ito shinji

Background: The development of acute multiple embolic infarctions (AMEI) resulting from cancer is known as Trousseau's syndrome (TS). At present, however, there is no good marker for predicting the prognosis of TS patients. In the present study, we evaluated the use of serial D-dimer levels as a prognostic marker for TS. Methods: This retrospective cohort study included 1,409 consecutive acute ischemic stroke patients. We selected a group of patients with TS showing AMEI (n = 38; TS group) and a group of patients with atrial fibrillation (Af) and AMEI (n = 35; Af group) as controls. Serial D-dimer levels were measured between days 7 and 28 after stroke (sub-acute phase) in 21 patients of the TS group and 24 patients of the Af group. Results: D-dimer levels at onset (acute phase) were significantly higher in the TS group (8.45 ± 1.79 μg/mL, n = 38) compared with the Af group (1.14 ± 0.14 μg/mL, n = 35) (p < 0.0001). In patients for whom serial D-dimer measurements were made, D-dimer levels measured at the sub-acute phase decreased to 0.48 ± 0.12 μg/mL (n = 24) in the Af group, but remained elevated in the TS group during the sub-acute phase (11.20 ± 2.77 μg/mL, n = 21) (p < 0.0001). In all TS patients in whom serial D-dimer measurements were made, D-dimer levels in 17 patients who died within 500 days (13.31 ± 3.23 μg/mL) were significantly higher than those of the four surviving patients (2.23 ± 0.38 μg/mL) (cut-off D-dimer level = 3.0 μg/mL) during this period. Moreover, serial D-dimer levels of 10 patients who died within 90 days (17.78 ± 4.60 μg/mL) were significantly higher than those of the 11 patients who survived up to 90 days (5.21 ± 2.12 μg/mL) (p < 0.05). Conclusions: Serial D-dimer levels may be a good biomarker for TS as well as a useful predictor of the prognosis of TS patients.

Background: Although single-photon emission computerized tomography of the dopamine transporter (DATSPECT) is useful for diagnosing parkinsonian syndrome, its applicability toward the early phase of Parkinson's disease remains unknown. Methods: We enrolled 32 patients showing parkinsonism with normal cardiac I-123-metaiodobenzylguanidine (MIBG) uptake and abnormal DAT-SPECT findings among 84 consecutive patients with parkinsonism. We divided these patients into two groups (group 1: Parkinson's disease, group 2: corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy), and compared their clinical characteristics, specific binding ratios, and striatal asymmetry indexes on DAT-SPECT examinations. Results: The striatal asymmetry indexes were significantly lower in group 1 than in group 2 (p &lt; 0.05), but there were no differences in the specific binding ratios between the two groups. Conclusion: The combined use of striatal asymmetry index on DAT-SPEC' and cardiac MIBG scintigraphy might offer useful clues for the differential diagnosis of the early phase Parkinson's disease from other parkinsonian syndromes. (C) 2017 Elsevier B.V. All rights reserved.

Introduction: To visualize peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), we used MR imaging. We also quantified the volumes of the brachial and lumbar plexus and their nerve roots. Methods: Thirteen patients with CIDP and 12 healthy volunteers were enrolled. Whole- body MR neurography based on diffusionweighted whole- body imaging with background body signal suppression ( DWIBS) was performed. Peripheral nerve volumes were calculated from serial axial MR images. Results: The peripheral nervous system was visualized with 3-dimensional reconstruction. Volumes ranged from 8.7 to 49.5 cm(3)/m(2) in the brachial plexus and nerve roots and from 10.2 to 53.5 cm(3)/m(2) in the lumbar plexus and nerve roots. Patients with CIDP had significantly larger volumes than controls ( P &lt; 0.05), and volume was positively correlated with disease duration. Conclusions: MR neurography and the measurement of peripheral nerve volume are useful for diagnosing and assessing CIDP.

Objective: Acute multifocal embolic infarction (AMEI) is conventionally caused by etiologies such as cardioembolism due to atrial fibrillation (AO, but can also be caused by serious underlying diseases such as cancer. We characterized cancer-related AMEI and identified useful indicators for cancer-associated strokes. Methods: A retrospective analysis was performed on 35 patients with Af-related AMEI and 35 patients with cancer -related AMEI selected from 1235 consecutive patients with acute infarcts. All patients received diffusion weighted magnetic resonance (MR) imaging. Cerebral MR angiography, carotid and cardiac ultrasonography, electrocardiogram-monitoring and whole body computed tomography were also performed on these patients. D-dimer levels were evaluated on admission, and were measured during the sub-acute phase in 19 of the patients with Af and 27 of the patients with cancer. Results: Acute phase D-dimer levels were significantly higher in patients with cancer than in patients with Af alone. The cut-off D-dimer value to identify cancer-associated infarcts was 2.0 mu g/mL. D-dimer levels during the sub-acute phase remained elevated in the cancer patients. Conclusions: We may differentiate cancer-associated AMEI from Af using a D-dimer level &gt;= 2.0 mu g/mL, which does not decrease during the sub-acute phase. (C) 2016 Elsevier B.V. All rights reserved.

A 47-year-old man with a subdural abscess was initially diagnosed with endogenous depression at another hospital. He presented with a chronic illness, but without any typical symptoms, such as headache and fever. Antidepressants were ineffective and brain magnetic resonance imaging showed areas of abnormal high-signal intensity along the surface of the bilateral frontoparietal lobes. We diagnosed him with a subdural abscess based on magnetic resonance imaging and cerebrospinal fluid findings, which was successfully managed with antibiotic treatment alone. This case highlights the possibility that depressive state can be an initial symptom of a subdural abscess.

Background: Although most patients with Parkinson's disease (PD) show decreased cardiac I-123-metaiodobenzylguanidine (MIBG) uptake, some exhibit normal uptake. We evaluated the clinical characteristics of such patients. Methods: We enrolled 154 non-demented patients showing parkinsonism with normal cardiac MIBG uptake and had been clinically followed up during 29.9 +/- 27.6 months. We defined the patients who did not fit the exclusion criteria for PD and demonstrated &gt;= 30% reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score after anti-Parkinson agent administration as probable PD. We compared clinical characteristics and the cardiac MIBG heart-to-mediastinum (H/M) ratio between the probable PD group (N = 37) and other groups (N = 117). Results: The probable PD group showed significantly higher UPDRS motor scores and greater incidence of tremor/rigidity than those of other groups. In addition, they showed a significantly lower cardiac MIBG HIM ratio in the delayed phase (delayed, p &lt; 0.0001). Washout-rate (WR) was significantly higher in probable PD cases (p &lt; 0.0001). Among 16 probable PD patients undergoing serial cardiac MIBG scintigraphy, the delayed phase cardiac MIBG H/M ratio showed a significant decrease and WR significantly increased during follow-up periods. Conclusions: An increase in WR and lower delayed phase cardiac MIBG uptake were found to be characteristics of such patients. (C) 2015 Elsevier B.V. All rights reserved.

To obtain the proof of concept of a novel therapy for Alzheimer's disease (AD), we conducted two prospective studies with hemodialysis patients who had amyloid beta protein (A beta) removed from their blood three times a week. One major pathological change in the brain associated with AD is A beta deposition, mainly 40 amino acids A beta(1-40) and 42 amino acids A beta(1-42). Impaired A beta clearance is proposed to be one cause of increased A beta in the AD brain. Thus, we hypothesized that an extracorporeal removal system of A beta from the blood may remove brain A beta and be a useful therapeutic strategy for AD. In the first prospective study, plasma A beta levels and the cognitive function of 30 hemodialysis patients (65-76 years old) were evaluated at baseline as well as 18 or 36 months after. Although plasma A beta(1-40) levels either decreased or remained unchanged, levels of A beta(1-42) either remained unchanged or increased at the second time point. Mini-Mental State Examination scores of most subjects increased or were maintained at the second time point. A beta(1-40) influx into the blood correlated with MMSE at the second time point. In the second prospective study, five patients (51-84 years old) with renal failure were evaluated before and after the initiation of hemodialysis. Plasma A beta levels decreased, while cognitive function improved after initiating blood A beta removal. Therefore, long-term hemodialysis, which effectively removes blood A beta, might alter A beta influx and help maintain cognitive function.

Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is considered to be caused by the binding of NMO-IgG to aquaporin 4 (AQP4) on astrocytes, which initiates complement-dependent cytotoxicity. AQP4 has two isoforms, i.e., M1 and M23. AQP4 is considered to form heterotetramers containing both isoforms in vivo. Most of the previous studies were performed using either one of the isoforms expressing cell lines. In this study, we generated a fluorescent epitope-tagged AQP4 M1 and M23 co-expressing astrocyte cell line and examined the subcellular targeting of AQP4. In this cell line, AQP4 was targeted mostly to membrane lipid rafts fraction evidenced by sucrose density gradient ultracentrifugation followed by Western blotting with anti-AQP4 antibody. Cholesterol depletion with methyl-beta-cyclodextrin or simvastatin resulted in the dislocation (relocation) of AQP4 from lipid rafts to non-rafts fraction of the membrane and AQP4 was not internalized intracellularly. This change in the localization of AQP4 on membrane significantly reduced complement-dependent cytotoxic effects of NMO-IgG obtained from patients with NMO without affecting AQP4 orthogonal arrays. Thus, these data strongly suggest that the targeting of AQP4 in the lipid rafts is closely related to the pathogenic effects of NMO-IgG. (C) 2014 Elsevier B.V. All rights reserved.

The pathological changes of Alzheimer's disease include the deposition of amyloid beta protein (A beta) as senile plaques in the brain. We hypothesized that the rapid removal of A beta s from the blood may act as a peripheral A beta drainage sink from the brain. In this study, the plasma A beta concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 +/- A 3.8 years), 26 renal-failure patients without hemodialysis (66.6 +/- 14.7 years), and 17 age-matched healthy controls (66.6 +/- 4.1 years). The concentrations of plasma A beta s increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of A beta(1-42) correlated with serum creatinine (P &lt; 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed A beta s in the blood during hemodialysis sessions. The plasma A beta concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of A beta s removed during a hemodialysis session was calculated to be comparable to the A beta s dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing A beta s from the blood is worthy of further investigation, including whether or not A beta s in the brain decrease.

Hypertrophic pachymeningitis (HP) is thought to have an autoimmune etiology but its precise cause and treatment remains to be elucidated. Here, we report the clinical details and therapeutic responses of 3 patients with HP and reviewed 66 previously reported cases in the literature. Among these patients, headache was the most frequent complaint. Cranial nerve involvement was also frequently observed, with the optic nerve being the most frequently impaired followed by the oculomotor, trochlear, and abducens nerves in frequency. Elevated C-reactive protein levels and erythrocyte sedimentation rates were found in approximately 97% of the patients. Steroids were the most commonly prescribed therapy, but no definite protocols for the standard dose and duration in HP have been proposed thus far. The average initial dose of prednisolone (PSL) was 42.7 mg/day, and the average maintenance dose was 12.4 mg/day in the chronic stage. Recurrence occurred in many patients when the dose of PSL was reduced to under 20 mg/day. Therefore, steroids should be tapered extremely slowly.

A 26-year-old man was admitted to our hospital because of high fever, drowsiness, memory disturbance, and disorientation due to H1N1 influenza virus-associated encephalitis/encephalopathy. All of his symptoms rapidly improved following methylprednisolone pulse therapy. The diffusion-weighted image of brain magnetic resonance imaging (MRI) revealed a large transient hyperintense signal lesion on the central splenium of the corpus callosum. This MRI finding in conjunction with a complete clinical recovery has been previously observed in cases of clinically mild seasonal influenza-associated encephalitis/encephalopathy, and can be also a useful clue for the diagnosis of new type of influenza, H1N1 influenza virus infection complicated by encephalitis/encephalopathy.

Background: The data on cerebrospinal fluid (CSF) levels of neurotrophins (NTs) in patients with meningoencephalitis are scarce, especially in adult patients. Methods: We measured CSF levels of NTs such as nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin-3 (NT-3) in adult patients with various meningitis (n = 10) and encephalitis (n = 10) in both acute phase and recovery phase and adult control subjects (n = 21) by the enzyme-linked immunosorbent assay for NTs. Results: Data show that NGF and NT-3 CSF levels were markedly elevated in the patient group in the acute phase compared with non-neurological controls (p &lt; 0.001 and p &lt; 0.05, respectively) and later returned to the levels of controls. Most intriguingly, we only recognized a significant correlation between NGF and NT-3 CSF levels in the patients in the acute phase. Conclusion: Such strong correlation of NGF and NT-3 CSF levels strongly suggests that in adult patients, some common regulatory mechanism(s) might be present among various kinds of NTs to cope with central nervous system infection. Copyright (C) 2011 S. Karger AG, Basel

Expression of brain-derived neurotrophic factor (BDNF) was stimulated in human neuroblastoma SH-SY5Y cells by a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin (R)), an analgesic widely used in Japan for treatment of disorders associated with chronic pain, with the optimal dosage at 10 mNU/mL This stimulation was accompanied by activations of p42/44 MAP kinase, CREB and c-Fos expression. Inhibitors of MAP kinases or PI 3-kinase prevented the stimulatory action of Neurotropin, indicating that neuronal TrkB/CREB pathway mediates the action. Repetitive oral administration of Neurotropin (200 NU/kg/day, 3 months) prevented the age-dependent decline in hippocampal BDNF expression in Ts65Dn mice, a model of Down&apos;s syndrome. This effect was associated with the improvement of spatial cognition of the mice. These results open an intriguing new strategy in which Neurotropin may prove beneficial treatment for neurodegenerative disorders. (C) 2010 Elsevier Inc. All rights reserved.

Objective: We examined the diagnostic difficulty in thiamine deficiency. Methods: We report on two patients with polyneuropathy associated with thiamine deficiency (i.e., beriberi neuropathy) that presented with acute motor symptoms mimicking Guillain-Barre syndrome. Results: The cause of the thiamine deficiency was associated with gastrectomy to treat cancer in a 46-y-old man and with dietary imbalance in a 33-y-old man. The thiamine deficiency was not related to alcohol intake in either patient. In both patients, the upper and lower extremities showed a rapidly progressive weakness over the course of 1 mo. Muscle weakness in the first patient progressed even after admission to the hospital, and urinary retention, Wernicke's encephalopathy, lactic acidosis, paralytic ileus, and heart failure appeared subsequently. Clinical symptoms in both patients showed improvement after initiation of thiamine administration, although some residual deficit remained. Conclusion: Thiamine deficiency must be actively considered as a possible cause of polyneuropathy, and variability in its clinical features should be taken into consideration. (C) 2008 Elsevier Inc. All rights reserved.