprotein (AGP), albumin, and γ-globulin) on alginic acid, pectin, dextran, and chitosan was examined in order to evaluate the potential of natural polysaccharides as therapeutic agents for multiple organ failure in sepsis. Alginic acid and pectin strongly adsorbed histones, whereas the adsorption abilities of dextran and chitosan toward histones were very low or negligible. Among the natural polysaccharides examined, only alginic acid did not adsorb any of the plasma proteins. These results demonstrated that alginic acid strongly adsorbed histones, but not plasma proteins; therefore, it has potential as a candidate drug for the treatment of multiple organ failure in sepsis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The effect of the solvent viscosity dependence of time-resolved magnetoluminescence (ML) on the delayed fluorescence of 9,10-diphenylanthracene (DPA) sensitized by platinum octaethylporphyrin has clarified the structure and dynamics of the triplet-triplet pair (TT), i.e., the transition state of triplet fusion. Phase inversion of the ML effect with time provides evidence for the recycle dynamics of the excited triplet state for DPA in triplet fusion. The electron spin-relaxation by random molecular rotation causes intersystem crossing among the different spin states of the triplet-triplet pair and allows the (3,5)TT to engage in triplet fusion. Therefore, slow-down of the molecular diffusion by an increase in the solvent viscosity can enhance the triplet fusion yield. However, the reduction of the ML effect observed in quite high viscosity solvents suggests that the substantially slow rotational motion decreases the triplet fusion yield due to steric factors in electron exchange from the triplet-triplet pair.

Purpose: The objective of this systematic review is to provide an unprecedented summary of the prognostic impact of PAX3/7-FOXO1 fusion status in alveolar rhabdomyosarcoma., Methods: Studies evaluating PAX3/7-FOXO1 fusion gene or its variants as a prognostic marker were systematically searched and comparative meta-analysis of overall survival was carried out., Results: A total of 7 studies comprising 993 patients with rhabdomyosarcoma were included. Three eligible studies showed no significant difference of survival between fusion positive and negative alveolar rhabdomyosarcoma. Four eligible studies showed that PAX3-FOXO1 fusion variant may indicate a lower survival probability than PAX7-FOXO1, although the effect did not reach a level of statistical significance (pooled hazard ratios, 1.66; 95% CI, 0.95-2.89; p=0.07)., Conclusions: There was no significant difference in the overall survival between patients with the positive and negative fusion gene, but there were indications of PAX3-FOXO1 being an unfavorable prognostic factor., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This retrospective study aimed to assess the risk of tuberculosis infection for the employees of a Japanese hospital using baseline interferon-gamma release assay (IGRA). The risk was defined as exposure to the hospital environment., Methods: In total, 870 hospital employees including 161 new employees, 582 for baseline assay, and 127 for contact examination (709 subjects in the post-employment group) were examined from December 2010 to April 2012. The new employees were considered as the "non-exposure" group, whereas the post-employment group was considered as the "exposure" group. Multiple logistic regression analyses were used to calculate the odds ratio (OR) for IGRA positivity, adjusted for gender, smoking history, and alcohol intake (model 1), and for years of employment (model 2)., Results: The exposure group was significantly associated with an increased risk of positive IGRA results, even when adjusted for years of employment (OR: 4.1; 95% confidence interval: 1.4-17.6; P = 0.007). Subgroup analyses stratified by profession indicated a significantly increased OR for laboratory technicians, doctors, and nurses in both models. No correlation was observed between the length of employment and IGRA positivity., Conclusion: Exposure to the hospital environment increased the risk of tuberculosis infection for employees irrespective of the length of employment. Laboratory technicians, doctors, and nurses were at the highest risk of infection.

Purpose: The histological assessment of tumor necrosis of the excised lesion after neoadjuvant chemotherapy is the most important prognostic factor for patients with osteosarcoma, but more early prognostic factors are needed for the adjustment of adjuvant treatment regimen. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the value of (201)thallium ((201)Tl) scintigraphy for the preoperative evaluation of the chemotherapy response of osteosarcoma., Methods: Studies evaluating (201)Tl scintigraphy for the preoperative evaluation of the chemotherapy response of osteosarcoma were systematically searched for in MEDLINE, EMBASE, and Web of Science. Pooled sensitivity and specificity for each study were calculated into 2 × 2 contingency tables. The DerSimonian-Laird random-effects method was used for determining the pooled diagnostic odds ratio and the area under curve (AUC) of the summary receiver operating characteristic (SROC) curve., Results: A total of six studies with 139 patients who fulfilled all of the inclusion criteria were considered for the meta-analysis. The pooled sensitivity and specificity were 0.93 (95% CI, 0.83-0.98) and 0.63 (95% CI, 0.52-0.74), respectively. A significant difference was found between the good and poor responders in the diagnostic odds ratio. The SROC curve showed that the AUC was 0.840, indicating excellent diagnostic accuracy. There was no statistically significant heterogeneity among the six studies., Conclusions: The alteration ratio derived from (201)Tl scintigraphy was useful for evaluating the histological response of patients to neoadjuvant chemotherapy in osteosarcoma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

SS18-SSX (formerly called SYT-SSX) fusion gene has been established clinically as a molecular diagnostic test for synovial sarcoma, but the prognostic value of the fusion gene variant for survival is controversial. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the prognostic impact of SS18-SSX fusion type in synovial sarcoma. Studies evaluating SS18-SSX fusion type as a prognostic marker in synovial sarcoma were systematically searched for in MEDLINE, EMBASE, and Web of Science. Comparative analysis of the pooled hazard ratios (HR) between fusion types was carried out, in order to assess the likelihood of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and metastasis-free survival (MFS). A total of 10 studies comprising 902 patients with synovial sarcoma were considered for the meta-analysis. The pooled HR for eight eligible studies evaluating for OS or DSS was 1.28 (95% confidence interval: 0.81-2.00), suggesting no significant difference between SS18-SSX1 and SS18-SSX2 (P = 0.29). For seven studies which evaluated for PFS or MFS, the presence of SS18-SSX1 may indicate a lower survival probability than that of SS18-SSX2, although the effect did not reach a level of statistical significance (P = 0.09). There was no significant difference in OS or DSS between SS18-SSX1 and SS18-SSX2, but there were indications of SS18-SSX1 being an unfavorable prognostic factor of PFS or MFS. Further studies including cohorts with a longer follow-up period are needed.

Background: The survival of patients who present with nonmetastatic extremity osteosarcoma has dramatically improved, but there are some patients who do not respond to chemotherapy. The ability to identify patients with a poorer prognosis might allow us to target different therapy for these patients. Glucose transporter protein-1 (Glut-1), one of the key factors in glucose metabolism, has been reported to be an independent prognostic factor in various tumors. However, little is known about the role of the Glut-1 pathway in osteosarcoma., Questions/purposes: We asked (1) if Glut-1 expression is a prognostic marker for survival in patients with osteosarcoma, and (2) if there is a relationship between Glut-1 expression and tumor angiogenesis., Patients and Methods: Thirty-seven patients with resectable high-grade osteosarcomas treated between 1982 and 2007 were reviewed retrospectively. Patients were excluded if representative biopsy material and followup data were not available. The expression of Glut-1 and the number of CD34-positive microvessels for angiogenic activity were measured immunohistochemically. The median followup was 6 years 6 months (range, 11-211 months). Survival analyses were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. The association between Glut-1 expression and microvessel density was analyzed using Student's t-test and chi-square test. For 12 (32.4%) of 37 patients with osteosarcoma, the expression of Glut-1 was positive, with four patients (10.8%) showing strong expression of Glut-1 protein., Results: The expression of Glut-1 correlated with a shorter disease-free survival period (relative risk, 20.13; 95% CI, 1.77-229.3; p=0.0016). The microvessel density mean value of positive Glut-1 expression (mean±SD, 26.5±19.4) was lower than that of negative expression (mean±SD, 46.4±35.3; Student's t-test, p=0.038). When more than 50 was defined as a high microvessel density, positive expression of Glut-1 was significantly associated with low microvessel density (chi-square test, p=0.049)., Conclusions: These findings indicate that Glut-1 is a potential predictor of survival in patients with osteosarcoma and that glucose metabolism may be negatively associated with angiogenesis. If substantiated in larger numbers of patients, these findings might stimulate the development of novel treatments for patients with a poorer prognosis., Level of Evidence: Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

A 71-year-old woman was referred to our department for evaluation of a right temporal headache. She had been diagnosed with Takayasu arteritis in her twenties but did not receive steroid therapy. A brain MRI scan detected thickened dura mater with abnormal enhancement on the right cerebral hemisphere. She was diagnosed with hypertrophic pachymeningitis, but she refused to be treated with steroids. Three months later, she noticed periorbital pain and blurred vision in her left eye, although the right temporal headache was reduced. A brain MRI scan detected thickened dura mater with abnormal enhancement on the left cerebral hemisphere adjacent to the left orbit and a swelled left superior rectus muscle with abnormal enhancement. However, the MRI results also showed that the thickening of the dura mater on the right cerebral hemisphere had improved. The new symptoms and the abnormalities revealed with imaging were resolved following steroid therapy. Takayasu arteritis mainly affects the large vessels, but can involve small and systemic vessels. This case presents a rare but possible link between hypertrophic pachymeningitis and Takayasu arteritis.

Background: A high serum alkaline phosphatase (ALP) level is valuable for the diagnosis of osteosarcoma in adults, but its use in teenagers is problematic because ALP levels are affected by age, gender, and pubertal stage. Because serum acid phosphatase (ACP) shows the same tetraphasic pattern as serum ALP in children and adolescents, we presumed that serum levels of ALP and ACP would have a strong correlation and that the ratio of ALP to ACP (ALP/ACP) would show little variation and would be useful for the diagnosis of osteosarcoma in teenagers. The purpose of this study was to evaluate the correlation between the serum levels of ALP and ACP and to investigate the validity of ALP/ACP in the differential diagnosis of osteosarcoma in children and adolescents., Methods: We retrospectively examined 538 patients aged 1-18 years, including 24 with osteosarcomas, 8 with other malignant bone tumors, 56 with benign bone tumors, and with 450 non-tumor lesions (controls). We evaluated the serum levels of ALP and ACP, both obtained by preoperative examination., Results: There were significant correlations between the serum ALP and ACP levels in the controls (r = 0.805 in males and r = 0.860 in females). The ratios of ALP to ACP in the controls showed little variation with age. In ROC curve analysis, to discriminate between the osteosarcomas and the controls, the cutoff levels of serum ALP and ALP/ACP were 956 (U/l) and 50.9 in males and 748 (U/l) and 43.3 in females, respectively. The sensitivity and specificity of serum ALP and ALP/ACP in the differential diagnosis of osteosarcoma were 50.0 and 89.0%, and 60.0 and 94.1%, respectively in males, and 61.5 and 72.7%, and 69.2 and 84.2%, respectively, in females., Conclusions: The results suggest that ALP/ACP is more useful than the serum ALP level in diagnosing osteosarcoma because it is little affected by the age.

In exceptional cases, patients with aseptic meningitis eventually develop aseptic meningoencephalitis. To find a candidate marker for the development of aseptic meningoencephalitis in adult patients diagnosed with aseptic meningitis, we compared 12 different cytokines/chemokines in cerebrospinal fluid (CSF) from 5 patients with aseptic meningoencephalitis, 8 patients with aseptic meningitis, and 8 patients with control disease. Only the CXCL13 concentration was significantly elevated in the CSF of the group with aseptic meningoencephalitis compared with the group with aseptic meningitis. Thus, CSF CXCL13 may be a useful marker for predicting the prognosis of aseptic meningitis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are immune-mediated peripheral neuropathies, and most of these cases were known to be associated with a preceding infection. Recent reports evidenced an increase in the number of infectious disease cases after the earthquake. The aim of this report is to investigate the incidence and clinical features of GBS and FS after the Great East Japan Earthquake. We found GBS and FS patients had markedly increased in 2011, the year of the earthquake. In regard to an antecedent illness, gastrointestinal infection was significantly increased in GBS patients after the earthquake. These results suggest environmental factors including infectious agents and stress caused by the earthquake might have been involved in the outbreak of the diseases.

Background: Benign schwannoma is the most common tumor of peripheral nerves. However, the clinical course of excision and risk factors associated with postoperative neurological deficits are not well known. We evaluated the incidence of preoperative symptoms, the incidence of postoperative neurological deficits, and the risk factors of neurological deficits., Methods: We retrospectively reviewed data of 76 patients with schwannomas treated at our institution. We reviewed the clinical characteristics, and postoperative results, and determined the possible risk factors influencing the development of complications., Results: Excision of schwannoma improved the Tinel-like signs in 47 of 51 patients and spontaneous pain in 14 of 15. Eleven of 17 patients with sensory deficits showed complete recovery, but six continued to show deficits with or without improvement. Motor deficits that were observed in four patients persisted in one. New neurological deficits developed in 21 patients and persisted until final follow-up in 8. Tinel-like signs was the risk factor of surgery-related neurological deficits (p = 0.009)., Conclusions: New deficits developed predominantly in patients with preoperative Tinel-like signs. Attention should be given to patients with the factor.

This report describes a 72-year-old woman presenting MPO-ANCA-associated hypertrophic pachymeningitis and venous thrombosis. Five years prior, positive MPO-ANCA and renal dysfunction had been indicated. At that time, oral steroids and tacrolimus were given to treat systemic vasculitis. During the course of the disease, she repeated otitis media. Saddle nose appeared. She was suspected of having localized type granulomatosis with polyangiitis (GPA). She was hospitalized because of consciousness disturbance and was diagnosed as having MPO-ANCA-associated hypertrophic pachymenigitis and venous thrombosis. Brain MRI detected thick dura mater with abnormal enhancement, predominantly on the right cerebral hemisphere, and tentorium cerebella partially along with the cerebral sulci. MRI revealed vasogenic brain edema lesions in the right occipital, parietal, and temporal lobes and cytotoxic edema lesions in the right parietal lobe and centrum semiovale. MR venography revealed stenosis of the venous sinus including confluence of sinuses, straight sinus, and right transverse sinus. Subsequent treatment with corticosteroids, an immunosuppressant, and an anticoagulant led to recovery. No patient with MPO-ANCA-associated hypertrophic pachymenigitis and venous thrombosis that developed alternation of consciousness has ever been reported. This is therefore regarded as a rare case.

Gaucher disease is an inherited autosomal-recessive disorder caused by the defective hydrolysis of glucocerebroside. The resultant hepatosplenomegaly, hematological changes, and orthopedic complications are the predominant symptoms. However, extraosseous manifestation of Gaucher disease, mimicking malignant bone tumor, is supposed to be rare. No reports of extraosseous manifestation of Gaucher disease caused by epidural hematoma were identified in the English literature. A 64-year-old man visited a nearby clinic for low back pain and was referred to our tumor clinic on suspicion of malignant bone tumor on sacral MRI. MRI revealed a demarcated solid lesion extending into the surrounding soft tissues on both sides of the sacral roots. During preoperative examination, he suffered from pathologic fracture in right mid-femur. We performed internal fixation with intramedullary nailing, simultaneously harvesting tissue specimens. Histopathological analysis showed aggregates of Gaucher cells in the right femur and hematoma in the sacrum. Epidural hematoma in Gaucher disease, usually attributed to thrombocytopenia, is a rare manifestation of skeletal complication, mimicking malignant processes.

Several studies have demonstrated that angiogenesis assessed by microvessel density (MVD) correlates with patient prognosis in various types of cancer, whereas data regarding the relevance of angiogenesis and prognosis in malignant bone tumors are scarce and controversial. The aim of this study was to examine MVD in representative malignant bone tumors, such as osteosarcoma, chondrosarcoma and Ewing's sarcoma, in order to clarify the role of angiogenesis in prognosis. A total of 69 patients with malignant bone tumors, including 44 osteosarcomas, 20 chondrosarcomas and 5 Ewing's sarcomas, were reviewed retrospectively and treated at our hospital between 1980 and 2007. Biopsy or pre-chemotherapy surgical specimens were immunohistochemically stained with anti-CD34 antibody. The MVD values of osteosarcomas and Ewing's sarcomas were significantly higher compared to chondrosarcoma. In osteosarcomas with high MVD, American Joint Committee on Cancer stage IIA, good histological response to chemotherapy was significantly correlated with better disease-free survival, while MVD was closely associated with age and chemotherapy response. In chondrosarcomas, the surgical margin (marginal and intralesional), MVD (high), tumor size (≥8) and histological grade (grades 2 and 3) significantly correlated with a shorter disease-free survival, while MVD was closely associated with age and histological grade. These findings showed that osteosarcomas and Ewing's sarcomas were hypervascular, compared to chondrosarcomas. In osteosarcomas, hypervascularity induced good chemotherapy response, leading to better prognosis, while in chondrosarcomas, high MVD was associated with histological grade and predicted poor prognosis.

Telomere studies in carcinomas have been extensively reported for prognostic utility and effective methods for targeting telomerase therapy has been described, but efficacy of telomerase inhibitor remained unknown in sarcoma cells. In this study, we investigated the effects of telomerase inhibitor cationic porphyrin TMPyP4 on telomerase activity, telomere length, cell growth, and apoptosis in osteosarcoma cell lines. TMPyP4 significantly inhibited telomerase activity in telomerase positive HOS and Saos-2, but not in MG-63. TMPyP4 significantly induced telomere shortening, and inhibition of the cell growth in HOS and Saos-2 with over 17% apoptosis rates. In terms of MG-63, TMPyP4 did not induce inhibition of both telomerase activity and cell growth, although it induced significant telomere shortening. Telomere length after treatment was 5.60 kb in HOS, 4.00 kb in Saos-2, and 9.89 kb in MG-63. These results may suggest that both telomerase activity loss and sufficient telomere shortening are necessary to inhibit cell growth in telomerase positive osteosarcoma cells. TMPyP4 did not induced telomere shortening but significantly inhibited the growth with 22.6% apoptosis rate in telomerase negative with extremely longer telomere-U2OS, may indicating the antitumor effect of TMPyP4 may be related to DNA damage including telomere dysfunction through G-quadruplex stabilization, independent on telomere length., (Copyright © 2011 Orthopaedic Research Society.)

A significant limitation to oncolytic virotherapy in vivo is the lack of a clinically relevant means of delivering the virus. We evaluated the oncolytic activity of vesicular stomatitis virus (VSV) in human osteosarcoma cells and explored isolated limb perfusion (ILP) as a novel oncolytic virus delivery system to extremity sarcoma in immune-competent rats. Human and rat osteosarcoma cells transduced with rVSV-lacZ uniformly expressed β-gal. VSV was fully capable of replicating its RNA genome in all osteosarcoma cell lines, and efficiently killed them in time- and dose-dependent manners, whereas normal bone marrow stromal cells were refractory to the virus. VSV delivered by ILP inhibited growth of osteosarcoma xenografts more potently than that injected intravenously and intratumorally in the hind limb of immune-competent rats. Histopathological sections of tumor lesions treated by ILP-delivered VSV showed positive for VSV-G protein. There were no VSV-G expressions in perfused leg muscle, nonperfused leg muscle, brain, lung, and liver in VSV-treated rats. Our findings show efficient VSV gene expression and replication in osteosarcoma cells, suggesting that osteosarcoma may be a promising target for oncolytic virotherapy with VSV. Furthermore, we firstly showed that ILP of VSV against extremity sarcoma caused antitumor activity., (Copyright © 2010 Orthopaedic Research Society.)

We visualized ponto-cerebellar tracts projecting through the middle cerebellar peduncle of 3 patients with early stage multiple system atrophy (MSA), 3 patients with advanced stage MSA, and a healthy control using diffusion tensor imaging (DTI) on 1.5T magnetic resonance imaging (MRI). We also examined whether the location of the degenerated ponto-cerebellar tracts coincided with that of the transverse part of the so-called "hot cross bun sign (HCB)" on MRI. DTI successfully demonstrated the degeneration of ponto-cerebellar tracts in MSA patients. The tracts in advanced stage MSA patients appeared more sparse than those in patients of the early stage. High apparent diffusion coefficient (ADC) values and low fractional anisotropy (FA) values also indicated the degeneration of the ponto-cerebellar tracts in MSA patients. The tracts in the ventral pons were more sparse than those in the central pons. The location of the degenerated ponto-cerebellar tracts of the central pons appeared to coincide with that of the transverse part of HCB. Visualization of degenerated ponto-cerebellar tracts that cross the ventral pons using DTI might be useful for the early diagnosis.

To investigate the antigen recognized by cerebrospinal fluid (CSF) high affinity IgG in patients with multiple sclerosis (MS), the phage display method was applied to the CSF from 15 MS and 10 control patients. Peptide sequences recognized by MS and control CSF IgG were individual specific, and no common motif was found. Peptide sequences frequently showed homology to various kinds of amino acid sequences of ubiquitous viruses such as epstein barr virus (EBV) and herpes simplex virus (HSV), although the frequency was not specific to MS patients. MS CSF IgG may recognize various types of ubiquitous viral antigen and may be increased by a bystander response.

Background: Malignant fibrous histiocytoma (MFH) of bone is a rare primary malignant neoplasm. Recent studies indicate a positive correlation between the telomere maintenance mechanism and tumour aggressiveness in sarcomas. This study was undertaken to analyse the clinical significance of telomere factors in primary tumour samples from patients with MFHs of bone., Materials and Methods: Telomerase activity was measured in ten bone MFH specimens using a PCR-based TRAP assay. Telomere length was assessed using gel hybridisation. Quantitative detection of human telomerase reverse transcriptase (hTERT) was performed by real-time PCR., Results: Telomerase activity and hTERT expression were detectable in 100% of tumour samples and 50% of tumour samples had evidence of engagement of the alternative lengthening of telomere (ALT) mechanisms. ALT was a significant prognostic risk factor (p = 0.0316)., Conclusion: This study suggests that the presence of ALT telomere maintenance mechanisms indicates a poor prognosis for bone MFH patients.

We report the case of a 65-year-old man who had encephalitis with a high titer of voltage-gated potassium channel antibodies (VGKC-Abs). His initial symptoms included memory disturbance, confusion, and seizures. Laboratory tests revealed a low plasma sodium concentration and a strong positive result for VGKC-Abs. A diffusion-weighted magnetic resonance imaging (MRI) scan showed a high intensity lesion within the right basal ganglia, which later showed normal intensity. The patient's initial symptoms resolved without any treatment. During the first relapse, the patient experienced consciousness disturbance and an increased number of seizures than that observed initially. A diffusion weighted MRI scan showed a high intensity lesion within the right hippocampus, and a fluid attenuated inversion recovery (FLAIR) weighted MRI scan showed high intensity lesions within the right hippocampus, right thalamus, and pons. The patient's symptoms and the MRI abnormalities resolved with prednisolone therapy. During the second relapse, he again experienced consciousness disturbance and an increased number of seizures than that observed initially. Diffusion-and FLAIR weighted MRI scans showed high intensity lesions within the right thalamus. However, the array of immunosuppressive treatments used during the first relapse was not as effective during the second relapse. The serum VGKC-Ab titers before steroid therapy during the first relapse and after immunosuppressive treatment during the second relapse were 1,252 pmol/L and 22.4 pmol/L, respectively. Brain MRI revealed signal changes in the basal ganglia at the onset of disease, in the limbic area during the first relapse, and in the thalamus during the second relapse. VGKC-Ab-associated encephalopathy is usually considered a benign autoimmune disorder; however, in our case, the encephalitis gradually became intractable to various immunosuppressive treatments, and unique MRI abnormalities were observed.

Telomeres of human tumor cells have two types of telomere maintenance mechanisms by telomerase activation and alternative lengthening of telomeres (ALT). Although over 80% of all carcinomas rely on telomerase activity to maintain stable telomere length, many types of sarcoma elongate telomeres consistent with ALT in the absence of telomerase activity. Recently, the presence of telomerase activity and ALT in several sarcomas was examined extensively, and recent studies indicate a positive correlation between the telomere maintenance mechanism and tumor aggressiveness in several sarcoma types. We reviewed both the activation of telomere maintenance in a variety of common bone and soft tissue sarcoma subtypes, and the consequences of telomere maintenance mechanisms with respect to the clinical characteristics.

We measured four chemokines in the cerebrospinal fluid (CSF) in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) with ELISA. CXCL10/IP-10, a T cell type 1 (Th1)-associated chemokine, was significantly elevated in HAM/TSP compared with controls, and the values were even significantly higher in HAM/TSP than in multiple sclerosis (MS) in which CXCL10/IP-10 up-regulation was previously reported. Among Th2-associated chemokines, CCL17/TARC and CCL11/Eotaxin in HAM/TSP were not different from those in controls. As shown in MS, CCL2/MCP-1 was significantly lower in HAM/TSP than in control. Following interferon (IFN)-alpha therapy in HAM/TSP, CCL2/MCP-1 became significantly higher than that before therapy, which may reflect a Th2 induction, while CXCL10/IP-10 remained elevated.

The Eudragit RS and polyethylene glycol 400 (PEG 400) blend polymer (EPG) membranes were prepared by the solvent casting method to pioneer a novel application of Eudragit RS to a thermo-sensitive material. The EPG membranes containing 2.5-10% PEG 400 (2.5-10% EPG) showed the glass transition temperatures (Tgs) around the body temperature (32-42 degrees C). Drug permeation studies through the EPG membranes were carried out using acetaminophen (AAP) and aminopyrine (AMP) as the model drugs. The permeability of AAP and AMP through the EPG membranes has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the Tg of the membranes. The amount of AMP permeated at 42 degrees C was nearly eight times as much as that at 36 degrees C. Arrhenius plots of the steady-state permeability coefficient (P) of AAP indicated two straight lines that intersect at the Tg of the 10% EPG membrane. In the water uptake study for the 10% EPG membrane, the degree of the swelling for the membrane tended to increase with increasing temperature above the Tg of the membrane. The thermo-sensitive permeation mechanism for the EPG membranes might be based on the structure change of the membranes caused by the glass transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RS and PEG 400, the EPG membranes might be used to develop a novel thermo-sensitive drug delivery system.