-
Yah-Huei Wu-Chou,
Ying-Ting Chen,
Tu-Hsueh Yeh,
Hsiu-Chen Chang,
Yi-Hsin Weng,
Szu-Chia Lai,
Chia-Ling Huang,
Rou-Shayn Chen,
Ying-Zu Huang,
Chiung-Chu Chen,
June Hung, Wen-Li Chuang,
Wey-Yil Lin,
Chien-Hsiun Chen,
Chin-Song Lu
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Parkinsonism & Related Disorders 11/2012; · 3.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Daily sessions of therapeutic transcranial brain stimulation are thought to prolong or amplify the effect of a single intervention. Here we show in patients with focal hand dystonia that additional, new effects build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. In a sham-controlled study, real or sham continuous theta burst stimulation (cTBS) was given once daily for five consecutive days to dorsolateral premotor cortex (PMd). Five days of real, but not sham, premotor cTBS improved intracortical inhibition in primary motor cortex (M1) to a similar extent on day 1 and day 5. However 5 days of cTBS were required to restore the abnormal PMd-M1 interactions observed on day 1. Similarly, excessive M1 plasticity seen at baseline was also significantly reduced by five days of real premotor cTBS. There was only a marginal benefit on writing. The results show that additional, new effects, at sites distant from the point of stimulation, build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. The results indicate that it may take many days of therapeutic intervention to rebalance activity in a complex network.
PLoS ONE 01/2012; 7(10):e47574. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that levodopa-induced dyskinesias might result from abnormal control of synaptic plasticity. In the present study, we aimed to explore control of plasticity in patients with Parkinson's disease with and without levodopa-induced dyskinesias by taking advantage of a newly developed protocol that tests depotentiation of pre-existing long-term potentiation-like synaptic facilitation. Long-term potentiation-like plasticity and its reversibility were studied in the motor cortex of 10 healthy subjects, 10 patients with Parkinson's disease and levodopa-induced dyskinesias, who took half of the regular dose of levodopa and 10 patients with Parkinson's disease without levodopa-induced dyskinesias, who took either half or the full dose of levodopa. Patients with Parkinson's disease without levodopa-induced dyskinesias had normal long-term potentiation- and depotentiation-like effects when they took their full dose of levodopa, but there was no long-term potentiation-like effect when they were on half dose of levodopa. In contrast, patients with levodopa-induced dyskinesias could be successfully potentiated when they were on half their usual dose of levodopa; however, they were unresponsive to the depotentiation protocol. The results suggest that depotentiation is abnormal in the motor cortex of patients with Parkinson's disease with levodopa-induced dyskinesias and that their long-term potentiation-like plasticity is more readily affected by administration of levodopa than their clinical symptoms.
Brain 08/2011; 134(Pt 8):2312-20. · 9.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Theta burst stimulation, a form of repetitive transcranial magnetic stimulation, can induce lasting changes in corticospinal excitability that are thought to involve long-term potentiation/depression (LTD/LTD)-like effects on cortical synapses. The pattern of delivery of TBS is crucial in determining the direction of change in synaptic efficiency. Previously we explained this by postulating (1) that a single burst of stimulation induces a mixture of excitatory and inhibitory effects and (2) those effects may cascade to produce long-lasting effects. Here we formalise those ideas into a simple mathematical model.
The model is based on a simplified description of the glutamatergic synapse in which post-synaptic Ca(2+) entry initiates processes leading to different amount of potentiation and depression of synaptic transmission. The final effect on the synapse results from summation of the two effects.
The model using these assumptions can fit reported data. Metaplastic effects of voluntary contraction on the response to TBS can be incorporated by changing time constants in the model.
The pattern-dependent after-effects and interactions with voluntary contraction can be successfully modelled by using reasonable assumptions about known cellular mechanisms of plasticity.
The model could provide insight into development of new plasticity induction protocols using TMS.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 05/2011; 122(5):1011-8. · 3.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute intermittent porphyria (AIP) is an inherited disorder of heme biosynthesis, the clinical manifestations of which are incompletely understood. In this report, we describe 12 cases of AIP, focusing on the neurological manifestations.
Twelve patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogen deaminase (PBGD) activity, and molecular genetics. Central and peripheral nervous system manifestations were noted, and electrophysiological and radiological studies performed. Potential precipitating factors were recorded.
Eleven PBGD gene mutations were identified in 12 patients. Nine patients experienced neurological symptoms involving the central nervous system (consciousness disturbance, n = 8; convulsion/seizure, n = 4; behavior change, n = 1), while 7 patients experienced peripheral neuropathies (motor paresis, n = 7; impairment of bulbar or respiratory function, n = 4). The electrophysiological and electroencephalographic findings were consistent with the neurological symptoms of AIP. Urinary PBG and δ-aminolevulinic acid levels were elevated in all patients. PBGD enzyme activity levels were below normal in all patients. Eight patients had documented exposure to porphyrogenic agents.
Our detailed description of a relatively large number of cases of AIP may help clinicians to recognize this often difficult-to-diagnose disorder.
European Neurology 01/2011; 66(5):247-52. · 1.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A number of experiments in animals have shown that successful induction of plasticity can be abolished if an individually ineffective intervention is given shortly afterwards. Such effects are termed depotentiation/de-depression. These effects contrast with metaplasticity/homeostatic plasticity in which pretreatment of the system with one protocol modulates the response to a second plasticity-inducing protocol. Homeostatic plasticity maintains the balance of plasticity in the nervous system at a stable level whereas depotentiation/de-depression abolishes synaptic plasticity that has just occurred in order to prevent ongoing learning. In the present study, we developed novel protocols to explore the reversal of LTP- and LTD-like effects in healthy conscious humans based on the recently developed theta burst form of repetitive transcranial magnetic stimulation (TBS). The potentiation effect induced by intermittent TBS (iTBS) was completely erased by a short form of continuous TBS (cTBS150) given 1 min after iTBS, whereas the depressive effect of continuous TBS (cTBS) was successfully abolished by a short form of iTBS (iTBS150). The reversal was specific to the nature of the second protocol and was time dependent since it was less effective when the intervention was given 10 min after induction of plasticity. All these features are compatible with those of depotentiation and de-depression demonstrated in animal studies. The development of the present protocols would be helpful to study the physiology of the reversal of plasticity and learning and to probe the abnormal depotentiation/de-depression shown in animal models of neurological diseases (e.g. Parkinson's disease with dyskinesia, dystonia and Huntingon's disease).
The Journal of Physiology 10/2010; 588(Pt 19):3683-93. · 4.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To identify clinical manifestations and neuropsychological effects of Alzheimer disease (AD) in apolipoprotein (ApoE) e4 carriers and to investigate the relationships between ApoE HhaI polymorphism and apolipoprotein C1 (APOC1) HpaI polymorphism in Taiwanese patients with AD.
A total of 127 patients with AD and 191 elderly individuals were screened for ApoE and APOC1 polymorphism. All patients underwent neuropsychological testing, including a Mini-Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and/or the Visual Association Memory Test (VAMT) with Cognitive Abilities Screening Instrument.
The frequencies of the e4 and A alleles were significantly higher in the AD group. In the patients with AD, the e4 and A allele effects on those with an age-of-onset of 60 to 79 years were stronger than those with an age-of-onset of 80 years or higher. Visual Association Memory Test performance was significantly worse in e4-allele carriers but not in A-allele carriers, in the early AD, particularly in those affected with AD for less than 2 years. Although there was no statistically significant difference in genotypic frequency between patients and controls, the 2 genes were linked. In addition, the presence of the AA genotype concomitant with the e4 allele may be better associated with AD diagnosis than either factor alone.
We conclude that the e4 allele affects neuropsychological performance and illness morbidity. Concomitantly, ApoE e4 and APOC1 A alleles have a better association with AD than ApoE e4 alone. In addition, APOC1 may partially contribute to the pathogenesis of AD, but the nature of its relationship with e4 requires further investigation.
Journal of Geriatric Psychiatry and Neurology 03/2010; 23(1):42-8. · 3.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to assess peripheral nerve involvement and DNA mutation of the neurofibromatosis type 2 (NF2) gene (NF2) in a Taiwanese family with classic NF2. Eleven members (six symptomatic and five asymptomatic) of a family carrying NF2 underwent clinical examination, neuroimaging, and electrophysiological analysis. Mutation and linkage analyses were conducted on DNA samples prepared from peripheral blood (all individuals), a sural nerve biopsy specimen (one symptomatic member), and a tumor specimen (another symptomatic member). Six of the 11 members were diagnosed with classic NF2. DNA sequencing of the tumor specimen demonstrated a frameshift mutation with 756delC on exon 8 of NF2. Three affected subjects showed clinical variability of the neuropathic disorders. Electrophysiological studies demonstrated variation in the disease pattern and severity of peripheral nerve involvement in five affected subjects. The morphometric assessment of the sural nerve biopsy specimen showed a marked reduction in both large myelinated and unmyelinated fibre density and increased density of non-myelinating Schwann cell nuclei. Apart from numerous pathological nuclei of isolated Schwann cells, multiple profiles of non-myelinating Schwann cell subunits were apparent in the endoneurium. Schwann cell proliferation in association with first-hit mutation of the merlin gene might be responsible for the NF2-associated neuropathy. Sural nerve biopsy showed a progressive neuropathy in the disease. Further, we suggest nonmyelinating Schwann cells are involved in NF2 neuropathy.
Neuropathology 01/2010; 30(5):515 - 523. · 2.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To understand the effect of continuous theta burst stimulation (cTBS) given to the premotor area, we studied the circuits within the primary motor cortex and spinal cord after cTBS over the dorsal premotor area (PMd).
Three sets of parameters, including corticospinal excitability, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) and forearm reciprocal inhibition (RI) were tested.
Paralleling the effects of cTBS applied directly to the primary motor cortex, cTBS over the left PMd suppressed corticospinal excitability as measured by the change in the size of MEPs evoked by single pulse TMS over primary motor cortex. Premotor cTBS appeared to have a longer lasting, but no more powerful effect on corticospinal excitability than motor cTBS, however, unlike motor cTBS it had no effect on SICI or ICF. Finally, although premotor cTBS had no effect on spinal H-reflexes, it did reduce the third phase of RI between forearm extensor and flexor muscles.
Premotor cTBS is a quick and useful way of modulating excitability in cortical and possibly subcortical motor circuits.
Premotor cTBS can be used as an alternative to regular rTMS to evaluate cortical function, motor behaviours and the response to disease therapy.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 03/2009; 120(4):796-801. · 3.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine neurophysiological evidence of functional involvement of the brainstem and spinal cord and motor cortical excitability in sialidosis type I, a rare inherited neurodegenerative disorder caused by mutations in the NEU1 gene.
We investigated particular pathways in the brainstem, spinal cord and motor cortex in 12 genetically proven cases of sialidosis type I by assessing blink reflex recovery cycle (BR), spinal reciprocal inhibition (RI), input-output curves (I/O), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and silent period (SP).
The BR and RI were normal. The slope of I/O was significantly increased, and SICI and the duration of SP were reduced in sialidosis patients.
Despite reports of pathology involving brainstem and anterior horn neurones, there were no obvious abnormalities in spinal and brainstem reflexes in the present patients, suggesting that the major clinical effects may be caused by changes at a level above the brainstem.
For the first time, the integrity of certain brainstem and spinal cord reflexes in addition to motor cortical facilitatory and inhibitory circuits has been assessed in genetically proven type I sialidosis. This provides new data to aid in understanding of the pathophysiology of motor system dysfunction in this condition.
Clinical Neurophysiology 06/2008; 119(5):1042-50. · 3.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report a patient with acute intermittent porphyria who presented with progressive motor neuropathy, particularly in the upper limbs. The electrophysiological studies showed an asymmetric motor neuropathy with a prominent involvement of both the radial and left peroneal nerves. During the 1-year follow-up period, 6 courses of hematin infusion, with 150 mg daily for 4 consecutive days every month, were administrated. The motor neuropathy showed a steady and gradual improvement following the hematin treatment. Molecular analysis of the porphobilinogen deaminase gene revealed a short segment deletion (1008-1019delCAGCCTGGCCAA) resulting in a truncated protein. The findings suggest that early hematin treatment is temporally associated with interval improvement of the patient's porphyric motor neuropathy.
Journal of the Neurological Sciences 10/2007; 260(1-2):231-5. · 2.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To understand cerebral blood circulation after long-term exposure to carbon disulfide (CS2), four patients with encephalopathy and polyneuropathy, who had worked in a viscose rayon plant, were studied. Clinical and laboratory examinations, including brain magnetic resonance images (MRI), computed tomography (CT), CT perfusion, and CT angiography, were carried out. Brain CT and MRI disclosed mild cortical atrophy in all four patients, and multiple lesions in the subcortical white matter, and basal ganglia in three patients. Brain CT angiography and perfusion revealed a statistically significant decrease of cerebral blood flow (CBF) in the total brain parenchyma and basal ganglia, and a decrease of the cerebral blood volume (CBV) in the basal ganglia and a prolonged mean transit time (MTT) in the total brain parenchyma, and the territories of the internal carotid artery (ICA), basal ganglia and occipital lobe. In conclusion, the decrease of CBV and CBF, and the prolonged MTT in the total brain parenchyma, ICA, basal ganglia and occipital lobes, indicated a microangiopathy in patients with CS2 encephalopathy.
NeuroToxicology 04/2007; 28(2):387-93. · 3.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report 2 patients with sciatic neuropathy immediately after hemorrhoidectomy and free gracilis muscle transfer operations, respectively. We compare the nerve conduction study and electromyography of the 2 patients and discuss the possible pathogenesis. We emphasize that postoperative sciatic neuropathies may occur in an inappropriate position and a prolonged duration of operation. The nerve conduction study and electromyography are useful in evaluating the severity and prognosis. The best way to avoid this complication is to prevent an inappropriate position and a prolonged duration under proper anesthesia.
Journal of Clinical Neuromuscular Disease 02/2007; 8(3):116-121.
-
[show abstract]
[hide abstract]
ABSTRACT: We studied the results of the Visual Association Memory Test (VAMT) in differentiating Alzheimer's disease (AD) and vascular dementia (VaD). In addition, other basic neuropsychological tests, including the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) were also used. Generally, with the VAMT, AD patients had a worse performance than VaD patients. Particularly among patients with a CDR = 0.5, the AD patients had statistically significantly lower VAMT scores (score less than 3) (p = 0.026) compared to those of VaD patients. However, the VAMT could not predict clinical severity or disease progression. The VAMT, as revealed in this study, is a brief, simply administered, and less biased test, and may offer a diagnostic adjunct to differentiate AD from VaD especially in an early dementia state.
Acta neurologica Taiwanica 07/2006; 15(2):98-104.
