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.

Disrupted Dynamic Functional Connectivity of the Visual Network in Episodic Patients with Migraine without Aura

Background. Visual symptoms are common in patients with migraine, even in interictal periods. The purpose was to assess the association between dynamic functional connectivity (dFC) of the visual cortex and clinical characteristics in migraine without aura (MwoA) patients. Methods. We enrolled fifty-five MwoA patients as well as fifty gender- and age-matched healthy controls. Regional visual cortex alterations were investigated using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF). Then, significant regions were selected as seeds for conducting dFC between the visual cortex and the whole brain. Results. Relative to healthy controls, MwoA patients exhibited decreased ReHo and ALFF values in the right lingual gyrus (LG) and increased ALFF values in the prefrontal cortex. The right LG showed abnormal dFC within the visual cortex and with other core brain networks. Additionally, ReHo values for the right LG were correlated with duration of disease and ALFF values of the right inferior frontal gyrus and middle frontal gyrus were correlated with headache frequency and anxiety scores, respectively. Moreover, the abnormal dFC of the right LG with bilateral cuneus was positively correlated with anxiety scores. Conclusions. The dFC abnormalities of the visual cortex may be involved in pain integration with multinetworks and associated with anxiety disorder in episodic MwoA patients.

Neuropsychological Profile in Pediatric Migraine without Aura: A Pilot Study

Despite the high prevalence of headache in developmental age, current reports about its neuropsychological effects are still lacking. The aim of the present pilot study is to assess the neuropsychological skills among children affected by migraine without aura (MwoA). Fifteen children (7M/8F) (mean age 10.73 ± 2.13) with MwoA, consecutively referred to the Center for Childhood Headache at Università degli Studi della Campania “Luigi Vanvitelli”, underwent the Italian version of the NEPSY-2 after cognitive evaluation. Moreover, to assess the pain level and disability grade during daily activity, the VAS and PedMIDAS scales were used. MwoA children were comparable with the control group of 38 children with respect to age, gender, language, and education level. Written informed consent was obtained from all parents and from children directly, when appropriate. MwoA children differed from controls significantly among the NEPSY-2 subscales, with a relevant relationship between the frequency and intensity of the attacks. In conclusion, the results of the present pilot study may suggest that MwoA could impact significantly neuropsychological functioning in children.

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.

Effect of Cervical Mobilization and Transcutaneous Supraorbital Nerve Stimulation in Migraine Without Aura

Migraine is one of the most common disabling headache disorders which is categorized into two broad types based on the number of headache days. It is called episodic or general migraine if the attacks occur less than 15 days per month, and it is categorized as chronic or transformed migraine if headache occur on 15 or more days per month. This study was conducted to find out the effect of strategy for pain using a modality and strategy using mobilization in reducing disability, frequency and pain in migraine without aura. Thirty-Two subjects were selected based on diagnostic criteria for migraine and divided into two groups. Group A received Cervical Mobilization and Myofascial Release with home exercise program and Group B received Transcutaneous Supraorbital Nerve Stimulation with home exercise program. Visual Analogue Scale, Questionnaire (HIT-6) were recorded as outcome on baseline and after 3 weeks. Results showed significant improvements in both the groups with, p<0.01. Between group comparisons elicited non-significant differences with p˃ 0.05. Following the results, it can be concluded that cervical mobilization and Transcutaneous Supraorbital nerve stimulation can be added as a valuable adjunct to medical management in the treatment of migraine without aura.

Regulatory Effects of Acupuncture on Emotional Disorders in Patients With Menstrual Migraine Without Aura: A Resting-State fMRI Study

Background: Menstrual migraine without aura (MMoA) refers to a specific type of migraine that is associated with the female ovarian cycle. It is particularly serious and has brought huge life pressure and mental burden to female patients. Acupuncture has been commonly used to prevent migraines and relieve concomitant emotional disorders; however, the physiological mechanism underlying this intervention remains unclear. This study aimed to use resting-state functional magnetic resonance imaging (rsfMRI) to investigate whether acupuncture can modulate brain function and if the potential influence on brain activity correlates with improving emotional symptoms in MMoA patients.Methods: Overall, 44 patients were randomly divided into a true acupuncture (TA) group and the sham acupuncture (SA) group. Patients underwent rsfMRI before and after 3-month treatment, the amplitude of low-frequency fuctuations (ALFF) and regional homogeneity (ReHo) in rsfMRI were calculated. Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS), frequency of migraine attacks, visual analog scale, and intensity of the migraine were used for evaluate the clinical effect. The clinical changes of variables were also used to further assess the correlation with brain activity in MMoA patients.Results: After acupuncture treatment, the emotional symptoms of both groups of patients improved, and the clinical symptoms of migraine were alleviated. The major finding of our study was that patients with MMoA showed lower ALFF value in the left anterior cingulate and the value was positively correlated with the decreases in the SAS and SDS scores. In the SA group, common brain regions responded both in ALFF and regional homogeneity values mainly in the insula, and no significant correlations were observed between brain regions and clinical variables.Conclusions: These results indicated that both two acupuncture treatments were helpful in treating migraine and could improve emotion symptoms. TA had a relatively better effect in reducing the frequency of migraine attack than SA. The two therapies have different modulation effects as TA regulates emotional disorders by modulating the frontal-limbic regions, and SA may modulate pain perception through the placebo effect on insula and by indirectly regulating emotional disorders. These findings provided evidence that acupuncture is a complementary and alternative therapy to relieve clinical symptoms in female patients with migraines and could help enhance clinical diagnosis and treatment.Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR-IOR-15006648. Registered 23 June 2015].

Type and severity of migraine determines long-term risk of atrial fibrillation in women: a nationwide population-based study

Background Migraine, especially when accompanied by aura, increases the risk of ischemic stroke and has also shown a close relationship with the occurrence of atrial fibrillation (AF). Although the risk of stroke and cardiovascular diseases is higher in women with migraine than in men, there is a lack of evidence for gender differences in the risk of AF in migraineurs. Purpose We sought to evaluate the gender-specific risk of AF according to the type and severity of migraine. Methods The study population included all national health checkup examinees (2009) without a history of AF from the Korean National Health Insurance Service data. The diagnosis and type or severity of migraine were determined using claims data, including diagnostic, procedural, and medication prescription codes. Newly developed non-valvular AF was identified during 10 years of follow-up. Gender-difference in the effect of migraine on AF occurrence was evaluated according to the type and severity of migraine. A multivariate Cox regression model was used to adjust for baseline differences between comparison groups, including age, smoking status, drinking habit, regular physical activity, income level, diabetes mellitus, hypertension, dyslipidemia, body mass index, and glomerular filtration rate as covariates. Results Of a total of 4,020,488 subjects (men, n=2,213,147, women, n=1,807,341) enrolled, 4,986 had migraine with aura (mean age 50.6±14.0, men 29.3%) and 105,029 without aura (mean age 51.6±14.3, men 30.9%). The proportion of migraine with aura among migraine patients was 4% in both gender groups. In the total population, migraine or migraine with aura did not significantly increase the risk of AF. The risk of AF did not increase in a mild degree of migraine, irrespective of gender or the presence of aura. Severe migraine without aura modestly increased the risk of AF in both men and women compared to the control group. (Men, incidence rate [IR] 4.51 per 1,000 person-year, adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.12–1.31; Female, IR 3.00 per 1,000 person-year, adjusted HR 1.16, 95% CI 1.09–1.22) The increase of AF risk was the most prominent in women who had severe migraine with aura (IR 3.39 per 1,000 person-year, adjusted HR 1.48, 95% CI 1.18–1.85). In contrast, no significant association was observed between AF and migraine with aura in men. (IR 2.28, adjusted HR 0.63, 95% CI 0.39–1.01; P for interaction 0.011) Conclusions Mild migraine was not associated with an increase in AF risk regardless of gender or the presence of aura. Severe migraine without aura showed a mild increase in AF risk without gender-difference, while severe migraine with aura significantly increased the risk of AF only in women, not in men. Surveillance for incident AF and prompt stroke prevention would be beneficial, particularly for young-aged women suffering from severe migraine with aura. FUNDunding Acknowledgement Type of funding sources: None. Figure 1