Min-yu Lan - Academia.edu (original) (raw)

Papers by Min-yu Lan

Frontiers in Neurology, Sep 30, 2022

Sung Y-F, Tu M-C and Chang Y-Y () Clinical and genetic characterization of a Taiwanese cohort wit... more Sung Y-F, Tu M-C and Chang Y-Y () Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.

Antioxidants

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s di... more Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease affecting more than 1% of the population over 65 years old. The etiology of the disease is unknown and there are only symptomatic managements available with no known disease-modifying treatment. Aging, genes, and environmental factors contribute to PD development and key players involved in the pathophysiology of the disease include oxidative stress, mitochondrial dysfunction, autophagic–lysosomal imbalance, and neuroinflammation. Recent epidemiology studies have shown that type-2 diabetes (T2DM) not only increased the risk for PD, but also is associated with PD clinical severity. A higher rate of insulin resistance has been reported in PD patients and is suggested to be a pathologic driver in this disease. Oral diabetic drugs including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors...

BMC Neurology

Background: Primary familial brain calcification (PFBC) is a rare inherited disease characterized... more Background: Primary familial brain calcification (PFBC) is a rare inherited disease characterized by multiple calcified foci in the brain parenchyma. MYORG is the first gene found to be associated with autosomal recessive PFBC. The precise pathogenic mechanism of neurodegeneration in PFBC remains unclear. The clinical phenotypes of PFBC are variable, and there is no clear correlation between clinical manifestations and radiological and pathological features of calcification. Case presentation: Two sisters in a Taiwanese family presented with young-onset Parkinsonism and multifocal dystonia. Their brain CTs showed multiple intracerebral calcifications. The genetic study detected two heterozygous novel variants, c.104 T > A (p.Met35Lys) and c.850 T > C (p.Cys284Arg) in the MYORG gene. In both patients, MR susceptibility weighted images revealed calcification of the deep medullary veins. Tc 99m ECD SPECT demonstrated a significant decrease of tracer uptake in the brain cortex and subcortical gray matter. Tc 99m TRODAT-1 SPECT revealed decreased tracer uptake in the bilateral striatum. Conclusion: Two novel MYORG variants were identified in Taiwanese family members presenting with PFBC. Abnormalities in the brain perfusion and dopamine transporter SPECTs suggest that cerebral ischemia due to extensive calcified vasculopathy, disruption of the basal ganglia-thalamo-cortical circuit, and nigrostriatal dopaminergic dysfunction are plausible pathogenic mechanisms of neurodegeneration in PFBC patients. Further investigation into the correlations between the pathogenicity-implicated imaging findings and the clinical phenotype are recommended.

International Journal of Environmental Research and Public Health

This study is intended to explore the associations between nutritional status and molecular bioma... more This study is intended to explore the associations between nutritional status and molecular biomarkers and the clinical severity of Parkinson’s disease (PD), as well as to examine the differences in related factors between PD patients with normal nutrition and those with at risk for malnutrition. A cross-sectional assessment of 82 consecutive outpatients with PD was conducted using the mini nutritional assessment (MNA), Unified Parkinson’s Disease Rating Scale (UPDRS), and the Hoehn and Yahr scale to determine the nutritional status, the clinical severity of PD, and the stage of the disease. Recordings of blood samples collected after 12 h of overnight fasting were also assessed in terms of serum levels of glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), hemoglobin (Hgb), folate, and vitamin B12. All participants were divided into normal nutrition and malnutrition risk groups via the MNA s...

PLOS ONE

Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mt... more Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.

BMC neurology, Jan 6, 2017

Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset au... more Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson's disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 3...

Journal of the neurological sciences, Jan 15, 2017

Oncotarget, 2014

In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neur... more In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memoryrelated activity.

Journal of the Formosan Medical Association

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating brain disease caused b... more Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating brain disease caused by JC virus (JCV). Genomic analysis of viral isolates in these cases often shows prototype-like JCV and its variants, which is a virulent strain compared to the latent archetype virions mostly found in the kidney. Here, we report a 57-year-old man who suffered from a subacute course of cognitive impairment and multiple neurologic deficits. Neuroimaging, pathology, and virology studies showed multifocal leukoencephalopathy and the presence of JCV deoxyribonucleic acid in the cerebrospinal fluid. The prototype type 1 (Mad-1) strain of JCV was identified on viral genotyping obtained from brain tissue. No immune deficits were found. He responded poorly to alpha-interferon and antiviral treatment. This case suggests that lack of immune deficiency cannot exclude the possibility of PML as a cause of subacute leukoencephalopathy. Accumulated data with respect to the disease course, pathologic fea...

Gaoxiong yi xue ke xue za zhi = The Kaohsiung journal of medical sciences, 1994

A sacral arachnoid cyst was found incidentally in a patient with ankylosing spondylitis. The clin... more A sacral arachnoid cyst was found incidentally in a patient with ankylosing spondylitis. The clinical manifestations were perithecal bony erosions and thecal sac displacement while no associated neurological deficit was detected. This peculiar situation is of special interest as cauda equina syndrome invariably presented in such clinical complex. The pathogenesis of the arachnoid cyst remains unclear. And surgical intervention is only indicated in patients with evidence of nerve root compression.

Journal of the Formosan Medical Association = Taiwan yi zhi, 1995

Although the correlation between fibromuscular dysplasia (FMD) and intracranial aneurysm is well ... more Although the correlation between fibromuscular dysplasia (FMD) and intracranial aneurysm is well established, the combination of FMD with a giant aneurysm is rare. This paper reports a patient with extracranial FMD associated with a giant intracavernous aneurysm compromising the trigeminal and abducens nerve. A review of the literature uncovered only four documented cases of FMD with concurrent giant intracranial aneurysms. The present case adds further weight to the argument for including FMD in the differential diagnosis list when confronted with a patient with a giant intracranial aneurysm. Absence of adequate collaterals in this patient eliminated ligation as a treatment strategy for the aneurysm.

Acta neurologica Taiwanica, 2006

To investigate the effect of botulinum toxin type A (BTX-A; Botox) in reducing saliva in patients... more To investigate the effect of botulinum toxin type A (BTX-A; Botox) in reducing saliva in patients with Parkinsonism. Fifteen patients with clinical diagnosis of idiopathic Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy were enrolled in this open clinical trial. A total of 40-unit dose of Botox was injected into the bilateral parotid and submandibular glands. Objective measuring of saliva production with dental rods, subjective Drooling Score, personal impression of clinical improvement, and the duration of response were used for the global assessment of sialorrhea after BTX-A treatment. All patients showed objective reduction in saliva production following BTX-A treatment and the mean production was reduced at a significant level. The severity of sialorrhea assessed by Drooling Score was 5.87 +/- 0.92 (range: 5-8) and 3.60 +/- 1.18 (range: 2-6) respectively (p<0.001) before and after BTX-A injection. The mean duration of BTX-A response extended for...

BMC neurology, Jan 25, 2014

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...

Journal of the Neurological Sciences, 2014

Vascular Parkinsonism (VP) is referred to as secondary Parkinsonian syndrome. It occurs with lacu... more Vascular Parkinsonism (VP) is referred to as secondary Parkinsonian syndrome. It occurs with lacunar state or sub-cortical white matter micro-angiopathy and is highly associated with vascular risk factors and leukoaraiosis, also known as cerebral white matter lesions (WML). This study aimed to assess the prevalence of different vascular risk factors and WML in patients with VP, and their impact on clinical features. Sixty-two consecutive VP patients (70.2 ± 9.2 years) were evaluated for clinical severity using the Unified Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Rating Scale (UPDRS). WML was assessed and scored on fluid-attenuated inversion recovery T2-weighted (FLAIR) magnetic resonance imaging (MRI). Cerebro-vascular risk factors, WML severity, and the UPDRS for clinical disability were analyzed statistically. There were no associations between WML score and age, sex, hypertension, diabetes, previous stroke, cardiac disease, cigarette smoking, or serum levels of cholesterol and triglyceride. The WML score positively correlated with UPDRS part I (p = 0.035) and part III (p = 0.041) scores. After adjustments for age, gender, stroke history, and use of levodopa, the WML score was associated with the UPDRS total (p = 0.020), part I (p = 0.012), part II (p = 0.039), and part III (p = 0.019) scores. The severity of WML is not associated with conventional vascular risk factors in VP patients but is significantly correlated with the UPDRS total and all sub-scores, which suggests that disruption of the cortico-sub-cortical circuits may lead to impaired mentation, behavior and mood, activities of daily living, and motor performance in these patients.

Journal of Neurology, Neurosurgery & Psychiatry, 1999

Cerebral metabolism during vegetative state and after recovery to consciousness

Internal Medicine, 2008

Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinoly... more Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time.

European Journal of Neurology, 2014

Spastic paraplegia type 5 (SPG5) is an autosomal recessive (AR) hereditary spastic paraplegia (HS... more Spastic paraplegia type 5 (SPG5) is an autosomal recessive (AR) hereditary spastic paraplegia (HSP) associated with pure or complicated phenotypes. This study aimed to screen SPG5 in Taiwanese HSP patients. Sequencing of the SPG5 gene, CYP7B1, was performed in a cohort of 25 ethnic Han Taiwanese patients with AR or sporadic HSP. Clinical information and magnetic resonance imaging (MRI) were analyzed in confirmed SPG5 patients. One (33%) AR kindred and four (18%) sporadic cases had CYP7B1 mutations. All of the SPG5 cases carried the mutation c.334 C&amp;amp;amp;gt;T (R112X). Haplotype analysis suggested a &amp;amp;amp;#39;founder effect&amp;amp;amp;#39; in ethnic Hans for this mutation. The phenotype was either pure or complicated by cerebellar ataxia. For the primary HSP phenotype, there were profound dorsal column sensory deficits in all patients. Spine MRI showed thoraco-lumbar cord atrophy in some patients. Spastic paraplegia type 5 is a common cause of AR and sporadic HSPs that has a higher frequency in Taiwanese than in other ethnic groups. It is associated with a CYP7B1 founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients.

Clinical Neurology and Neurosurgery, 2008

To investigate association between cerebral microbleeds (CMB) and prior intracerebral hemorrhage ... more To investigate association between cerebral microbleeds (CMB) and prior intracerebral hemorrhage (ICH) on MRI and topographic correlation of the two types of lesions. Two hundred and sixty consecutive patients (67.0+/-11.1 years) with ischemic stroke were included. CMB and prior ICH were assessed on T2-gradient-echo MRI. The presence and number of CMB as predictors for prior ICH were examined. Topographic correlations between CMB and ICH lesions in patients with prior ICH in the infratentorial, basal ganglionic/thalamic and cortico-subcortical regions were tested. CMB were observed in 113 (43.5%) patients and a total of 50 prior primary ICH lesions were observed in 39 (15.0%) patients. Among the ICH lesions, 39 (78%) were asymptomatic. Presence of CMB (odds ratio 2.53, p=0.015) and number of CMB (odds ratio 1.11, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) were independent determinants for prior ICH. Topographic correlation between CMB and ICH was significant in the basal ganglionic/thalamic region (p=0.017), but not in the infratentorial (p=0.548) or cortico-subcortical regions (p=0.389). CMB were associated with prior ICH on MRI of patients with ischemic stroke. CMB in the basal ganglion or thalamus was associated with prior ICH in the same region.