Gaoxiong yi xue ke xue za zhi = The Kaohsiung journal of medical sciences, 1988
As utilization of radioimmunoassay becomes increasingly popular, so too the amount of laboratory ... more As utilization of radioimmunoassay becomes increasingly popular, so too the amount of laboratory tasks and documenting tasks. Computerized processing can afford means of dealing with such increasing tasks. Computerized processing can afford means of dealing with such increasing tasks. In this study an ABBOTT ANSR gammacounter was connected with a TATUNG TCS-5000 microcomputer to record the output cpm and to calculate the cut-off value. The result of assays were on-line stored on the diskettes, and than transferred to the main database. By this on –line system the loading of document key-in task was decreased, enhancing the accuracy of transfer of the results and decreasing the possibility of human error. Developing a database management if another joy of this laboratory, and the details of such a job will be described in the near future. A 16 year-old male developed recurrent muscle weakness and distal numbness of all 4 limbs for 1 year. A moderate degree of muscle weakness with int...
Background: Parkinson’s disease (PD) is the most common neurodegenerative motor disorder, which i... more Background: Parkinson’s disease (PD) is the most common neurodegenerative motor disorder, which is currently incurable. Mutations in many genes have been demonstrated to be the primary risk factors associated with the familial or idiopathic PD; however, the mechanisms underlying these genetic mutations resulting in parkinsonism remains unclear. Phospholipase A2 group VI (PLA2G6) has been shown to regulate lipid metabolism and homeostasis in the nervous system. Previous studies have shown that point mutations in PLA2G6 might be the risk factors associated with the young–onset of dystonia–parkinsonism type 14 (PARK14). However, limited information is available regarding its pathogenic role and the mechanism underlying its function. Methods: To study the role of PLA2G6 mutations in zebrafish PARK14 models, we injected different mutation constructs of human PLA2G6 genes and zebrafish pla2g6 deletion constructs in the zebrafish larvae. We analyzed the locomotion behavior, performed immun...
Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and s... more Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the function of C9orf72 in neural development and the pathogenic mechanism underlying neurodegeneration are unknown. We found that disrupting C9orf72 expression by using C9orf72 constructs that lack the complete DENN domain result in reduced GTPase activity in zebrafish embryos, demonstrating the indispensability of the complete DENN domain. This effect was phenocopied by knocking down endogenous C9orf72 expression by using morpholinos. C9orf72-deficient zebrafish embryos exhibited impaired axonogenesis and motility defects. The C9orf72 deficiency upregulated the expression of tp53 and caused neuronal apoptosis. Knockdown Tp53 in the C9orf72-deficient embryos rescued only the apoptotic phenotype but not the phenotype with axonal and motility defects. The C9orf72 deficiency also induced ccng1 (encodes ...
Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with L... more Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's dis...
Mutations in the gene encoding Ca 2+-independent phospholipase A 2 group 6 (PLA2G6) cause the rec... more Mutations in the gene encoding Ca 2+-independent phospholipase A 2 group 6 (PLA2G6) cause the recessive familial type 14 of Parkinson's disease (PARK14). Mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). PLA2G6 is believed to be required for maintaining mitochondrial function. In the present study, rotenone-induced cellular model of PD was used to investigate possible molecular pathogenic mechanism of PARK14 mutant PLA2G6-induced PD. Overexpression of wild-type (WT) PLA2G6 ameliorated rotenone-induced apoptotic death of SH-SY5Y dopaminergic cells. PARK14 mutant (D331Y), (G517C), (T572I), (R632W), (N659S) or (R741Q) PLA2G6 failed to prevent rotenone-induced activation of mitochondrial apoptotic pathway and exert a neuroprotective effect. WT PLA2G6, but not PARK14 mutant PLA2G6, prevented rotenone-induced mitophagy impairment. In contrast to WT PLA2G6, PARK14 mutant PLA2G6 was ineffective in attenuating rotenone-induced decrease in mitochondrial membrane potential and increase in the level of mitochondrial superoxide. WT PLA2G6, but not PARK14 PLA2G6 mutants, restored enzyme activity of mitochondrial complex I and cellular ATP content in rotenone-treated SH-SY5Y dopaminergic cells. In contrast to WT PLA2G6, PARK14 www.impactjournals.com/oncotarget/
Movement disorders : official journal of the Movement Disorder Society, Jul 19, 2016
ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fat... more ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations. Clinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed. The first sibling is 17 years old and presents with generalized dystonia and severe bilateral pallidal MRI lesions after 1 episode of infantile subacute metabolic encephalopathy (Leigh-like syndrome). In contrast, the younger sibling (15 years old) only suffers from paroxysmal exercise-induced dystonia and has very mild pallidal MRI abnormalities. Both patients carry compound heterozygous ECHS1 mutations: c.232G>T (predicted protein effect: p.Glu78Ter) and ...
Mutations of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both famili... more Mutations of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our resul...
Journal of the Formosan Medical Association = Taiwan yi zhi, 1993
We herein report on an 18-year-old Taiwanese man who developed acute onset of generalized continu... more We herein report on an 18-year-old Taiwanese man who developed acute onset of generalized continuous contractions of the muscles. The involuntary cramps caused a dystonic posture of the neck and limbs. Opisthotonos was noted when the cramps were exacerbated. The cramps were painful and sensitive to movement, so the patient limited movement of his body. External stimulation, such as a pin prick or a loud noise, would aggravate them. The contractions of the muscles persisted during sleep. No other neurologic abnormalities were noted. Electromyography showed spontaneous continuous muscle fiber activity. The symptoms did not respond to baclofen or diazepam; however, remarkable improvement was noted after giving phenytoin. The clinical presentation, electromyographic findings, and the patient's beneficial response to phenytoin fulfilled the diagnostic characteristics of Isaacs syndrome.
BackgroundHereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases charact... more BackgroundHereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs.MethodsA total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed.ResultsMutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20¿±¿18 years) compared with those with preservation of...
To examine the usefulness of diffusion kurtosis imaging for the diagnosis of Parkinson disease (P... more To examine the usefulness of diffusion kurtosis imaging for the diagnosis of Parkinson disease (PD). Examinations were performed with the understanding and written consent of each subject, with local ethics committee approval, and in compliance with national legislation and Declaration of Helsinki guidelines. Diffusion-weighted magnetic resonance imaging was performed in 30 patients with idiopathic PD (mean age, 64.5 years ± 3.4 [standard deviation]) and 30 healthy subjects (mean age, 65.0 years ± 5.1). Mean kurtosis, fractional anisotropy, and mean, axial, and radial diffusivity of the basal ganglia were compared between the groups. Disease severity was assessed by using Hoehn and Yahr staging and the motor section of the Unified Parkinson's Disease Rating Scale (mean scores, 2.0 and 33.6, respectively). Receiver operating characteristic (ROC) analysis was used to compare the diagnostic accuracies of the indexes of interest. Pearson correlation coefficient analysis was used to correlate imaging findings with disease severity. Mean kurtosis in the putamen was higher in the PD group (0.93 ± 0.15) than in the control group (0.71 ± 0.09) (P < .000416). The area under the ROC curve (AUC) was 0.95 for both the ipsilateral putamen and the ipsilateral substantia nigra. The mean kurtosis for the ipsilateral substantia nigra had the best diagnostic performance (mean cutoff, 1.10; sensitivity, 0.92; specificity, 0.87). In contrast, AUCs for the tensor-derived indexes ranged between 0.43 (axial and radial diffusivity in substantia nigra) and 0.65 (fractional anisotropy in substantia nigra). Diffusion kurtosis imaging in the basal ganglia, as compared with conventional diffusion-tensor imaging, can improve the diagnosis of PD.
Parkinson&amp... more Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative diseases and usually refers to a complex disorder with multiple genetic and environmental factors influencing disease risk. We here performed a gene-based case-control association study to scrutinize whether genetic variants in SNCA and LRRK2 genes could predispose to sporadic, late-onset form of PD in Taiwanese population. 17 Single Nucleotide Polymorphisms (SNPs) markers located within SNCA gene as well as the 16 SNP markers within LRRK2 gene were chosen for genotyping and evaluated their haplotype structure in a cohort of sporadic PD patients and control individuals. This study showed that two SNPs near the promoter region (rs2301134 and rs2301135) of SNCA gene gave the greatest evidence for an association with PD (p ≤ 0.01) and a haplotype block with two SNPs in the 3' UTR (rs356221 and rs11931074) revealed another evidence of association (p ≤ 0.02). For the LRRK2 gene, only R1628P variants of total 16 SNPs giving a marginal significant association with PD across the whole gene (p = 0.0058) and no haplotype block was constructed. Many genetic variants (A419V, I1122V, R1441C, R1441G, R1441H, Y1699C, M1869V, M1869T, I2012T, G2019S, and I2020T) from previous reports were not detected in our cohort. We have replicated a population-based PD association study in a collection of 626 cases and 473 control subjects and confirm that genetic variants of both SNCA and LRRK2 genes are associated with susceptibility to sporadic PD but in a different distribution.
To analyze the Gly2385Arg (G2385R) mutation in Taiwanese Alzheimer&am... more To analyze the Gly2385Arg (G2385R) mutation in Taiwanese Alzheimer's disease (AD) patients. The leucine-rich repeat kinase 2 (LRRK2) gene is well known to predispose subjects to Parkinson's disease (PD). The Gly2385Arg (G2385R) variant of LRRK2 is believed to be "East Asian"-specific, particularly in the Han Chinese population; however, whether the LRRK2 G2385R is associated with a risk of AD in pure Han-Chinese patients has not often been studied. A total of 209 AD patients (87 men, 122 women) and 180 age- and gender-matched controls were recruited and the demographic data of the AD patients were analyzed. Genotyping of the Gly2385Arg variant was studied using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Subjects with the Gly2385Arg variant were all heterozygous carriers. The frequency of Gly2385Arg carriers did not differ significantly between the AD patients and controls (4.78% versus 4.44%, odds ratio=1.04, 95% CI=0.62-1.77, P=0.87). In the AD patient group, the age of symptom onset, the length of education, or the MMSE score showed no significant differences between wild-type carriers and heterozygous variant carriers (P=0.51, 0.43, and 0.09). The Gly2385Arg variant of LRRK2 may not be a major risk factor for AD in pure Han Chinese patient. Among the AD patients, Gly2385Arg carriers were not clinically different from wild-type carriers.
We report childhood-onset autosomal-dominant limb-girdle muscular dystrophy (LGMD) in a Chinese f... more We report childhood-onset autosomal-dominant limb-girdle muscular dystrophy (LGMD) in a Chinese family with complete atrioventricular conduction block in the adult members. Six patients, including 5 men and 1 woman with an age of onset from 3 to 7 years, were affected. The grandfather had exercise intolerance since childhood and complete heart block with pace-maker placement at age 52. Three siblings had proximal muscle weakness and/or wasting since age 5 and heart block in their 40s. Two grandsons at the ages 7 and 3 showed exercise intolerance, and proximal muscle weakness and wasting. Sinus bradycardia was present in the elder grandson. Muscle enzymes were elevated in 3, particularly in childhood. Muscle biopsies from the proband showed myopathic changes with fatty degeneration, whorled fibers, and rimmed vacuoles. In adult patients, muscle magnetic resonance imaging scans disclosed atrophic changes and fatty degeneration in the gluteal, quadriceps, adductors, hamstrings, gastrocnemius, and soleus muscles, while in child probands the early atrophic changes were seen in the gluteal and hamstrings muscles. We conclude that this distinct family is characterized by childhood-onset autosomal-dominant LGMD with heart block and that prevention of sudden death in these patients is important.
We studied the inhibition of median H-reflexes by conditioning stimuli on the radial nerve in 13 ... more We studied the inhibition of median H-reflexes by conditioning stimuli on the radial nerve in 13 patients with writer's cramp, eight of the simple type and five of the dystonic type, and in 14 normal volunteers. The patients and controls were right-handed, and their right arms were studied. Asymptomatic left arms were also studied in nine of 13 patients. In the control group we identified three periods of inhibition, with maximum peaks at conditioning-test intervals of 0 ms (41 ? 17%), 20 ms (40 * 13%), and 100 ms (36 k 20%). In the patient group, the amplitudes of inhibition of these three periods in both arms were significantly less than those in the control group. However, there were no significant differences in the amplitudes of inhibition of these three periods between symptomatic and asymptomatic arms. There were also no significant differences between simple and dystonic writer's cramps. Our results indicate that the attenuation of reciprocal inhibition was present not only in symptomatic arms but also in asymptomatic arms of patients with writer's cramp. The defect of reciprocal inhibition in the asymptomatic hand has never been documented. We suggest that the preexistent electrophysiological abnormality may provide an explanation for the development of hand cramp after shifted writing.
The occurrence of persistent hemiballism after subthalamotomy for Parkinson&a... more The occurrence of persistent hemiballism after subthalamotomy for Parkinson's disease (PD) has not been described as frequently as mild or transient dyskinesia. We report on 2 patients with advanced PD who developed hemiballism and/or dyskinesia after subthalamotomy. One patient with a small lesion confined to the subthalamic nucleus (STN) developed persistent hemiballism; the other with a larger lesion involving the STN and also the zona incerta presented with a transient dyskinesia in a single limb. We conclude that a precise STN lesion might bear a potential risk of persistent hemiballism.
Gaoxiong yi xue ke xue za zhi = The Kaohsiung journal of medical sciences, 1988
As utilization of radioimmunoassay becomes increasingly popular, so too the amount of laboratory ... more As utilization of radioimmunoassay becomes increasingly popular, so too the amount of laboratory tasks and documenting tasks. Computerized processing can afford means of dealing with such increasing tasks. Computerized processing can afford means of dealing with such increasing tasks. In this study an ABBOTT ANSR gammacounter was connected with a TATUNG TCS-5000 microcomputer to record the output cpm and to calculate the cut-off value. The result of assays were on-line stored on the diskettes, and than transferred to the main database. By this on –line system the loading of document key-in task was decreased, enhancing the accuracy of transfer of the results and decreasing the possibility of human error. Developing a database management if another joy of this laboratory, and the details of such a job will be described in the near future. A 16 year-old male developed recurrent muscle weakness and distal numbness of all 4 limbs for 1 year. A moderate degree of muscle weakness with int...
Background: Parkinson’s disease (PD) is the most common neurodegenerative motor disorder, which i... more Background: Parkinson’s disease (PD) is the most common neurodegenerative motor disorder, which is currently incurable. Mutations in many genes have been demonstrated to be the primary risk factors associated with the familial or idiopathic PD; however, the mechanisms underlying these genetic mutations resulting in parkinsonism remains unclear. Phospholipase A2 group VI (PLA2G6) has been shown to regulate lipid metabolism and homeostasis in the nervous system. Previous studies have shown that point mutations in PLA2G6 might be the risk factors associated with the young–onset of dystonia–parkinsonism type 14 (PARK14). However, limited information is available regarding its pathogenic role and the mechanism underlying its function. Methods: To study the role of PLA2G6 mutations in zebrafish PARK14 models, we injected different mutation constructs of human PLA2G6 genes and zebrafish pla2g6 deletion constructs in the zebrafish larvae. We analyzed the locomotion behavior, performed immun...
Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and s... more Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the function of C9orf72 in neural development and the pathogenic mechanism underlying neurodegeneration are unknown. We found that disrupting C9orf72 expression by using C9orf72 constructs that lack the complete DENN domain result in reduced GTPase activity in zebrafish embryos, demonstrating the indispensability of the complete DENN domain. This effect was phenocopied by knocking down endogenous C9orf72 expression by using morpholinos. C9orf72-deficient zebrafish embryos exhibited impaired axonogenesis and motility defects. The C9orf72 deficiency upregulated the expression of tp53 and caused neuronal apoptosis. Knockdown Tp53 in the C9orf72-deficient embryos rescued only the apoptotic phenotype but not the phenotype with axonal and motility defects. The C9orf72 deficiency also induced ccng1 (encodes ...
Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with L... more Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's dis...
Mutations in the gene encoding Ca 2+-independent phospholipase A 2 group 6 (PLA2G6) cause the rec... more Mutations in the gene encoding Ca 2+-independent phospholipase A 2 group 6 (PLA2G6) cause the recessive familial type 14 of Parkinson's disease (PARK14). Mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). PLA2G6 is believed to be required for maintaining mitochondrial function. In the present study, rotenone-induced cellular model of PD was used to investigate possible molecular pathogenic mechanism of PARK14 mutant PLA2G6-induced PD. Overexpression of wild-type (WT) PLA2G6 ameliorated rotenone-induced apoptotic death of SH-SY5Y dopaminergic cells. PARK14 mutant (D331Y), (G517C), (T572I), (R632W), (N659S) or (R741Q) PLA2G6 failed to prevent rotenone-induced activation of mitochondrial apoptotic pathway and exert a neuroprotective effect. WT PLA2G6, but not PARK14 mutant PLA2G6, prevented rotenone-induced mitophagy impairment. In contrast to WT PLA2G6, PARK14 mutant PLA2G6 was ineffective in attenuating rotenone-induced decrease in mitochondrial membrane potential and increase in the level of mitochondrial superoxide. WT PLA2G6, but not PARK14 PLA2G6 mutants, restored enzyme activity of mitochondrial complex I and cellular ATP content in rotenone-treated SH-SY5Y dopaminergic cells. In contrast to WT PLA2G6, PARK14 www.impactjournals.com/oncotarget/
Movement disorders : official journal of the Movement Disorder Society, Jul 19, 2016
ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fat... more ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations. Clinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed. The first sibling is 17 years old and presents with generalized dystonia and severe bilateral pallidal MRI lesions after 1 episode of infantile subacute metabolic encephalopathy (Leigh-like syndrome). In contrast, the younger sibling (15 years old) only suffers from paroxysmal exercise-induced dystonia and has very mild pallidal MRI abnormalities. Both patients carry compound heterozygous ECHS1 mutations: c.232G>T (predicted protein effect: p.Glu78Ter) and ...
Mutations of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both famili... more Mutations of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our resul...
Journal of the Formosan Medical Association = Taiwan yi zhi, 1993
We herein report on an 18-year-old Taiwanese man who developed acute onset of generalized continu... more We herein report on an 18-year-old Taiwanese man who developed acute onset of generalized continuous contractions of the muscles. The involuntary cramps caused a dystonic posture of the neck and limbs. Opisthotonos was noted when the cramps were exacerbated. The cramps were painful and sensitive to movement, so the patient limited movement of his body. External stimulation, such as a pin prick or a loud noise, would aggravate them. The contractions of the muscles persisted during sleep. No other neurologic abnormalities were noted. Electromyography showed spontaneous continuous muscle fiber activity. The symptoms did not respond to baclofen or diazepam; however, remarkable improvement was noted after giving phenytoin. The clinical presentation, electromyographic findings, and the patient's beneficial response to phenytoin fulfilled the diagnostic characteristics of Isaacs syndrome.
BackgroundHereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases charact... more BackgroundHereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs.MethodsA total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed.ResultsMutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20¿±¿18 years) compared with those with preservation of...
To examine the usefulness of diffusion kurtosis imaging for the diagnosis of Parkinson disease (P... more To examine the usefulness of diffusion kurtosis imaging for the diagnosis of Parkinson disease (PD). Examinations were performed with the understanding and written consent of each subject, with local ethics committee approval, and in compliance with national legislation and Declaration of Helsinki guidelines. Diffusion-weighted magnetic resonance imaging was performed in 30 patients with idiopathic PD (mean age, 64.5 years ± 3.4 [standard deviation]) and 30 healthy subjects (mean age, 65.0 years ± 5.1). Mean kurtosis, fractional anisotropy, and mean, axial, and radial diffusivity of the basal ganglia were compared between the groups. Disease severity was assessed by using Hoehn and Yahr staging and the motor section of the Unified Parkinson's Disease Rating Scale (mean scores, 2.0 and 33.6, respectively). Receiver operating characteristic (ROC) analysis was used to compare the diagnostic accuracies of the indexes of interest. Pearson correlation coefficient analysis was used to correlate imaging findings with disease severity. Mean kurtosis in the putamen was higher in the PD group (0.93 ± 0.15) than in the control group (0.71 ± 0.09) (P < .000416). The area under the ROC curve (AUC) was 0.95 for both the ipsilateral putamen and the ipsilateral substantia nigra. The mean kurtosis for the ipsilateral substantia nigra had the best diagnostic performance (mean cutoff, 1.10; sensitivity, 0.92; specificity, 0.87). In contrast, AUCs for the tensor-derived indexes ranged between 0.43 (axial and radial diffusivity in substantia nigra) and 0.65 (fractional anisotropy in substantia nigra). Diffusion kurtosis imaging in the basal ganglia, as compared with conventional diffusion-tensor imaging, can improve the diagnosis of PD.
Parkinson&amp... more Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative diseases and usually refers to a complex disorder with multiple genetic and environmental factors influencing disease risk. We here performed a gene-based case-control association study to scrutinize whether genetic variants in SNCA and LRRK2 genes could predispose to sporadic, late-onset form of PD in Taiwanese population. 17 Single Nucleotide Polymorphisms (SNPs) markers located within SNCA gene as well as the 16 SNP markers within LRRK2 gene were chosen for genotyping and evaluated their haplotype structure in a cohort of sporadic PD patients and control individuals. This study showed that two SNPs near the promoter region (rs2301134 and rs2301135) of SNCA gene gave the greatest evidence for an association with PD (p ≤ 0.01) and a haplotype block with two SNPs in the 3' UTR (rs356221 and rs11931074) revealed another evidence of association (p ≤ 0.02). For the LRRK2 gene, only R1628P variants of total 16 SNPs giving a marginal significant association with PD across the whole gene (p = 0.0058) and no haplotype block was constructed. Many genetic variants (A419V, I1122V, R1441C, R1441G, R1441H, Y1699C, M1869V, M1869T, I2012T, G2019S, and I2020T) from previous reports were not detected in our cohort. We have replicated a population-based PD association study in a collection of 626 cases and 473 control subjects and confirm that genetic variants of both SNCA and LRRK2 genes are associated with susceptibility to sporadic PD but in a different distribution.
To analyze the Gly2385Arg (G2385R) mutation in Taiwanese Alzheimer&am... more To analyze the Gly2385Arg (G2385R) mutation in Taiwanese Alzheimer's disease (AD) patients. The leucine-rich repeat kinase 2 (LRRK2) gene is well known to predispose subjects to Parkinson's disease (PD). The Gly2385Arg (G2385R) variant of LRRK2 is believed to be "East Asian"-specific, particularly in the Han Chinese population; however, whether the LRRK2 G2385R is associated with a risk of AD in pure Han-Chinese patients has not often been studied. A total of 209 AD patients (87 men, 122 women) and 180 age- and gender-matched controls were recruited and the demographic data of the AD patients were analyzed. Genotyping of the Gly2385Arg variant was studied using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Subjects with the Gly2385Arg variant were all heterozygous carriers. The frequency of Gly2385Arg carriers did not differ significantly between the AD patients and controls (4.78% versus 4.44%, odds ratio=1.04, 95% CI=0.62-1.77, P=0.87). In the AD patient group, the age of symptom onset, the length of education, or the MMSE score showed no significant differences between wild-type carriers and heterozygous variant carriers (P=0.51, 0.43, and 0.09). The Gly2385Arg variant of LRRK2 may not be a major risk factor for AD in pure Han Chinese patient. Among the AD patients, Gly2385Arg carriers were not clinically different from wild-type carriers.
We report childhood-onset autosomal-dominant limb-girdle muscular dystrophy (LGMD) in a Chinese f... more We report childhood-onset autosomal-dominant limb-girdle muscular dystrophy (LGMD) in a Chinese family with complete atrioventricular conduction block in the adult members. Six patients, including 5 men and 1 woman with an age of onset from 3 to 7 years, were affected. The grandfather had exercise intolerance since childhood and complete heart block with pace-maker placement at age 52. Three siblings had proximal muscle weakness and/or wasting since age 5 and heart block in their 40s. Two grandsons at the ages 7 and 3 showed exercise intolerance, and proximal muscle weakness and wasting. Sinus bradycardia was present in the elder grandson. Muscle enzymes were elevated in 3, particularly in childhood. Muscle biopsies from the proband showed myopathic changes with fatty degeneration, whorled fibers, and rimmed vacuoles. In adult patients, muscle magnetic resonance imaging scans disclosed atrophic changes and fatty degeneration in the gluteal, quadriceps, adductors, hamstrings, gastrocnemius, and soleus muscles, while in child probands the early atrophic changes were seen in the gluteal and hamstrings muscles. We conclude that this distinct family is characterized by childhood-onset autosomal-dominant LGMD with heart block and that prevention of sudden death in these patients is important.
We studied the inhibition of median H-reflexes by conditioning stimuli on the radial nerve in 13 ... more We studied the inhibition of median H-reflexes by conditioning stimuli on the radial nerve in 13 patients with writer's cramp, eight of the simple type and five of the dystonic type, and in 14 normal volunteers. The patients and controls were right-handed, and their right arms were studied. Asymptomatic left arms were also studied in nine of 13 patients. In the control group we identified three periods of inhibition, with maximum peaks at conditioning-test intervals of 0 ms (41 ? 17%), 20 ms (40 * 13%), and 100 ms (36 k 20%). In the patient group, the amplitudes of inhibition of these three periods in both arms were significantly less than those in the control group. However, there were no significant differences in the amplitudes of inhibition of these three periods between symptomatic and asymptomatic arms. There were also no significant differences between simple and dystonic writer's cramps. Our results indicate that the attenuation of reciprocal inhibition was present not only in symptomatic arms but also in asymptomatic arms of patients with writer's cramp. The defect of reciprocal inhibition in the asymptomatic hand has never been documented. We suggest that the preexistent electrophysiological abnormality may provide an explanation for the development of hand cramp after shifted writing.
The occurrence of persistent hemiballism after subthalamotomy for Parkinson&a... more The occurrence of persistent hemiballism after subthalamotomy for Parkinson's disease (PD) has not been described as frequently as mild or transient dyskinesia. We report on 2 patients with advanced PD who developed hemiballism and/or dyskinesia after subthalamotomy. One patient with a small lesion confined to the subthalamic nucleus (STN) developed persistent hemiballism; the other with a larger lesion involving the STN and also the zona incerta presented with a transient dyskinesia in a single limb. We conclude that a precise STN lesion might bear a potential risk of persistent hemiballism.
Uploads
Papers by Chin-song Lu