The Cumulative Therapeutic Effect of Acupuncture Treatment in Patients with Migraine without Aura: Evidence from Dynamic Alterations of Intrinsic Brain Activity and Effective Connectivity Analysis

We explored the dynamic alterations of intrinsic brain activity and effective connectivity after acupuncture treatment to investigate the underlying neurological mechanism of acupuncture treatment in patients with migraine without aura (MwoA). The fMRI scans were separately obtained at baseline, after the first and after the 12th acupuncture sessions in 40 patients with MwoA. Compared with HCs, patients with MwoA showed mostly decreased dynamic amplitude of low-frequency fluctuation (dALFF) variability in regions with differences. After acupuncture treatment, the decreased dALFF variability of the rostral ventromedial medulla (RVM), the superior lobe of left cerebellum (Cerebelum_Crus1_L), and the right precuneus (PCUN.R) progressively recovered. The RVM revealed gradually increased dynamic effective connectivity (DEC) variability outflow to the right middle frontal gyrus, the left insula, the right precentral gyrus, and the right supramarginal gyrus, and enhanced DEC variability from the right fusiform gyrus inflow to RVM. Furthermore, the increased DEC variability were found from Cerebelum_Crus1_L outflow to the left middle occipital gyrus and the left precentral gyrus, from PCUN.R outflow to the right thalamus. These dALFF variabilities were positive correlated with frequency of migraine attack and negative correlated with disease duration, dynamic GCA coefficients were positive correlated with Migraine-Specific Quality of Life Questionnaire score, negative correlated with frequency of migraine attack and visual analog scale score postacupuncture treatment. Our results provide insight into dynamic alterations from the perspective of dynamic local brain activity and effective connectivity for the understanding mechanisms of cumulative therapeutic effect of acupuncture in patients with MwoA.

КЛІНІЧНИЙ ВИПАДОК МОЖЛИВОЇ МІГРЕНІ З АУРОЮ, УСКЛАДНЕНОЇ МІГРЕНОЗНИМ ІНФАРКТОМ

We present a clinical case of ischemic stroke in a man with a new-onset migraine attack. Clinical case. A 25-year-old man was admitted to the acute cerebrovascular department due to severe throbbing headache in the left temporal area, vomiting, impaired vision on the right and numbness of the right leg. Complaints appeared abruptly in the form of scotoma in the right visual field. 20 minutes later, severe throbbing headache, nausea and numbness of the right leg developed. The event was preceded by sleep deprivation for 2 days. The patient’s mother has migraine with aura. Previously, the patient never had such attacks. On examination: right-sided homonymous upper-quadrant hemianopsia, hypoesthesia of the right leg. Brain MRI - focal hyperintensity at T2 and DWI in the left occipital region (acute ischemic stroke). The patient took aspirin at a dose of 300 mg for the first day, then 100 mg per day and valproic acid at a dose of 1200 mg per day. Two days after hospitalization, the patient experienced recovery of sensitivity in the right leg and regression of right-sided homonymous upper quadrant hemianopsia to small scotoma. The patient was discharged on the 5th day with a small right scotoma. It is recommended to continue taking aspirin 100 mg/day and valproic acid 1200 mg/day for the secondary prevention of migraine attacks and stroke. Discussion. The peculiarities of this case include the lack of history of migraine (at least 5 or more migrainous headache attacks) and the development of severe migraine attack with prolonged aura symptoms, which was triggered by sleep deprivation and eventually evolved into ischemic stroke. Conclusions. It is necessary to consider the possibility of ischemic stroke even in the cases of a new-onset migraine attack. If migrainous aura duration exceeds 60 minutes, it is necessary to perform a brain MRI to detect the early signs of cerebral ischemia.

Efficacy and Safety of Chuanxiong Qingnao Granule in Patients with Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective. To evaluate the efficacy and safety of Chuanxiong Qingnao Granule (CQG) to treat migraine. Method. This study was a randomized, double-blind, placebo-controlled trial. All migraineurs were recruited and randomly assigned into a treatment group treated with CQG and a control group treated with a placebo. The whole research process included a 4-week baseline, 12-week intervention, and 12-week follow-up. The primary outcome was responder rate, defined as the percentage of migraineurs with 50% or more reduction in the frequency of migraine attack during treatment and posttreatment period compared with the baseline. The secondary outcomes were the number of migraine days, migraine attack frequency, visual analogue scale (VAS), Fatigue Severity Scale (FSS), Hamilton Depression Scale (HAMD), and Migraine Disability Assessment (MIDAS). Results. A total of 346 migraineurs completed the research and were included in the intention-treatment analyses. The response rates differed significantly between the treatment group and the control group (71.5% vs. 12.1% at week 12 and 83.1% vs. 3.4% at week 24). Attack frequency, days of headache attack, VAS, FSS, HAMD, and MIDAS decreased at week 12 in both groups with more reduction in the treatment group ( P < 0.001 ). No severe adverse events were observed in this trial. Conclusion. Chuanxiong Qingnao Granule can significantly improve headache symptoms in patients with migraine while improving disability, fatigue, and depression with a good safety profile.

Expression of Selected microRNAs in Migraine: A New Class of Possible Biomarkers of Disease?

Preliminary but convergent findings suggest a role for microRNAs (miRNAs) in the generation and maintenance of chronic pain and migraine. Initial observations showed that serum levels of miR-382-5p and miR-34a-5p expression were increased in serum during the migraine attack, with miR-382-5p increasing in the interictal phase as well. By contrast, miR-30a-5p levels were lower in migraine patients compared to healthy controls. Of note, antimigraine treatments proved to be capable of influencing the expression of these miRNAs. Altogether, these observations suggest that miRNAs may represent migraine biomarkers, but several points are yet to be elucidated. A major concern is that these miRNAs are altered in a broad spectrum of painful and non-painful conditions, and thus it is not possible to consider them as truly “migraine-specific” biomarkers. We feel that these miRNAs may represent useful tools to uncover and define different phenotypes across the migraine spectrum with different treatment susceptibilities and clinical features, although further studies are needed to confirm our hypothesis. In this narrative review we provide an update and a critical analysis of available data on miRNAs and migraines in order to propose possible interpretations. Our main objective is to stimulate research in an area that holds promise when it comes to providing reliable biomarkers for theoretical and practical scientific advances.

Transient and Recurrent Vision Loss in a High-Altitude Porter from Pakistan on a Polish Winter Karakoram Expedition

Visual sensations appear in most migraine auras, but binocular blindness is uncommon. We described a case of multiple transient losses of vision in a man on a winter expedition to K2. His symptoms were later diagnosed as recurrent visual auras without pain. Sojourns at altitude can induce migraine attack; therefore, susceptible individuals should avoid factors that might provoke migraines at high altitude, such as improper acclimatization, dehydration and an inadequate sleep regime.

Old Habits Die Hard: Dietary Habits of Migraine Patients Challenge our Understanding of Dietary Triggers

Introduction: Migraine is a multifactorial neurological disorder with a major metabolic facet. Dietary approaches represent a commonly implemented lifestyle modifying strategy in headache clinics, yet the precise relationship between diet and migraine is still a matter of debate.Materials and Methods: The study consisted of two parts: first, in a cross-sectional design, we compared alimentary habits of migraine subjects and a control group of healthy volunteers. For the second part, we prospectively evaluated patients' daily consumption of various potentially migraine-triggering foods over a two-month period in order to examine their possible association with the occurrence of a migraine attack.Results: Most migraine patients reported avoiding at least one potentially migraine-triggering food/drink from their diet. In spite of that, with the sole exemption of citrus fruits, there were no statistically significant differences with respect to consumption patterns between migraine patients and controls (including wine and chocolate). Consumption frequency over time was proportional to intake of potentially migraine-triggering foods the day before a migraine attack.Conclusion: Our results underline the need of performing trigger challenges in order to avoid falling into an association-causation fallacy when attempting to identify possible alimentary migraine triggers. Indeed, it is possible that intake of certain foods like chocolate before attacks is a consequence of pre-attack cravings or a simple coincidence facilitated by previously established dietary habits.

The Cumulative Therapeutic Effect of Acupuncture Treatment in Patients With Migraine Without Aura: Evidence From Dynamic Alterations of Intrinsic Brain Activity and Effective Connectivity Analysis

Background: The underlying neurological mechanism of acupuncture treatment in migraine without aura (MwoA) remains unclear. Therefore, we explored the dynamic alterations of intrinsic brain activity and effective connectivity in patients with MwoA after acupuncture treatment.Methods:The fMRI scans were separately obtained at baseline, after the first and after the 12th acupuncture sessions in 40 patients with MwoA. The acupuncture treatments were finished within 6 weeks as twice a week. 36 matched healthy controls (HCs) were recruited and performed once fMRI scan. The dynamic amplitude of low-frequency fluctuation (dALFF) and dynamic granger causality analysis(GCA) were used to analyze the difference of different time points in patients with MwoA. The correlation analyses were performed in dALFF variability, dynamic effective connectivity (DEC) variability with clinical variables in patients with MwoA.Results:Compared with HCs, Patients with MwoA at baseline showed decreased dALFF variability in regions within rostral ventromedial medulla (RVM), the superior lobe of left cerebellum (Cerebelum_Crus1_L), the right inferior frontal gyrus, triangular part (IFGtriang.R), the right median cingulate and paracingulate gyri (DCG.R), the right precuneus (PCUN.R), and the left inferior parietal, supramarginal and angular gyri (IPL.L), increased dALFF variability only in the left inferior occipital gyrus (IOG.L). After acupuncture treatment, the decreased dALFF variability of the RVM, Cerebelum_Crus1_L , and PCUN.R progressively recovered, the RVM revealed gradually increased DEC variability to the right middle frontal gyrus (MFG.R), the left insula (INS.L), the right precentral gyrus (PreCG.R), and the right supramarginal gyrus (SMG.R). And enhanced DEC variability from the right fusiform gyrus (FFG.R) to RVM. Furthermore, the increased DEC variability were found from Cerebelum_Crus1_L to the left middle occipital gyrus (MOG.L) and the left precentral gyrus (PreCG.L), from PCUN.R to the right thalamus (THA.R). These dALFF variabilities were significantly positive correlated with frequency of migraine attack and negative correlated with disease duration at baseline, dynamic GCA coefficients were significantly positive correlated with Migraine-Specific Quality of Life Questionnaire (MSQ) score, negative correlated with frequency of migraine attack and visual analog scale (VAS) score postacupuncture treatment.Conclusions:Our results provide insight into dynamic alterations from the perspective of dynamic local brain activity and effective connectivity for the understanding mechanisms of cumulative therapeutic effect of acupuncture in patients with MwoA.Trial registration: ChiCTR, ChiCTR1900023105. Registered 11 May 2019, http://www.chictr.org.cn/showproj.aspx?proj=36959.

P.027 Efficacy and Safety of Eptinezumab Initiated During a Migraine Attack: Results from the RELIEF Study

Background: Eptinezumab is approved for migraine prevention, with demonstrated rapid onset of preventive benefit. RELIEF evaluated the efficacy and safety of eptinezumab initiated during a migraine attack. Methods: RELIEF (NCT04152083; parallel-group, double-blind, placebo-controlled) randomized adults with migraine (4-15d/mo in 3mo prior to screening) to eptinezumab 100mg or placebo, administered IV within 1-6h of qualifying migraine onset. Co-primary efficacy endpoints were time to headache pain freedom and time to absence of most bothersome symptom (MBS). Results: Eptinezumab (n=238) compared with placebo (n=242) achieved significantly faster headache pain freedom (median 4h vs 9h; hazard ratio=1.54, P=0.0006) and absence of MBS (2h vs 3h; 1.75, P<0.0001). At 2h, 23.5% and 12.0% (P=0.0009) of eptinezumab-treated and placebo patients, respectively, reported headache pain freedom, and 55.5% and 35.8% (P<0.0001) reported absence of MBS. Significantly fewer eptinezumab-treated patients used rescue medication within 24h (31.5% vs 59.9%; P<0.0001). Treatment-emergent adverse events occurred in 10.9% eptinezumab-treated and 10.3% placebo patients; no serious adverse events occurred. Conclusions: Infusion of the preventive migraine treatment, eptinezumab, during a migraine resulted in rapid and sustained freedom from headache pain and MBS vs placebo, starting 2h post-infusion, decreasing need for acute medication within 24h post-infusion. No notable safety findings were identified.