Chronic Migraine Patients Research Articles

Cost of chronic and episodic migraine patients in continuous treatment for two years in a tertiary level headache Centre

BackgroundMigraine is one of the most common neurological diseases and an estimated 1.04 billion people worldwide have been diagnosed with migraine. Available data suggest that migraine is world widely associated with a high economic burden, but there is great variability in estimated costs that depends on the geographical, methodological and temporal differences between the studies. The purpose of this study was to quantify the annual direct cost of episodic migraine (EM) and chronic migraine (CM), both for the patient and for the National Health System (NHS), using data from subjects who attended an Italian tertiary headache centre. Furthermore, we evaluated comparatively the impact of gender and age on the economic burden of migraine.MethodsWe conducted a retrospective and non-interventional observational analysis of the electronic medical records of subjects with EM and CM who consecutively attended the Regional Referral Headache Centre of Rome and undergoing continuous treatment in the 2 years prior to 31 January 2019. This approach was intended to prevent distorsions due to natural fluctuations in migraine status over time. The collected data included demographic characteristics, number of specialist visits, consumption of medications, diagnostic tests, accesses in the emergency department (ED) and days of hospitalization due to the pathology.ResultsOur sample consisted of 548 patients (85.4% women and 14.6% men): 65.5% had CM and 34.5% had EM. The average annual expenditure per patient was €1482. 82.8% of the total cost (€1227) was covered by the NHS. The main item of expenditure were medications that represented 86.8% (€1286), followed by specialist visits (10.2%), hospitalizations for (1.9%), diagnostic tests for (1%) and ED visits for (0.1%). Costs were significantly higher for women than men (€1517 vs. €1274, p = 0.013) and increased with age (p = 0.002). The annual direct cost of CM was 4.8-fold higher than that of EM (€2037 vs. €427, p = 0.001).ConclusionOur results provide a valuable estimate of the annual direct cost of CM and EM patients in the specific setting of a tertiary headache centre and confirm the high economic impact of migraine on both the NHS and patients.

TRPM8 genetic variant is associated with chronic migraine and allodynia

BackgroundMany single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or subtypes are scarce. We aimed to investigate the associations of pre-identified migraine susceptibility loci in Taiwanese with migraine endophenotypes or subtypes, including chronic migraine and allodynia.MethodsThe associations of six SNPs identified from our previous study, including TRPM8 rs10166942, LRP1 rs1172113, DLG2 rs655484, GFRA1 rs3781545, UPP2 rs7565931, and GPR39 rs10803531, and migraine endophenotypes, including chronic migraine and allodynia were tested. Significant associations in the discovery cohort were validated in the replication cohort. The adjusted odds ratios (aOR) were calculated after controlling for confounders.ResultsIn total, 1904 patients (mean age 37.5 ± 12.2 years old, female ratio: 77.7%) including 1077 in the discovery cohort and 827 in the replication cohort were recruited. Of them, 584 (30.7%) had chronic migraine. Of the 6 investigated SNPs, TRPM8 rs10166942 T allele-carrying patients were more likely to have chronic migraine than non-T allele carriers in both discovery and replication cohorts and combined samples (33.7% vs. 25.8%, p = 0.004, aOR = 1.62). In addition, T allele carriers reported more allodynic symptoms than non-T allele carriers (3.5 ± 3.7 vs. 2.6 ± 2.8, p < 0.001). However, allodynia severity did not differ between episodic and chronic migraine patients. No further correlations between genetic variants and endophenotypes were noted for the other SNPs.ConclusionsTRPM8 may contribute to the pathogenesis of chronic migraine. However, our study did not support allodynia as a link between them. The underlying mechanisms deserve further investigations.

Multi-modal MRI Reveals the Neurovascular Coupling Dysfunction in Chronic Migraine

Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG and AG were negatively related to headache frequency and positively related to health condition and disease history. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain on the brain.

Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study.

To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data. Fifty-four episodic migraine, 56 chronic migraine patients and 50 controls underwent T1-weighted and diffusion-weighted magnetic resonance imaging acquisitions. Number of streamlines (trajectories of estimated fiber-tracts), mean fractional anisotropy, axial diffusivity and radial diffusivity were the connectome measures. Correlation analysis between connectome measures and duration and frequency of migraine was performed. Higher and lower number of streamlines were found in connections involving regions like the superior frontal gyrus when comparing episodic and chronic migraineurs with controls (p < .05 false discovery rate). Between the left caudal anterior cingulate and right superior frontal gyri, more streamlines were found in chronic compared to episodic migraine. Higher and lower fractional anisotropy, axial diffusivity, and radial diffusivity were found between migraine groups and controls in connections involving regions like the hippocampus. Lower radial diffusivity and axial diffusivity were found in chronic compared to episodic migraine in connections involving regions like the putamen. In chronic migraine, duration of migraine was positively correlated with fractional anisotropy and axial diffusivity. Structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine.

Couples Living with Chronic Migraines: A Phenomenological Study

Chronic migraine (CM) is a leading cause of disability, worldwide. Research examining the systemic effects of CM is scant. Specifically, little is understood about the effects of migraine on CM patients’ partners. Furthermore, the relational experiences of couples who deal with CM has been largely unexplored. Coming to better understand the systemic effects of migraine on couple relationships could enable more holistic biopsychosocial care for CM patients and their families. We utilized a phenomenological approach to study the CM experience in the context of couple relationships. We conducted dyadic interviews with eight chronic migraine patients and their partners about their experiences dealing with CM (N = 16). Six of the eight partners in our sample were also interviewed individually about their experience (14 interviews total). Data were gathered and analyzed using an iterative process. A team of seven researchers utilized an immersion/crystallization technique to analyze the data. Three major themes emerged from the analyses: (1) burdens and costs of migraines on partners, (2) coping with CM for partners, and (3) couple experience. Findings indicated that: partners of CM patients experience caregiving burdens; accepting the disorder’s burdens and long-term presence appears to vitally improve coping for CM patients and partners alike; and couples dealing with CM experience both balance and imbalance in the perceived relational giving and taking that occurs between them. Suggestions for future research and the clinical implications of our study are provided.

Headache Related Alterations of Visual Processing in Migraine Patients

Migraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta).We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 interictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analyzed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days.Compared to healthy controls, interictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days.Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. PerspectiveThis study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signaling that differ with the presence of headache.

Reductions in migraine and headache days in chronic migraine patients with and without prior migraine preventive treatment use: Subgroup analysis of the HALO CM study

Reductions in migraine and headache days in chronic migraine patients with and without prior migraine preventive treatment use: Subgroup analysis of the HALO CM study

Reduction in acute headache medication use with fremanezumab in chronic migraine patients by prior migraine preventive treatment use: Subgroup analysis of the HALO CM study

Reduction in acute headache medication use with fremanezumab in chronic migraine patients by prior migraine preventive treatment use: Subgroup analysis of the HALO CM study

Episodic and chronic migraine in children.

Migraine is the most common acute and recurrent headache syndrome in children. This condition has unique clinical characteristics in the pediatric population, that can evolve with age, and significantly impact a child's quality of life, affecting their education, socialization, and family life. The purpose of this review is to describe the varied clinical features of migraine seen in children, and discuss potential treatment options for pediatric migraine, including chronic migraine. In many patients a multifaceted approach involving lifestyle changes, treatment of comorbid conditions, and pharmacological treatments are needed for optimal headache control. WHAT THIS PAPER ADDS: Migraine presents as various phenotypes in children, sometimes evolving as the child ages. An expanded range of treatment options exists for the challenging chronic migraine patient.

Comparison of Pain-Related and Psychological Variables between Acute and Chronic Migraine Patients, and Factors Affecting Headache Chronicity.

ABSTRACTBackground:Migraine headache is classified as acute or chronic. In recent years, efforts have been made to identify the factors that might predispose individuals to develop the chronic-type headache. The present study aimed to draw a comparison between patients with acute and chronic migraine in terms of demographic, pain-related, and psychological variables. In addition, we also investigated factors affecting headache chronicity in such patients. Methods:The present cross-sectional study was conducted during 2017-2018. The target sample consisted of 250 patients with acute or chronic migraine who referred to various clinics affiliated to Shiraz University of Medical Sciences (SUMS), Shiraz, Iran, recruited by convenience sampling. All the participants filled in the questionnaires related to demographic characteristics, pain intensity, disability, depression, emotional intelligence, and anger. The data were analyzed using SPSS software (version 22.0) with t test, Chi-square test, and logistic regression analysis. P<0.05 was considered statistically significant. Results:Patients suffering from chronic migraine experienced higher levels of disability, depression, anger, and had lower levels of emotional intelligence compared to those with acute migraine. Based on the logistic regression analysis, variables that had a significant effect on headache chronicity were female gender (OR=5.81), married status (OR=3.77), patients with lower level of education (OR=0.26), headache duration (OR=1.53), disability (OR=0.28), depression (OR=3.66), and anger (OR=5.04). Conclusion:Variables such as disability, depression, and lack of anger control were among the key factors associated with headache chronicity in migraine patients.

State and trait anger and its expression in cluster headache compared with migraine: a cross-sectional study.

Anger is involved in the emotional experience of pain. Individuals with migraine are more likely to hold their anger-in than controls. However, only one study evaluated anger in cluster headache (CH). The objective is to compare anger between migraine and CH patients. One hundred thirty-five migraine and 108 CH patients completed the State Trait Anger Expression Inventory (STAXI-2), composed of 7 subscales. State Anger measures the intensity of the individual's angry feelings at the time of testing. Trait Anger evaluates general predisposition to become angry. Anger Expression Out and Anger Expression In measure the extent to which anger could be overtly expressed or suppressed. Anger Control Out and Anger Control In evaluate how individual try to control the outward or inward expression of anger. Anger Expression Index is a general index. CH patients have higher median scores than migraine patients in State Anger (46 vs 44, p = 0.012). CH patients have lower scores in Anger Control Out (44 vs 50, p = 0.016). In subgroup analysis, CH patients during the cluster period have higher scores than chronic migraine patients in State Anger (47 vs 44, p = 0.035), while CH patients in headache-free period did not differ from migraine patients. Migraine and CH patients differ in state anger, indicating that CH patients experienced higher intensity of anger during the time of testing. These data add new information about emotional regulation in headache patients and could support the hypothesis of different emotional and behavioral responses to pain in migraine and CH patients.

Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls.

Calcitonin gene-related peptide (CGRP) released from trigeminal nerve fibres indicates trigeminal activation and has a key role in migraine pathophysiology. The trigeminal nerve directly innervates the eye. Therefore, in this study, we compared Calcitonin gene-related peptide in tear fluid of migraine patients and healthy controls. Calcitonin gene-related peptide concentrations in tear fluid and plasma of 48 episodic and 45 chronic migraine patients and 48 controls were assessed using ELISA. Calcitonin gene-related peptide levels in tear fluid (0.94 ± 1.11 ng/ml) were ∼140 times higher than plasma concentrations (6.81 ± 4.12 pg/ml). Tear fluid CGRP concentrations were elevated in interictal migraine patients (1.10 ± 1.27 ng/ml, n = 49) compared to controls (0.75 ± 0.80 ng/ml, p = 0.022). There was no difference in tear fluid CGRP levels between interictal episodic and chronic migraine patients (episodic: 1.09 ± 1.47 ng/ml, n = 30 and chronic: 1.10 ± 0.89 ng/ml, n = 19) and no correlation of tear fluid CGRP levels with headache frequency in interictal patients (rho = 0.062, p = 0.674). Unmedicated ictal migraine patients had even more elevated tear fluid CGRP levels than interictal migraine patients (1.92 ± 1.84 ng/ml, n = 13, p = 0.102), while medicated ictal migraine patients had lower levels (0.56 ± 0.47 ng/ml, n = 25, p = 0.011 compared to interictal patients), which were undistinguishable from controls (p = 0.609). In contrast to tear fluid, no significant group differences were found in plasma CGRP levels. To the best of our knowledge, this study shows, for the first time, increased CGRP tear fluid levels in migraine patients compared to healthy subjects. Detection of calcitonin gene-related peptide in tear fluid is non-invasive, and likely allows a more direct access to CGRP released from the trigeminal nerve than plasma sampling.

Migraine and cluster headache show impaired neurosteroids patterns

BackgroundPerturbation of neuronal excitability contributes to migraine. Neurosteroids modulate the activity of γ-aminobutyric acid A and N-methyl-d-aspartate receptors, and might be involved in the pathogenesis of migraine. Here, we measured plasma levels of four neurosteroids, i.e., allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate, in patients affected by episodic migraine, chronic migraine, or cluster headache.MethodsNineteen female patients affected by episodic migraine, 51 female patients affected by chronic migraine, and 18 male patients affected by cluster headache were recruited to the study. Sex- and age-matched healthy control subjects (31 females and 16 males) were also recruited. Patients were clinically characterized by using validated questionnaires. Plasma neurosteroid levels were measured by liquid chromatography-tandem mass spectrometry.ResultsWe found disease-specific changes in neurosteroid levels in our study groups. For example, allopregnanolone levels were significantly increased in episodic migraine and chronic migraine patients than in control subjects, whereas they were reduced in patients affected by cluster headache. Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were reduced in patients affected by chronic migraine, but did not change in patients affected by cluster headache.ConclusionWe have shown for the first time that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders, raising the interesting possibility that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache. Whether the observed changes in neurosteroids are genetically determined or rather result from exposure to environmental or intrinsic stressors is unknown. This might also be matter for further investigation because stress is a known triggering factor for headache attacks in both migraineurs and cluster headache patients.

Response to BotulinumtoxinA in a migraine cohort with multiple comorbidities and widespread pain

BackgroundThe phase III research evaluating migraine prophylaxis therapy (PREEMPT) protocol was developed in low-risk migraine patients. We studied longitudinal response to treatment in a sequential retrospective observational cohort to evaluate...

Is there a correlation between levels of calcitonin gene related peptide in the serum and gingival crevicular fluid of chronic migraine patients

Is there a correlation between levels of calcitonin gene related peptide in the serum and gingival crevicular fluid of chronic migraine patients

Cognitive Decline in Chronic Migraine with Nonsteroid Anti-inflammation Drug Overuse: A Cross-Sectional Study.

Background Chronic migraine with medication overuse headache (CM-MOH) is the most common type of chronic migraine, and it increases risk of stroke and white matter lesions. These pathologic changes could induce cognitive decline. However, the alteration of cognitive function in CM-MOH patients is not established. Therefore, we took this study to reveal the cognitive performances in CM-MOH. Methods This cross-sectional study was conducted between December 2015 and January 2017. Patients were divided into CM-MOH, CMwoMOH (chronic migraine without medication overuse), and MO (migraine without aura) groups. Cognitive function was assessed in all cases during interictal periods using Addenbrooke's Cognitive Examination Test (ACE-R), Trail Making Test A/B (TMT A/B), and Digit Symbol Test (DST). Detailed headache characteristics and evaluation of anxiety, depression, and living and sleep quality were collected. Results 116 patients were included in this study. There were 21 CM-MOHs, 20 CMwoMOHs, 35 MOs, and 40 controls. Age and education were the independent risk factors of cognitive decline (P < 0.05). After adjusting, the risk of cognitive decline was higher in CM compared with control in ACE-R score and language fluency (P < 0.05). In addition, CM-MOH sufferers were in higher risk of memory and executive dysfunction (P < 0.05). The cognitive function had no difference between CM-MOH and CMwoMOH (P > 0.05). Meanwhile, CM-MOH got significantly higher scores than MO in anxiety and depression, with poorer performances in sleep and life quality (P < 0.05). Conclusion The risk of cognitive decline increased in chronic migraine patients. Nonsteroid anti-inflammatory drugs overuse had no influence on cognitive performances among chronic migraine sufferers.

Aberrant interactions of cortical networks in chronic migraine: A resting-state fMRI study.

We investigated resting-state (RS)-fMRI using independent component analysis (ICA) to determine the functional connectivity (FC) between networks in chronic migraine (CM) patients and their correlation with clinical features. Twenty CM patients without preventive therapy or acute medication overuse underwent 3T MRI scans and were compared to a group of 20 healthy controls (HC). We used MRI to collect RS data in 3 selected networks, identified using group ICA: the default mode network (DMN), the executive control network (ECN), and the dorsal attention system (DAS). Compared to HC, CM patients had significantly reduced functional connectivity between the DMN and the ECN. Moreover, in patients, the DAS showed significantly stronger FC with the DMN and weaker FC with the ECN. The higher the severity of headache, the increased the strength of DAS connectivity, and the lower the strength of ECN connectivity. These results provide evidence for large-scale reorganization of functional cortical networks in chronic migraine. They suggest that the severity of headache is associated with opposite connectivity patterns in frontal executive and dorsal attentional networks.

CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA

BackgroundSome variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA.MethodsWe included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16–74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher’s exact test.ResultsResponse to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33–7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28–8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found.ConclusionsPolymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.

The Association between Chronicity of Migraine and Complementary and Alternative Medication Use: The Turkish Perspective

Background and Purpose: The term of Complementary and Alternative Medication (CAM) is described by patients as all types of practices to prevent or treat illnesses, which are not currently considered as a part of conventional medicine. Although the advance in treatment for migraine, some patients prefer CAM therapies due to their concerns about conventional therapies. The aim of this study was to evaluate the association between CAM use and chronicity of migraine among Turkish migraineurs. Methods: Consecutive episodic and chronic migraine patients were recruited. A questionnaire of a list of CAM modalities including traditional therapies specific to Turkish culture, which was constructed by researcher through a literature review was given to all participants. Patterns of CAM treatments and patients’ reluctance to share CAM use with their doctors were evaluated. Results: Sixty-nine patients with episodic migraine and 31 with chronic migraine enrolled in the study. Thirty-six patients reported that they had tried CAM at least once within the last year. Massage, exercise, acupuncture, holistic methods, herbalism, vitamins, psychotherapy, hypnose, cupping, and neural therapy were used. Sociodemographic and clinical variables were not differed in CAM users of both groups. Eighty-one per cent of CAM users stated that they preferred not to tell their doctors about their CAM use if not asked. Conclusions: Patterns of CAM use in Turkey for migraine differ from western practices. Due to fear of disapproval, patients tend to hide CAM use from their doctors. Exploring the CAM use among migraineurs is essential to prevent potential interactions of CAM therapies with conventional treatments.

Efficacy of Erenumab in Chronic Migraine Patients With and Without Allodynia (P2.10-025)

Efficacy of Erenumab in Chronic Migraine Patients With and Without Allodynia (P2.10-025)