Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood.

BACKGROUND: Many alternating hemiplegia of childhood (AHC) patients have received Cannabidiol (CBD) but, to our knowledge, there are no published data available. GOALS: Test the hypothesis that CBD has favorable effects on AHC spells. METHODS: Retrospective review of available data of AHC patients who received CBD. Primary analysis: Clinical Global Impression Scale of Improvement (CGI-I) score for response of AHC spells to CBD with calculation of 95% confidence interval (CI) for rejection of the null hypothesis. Secondary analyses, performed to achieve an understanding of the effect of CBD as compared to flunarizine, were CGI-I scores of 1) epileptic seizures to CBD, 2) AHC spells to flunarizine, 3) epileptic seizures to flunarizine. Also, Mann-Whitney test was done for comparison of CGI-I scores of CBD and flunarizine to both AHC spells and seizures. RESULTS: We studied 16 AHC patients seen at Duke University and University of Lyon. CI of CGI-I scores for AHC spells in response to CBD and to flunarizine, each separately, indicated a positive response to each of these two medications: neither overlapped with the null hypothesis score, 4, indicating significant positive responses with p < 0.05 for both. These two scores also did not differ (p = 0.84) suggesting similar efficacy of both: CBD score was 2 ± 1.1 with a 95% CI of 1.5-2.6 and flunarizine score was 2.3 ± 1.3 with a 95% CI of 1.7-3.1. In patients who had seizures, CI calculations indicated a positive effect of CBD on seizure CGI scores but not of flunarizine on seizure scores. CBD was well tolerated with no patients discontinuing it due to side effects and with some reporting positive behavioral changes. CONCLUSION: Our study indicates a real-life positive effect of CBD on AHC type spells.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 2: flunarizine.

OBJECTIVE: Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis. METHODS: A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo-controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation. RESULTS: Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06). CONCLUSIONS: Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large-scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.

Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial.

Nutraceuticals like alpha-lipoic acid (ALA) may have potential benefits as prophylactic agents for adolescent migraine, with fewer adverse events than existing medications. The present study was conducted to evaluate the safety and efficacy of add-on ALA for prophylaxis in adolescent migraine. A randomized, open-label, add-on clinical trial was conducted with 60 adolescent migraineurs, who were randomized to receive flunarizine or flunarizine with an add-on ALA. A clinical evaluation of the frequency and severity of migraine, responder rate, Pediatric Migraine Disability Assessment (PedMIDAS) scoring, serum thiol, and serum calcitonin gene-related peptide (CGRP) was performed both at baseline and following 12 weeks of treatment. The frequency of acute attacks of migraine decreased significantly (P = .001) in the test group compared with the control group. The responder rate was found to be significantly higher (80%) in the test group than in the control group (33.3%) (P = .001). The mean monthly migraine headache days in the test group showed a significant reduction (-7.7 days, 95%CI -9.1 to -6.3 days; P = .010). The severity of acute migraine attacks (mild, moderate, severe) also showed a significant reduction in the test group (P = .001). PedMIDAS scores showed significant improvement in the test group (P = .021), in comparison with the control group. Serum thiol levels were significantly increased in the test group (18 mmol/L, 95%CI 13.5 to 36.1 mmol/L; P = .001). Serum CGRP levels showed a significant reduction with adjunctive ALA therapy (-122.4 pg/mL, 95%CI -142.3 to -89.0 pg/mL; P = .006). Add-on ALA with flunarizine as a prophylactic agent for migraine in adolescents can improve clinical outcomes by improving clinical and biochemical parameters.

Interventional Study of Flunarizine Therapy on Symptom Relief and Vestibular Evoked Myogenic Potential Changes in Individuals with Vestibular Migraine.

INTRODUCTION: Migraine is the third most common disease in the world with an estimated prevalence of 14.7%. The purpose of this study was to identify the characteristic changes in cervical and ocular vestibular evoked myogenic potential (VEMP) and analyse changes in symptoms and VEMP after flunarizine therapy in patients diagnosed with vestibular migraine (VM). METHODS: Prospective interventional study was conducted on 31 VM patients. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) were recorded. Flunarizine (10 mg) was given once daily for two consecutive months. Prophylactic therapy was monitored with a monthly follow-up assessment of their symptoms and VEMP was repeated after 2 months. RESULTS: Headache was the chief complaint (67.7%). Vertigo was spontaneous and mostly moderate in intensity (93%). cVEMP was absent in 1 patient and oVEMP was absent in 3 patients. Post prophylactic treatment with flunarizine, there was significant reduction in the frequency (p = 0.001) and duration (p = 0.001) of headache and frequency (p = 0.001), duration (p = 0.001), and intensity (p = 0.009) of vertigo. cVEMP and oVEMP showed no significant differences (p > 0.05) between pre- and post-treatment recordings. CONCLUSION: Treatment with flunarizine helps in considerably reducing the episodes and duration of headache, as well as episodes, duration, and intensity of vertigo.

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.

The effect of topiramate versus flunarizine on the non-headache symptoms of migraine.

OBJECTIVES: To investigate the impact of topiramate versus flunarizine on the non-headache symptoms (NHS) of migraine, and to observe the changes of dopamine (DA) and prolactin (PRL) before and after prophylactic treatment. METHODS: Sixty-six episodic migraine patients were enrolled and randomized 1:1 to receive either flunarizine or topiramate treatment. Clinical characteristics and NHS associated with migraine were investigated before and after prophylactic treatment. The DA and PRL levels were also determined before and after prophylactic treatment. RESULTS: The NHS of migraine in the two groups were significantly better after treatment than before treatment in premonitory phase (PP), headache phase (HP), and resolution phase (RP). The NHS in the two groups had no significant difference in PP, HP, and RP before and after treatment. In the flunarizine group, the PRL content after treatment was significantly higher than that before treatment (t = -4.097, p < 0.001), but the DA content was decreased slightly compared with that before treatment (t = 1.909, p = 0.066). There was no significant difference in PRL content (t = 1.099, p = 0.280) and DA content (t = 1.556, p = 0.130) in topiramate group before and after treatment. CONCLUSIONS: The two classical prophylactic drugs of migraine were significantly effective in treating the NHS of migraine, but there was no significant difference between the two drugs. The DA-PRL axis may be involved in the underlying mechanism of the flunarizine treatment for the NHS of migraine.

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.

Clinical effect of flunarizine combined with duloxetine in the treatment of chronic migraine comorbidity of depression and anxiety disorder.

BACKGROUND: Migraine is common in primary headaches, and with the development of social economy and the increase in living pressure, the prevalence of migraine has an upward trend. OBJECTIVE: To observe the clinical effect of flunarizine combined with duloxetine in the treatment of chronic migraine with comorbid depression and anxiety disorders and to provide a reference for clinical treatment. METHODS: A total of 118 patients with chronic migraine complicated with depression and anxiety disorder admitted to our hospital from June 2018 to August 2020 were selected and divided into two groups according to treatment methods, 59 cases in each group. The control group was treated with flunarizine combined with loxoprofen sodium, and the observation group was treated with flunarizine combined with duloxetine. The changes of electroneurophysiological indexes, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitivity-C reactive protein (hs-CRP), Hamilton depression scale (HAMD) score, and Hamilton anxiety scale (HAMA) score before and after treatment in the two groups were recorded, and the total effective rate of clinical treatment in the two groups was counted. RESULTS: After treatment, TNF-α, IL-6, and hs-CRP in the two groups decreased gradually (p < .05). Further comparison between groups showed that TNF-α, IL-6, and hs-CRP in the observation group were lower than those in the control group (p < .05). After treatment, the HAMD score and the HAMA score of the two groups decreased gradually (p < .05). Further comparison between the two groups showed that HAMD score and HAMA score of the observation group were lower than those of the control group (p < .05). CONCLUSION: Flunarizine combined with duloxetine in the treatment of chronic migraine with depression and anxiety disorder can effectively improve neuroelectrophysiological indexes, reduce inflammation, and reduce depression and anxiety.

Can flunarizine be used routinely as the first option for childhood headache treatment?: Flunarizine and childhood headache.

The prevalence of headache in childhood increases due to environmental factors. Various risk factors in children whose playgrounds are restricted outside and therefore remain inactive. So diagnosis and treatment can be challenging. The aim of this study was to evaluate the experience of flunarizine in childhood headache with a focus on efficacy and success. We conducted a retrospective observational study of 185 pediatric patients at the tertiary pediatric emergency and pediatric neurology unit between May 2018 and May 2020. Patients with headache for >15 days of a month for at least 3 months were included in the study, whether or not receiving treatment. Also, all patients who had an adequate follow-up period were included in the study. All patients were evaluated by history, physical-neurological examination, blood tests, blood pressure, eye examination, and cranial magnetic resonance imaging. All data were evaluated statistically. Ninety-eight (53%) of 185 cases were female and 87 (47%) were male. Average age was 11.4 years (min-max, 4-17). There was family history in 51.3% of the cases. The most frequent applicants were in the autumn season (43%), when schools were opened. Organic causes were hypertension in 1 case, brain tumor in 1 case, and papilledema due to idiopathic intracranial hypertension in 2 cases. The other cases were asked to make a 1-month pain chart and grading according to the visual analog scale. In this process, it was stated that painkillers could be used if needed. At the end of the first month, these patients were reevaluated. Flunarizine treatment was initiated in 95 patients who had to use painkillers for >4 times and who described ≥6 pain score according to the visual analog scale. The treatment was discontinued due to sleepiness and weakness in 2 patients. At the end of the third month, a 50% reduction in headache was observed in 82 cases (86.3%). We used flunarizine as the first choice in all patients and we achieved a high rate of treatment success. Flunarizine can be considered as an alternative option for headache management in terms of low side effects, easy accessibility, and compliance with treatment.

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.

Pain sensitivities predict prophylactic treatment outcomes of flunarizine in chronic migraine patients: A prospective study.

BACKGROUND: We aimed to assess the differences in quantitative sensory testing between chronic migraine and healthy controls and to explore the association between pain sensitivities and outcomes in chronic migraine following preventive treatment. METHODS: In this prospective open-label study, preventive-naïve chronic migraine and healthy controls were recruited, and cold, heat, mechanical punctate, and pressure pain thresholds over the dermatomes of first branch of trigeminal nerve and first thoracic nerve were measured by quantitative sensory testing at baseline. Chronic migraines were treated with flunarizine and treatment response was defined as ≥50% reduction in the number of monthly headache days over the 12-week treatment period. RESULTS: Eighty-four chronic migraines and fifty age-and-sex-matched healthy controls were included in the analysis. The chronic migraine had higher cold pain thresholds over the dermatomes of the first branch of trigeminal nerve and the first thoracic nerve (p < 0.001 and < 0.001), lower pressure pain thresholds over the dermatomes of the first thoracic nerve (p = 0.003), heat pain thresholds over the dermatomes of the first branch of the trigeminal nerve and the first thoracic nerve (p < 0.001 and p = 0.015) than healthy controls. After treatment, 24/84 chronic migraine had treatment response. The responders with relatively normal pain sensitivity had higher heat pain thresholds over the dermatome of the first branch of the trigeminal nerve (p = 0.002), mechanical punctate pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.023), and pressure pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.026) than the hypersensitive non-responders. Decision tree analysis showed that patients with mechanical punctate pain threshold over the dermatomes of the first branch of the trigeminal nerve > 158 g (p = 0.020) or heat pain threshold over the dermatome of the first branch of the trigeminal nerve > 44.9°C (p = 0.002) were more likely to be responders. CONCLUSIONS: Chronic migraine were generally more sensitive compared to healthy controls. Preventive treatment with flunarizine should be recommended particularly for chronic migraine who have relatively normal sensitivity to mechanical punctate or heat pain.Trial registration: This study was registered on ClinicalTrials.gov (Identifier: NCT02747940).

The effectiveness of propranolol, flunarizine, amitriptyline and botulinum toxin in vestibular migraine complaints and prophylaxis: a non-randomized controlled study.

INTRODUCTION: Vestibular migraine is the most common cause of spontaneous episodic vertigo in adult patients and the second most common cause of vertigo in patients of all ages. OBJECTIVE: To assess the effectiveness of oral medication type (propranolol, flunarizine, and amitriptyline) and botulinum toxin A application on vestibular symptoms, headache severity and attack frequency for vestibular migraine patients. METHODS: Sixty patients with vestibular migraine were enrolled. Thirty patients received botulinum toxin A treatment (B+ group) in addition to the oral medication, whereas 30 patients received only oral medication (B- group). Headache severity was evaluated with Migraine Disability Assessment Scale and vertigo severity was evaluated with Dizziness Handicap Inventory scale. Vestibular migraine attack frequencies in the last three months were also evaluated. RESULTS: There was a statistically significant decrement in mean Dizziness Handicap Inventory scores, Migraine Disability Assessment Scale scores and vertigo attack frequencies after treatment for all patients, B+ and B- group patients (p<0.001 for all). The mean Migraine Disability Assessment Scale score gains (p<0.001) and vertigo attack frequency gains (p= 0.003) were significantly higher in the B+ patients than B- patients. CONCLUSIONS: Both B+ and B- group patients exhibited significant improvement in vestibular migraine attack frequencies, Dizziness Handicap Inventory score and Migraine Disability Assessment Scale score values. However, botulinum toxin A application had a more pronounced effect for Migraine Disability Assessment Scale score gain and vestibular migraine attack frequency values, but not for Dizziness Handicap Inventory score gain values. Thus, botulinum toxin A application should be considered for vestibular migraine patients whose headache severity degrees are more profound. The oral medication type (propranolol, flunarizine or amitriptyline) did not differ in influencing the vestibular migraine attack frequency, Dizziness Handicap Inventory score gain and Migraine Disability Assessment Scale score gain values.

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.

Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report.

RATIONALE: Familial hemiplegic migraine (FHM) is a rare, autosomal dominant migraine with aura. CACNA1A encodes the α1A subunit of P/Q-type voltage-gated calcium channels, and its mutations have been associated with a wide spectrum of episodic and chronic neurological disorders, including FHM type 1 (FHM1). PATIENT CONCERNS: A Chinese girl and some of her relatives who presented with hemiplegia with or without migraine were found to carry a novel heterozygous missense variant, I1379F, in CACNA1A by whole-exome sequencing. The variant consegregated with the disease and was predicted to be pathogenic. DIAGNOSIS: The patient was diagnosed with FHM1 clinically and genetically. INTERVENTIONS: Prophylactic therapy with flunarizine 5 mg daily was prescribed to the patient. OUTCOMES: Therapy with flunarizine was terminated after a few weeks. The intensity of the attacks was the same as before. LESSONS: This case indicates that FHM should be considered when a patient manifests with episodic hemiplegia without migraine. In addition, genetic testing is an indispensable method to identify atypical attacks of hemiplegic migraine.

[The efficacy of topiramate and flunarizine hydrochloride for prophylactic treatment of vestibular migraine].

Objective:To evaluate the efficacy and safety of topiramate and flunarizine hydrochloride in the prophylactic treatment of vestibular migraine prophylaxis. Methods:47 patients with confirmed or probable vestibular migraine（VM） treated at the vertigo clinic of our neurology department from August 2020 to April 2021 were reviewed, and 42 patients were finally included. They were divided into topiramate group （n=22） and flunarizine hydrochloride group （n=20）. The two groups were treated with topiramate 50 mg daily and flunarizine hydrochloride 10 mg daily, respectively. The visual analogue scale, vertigo duration, vertigo frequency, and Dizziness Handicap Inventory （DHI） scores of patients with VM before and 3 months after treatment were compared. The anxiety screening scale （GAD-7） and depression screening scale （PHQ-9） were recorded to assess the improvement of patients' anxiety and depression, and the occurrence of adverse events. Results:Topiramate and flunarizine hydrochloride effectively reduced vertigo intensity, vertigo duration, and vertigo frequency in VM patients （P<0.05）. Meanwhile, total DHI score, DHI physical （DHI-P）, DHI emotional （DHI-E）, DHI functional （DHI-F）, PHQ-9 and GAD-7 were significantly decreased（P<0.05）. Furthermore, topiramate was superior to flunarizine hydrochloride in reducing vertigo intensity, vertigo duration, vertigo frequency, DHI-P, and DHI-F, while there was no significant difference between two drugs in improving patients' mood（P>0.05）. No serious adverse events were reported in either group. Conclusion:This study suggests that topiramate and flunarizine hydrochloride are safe and effective in the prevention of VM, and the daily dose of topiramate 50 mg is superior to the daily dose of flunarizine hydrochloride 10 mg. However, there was no significant difference between the two drugs in terms of mood improvement.

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.