Inter-individual differences in pain anticipation and pain perception in migraine: Neural correlates of migraine frequency and cortisol-to-dehydroepiandrosterone sulfate (DHEA-S) ratio

Previous studies targeting inter-individual differences in pain processing in migraine mainly focused on the perception of pain. Our main aim was to disentangle pain anticipation and perception using a classical fear conditioning task, and investigate how migraine frequency and pre-scan cortisol-to-dehydroepiandrosterone sulfate (DHEA-S) ratio as an index of neurobiological stress response would relate to neural activation in these two phases. Functional Magnetic Resonance Imaging (fMRI) data of 23 participants (18 females; mean age: 27.61± 5.36) with episodic migraine without aura were analysed. We found that migraine frequency was significantly associated with pain anticipation in brain regions comprising the midcingulate and caudate, whereas pre-scan cortisol-to DHEA-S ratio was related to pain perception in the pre-supplementary motor area (pre-SMA). Both results suggest exaggerated preparatory responses to pain or more general to stressors, which may contribute to the allostatic load caused by stressors and migraine attacks on the brain.

Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time

Background An imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time. Methods We observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time. Results The results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = − 0.51, p = 0.03), intensity (r = − 0.51, p = 0.03) and disability (r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8). Conclusion The correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

Relationship between the Somatosensory Cortex Morphology, Cutaneous Allodynia, and Clinical Features of Patients with Migraine

Recent studies have demonstrated the presence of brain alterations in patients with migraine. Functional and vascular changes in the brain are related to the presence and severity of cutaneous allodynia. However, the association between brain structural changes and cutaneous allodynia has not been yet investigated in patients with migraine. Thus, the purpose of this study was to evaluate the correlation between the severity of cutaneous allodynia, migraine features, and the thickness and volume of the somatosensory cortex. Forty-five patients with migraine, with and without aura and chronic migraine, were included. Volunteers filled out the Allodynia Symptom Questionnaire (ASC-12/Brazil) and were evaluated via magnetic resonance imaging (MRI). The images were inspected by a blinded neuroradiologist and analyzed with Freesurfer software. Correlation tests and a linear regression model were used to evaluate the relationship among the outcomes. The somatosensory cortex thickness and volume were not different among migraine subgroups (p > 0.05). There was no significant correlation between the somatosensory thickness and volume with the ASC-12/Brazil, migraine frequency, intensity, migraine onset or aura frequency. The ASC-12/Brazil score variability cannot be predicted by the somatosensory cortex thickness or volume. The results show that the somatosensory cortex morphology is neither associated with cutaneous allodynia nor with migraine features among migraineurs.

Beneficial Effects of Kiatsu™ with Ki Training on Episodic Migraine: An Exploratory Study

Objective. To conduct an exploratory study of KiatsuTM with Ki training as a potential therapy for treating episodic migraine in women. Background. Current therapies for migraine have proven partially effective, highlighting the need for alternative treatment options. In preparation for development of a randomized controlled study, the authors conducted a single arm pilot exploratory study to evaluate the effect of Kiatsu with Ki training in adult females with episodic migraine. Methods. Study subjects established a baseline migraine frequency over 4 weeks. During the following 4 weeks, each subject received instruction in Ki training (to improve concentration, balance, and relaxation), accompanied by Kiatsu (a focused touch method that reduces tension, swelling, and pain). Subjects then participated in one session a month for additional 6 months. The initial session was 1 hour; subsequent sessions averaged 30 minutes. Subjects documented migraine frequency, migraine-specific quality of life scores, and medication use. Result. Sixty-nine subjects met the study inclusion criteria, and 21 completed the study. Subjects reported a significant reduction in migraine frequency after 1 month (from 7.2 to 3.8 migraines/month; p < 0.05 ), with an overall 53% reduction at 6 months ( p < 0.001 ). Significant improvements in quality of life (QoL) were reported after 1 month, with continued improvements until study completion ( p < 0.0001 ). A moderate reduction in medication use was also documented ( p < 0.03 ), corresponding to improved QoL scores. Conclusion. Kiatsu with Ki training may be an effective treatment option for females with migraines, either in combination with medications or as a potential alternative to medications for patients who do not benefit from conventional therapies. The results of this pilot study justify the development of a randomized controlled study designed to investigate the potential benefits of this novel therapeutic method for treating migraine.

Efficacy and safety of exogenous beta-hydroxybutyrate for preventive treatment in episodic migraine: A single-centred, randomised, placebo-controlled, double-blind crossover trial

Background Several studies propose that brain energy deficit might be partially involved in the pathophysiology of migraine. Previously, studies demonstrated that ketogenic diet causes a substantial reduction in migraine frequency. Since the ketogenic diet is restricting and its adherence is difficult, we proposed to supplement ketone bodies exogenously to provide a prophylactic effect in migraineurs. Aim To evaluate the prophylactic effect of exogenous DL-beta-hydroxybutyrate supplementation in episodic migraineurs. Methods A double-blind, placebo-controlled, randomised crossover trial was conducted, involving 41 patients with episodic migraine. Patients were randomised 1:1 into placebo or beta-hydroxybutyrate group before entering the first treatment period. Each treatment period was 12 weeks long, followed by four weeks of washout phase and four weeks of run-in phase before entering into the corresponding second treatment period. The primary endpoint was the number of migraine days in the last four weeks of treatment, adjusted for baseline. Results We observed no clinically significant amelioration of migraine frequency or intensity under DL-beta-hydroxybutyrate treatment as compared to placebo regarding number of migraine days (mean difference [95% CI]: −1.1[−5.07, 2.85]), migraine intensity (0–10 VAS: 1.5[−0.8, 3.7]). Conclusion The selected dose of supplemented exogenous DL-beta-hydroxybutyrate did not demonstrate efficacy in episodic migraineurs. ClinicalTrials.gov Identifier: NCT03132233

Can Ketogenic Diet Therapy Improve Migraine Frequency, Severity and Duration?

Migraine is the third most common condition worldwide and is responsible for a major clinical and economic burden. The current pilot trial investigated whether ketogenic diet therapy (KDT) is superior to an evidence-informed healthy “anti-headache” dietary pattern (AHD) in improving migraine frequency, severity and duration. A 12-week randomised controlled crossover trial consisting of the two dietary intervention periods was undertaken. Eligible participants were those with a history of migraines and who had regularly experienced episodes of moderate or mildly intense headache in the previous 4 weeks. Migraine frequency, duration and severity were assessed via self-report in the Migraine Buddy© app. Participants were asked to measure urinary ketones and side effects throughout the KDT. Twenty-six participants were enrolled, and 16 participants completed all sessions. Eleven participants completed a symptom checklist; all reported side-effects during KDT, with the most frequently reported side effect being fatigue (n = 11). All completers experienced migraine during AHD, with 14/16 experiencing migraine during KDT. Differences in migraine frequency, severity or duration between dietary intervention groups were not statistically significant. However, a clinically important trend toward lower migraine duration on KDT was noted. Further research in this area is warranted, with strategies to lower participant burden and promote adherence and retention.

Sleep Disorders in Pediatric Migraine: A Questionnaire-Based Study

There is a high comorbidity between migraine and sleep disorders (SD), with a mutual dependence between sleep and headache. This study aimed to analyze the relationship between headache features (migraine frequency and severity, migraine equivalents, use and efficacy of treatments) and sleep in pediatric migraine. Parents of children and adolescents with migraine completed the Children’s Sleep Habits Questionnaire (CSHQ) and the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) and answered questions about headache characteristics. The presence of SD was defined according to CSHQ score. SD were detected in 72.9% of 140 subjects, but only 5.0% already received a diagnosis. Patients with SD presented statistically significant higher headache frequency (p = 0.031) and higher prevalence of migraine equivalents (p = 0.007). A higher CSHQ total score was associated with higher frequency of severe attacks (p = 0.012) and lower acute drug efficacy (p = 0.003). Significant positive correlations of sleep onset delay, sleep duration and nightwakings subscales with migraine frequency emerged. Our findings indicate that SD are highly prevalent in pediatric migraine and frequently associated with a higher headache severity and lower response to acute therapy, but often remain underdiagnosed. Improving sleep quality could help to reduce migraine intensity and disability and vice versa.

Migraine and premenstrual syndrome: comorbid disorders?

IntroductionHeadache is a common symptom among women, including during the menstrual cycle. The migraine frequency in women who present migraine associated with the menstrual period ranges from 50% to 70%. Premenstrual syndrome (PMS) is prevalent among women, affecting 80% to 90% of them throughout their lives.ObjectiveThe objectives of this study were to verify PMS prevalence and its characteristics among women who present with cephalalgia in the neurology ambulatory care unit and show the prevalence of headache and its association with PMS in the gynecology ambulatory care unit.MethodsIt is a descriptive and qualitative study which was carried out at Emilio Carlos Teaching Hospital in the neurology and gynecology ambulatory care units with women aged 18 to 52 years old. Eighty-seven questionnaires were distributed and self-applied throughout the year of 2018 for data collection. Each questionnaire consisted of 27 questions about the life cycle of the women and their headache episodes. The diagnostic criteria for headache and migraine from the International Headache Society were used. Criteria for PMS were met according to the quality of life questionnaire.ResultsIn gynecology unit group, 9% of the women did not present headache, 76% had PMS and 94% presented with headache during PMS. In neurology, 79% of the women had PMS and 79% of the women who presented with cephalalgia also had PMS.ConclusionThere is a large percentage of PMS in both groups, i.e. neurological unit and gynecological unit, showing it is not a spurious correlation.

Comparison of cervical muscle isometric force between migraine subgroups or migraine-associated neck pain: a controlled study

This study aimed to verify if migraine frequency or migraine-associated neck pain were associated with a reduction of normalized force and altered electromyographic activity during maximal cervical muscle isometric contractions. Additionally, it aimed to assess the correlation of normalized isometric force with years with migraine, headache frequency, headache intensity, migraine-related disability, and severity of cutaneous allodynia. The sample comprises 71 women with migraine (40/31 episodic/chronic, 42/18 with/without neck pain) and 32 women without headache. Cervical muscle isometric force in flexion, extension, and lateral flexion was assessed synchronized with the acquisition of superficial electromyography from the cervical muscles. Women with episodic migraine presented lower normalized isometric force in extension, flexion, and right and left lateral flexions than controls (P < 0.05). Women with migraine and neck pain exhibited lower cervical extension and right/left lateral-flexions normalized isometric force than controls (P < 0.05). No significant differences were observed in antagonist activity. Normalized isometric force in all directions showed weak to moderate correlations with the severity of self-reported symptoms of cutaneous allodynia (− 0.25 ≥ r ≥ − 0.39). No additional linear correlation with clinical migraine features was observed. In conclusion, cervical muscle weakness may be associated with episodic migraine and neck pain concurrent with migraine attacks without altered antagonist activity. Additionally, it may also be related to the severity of cutaneous allodynia.