Hsiu-Chen Chang

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 [99mTc]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 Parkinsons disease who had asymmetrical impairment. These results suggest that patients with familial parkinsonism who present with typical Parkinsons 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.

PINK1 mutation in Taiwanese early-onset parkinsonism : clinical, genetic, and dopamine transporter studies.

The PINK1 gene mutation is probably the second most common genetic cause of early-onset Parkinsons disease (EOPD). The frequency and the characteristics of the PINK1 mutation in the Taiwanese population are unknown. This study was designed to investigate the genotype, phenotype and dopaminergic function of PINK1 in a cohort of EOPD patients. The genetic settings were to detect the PINK1 gene mutations in 138 EOPD patients and in 191 controls. Using the 99mTc-TRODAT-1 (TRODAT) scan, we investigated the differences in the dopamine transporter (DAT) activities between the PINK1 patients, late-onset Parkinsons disease (LOPD) patients and healthy controls. Four EOPD patients with 3 genotypic mutations in the PINK1 gene were found: a compound heterozygous mutation (Q239X/R492X) in 2 sisters, a novel homozygous mutation (R492X) in a woman, and a novel heterozygous mutation (G193R) in a man. The three PINK1 patients had typical phenotype with juvenile onset, benign course, and frequently with dyskinesias. The TRODAT scan showed a rather even and symmetrical reduction of uptake in PINK1 patients, unlike the dominant decline in the putamen in the LOPD patients. The annual reduction rate of uptake in the striatum was much slower in PINK1 patients than that in the LOPD patients (1.7 % vs. 4.1%; p<0.005). In the patient with a heterozygous mutation in the PINK1 gene, the reduction ratio in the striatum, as well as the annual reduction rate, were closer to those in the LOPD group. We conclude that the incidence of carrying PINK1 mutations in the present cohort of Taiwanese EOPD patients was low, accounting for 2/39 (5.1 %) in familial cases, and 2/99 (2 %) in sporadic cases. The slower annual reduction of DAT activity might indicate the insidious degeneration of dopamine neurons and a benign prognosis.

Emotional symptoms are secondary to the voice disorder in patients with spasmodic dysphonia

The aims of this study were to evaluate the emotional status and life quality of the patients with spasmodic dysphonia (SD) before and after botulinum toxin treatment, and to ascertain whether SD is a somatoform disorder. Ten patients with spasmodic dysphonia were injected unilaterally into the vocal cord with botulinum toxin. Before botulinum toxin treatment, two clinicians rating scales--Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), and three self-rating psychometrics--Zungs Self-Rating Depression Scale (SDS), Life Quality Scale (GHQ/QL-12), and Symptom Distress Checklist (SCL-90) were applied. Self-rating scales were also administered in 20 matched normal controls. The patients were reevaluated 1 month after botulinum toxin treatment. The Clinical Global Impression Scale (CGI) was also rated by the patients themselves and a speech pathologist. The mean scores of SD patients were significantly higher than that of controls in SDS, and subscales of somatization, obsessive-compulsive symptoms, depression, anxiety, and psychoticism in SCL-90. The mean score of GHQ/QL-12 was significantly higher in the control group. The scores of HDRS, SDS, GHQ/QL-12 and subscales of somatization, depression, and anxiety in SCL-90 showed significant improvement after botulinum treatment. In CGI, seven patients were rated as improved by patients themselves and the speech pathologist. The patients with SD had more anxiety, depression and somatization symptoms, and poor life quality than normal controls. Their emotional status and life quality improved after botulinum toxin treatment. The results suggest that the emotional symptoms of patients with SD are mainly secondary to voice disorder.

Imaging early-stage corticobasal degeneration with [99mTc]TRODAT-1 SPET

AimThe aim of this study was to investigate the nigrostriatal dopaminergic function in patients with corticobasal degeneration (CBD) using [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)]-[99mTc]technetium ([99mTc]TRODAT-1) brain single-photon emission tomography (SPET). MethodsFive patients with probable CBD, 10 age- and duration-matched patients with idiopathic Parkinsons disease (IPD) and 10 age-matched healthy volunteers completed the SPET study. The images were obtained 4 h after intravenous injection of 925 MBq of [99mTc]TRODAT-1. Using a magnetic resonance imaging atlas of the striatum, the ratios of specific striatal binding to non-specific occipital binding were calculated. ResultsClinical analysis showed that the CBD patients obtained significantly higher scores on the Unified Parkinsons Disease Rating Scale and a significantly worse score for activities of daily living. In the CBD and IPD groups, striatum−occipital/occipital, caudate nucleus−occipital/occipital and putamen−occipital/occipital ratios decreased significantly relative to those of healthy subjects. No statistical difference could be found between the CBD and IPD groups for these ratios, although relatively even, decreased uptakes in the caudate nucleus and putamen were found in the CBD group. On further analysis of the index of binding reduction, the differences between the caudate nucleus and putamen were significantly lower in the CBD group than in the IPD group. The striatal uptake of [99mTc]TRODAT-1 showed a distinct asymmetry in both the CBD and IPD patients. ConclusionFrom this study, it can be concluded that early-stage CBD patients have a worse performance and more difficulties with daily activities than IPD patients. CBD patients demonstrated essentially similar patterns of [99mTc]TRODAT-1 binding as those with IPD. However, there was relatively more homogeneous involvement of the caudate nucleus and putamen in the CBD patients. This provides information about the differences between these patients in the early stages.

Large SGCE deletion contributes to Taiwanese myoclonus-dystonia syndrome.

We report three novel deletions of the SGCE gene in three families with myoclonus-dystonia (M-D) syndrome in Taiwan. Their clinical characteristics included: early onset, dominant myoclonus and dystonia in the neck, trunk and upper limbs. By direct sequencing of the SGCE gene coding regions, we identified a small heterozygous deletion (c.842delA) in exon 7 of the three sibs and asymptomatic father in the first family and an eight-base heterozygous deletion (c.524_531del) in exon 5 of the mother and a daughter in the second family. Using multiple ligation-dependent probe amplification (MLPA), a large heterozygous deletion of 2-11 exons was identified in the father and a son in the third family which was undetected by initial sequencing. It is the largest intragenic deletion ever reported. In conclusion, we have identified three novel mutations of SGCE in the respective three M-D families. The large deletion was responsible for one third of these M-D families which might implicate an important contribution to Taiwanese M-D syndrome. We suggest that the contribution of large deletion should be further verified in a large cohort of patients with M-D syndrome in Han Chinese.

Analysis of the LRRK2 Gly2385Arg variant in primary dystonia and multiple system atrophy in Taiwan

The c.G7153A variant in the LRRK2 gene (protein effect: Gly2385Arg) is emerging as an important risk factor for Parkinsons disease (PD) in the Han Chinese and Japanese populations. The prevalence of this variant in other neurodegenerative diseases and movement disorders remains almost completely unexplored. Using MALDI-TOF, we studied the Gly2385Arg variant in a large cohort of patients with primary dystonia (n=335) and a smaller series of patients with clinically diagnosed multiple system atrophy (MSA, n=57). The Gly2385Arg variant was identified in heterozygous state in 14 patients with primary dystonia (4.18%) and in three patients with MSA (5.26%). These frequencies do not differ statistically from that reported previously by us in Taiwanese controls (5%). We conclude that the Gly2385Arg variant is not associated with primary dystonia in Taiwan, supporting the specificity of the association between this variant and PD. Whether the Gly2385Arg variant modifies the risk for MSA deserves further study in larger samples.