Granulovacuolar Degenerations Appear in Relation to Hippocampal Phosphorylated Tau Accumulation in Various Neurodegenerative Disorders

BACKGROUND: Granulovacuolar degeneration (GVD) is one of the pathological hallmarks of Alzheimer's disease (AD), and it is defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. Several lines of evidence have suggested that GVDs appear within hippocampal pyramidal neurons in AD when phosphorylated tau begins to aggregate into early-stage neurofibrillary tangles. The aim of this study is to investigate the association of GVDs with phosphorylated tau pathology to determine whether GVDs and phosphorylated tau coexist among different non-AD neurodegenerative disorders. METHODS: An autopsied series of 28 patients with a variety of neurodegenerative disorders and 9 control patients were evaluated. Standard histological stains along with immunohistochemistry using protein markers for GVD and confocal microscopy were utilized. RESULTS: The number of neurons with GVDs significantly increased with the level of phosphorylated tau accumulation in the hippocampal regions in non-AD neurodegenerative disorders. At the cellular level, diffuse staining for phosphorylated tau was detected in neurons with GVDs. CONCLUSIONS: Our data suggest that GVDs appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders, while the presence of phosphorylated tau in GVD-harbouring neurons in non-AD neurodegenerative disorders was indistinguishable from age-related accumulation of phosphorylated tau. Although GVDs in non-AD neurodegenerative disorders have not been studied thoroughly, our results suggest that they are not incidental findings, but rather they appear in relation to phosphorylated tau accumulation, further highlighting the role of GVD in the process of phosphorylated tau accumulation

Relationship Between 3-O-methyldopa and the Clinical Effects of Entacapone in Advanced Parkinson's Disease

The aim of this study is to clarify the relationship between serum 3-O-methyldopa (3-OMD) and the clinical effects of entacapone. The 3-OMD and maximum serum concentration (Cmax) of levodopa were measured in 21 Parkinson's Disease patients who took 100 mg levodopa / dopa decarboxylase inhibitor. After the administration of entacapone, the 3-OMD concentration and percentage of "on" time during waking hours (% of "on" time) were studied for 8 weeks. The 3-OMD concentration was reduced by 34%, and the increase in % of "on" time was 28% at the 8th week compared with baseline. We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. The COMTindex was significantly correlated with the increase in % of "on" time at the 8th week. In conclusion, the measurement of baseline 3-OMD and levodopa pharmacokinetics is useful for predicting the clinical effects of entacapone

Amelioration of Persistent, Non-Ketotic Hyperglycemia-Induced Hemichorea by Repetitive Transcranial Magnetic Stimulation

Diabetic hemichorea-hemiballism with non-ketotic hyperglycemia is usually a benign syndrome. Here, we report a 78-year-old woman with persistent hemichorea (HC) for longer than 1 year with a recurrence after rapid correction of hyperglycemia. Following the disappearance of the characteristic T1 hyperintensity at 3 months after onset, an MRI demonstrated T2* hypointensity and atrophic changes in the contralateral striatum, suggesting irreversible neuronal loss and some vascular proliferation. The electrophysiological examination using transcranial magnetic stimulation revealed significantly shorter cortical silent periods (CSPs) on the contralateral primary motor cortex (M1), possibly in relation to cortical hyperexcitability. We have applied 10 daily sessions of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralateral M1 to reduce the hyperexcitability. The HC was suppressed during and for several minutes after rTMS with prolongation of CSPs. After rehabilitation therapy, the patient was able to walk independently with a walker. We suggest that the combination of low-frequency rTMS and rehabilitation therapy may be a possible choice in medically refractory involuntary movements