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Inflammation theory has been consolidated by accumulating evidence, and many studies have suggested that the peripheral cytokine levels could be biomarkers for disease status and treatment outcome in major depressive disorder (MDD). Theta burst stimulation (TBS), a new form of repetitive transcranial magnetic stimulation (TMS) for MDD, has been demonstrated to improve depression via modulating dysfunctional neural network or hypothalamic–pituitary–adrenal axis hyperactivities in MDD. However, there is lack of exploratory studies investigating its effect on serum inflammatory cytokines. Here, we aimed to investigate the antidepressant efficacy of bilateral TBS monotherapy and its effects on the serum cytokine levels in MDD. We conducted a double-blind, randomized, sham-controlled trial, with 53 MDD patients who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode assigned randomly to one of two groups: bilateral TBS monotherapy (n = 27) or sham stimulation (n = 26). The TBS treatment period was 22 days. Blood samples from 31 study subjects were obtained for analyses. The bilateral TBS group exhibited significantly greater decreases in depression scores than the sham group at week 4 (56.5% vs. 33.1%; p0.001 [effect size (Cohen ’ s d) = 1.00]) and during the 20-week follow-up periods. Significantly more responders were also found at week 4 (70.3% vs. 23.1%, p = 0.001) and during the 20-week follow-up periods. However, we did not detect any significant effects of TBS on the cytokine panels or any correlations between improvement in depressive symptoms and changes in serum inflammatory markers. Our findings provided the first evidence that the antidepressant efficacy of bilateral TBS monotherapy might not work via immune-modulating mechanisms.

Hyperuricemia has been identified as an independent risk factor for coronary artery disease (CAD), with a dose-response association. In this study, we explored the causal association between gout and antigout medication and the risk of incidental CAD. We sampled data from the National Health Insurance Research Database and recruited 37,091 patients as the gout cohort, and 37,091 controls. Our primary endpoint was the diagnosis of CAD during follow-up. The overall study population was followed up until CAD diagnosis, withdrawal from the National Health Insurance program, or the end of the study. Cox proportional hazards regression models were used to examine the effect of gout on the risk of CAD, represented by the HR with the 95% CI. Patients with gout were at greater risk of CAD, compared with those without gout: HR=1.49 after adjusting for potential confounders. Non-steroidal anti-inflammatory drugs and prednisolone use was associated with a reduced risk of CAD: HR=0.63 and 0.50, respectively. Patients with gout, treated with antigout medication, exhibited a reduced risk of CAD compared with non-gout patients. Among patients with gout, those on antigout therapy had 32% lower risk compared with those not on antigout therapy: adjusted HR=0.68, 95% CI 0.63 to 0.73. Gout increases the risk of CAD, and the use of antigout medication reduces CAD risk. These results indicate that gout or hyperuricemia is a modifiable risk factor for CAD.

Background: Freezing of gait (FOG) in Parkinson's disease (PD) is a devastating clinical phenomenon that has a detrimental impact on patients. It tends to be triggered more often during turning (complex) than during forwarding straight (simple) walking. The neural mechanism underlying this phenomenon remains unclear and requires further elucidation.Objective: To investigate the differences in cerebral functional magnetic resonance imaging responses between PD patients with and without FOG during explicitly video-guided motor imagery (MI) of various complex (normal, freezing) and simple (normal, freezing) walking conditions.Methods: We recruited 34 PD patients, namely, 20 with FOG and 14 without FOG, and 15 normal controls. Participants underwent video-guided MI of turning and straight walking, with and without freezing, while their brain blood oxygen level-dependent (BOLD) activities were measured. Gait analysis was performed.Results: While comparing FOG turning with FOG straight walking, freezers showed higher activation of the superior occipital gyrus, left precentral gyrus, and right postcentral gyrus compared with non-freezers. Normal controls also manifest similar findings compared with non-freezers, except no difference was noted in occipital gyrus activity between the two groups. Freezers also displayed a higher effect size in the locomotor regions than non-freezers during imagery of normal turning.Conclusions: Our findings suggest that freezers require a higher drive of cortical and locomotion regions to overcome the overinhibition of the pathways in freezers than in non-freezers. Compared with simple walking, increased dorsal visual pathway and deep locomotion region activities might play pivotal roles in tackling FOG in freezers during complex walking.

Objective: Stroke in young adults is uncommon, and the etiologies and risk factors of stroke in young adults differ from those in older populations. Smoker's paradox is an unexpected favorable outcome, and age difference is used to explain the association between smoking and the favorable functional outcome. This study aimed to investigate the existence of this phenomenon in young stroke patients.Methods: We analyzed a total of 9,087 young stroke cases registered in the nationwide stroke registry system of Taiwan between 2006 and 2016. Smoking criteria included having a current history of smoking more than one cigarette per day for more than 6 months. After matching for sex and age, a Cox model was used to compare mortality and function outcomes between smokers and non-smokers.Results: Compared with the non-smoker group, smoking was associated with older age, higher comorbidities, and higher alcohol consumption. Patients who report smoking with National Institutes of Health Stroke Scale scores of 11–15 had a worse functional outcome (adjusted odds ratio, 0.81; 95% confidence interval, 0.76 – 0.87).Conclusion: Smokers had a higher risk of unfavorable functional outcomes at 3 months after stroke, and therefore, we continue to strongly advocate the importance of smoking cessation.

Objective: Multiple system atrophy (MSA) is a neurodegenerative disorder manifesting as parkinsonism, cerebellar ataxia, and autonomic dysfunction. It is categorized into MSA with predominant parkinsonism (MSA-P) and into MSA with predominant cerebellar ataxia (MSA-C). The pathophysiology of motor control circuitry involvement in MSA subtype is unclear. Bereitschaftspotential (BP) is a feasible clinical tool to measure electroencephalographic activity prior to volitional motions. We recorded BP in patients with MSA-P and MSA-C to investigate their motor cortical preparation and activation for volitional movement.Methods: We included eight patients with MSA-P, eight patients with MSA-C, and eight age-matched healthy controls. BP was recorded during self-paced rapid wrist extension movements. The electroencephalographic epochs were time-locked to the electromyography onset of the voluntary wrist movements. The three groups were compared with respect to the mean amplitudes of early (1,500–500 ms before movement onset) and late (500–0 ms before movement onset) BP.Results: Mean early BP amplitude was non-significantly different between the three groups. Mean late BP amplitude in the two patient groups was significantly reduced in the parietal area contralateral to the movement side compared with that in the healthy control group. In addition, the late BP of the MSA-C group but not the MSA-P group was significantly reduced at the central parietal area compared with that of the healthy control group.Conclusions: Our findings suggest that patients with MSA exhibit motor cortical dysfunction in voluntary movement preparation and activation. The dysfunction can be practicably evaluated using late BP, which represents the cerebello-dentato-thalamo-cortical pathway.

Background: This study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with kidney function measured by estimated glomerular filtration rate (eGFR) levels at admission for patients with intracerebral hemorrhage. Methods: From the Taiwan Stroke Registry data, we identified and stratified patients with intracerebral hemorrhage into 5 subgroups by the eGFR levels at admission: ≥ 90, 60-89, 30-59, 15-29, and < 15 mL/min/1.73m2 or on dialysis from April 2006 to December 2016. Risks of 1-month mortality and 1-year mortality rates after intracerebral hemorrhage were investigated by the eGFR levels. Results: Both the 1-month mortality and 1-year mortality rates increased as the eGFR level decreased. The 1-month mortality rate was over 5-fold greater in patients with eGFR < 15 mL/min/1.73m2 or on dialysis than in patients with eGFR levels ≥ 90 mL/min/1.73m2 (8.31 versus 1.50 per 1000 person-days), with an adjusted hazard ratio (HR) of 4.59 [95% confidence interval (CI) = 2.71-7.78]. Similarly, the 1-year mortality rate was 7.5-fold greater in patients with eGFR < 15 mL/min/1.73m2 or on dialysis than in patients with eGFR ≥ 90 mL/min/1.73m2, with an adjusted HR of 4.54 (95% CI 2.95-6.98). Conclusion: The eGFR level can be an indicator of prognosis for patients with intracerebral hemorrhage.

Objective: Stroke in young adults is uncommon, and the etiologies and risk factors of stroke in young adults differ from those in the older populations. Smoker’s paradox is an unexpected favorable outcome, and age difference was used to explain the association between smoking and the favorable functional outcome. This study aimed to investigate the existence of this phenomenon in young stroke patients.Methods: We analyzed a total of 9,460 young stroke cases registered in the nationwide stroke registry system of Taiwan between 2006 and 2016. Smoking criteria included having a past or current history of smoking more than 1 cigarette per day for more than 6 months. After matching for sex and age, a Cox model was used to compare complications, mortality and outcomes between smokers and non-smokers.Results: Smoking was associated with older age, higher comorbidities, and higher alcohol consumption. Smoking patients with NIHSS scores of 11–15 had a worse functional outcome (adjusted OR, 0.81; 95% CI, 0.76–0.87), and smoking cessation would substantially reverse those effects.Conclusion: The smoker’s paradox definitely does not exist, and therefore we continue to strongly advocate the importance of smoking cessation.

Background Altered γ-aminobutyric acid signaling is believed to disrupt the excitation/inhibition balance in the striatum, which may account for the motor symptoms of Huntington's disease. Na-K-2Cl cotransporter-1 is a key molecule that controls γ-aminobutyric acid-ergic signaling. However, the role of Na-K-2Cl cotransporter-1 and efficacy of γ-aminobutyric acid-ergic transmission remain unknown in Huntington's disease. Methods We determined the levels of Na-K-2Cl cotransporter-1 in brain tissue from Huntington's disease mice and patients by real-time quantitative polymerase chain reaction, western blot, and immunocytochemistry. Gramicidin-perforated patch-clamp recordings were used to measure the Eγ-aminobutyric acid in striatal brain slices. To inhibit Na-K-2Cl cotransporter-1 activity, R6/2 mice were treated with an intraperitoneal injection of bumetanide or adeno-associated virus-mediated delivery of Na-K-2Cl cotransporter-1 short-hairpin RNA into the striatum. Motor behavior assays were employed. Results Expression of Na-K-2Cl cotransporter-1 was elevated in the striatum of R6/2 and Hdh150Q/7Q mouse models. An increase in Na-K-2Cl cotransporter-1 transcripts was also found in the caudate nucleus of Huntington's disease patients. Accordingly, a depolarizing shift of Eγ-aminobutyric acid was detected in the striatum of R6/2 mice. Expression of the mutant huntingtin in astrocytes and neuroinflammation were necessary for enhanced expression of Na-K-2Cl cotransporter-1 in HD mice. Notably, pharmacological or genetic inhibition of Na-K-2Cl cotransporter-1 rescued the motor deficits of R6/2 mice. Conclusions Our findings demonstrate that aberrant γ-aminobutyric acid-ergic signaling and enhanced Na-K-2Cl cotransporter-1 contribute to the pathogenesis of Huntington's disease and identify a new therapeutic target for the potential rescue of motor dysfunction in patients with Huntington's disease. © 2019 International Parkinson and Movement Disorder Society.

People with heightened emotional sensitivity can perceive better how others feel. Students admitted to medical school by interviews for assessing pre-set personal qualities, such as emotional sensitivity, may be more likely to meet patients' satisfaction in the future. We tested whether a student enrolled by passing the interview would have more emotional sensitivity than those by taking an exam. We also investigated what impact the enrolment protocols might have on students' internship performance.Participants were first- and second-year medical students and assigned into the interviewed group or examined group according to the entrance protocols. Two emotion-related tasks and one control task were adopted. Subsequently, the performance evaluation of clinical work from students' advisors about these two groups of participants were collected after they finished the internship training at the hospital.Students selected through the pre-programmed interview which is based on personal qualities showed greater emotional sensitivity than those selected by the exam. Those students with better emotional sensitivity also performed better when they were in the internship training. Emotional sensitivity is a valid index to predict students' future performance and could be used in the selection protocol for medical students.

Background: In most countries, large cerebral artery occlusion is identified as the leading cause of disability. In 2015, five large-scale clinical trials confirmed the benefit of intra-arterial thrombectomy. However, thrombectomy is a highly technical and facility-dependent procedure. Primary stroke centers need to transfer patients to comprehensive stroke centers to perform thrombectomy. The time-lapse during interhospital transfer would decrease the chance of the patient's proper recovery. Communication barriers also contribute to this delay.Aims: We used a smartphone application to overcome communication barriers between hospitals. We aimed to shorten the door-to-puncture time of interhospital transfer patients.Methods: We began using a smartphone application, “LINE,” to facilitate interhospital communication on May 01, 2018. We carried out retrospective data analyses for all the transfer patients (n = 351), with the primary outcome being the door-to-puncture time in our comprehensive stroke center (China Medical University Hospital). We compared the three periods: May 01 to Dec 31, 2017 (before the use of the smartphone application); May 01 to Dec 31, 2018 (the 1st year of using the smartphone application); and May 01 to Dec 31, 2019 (the 2nd year of using the smartphone application). We also compared the transfer data with non-transfer thrombectomies in the same period.Results: We compared 2017, 2018, and 2019 data. The total number of transfer patients increased over the years: 63, 113, 175, respectively. The mean door-to-puncture time decreased significantly, going from 109, through 102, to 92 min. Meanwhile, the mean door-to-puncture time in non-transfer patients were 140.3, 122.1, and 129.3 min. The main reason of time saving was the change of the way of communication, from point-to-point interhospital communication to hub-to-spoke interhospital communication.Conclusions: We used this smartphone application to enhance interhospital communication, changed from the point-to-point to hub-to-spoke method. It made us overcome the communication barrier and build up interhospital connection, thus shortening the door-to-puncture time. Our experience demonstrated the importance of close communication and teamwork in hyperacute stroke care, especially in interhospital transfer for thrombectomy.

Objective: Associative motor cortical plasticity can be non-invasively induced by paired median nerve electric stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). This study investigates whether a simultaneous motor reaction of the other hand advances the associative plasticity in M1. Methods: Twenty-four right-handed subjects received conventional paired associative stimulation (PAS) and PAS with simultaneous motor reaction (PASmr) with at least a 1-week interval. The PASmr protocol additionally included left abductor pollicis brevis muscle movement responding to a digital sound. The motor reaction time was individually measured. The M1 excitability was examined by the motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) before and after the PAS protocols. Results: The conventional PAS protocol significantly facilitated MEP and suppressed SICI. A negative correlation between the reaction time and the MEP change, and a positive correlation between the reaction time and the ICF change were found in the PASmr protocol. By subgrouping analysis, we further found significant facilitation of MEP and a reduction of ICF in the subjects with fast reaction times but not in those with slow reaction times. Conclusion: Synchronized motor reaction ipsilateral to the stimulated M1 induces associative M1 motor plasticity through the spike-timing dependent principle. MEP and ICF change could represent this kind of plasticity. The current findings provide a novel insight into designing rehabilitation programs concerning motor function.

Objective: Review and integrate the neurologic manifestations of the Coronavirus Disease 2019 (COVID-19) pandemic, to aid medical practitioners who are combating the newly derived infectious disease. Methods: We reviewed the clinical research, consisting of mainly case series, on reported neurologic manifestations of COVID-19. We also reviewed basic studies to understand the mechanism of these neurologic symptoms and signs. Results: We included 79 studies for qualitative synthesis and 63 studies for meta-analysis. The reported neurologic manifestations were olfactory/taste disorders (35.6%), myalgia (18.5%), headache (10.7%), acute cerebral vascular disease (8.1%), dizziness (7.9%), altered mental status (7.8%), seizure (1.5%), encephalitis, neuralgia, ataxia, Guillain-Barre syndrome, Miller Fisher syndrome, intracerebral hemorrhage, polyneuritis cranialis, and dystonic posture. Conclusions: Neurologic manifestations in COVID-19 may alert physicians and medical practitioners to rule in high-risk patients. The increasing incidence of olfactory/taste disorders, myalgia, headache, and acute cerebral vascular disease renders a possibility that COVID-19 could attack the nervous system. The cytokine secretion and bloodstream circulation (viremia) are among the most possible routes into the nervous system.

Patients with Parkinson’s disease (PD) suffer from motor and non-motor symptoms; 40% would develop dementia (PD-D). Impaired face and emotion processing in PD has been reported; however, the deficits of face processing in PD-D remain unclear. We investigated three essential aspects of face processing capacity in PD-D, and the associations between cognitive, neuropsychiatric assessments and task performances. Twenty-four PD-D patients (mean age: 74.0 ± 5.55) and eighteen age-matched healthy controls (HC) (mean age: 71.0 ± 6.20) received three computerized tasks, morphing-face discrimination, dynamic facial emotion recognition, and expression imitation. Compared to HC, PD-D patients had lower sensitivity (d’) and greater neural internal noises in discriminating faces; responded slower and had difficulties with negative emotions; imitated some expressions but with lower strength. Correlation analyses revealed that patients with advancing age, slow mentation, and poor cognition (but not motor symptoms) showed stronger deterioration in face perception. Importantly, these correlations were absent in the age-matched HC. The present study is among the first few examined face processing in patients with PD-D, and found consistent deficits correlated with advancing age and slow mentation. We propose that face discrimination task could be included as a potential test for the early detection of dementia in PD.

Background: Prior literatures have shown inflammatory bowel disease (IBD) could increase fibromyalgia (FM) risk. However, studies about gender and age distributions of FM risk among patients with IBD are rare. With large study samples, this study aimed to evaluate the FM risk among IBD patients with different gender and different age. Objective: We aim to estimate the FM risk among male and younger IBD patients with a large patient sample. Study Design: A retrospective cohort study was arranged in this research. Setting: The data used in this research were selected from the Taiwan National Health Insurance Research Database (NHIRD). Methods: From the Taiwan NHIRD, we selected 4,510 patients with IBD and 18,040 randomly gender- and age-matched patients without a history of IBD from the beginning of 2000 to the end of 2005 to analyze the development of FM over a 12-year follow-up period (2000– 2011). The Cox regression model was used to assess the effects of IBD on the risk of FM by adjusting for gender, age, and comorbidities, including hypertension, diabetes, hyperlipidemia, depression, anxiety, and sleep disorder. Results: After adjusting suitable covariates, the IBD patients had a greater FM risk (adjusted hazard ratio [aHR] 1.70, 95% confidence interval [CI] 1.59–1.83) than the controls. Male IBD patients had a higher FM risk than female IBD patients did (aHR 2.00, 95% CI 1.79–2.23 and aHR 1.52, 95% CI 1.38–1.67, respectively). The greatest age-specific FM risk occurred in the youngest IBD subgroup (≤ 39 years old) (aHR 1.92, 95% CI 1.68–2.19). Limitations: The information about personal behaviors was unobtainable in the Taiwan NHIRD. Other risk factors for cardiovascular disease that might augment FM cannot be excluded entirely in this study. Conclusion: IBD is disclosed to be correlated with an enhanced risk to develop FM, particularly in male and younger IBD patients. For preventing FM, it is necessary to pay more attention to the management of the IBD patients. Future researches are needed to further confirm the findings in this study. Key words: Inflammation, inflammatory bowel disease, fibromyalgia, Taiwan National Health Insurance Research Database

BACKGROUND Prior investigations with few cases have disclosed lack of pressure sore (PrS) formation was characteristic in amyotrophic lateral sclerosis (ALS) patients. However, studies with larger samples are lacking to ascertain this concept. OBJECTIVE To investigate whether patients with ALS have higher risk of PrS. METHODS Utilizing a Taiwan National Insurance claims data set with 23 million participants, we extracted 514 patients with ALS and 2056 controls from 1 January 2000 to 31 December 2008. Both groups were followed up until PrS occurrence during study period (2000-2011). The PrS risk was calculated with Cox proportional regression model. RESULTS The patients with ALS had a greater PrS risk (adjusted hazard ratio [aHR] = 8.82, 95% confidence interval [CI] = 4.90-15.9, P

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Background Colonic diverticular disease is a chronic gastrointestinal disorder. Previous studies have suggested that chronic gastrointestinal tract is involved in the pathophysiology of Parkinson's disease. Object This study investigated the potential link between colonic diverticular disease and risk of Parkinson's disease. Methods Data in this nationwide population-based cohort study were obtained from the National Health Insurance Research Database. Patients with colonic diverticular disease were identified from among 23.22 million insured Taiwanese residents who had been diagnosed between 2000 and 2005 and were aged ≥20 years ( n = 23367). The comparison cohort included patients without colonic diverticular disease, matched by sex, age, and all comorbidities with the colonic diverticular disease patients cohort ( n = 23367). Using univariable and multivariable Cox proportional hazard regression models, we estimated the adjusted hazard ratio (aHR) for PD with a 95% confidence interval (CI) after adjusting for age, sex, and all of comorbidities. Results The risk of Parkinson's disease was higher in the CDD cohort than in the comparison cohort (HR = 1.27, 95%CI = 1.10–1.47). Compared with patients aged ≥65 years without CDD, the CDD patients in the equal age group had a 1.25-fold increased risk of PD (95% CI = 1.07–1.46). Conclusion Colonic diverticular disease may be associated with an increased risk of Parkinson's disease. Thus, the risk of this neurodegenerative disease should be considered in patients with colonic diverticular disease.

Background: Disruptions in gamma-aminobutyric (GABA) acid signaling are believed to be involved in Huntington's disease pathogenesis, but the regulation of GABAergic signaling remains elusive. Here we evaluated GABAergic signaling by examining the function of GABAergic drugs in Huntington's disease and the expression of GABAergic molecules using mouse models and human brain tissues from Huntington's disease. Methods: We treated wild-type and R6/2 mice (a transgenic Huntington's disease mouse model) acutely with vehicle, diazepam, or gaboxadol (drugs that selectively target synaptic or extrasynaptic GABAA receptors) and monitored their locomotor activity. The expression levels of GABAA receptors and a major neuron-specific chloride extruder (potassium-chloride cotransporter-2) were analyzed by real-time quantitative polymerase chain reaction, Western blot, and immunocytochemistry. Results: The R6/2 mice were less sensitive to the sedative effects of both drugs, suggesting reduced function of GABAA receptors. Consistently, the expression levels of α1/α2 and δ subunits were lower in the cortex and striatum of R6/2 mice. Similar results were also found in 2 other mouse models of Huntington's disease and in Huntington's disease patients. Moreover, the interaction and expression levels of potassium-chloride cotransporter-2 and its activator (brain-type creatine kinase) were decreased in Huntington's disease neurons. These findings collectively suggest impaired chloride homeostasis, which further dampens GABAA receptor-mediated inhibitory signaling in Huntington's disease brains. Conclusions: The dysregulated GABAergic responses and altered expression levels of GABAA receptors and potassium-chloride cotransporter-2 in Huntington's disease mice appear to be authentic and may contribute to the clinical manifestations of Huntington's disease patients. © 2017 International Parkinson and Movement Disorder Society

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Chronic inflammation, which changes the neurotransmitter metabolism and kindles neuroendocrine system dysfunction in the central nervous system, might cause fibromyalgia (FM) formation. In FM patients without traditional FM risk factors, such as hypertension, hyperlipidemia, diabetes, sleep disorder, depression, and anxiety, the chronic inflammatory process is a possible risk factor for FM. Thus, we investigated whether chronic osteomyelitis (COM), a disease characterized by chronic inflammation, increases FM risk. Including data for 1 million enrollees, the Longitudinal Health Insurance Database was used, and 1,244 COM patients without FM history and 4,976 randomly selected sex- and age-matched control subjects without COM or FM history were extracted. The development of FM over a 13-year follow-up period from 1999 to 2011 was evaluated, and FM risk was estimated using the Cox proportional regression model. The aforementioned FM risk factors were more common in COM patients, who had a significantly greater FM risk than did the control subjects. Compared with those who had no associated risk factors, patients with COM had a greater FM risk than did the control subjects (adjusted hazard ratio [aHR] = 1.32, 95% confidence interval [CI], .99–1.75). Younger people had an even greater risk (age younger than 35 years: aHR = 1.58, 95% CI, 1.03–2.44; age 60 years or older: aHR = 1.03, 95% CI, .78–1.36). To our knowledge, this is the first study to link COM to an enhanced risk of FM development. The results imply that COM is a predictor of FM, suggesting that close follow-up for patients with COM is required to prevent FM, especially in younger populations. Perspective COM is associated with the augmented risk of developing FM, and rigorous treatments for COM patients might decrease the future risk of FM formation, especially in those with relatively younger ages.

Introduction: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant, cerebellar degeneration predominant disease caused by excessive CAG repeats. We examined event-related dysynchronization/synchronization (ERD/ERS) in patients with SCA3. Methods: We assessed ERD/ERS of self-paced voluntary hand movements in 15 patients with genetically proven SCA3 in comparison with healthy controls. Results: In ERS, a significant interaction effect between group, frequency, and period (F = 1.591; p = 0.005; ρI = 0.86) was observed. The post-hoc two-tailed independent t-test showed significant differences in high beta and low beta ERS. By contrast, in ERD, no apparent differences were observed in the pattern of patients with SCA3 in comparison with healthy controls (F = 1.01; p = 0.442). Conclusion: The study revealed a decreased ERS in patients with SCA3, especially at the frequency of 20–30 Hz. This study elucidates the significant role of cerebellum in motor control.

The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging.We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline.After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days.Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

Glioblastoma (GBM) is the most commonly occurring tumor in the cerebral hemispheres. Currently, temozolomide (TMZ), an alkylating agent that induces DNA strand breaks, is considered the frontline chemotherapeutic agent for GBM. Despite its frontline status, GBM patients commonly exhibit resistance to TMZ treatment. We have recently established and characterized TMZ-resistant human glioma cells. The aim of this study is to investigate whether curcumin modulates cell apoptosis through the alternation of the connexin 43 (Cx43) protein level in TMZ-resistant GBM. Overexpression of Cx43, but not ATP-binding cassette transporters (ABC transporters), was observed (approximately 2.2-fold) in TMZ-resistant GBM cells compared to the Cx43 levels in parental GBM cells. Furthermore, at a concentration of 10[Formula: see text][Formula: see text]M, curcumin significantly reduced Cx43 protein expression by about 40%. In addition, curcumin did not affect the expression of other connexins like Cx26 or epithelial-to-mesenchymal transition (EMT) proteins such as [Formula: see text]-catenin or [Formula: see text]E-catenin. Curcumin treatment led to an increase in TMZ-induced cell apoptosis from 4% to 8%. Importantly, it did not affect the mRNA expression level of Cx43. Concomitant treatment with the translation inhibitor cycloheximide (CHX) exerted additional effects on Cx43 degradation. Treatment with the autophagy inhibitor 3-MA (methyladenine) did not affect the curcumin-induced Cx43 degradation. Interestingly, treatment with the proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) significantly negated the curcumin-induced Cx43 degradation, which suggests that curcumin-induced Cx43 degradation occurs through the ubiquitin-proteasome pathway.

Pairing transcutaneous electric nerve stimulation (TENS) and transcranial magnetic stimulation (TMS) with specific stimulus-intervals induces associative motor plasticity at the primary motor cortex (M1). Electroacupuncture (EA) is an established medical technique in the eastern countries. This study investigates whether EA paired with TMS induces distinct M1 motor plasticity. Fifteen healthy, right-handed subjects (aged 23.6 ± 2.0 years, eight women) were studied. Two-hundred and twenty-five pairs of TMS of the left M1 preceded by right EA at acupoint “Neiguan” [Pericardium 6 (PC6), located 2 decimeters proximal from the wrist wrinkle] were respectively applied with the interstimulus interval (ISI) of individual somatosensory evoked potential (SSEP) N20 latency plus 2 ms (N20+2) and minus 5 ms (N20-5) with at least 1-week interval. The paired stimulation was delivered at a rate of 0.25 Hz. Sham TMS with a sham coil was adopted to examine the low-frequency EA influence on M1 in eleven subjects. M1 excitability was assessed by motor-evoked potential (MEP) recruitment curve with five TMS intensity levels, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) at the abductor pollicis brevis (APB) muscle of the right hand before and after the EA-M1 paired associative stimulation (PAS). In addition, median nerve SSEPs and H-reflex were respectively measured to monitor somatosensory and spinal excitability. The MEP showed significantly facilitated after the sham EA-M1 PAS while tested with 80% of the TMS intensity producing on average 1 mV amplitude (i.e., MEP1 mV) in the resting APB muscle. It was also facilitated while tested with 90% MEP1 mV irrespective of the stimulation conditions. The SSEP showed a higher amplitude from the real EA-M1 PAS compared to that from the sham EA-M1 PAS. No significant change was found on SICI, ICF, CBI and H-reflex. Findings suggest that repetitive low frequency EA paired with real TMS did not induce spike-timing dependent motor plasticity but EA paired with sham TMS induced specific M1 excitability change. Complex sensory afferents with dispersed time locked to the sensorimotor cortical area could hamper instead of enhancing the induction of the spike-timing dependent plasticity (STDP) in M1.

BackgroundDystonia is a neurological syndrome typically resulting in abnormal postures.ObjectivesWe tested the role of physical injury as potential risk factor for development of dystonia using The National Health Insurance Research Database of Taiwan.MethodsWe identified 65704 people who were coded in the database as having had peripheral traumatic injuries (ICD-9-CM 807-848 and 860-959) in the year 2000. Patients with traumatic brain or spine injuries were excluded from analysis. We matched them using purposive sampling with 65704 people in the database who had not suffered peripheral trauma. We looked then at the incidence of dystonia occurring at least 1 year from the date of the peripheral trauma until 2011. Psychiatric symptoms (depression and anxiety) and sleeps difficulties have been investigated as potential covariates.ResultsWe found 189 patients with dystonia (0.28%) in the trauma group, and 52 patients with dystonia (0.08%) in the non-trauma group. Trauma was independently associated with dystonia (adjusted HR = 3.12, 95% CI = 2.30-4.24). The incidence density of dystonia in the trauma group was 2.27 per 10000 person-years, while it was 0.71 per 10000 person-years in the non-trauma group Beyond the peripheral trauma, other variables associated to the incidence of dystonia included female sex, aged 40 years and above, depression and sleep disorders.ConclusionThese data from a large population dataset support traumatic injury as a risk factor for the development of dystonia.

Aim: The ability to predict outcomes can help clinicians to better triage and treat stroke patients. We aimed to build prediction models using clinical data at admission and discharge to assess predictors highly relevant to stroke outcomes. Methods: A total of 37,094 patients from the Taiwan Stroke Registry (TSR) were enrolled to ascertain clinical variables and predict their mRS outcomes at 90 days. The performances (i.e., the area under the curves (AUCs)) of these independent predictors identified by logistic regression (LR) based on clinical variables were compared. Results: Several outcome prediction models based on different patient subgroups were evaluated, and their AUCs based on all clinical variables at admission and discharge were 0.85-0.88 and 0.92-0.96, respectively. After feature selections, the input features decreased from 140 to 2-18 (including age of onset and NIHSS at admission) and from 262 to 2-8 (including NIHSS at discharge and mRS at discharge) at admission and discharge, respectively. With only a few selected key clinical features, our models can provide better performance than those previously reported in the literature. Conclusion: This study proposed high performance prognostics outcome prediction models derived from a population-based nationwide stroke registry even with reduced LR-selected clinical features. These key clinical features can help physicians to better focus on stroke patients to triage for best outcome in acute settings.

Robot-assisted gait training (RAGT) systems offer the advantages of standard rehabilitation and provide precise and quantifiable control of therapy. We examined the clinical outcome of RAGT and analyzed the correlations between gait analysis data and event-related desynchronization (ERD) and event-related synchronization (ERS) in patients with chronic stroke. We applied the Berg balance scale (BBS) and analyzed gait parameters and the ERD and ERS of self-paced voluntary leg movements performed by patients with chronic stroke before and after undergoing RAGT. A significant change was observed in BBS (p = 0.011). We also showed preliminary outcomes of changes in gait cycle duration (p = 0.015) and in ipsilesional ERS in the low-beta (p = 0.033) and high-beta (p = 0.034) frequency bands before and after RAGT. In addition, correlations were observed between BBS and ipsilesional ERS in the alpha and low-beta bands (r = &minus, 0.52, p = 0.039, r = &minus, 0.52, p = 0.040). The study demonstrated that RAGT can improve balance and provided an idea of the possible role of brain oscillation and clinical outcomes in affecting stroke rehabilitation.

Aim: LG72 can increase mitochondrial ROSs and oxidative stress has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). The serum level of LG72 or LG72-related molecules might therefore be associated with ALS. Here, we aim to determine the serum autoantibody against LG72 has potential as a biomarker for the diagnosis of ALS. Materials: Seventy-eighty patients with ALS, 45 patients with AD, 43 patients with PD and 88 healthy adults were enrolled. Results: The concentration of serum autoantibody against LG72 was more than fourfold lower in ALS than other control groups (p < 0.001). The AUC was 0.9627 when the cut-off value for autoantibody concentration was 0.167 μg/ml. Conclusion: This finding suggests that the autoantibody against LG72 might serve as a surrogate biomarker for ALS.

Objectives Parkinson's disease (PD) is a neurodegenerative disease. A decreased risk of cancer, except for melanoma, has been observed in patients with PD. The aim of this study was to evaluate the association between brain tumor and PD in a Taiwanese population. Materials and methods We used data from the National Health Insurance program of Taiwan. The PD cohort contained 2998 patients, and each patient was frequency-matched, based on age and sex, with 4 people without PD, who were randomly selected from the general population. Cox's proportional hazard regression analysis was conducted to estimate the effects of PD on the risk of brain tumor. Results The risk of developing brain tumor was significantly higher in patients with PD than in those without PD (adjusted hazard ratio = 2.11; 95% confidence interval (CI) = 1.24–3.59), and benign brain tumor exhibited a particularly elevated risk of 2.16-fold (95% CI = 1.26–3.68). The hazard ratio (HR) for developing a benign brain tumor was higher in female patients with PD than in female patients without PD, with the risk being 2.65-fold (95% CI = 1.30–5.43). An analysis of the two age groups, 50–64 years and ≥65 years, showed that the HR of only the 50–64-year group was significantly higher between the PD and non-PD groups (HR = 2.77, 95% CI = 1.07–7.14). Conclusion The present study showed that Taiwanese patients with PD are at a higher risk of developing brain tumor than the general population. The exact underlying etiologies require further investigation.

Objectives According to the data of Organisation for Economic Cooperation and Development, almost all the countries got increased medical expenditures in these years. Among the diseases, migraine is a condition that affects predominantly young and middle-aged people. It results in great economic losses. So we perform this research to investigate the acupuncture effect of reducing medical expenditure and medical resources use. Perspective Acupuncture is a non-pharmacologic treatment and it became popular in recent years. In Taiwan, about 13% migraine patients visited acupuncture doctor. We hypothesized that the acupuncture had the additional effect than the medical treatment. Setting We analysed the economic cost and medical visits in the real word. Methods We used national cohort data from Taiwan, retrospectively gathered between 2000 and 2010. We selected newly diagnosed migraine patients who were diagnosed by registered neurologists formally licensed by the Taiwan Neurological Society. We divided these patients into two groups: with and without acupuncture treatment. The main outcome was medical expenditures and visits within 1 year after acupuncture. Results In migraine patients who received acupuncture treatment, medical expenditures on emergency care and hospitalization were significantly lower than the group without acupuncture treatment. Conclusion According to our real-world data, acupuncture can reduce the medical expenditure in migraine patients within 1 year after diagnosis. For the health policy maker, it is cost effective to encourage combining acupuncture and western medicine to treat migraine patients. For the doctors in routine clinical practice, who may consider to consult acupuncture doctors to deal with the migraine patients together.

OBJECTIVE: Previous electrophysiological and psychophysical tests have suggested that somatosensory integration is abnormal in dystonia. Here, we hypothesised that this abnormality could relate to a more general deficit in pre-attentive error/deviant detection in patients with dystonia. We therefore tested patients with dystonia and healthy subjects using a mismatch negativity paradigm (MMN), where evoked potentials generated in response to a standard repeated stimulus are subtracted from the responses to a rare "odd ball" stimulus. METHODS: We assessed MMN for somatosensory and auditory stimuli in patients with cervical dystonia and healthy age matched controls. RESULTS: We found a significant group ∗ oddball type interaction effect (F (1, 34) = 4.5, p = 0.04, ρI = 0.63). A follow up independent t-test for sMMN data, showed a smaller sMMN amplitude in dystonic patients compared to controls (mean difference control-dystonia: -1.0 µV ± 0.3, p

A 23-year-old man presented to our clinic with acute left-sided numbness for one week. He had been given a diagnosis of lymphoma as a child and had been in remission for more than 10 years. The neurologic examination showed decreased sensation to pinprick over the left side of the patient’s face

Background: Inflammation may trigger migraine development through neurovascular reactions in the brain. Most of the migraine patients, particularly the younger ones, do not have any risk factors for this disease. Hence, we assessed whether chronic osteomyelitis (COM), a chronic inflammatory disease, increases the risk of migraine. Objective: We aim to evaluate the risk of migraine among female and middle-age COM patients with a large patient sample. Study Design: A retrospective cohort study was conducted in this study. Setting: The data used in this study were extracted from the Taiwan National Health Insurance (NHI) Research Database. Methods: A study group with 2,012 COM patients and 8,048 randomly chosen gender- and age-matched controls were chosen from the Taiwan NHI Research Database (NHIRD) from the start of 2000 to the end of 2009. The risk of migraine was estimated with Cox proportional regression model. Both COM and control groups were followed-up until the occurrence of migraine during the study period (2000–2011). Prevalent covariates, such as age, gender, hypertension, diabetes, hyperlipidemia, stroke, coronary artery disease, depression, anxiety, sleep disorder, bipolar disorder, and epilepsy, were included for further evaluation. The hazard ratio (HR) of migraine was measured with Cox proportional hazard regression model. The primary outcome was the overall migraine risk among COM patients, and the secondary outcome was the migraine risk among COM patients lacking the comorbidities. Additional outcomes included migraine risk among COM patients in different age and gender subgroups. Results: The overall migraine risk was increased in COM patients (adjusted hazard ratio [aHR] 1.74, 95% confidence interval [CI] 1.14–2.65). Even without any prevalent comorbidities, COM patients still exhibited an increased risk of migraine (aHR 2.05, 95% CI 1.06–3.97) than the controls did. Moreover, this risk was relatively higher in COM patients aged < 40 and 45–54 years (aHR 2.07, 95% CI 0.97–4.46 and aHR 2.11, 95% CI 0.97–4.57, respectively) than in their counterparts. Female COM patients had a relatively higher migraine risk (aHR 1.85, 95% CI 1.05–3.24) than male patients did (aHR 1.68, 95% CI 0.89–3.16). Limitations: The messages about personal behaviors were unavailable in the Taiwan NHIRD. Other neurovascular risk factors that might increase migraine cannot be excluded completely in this research. Conclusion: An association between COM and increased risk of migraine was shown in this study. The results suggest that COM is a significant migraine predictor, and thus imply the necessity for rigorous migraine prevention in COM patients, especially female and younger ones. Key words: Inflammation, migraine, chronic osteomyelitis, Taiwan National Health Insurance Research Database

We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a 99mTc-TRODAT-1 (TRODAT) scan in a dopa-responsive dystonia (DRD) family with the guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation. Clinically, there was presentation of intrafamilial variability in the DRD family. The index patient was a 10-year-old girl with classic DRD and normal presynaptic nigrostriatal dopaminergic function. However, her grandmother, a 79-year-old woman, presented with slowly progressive Parkinson’s disease (PD) without dystonic symptoms and excellent response to dopaminergic therapy for 21 years. Her brain TRODAT SPECT imaging revealed a markedly and asymmetrically reduced uptake of dopamine transporter at the bilateral striatum. Her father, a 54-year-old man, was an asymptomatic gene carrier and his brain TRODAT SPECT imaging revealed asymmetrically reduced nigrostriatal dopaminergic transmission in the bilateral striatum. We conclude variability of presynaptic nigrostriatal dopaminergic function in patients with DRD is related to their clinical heterogeneity. Significantly, impairment of presynaptic dopamine function actually occurs in the asymptomatic gene carrier.

Cobalt protoporphyrin (CoPP) is a potent HO-1 inducer and generally known to be an antioxidant in various cell types. Little is known about the CoPP-induced cyclooxygenase-2 (COX-2) expression and its downstream signaling in microglial cells. In current study, CoPP caused concentration- and time-dependent increases in COX-2 expression in microglial cells. Furthermore, activation of apoptosis signal-regulating kinase (ASK) 1/MAP kinase involved in CoPP-induced COX-2 expression in microglia. CoPP also induced P2X7 receptor activation, and treatment of P2X7 inhibitors effectively reduced CoPP-induced COX-2 expression. Protein inhibitor of activated STAT (PIAS) 1 is reported to be involved in modulating anti-inflammatory response through negative regulation of transcription factors. Interestingly, treatment with CoPP markedly induced PIAS1 degradation which is regulated by PI3K, Akt, and glycogen synthase kinase 3α/β (GSK3α/β) signaling pathways. These results suggest that CoPP induces COX-2 expression through activating P2X7 receptors and ASK1/MAP kinases as well as PIAS1 degradation signaling pathways. Our study provides a new insight into the regulatory effect of CoPP on neuroinflammation in microglial cells.

Background Functional perturbation of the cerebellum-motor cortex (M1) interactions may underlie pathophysiology of movement disorders such as Parkinson’s disease (PD) and spinocerebellar ataxia type 3 (SCA3). Recently M1 motor excitability can be bidirectionally modulated in young subjects by corticocortical paired associative stimulation (PAS) on cerebellum and contralateral M1 with transcranial magnetic stimulation (TMS), probably through the cerebello-dentato-thalamo-cortical (CDTC) circuit. In this study, we investigated the cerebellum to M1 associative plasticity in healthy elderly, PD and SCA3. Methods Ten right-handed PD patients, nine gene-confirmed SCA3 patients and ten age-matched healthy controls (HC) were studied. One hundred and twenty pairs of TMS of the left M1 preceded by right lateral cerebellum (CB) TMS at an interstimulus interval of 2 ms (CB-M1 PAS2ms) and 6 ms (CB-M1 PAS6ms) were respectively applied with at least one week interval. M1 excitability was assessed by motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) at the first dorsal interosseous muscle of the right hand before and after the CB-M1 PAS. Results The M1 excitability represented by MEP amplitude was significantly facilitated and suppressed in the HC group by CB-M1 PAS2ms and CB-M1 PAS6ms, respectively. The bidirectional modulation on MEP amplitude was absent in the PD and SCA3 groups. SICI and the baseline CBI were significantly reduced in the SCA3 group compared to those of the HC group irrespective of the CB-M1 PAS protocols. There was a significant reduction of CBI immediately and 60 minutes after the CB-M1 PAS protocols in the HC group but not in the patient groups. No significant change of ICF was found. Conclusions Corticocortical CB-M1 PAS can induce bidirectional motor cortical plasticity in M1 for healthy aged subjects. The modulation may be independent of the inhibitory neurocircuits such as SICI and CBI and the facilitatory mechanism like ICF. Both patients with PD and SCA3 showed impairment of such plasticity, suggesting significant functional perturbation of the CDTC circuit.

Background Previous studies revealed that chronic exposure to air pollution can significantly increase the risk of the development of Parkinson’s disease (PD), but this relationship is inconclusive as large-scale prospective studies are limited and the results are inconsistent. Therefore, the purpose of this study was to ascertain the adverse health effects of air pollution exposure in a nationwide population using a longitudinal approach. Materials and methods We conducted a nested case-control study using the National Health Insurance Research Dataset (NHIRD), which consisted of 1,000,000 beneficiaries in the National Health Insurance Program (NHI) in the year 2000 and their medical records from 1995 to 2013 and using public data on air pollution concentrations from monitoring stations across Taiwan released from the Environmental Protection Administration to identify people with ages ≥ 40 years living in areas with monitoring stations during 1995–1999 as study subjects. Then, we excluded subjects with PD, dementia, stroke and diabetes diagnosed before Jan. 1, 2000 and obtained 54,524 subjects to follow until Dec. 31, 2013. In this observational period, 1060 newly diagnosed PD cases were identified. 4240 controls were randomly selected from those without PD using a matching strategy for age, sex, the year of PD diagnosis and the year of entering the NHI program at a ratio of 1:4. Ten elements of air pollution were examined, and multiple logistic regression models were used to measure their risks in subsequent PD development. Results The incidence of PD in adults aged ≥ 40 years was 1.9%, and the median duration for disease onset was 8.45 years. None of the chemical compounds (SO2, O3, CO, NOx, NO, NO2, THC, CH4, or NMHC) significantly affected the incidence of PD except for particulate matter. PM10 exposure showed significant effects on the likelihood of PD development (T3 level: > 65μg/m3 versus T1 level: ≤ 54μg/m3; OR = 1.35, 95% CI = 1.12–1.62, 0.001 ≤ P < 0.01). In addition, comorbid conditions such as dementia (ORs = 3.53–3.93, Ps < 0.001), stroke (ORs = 2.99–3.01, Ps < 0.001), depression (ORs = 2.51–2.64, Ps < 0.001), head injury (ORs = 1.24–1.29, 0.001 ≤ Ps < 0.01 or 0.01 ≤ Ps < 0.05), sleep disorder (OR = 1.23–1.26, 0.001 ≤ Ps < 0.01), and hypertension (ORs = 1.18–1.19, 0.01 ≤ Ps < 0.05) also significantly increased the risk for PD development. Conclusions Although PM10 plays a significant role in PD development, the associated chemical/metal compounds that are capable of inducing adverse biological mechanisms still warrant further exploration. Because of a link between comorbid conditions and PM exposure, research on the causal relationship between long-term exposure to PM and the development of PD should be considered with caution because other possible modifiers or mediators, comorbid diseases in particular, may be involved.

Background and aims This cohort study assessed the association between inflammatory bowel disease (IBD) and the risk of future ischemic stroke. Methods The IBD cohort comprised adult patients (≥ 20 years old) who had received either ambulatory or inpatient care between 1998 and 2011 and IBD-free controls were randomly selected from the general population and frequency matched according to age, sex, and index year (included 18,392 patients with IBD and 73,568 control patients). Both cohorts with ischemic stroke before the index date and the ischemic stroke cases diagnosed within one year after the index date were excluded. We observed the study patients until the incidence of ischemic stroke, death, withdrawal from the insurance program, or they were lost to follow-up, or the end of 2011. Results The risk of ischemic stroke was 1.12-fold (95% CI, 1.02–1.23) higher among the IBD cohort than among the non-IBD cohort. Compared to the subjects without IBD, the adjusted HR of ischemic stroke was 1.15 (95% CI 1.04–1.28) in the Crohn's disease (CD) patients and 1.01 (95% CI 0.84–1.21) in the ulcerative colitis (UC) group. The risk of developing ischemic stroke significantly increased with the increased frequency of IBD exacerbation and hospitalization. Furthermore, the adjusted HR among the CD patients increased in conjunction with the number of medical visits, from 1.07 to 6.36 and the adjusted HR among the UC patients also increased in conjunction with the number of medical visits, from 1.11 to 2.10. Conclusions IBD exhibited an increased risk of developing ischemic stroke.

Aim We have previously found that sarcosine, a glycine transporter I inhibitor, can improve the psychiatric symptoms of schizophrenia. In this study, we aimed to investigate whether the agent can also ameliorate neuropsychiatric symptoms of Parkinson's disease (PD) patients with dementia. Methods An 8-week, double-blind, placebo-controlled trial was conducted in patients who had PD with dementia (PD-D). Neuropsychiatric manifestations were measured before and at week 2 (V1), week 4 (V2) and week 8 (V3) after treatment. Linear regression with the generalized estimating equations was applied for data analysis. Results Fifteen patients were randomized into a sarcosine group; the other 15 into a placebo group. The generalized estimating equations model revealed significant differences in Hamilton Depression Rating Scale score (P = 0.049) at V1 and Neuropsychiatry Inventory (P = 0.039) at V2 between the treatment and placebo groups. By excluding the advanced patients from analysis, there were significant differences in Unified Parkinson's Disease Rating Scale V2 (P = 0.004) and V3 (P = 0.040), Hamilton Depression Rating Scale V1 (P = 0.014) and V2 (P = 0.047), Neuropsychiatry Inventory V1 (P = 0.002) and V2 (P

Appropriate orientation towards potentially salient novel environmental stimuli requires a system capable of detecting change in the sensorium. Mismatch negativity (MMN), an evoked potential calculated by subtracting the response to a standard repeated stimulus and a rare 'oddball' stimulus, is proposed as such a change detection mechanism. It is most widely studied in the auditory domain, but here we chose to explore the mechanism of somatosensory MMN, and specifically its dependence on the cerebellum. We recorded event-related potentials (ERPs) evoked in response to auditory and sensory stimuli from 10 healthy subjects before and after anodal, cathodal and sham transcranial direct current stimulation (tDCS) of the right cerebellar hemisphere. There was a significant increase in peak amplitude of somatosensory MMN after anodal tDCS (F(1,9) = 8.98, P < 0.02, mean difference anodal pre-post: -1.02 μV) and a significant reduction in peak amplitude of somatosensory MMN after cathodal tDCS (F(1,9) = 7.15, P < 0.03, mean difference cathodal pre-post: 0.65 μV). The amplitude of auditory MMN was unchanged by tDCS. These results reveal the capability of tDCS to cause bidirectional modulation of somatosensory MMN and the dependence of somatosensory MMN on the cerebellum.

In a previous multinational, randomized, double-blind, double-dummy study, levodopa–carbidopa intestinal gel (LCIG) was tolerable and significantly improved ‘off’ time in advanced Parkinson’s disease (PD) patients. However, efficacy and safety in the Asian population has not yet been demonstrated. In this open-label study, efficacy and safety of LCIG were assessed in Japanese, Korean, and Taiwanese advanced PD patients with motor complications not adequately controlled by available PD medication. The patients were treated with LCIG monotherapy for 12 weeks. The primary end point was the mean change from baseline to week 12 in ‘off’ time, as reported in the PD Symptom Diary, normalized to a 16 h waking day and analyzed by a mixed-model repeated-measures analysis. Adverse events (AEs) were recorded. Thirty-one patients were enrolled (23 Japanese, 4 Taiwanese, 4 Korean) and 28 (90%) completed the study. For those who completed the study, the mean (s.d.) total daily levodopa dose from LCIG was 1,206.3 (493.6) mg/day at final visit (n=28); last observation carried forward (n=30) was 1,227.6 (482.8) mg/day. There was a significant mean change (s.d.) of −4.6 (3.0) hours of ‘off’ time from baseline (mean (s.d.)=7.4 (2.3)) to week 12 (n=29), P

Introduction Stiff person syndrome (SPS) is a rare disease entity and the pivotal clinical features contain progressive course of fluctuating stiffness of the low back and lower limbs. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is one of the unique variants of stiff person syndrome, and it was characterized with rigidity, stimulus-sensitive spasms, myoclonus, autonomic disturbance, and brainstem signs. These features resemble those of hyperekplexia. The accurate diagnosis of SPS is difficult but is crucial for the in time intervention with immunotherapy for life saving. In addition to the detection of responsible antibody, clinical electrophysiological manifestation, spasmodic reflex myoclonus, would be of great help in establishing the diagnosis. Methods Multichannel surface electromyogram (sEMG) and accelerometer recordings were conducted over the lumbar paraspinalis, rectus abdominalis, quadriceps, and hamstring muscles. Stimulus sensitive phenomenon was illustrated with accelerometer tapped over the pinprick. The signals were processed and digitized with CED power1401 with Spike2. The band pass for sEMG was set from 80 Hz to 1000 Hz. Results The results demonstrated that episodes of spontaneous onset of spasm of the low trunk and legs lasted about seconds to minutes. Stimuli with nose tip tapping, would elicit vigorous jerks with dissemination of long lasting muscle spasm of the neck, paraspinal muscle, rectus abdominalis muscle, to quadriceps and hamstring muscles in a descending spreading pattern. The unique electrophysiological manifestations illustrate the characteristic feature of spasmodic reflex myoclonus. The surface EMG recording also showed the phenomena of habituation, in which a trend of amplitude decrescendo from the first toward the third EMG responses were observed during consecutive auditory stimulus. The serum levels of anti-glutamic acid decarboxylase 65 antibodies was 164 IU. Conclusion The unique EMG pattern can help identify SPS. The clinical features of spasmodic reflex myoclonus are similar to hyperekplexia. However, there are some differences between the two phenomena. Unlike hyperekplexia, the spasmodic reflex myoclonus can be habituated after repetitive stimulation in the SPS patient. Furthermore, the initial myoclonic bursts of spasmodic reflex myoclonus were not present in hyperekplexia and the EMG burst duration was much shorter of the hyperekplexia as compared with that of spasmodic reflex myoclonus. These neurophysiological features discern spasmodic reflex myoclonus from hyperekplexia and are helpful in making diagnosis of SPS.