Clinical efficacy of the shallow puncture and more-twirling acupuncture method in migraine treatment and its effects on serum 5-HT and ß-EP levels.

BACKGROUND: The incidence rate for migraine is 12% worldwide, and recurrence is common, which seriously affects the physical and mental health of patients. OBJECTIVE: To observe the clinical effect of Shallow Puncture and More Twirling method of acupuncture in treating migraine and its impact on serum 5-HT and ß-EP. METHODS: A total of 76 patients with migraine were randomized into a control group and acupuncture group with 38 cases in each. In the control group, patients were orally administered flunarizine hydrochloride before sleep, 2 capsules once daily for 4 weeks. In the acupuncture group, Shallow Puncture and More Twirling method was adopted for the acupoints of Sizhukong (SJ 23), Toulinqi (GB 15) Shuaigu (GB 8), Xuanlu (GB 5), Fengchi (GB 20), Waiguan (SJ 5), Zulinqi (GB 41). Patients were given acupuncture 3 times per week for 4 weeks. Then, the total VAS (Visual Analogue Scale) scores, composite score of migraine, serum level of 5-HT and ß-EP, and the clinical efficacy differences were observed before and after treatment and the side-effects were recorded among the two groups. RESULTS: The total VAS scores and composite score of migraine were significantly reduced among both groups after the treatment (P< 0.05), and the serum level of 5-HT and ß-EP was significantly improved (P< 0.05). Compared with control group, the acupuncture group reported lower results in VAS score and migraine composite score (P< 0.05), and higher results in serum 5-HT and ß-EP level (P< 0.05). The acupuncture group with shallow puncture and more twirling method showed a total effective rate of 86.5%, which is higher than the control group (78.4%). The difference is statistically significant (P< 0.05). CONCLUSION: Shallow Puncture and More Twirling method was superior to flunarizine hydrochloride in the treatment of clinical symptoms of migraine. Acupuncture also increases the serum level of 5-HT and ß-EP in migraine.

Ratanasampil is more effective than flunarizine in relieving migraine.

Aims: Migraine is a common neurological disorder with high incidence in population. This study aimed to investigate the therapeutic efficacy of Tibetan medicine Ratanasampil (RNSP) and to identify the serum biomarkers for diagnosis and response assessment.Materials and methods: We prospectively recruited 108 migraine patients living at high altitude (2,260 m), including 40 patients for RNSP group, 40 patients for flunarizine (FLZ) group, and 28 patients for placebo group. Serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene related peptide (CGRP), nerve growth factor (NGF) and ß-endorphin (ß-EP) before and after therapy were measured.Results: In comparison with placebo, both FLZ and RNSP significantly reduced the migraine days, HIT-6 score and verbal rating scale, headache intensity, duration, accompanying symptoms and headache score in four and eight weeks treatment. RNSP showed no significant difference to FLZ in the above parameters after four weeks treatment, but showed significantly better relief after eight weeks treatment. The overall effective rate of RNSP (92.5%) was also significantly higher than FLZ (74.4%, p < 0.05), mainly due to significantly higher ratio of patients with full recovery. The serum levels of biomarkers, including 5-HT, BDNF, NGF and ß-EP, significantly elevated after eight weeks of treatment with RNSP, whereas the level of CGRP significantly decreased. The serum level of 5-HT exhibited significantly bigger percentage changes than other markers.Conclusion: In conclusion, RNSP was more effective than FLZ in relieving migraine after eight weeks continuous treatment. Serum 5-HT, BDNF, CGRP, NGF and ß-EP were effective markers reflecting the response to RNSP and FLZ therapy.

2022 Taiwan Guidelines for Preventive Treatment of Migraine.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice.

INTRODUCTION: Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) leads to blindness. It has been widely reported that increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) diets reduce CNV. Of the three major pathways metabolizing ω-3 (and ω-6 LCPUFA), the cyclooxygenase and lipoxygenase pathways generally produce pro-angiogenic metabolites from ω-6 LCPUFA and anti-angiogenic ones from ω-3 LCPUFA. Howevehr, cytochrome P450 oxidase (CPY) 2C produces pro-angiogenic metabolites from both ω-6 and ω-3 LCPUFA. The effects of CYP2J2 products on ocular neovascularization are still unknown. Understanding how each metabolic pathway affects the protective effect of ω-3 LCPUFA on retinal neovascularization may lead to therapeutic interventions. OBJECTIVES: To investigate the effects of LCPUFA metabolites through CYP2J2 pathway and CYP2J2 regulation on CNV both in vivo and ex vivo. METHODS: The impact of CYP2J2 overexpression and inhibition on neovascularization in the laser-induced CNV mouse model was assessed. The plasma levels of CYP2J2 metabolites were measured by liquid chromatography and tandem mass spectroscopy. The choroidal explant sprouting assay was used to investigate the effects of CYP2J2 inhibition and specific LCPUFA CYP2J2 metabolites on angiogenesis ex vivo. RESULTS: CNV was exacerbated in Tie2-Cre CYP2J2-overexpressing mice and was associated with increased levels of plasma docosahexaenoic acids. Inhibiting CYP2J2 activity with flunarizine decreased CNV in both ω-6 and ω-3 LCPUFA-fed wild-type mice. In Tie2-Cre CYP2J2-overexpressing mice, flunarizine suppressed CNV by 33 % and 36 % in ω-6, ω-3 LCPUFA diets, respectively, and reduced plasma levels of CYP2J2 metabolites. The pro-angiogenic role of CYP2J2 was corroborated in the choroidal explant sprouting assay. Flunarizine attenuated ex vivo choroidal sprouting, and 19,20-EDP, a ω-3 LCPUFA CYP2J2 metabolite, increased sprouting. The combined inhibition of CYP2J2 with flunarizine and CYP2C8 with montelukast further enhanced CNV suppression via tumor necrosis factor-α suppression. CONCLUSIONS: CYP2J2 inhibition augmented the inhibitory effect of ω-3 LCPUFA on CNV. Flunarizine suppressed pathological choroidal angiogenesis, and co-treatment with montelukast inhibiting CYP2C8 further enhanced the effect. CYP2 inhibition might be a viable approach to suppress CNV in AMD.

[Electroacupuncture at Siguan points for migraine of liver yang hyperactivity: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity. METHODS: A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups. RESULTS: After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (ï¼°<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (ï¼°<0.05). After treatment, the migraine symptom scores in the two groups were decreased (ï¼°<0.05), the change in the electroacupuncture group was greater than the western medication group (ï¼°<0.05). CONCLUSION: Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.

Electroacupuncture at Siguan points for migraine of liver yang hyperactivity: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity.@*METHODS@#A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups.@*RESULTS@#After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (Ｐ<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (Ｐ<0.05). After treatment, the migraine symptom scores in the two groups were decreased (Ｐ<0.05), the change in the electroacupuncture group was greater than the western medication group (Ｐ<0.05).@*CONCLUSION@#Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.

Comparison of Therapeutic Results with/without Additional Hyperbaric Oxygen Therapy in Idiopathic Sudden Sensorineural Hearing Loss: A Randomized Prospective Study.

OBJECTIVE: To assess the efficacy of the combination of hyperbaric oxygen (HBO) and pharmacological treatment in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and define patients amenable for HBO therapy. METHODS: Prospective, randomized, trial involving 136 cases with unilateral ISSNHL that were randomly divided into 2 groups: the pharmacological treatment (P) group and HBO + pharmacological treatment (HBO+P) group, which received additional HBO for 14 days besides the pharmacological treatments. Pure tone audiometry gain larger than 15 dBHL was defined as success, and the success rate of each group was calculated. RESULTS: The overall success rate of the HBO+P group and the P group is 60.6% (40/66) and 42.9% (30/70), respectively (p < 0.05). Furthermore, patients with mild-moderate baseline hearing loss, aged ≤50 years, receiving treatment in ≤14 days, or without accompanied dizziness/vertigo in the HBO+P group had higher success rate than the P group (p < 0.05). CONCLUSIONS: HBO combined with pharmacological treatments leads to better hearing recovery than pharmacological treatments alone.

[Systematic review and Meta-analysis on randomized controlled trial of efficacy and safety for acupuncture versus Flunarizine in treatment of migraine].

To systematically evaluate the efficacy and safety of acupuncture versus Flunarizine hydrochloride in the treatment of migraine. Four Chinese databases(CNKI, VIP, WanFang, CBM), three English databases(Cochrane Library, EMbase, Medline) and ClinicalTrail.gov were systematically and comprehensively retrieved. The retrieval time was from the establishment of each database to January 8, 2020. Randomized controlled trial(RCT) for acupuncture versus Flunarizine in the treatment of migraine were screened out according to inclusion criteria and exclusion criteria. The included studies were evaluated with the Cochrane bias risk assessment tool. The included studies was conducted by RevMan 5.3, and the outcome indicators were evaluated for evidence quality and strength of recommendation by the GRADE system. A total of 1 033 literatures were retrieved, and 23 studies were finally included. Except for 4 multiarm tests, the total sample size was 1 548, including 785 in acupuncture group and 763 in Flunarizine group. The overall quality of the included studies was not high. Meta-analysis results showed that the acupuncture group was superior to the Flunarizine group in reduction of headache frequency(SMD=-1.00, 95%CI[-1.45,-0.54], P<0.000 1). In reduction of headache intensity, acupuncture group was superior to Flunarizine group(SMD=-1.05, 95%CI[-1.41,-0.68], P<0.000 01). In reduction of headache duration, acupuncture group was superior to Flunarizine group(SMD=-1.42, 95%CI[-1.83,-1.02], P<0.000 1). The acupuncture group was superior to Flunarizine group(MD=-0.17, 95%CI[-0.21,-0.13], P<0.000 01) in reduction of the painkillers taking frequency. The acupuncture group was superior to Flunarizine group(SMD=-0.94, 95%CI[-1.35,-0.52], P<0.000 1) in allevia-tion of paroxysmal symptoms, such as nausea and vomiting. The GRADE system showed that the evidence level of the above indicators was extremely low, and the strength of recommendation was low. As for the occurrence of adverse reactions, the adverse reactions reported in the acupuncture group included in the study were all mild adverse reactions, like drowsiness, subcutaneous bleeding, local pain, subcutaneous hematoma and dizziness needle. The available evidence showed that acupuncture has a better efficacy than Flunarizine hydrochloride in the treatment of migraine in adult patients. However, due to the high bias risk in the included studies, the conclusions of this study shall be adopted with caution, and more high-quality studies shall be carried out for verification in the future.

Tuling Wendan Decoction combined with flunarizine in the treatment of migraine patients and the effect of intervention on serum cyclooxygenase-2, endothelin-1 and nitric oxide.

This experiment aimed to explore the curative effect of Tuling Wendan Decoction combined with flunarizine on migraine patients and the intervention effect on serum cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), nitric oxide(NO) levels. For this purpose, from January 2019 to January 2020, 96 patients with migraine in our hospital were selected as the research object. Using a simple randomization method, patients who meet the criteria were assigned 1:1, and each patient was assigned a random number, of which the number 1 to 48 were the observation group, and the number 49 to 96 were the control group. The control group was treated with flunarizine, and the observation group was treated with Tuling Wendan Decoction combined with flunarizine. Comparing the efficacy, incidence of adverse reactions, the incidence of headache, cerebral blood flow rate [basal artery (BA), vertebral artery (VA), middle cerebral artery (MCA)], vascular endothelial function (serum COX-2, ET-1, NO levels), neurological function [5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene-related peptide (CGRP)] before treatment, 4 weeks and 8 weeks after treatment between the two groups. The results for efficacy showed that after 8 weeks of treatment, the total effective rate of the observation group (93.75%) was higher than that of the control group (77.08%, P<0.05). In regards to the situation of headache attack, the number of headache attacks, duration, pain degree and accompanying symptom scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group (P<0.05). Results of cerebral blood flow velocity showed that the blood flow velocity of BA, VA, MCA in the observation group was lower than that in the control group after 4 and 8 weeks of treatment (P<0.05). Vascular endothelial function results indicated that the serum COX-2 and ET-1 levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum NO levels were higher than that of the control group (P<0.05). The serum BDNF and CGRP levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum 5-HT levels were higher than the control group (P<0.05). The incidence of adverse reactions between the two groups was not statistically significant (P>0.05). It was concluded that Tuling Wendan Decoction combined with flunarizine is the first treatment for migraine, with definite curative effect and can effectively improve the onset of headache, reduce the speed of cerebral blood flow, regulate vascular endothelial function and nerve function, and ensure safety.

Efficacy and safety of the classic Chinese herbal prescription Sanpian decoction on migraine: A meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of the classic Chinese herbal prescription Sanpian decoction for curing migraine. METHODS: Scopus, PubMed, EMBASE, SPRINGER LINK, China National Knowledge Infrastructure (CNKI), Weipu Database and WanFang Database were searched from inception through January 2019 to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of Sanpian decoction. RESULTS: Fifteen RCTs with a total of 1377 participants were identified. Compared with the control drugs, Sanpian decoction and Sanpian decoction combined with Sibelium significantly improved the clinical efficacy separately (relative risk [RR] 4.19, 95% confidence intervals [CI] 2.91 to 6.04, P < 0.00001; RR 1.29, 95% CI 1.09 to 1.54, P = 0.003 separately); the Sanpian decoction significantly improved the visual analogue scale score (VAS) (mean differences [MD] -1.83, 95% CI -2.69 to -0.97, P < 0.0001), headache score (MD -3.77, 95% CI -7.20 to -0.34, P = 0.03) and reduced the frequency of headache attacks (MD -1.61, 95% CI -2.07 to -1.14, P < 0.00001) and the concentration of endothelin (ET) (MD -11.90, 95% CI -23.22 to -0.58, P = 0.04) when compared with control drugs. There were minor side effects related to Sanpian decoction which were well tolerated. CONCLUSIONS: Sanpian decoction is of significant benefits and relative safety in treating migraine. However, more rigorous studies with larger sample sizes are needed due to methodological flaws and low quality of the included trials in this meta-analysis.

Systematic review and Meta-analysis on randomized controlled trial of efficacy and safety for acupuncture versus Flunarizine in treatment of migraine / 中国中药杂志

To systematically evaluate the efficacy and safety of acupuncture versus Flunarizine hydrochloride in the treatment of migraine. Four Chinese databases(CNKI, VIP, WanFang, CBM), three English databases(Cochrane Library, EMbase, Medline) and ClinicalTrail.gov were systematically and comprehensively retrieved. The retrieval time was from the establishment of each database to January 8, 2020. Randomized controlled trial(RCT) for acupuncture versus Flunarizine in the treatment of migraine were screened out according to inclusion criteria and exclusion criteria. The included studies were evaluated with the Cochrane bias risk assessment tool. The included studies was conducted by RevMan 5.3, and the outcome indicators were evaluated for evidence quality and strength of recommendation by the GRADE system. A total of 1 033 literatures were retrieved, and 23 studies were finally included. Except for 4 multiarm tests, the total sample size was 1 548, including 785 in acupuncture group and 763 in Flunarizine group. The overall quality of the included studies was not high. Meta-analysis results showed that the acupuncture group was superior to the Flunarizine group in reduction of headache frequency(SMD=-1.00, 95%CI[-1.45,-0.54], P<0.000 1). In reduction of headache intensity, acupuncture group was superior to Flunarizine group(SMD=-1.05, 95%CI[-1.41,-0.68], P<0.000 01). In reduction of headache duration, acupuncture group was superior to Flunarizine group(SMD=-1.42, 95%CI[-1.83,-1.02], P<0.000 1). The acupuncture group was superior to Flunarizine group(MD=-0.17, 95%CI[-0.21,-0.13], P<0.000 01) in reduction of the painkillers taking frequency. The acupuncture group was superior to Flunarizine group(SMD=-0.94, 95%CI[-1.35,-0.52], P<0.000 1) in allevia-tion of paroxysmal symptoms, such as nausea and vomiting. The GRADE system showed that the evidence level of the above indicators was extremely low, and the strength of recommendation was low. As for the occurrence of adverse reactions, the adverse reactions reported in the acupuncture group included in the study were all mild adverse reactions, like drowsiness, subcutaneous bleeding, local pain, subcutaneous hematoma and dizziness needle. The available evidence showed that acupuncture has a better efficacy than Flunarizine hydrochloride in the treatment of migraine in adult patients. However, due to the high bias risk in the included studies, the conclusions of this study shall be adopted with caution, and more high-quality studies shall be carried out for verification in the future.

[Observation on therapeutic effect and mechanism research of acupuncture on headache in the recovery phase of ischemic stroke].

OBJECTIVE: To explore the clinical therapeutic effect and mechanism of acupuncture on headache in the recovery phase of ischemic stroke. METHODS: A total of 97 patients with headache in the recovery phase of ischemic stroke were randomized into an acupuncture group (57 cases) and a western medication group (40 cases). In the western medication group, flunarizine hydrochloride capsule was taken orally 5 mg each time, once a day. In the acupuncture group, acupuncture was applied at Qiuxu (GB 40), Zulinqi (GB 41), Xuanli (GB 6), Shuaigu (GB 8), Fengchi (GB 20) and Baihui (GV 20) for migraine; Chongyang (ST 42), Neiting (ST 44), Jiexi (ST 41), Zusanli (ST 36), Hegu (LI 4), Cuanzhu (BL 2) and Baihui (GV 20) for forehead pain; Jinggu (BL 64), Kunlun (BL 60), Tianzhu (BL 10), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for occipital headache; Taichong (LR 3), Yongquan (KI 1), Sanyinjiao (SP 6), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for parietal headache. The needles were retained for 30 min each time, once a day and 5 times a week. Both of the two groups were given consecutive treatment for 14 days. The visual analogue scale (VAS) and the headache scores before and after treatment and the recurrence rate 1 month after treatment were observed to evaluate the therapeutic effect, before and after treatment, the contents of substance P (SP), dopamine (DA), serotonin (5-HT), alpha-endorphin (α-EP) and beta-endorphin (ß-EP) in plasma were determined by ELISA in the two groups. RESULTS: Compared before treatment, the VAS scores, the headache scores and the contents of SP, DA and 5-HT in plasma were reduced and the contents ofα-EP andß-EP in plasma were increased in the two groups (all P<0.01). After treatment, the changes of the VAS score, the headache score and the contents of pain-related factors and endogenous opioid peptides in plasma in the acupuncture group were larger than the western medication group (all P<0.05). The total effective rate in the acupuncture group was 84.2% (48/57), which was superior to 62.5% (25/40) in the western medication group, and the recurrence rate in the acupuncture group was lower than the western medication group (both P<0.01). CONCLUSION: The therapeutic effect of acupuncture on headache in the recovery phase of ischemic stroke is superior to flunarizine hydrochloride capsule, and the mechanism may relate to down-regulate the pain-related factors and up-regulate endogenous opioid peptides in plasma.

The Effectiveness of Acupuncture Combined with Tuina Therapy in Patients with Migraine.

BACKGROUND: This study aimed to explore the effectiveness of acupuncture combined with tuina therapy in patients with migraine. METHODS: A prospective, randomized controlled assessor-blind clinical trial was performed between January 2017 and May 2018, and 135 patients were assigned into acupuncture combined with tuina (A), acupuncture (B), and control (flunarizine hydrochloride) (C) groups, each with 45 patients. Treatments were performed for 12 weeks and a 4-week follow-up. Frequency of attacks, severity of pain, duration of migraine, associated symptoms, patient-reported outcome (PRO) scores, and frequency of analgesic consumption were assessed. RESULTS: The total effective rate was 95.6, 88.9, and 75.6% for group A, B, and C, respectively, with a significant reduction in attack frequency, severity of pain, duration of migraine, and associated symptoms at post-treatment and follow-up compared to pre-treatment. The PRO scores and frequency of analgesic consumption were significantly improved (group A, p < 0.01; groups B and C, - p < 0.05). The differences in pre-/post-treatment and in pre-treatment/follow-up in groups A and B were significantly improved compared to group C (A vs. C, p < 0.01; B vs. C, A vs. B, p < 0.05). No significant adverse events occurred. CONCLUSION: Acupuncture combined with tuina could significantly increase the therapeutic effect of acupuncture in migraine treatment.

Calcium antagonists for acute ischemic stroke.

BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke. OBJECTIVES: To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes. SEARCH METHODS: The evidence is current to 6 February 2018. We searched the Cochrane Stroke Group Trials Register (6 February 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), MEDLINE Ovid (1950 to 6 February 2018), Embase Ovid (1980 to 6 February 2018), and four Chinese databases (6 February 2018): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese Scientific Periodical Database of VIP information, and Wanfang Data. We also searched the following trials registers: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN registry, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, and we contacted trialists and researchers. SELECTION CRITERIA: Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. We used standard Cochrane methodological procedures. MAIN RESULTS: We included 34 trials involving 7731 participants. All the participants were in the acute stage of ischemic stroke, and their age ranged from 18 to 85 years, with the average age ranging from 52.3 to 74.6 years across different trials. There were more men than women in most trials. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine. More than half of these trials followed participants for at least three months. Calcium antagonists showed no effects on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13; 22 trials; 22 studies; 6684 participants; moderate-quality evidence) or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17; 31 trials; 7483 participants; moderate-quality evidence). Thirteen trials reported adverse events, finding no significant differences between groups. Most trials did not report the allocation process or how they managed missing data, so we considered these at high risk of selection and attrition bias. Most trials reported double-blind methods but did not state who was blinded, and none of the trial protocols were available. AUTHORS' CONCLUSIONS: We found no evidence to support the use of calcium antagonists in people with acute ischemic stroke.

Efficacy of Nimodipine Plus Yufeng Ningxin Tablets for Patients with Frequent Migraine.

BACKGROUND/AIMS: To test the effects of Nimodipine plus Yufeng Ningxin tablets on frequent migraine. METHODS: Two hundred forty-two patients with frequent migraine were divided into the control group with those consuming Flunarizine (120 cases) and the treatment group with those consuming Nimodipine plus Yufeng Ningxin tablets (122 cases). The course of frequent migraine treatment lasted 7 weeks. The number of migraine days, visual analogue scale (VAS) score, and response rate were measured. RESULTS: There was significant difference in the cure rate as the Nimodipine plus Yufeng Ningxin tablets group compared with the Flunarizine group (78.7 vs. 21.7%; p < 0.001). Fewer migraine days and VAS score were observed in the treatment group when compared with the control group (p < 0.05). Nimodipine plus Yufeng Ningxin tablets were superior to Flunarizine in terms of the response rate at week 7 (p < 0.05). CONCLUSION: Due to its high cure rate, treatment with Nimodipine plus Yufeng Ningxin tablets is recommended to control frequent migraine, and this hypothesis needs to be confirmed through further studies conducted on a more extensive population.

Role of flunarizine hydrochloride in secondary brain injury following intracerebral hemorrhage in rats.

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.

[Therapy of migranes]. / Therapie der Migräne.

In migraine attack treatment analgesics such as nonsteroidal anti-inflammatory drugs and triptans can be utilized. The efficacy of acute attack treatment is relevant to prevent migraine chronification. For prophylactic treatment ß­blockers, tricyclic antidepressants, flunarizine, antiepileptics and onabotulinumtoxin A are available. There is evidence that some other substances (e. g. sartans) are also efficacious in this regard. Furthermore, nondrug approaches are essential in migraine therapy. Early education and prophylactic treatment of patients at risk may prevent from medication overuse headache. Noninvasive neuromodulatory approaches as supraorbital or vagal nerve stimulation are emerging methods for prophylactic treatment. Ongoing clinical trials investigate an oral calcitonin gene-related peptide (CGRP) antagonist for acute treatment and several prophylactic monoclonal CGRP or CGRP receptor-antibodies regarding safety, side effects and efficacy as new therapeutic options.

Zhengtian Capsule versus flunarizine in patients with migraine: a multi-center, double-blind, double-dummy, randomized controlled, non-inferior clinical trial.

BACKGROUND: The primary objective of this study was to assess whether Zhengtian Capsule was non-inferior to flunarizine in efficacy and safety profile for prevention of migraine in adults. METHODS: This was a double-dummy, double-blind, multicenter, positive drug (flunarizine), parallel randomized controlled, non-inferior clinical trial. Patients (n = 360) were randomized in a 1:1 to receive either Zhengtian Capsule or flunarizine, including 12 weeks' intervention and 4 weeks' follow-up. The primary outcome measure was responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period). The secondary outcome measures included migraine attack frequency, the number of migraine days, pain evaluated by visual analogue scale (VAS) score, duration of migraine attacks, the times of using analgesics, patient-reported outcome (PRO) measure of migraine and the scores of short-form 36 Health Survey Scale (SF-36). Weight variation in both groups was also evaluated. Adverse events were monitored throughout the trial. RESULTS: Zhengtian Capsule was non-inferior to flunarizine in responder rate at week 12 and follow-up period (P = 0.002, P < 0.001). There was fewer migraine days in Zhengtian Capsule group at follow-up period compared with flunarizine (P = 0.001). For the total duration of migraine attacks, there was significant group difference at week 4 which favored the control group (P = 0.009). For the total score of PRO scale, there was statistical difference between the two groups at follow-up period (P = 0.021). There were also group differences between the two groups in the dimensions of somatization symptoms at week 4 (P = 0.022) and functional status at week 12 and follow-up period (P < 0.001, P < 0.001). However, there were no significant differences between the two groups in migraine attack frequency, VAS scores reduction, consumption of acute pain drugs and the dimension scores of SF-36 at any time interval of the treatment period (P > 0.05). No severe adverse events occurred in the trial. Flunarizine was found associated with a weight gain. CONCLUSION: Zhengtian Capsule was non-inferior to flunarizine with regard to the primary endpoint. In addition, it could reduce migraine days and improve the functional status and somatization symptoms of migraine patients with good safety profile. TRIAL REGISTRATION: This trial was registered at Chinese Clinical Trial Register (ChiCTR), ChiCTR-TRC-13004412.

Acupuncture for migraine prevention.

BACKGROUND: Migraine is a complex and multifactorial brain disorder affecting approximately 18% of women and 5% of men in the United States, costing billions of dollars annually in direct and indirect healthcare costs and school and work absenteeism and presenteeism. Until this date, there have been no medications that were designed with the specific purpose to decrease the number of migraine attacks, which prompts a search for alternative interventions that could be valuable, such as acupuncture. METHODS: Acupuncture origins from ancient China and encompasses procedures that basically involve stimulation of anatomical points of the body. RESULTS: This manuscript reviews large and well-designed trials of acupuncture for migraine prevention and also the effectiveness of acupuncture when tried against proven migraine preventative medications. CONCLUSION: Acupuncture seems to be at least as effective as conventional drug preventative therapy for migraine and is safe, long lasting, and cost-effective. It is a complex intervention that may prompt lifestyle changes that could be valuable in patients' recovery.

Increase in body temperature during migraine attacks.

INTRODUCTION: Intermittent fever has been occasionally related to migraine, either as a migraine equivalent or as a migraine accompaniment. We present a case of recurrent increase in body temperature consistently associated with migraine headaches. METHODS: A 15-year-old girl reported a 3-year lasting history of migraine without aura, with a feeling of warmth occurring in each episode. Ancillary tests did not show any evidence of secondary headaches or any systemic disease. A 2-month headache diary was obtained, with daily records of headache intensity (0, no headache; 1, mild pain; 2, moderate pain; 3, severe pain) and simultaneous measurements of axillary temperature. Both parameters were registered in the evening, at 6:00 pm every day. The distribution of headache intensity and body temperature as well as the relationship between both variables over time were analyzed with nonparametric tests. RESULTS: The number of days without pain was 28 (45.2%); a mild headache was present on 13 days (21%), a moderate headache on 15 days (24.2%), and a severe headache on 6 days (9.7%). Headache days were associated with higher body temperature than headache-free days (median values: 37.3°C vs 36.6°C; Mann-Whitney U-test, P < 0.001). Moreover, a positive correlation was found between headache intensity and body temperature (Spearman's rho coefficient: 0.83, P < 0.001). CONCLUSIONS: Recurrent increase in body temperature may be another manifestation of the complex clinical spectrum of migraine. This symptom is probably related to hypothalamic involvement.