This study developed a predictive model for cognitive degeneration in patients with Parkinson’s d... more This study developed a predictive model for cognitive degeneration in patients with Parkinson’s disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.
1 Abstract- Primary hepatocellular carcinoma is one of the most common cancers in Taiwan, but orb... more 1 Abstract- Primary hepatocellular carcinoma is one of the most common cancers in Taiwan, but orbital metastases are rare. To the best of our knowledge, only 10 cases of metastases to the orbit have been described in the literature. This may be related to the short clinical course of the malignancy and the fact that most patients died before metastasis occurred. We describe a 69-year-old man who developed progres- sive painful ophthalmoplegia for two weeks. Magnetic resonance imaging of the brain showed a right supra- orbital mass invading the orbital cavity. The diagnosis of hepatocellular carcinoma with orbital metastasis was made after surgical removal of the orbital mass. This is the first reported case of hepatocellular carcino- ma with the unusual mode of presentation in Taiwan. We emphasize the importance of early recognition and treatment of this clinical condition.
BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of t... more BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of the central nervous system, typically occurring after infections or vaccinations. To our knowledge, scrub typhus has not been described in association with ADEM. CASE REPORT A 77-year-old man was admitted with fever, convulsions and an altered level of consciousness. On neurological examination, the patient was stuporous and had nuchal rigidity and left hemiparesis. A generalized tonic-clonic seizure was observed. Serum and cerebrospinal fluid samples were positive for anti-Orientia tsutsugamushi antibody. Despite a 10-day course of parenteral minocycline, his clinical condition deteriorated. Serial cranial magnetic resonance images demonstrated progressively extensive areas of signal hyperintensity on conventional T2-weighted and fluid attenuated inversion recovery sequence images, mainly affecting the periventricular white matter. After administration of intravenous high-dose corticoste...
We conducted an observational study to investigate clinical predictors of cognitive decline in pa... more We conducted an observational study to investigate clinical predictors of cognitive decline in patients with mild cognitive impairment (MCI), with a focus on patients with Parkinson’s disease (PD) and Alzheimer’s disease (AD). The study was performed with detailed neuropsychological testing, a portable device for gait analysis, and a comprehensive geriatric assessment for patients with MCI. Cognitive decline was defined as subjective cognitive impairment with an objective decline in the Mini-Mental State Examination (MMSE) ≥2 points at the one-year follow-up. Participants (n = 74) had a median age of 70 (interquartile range 60–79) years, and 45.9% of them were women. At the end of the study, 17.6% of the patients with MCI had a cognitive decline. Although no differences were observed between groups at the baseline cognitive study, patients with PD-MCI demonstrated more cognitive decline than patients with AD-MCI (28.6% vs. 7.7% p = 0.03). Patients with PD-MCI had more physical disa...
Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subj... more Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. Methods A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into 2 groups, MCR (n = 33) and MCI (n = 44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, “pure” MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, an...
Dementia with Lewy bodies (DLB) is a complex, multisymptom disorder. When making decisions regard... more Dementia with Lewy bodies (DLB) is a complex, multisymptom disorder. When making decisions regarding the treatment of DLB, the patient’s quality of life (QoL) should always be the main consideration. To our knowledge, this is the first review article focusing on the QoL in DLB patients. We searched the PubMed database using the keywords “quality of life” and “dementia with Lewy bodies.” Previously, no specific instrument had been developed for assessing the QoL in DLB patients. Patients with DLB have a decreased QoL compared to patients with Alzheimer’s disease, which is reportedly caused by several factors including level of independence in instrumental activities of daily living, whether the patient is living with the caregiver, apathy, delusion, and dysautonomia. The direct effect of visual hallucination, sleep, and movement disorders on the QoL in DLB patients has not been previously studied. The role of cognitive function on the QoL is still controversial. In a randomized contr...
Background: This study aimed to evaluate the effects of cueing on circular walking in patients wi... more Background: This study aimed to evaluate the effects of cueing on circular walking in patients with Parkinson's disease. Methods: Parkinson's disease patients in the "off" state were asked to walk on a designed route at their preferred speed. The experimental protocol was divided into two sessions. The first session was to be performed with no manual task. During the second session, the participant had to perform a manual task. Each session was measured for each of four conditions performed in the following order: without cues, with a visual cue, with an auditory cue, and with dual cues simultaneously. Temporospatial gait parameters and freezing of gait (FOG) events regarding the cueing-on and cueing-off situations were the main measures of gait performance. Results: Twelve patients with Parkinson's disease were recruited. Demographic and clinical characteristics of the participants were the following [median (interquartile range)]: age 63 years (57e67.3 years), Hoehn and Yahr stage 3.0 (3.0e3.25), and Unified Parkinson's Disease Rating Scale motor subsection off medication 22.5 (20.3e35.5). Walking turns of 180 in combination with a manual task were the most important triggers for FOG. On circular walking either with or without a manual task, visual or dual cues improved festinating gait patterns and increased step length. Visual or dual cues further improved the velocity of walking with a manual task. All types of cueing decreased FOG scores either with or without a manual task. Conclusion: Our study suggests that cueing improves festinating gait and decreases the incidence of FOG. Future studies with much larger sample sizes are warranted to support our findings.
Background: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neuro... more Background: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by deficits in executive function that frequently overlaps with parkinsonism and motor neuron disorders. Several genes have been identified to cause autosomal dominant forms of FTD, including the gene coding for the protein associated with microtubule tau (MAPT). While most reported pathogenic mutations in MAPT occur in exons 9-13, few families have been reported with mutations outside of this region. Herein, we report a first Taiwanese family having the exon 1 p.Arg5His mutation in MAPT with intrafamilial phenotype heterogeneity. Case presentation: A 63-year-old man presented with progressive non-fluent speech and impaired memory for 3 years. He then developed apraxia, myoclonus and parkinsonism feature at his right hand. Extensive neurologic and neurocognitive examination lead to a diagnosis of FTD mixed with corticobasal syndrome. Magnetic resonance imaging revealed asymmetric atrophy in the left frontal and temporal lobes and single-photon emission computed tomography indicated decreased metabolism in the same areas as well as the left basal ganglia. The patient's mother had been diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 60 and was deceased 10 years later due to respiratory failure. The patient's younger sister had persistent depressive disorder in her early forties and did not have any prominent cognitive or motor dysfunctions. We performed genetic analysis applying a targeted next generation sequencing (NGS) panel covering MAPT, GRN, VCP, FUS, CHMP2B, and TARDBP on the proband, followed by Sanger sequencing of candidate genes in eight family members. Hexanucleotide repeat expansion of C9Orf72 was determined by repeat-primed PCR. We identified a missense mutation in exon 1 of MAPT gene, c. 14G > A (p.R5H), which was previously reported in only two Japanese patients in a literature review. This substitution co-segregated with the disease phenotypes in the family. Conclusions: This is the first report of the occurrence of the MAPT p.R5H mutation in the Taiwanese population. Our findings extend the current knowledge of phenotypic heterogeneity among family members carrying the MAPT p.R5H mutation.
Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and n... more Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and non-cartilaginous structures. Neurological involvement is rarer but results in profound disability. Early identification and treatment of underlying RP may promote neurological recovery. We illustrated a 53-year-old man diagnosed with dementia. Neuroimaging and cerebrospinal fluid studies disclosed meningoencephalitis. "Prominent ear sign" was evident on diffusion-weight magnetic resonance imaging. After glucocortisone administration, the improvement of clinical manifestations was closely correlated subsequent neuroimaging findings. The importance of better understanding of this disease in terms of the prevention of further tissue damage in patients with RP cannot be overemphasized.
Taiwanese Journal of Obstetrics and Gynecology, 2010
Illnesses associated with stroke during pregnancy include hypertension, diabetes, heart disease, ... more Illnesses associated with stroke during pregnancy include hypertension, diabetes, heart disease, smoking, and thrombophilia. Multiparity, increased gestational age,
The goal of this study was to assess the prevalence and clinical correlates of restless legs synd... more The goal of this study was to assess the prevalence and clinical correlates of restless legs syndrome (RLS) among pregnant Taiwanese women. We enrolled 461 pregnant women (18-45 years) admitted at Mackay Memorial Hospital for delivery from September 2010 to May 2011. The face-to-face questionnaire used to gather data included assessment of RLS diagnostic criteria, and questions related to RLS. The overall prevalence rate of RLS among the study participants was 10.4%; 2.8% were categorized as having chronic RLS. Participants without RLS reported higher folate and iron supplement consumption than those with RLS. Multivariate analysis revealed significant associations of RLS with anemia and peptic ulcer disease. Participants with transient RLS during pregnancy reported more regular coffee consumption before pregnancy, and better sleep latency, duration, and efficiency, than those with chronic RLS. Overall, 81.2% of RLS sufferers reported sleep disturbances. Our study revealed highly prevalent but poorly recognized RLS among Taiwanese pregnant women. The identification of predictors such as medical comorbidities, and protectors such as folate and iron supplements, is warranted for obstetric RLS. In most cases, symptoms began during the second or third trimester and resolved within a week after delivery. Restricted coffee consumption before pregnancy is encouraged, but further evidence is needed to support this recommendation.
The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeds the formation of senile p... more The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeds the formation of senile plaques and contributes to synaptic and memory deficits in Alzheimer's disease (AD). The mechanism of mediating microglial oAβ clearance remains unclear and thought to occur via scavenger receptors (SRs) in microglia. SRs respond to their ligands in a subtype-specific manner. Therefore, we sought to identify the specific subtypes of SRs that mediate oAβ internalization and proteases that degrade oAβ species in naïve primary microglia. The component of oAβ species were characterized by western blot analysis, analytical ultracentrifugation analysis, and atomic force microscopy. The oAβ species remained soluble in the medium and microglial lysates during incubation at 37°C. SR-A, but not CD36, mediated oAβ internalization in microglia as suggested by the use of subtype-specific neutralizing antibodies and small interfering RNAs (siRNAs). Immunoprecipitation analysis showed that oAβ interacted with SR-A on the plasma membrane. After internalization, over 40% of oAβ vesicles were trafficked toward lysosomes and degraded by cysteine proteases, including cathepsin B. The inhibitors of proteasome, neprilysin, matrix metalloproteinases, and insulin degrading enzyme failed to protect internalized oAβ from degradation. Our study suggests that SR-A and lysosomal cathepsin B are critical in microglial oAβ clearance, providing insight into how microglia are involved in the clearance of oAβ and their roles in the early stages of AD.
Dementia in the elderly is the most common neurodegenerative disease and places a huge burden on ... more Dementia in the elderly is the most common neurodegenerative disease and places a huge burden on public health. Sporadic CreutzfeldteJacob disease (sCJD) is sometimes diagnosed in people with dementia; it develops in a rapid and progressive manner and has a short survival duration. The critical issue for sCJD is its transmissible nature. Besides rapid and progressive dementia, two out of four motor symptoms are assessed for a definitive diagnosis, including myoclonus, cerebellar problems, extrapyramidal/pyramidal features, and akinetic mutism. Here we report on a 77-year-old woman with initially pure dementia. Sequential neuroimaging revealed progressive isolated cortical effects over a period of 3 years. Basal ganglia involvement on neuroimaging and generalized periodic sharp wave complexes on electroencephalogram were delayed until the onset of reflex myoclonic jerks occurred 3 years after the onset of dementia. The patient survives, with an unusually long duration for sCJD. According to the clinical and laboratory features observed in this case, awareness of pure dementia with delayed onset of characteristic electroencephalogram features and isolated cortical effects on neuroimaging may predict unusually long survival in sCJD.
Restless legs syndrome is a sleep and movement disorder that affects 5-15% of the general populat... more Restless legs syndrome is a sleep and movement disorder that affects 5-15% of the general population, with an increased prevalence among the elderly population. It not only affects quality of life but also increases risk of mortality among older adults. The diagnosis is based on clinical symptoms of the patient by four minimal essential criteria. Restless legs syndrome can be divided into primary or secondary causes. Examination should be performed to rule out potentially treatable illnesses, such as iron deficiency, renal failure or peripheral neuropathy, especially among elderly patients. The initial approach to restless legs syndrome should be nonpharmacologic management, such as good sleep hygiene, regular exercise, cognitive behavioral therapy and avoidance of certain aggravating drugs. An algorithm based on scientific evidence and expert opinion was developed for guidance of treatment. Combination or change of medication can be applied to resistant or difficult cases. Since elderly patients are prone to treatment-related side effects, the best strategy is to start medication cautiously and at the lowest recommended dosage. [
Depression has a negative impact on activities of daily living, cognitive performance, and qualit... more Depression has a negative impact on activities of daily living, cognitive performance, and quality of life. Despite the high prevalence of depressive symptoms in Parkinson disease (PD), this important clinical feature is underrecognized by physicians. Effective diagnosis, assessment and treatment of depression are, therefore, important aspects of PD management. In this article, we review the literature concerning depression associated with PD, paying specific attention to clinical presentation, diagnosis, etiology, and the principles of management and treatment. The efficacy and safety of antidepressants must rely on empiric assessments of known risks and putative benefits to guide treatment decisions. [
Gait disorder, a major cause of morbidity in the elderly population, is one of the cardinal featu... more Gait disorder, a major cause of morbidity in the elderly population, is one of the cardinal features of Parkinson's disease. Owing to the characteristics of these gaits varying widely from festination to freezing of gait, analysis can be hardly identified in the clinical setting. Instrumented gait analysis has been widely used in a traditional gait laboratory. Recently, wireless monitoring systems have become highly informative by allowing long-term data collection in a variety of environments outside the labs. The quantitative analysis of gait patterns is probably the first step to a successful management of an individual patient. The presence of abnormal gait usually indicates advanced stages of disease and is often associated with cognitive impairment, falls, and injuries. Besides pharmacological and surgical treatments, parkinsonian gait can benefit from a variety of interventions. Assistive devices prevent patients from falls, and cueing strategies help them decrease episodes of freezing. Therefore, a multidisciplinary team approach to the optimal management is essential for an elderly patient with Parkinson's disease.
Ischemic stroke classification is critical in conducting basic research and clinical practice. A ... more Ischemic stroke classification is critical in conducting basic research and clinical practice. A precise analysis of stroke subtypes requires the integration of clinical features, findings from diagnostic tests, and knowledge about potential etiologic factors by competent diagnostic investigators. We performed a literature review of the published stroke classification systems and examined each for its benefits and limitations in the evaluation of the stroke etiology. Two major approaches to etiologic classifications of ischemic stroke are currently being used: the causative and phenotypic subtyping. The most widely used causative system is the Trial of Org 10172 in acute stroke treatment (TOAST) classification. With the advances in modern diagnostic technology, new stroke subclassification systems, such as the causative classification system (CCS) and Chinese ischemic stroke subclassification (CISS) system, have been developed to enhance the accuracy of TOAST. The AS -CO (Atherosclerosis, Smallvessel disease, Cardiac source, Other cause) phenotypic classification system makes efforts to identify the most likely etiology but not neglecting the possibility of other potential multiple causes. We conclude that the ideal stroke classification system needs to be valid, easy to use, evidence-based, and incorporate new information as it emerges.
Journal of Stroke and Cerebrovascular Diseases, 2018
Background: This study intended to investigate whether etiological stroke subtypes and their corr... more Background: This study intended to investigate whether etiological stroke subtypes and their corresponding major risk factors have differential effects on outcomes between genders. Patients and Methods: We enrolled 403 consecutive patients with first-ever acute ischemic stroke (170 women, 233 men), from a referral hospital in Taiwan over a 2-year period. Gender differences in demographics, vascular risk factors, access to health care, etiological stroke subtypes, stroke severity, and outcomes were examined. The primary outcome variable of the study was any unfavorable outcome due to acute ischemic stroke, defined as a modified Rankin Scale score of 3 or higher at 90 days after stroke. Multivariable logistic regression models were used to identify predictors of poor outcomes. Results: There were no gender disparities in baseline severity, stroke subtypes, access to health care, and medical comorbidities. Although women had poorer outcomes, female gender was not a predictor of unfavorable outcomes. Important predictors included age of 75years or older (odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.46-4.90), National Institutes of Health Stroke Scale greater than or equal to 8 (OR = 8.38; 95% CI, 4.61-15.2), lack of cohabitation (OR = 2.13; 95% CI, 1.26-3.61), subtypes of cardioembolism (OR = 2.76; 95% CI, 1.29-5.93), and largeartery atherosclerosis (OR = 2.93; 95% CI, 1.47-5.85). In subgroup analyses, the genderspecific independent predictors were cardioembolism (OR = 7.42; 95% CI, 2.21-24.9) or atrial fibrillation (OR = 3.57; 95% CI, 1.31-9.74) in women, and largeartery atherosclerosis (OR = 3.35; 95% CI, 1.30-8.64) or symptomatic large-artery stenosis (OR = 3.42; 95% CI, 1.69-6.96) in men. The differential effects of these predictors according to gender were revealed by interaction tests. Conclusion: Atrial fibrillation and symptomatic large-artery stenosis are predictors of poor stroke outcomes in women and men, respectively.
This study developed a predictive model for cognitive degeneration in patients with Parkinson’s d... more This study developed a predictive model for cognitive degeneration in patients with Parkinson’s disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.
1 Abstract- Primary hepatocellular carcinoma is one of the most common cancers in Taiwan, but orb... more 1 Abstract- Primary hepatocellular carcinoma is one of the most common cancers in Taiwan, but orbital metastases are rare. To the best of our knowledge, only 10 cases of metastases to the orbit have been described in the literature. This may be related to the short clinical course of the malignancy and the fact that most patients died before metastasis occurred. We describe a 69-year-old man who developed progres- sive painful ophthalmoplegia for two weeks. Magnetic resonance imaging of the brain showed a right supra- orbital mass invading the orbital cavity. The diagnosis of hepatocellular carcinoma with orbital metastasis was made after surgical removal of the orbital mass. This is the first reported case of hepatocellular carcino- ma with the unusual mode of presentation in Taiwan. We emphasize the importance of early recognition and treatment of this clinical condition.
BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of t... more BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of the central nervous system, typically occurring after infections or vaccinations. To our knowledge, scrub typhus has not been described in association with ADEM. CASE REPORT A 77-year-old man was admitted with fever, convulsions and an altered level of consciousness. On neurological examination, the patient was stuporous and had nuchal rigidity and left hemiparesis. A generalized tonic-clonic seizure was observed. Serum and cerebrospinal fluid samples were positive for anti-Orientia tsutsugamushi antibody. Despite a 10-day course of parenteral minocycline, his clinical condition deteriorated. Serial cranial magnetic resonance images demonstrated progressively extensive areas of signal hyperintensity on conventional T2-weighted and fluid attenuated inversion recovery sequence images, mainly affecting the periventricular white matter. After administration of intravenous high-dose corticoste...
We conducted an observational study to investigate clinical predictors of cognitive decline in pa... more We conducted an observational study to investigate clinical predictors of cognitive decline in patients with mild cognitive impairment (MCI), with a focus on patients with Parkinson’s disease (PD) and Alzheimer’s disease (AD). The study was performed with detailed neuropsychological testing, a portable device for gait analysis, and a comprehensive geriatric assessment for patients with MCI. Cognitive decline was defined as subjective cognitive impairment with an objective decline in the Mini-Mental State Examination (MMSE) ≥2 points at the one-year follow-up. Participants (n = 74) had a median age of 70 (interquartile range 60–79) years, and 45.9% of them were women. At the end of the study, 17.6% of the patients with MCI had a cognitive decline. Although no differences were observed between groups at the baseline cognitive study, patients with PD-MCI demonstrated more cognitive decline than patients with AD-MCI (28.6% vs. 7.7% p = 0.03). Patients with PD-MCI had more physical disa...
Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subj... more Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. Methods A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into 2 groups, MCR (n = 33) and MCI (n = 44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, “pure” MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, an...
Dementia with Lewy bodies (DLB) is a complex, multisymptom disorder. When making decisions regard... more Dementia with Lewy bodies (DLB) is a complex, multisymptom disorder. When making decisions regarding the treatment of DLB, the patient’s quality of life (QoL) should always be the main consideration. To our knowledge, this is the first review article focusing on the QoL in DLB patients. We searched the PubMed database using the keywords “quality of life” and “dementia with Lewy bodies.” Previously, no specific instrument had been developed for assessing the QoL in DLB patients. Patients with DLB have a decreased QoL compared to patients with Alzheimer’s disease, which is reportedly caused by several factors including level of independence in instrumental activities of daily living, whether the patient is living with the caregiver, apathy, delusion, and dysautonomia. The direct effect of visual hallucination, sleep, and movement disorders on the QoL in DLB patients has not been previously studied. The role of cognitive function on the QoL is still controversial. In a randomized contr...
Background: This study aimed to evaluate the effects of cueing on circular walking in patients wi... more Background: This study aimed to evaluate the effects of cueing on circular walking in patients with Parkinson's disease. Methods: Parkinson's disease patients in the "off" state were asked to walk on a designed route at their preferred speed. The experimental protocol was divided into two sessions. The first session was to be performed with no manual task. During the second session, the participant had to perform a manual task. Each session was measured for each of four conditions performed in the following order: without cues, with a visual cue, with an auditory cue, and with dual cues simultaneously. Temporospatial gait parameters and freezing of gait (FOG) events regarding the cueing-on and cueing-off situations were the main measures of gait performance. Results: Twelve patients with Parkinson's disease were recruited. Demographic and clinical characteristics of the participants were the following [median (interquartile range)]: age 63 years (57e67.3 years), Hoehn and Yahr stage 3.0 (3.0e3.25), and Unified Parkinson's Disease Rating Scale motor subsection off medication 22.5 (20.3e35.5). Walking turns of 180 in combination with a manual task were the most important triggers for FOG. On circular walking either with or without a manual task, visual or dual cues improved festinating gait patterns and increased step length. Visual or dual cues further improved the velocity of walking with a manual task. All types of cueing decreased FOG scores either with or without a manual task. Conclusion: Our study suggests that cueing improves festinating gait and decreases the incidence of FOG. Future studies with much larger sample sizes are warranted to support our findings.
Background: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neuro... more Background: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by deficits in executive function that frequently overlaps with parkinsonism and motor neuron disorders. Several genes have been identified to cause autosomal dominant forms of FTD, including the gene coding for the protein associated with microtubule tau (MAPT). While most reported pathogenic mutations in MAPT occur in exons 9-13, few families have been reported with mutations outside of this region. Herein, we report a first Taiwanese family having the exon 1 p.Arg5His mutation in MAPT with intrafamilial phenotype heterogeneity. Case presentation: A 63-year-old man presented with progressive non-fluent speech and impaired memory for 3 years. He then developed apraxia, myoclonus and parkinsonism feature at his right hand. Extensive neurologic and neurocognitive examination lead to a diagnosis of FTD mixed with corticobasal syndrome. Magnetic resonance imaging revealed asymmetric atrophy in the left frontal and temporal lobes and single-photon emission computed tomography indicated decreased metabolism in the same areas as well as the left basal ganglia. The patient's mother had been diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 60 and was deceased 10 years later due to respiratory failure. The patient's younger sister had persistent depressive disorder in her early forties and did not have any prominent cognitive or motor dysfunctions. We performed genetic analysis applying a targeted next generation sequencing (NGS) panel covering MAPT, GRN, VCP, FUS, CHMP2B, and TARDBP on the proband, followed by Sanger sequencing of candidate genes in eight family members. Hexanucleotide repeat expansion of C9Orf72 was determined by repeat-primed PCR. We identified a missense mutation in exon 1 of MAPT gene, c. 14G > A (p.R5H), which was previously reported in only two Japanese patients in a literature review. This substitution co-segregated with the disease phenotypes in the family. Conclusions: This is the first report of the occurrence of the MAPT p.R5H mutation in the Taiwanese population. Our findings extend the current knowledge of phenotypic heterogeneity among family members carrying the MAPT p.R5H mutation.
Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and n... more Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and non-cartilaginous structures. Neurological involvement is rarer but results in profound disability. Early identification and treatment of underlying RP may promote neurological recovery. We illustrated a 53-year-old man diagnosed with dementia. Neuroimaging and cerebrospinal fluid studies disclosed meningoencephalitis. "Prominent ear sign" was evident on diffusion-weight magnetic resonance imaging. After glucocortisone administration, the improvement of clinical manifestations was closely correlated subsequent neuroimaging findings. The importance of better understanding of this disease in terms of the prevention of further tissue damage in patients with RP cannot be overemphasized.
Taiwanese Journal of Obstetrics and Gynecology, 2010
Illnesses associated with stroke during pregnancy include hypertension, diabetes, heart disease, ... more Illnesses associated with stroke during pregnancy include hypertension, diabetes, heart disease, smoking, and thrombophilia. Multiparity, increased gestational age,
The goal of this study was to assess the prevalence and clinical correlates of restless legs synd... more The goal of this study was to assess the prevalence and clinical correlates of restless legs syndrome (RLS) among pregnant Taiwanese women. We enrolled 461 pregnant women (18-45 years) admitted at Mackay Memorial Hospital for delivery from September 2010 to May 2011. The face-to-face questionnaire used to gather data included assessment of RLS diagnostic criteria, and questions related to RLS. The overall prevalence rate of RLS among the study participants was 10.4%; 2.8% were categorized as having chronic RLS. Participants without RLS reported higher folate and iron supplement consumption than those with RLS. Multivariate analysis revealed significant associations of RLS with anemia and peptic ulcer disease. Participants with transient RLS during pregnancy reported more regular coffee consumption before pregnancy, and better sleep latency, duration, and efficiency, than those with chronic RLS. Overall, 81.2% of RLS sufferers reported sleep disturbances. Our study revealed highly prevalent but poorly recognized RLS among Taiwanese pregnant women. The identification of predictors such as medical comorbidities, and protectors such as folate and iron supplements, is warranted for obstetric RLS. In most cases, symptoms began during the second or third trimester and resolved within a week after delivery. Restricted coffee consumption before pregnancy is encouraged, but further evidence is needed to support this recommendation.
The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeds the formation of senile p... more The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeds the formation of senile plaques and contributes to synaptic and memory deficits in Alzheimer's disease (AD). The mechanism of mediating microglial oAβ clearance remains unclear and thought to occur via scavenger receptors (SRs) in microglia. SRs respond to their ligands in a subtype-specific manner. Therefore, we sought to identify the specific subtypes of SRs that mediate oAβ internalization and proteases that degrade oAβ species in naïve primary microglia. The component of oAβ species were characterized by western blot analysis, analytical ultracentrifugation analysis, and atomic force microscopy. The oAβ species remained soluble in the medium and microglial lysates during incubation at 37°C. SR-A, but not CD36, mediated oAβ internalization in microglia as suggested by the use of subtype-specific neutralizing antibodies and small interfering RNAs (siRNAs). Immunoprecipitation analysis showed that oAβ interacted with SR-A on the plasma membrane. After internalization, over 40% of oAβ vesicles were trafficked toward lysosomes and degraded by cysteine proteases, including cathepsin B. The inhibitors of proteasome, neprilysin, matrix metalloproteinases, and insulin degrading enzyme failed to protect internalized oAβ from degradation. Our study suggests that SR-A and lysosomal cathepsin B are critical in microglial oAβ clearance, providing insight into how microglia are involved in the clearance of oAβ and their roles in the early stages of AD.
Dementia in the elderly is the most common neurodegenerative disease and places a huge burden on ... more Dementia in the elderly is the most common neurodegenerative disease and places a huge burden on public health. Sporadic CreutzfeldteJacob disease (sCJD) is sometimes diagnosed in people with dementia; it develops in a rapid and progressive manner and has a short survival duration. The critical issue for sCJD is its transmissible nature. Besides rapid and progressive dementia, two out of four motor symptoms are assessed for a definitive diagnosis, including myoclonus, cerebellar problems, extrapyramidal/pyramidal features, and akinetic mutism. Here we report on a 77-year-old woman with initially pure dementia. Sequential neuroimaging revealed progressive isolated cortical effects over a period of 3 years. Basal ganglia involvement on neuroimaging and generalized periodic sharp wave complexes on electroencephalogram were delayed until the onset of reflex myoclonic jerks occurred 3 years after the onset of dementia. The patient survives, with an unusually long duration for sCJD. According to the clinical and laboratory features observed in this case, awareness of pure dementia with delayed onset of characteristic electroencephalogram features and isolated cortical effects on neuroimaging may predict unusually long survival in sCJD.
Restless legs syndrome is a sleep and movement disorder that affects 5-15% of the general populat... more Restless legs syndrome is a sleep and movement disorder that affects 5-15% of the general population, with an increased prevalence among the elderly population. It not only affects quality of life but also increases risk of mortality among older adults. The diagnosis is based on clinical symptoms of the patient by four minimal essential criteria. Restless legs syndrome can be divided into primary or secondary causes. Examination should be performed to rule out potentially treatable illnesses, such as iron deficiency, renal failure or peripheral neuropathy, especially among elderly patients. The initial approach to restless legs syndrome should be nonpharmacologic management, such as good sleep hygiene, regular exercise, cognitive behavioral therapy and avoidance of certain aggravating drugs. An algorithm based on scientific evidence and expert opinion was developed for guidance of treatment. Combination or change of medication can be applied to resistant or difficult cases. Since elderly patients are prone to treatment-related side effects, the best strategy is to start medication cautiously and at the lowest recommended dosage. [
Depression has a negative impact on activities of daily living, cognitive performance, and qualit... more Depression has a negative impact on activities of daily living, cognitive performance, and quality of life. Despite the high prevalence of depressive symptoms in Parkinson disease (PD), this important clinical feature is underrecognized by physicians. Effective diagnosis, assessment and treatment of depression are, therefore, important aspects of PD management. In this article, we review the literature concerning depression associated with PD, paying specific attention to clinical presentation, diagnosis, etiology, and the principles of management and treatment. The efficacy and safety of antidepressants must rely on empiric assessments of known risks and putative benefits to guide treatment decisions. [
Gait disorder, a major cause of morbidity in the elderly population, is one of the cardinal featu... more Gait disorder, a major cause of morbidity in the elderly population, is one of the cardinal features of Parkinson's disease. Owing to the characteristics of these gaits varying widely from festination to freezing of gait, analysis can be hardly identified in the clinical setting. Instrumented gait analysis has been widely used in a traditional gait laboratory. Recently, wireless monitoring systems have become highly informative by allowing long-term data collection in a variety of environments outside the labs. The quantitative analysis of gait patterns is probably the first step to a successful management of an individual patient. The presence of abnormal gait usually indicates advanced stages of disease and is often associated with cognitive impairment, falls, and injuries. Besides pharmacological and surgical treatments, parkinsonian gait can benefit from a variety of interventions. Assistive devices prevent patients from falls, and cueing strategies help them decrease episodes of freezing. Therefore, a multidisciplinary team approach to the optimal management is essential for an elderly patient with Parkinson's disease.
Ischemic stroke classification is critical in conducting basic research and clinical practice. A ... more Ischemic stroke classification is critical in conducting basic research and clinical practice. A precise analysis of stroke subtypes requires the integration of clinical features, findings from diagnostic tests, and knowledge about potential etiologic factors by competent diagnostic investigators. We performed a literature review of the published stroke classification systems and examined each for its benefits and limitations in the evaluation of the stroke etiology. Two major approaches to etiologic classifications of ischemic stroke are currently being used: the causative and phenotypic subtyping. The most widely used causative system is the Trial of Org 10172 in acute stroke treatment (TOAST) classification. With the advances in modern diagnostic technology, new stroke subclassification systems, such as the causative classification system (CCS) and Chinese ischemic stroke subclassification (CISS) system, have been developed to enhance the accuracy of TOAST. The AS -CO (Atherosclerosis, Smallvessel disease, Cardiac source, Other cause) phenotypic classification system makes efforts to identify the most likely etiology but not neglecting the possibility of other potential multiple causes. We conclude that the ideal stroke classification system needs to be valid, easy to use, evidence-based, and incorporate new information as it emerges.
Journal of Stroke and Cerebrovascular Diseases, 2018
Background: This study intended to investigate whether etiological stroke subtypes and their corr... more Background: This study intended to investigate whether etiological stroke subtypes and their corresponding major risk factors have differential effects on outcomes between genders. Patients and Methods: We enrolled 403 consecutive patients with first-ever acute ischemic stroke (170 women, 233 men), from a referral hospital in Taiwan over a 2-year period. Gender differences in demographics, vascular risk factors, access to health care, etiological stroke subtypes, stroke severity, and outcomes were examined. The primary outcome variable of the study was any unfavorable outcome due to acute ischemic stroke, defined as a modified Rankin Scale score of 3 or higher at 90 days after stroke. Multivariable logistic regression models were used to identify predictors of poor outcomes. Results: There were no gender disparities in baseline severity, stroke subtypes, access to health care, and medical comorbidities. Although women had poorer outcomes, female gender was not a predictor of unfavorable outcomes. Important predictors included age of 75years or older (odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.46-4.90), National Institutes of Health Stroke Scale greater than or equal to 8 (OR = 8.38; 95% CI, 4.61-15.2), lack of cohabitation (OR = 2.13; 95% CI, 1.26-3.61), subtypes of cardioembolism (OR = 2.76; 95% CI, 1.29-5.93), and largeartery atherosclerosis (OR = 2.93; 95% CI, 1.47-5.85). In subgroup analyses, the genderspecific independent predictors were cardioembolism (OR = 7.42; 95% CI, 2.21-24.9) or atrial fibrillation (OR = 3.57; 95% CI, 1.31-9.74) in women, and largeartery atherosclerosis (OR = 3.35; 95% CI, 1.30-8.64) or symptomatic large-artery stenosis (OR = 3.42; 95% CI, 1.69-6.96) in men. The differential effects of these predictors according to gender were revealed by interaction tests. Conclusion: Atrial fibrillation and symptomatic large-artery stenosis are predictors of poor stroke outcomes in women and men, respectively.
Uploads
Papers by Pei-Hao Chen