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The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four-repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p-CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr-CBD) at the later stage. Only two patients fulfilled the criteria for either p-CBD or cr-CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset., (© 2013 Movement Disorder Society.)

Background: The purpose of this study was to investigate whether heart rate variability parameters can be useful for evaluating cardiac autonomic dysfunction in multiple system atrophy patients., Methods: Both the time and frequency domains of heart rate variability were investigated among 17 multiple system atrophy patients and 27 normal control subjects., Results: All time- and frequency-domain measures, except the low- to high-frequency ratio, were significantly lower in multiple system atrophy patients than in controls. In multiple system atrophy patients, there were significant inverse correlations between heart rate variability parameters and disease duration, as well as disease severity, but heart rate variability parameters were not affected by other autonomic dysfunctions., Conclusions: The cardiac autonomic state of multiple system atrophy was characterized by decreases in both sympathetic and parasympathetic tones. Because heart rate variability parameters were not affected by other autonomic dysfunctions, this may be a useful method for evaluating cardiac autonomic dysfunction in multiple system atrophy., (Copyright © 2012 Movement Disorder Society.)

Background: The aim of this study was to find biomarkers of disease severity in multiple system atrophy of cerebellar type by imaging disease specific regions using proton magnetic resonance spectroscopy on a 3.0 T system., Methods: We performed proton magnetic resonance spectroscopy separately in the pons and medulla on 12 multiple system atrophy of cerebellar type patients and 12 age and gender matched control subjects. The metabolite concentrations were estimated from single-voxel proton magnetic resonance spectra measured by point resolved spectroscopy, which were then correlated with clinical severity using Part I, II, and IV of the unified multiple system atrophy rating scale., Results: Proton magnetic resonance spectroscopy showed that myo-inositol concentrations in both the pons and medulla were significantly higher in multiple system atrophy of cerebellar type patients compared to those of the control subjects (P < 0.05). By contrast, total N-acetylaspartate (the sum of N-acetylaspartate and N-acetylaspartylglutamate) and total choline compounds concentrations in both the pons and medulla were significantly lower in multiple system atrophy of cerebellar type patients compared to control subjects (P < 0.05). Creatine concentration in the pons was significantly higher in multiple system atrophy of cerebellar type patients compared to the control subjects (P < 0.05). Furthermore, a significant correlation was found between the myo-inositol/creatine ratio in the pons and clinical severity, defined by the sum score of unified multiple system atrophy rating scale (I+II+IV) (r = 0.76, P < 0.01)., Conclusion: Proton magnetic resonance spectroscopy, in conjunction with a 3.0 T system, can be feasible to detect part of pathological changes in the brainstem, such as gliosis and neuronal cell loss, and the metabolites can be used as biomarkers of clinical severity in multiple system atrophy of cerebellar type patients., (Copyright © 2011 Movement Disorder Society.)

To determine whether tremulous arytenoid movements predict the severity of glottic stenosis in patients with multiple system atrophy (MSA), 28 MSA patients and 14 age-matched controls underwent fiberoptic laryngoscopy with video monitoring during wakefulness and under anesthesia induced by intravenous injection of propofol. Presence or absence of tremulous arytenoid movements was recorded during wakefulness. The ratio of glottic stenosis (%), which represents the extent of airway narrowing under anesthesia, was obtained by measuring the inspiratory glottic angle during wakefulness and under anesthesia. The median ratio of glottic stenosis was significantly higher in patients with MSA (57.5%) than in control subjects (0.5%). Tremulous arytenoid movements were characterized by shaking movements of the arytenoid region including the vocal folds, which are most apparent in the arytenoid cartilage. In this study, tremulous arytenoid movements were observed in 18 (64.2%) of 28 patients with MSA, who displayed a significantly higher median ratio of glottic stenosis (71.2%) than other patients (34.9%). None of the control subjects exhibited tremulous arytenoid movements. A clear correlation existed between the ratio of glottic stenosis and disease duration. Our observations indicate that tremulous arytenoid movements are a marker of the severity of glottic stenosis, which confers an increased risk of upper airway obstruction in patients with MSA., ((c) 2010 Movement Disorder Society.)

The clinical heterogeneity of progressive supranuclear palsy (PSP), which is classified as classic Richardson's syndrome (RS) and PSP-Parkinsonism (PSP-P), has been previously discussed. We retrospectively analyzed 22 consecutive Japanese patients with pathologically proven PSP to investigate the clinicopathological heterogeneity. We investigated the clinical features both early in and at any time during the disease course. The pathological severities of neuronal loss with gliosis and tau pathology were also evaluated. On the basis of the clinical features, 10 patients were categorized as having RS, and 8 were categorized as having PSP-P. Four patients presenting with cerebellar ataxia or cerebral cortical signs were categorized as having unclassifiable PSP. Among them, 3 developed cerebellar ataxia as the initial and principal symptom. Notably, tau-positive inclusion bodies in Purkinje cells were significantly more frequently observed in the patients with cerebellar ataxia than in those without cerebellar ataxia. All the patients with cerebellar ataxia exhibited more neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus than those without cerebellar ataxia. This study confirms the wide spectrum of clinicopathological manifestations associated with PSP regardless of different ethnic origin, and demonstrates that PSP patients manifest cerebellar ataxia., (2009 Movement Disorder Society.)

Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion. In the present study of DRPLA, we have demonstrated immunohistochemically that diffuse accumulation of mutant atrophin-1 in the neuronal nuclei, rather than the formation of neuronal intranuclear inclusions (NIIs), was the predominant pathologic condition and involved a wide range of central nervous system regions far beyond the systems previously reported to be affected. In the neuronal nuclei harboring NIIs, promyelocytic leukemia protein (PML) nuclear bodies were redistributed into a single NII, and the CREB (cAMP-responsive element-binding protein)-binding protein was also recruited into NIIs. The results suggest that the novel lesion distribution revealed by the diffuse nuclear labeling may be responsible for a variety of clinical features, such as dementia and epilepsy in DRPLA, and that certain transcriptional abnormalities may be induced secondarily in neuronal nuclei with the formation of NIIs.