Non-invasive brain stimulation for fatigue in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND: To investigate the efficacy and safety of non-invasive brain stimulation for fatigue in multiple sclerosis patients. METHODS: We searched MEDLINE, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang databases up to October 25, 2018 (PROSPERO registration number: CRD42018112823). Randomized or pseudo-randomized, sham-controlled clinical trials evaluating the effect of non-invasive brain stimulation (NIBS) such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), transcranial random noise stimulation (tRNS), transcranial alternating current stimulation (tACS), cranial electrotherapy stimulation, and reduced impedance non-invasive cortical electrostimulation were included. Two authors independently performed data extraction and risk of bias assessment according to Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The primary outcome was fatigue scores before and after stimulation and the secondary outcome was adverse events. RESULTS: Data from cross-over and parallel group studies were pooled using a generic inverse-variance approach. A total of 14 studies (11 for tDCS, 2 for TMS, and 1 for tRNS) recruiting 207 patients were included in the systematic review and meta-analysis. No eligible tACS, cranial electrotherapy stimulation or reduced impedance non-invasive cortical electrostimulation studies were found. Short-term and long-term treatment effects were significant for tDCS, whereas TMS and tRNS were not superior to sham stimulation. The available evidence supported the effectiveness of the 1.5 mA subgroup and bilateral S1 subgroup of tDCS. Adverse events were minor and transient but comparable between real and sham stimulation. CONCLUSIONS: tDCS is a safe and effective treatment for fatigue in MS patients. However, further studies are required to confirm our results in a large-scale population and to investigate the effectiveness of other NIBS subtypes.

Stroke in China: advances and challenges in epidemiology, prevention, and management.

With over 2 million new cases annually, stroke is associated with the highest disability-adjusted life-years lost of any disease in China. The burden is expected to increase further as a result of population ageing, an ongoing high prevalence of risk factors (eg, hypertension), and inadequate management. Despite improved access to overall health services, the availability of specialist stroke care is variable across the country, and especially uneven in rural areas. In-hospital outcomes have improved because of a greater availability of reperfusion therapies and supportive care, but adherence to secondary prevention strategies and long-term care are inadequate. Thrombolysis and stroke units are accepted as standards of care across the world, including in China, but bleeding-risk concerns and organisational challenges hamper widespread adoption of this care in China. Despite little supporting evidence, Chinese herbal products and neuroprotective drugs are widely used, and the increased availability of neuroimaging techniques also results in overdiagnosis and overtreatment of so-called silent stroke. Future efforts should focus on providing more balanced availability of specialised stroke services across the country, enhancing evidence-based practice, and encouraging greater translational research to improve outcome of patients with stroke.

Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily. METHODS: A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude. RESULTS: The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave. CONCLUSIONS: Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.

Mechanism hypotheses for the electrophysiological manifestations of two cases of endplate acetylcholinesterase deficiency related congenital myasthenic syndrome.

OBJECTIVE: To summarize the electrophysiological characteristics of two cases of endplate acetylcholinesterase deficiency (EAD) related congenital myasthenic syndrome (CMS) caused by COLQ mutation and to discuss the possible mechanism of these electrophysiological phenomena. METHODS: Electrophysiological examinations were conducted including nerve conduction studies, routine electromyography (EMG), repetitive nerve stimulation (RNS) and single fiber EMG (SFEMG). The ulnar nerve was also stimulated at 50 Hz followed by 0.5 Hz to record the recovery process of compound muscle action potential (CMAP). RESULTS: Repetitive CMAP (R-CMAP) was found in motor nerve conduction in both cases. Needle EMG showed myogenic damages and SFEMG showed remarkably increased jitter values. Of note, the amplitude of CMAP and R-CMAP showed regular changing trends, and so did their time intervals in RNS studies. CONCLUSIONS: The change patterns of CMAP and R-CMAP, in combination with other electrophysiological features are very useful for the diagnosis of EAD related CMS, especially in predicting the presence of correct gene mutations.

Efficacy and safety of Qing-Feng-Gan-Ke Granules in patients with postinfectious cough: study protocol of a novel-design phase III placebo-controlled, double-blind randomized trial.

BACKGROUND: Postinfectious cough (PIC) is a common condition that affects millions of people worldwide every year. There is Western medicine for this condition but the treatment effect is often incomplete. Traditional Chinese medicine (TCM) has been increasingly prescribed for patients with PIC. Preliminary trials on Qing-Feng-Gan-Ke-Granules (QFGKG) conveyed promising results in treating PIC. This protocol describes an ongoing phase III randomized controlled clinical trial, designed according to a novel methodology of "one study, one primary outcome", with the objective of evaluating the efficacy and safety of QFGKG in patients suffering from PIC. METHODS/DESIGN: This is a multicenter, phase III, randomized, double-blind, parallel-group, placebo-controlled clinical trial, comprising two simultaneously conducted study parts, part A and part B, intending to investigate two primary outcomes, i.e. time to cough resolution and cough symptom score, respectively. A total of 480 patients, aged 18 to 65 years, who complain of an ongoing persistent cough that has been lasting ≥ 3 weeks, will be recruited from six participating sites and then randomized to receive QFGKG 12.0 g twice daily or placebo 12.0 g twice daily. Each part will enroll 240 patients, with 180 patients being allocated to the QFGKG group and 60 to the placebo group. DISCUSSION: Although traditional Chinese medicine is a structured intervention that has shown some promise in treating persistent cough, existing unconvincing evidence has noted limitations. This is a rare well-designed and rigorously-controlled, randomized, double-blind trial to evaluate the effects and safety of a Chinese herbal medicine in patients with postinfectious cough, providing tangible benefits for clinical research. Results of this trial are inclined to be conjectured as more truthful by implementing separate study parts that specifically estimate exclusive primary outcome. It will not only provide robust clinical evidence on the efficacy and safety of QFGKG for postinfectious cough, but will also provide a critical piece of information on the availability and superiority of a novel methodology for future clinical trials. The current trial is ongoing with recruitment of the predetermined number of patients being in progress. TRIAL REGISTRATION: The two parts of this trial were separately registered with the Chinese Clinical Trial Registry: ChiCTR-TRC-13003278 (part A); and ChiCTR-TRC-13003337 (part B).

[Treatment of Mild-to-moderate Bronchial Asthma (Heat Wheezing Syndrome) Patients at Acute Onset with Western Medicine Combined Danlong Oral Liquid: a Multi-center, Randomized Double- blinded, Positive-controlled Clinical Trial].

OBJECTIVE: To observe the efficacy and safety of Danlong Oral Liquid (DOL) combined Western medicine (WM) in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset. METHODS: Totally 480 mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset were randomly assigned to two groups in the ratio 3:1, the treatment group (360 cases) and the control group (120 cases). All patients received basic WM treatment. Patients in the treatment group took DOL, 10 mL each time, 3 times per day for 7 days in total, while those in the control group took Kechuanning Oral Liquid (KOL) , 10 mL each time, 3 times per day for 7 days in total. Efficacy for asthma symptoms, lung functions and scores of TCM syndrome and/or main symptoms were evaluated. RESULTS: The percentage of clinical control and significant effectiveness of asthma symptoms in the treatment group was significantly higher than that of the control group (77.36% vs 56.07%, P < 0.01). The percentage of clinical control and significant effectiveness of lung functions in the treatment group was significantly higher than that of the control group (74.28% vs 50.00%, P < 0.01). The anterior-posterior difference in scores of TCM syndrome was significantly superior in the treatment group than in the control group (-11.26 ± 4.70 vs -9.21 ± 5.09, P < 0.01). The anterior-posterior difference in scores of main symptoms was significantly better in the treatment group than in the control group (-6.58 ± 3.08 vs -5.16 ± 3.45, P < 0.01). The incidence of adverse reactions was significantly lower in the treatment group than in the control group [1.73% (6/346 cases) vs 10.17% (12/118 cases) , P < 0.05]. CONCLUSION: DOL combined WM was superior to KOL in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.

Safflower yellow for acute ischemic stroke: A systematic review of randomized controlled trials.

OBJECTIVES: Stroke is one of the most common causes of mortality worldwide. Safflower yellow is widely used for the treatment of acute ischemic stroke in China. Several trials comparing safflower yellow and placebo or no intervention were unavailable for prior meta-analysis. Here, we present an updated and expanded systematic review, including four new trials, to evaluate the efficacy and safety of safflower yellow for the treatment of acute ischemic stroke. METHODS: A comprehensive search was performed in Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, the Allied and Complementary Medicine Database (AMED), China National Knowledge Infrastructure (CNKI), China Biological Medicine Database (CBM), CQVIP Information and Wanfang Database until January 2013. Only randomized controlled trials (RCTs) evaluating the efficacy and safety of safflower yellow for acute ischemic stroke were included. Two researchers (Fan, S.Y. and Lin, N.) independently extracted data, assessed the study quality, and selected trials for inclusion. RESULTS: 7 RCTs with 762 participants were included. None of the included studies were of high methodological quality. The meta-analysis showed that safflower yellow was more effective assessed by neurological improvement rate [odds ratio (OR), 3.11; 95% confidence interval (CI) 2.06-4.68, P<0.05] compared with control group. No death was reported in any of the included studies during the follow up period. Only four trials reported adverse events, and skin rash was observed in the treatment group of one trial. CONCLUSIONS: Safflower yellow seems to be effective and safe in the treatment of acute ischemic stroke. However, RCTs of high methodological quality are warranted before drawing any conclusion on the efficacy or safety of safflower yellow for acute ischemic stroke.