伊藤 信二

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 < 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 < 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 >= 2.0 mu g/mL, which does not decrease during the sub-acute phase. (C) 2016 Elsevier B.V. All rights reserved.

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 >= 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 < 0.0001). Washout-rate (WR) was significantly higher in probable PD cases (p < 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.

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.

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 < 0.001 and p < 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'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.