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Rou-Shayn Chen

Publications and source records attributed to Rou-Shayn Chen.

10 recordsLinked to original sources
PubMed2006

A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan.

Mutations in the LRRK2 gene are a cause of autosomal dominant Parkinson's disease (PD). Whether LRRK2 variants influence susceptibility to the commoner, sporadic forms of PD remains largely unknown. Data are particularly limited concerning the Asian population. In search for novel, biologically relevant variants, we sequenced the LRRK2 coding region in Taiwanese patients with PD. Four newly identified variants and another variant recently found in a Taiwanese PD family were tested for association with the disease in a sample of 608 PD cases and 373 ethnically matched controls. Heterozygosity for the Gly2385Arg variant was significantly more frequent among PD patients than controls (nominal p value=0.004, corrected for multiple comparisons=0.012, gender- and age-adjusted odds ratio=2.24, 95% C.I.: 1.29-3.88); this variant was uniformly distributed across genders and age strata. Two novel variants, Met1869Val and Glu1874Stop, were found in one PD case each; their pathogenic role remains, therefore, uncertain. The remaining two novel variants (Ala419Val and Pro755Leu) were present with similar frequency in cases and controls, and were therefore, interpreted as disease-unrelated polymorphisms. Our findings suggest that the LRRK2 Gly2385Arg is the first identified, functionally relevant variant, which acts as common risk factor for sporadic PD in the population of Chinese ethnicity.

Adolescent↗
PubMed2005

DYT1 mutation in a cohort of Taiwanese primary dystonias.

To investigate the DYT1 gene mutation in Chinese ethnic, we examined a series of 200 patients with primary dystonias (11 familial and 189 sporadic), 53 of their asymptomatic relatives, 97 patients with familial or early-onset parkinsonism, and 200 healthy subjects. The GAG deletion at codon 946 was only found in three sporadic dystonia patients and seven of their asymptomatic familial members. The frequency of GAG deletion was 1.5% in dystonia patients, and was 6.7% in early-onset dystonias (< or = 26 years). We conclude that DYT1 mutation is a minor cause of primary dystonias in a cohort of Taiwanese population.

Adolescent↗
PubMed2005

Autonomic dysfunction in Machado-Joseph disease.

OBJECTIVE: Machado-Joseph disease is an autosomal dominant spinocerebellar ataxia with expanded trinucleotide repeats. Although autonomic nervous system degeneration was documented in postmortem reports, the autonomic dysfunction in patients with Machado-Joseph disease, either in clinical analysis or electrophysiological investigations, has not yet been studied in detail. METHODS: Fifteen patients with genetically confirmed Machado-Joseph disease and 34 healthy subjects were studied. The study design included a detailed questionnaire, R-R interval variation on deep breathing or Valsalva maneuver, and sympathetic skin response evoked by electrical stimulation of the median nerve or magnetic stimulation of the neck. RESULTS: Sixty-seven percent of patients had at least 3 symptoms involving different aspects of autonomic functions. Voiding problems and thermoregulatory disturbance were the most common symptoms. Ten (71%) of 14 patients had abnormal R-R interval variation with a significant reduction of the mean ratio. Prolonged latency or absence of sympathetic skin response to electrical stimulation was identified in 73% of patients and to magnetic stimulation, in 53%. R-R interval variation and sympathetic skin response showed good correlation with the functional stage. Electrical stimulation revealed the highest sensitivity, specificity, and positive predictive value compared with other tests. CONCLUSION: The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.

Adult↗
PubMed2005

Pallidotomy effect on the cortical excitability in patients with severe Parkinson's disease.

Surgical lesions in the medial pallidum have been shown to ameliorate motor deficits in patients with Parkinson's disease (PD). It is believed that interruption of the pallidothalamocortical projections to the motor cortex is required for the satisfactory results. In this report, we adopt cortico-cortical inhibition as the tool to assess the pallidotomy effect on cortical excitability in PD. Interstimulus interval between 1 and 15 msec were investigated. The average peak-to-peak amplitude was measured and calculated at each delay. A total of 8 patients (M:F = 4:4) 54.9 years of age (SD = 9.6) and 10 controls were recruited for the study. In the controls, the inhibitory phenomenon was observed from the 1-msec to the 4-msec delay points and the maximal inhibition was at the 3-msec delay point (33.69% +/- 6.50% of the control response). Mild facilitation was noticed since the 5-msec delay point and thereafter. In patients before operation, a similar trend of inhibition was also observed in the initial 4 msec with the maximal inhibition also at the 3-msec delay point (64.66 +/- 6.77% of the control response). In the postoperative group, the short interstimulus interval inhibition can no longer be observed and the conditioned response was 95.06 +/- 23.68% of the control at the 3-msec delay point. The suppression was gone at and after the 7-msec delay point. Results of repeated-measures analysis of variance show a significant difference among the controls and PD patients before and 3 months after pallidotomy (F = 3.40, P = 0.05). Post hoc examination revealed a significant difference between the controls and PD patients 3 months after pallidotomy at the 3-msec delay point (P = 0.004). However, no correlation was observed between the 3-msec inhibition and the Unified Parkinson's Disease Rating Scale Motor score or the dyskinesia score. The results suggest that pallidotomy can modulate the cortical inhibitory circuitry in patients with PD.

Adult↗
PubMed2005

Taiwanese cases of SCA2 are derived from a single founder.

We have assessed the haplotypes at the ATXN2 locus in Taiwanese controls and in individuals with SCA2 ataxia with both ataxic and parkinsonian features. Our intention was to determine whether a different ataxin 2 haplotypes predisposed to the two phenotypes. In fact, our analysis showed that all SCA2 mutations carriers had the same ataxin 2 haplotype: haplotype B, which accounts for only 15% of control haplotypes, implying that there is a common founder for all Taiwanese SCA2 patients.

Adult↗
PubMed2004

99mTc-TRODAT-1 imaging of multiple system atrophy.

UNLABELLED: Using (99m)Tc-TRODAT-1 ((99m)Tc-[2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2-mercaptoethyl) amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT imaging, we measured striatal dopamine transporters (DATs) activity in multiple system atrophy (MSA) to investigate the possibility of differentiating it from Parkinson's disease (PD) and to correlate the findings with the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes of MSA. METHODS: Forty-nine patients with probable MSA (30 MSA-P, 19 MSA-C), a disease control group of 36 age- and disease duration-matched patients with probable PD, and a healthy control group of 33 age-matched healthy volunteers participated in a SPECT study. The ratios of specific striatal binding-to-nonspecific occipital binding, including the striatum-to-occipital ratio (S/O), putamen-to-occipital ratio (P/O), caudate nucleus-to-occipital ratio (C/O), and putamen-to-caudate nucleus ratio (P/C), were calculated. The statistical analyses of uptakes among 4 groups used ANOVA followed by Games-Howell's multiple comparisons. The Spearman correlation coefficient between the motor scores of Unified Parkinson's Disease Rating Scale (UPDRS-III) and those binding ratios of the MSA-P and MSA-C groups and the PD group was also performed. RESULTS: The striatal binding was more symmetrically reduced in the MSA-P (asymmetric index, 14.2) and MSA-C (asymmetric index, 8.1) groups, in contrast to the greater asymmetric reduction in the PD group (asymmetric index, 28.6). Overall striatal binding was significantly reduced in the MSA-P (-59.8%), MSA-C (-29.9%), and PD (-58.0%) groups with no overlap between these values and those of the control group. Like the PD group, bilateral P/O, C/O, and S/O ratio values were significantly reduced in the MSA-P and MSA-C groups. Nevertheless, the reduction of bilateral P/O and S/O ratios was more for the MSA-P group than for the MSA-C group. P/C ratios showed that the MSA-P and PD groups had similar patterns of nigral impairment, but the MSA-C group had a different pattern. No correlation between the UPDRS-III scores and (99m)Tc-TRODAT-1 bindings was found in both MSA-P and MSA-C groups; in contrast, a significant negative correlation was noted in the PD group. CONCLUSION: (99m)Tc-TRODAT-1 brain SPECT is capable of scientifically differentiating between the MSA-P and MSA-C subtypes, and MSA-P has more symmetric nigrostriatal damage than that in PD. (99m)Tc-TRODAT-1 brain SPECT imaging probably could provide important information to differentiate MSA from PD.

Corpus Striatum↗
PubMed2004

Sensitivity and specificity of 99mTc-TRODAT-1 SPECT imaging in differentiating patients with idiopathic Parkinson's disease from healthy subjects.

UNLABELLED: The imaging of dopamine transporter (DAT) with (99m)Tc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]-(99m)Tc-technetium) and SPECT has been recently proposed to be a valuable and feasible means of assessment of the integrity of dopamine neurons. The purpose of this study was to further investigate the clinical correlations and the age-specific sensitivity and specificity of this new approach in the diagnosis of patients with idiopathic Parkinson's disease (PD) that manifests in patients >50 y of age. METHODS: SPECT imaging with (99m)Tc-TRODAT-1 was conducted in 78 consecutive PD patients and in 40 age-matched healthy subjects. The images were obtained 4 h after the intravenous injection of the tracer. The ratios of specific striatal binding to nonspecific occipital binding were calculated. S/O represents the ratio for whole striatal binding, whereas P/O and C/O represent the putamen and caudate nucleus, respectively. Statistical analyses of the sensitivity and specificity of these ratios in different age-specific subgroups were performed. The correlations between these ratios and clinical assessments were also analyzed. The age-related declines in the striatal binding in both patients and controls were given particular focus. RESULTS: The S/O, C/O, and P/O ratios decreased significantly both contralaterally and ipsilaterally to the dominant symptomatic side in the PD group (P < 0.0001). The mean reduction of binding was found in the order of putamen (contralateral side, -81%; ipsilateral side, -67%) and caudate nucleus (contralateral side, -46%; ipsilateral side, -40%). The sensitivity and specificity of both P/O and S/O ratios were 100% in discriminating PD patients from healthy subjects in the age-specific groups. The binding ratios correlated negatively with the Unified Parkinson's Rating Scale and Hoehn and Yahr (H-Y) staging. Of particular interest, the binding of the striatum contralateral to the asymptomatic side in H-Y stage I patients also decreased significantly. The age-related decline of these ratios was significant in the control group. CONCLUSION: We have demonstrated that (99m)Tc-TRODAT-1 SPECT has a high sensitivity and specificity for measuring the decrement of DAT in PD patients. In addition to its wide availability, we suggest that this new approach may serve as a diagnostic marker for PD.

Age Factors↗
PubMed2002

Dopa-responsive parkinsonism phenotype of spinocerebellar ataxia type 2.

We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa therapy was observed throughout the disease course. No gait or limb ataxia, slow saccades, or decreased tendon reflexes were detected, but unsteadiness of gait with propulsion developed recently in Patient 1 approximately 25 years after disease onset. Magnetic resonance imaging demonstrated mild atrophy of the pons and cerebellum in Patient 1 and cerebellar atrophy in Patient 2. Expanded CAG repeats, numbering 36, in one allele of the ataxin-2 gene were identified in Patient 1 only; his brother was not available for this investigation. With [(99m)Tc]TRODAT-1 single photon emission computed tomography of the brain, a significant bilateral and asymmetrical reduction of striatal dopamine transporters was found in Patient 1 compared to healthy controls. This bilateral reduction of striatal dopamine transporters resembled that observed in a set of controls with Parkinson's disease who had asymmetrical impairment. These results suggest that patients with familial parkinsonism who present with typical Parkinson's disease should be screened for the genetic defect of spinocerebellar ataxia type 2. The presynaptic impairment of nigrostriatal function is very likely to be the reason for levodopa responsiveness.

Aged↗
PubMed2002

Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers.

UNLABELLED: Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using (99m)Tc-TRODAT-1 ([(99m)Tc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD patients, and 10 age-matched healthy control subjects. METHODS: Brain SPECT images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) (99m)Tc-T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI, binding of this tracer in the entire striatum was measured and the uptake values in bilateral striatal areas were compared between these 3 groups. RESULTS: The uptake values of the aMJD gene carriers (P < 0.001) and MJD patients (P < 0.001) displayed a significant reduction compared with those of the control subjects. The reduction was more severe in the MJD patient group (P < 0.05). Bilateral putamen-to-caudate ratios were significantly lower in the aMJD gene carrier and MJD patient groups (P < 0.001). The dopamine neuronal activity, as represented by the tracer binding, was more prominently affected in the putamen in these patients and gene carriers. CONCLUSION: (99m)Tc-TRODAT-1 brain SPECT is capable of detecting early alteration of dopamine neurons in the striatal region. Significantly, the results suggest that this impairment of presynaptic dopamine function actually occurs at an early stage, which was previously unrecognized in these aMJD gene carriers.

Adult↗