Intravenous Alteplase in a Patient With Acute Ischemic Stroke Subsequent to Purulent Meningitis: A Case Report and Literature Review.

This report highlights the outcome of intravenous alteplase in a patient with acute ischemic stroke subsequent to purulent meningitis. This type of meningitis has not been defined in the guideline for early treatment of acute ischemic stroke. A 58-year-old woman with purulent meningitis developed a sudden stroke and was admitted to our emergency department. She received 0.6 mg/kg of alteplase intravenously 90 minutes after stroke onset. At 1 hour after thrombolysis, the patient's National Institute of Health Stroke Scale score improved from 9 to 4. At 2 hours, she developed a sudden severe headache that progressed to coma, and her National Institute Health Stroke Scale score rapidly deteriorated to 20. Cranial computed tomography revealed subarachnoid hemorrhage and multiple bilateral lobar brain hemorrhages. She died of a cerebellar tonsillar hernia. Intravenous alteplase might be hazardous in patients with acute ischemic stroke subsequent to purulent meningitis.

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.

BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinated disease of the central nervous system. Activation of microglia is involved in the pathogenesis of myelin loss. OBJECTIVE: This study is focused on the role of Hv1 in regulating demyelination and microglial activation through reactive oxygen species (ROS) production after lysophosphatidylcholine (LPC)-mediated demyelination. We also explored autophagy in this process. METHODS: A model of demyelination using two-point LPC injection into the corpus callosum was established. LFB staining, immunofluorescence, Western blot, and electron microscopy were used to study the severity of demyelination. Microglial phenotype and autophagy were detected by immunofluorescence and Western blot. Morris water maze was used to test spatial learning and memory ability. RESULTS: We have identified that LPC-mediated myelin damage was reduced by Hv1 deficiency. Furthermore, we found that ROS and autophagy of microglia increased in the demyelination region, which was also inhibited by Hv1 knockout. CONCLUSION: These results suggested that microglial Hv1 deficiency ameliorates demyelination through inhibition of ROS-mediated autophagy and microglial phenotypic transformation.

Subacute Combined Degeneration: A Retrospective Study of 68 Cases with Short-Term Follow-Up.

PURPOSE: The study aimed to analyze the clinical characteristics, laboratory test results, neuroimaging findings, and outcomes in patients diagnosed with subacute combined degeneration (SCD). MATERIALS AND METHODS: A total of 68 patients with SCD who had been appropriately treated for no less than 6 months were included in our study. Histories, results of routine blood tests, biochemical indices, serum vitamin B12 levels, and spinal magnetic resonance imaging (MRI) findings from the patients were studied and analyzed. Clinical signs and symptoms, graded using a functional disability rating scale, were scored at the time of admission and 3 and 6 months after admission. RESULTS: Limb numbness, limb weakness, and gait disturbances were the most common symptoms in patients with SCD. All patients showed clinical improvement to different degrees at the follow-up visits after vitamin B12 treatment. No differences in rating score were found in patients grouped by sex, hemoglobin level, serum vitamin B12, or MRI manifestations at the time of admission or at the follow-up visits. Younger patients and those with shorter disease courses had better rating scores at the short-term follow-up visits. CONCLUSION: Anemia, low levels of serum vitamin B12, and MRI abnormalities in the spinal cord are not expected to be associated with worse clinical manifestations. The age of onset and course of disease are important in evaluating the short-term prognosis of patients with SCD.

Effectiveness of strengthened stimulation during acupuncture for the treatment of Bell palsy: a randomized controlled trial.

BACKGROUND: The traditional Chinese theory of acupuncture emphasizes that the intensity of acupuncture must reach a threshold to generate de qi, which is necessary to achieve the best therapeutic effect. De qi is an internal compound sensation of soreness, tingling, fullness, aching, cool, warmth and heaviness, and a radiating sensation at and around the acupoints. However, the notion that de qi must be achieved for maximum benefit has not been confirmed by modern scientific evidence. METHODS: We performed a prospective multicentre randomized controlled trial involving patients with Bell palsy. Patients were randomly assigned to the de qi (n = 167) or control (n = 171) group. Both groups received acupuncture: in the de qi group, the needles were manipulated manually until de qi was reached, whereas in the control group, the needles were inserted without any manipulation. All patients received prednisone as a basic treatment. The primary outcome was facial nerve function at month 6. We also assessed disability and quality of life 6 months after randomization. RESULTS: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR] 4.16, 95% confidence interval [CI] 2.23-7.78), better disability assessment (differences of least squares means 9.80, 95% CI 6.29-13.30) and better quality of life (differences of least squares means 29.86, 95% CI 22.33-37.38). Logistic regression analysis showed a positive effect of the de qi score on facial-nerve function (adjusted OR 1.07, 95% CI 1.04-1.09). INTERPRETATION: Among patients with Bell palsy, acupuncture with strong stimulation that elicited de qi had a greater therapeutic effect, and stronger intensity of de qi was associated with the better therapeutic effects. TRIAL REGISTRATION: Clinicaltrials.gov no. NCT00685789.

Prevalence and risk factors of stroke in China: a national serial cross-sectional study from 2003 to 2018.

Stroke imposes a substantial burden worldwide. With the rapid economic and lifestyle transition in China, trends of the prevalence of stroke across different geographic regions in China remain largely unknown. Capitalizing on the data in the National Health Services Surveys (NHSS), we assessed the prevalence and risk factors of stroke in China from 2003 to 2018. In this study, data from 2003, 2008, 2013, and 2018 NHSS were collected. Stroke cases were based on participants' self-report of a previous diagnosis by clinicians. We estimated the trends of stroke prevalence for the overall population and subgroups by age, sex, and socioeconomic factors, then compared across different geographic regions. We applied multivariable logistic regression to assess associations between stroke and risk factors. The number of participants aged 15 years or older were 154,077, 146,231, 230,067, and 212,318 in 2003, 2008, 2013, and 2018, respectively, among whom, 1435, 1996, 3781, and 6069 were stroke patients. The age and sex standardized prevalence per 100,000 individuals was 879 in 2003, 1100 in 2008, 1098 in 2013, and 1613 in 2018. Prevalence per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018, while urban areas had a stable trend from 1261 in 2003 to 1365 in 2018. Across geographic regions, the central region consistently had the highest prevalence, but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018 (P trend<0.001), surpassing the eastern region in 2013. Advanced age, male sex, rural area, central region, hypertension, diabetes, depression, low education and income level, retirement or unemployment, excessive physical activity, and unimproved sanitation facilities were significantly associated with stroke. In conclusion, the increasing prevalence of stroke in China was primarily driven by economically underdeveloped regions. It is important to develop targeted prevention programs in underdeveloped regions. Besides traditional risk factors, more attention should be paid to nontraditional risk factors to improve the prevention of stroke.

Hemorrhagic transformation after acute ischemic stroke caused by polycythemia vera: Report of two case.

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by an increase in red blood cells in the peripheral blood. Previous work has reported the occurrence of thrombosis or hemorrhage arising in the cerebral vasculature secondary to PV. However, hemorrhagic transformation after PV-associated acute ischemic stroke has not been previously described. CASE SUMMARY: We herein present two cases of PV where hemorrhagic transformation occurred after an acute ischemic stroke. Case 1 was a 57-year-old woman with a history of hypertension who was admitted for left-sided weakness. Case 2 was a 68-year-old man who was admitted for a 10-d sudden left arm weakness. Imaging examinations for the two patients revealed hemorrhagic transformation after acute ischemic stroke. Both patients had JAK-2-V617F mutation and received antiplatelet therapy. Both of them had a good prognosis during the follow-up. CONCLUSION: This report suggested that hemorrhagic transformation may occur in acute ischemic stroke caused by PV. Antiplatelet drugs do not seem to influence the long-term outcomes in such patients. Future research should focus on establishing a standard antiplatelet treatment strategy for this condition.

Case Report: Clinical and Imaging Characteristics of a Patient with Anti-flotillin Autoantibodies: Neuromyelitis Optica or Multiple Sclerosis?

Background: Demyelination diseases are complex puzzles that are not always straightforward to diagnose. Multiple sclerosis and neuromyelitis optica are two that are frequently encountered. Numerous autoantibodies newly discovered in recent years have significantly aided clinical reasoning and diagnosis in differentiating demyelination disorders. Here we report a case of demyelination disease with anti-flotillin autoantibodies positive, which is not common in past references. Case summary: The patient presented with characteristic neuromyelitis optica symptoms and had remission and relapse. But his images exhibited characteristics of both neuromyelitis optica spectrum illness and multiple sclerosis. Conclusion: This is the first case report describing the clinical course and imaging characteristics of demyelination illness associated with anti-flotillin autoantibodies. Although so far it appears to be a subtype of multiple sclerosis, there is still a potential that it is separate from MS and NMOSD.

Efficacy of Electro-acupuncture in Treatment of Functional Constipation: A Randomized Controlled Trial.

Functional constipation (FC) is a chronic disease that significantly affects the life quality of patients. Acupuncture has been used for the treatment of FC for many years, but its effectiveness has not been scientifically assessed. The present study aimed to evaluate the efficacy of electro-acupuncture (EA) in relieving the symptoms, mental states and quality of life (QOL) of FC patients. A total of 96 FC patients were randomly allocated into EA, mosapride & sham EA group (MS) and mosapride control group (MC). In the EA group, patients were treated with 16 sessions of needling at Quchi (LI11) and Shangjuxu (ST37) bilaterally, 5 times a week in the first 2 weeks, and 3 times a week in the last 2 weeks. In the MC group, patients were treated with 5 mg mosapride citrate three times a day for 4 weeks. In the MS group, patients underwent sham EA and the same mosapride citrate treatment as in the MC group. The primary outcome was the number of weekly spontaneous bowel movements (SBMs). The secondary outcomes included stool consistency, intensity of defecating difficulty, 36-Item Short-Form Health Survey (SF-36), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and the validated Patient Assessment of Constipation-Quality of Life (PAC-QOL). The results showed that as compared with the baseline, EA significantly improved the weekly SBMs, stool consistency and intensity of defecating difficulty (P<0.05). It also partly ameliorated the PAC-QOL, SF-36, SDS and SAS scores when compared with MC or MS group (P<0.05). However, no significant difference was observed between MS and MC groups in bowel function outcomes and QOL scores. It was concluded that EA could effectively improve bowel function, mental states and QOL of FC patients.

[Progress of fMRI Research on "Deqi" of Acupuncture and Our Considerations About Further Studies].

The objectification of "Deqi" of acupuncture is a hot topic in acupuncture research at present, and functional magnetic resonance imaging (fMRI) is one of the most frequently-used techniques for revealing its brain responses. We searched literature about "Deqi" from PubMed in recent 10 years by using key words "Deqi""acupuncture sensation""needling sensation" and fMRI, trying to expound the central mechanism of "Deqi" and to put forward our understandings. Acupuncture "Deqi" evoked deactivation of the limbic-paralimbic-neocortical network (LPNN)/ default mode network (DMN), including medial prefrontal cortex (frontal pole, anterior cingulate), temporal lobe (amygdala, hippocampus, parahippocampus gyrus, temporal pole), and apparent activation of brain regions as the somatosensory cortex, thalamic-somatosensory area-insular lobe, orbitofrontal cortex, etc., which may enhance the connectivity of brain networks and function in analgesia, anti-anxiety, anti-depression, etc., but the activated and deactivated brain regions are different from study to study possibly due to the stimulated different acupoints, subjects' psychophysical conditions, scanning parameters, image acquiring sequences, etc. It is recommended that the coming stu-dies should pay more attention to the influence of acupuncture "Deqi" on brain functions in subjects suffering from diseases, the brain response characteristics of the longer post-effects and the accumulated effects of acupuncture treatment.

Efficacy and safety of direct aspiration versus stent-retriever for recanalization in acute cerebral infarction: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Whether the direct aspiration approach of thrombectomy for recanalization in patients with acute ischemic stroke has a similar efficacy and safety compared to the stent-retriever remains uncertain. METHODS: We conducted a meta-analysis of 9 studies obtained through PubMed and Embase database searches to determine whether successful recanalization rate, good functional outcome at 3 months (modified Rankin score, mRS≤2), procedure time from groin puncture to maximal revascularization and procedure-related adverse events differed between patients who underwent the direct aspiration and those receiving stent-retriever for recanalization in acute cerebral infarction. RESULTS: There was no significant difference between the direct aspiration group and the stent-retriever group in rate of successful recanalization (summary odds ratio [OR], 0.86 [95% confidence interval (CI), 0.45-1.52]; P = .60), but a better functional outcomes in the direct aspiration group at 3 months defined as a mRS score of 0 to 2 (OR, 0.77; 95% CI, 0.66-0.97; P = .03). Furthermore, the direct aspiration patients compared with the stent-retriever patients had a tendency of shorter procedural time (Mean difference [MD], -8.77 [95% CI, from-18.90 to 1.37]; P = .09). Finally, there were less adverse events especially in symptomatic intracerebral hemorrhage (sICH) (OR, 0.56; 95% CI, 0.33-0.98; P = .04) and embolization to a new territory (ENT) (OR, 0.49; 95% CI, 0.28-0.84; P = .01) in the direct aspiration group when compared with the stent-retriever group, although no difference between them in the rate of any ICH (OR, 0.81; 95% CI, 0.41-1.60; P = .54). CONCLUSIONS: The results support that the direct aspiration technique for those acute ischemic stroke patients may have better functional outcomes, less procedure related-adverse events and a tendency of faster revascularization time as compared to the stent-retriever thrombectomy, with a similar successful recanalization rate. However, major limitations of current evidence (mainly from retrospective and observational studies and a small number of patients population) indicate a need for adequately powered, multicenter randomized controlled trials (RCT) to answer this question.

MRI Features and Site-specific Factors of Ischemic Changes in White Matter: A Retrospective Study.

Brain magnetic resonance imaging (MRI) of the elderly often reveals white matter changes (WMCs) with substantial variability across individuals. Our study was designed to explore MRI features and site-specific factors of ischemic WMCs. Clinical data of consecutive patients diagnosed with ischemic cerebral vascular disease who had undergone brain MRI were collected and analyzed. Multi-logistic regression analysis comparing patients with mild versus severe WMCs was performed to detect independent associations. Analyses of variance (ANOVAs) were used to detect regionally specific differences in lesions. We found that lesion distribution differed significantly across five cerebral areas, with lesions being predominant in the frontal lobe and parieto-occipital area. To explore WMCs risk factors, after adjusting for gender, diabetes mellitus, and hypertension, only age (P<0.01), creatinine (P=0.01), alkaline phosphatase (ALP) (P=0.01) and low-density lipoprotein cholesterol (LDL-C) (P=0.03) were found to be independently associated with severe WMCs. Age (P<0.001) was strongly associated with WMCs in the frontal lobe while hypertension was independently related to lesions in the basal ganglia (P=0.048) or infratentorial area (P=0.016). In conclusion, MRI of WMCs showed that ischemic WMCs occurred mostly in the frontal lobe and parieto-occipital area. The infratentorial area was least affected by WMCs. Typically, age-related WMCs were observed in the frontal lobes, while hypertension-related WMCs tended to occur in the basal ganglia and infratentorial area.

Endovascular thrombectomy versus medical treatment for large vessel occlusion stroke with mild symptoms: A meta-analysis.

It remains controversial as to whether mechanical thrombectomy (MT) is safer and more beneficial in patients with large vessel occlusion stroke (LVOS) presenting with a National Institutes of Health Stroke Scale score ≤ 8. We therefore conducted a meta-analysis of the published data.We searched PubMed and Embase and pooled relevant data in the meta-analyses using fixed effects models. Only studies that directly compared best medical therapy alone (BMT) with MT were included. We used odds ratios to analyze the associations between MT and 90-day functional outcome (evaluated using the modified Rankin Scale (mRS)), mortality, and rates of symptomatic intracerebral hemorrhage (sICH) in patients with LVOS and minor symptoms. Five studies including a total of 581 patients met our inclusion criteria. A significant difference was found that the patients treated with MT were associated with improved 90-day mRS score (OR, 1.68; 95% CI, 1.08-2.61) compared with BMT group. There was no difference in 90-day mortality between the two groups. However, sICH occurred more frequently in the MT group than the BMT group (OR, 3.89; 95% CI, 1.83-8.27). Patients with LVOS with minor or mild symptoms who underwent primary thrombectomy had a significantly improved 90-day mRS score compared to those who received BMT alone. Meanwhile, the risk of sICH was higher in the MT group than that in BMT group. Future randomized clinical controlled trials evaluating the role of endovascular reperfusion for LVOS with minimal symptoms are warranted.

Needle Sensation and Personality Factors Influence Therapeutic Effect of Acupuncture for Treating Bell's Palsy: A Secondary Analysis of a Multicenter Randomized Controlled Trial.

BACKGROUND: It has not been solved what kind of needle sensation might influence outcomes of acupuncture treatment. Effects of personality factors on the therapeutic effect of acupuncture have not been investigated. This study aimed to find the effects of the traits of personality on the objective outcome when different acupuncture techniques were used in treating patients with Bell's palsy. METHODS: We performed a secondary analysis of a prospective multicenter randomized controlled trial of acupuncture for Bell's palsy. Patients were randomly assigned to the de qi and control groups, respectively. The primary outcome was facial nerve function at month 6. The intensity of each needle sensation was rated by a visual analog scale. Psychosocial factors were assessed by the pretreatment mediator questionnaire; 16 Personality Factor Questionnaire (16PF) was used for assessing personality factors and digit cancellation test for assessing attention. RESULTS: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR]: 4.16, 95% confidence interval [CI]: 2.23-7.78). Path analysis showed that intensity of needle sensation of fullness had direct effect on House-Brackmann (HB) score at month 6. In de qi group, the low HB score on day 1 (OR: 0.13, 95% CI: 0.03-0.45) and the low Social Boldness score (OR: 0.63, 95% CI: 0.41-0.97) in 16PF were associated with better facial function. In control group, low HB score on day 1 (OR: 0.25, 95% CI: 0.13-0.50), low Vigilance score (OR: 0.66, 95% CI: 0.50-0.88), and high Tension score (OR: 1.41, 95% CI: 1.12-1.77) in 16PF were related to better facial function. CONCLUSIONS: The needle sensation of fullness could predict better facial function and personality traits might influence outcomes of acupuncture treatment. Both of them should be considered seriously in acupuncture treatment and research.

De qi, a threshold of the stimulus intensity, elicits the specific response of acupoints and intrinsic change of human brain to acupuncture.

Objectives. De qi is the subjective constellation of sensations perceived by the acupuncturists and patients as described in several literatures, but the absence of quantitative evaluation methods in de qi restricts the use of acupuncture treatment widely in the world. In the present study, we tried to investigate the intrinsic property of de qi is and how evaluate it quantitatively. Methods. 30 healthy adult volunteers were determined to investigate intrinsic changes in the human body after acupuncture with de qi. Results. Acupuncture treatment with de qi apparently increased acupoint blood flow, tissue displacement, and the amplitude of myoelectricity after de qi on acupoints. Furthermore, acupuncture treatment induced fMRI signal increase/decrease in different brain regions although no significant change in electroencephalography. Interpretation. The intrinsic change of the subjects representing the specific response of acupoints and human brain to acupuncture indicated that de qi might be evaluated quantitatively by those above aspects, which facilitated the confirmation in validity and propagation of this treatment modality widely in the world.