Electrical Abnormalities in Dopaminergic Neurons of the Substantia Nigra in Mice With an Aromatic L-Amino Acid Decarboxylase Deficiency

Aromatic L-acid decarboxylase (AADC) deficiency causes severe motor disturbances in affected children. A putamen-targeted gene therapy improves the motor function of patients. The present study investigated the electrical properties of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) of mice with an AADC deficiency (DdcKI). The basal firing of DA neurons, which determines DA release in the putamen, was abnormal in the DdcKI mice, including a low frequency and irregular firing pattern, because of a decrease in the after-hyperpolarization (AHP) amplitude of action potentials (APs). The frequency of spontaneous excitatory postsynaptic currents (sEPSCs) increased and that of spontaneous inhibitory PSCs (sIPSCs) decreased in the SNc DA neurons from the DdcKI mice, suggesting an elevation in glutamatergic excitatory stimuli and a reduction in GABAergic inhibitory stimuli, respectively. Altered expression patterns of genes encoding receptors and channels were also observed in the DdcKI mice. Administration of a widespread neuron-specific gene therapy to the brains of the DdcKI mice partially corrected these electric abnormalities. The overexcitability of SNc DA neurons in the presence of generalized dopamine deficiency likely underlies the occurrence of motor disturbances

Effect of Acupressure and Trigger Points in Treating Headache: A Randomized Controlled Trial

Abstract: The efficacy of acupressure in relieving pain has been documented; however, its effectiveness for chronic headache compared to the muscle relaxant medication has not yet been elucidated. To address this, a randomized, controlled clinical trial was conducted in a medical center in Southern Taiwan in 2003. Twenty-eight patients suffering chronic headache were randomly assigned to the acupressure group (n = 14) or the muscle relaxant medication group (n = 14). Outcome measures regarding self-appraised pain scores (measured on a visual analogue scale; VAS) and ratings of how headaches affected life quality were recorded at baseline, 1 month after treatment, and at a 6-month follow-up. Pain areas were recorded in order to establish trigger points. Results showed that mean scores on the VAS at post-treatment assessment were significantly lower in the acupressure group (32.9 ± 26.0) than in the muscle relaxant medication group (55.7 ± 28.7) (p = 0.047). The superiority of acupressure over muscle relaxant medication remained at 6-month follow-up assessments (p = 0.002). The quality of life ratings related to headache showed similar differences between the two groups in the post treatment and at six-month assessments. Trigger points BL2, GV20, GB20, TH21, and GB5 were used most commonly for etiological assessment. In conclusion, our study suggests that 1 month of acupressure treatment is more effective in reducing chronic headache than 1 month of muscle relaxant treatment, and that the effect remains 6 months after treatment. Trigger points help demonstrate the treatment technique recommended if a larger-scale study is conducted in the future

Molecular and clinical analyses of 84 patients with tuberous sclerosis complex

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of multiple hamartomas in many internal organs. Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the development of TSC. More than two-thirds of TSC patients are sporadic cases, and a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have been reported. METHODS: Mutational analysis of TSC1 and TSC2 genes was performed in 84 Taiwanese TSC families using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. RESULTS: Mutations were identified in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2 familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty-one of the 64 mutations found have not been described previously. The phenotype association is consistent with findings from other large studies, showing that disease resulting from mutations to TSC1 is less severe than disease due to TSC2 mutation. CONCLUSION: This study provides a representative picture of the distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained TSC cases in the Taiwanese population. Although nearly half of the mutations identified were novel, the kinds and distribution of mutation were not different in this population compared to that seen in larger European and American studies

The impact of active community-based survey on dementia detection ratio in Taiwan: A cohort study with historical control

BackgroundAlthough early dementia detection is crucial to optimize the treatment outcomes and the management of associated symptoms, the published literature is scarce regarding the effectiveness of active screening protocols in enhancing dementia awareness and increasing the rate of early detection. The present study compared the detection ratio of an active community-based survey for dementia detection with the detection ratio of passive screening during routine clinical practice. Data for passive screening were obtained from the National Health Insurance (NHI) system, which was prospectively collected during the period from 2000 to 2003.DesignA population-based cohort study with historical control.SettingTaiwan.ParticipantsA total of 183 participants aged 65 years or older were involved in a community-based survey. Data from 1,921,308 subjects aged 65 years or older were retrieved from the NHI system.MeasurementsAn adjusted detection ratio, defined as a ratio of dementia prevalence to incidence was used.ResultsThe results showed that the dementia prevalence during the 2000–2003 period was 2.91% in the elderly population, compared with a prevalence of 6.59% when the active survey was conducted. The incidence of dementia in the active survey cohort was 1.83%. Overall, the dementia detection ratio was higher using active surveys [4.23, 95% confidence interval (CI): 2.68–6.69] than using passive detection (1.45, 95% CI: 1.43–1.47) for those aged 65–79 years. Similar findings were observed for those aged 80 years and older.ConclusionThe implementation of an active community-based survey led to a 3-fold increase in the detection rate of early dementia detection compared to passive screening during routine practice

Lovastatin Modulates Glycogen Synthase Kinase-3β Pathway and Inhibits Mossy Fiber Sprouting after Pilocarpine-Induced Status Epilepticus

This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis

Health Related Quality of Life in Adult Patients with Epilepsy Compared with a General Reference Population in Taiwan

To compare the health-related quality of life (HRQL) for patients with epilepsy and health subjects, we collected the clinical and demographic data and information on health states by using the Taiwan version of World Health Organization quality of life (WHOQOL)-BREF questionnaire in 296 patients (aged 19-73 years) with confirmed active epilepsy visiting the clinic of National Taiwan University Hospital, and 296 age-, gender-, municipal- and education- matched Taiwanese healthy subjects sampled from a national health interview survey. Multiple regression analyses with stepwise selection strategy were conducted to study risk factors for impairment of HRQL. Patients with epilepsy have poorer HRQL than the healthy population in physical, psychological and social domains but not in environment domain (p<0.005). Patients with less than 4 attacks during the previous 1 month had a better score in the availability and quality of health and social care in environment domain than healthy subjects (p<0. 05). After controlling other determinants, seizure frequency, and comobid with other diseases are the important factors in predicting HRQL for epilepsy patients. Patients with employment and married had a significantly better HRQL. Effective control of seizure frequency and thoughtful promotion of positive attitudes in community are essential to improve the HRQL of epilepsy patients

Attenuation of Paraquat-Induced Dopaminergic Toxicity on the Substantia Nigra by (-)-Deprenyl in Vivo

(-)-Deprenyl (DEP) had been shown to slow of progression of Parkinson's disease (PD). The present study sought to determine whether DEP would attenuate the nigrostriatal system damage induced by intranigral administration of the herbicide paraquat (PQ) as a model of parkinsonism in vivo. Neurochemical and behavioral observations of Wistar rats were the focus of our study. In the neurochemical observation, the PQ injected in the rats caused dose- dependent depletion of dopamine (DA) in the ipsilateral striata. The coadministration of DEP with PQ partially increased the striatal DA level. The prediction of the striatal DA levels was calculated by regression coefficients obtained from multiple linear regression (r(2) = 0.82): DA level (% of control) = 103.34 - 9.58 PQ (nmol ) + 0.79 DEP ( nmol). It was demonstrated that the high dose of 20 nmol DEP could significant attenuate the PQ (5 nmol)-elicited dopaminergic toxicity (p < 0.05). In the behavioral observation, the intranigral injection of PQ into the rats caused a rotation behavior contralateral to the lesioned side in response to apomorphine administration (0.5 mg/kg, sc ). This apomorphine-induced rotational behavior could also be attenuated significantly by coadministration of DEP (20 nmol) and PQ (5 nmol) compared with PQ-treated (5 nmol) animals (p < 0.05). The above observations indicate that DEP could provide a protective effect on the moderate injury elicited by PQ toxicity of the nigro-strital dopaminergic system. DEP might be a useful therapeutic agent in treating patients with early-stage PD. (C) 2001 Academic Press