Phosphorylated alpha-synuclein in Iba1-positive macrophages in the skin of patients with Parkinson's disease.

BACKGROUND: Increasing evidence suggests that alpha-synuclein (αSyn) accumulation in cholinergic and adrenergic fibers in the skin is a useful biomarker to diagnose idiopathic Parkinson's disease (IPD). It has been widely reported that phosphorylated αSyn (p-αSyn) deposits in autonomic fibers in IPD are a biomarker in the skin, but other tissue localizations have not been fully investigated. OBJECTIVE: It has been previously suggested that αSyn aggregates activate peripheral macrophages and that peripheral macrophages ingest pathological αsyn aggregates in aged rats or IPD patients. However, it remains to be elucidated whether peripheral macrophages in the skin of IPD patients accumulate αSyn. We evaluated whether (1) p-αSyn deposits in dermal macrophages might represent a useful biomarker for IPD and (2) dermal macrophages play a role in the underlying pathogenesis of IPD. METHODS: We performed an immunohistological analysis of skin biopsy specimens from IPD patients and controls. RESULTS: We found that (1) p-αSyn accumulation is present in dermal macrophages in skin biopsy specimens from patients with IPD, (2) not only dermal adrenergic fibers with p-αSyn deposits but also dermal macrophages with p-αSyn deposits are useful biomarkers for IPD patients and (3) the number of macrophages was significantly positively correlated with the number of macrophages with p-αSyn deposits in the dermis of IPD patients. INTERPRETATION: Our results suggest that dermal macrophages, which are innate immune cells, play an important role in IPD patients and are a novel biomarker for IPD.

The characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 patients especially concerning swallowing function evaluated by endoscopy.

OBJECTIVE: The objectives of the study were to clarify the characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 (DM1) patients, and to investigate the relationship between the development of pneumonia and the DM1 patient's background, especially concerning swallowing function evaluated by endoscopy. METHODS: The subjects were 88 DM1 patients who underwent swallowing function evaluation. The severity of disease in DM1patients was assessed based on the muscular impairment rating scale (MIRS), and the number of CTG repeats. Patients were divided into two groups; those who developed aspiration pneumonia within two years after swallowing assessment and those who did not develop aspiration pneumonia. Swallowing function was assessed using the food intake level scale (FILS), repetitive saliva swallowing test (RSST), the modified water swallowing test (MWST), and the Hyodo score. RESULTS: Onset of pneumonia within two years of assessment was observed in 22 cases (25%). Age, FILS, and Hyodo score were significantly different between pneumonia and non-pneumonia groups. There was a significant difference in swallowing function tests such as FILS, RSST, and Hyodo score between males and females. The Hyodo score cutoff value for predicting pneumonia within two years was determined by ROC analysis. A cutoff value of 6 was found to have a sensitivity of 0.545 and a specificity of 0.833 (area under the curve=0.722). CONCLUSION: It is important to evaluate the swallowing function of DM1 patients by endoscopy to prevent aspiration pneumonia. In addition, male patients are more likely to deteriorate in swallowing function and should be carefully monitored.

Predominant vasogenic edema in a patient with fatal cerebral air embolism.

Cerebral air embolism (CAE) is a rare neurologic complication that can occur in patients undergoing various medical procedures or trauma. CAE can sometimes result in death caused by severe brain edema. In spite of these implications, the pathophysiologic mechanisms and radiologic features of fatal CAE remain to be elucidated. In this case report, a patient with carcinomatous pleuritis lost consciousness and developed quadriplegia and had generalized seizures during intrathoracic lavage. Serial computed tomography (CT) revealed the presence of air in intracranial blood vessels following severe brain edema; these are typically observed on the CT scans of patients with fatal CAE. Diffusion-weighted imaging (DWI) of the brain obtained at 24 hours after the onset of CAE revealed scattered cortical gyriform high signal intensity often observed in CAE cases, whereas the apparent diffusion coefficient and T2-weighted imaging revealed diffuse hyperintensity in the subcortical deep white matter, indicating vasogenic edema. Our case showed predominant vasogenic edema rather than cortical ischemic changes in the subcortical deep white matter area. These findings indicate that diffuse subcortical vasogenic edema could be the main cause of mortality in fatal CAE.

A case of cerebral embolism with metastatic chondrosarcoma in the left atrium.

Cardiac tumor is a rare, but clinically important source of cerebral embolism. We report a case of metastatic chondrosarcoma in the left atrium with multiple cerebral emboli. A computed tomography scan of the chest revealed a large mass in the left atrium and pulmonary vein. The patient underwent heart surgery to remove the metastatic chondrosarcoma in the left atrium, to prevent the formation of further systemic emboli and possible sudden death. The cardiac tumor resection was successful, and the patient was discharged from the hospital without any handicap. This is a rare case of metastatic cardiac tumor that was a source of emboli into the brain and was eradicated.

Chondrosarcoma with atypical clinical presentation treated by gamma knife radiosurgery for multiple brain metastases--case report.

A 60-year-old male was first treated for World Health Organization (WHO) grade II chondrosarcoma arising from the ring finger manifesting as painful swelling. Four years later, the patient presented with cerebral infarction. Echocardiography revealed a tumor occupying the left atrium. He underwent open heart surgery and the tumor was identified as metastatic chondrosarcoma with malignant transformation to WHO grade III lesion. Five months following the cardiac surgery, the patient suffered generalized seizure. Cerebral magnetic resonance imaging revealed multiple parenchymal lesions. Surgical tumor extirpation confirmed the histological diagnosis as metastatic grade III chondrosarcoma. Gamma knife radiosurgery (GKS) performed postoperatively controlled the parenchymal lesions for more than 10 months without relapse. GKS may be effective for the treatment of brain metastasis from high grade chondrosarcoma.

Alteration in the differentiation-related molecular expression in the subventricular zone in a mouse model of Parkinson's disease.

Enhancement of neurogenesis could be a suitable treatment approach to up-regulate dopaminergic neurons in Parkinson's disease (PD). In the present study, we focused on the kinetics of the subventricular zone (SVZ) in a mouse model of PD induced by MPTP injection. We showed recently the proliferation potential of neuronal stem cells (NSCs) prepared from the olfactory bulb of an animal model of PD [Hayakawa, H., Hayashita-Kinoh, H., Nihira, T., Seki, T., Mizuno, Y., Mochizuki, H., 2007. The isolation of neural stem cells from the OB of Parkinson's disease model. Neurosci. Res.]. In this study, we examined the relationship between proliferation and differentiation of NSCs in SVZ of both acute and chronic PD models. Only acute MPTP treatment significantly increased the areas of glial fibrillary acidic protein (GFAP)-expressing cells and decreased the areas of polysialylated neural cell adhesion molecule (PSA-NCAM)-expressing cells in the SVZ. In the case of caspase-11 knockout mice, MPTP did not induce alteration in the areas of GFAP-expressing cells and PSA-NCAM-expressing cells. Our results suggest that neuroinflammation related to the caspase-11 cascade in the striatum regulates differentiation of neural stem cells in the SVZ of our mouse model of PD.

Recombinant human granulocyte colony-stimulating factor protects against MPTP-induced dopaminergic cell death in mice by altering Bcl-2/Bax expression levels.

Granulocyte colony-stimulating factor (G-CSF) has been used for the treatment of neutropenia in hematologic disorders. The neuroprotective effects of G-CSF were reported in neurological disease models. In the present study, we examined whether G-CSF can protect dopaminergic neurons against MPTP-induced cell death in a mouse model of Parkinson's disease. Mice of one group were injected intraperitoneally with MPTP for five consecutive days, those of another group with MPTP and intraperitoneal G-CSF at 2 days and 1 day before the first MPTP injection, and 30 min before each MPTP injection, while control mice received saline injections. Immunohistochemistry, western blotting analysis, and HPLC were performed to evaluate damage of substantia nigra dopaminergic neurons and expression of Bcl-2 and Bax protein. MPTP induced dopaminergic cell death in the substantia nigra. G-CSF significantly prevented MPTP-induced loss of tyrosine hydroxylase-positive neurons (p < 0.05), increased Bcl-2 protein and decreased Bax protein expression. Our findings indicate that G-CSF provides neuroprotection against MPTP-induced cell death and this effect is mediated by increasing Bcl-2 expression levels and decreasing Bax expression levels in C57BL/6 mice.

Expression levels of vascular endothelial growth factor and its receptors in Parkinson's disease.

Recently, we confirmed the presence of enhanced neural reconstruction in Parkinson's disease and in an animal model of Parkinson's disease based on increased polysialic acid-like immunoreactivity. Changes in neurogenesis often appear parallel to changes in angiogenesis. Moreover, both these processes share similar modulating factors, like vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1). Using immunohistochemistry, we identified in this study upregulation of VEGF in the substantia nigra but not in the striatum of patients with Parkinson's disease by enzyme-linked immunosorbent assay. Such overexpression may participate in vascular remodeling and neurogenesis in the substantia nigra of Parkinson's disease.