Similarities and differences between chronic migraine and episodic migraine

OBJECTIVE: To quantify and characterize the similarities and the differences between chronic migraine (CM) patients with medication overuse and episodic migraine (EM) patients with only occasional analgesic use. BACKGROUND: Population-level epidemiology, characteristics, mechanisms of chronic daily headache, and medication-overuse headache have been widely studied but patient characteristics have received less attention. Methods.-We compared sociodemographic data, family history, physiological and medical history, health services utilized, drugs taken/prescribed, and outcome of 2 groups of subjects: 150 patients, suffering from CM, complicated by probable medication-overuse headache (CM group), consecutively admitted during 2005 to the inpatients' ward of the Headache Centre of the University Hospital of Modena and Reggio Emilia, Italy, to undergo withdrawal from their overused medications; 100 patients suffering from EM, uncomplicated by medication overuse (EM group), consecutively referred to the outpatients' ward of the Headache Centre during November and December 2005. RESULTS: All sociodemographic characteristics were significantly different between the 2 groups. As a whole, the CM group began to suffer from migraine earlier than the EM group. Drug and/or alcohol abuse was significantly higher among first-degree relatives of CM (19%) than of EM (6%) patients. The most frequent comorbid disorders were psychiatric (67%) and gastrointestinal diseases (43%) in the CM group, and allergies in the EM group (31%). Seventy percent of CM patients and 42% of EM patients were taking daily at least another drug, besides those for headache treatment. Most overused medications in the CM group were triptans (43%); the EM group used above all single NSAIDs (56%). At 3-month follow-up, prophylactic treatments reduced, by at least 50%, the frequency of headache in about three-fourths of patients of both the groups; however, headache remained significantly more frequent in the CM than in EM group: only a minority (15%) of CM patients reverted to a headache frequency comparable to that of the EM group. CONCLUSIONS: CM patients present more multiple comorbid disorders, polypharmacy, and social impediments than EM patients. These associated conditions complicate CM clinical management. Even after withdrawal from medication overuse, CM could not be completely reverted by current prophylactic treatments.     

Obsessive-Compulsive Disorder and Migraine With Medication-Overuse Headache

Objective.— A strong association has been demonstrated between migraine, particularly in the chronic form and with medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD and MOH in migraineurs.
Methods.— A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Results.— In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent compared with CM, EM, and controls ( P  < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect to other groups ( P  < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found in both MOH and CM compared with controls and EM.
Conclusions.— The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.     

Glutamate levels in cerebrospinal fluid and triptans overuse in chronic migraine

OBJECTIVE: Chronic migraine (CM) is a common disorder, affecting 2% to 3% of the general population. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, central sensitization, and may be linked to migraine chronification. Triptans brought a novel option for the acute migraine treatment. As the development of central sensitization impacts upon the effectiveness of triptan therapy, we hypothesized that glutamate might be related to triptan response mechanisms. METHODS: We studied 19 patients diagnosed with CM according to the International Headache Society (2004) criteria. Patients were divided in those overusing analgesics (NSAIDs); those without overuse, and those overusing triptans. RESULTS: Cerebrospinal fluid (CSF) glutamate levels were similar in patients overusing acute medications (0.335 +/- 0.225 micromol) compared to those without overuse (0.354 +/- 0.141 micromol), P= NS). In contrast, patients overusing triptans had CSF glutamate levels significantly lower than that observed in nonoverusers (0.175 +/- 0.057 vs 0.354 +/- 0.141 micromol, P= 0.015), and significantly higher than controls (0.175 +/- 0.057 vs 0.109 +/- 0.066 micromol, P= 0.039). In triptan overusers, CSF glutamate levels, although lower, were not significantly different from patients overusing other types of analgesics. CONCLUSIONS: Our study showed lower glutamate levels in CSF of CM patients overusing triptans. Glutamate may be implicated in triptan response mechanisms, triptans may work in part by reducing extracellular glutamate levels in the brain.     

Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine and medication-overuse headache: findings from cerebrospinal fluid

The study set out to investigate the role of corticotrophin-releasing factor (CRF) and orexin-A in chronic migraine (CM) and medication-overuse headache (MOH). Twenty-seven patients affected by CM and 30 with MOH were enrolled. Control CSF specimens were obtained from 20 age-matched subjects who underwent lumbar puncture for diagnostic purposes, and in all of them CSF and blood tests excluded central nervous system or systemic diseases. Orexin-A and CRF were determined by radioimmunoassay methods. Significantly higher levels of orexin-A and CRF were found in the CSF of MOH and to a lesser extent in patients with CM compared with control subjects (orexin-A: P  < 0.001 and P  < 0.02; CRF: P  < 0.002 and P  < 0.0003). A significant positive correlation was also found between CSF orexin-A values and those of CRF ( R  = 0.71; P  < 0.0008), monthly drug intake group ( R  = 0.39; P  < 0.03) and scores of a self-completion 10-item instrument to measure dependence upon a variety of substances, the Leeds Dependence Questionnaire (LDQ) in the MOH group ( R  = 0.68; P  < 0.0003). The significantly higher orexin-A levels found in CM and MOH can be interpreted as a compensatory response to chronic head pain or, alternatively, as an expression of hypothalamic response to stress due to chronic pain. A potential role for orexin-A in driving drug seeking in MOH patients through activation of stress pathways in the brain can also be hypothesized.     

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study

BackgroundMedication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC).MethodsRS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation.ResultsIncreased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients.ConclusionsThe current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.     

Need for analgesics/drugs of abuse: a comparison between headache patients and addicts by the Leeds Dependence Questionnaire (LDQ)

Our aim was to compare the need for analgesics/drugs of abuse between headache patients--chronic and episodic headache sufferers--and addicts, by the Leeds Dependence Questionnaire (LDQ). This is a self-completion 10-item instrument to measure dependence upon a variety of substances. We administered the LDQ questionnaire to 122 chronic daily headache (CDH) sufferers who had been taking one dose of analgesic drug every day for at least 1 year; 71 subjects suffering from episodic headache (EH) using analgesics only occasionally; 115 consecutive drug addicts (DA) with a diagnosis of substance dependence. The mean LDQ total score was similar in the CDH (11.58+/-6.35) and DA (10.37+/-6.51) groups, and for both it was significantly higher than the score in the EH (5.61+/-3.00) group (P<0.001). The CDH group had the highest scores, and higher scores than the DA group (Z=-8.18, P<0.001) in item 8, assessing the primacy of effect over the kind of analgesic used, and in item 10 (Z=-5.03, P<0.001), asking if it is difficult to live without the analgesic; the DA group had the highest scores, and higher scores than the CDH group, in item 9 (Z=-5.07, P<0.001) addressing the need for the continued administration of the drug to maintain well-being, and in item 3 (Z=-2.39, P<0.05), exploring compulsion to start the use of the drug. The EH group had lower scores in all items (P<0.05) except for item 9, where there was no difference from CDH group; the EH group had also lower scores (P<0.001) than the DA group, except for item 8, where, instead, the score was higher than in the DA group (Z=-5.33, P<0.001). A strong link develops between chronic headache patients and the analgesics they use. This sort of 'dependence' appears to be a consequence of headache, originating from the necessity for the analgesic to cope with everyday life.     

IL-6 Levels in Migraine Patients Receiving Topiramate

There is considerable evidence suggesting that cytokines play important roles in pain and in mediating neurovascular inflammation associated with migraine headaches. Although consensus exists to recommend topiramate (TPM) for migraine prevention, the mechanism of action in this regard is unknown. We measured serum interleukin-6 (IL-6) levels in 66 migraine patients. Of these patients, 23 (34.9%) were taking TPM for migraine, and 43 (65.1%) were not. The IL-6 levels were compared with those of healthy controls without migraine, from the population living in the same region. The mean IL-6 levels in migraine patients taking TPM and patients who did not were 67.06 ± 92.09 pg/mL and 44.09 ± 59.19 pg/mL, respectively ( P  > 0.05). The IL-6 levels were higher in the patients taking TPM. The IL-6 level in the controls was 8.60 ± 7.36 pg/mL, which was significantly lower than the patient group using TPM ( P  = 0.001). Our results show that, although IL-6 may be involved in pain induction or inflammatory mechanisms of migraine attacks, the serum IL-6 level was not reduced in migraine patients receiving TPM therapy. In conclusion, we found high IL-6 levels in migraine patients both with and without TPM therapy, suggesting that high IL-6 levels during pain-free periods could be a conditioning factor, making patients more vulnerable to pain attacks in chronic migraine. Further studies investigating the possible mechanism of TPM in migraine are needed.     

Structural brain network characteristics in patients with episodic and chronic migraine

BackgroundMigraine is a primary headache disorder that can be classified into an episodic (EM) and a chronic form (CM). Network analysis within the graph-theoretical framework based on connectivity patterns provides an approach to observe large-scale structural integrity. We test the hypothesis that migraineurs are characterized by a segregated network.Methods19 healthy controls (HC), 17 EM patients and 12 CM patients were included. Cortical thickness and subcortical volumes were computed, and topology was analyzed using a graph theory analytical framework and network-based statistics. We further used support vector machines regression (SVR) to identify whether these network measures were able to predict clinical parameters.ResultsNetwork based statistics revealed significantly lower interregional connectivity strength between anatomical compartments including the fronto-temporal, parietal and visual areas in EM and CM when compared to HC. Higher assortativity was seen in both patients’ group, with higher modularity for CM and higher transitivity for EM compared to HC. For subcortical networks, higher assortativity and transitivity were observed for both patients’ group with higher modularity for CM. SVR revealed that network measures could robustly predict clinical parameters for migraineurs.ConclusionWe found global network disruption for EM and CM indicated by highly segregated network in migraine patients compared to HC. Higher modularity but lower clustering coefficient in CM is suggestive of more segregation in this group compared to EM. The presence of a segregated network could be a sign of maladaptive reorganization of headache related brain circuits, leading to migraine attacks or secondary alterations to pain.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01216-8.     

Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS)

Migraine is a disabling neurological disease that affects 14.7 % of Europeans. Studies evaluating the economic impact of migraine are complex to conduct adequately and with time become outdated as healthcare systems evolve. This study sought to quantify and compare direct medical costs of chronic migraine (CM) and episodic migraine (EM) in five European countries. Cross-sectional data collected via a web-based survey were screened for migraine and classified as CM (≥15 headache days/month) or EM (<15 headache days/month), and included sociodemographics, resource use data and medication use. Unit cost data, gathered using publicly available sources, were analyzed for each type of service, stratified by migraine status. Univariate and multivariate log-normal regression models were used to examine the relationship between various factors and their impact on total healthcare costs. This economic analysis included data from respondents with migraine in the UK, France, Germany, Italy, and Spain. CM participants had higher level of disability and more prevalent psychiatric disorders compared to EM. CM participants had more provider visits, emergency department/hospital visits, and diagnostic tests; the medical costs were three times higher for CM than EM. Per patient annual costs were highest in the UK and Spain and lower in France and Germany. CM was associated with higher medical resource use and total costs compared to EM in all study countries, suggesting that treatments that reduce headache frequency could decrease the clinical and economic burden of migraine in Europe. Comparing patterns of care and outcomes among countries may facilitate the development of more cost-effective care, and bring greater recognition to patients affected by migraine.     

Derangement of Serotonin System in Migrainous Patients With Analgesic Abuse Headache: Clues From Platelets

Accumulating evidence indicates that serotonin (5-HT) may be involved in the process of analgesic-induced headache transformation. In order to clarify this hypothesis, we investigated the 5-HT system in migraine patients with analgesic abuse headache by using platelets as a neuronal model. Our results revealed a significant decrease in platelet 5-HT content in these patients compared to migraine patients and nonheadache controls (179.24 ± 10.18, 451.22 ± 14.35, and 480.22 ± 13.98 ng/10⁹ platelets, respectively; P <0.001). This biochemical result was well correlated with a significant decrease ( P 2/cells, respectively). As this canaliculi system plays a significant role in the platelet secretory response, such dilatation may imply an excessive release of substances from this system. Based on this platelet model, we suggest that excessive use of analgesics alters the central 5-HT system by depleting 5-HT from its storage sites and results in the hyposerotonergic state. This analgesic-induced 5-HT alteration may be a possible mechanism of headache transformation observed in this condition.     

Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: a case-control study with a focus on NGF,BDNF, VEGF,and PGE2

BackgroundSeveral inflammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls.MethodsFrom September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index.ResultsSerum levels of NGF were significantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were significantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were significantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were significantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ= -0.025 and P-value=0.850).ConclusionsOur findings suggest that NGF, BDNF, PGE2, and VEGF may play a significant role in migraine pathogenesis and/or chronification, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these findings.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01377-6.     

Out-patient detoxification in chronic migraine: comparison of strategies

Chronic migraine (CM) patients frequently overuse symptomatic medications (SM). These medications may create a cycle of rebound, worsening of headache and withdrawal symptoms that perpetuate the headache itself. In addition, the overuse of such substances is believed to counteract the efficacy of preventive treatments. We conducted a prospective randomized open-label trial comparing approaches to out-patient management in 150 CM patients (125 women, 25 men; ages 18-80 years, mean 40.3 +/- 13.8) with overuse of SM. In each group, 50 patients received education and orientation and were then abruptly withdrawn from all SM. Immediately following withdrawal, the first group took prednisone (60 mg/ day 2 days, 40 mg/day 2 days and 20 mg/day 2 days) for 6 days, the second group did not have any regular medications to take and the third group took naratriptan (2.5 mg twice a day) during this initial period. All patients had similar profiles of headache characteristics and consumption (quality and quantity) of SM before initiation of the treatment, but most were not severe headache sufferers, heavy SM overusers or were overusing opioids. After 5 weeks the headache frequency and intensity, the prevalence and frequency of withdrawal symptoms and consumption of rescue medications during the first 6 days were compared between groups. In addition, adherence to treatment (who returned or not and for which reasons, between groups) and headache frequency, week by week, among the groups of patients were also compared. Forty-four (88%) patients from the prednisone group, 41 (82%) from the 'nothing' group and 35 (70%) from the naratriptan group adhered to the treatment and returned. The were no differences between groups with regard to treatment adherence (P = 0.072), headache frequency as well as intensity (P = 0.311) and decreasing of days with headache after 5 weeks and weekly (P = 0.275). However, the incidence of withdrawal symptoms and consumption of rescue drugs was higher among the patients who did not take regular medications during the first 6 days (P = 0.0001 and P = 0.006). We concluded that CM patients with moderate overuse of SM other than opioids may be detoxified on an out-patient basis regardless of the strategy adopted with regard to the use of regular drugs during the initial days of withdrawal, but prednisone and naratriptan may be useful for reducing withdrawal symptoms and rescue medication consumption. Further controlled studies are necessary to confirm these observations.     

Comparison of CGRP and NO responses in the human peripheral microcirculation of migraine and control subjects

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are two molecules shown to have a role in migraine pathophysiology . Our objective was to test the hypothesis that migraine subjects are particularly sensitive to these signal molecules. The cutaneous microvascular responses to endothelial and non-endothelial dependent dilators were tested using laser Doppler flowmetry in combination with iontophoresis. The blood flow responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and CGRP, and to local warming (44 °C) were compared in this controlled trial. The design was that of two arms: patients diagnosed with migraine without aura ( n  = 9) for >10 years were compared with nine healthy subjects matched for age and gender (seven female and two male, age range 30–60 years). Iontophoretic administration resulted in local vasodilation. ACh induced a relaxation of 1225 ± 245% (relative to baseline) in controls and 1468 ± 368% ( P  > 0.05) in migraine. The responses to SNP were 873 ± 193% in controls and 1080 ± 102% ( P  > 0.05) in migraine subjects. The responses to CGRP were 565 ± 89% in controls and 746 ± 675% ( P  > 0.05) in migraine patients. The responses to local heating which induced maximum dilation did not differ between the groups (1976 ± 314% for controls and 1432 ± 226% in migraine; P  > 0.05. We conclude that there is no change in the microvascular responsiveness of the subcutaneous microvasculature in migraine.     

Peri-ictal normalization of visual cortex excitability in migraine: an MEG study

To delineate if the change in cortical excitability persists across migraine attacks, visual evoked magnetic fields (VEF) were measured in patients with migraine without aura during the interictal ( n  = 26) or peri-ictal ( n  = 21) periods, and were compared with 30 healthy controls. The visual stimuli were checkerboard reversals with four different check sizes (15', 30', 60' and 120'). For each check size, five sequential blocks of 50 VEF responses were recorded to calculate the percentage change of the P100m amplitude in the second to the fifth blocks in comparison with the first block. At check size 120', interictal patients showed a larger amplitude increment than controls [28.1 ± 38.3% ( s.d. ) vs. 8.7 ± 21.3%] in the second block and a larger increment than peri-ictal patients in the second (28.1 ± 38.3% vs. −3.2 ± 19.2%), fourth (22.7 ± 31.2% vs. −5.7 ± 22.3%) and fifth (20.5 ± 30.4% vs. −10.8 ± 30.1%) blocks ( P  < 0.05). There was no significant difference at other check sizes or between peri-ictal patients and controls. In conclusion, there may be peri-ictal normalization of visual cortical excitability changes in migraine that is dependent on the spatial frequency of the stimuli and reflects a dynamic modulation of cortical activities.     

Comparison Between Neck Pain Disability and Cervical Range of Motion in Patients With Episodic and Chronic Migraine: A Cross-Sectional Study

ObjectiveThe purpose of this study was to evaluate neck pain–related disability and cervical range of motion (CROM) in patients with episodic migraine (EM) and chronic migraine (CM) and to examine the correlation of both outcomes.MethodsThis cross-sectional study consisted of 91 patients with EM and 34 with CM. Cervical range of motion was measured with the CROM device, and pain during the cervical movement was recorded. Self-reported disability related to neck pain was assessed with the Neck Disability Index.ResultsPatients with CM showed higher Neck Disability Index scores and more moderate and severe disability (P = .01). Severe disability as a result of neck pain was associated with 7.6-fold risk of developing CM (P = .003). No significant differences in CROM were identified between groups. Moderate negative correlations between CROM and disability were found for 4 motions within the CM group (− 0.60 < r < − 0.39) and with 3 in the EM group (− 0.48 < − 0.45). Disability was positively and moderately correlated to pain evoked during CROM in both groups (0.34 < r < 0.51).ConclusionThis study found that neck pain was highly prevalent in patients with migraine. Neck pain–related disability increased with increased frequency of the migraine attacks and was associated with the risk of migraine chronicity. The correlation between CROM and neck pain disability was more evident in patients with CM and in patients with pain during cervical movement.     

Clinical characteristics and patient-reported outcomes of chronic and episodic migraine patients at a US tertiary headache center: A retrospective observational study

Objective

To describe differences in clinical and demographic characteristics between patients with episodic migraine (EM) or chronic migraine (CM) and determine the effect of migraine subtype on patient-reported outcome measures (PROM).

Background

Prior studies have characterized migraine in the general population. While this provides a basis for our understanding of migraine, we have less insight into the characteristics, comorbidities, and outcomes of migraine patients who present to subspecialty headache clinics. These patients represent a subset of the population that bears the greatest burden of migraine disability and are more representative of migraine patients who seek medical care. Valuable insights can be gained from a better understanding of CM and EM in this population.

Methods

We conducted a retrospective observational cohort study of patients with CM or EM seen in the Cleveland Clinic Headache Center between January 2012 and June 2017. Demographics, clinical characteristics, and patient-reported outcome measures (3-Level European Quality of Life 5-Dimension [EQ-5D-3L], Headache Impact Test-6 [HIT-6], Patient Health Questionnaire-9 [PHQ-9]) were compared between groups.

Results

Eleven thousand thirty-seven patients who had 29,032 visits were included. More CM patients reported being on disability 517/3652 (14.2%) than EM patients 249/4881 (5.1%) and had significantly worse mean HIT-6 (67.3 ± 7.4 vs. 63.1 ± 7.4, p < 0.001) and median [interquartile range] EQ-5D-3L (0.77 [0.44–0.82] vs. 0.83 [0.77–1.00], p < 0.001), and PHQ-9 (10 [6–16] vs. 5 [2–10], p < 0.001).

Conclusions

There are multiple differences in demographic characteristics and comorbid conditions between patients with CM and EM. After adjustment for these factors, CM patients had higher PHQ-9 scores, lower quality of life scores, greater disability, and greater work restrictions/unemployment.     

Headache Prophylaxis With BoNTA: Patient Characteristics

( Headache 2010;50:63-70)
Objective.— To assess the characteristics of patients receiving botulinum toxin type A (BoNTA; BOTOX^®) in the treatment of headache (HA) disorders.
Methods.— The following observational epidemiologic data and baseline patient characteristics were prospectively collected from eligible patients treated with BoNTA at 10 US HA specialty centers: demographics; HA diagnoses and characteristics (frequency, severity, and disability); prior and current HA treatments and response; clinical response to BoNTA; Migraine Disability Assessment (MIDAS) questionnaire; and adverse events. Patients maintained a daily HA diary and were evaluated at each follow-up visit.
Results.— Of 703 patients enrolled (mean age 43.1 years, 78.5% females, 95.4% white), nearly 66% had a diagnosis of chronic migraine (CM), with or without medication overuse. Approximately 75% had severe disability (MIDAS grade IV), and the mean pain rating was 6.5 (where 0 = no pain, 10 = pain as bad as it can be). More than 90% of patients had ≥1 prophylactic HA treatment failure; median number of failures was 4. Significant association was observed between HA frequency and MIDAS grade ( P  < .001). Approximately 80% of patients with CM had severe (grade IV) disability. The median number of monthly medication days was higher in the group with MIDAS grade IV ( P  < .001). HA frequency and severity, failed prophylactic therapies, and greater number of coexisting medical conditions were all negatively associated with measures of health-related quality of life.
Conclusions.— Majority of patients treated with BoNTA in a specialty HA center presented with a CM diagnosis. HA disability was correlated with measures of frequency and treatment utilization.     

Depressive symptoms and insecure attachment as predictors of disability in a clinical population of patients with episodic and chronic migraine

OBJECTIVES: To define predictors of migraine-related disability in patients with episodic and chronic migraine referred to a specialty migraine clinic, focusing on depressive symptoms and insecure attachment style that, because of their association with responses to pain and physical illness, might be predictive of greater migraine-related disability. BACKGROUND: The Migraine Disability Assessment questionnaire (MIDAS) has proved to be a reliable and easy-to-use instrument to assess migraine-related disability. As clinicians are increasingly using MIDAS in their diagnostic and treatment decisions for patient care, an understanding of the factors influencing migraine-related disability is essential for a rationale use of such an instrument. METHODS: Two-hundred patients suffering from episodic migraine without aura (EM), and chronic migraine (CM) with and without medication overuse, and referred to a specialty headache clinic were evaluated using the MIDAS, the Beck Depression Inventory (BDI), and the Attachment Style Questionnaire (ASQ). Diagnosis of episodic and chronic migraine was operationally defined according to the International Headache Society (IHS) and Silberstein-Lipton criteria. RESULTS: Multiple regression analysis showed that, in the total sample, disability was higher in those patients with CM, more severe depressive symptoms, an insecure style of attachment (as reflected by a lower score on the ASQ confidence scale), and experiencing more severe headache pain intensity. In the subgroup of patients with episodic migraine, an insecure style of attachment emerged as the most significant predictor of disability (other significant predictors were female sex and number of headache days per month). In contrast, in the subgroup of patients with CM, the only significant predictor of the total MIDAS score was a greater severity of depressive symptoms. CONCLUSIONS: Our findings demonstrate the relevance of attachment style, an enduring psychological trait not evaluated in previous studies, in influencing the disability level in patients with migraine and confirm the role of comorbid depressive symptoms in modulating the impact of migraine on every day functioning.     

Validating Migraine-Specific Quality of Life Questionnaire v2.1 in episodic and chronic migraine

Objective.— To provide evidence for the reliability and validity of the Migraine‐Specific Quality of Life Questionnaire Version 2.1 (MSQ) for use in chronic migraine (CM) in adults. Background.— MSQ is one of the most frequently utilized disease‐specific tools assessing impact of migraine on health‐related quality of life (HRQL). However, evidence for its reliability and validity are based on studies in episodic migraine (EM) populations. Additional studies assessing the reliability and validity of the MSQ in patients with CM are needed. Methods.— Cross‐sectional data were collected via web‐based survey in 9 countries/regions. Participants were classified as having CM (≥15 headache days/month) or EM (<15 headache days/month). Three MSQ domains – Role Function‐Preventive (RP), Role Function‐Restrictive (RR), and Emotional Function (EF) – were rescaled to 0‐100, where higher scores indicate better HRQL, and analyzed for internal consistency reliability (Cronbach's α), construct validity (correlations between MSQ scales and measures of depression/anxiety [Patient Health Questionnaire; PHQ‐4], disability [Migraine Disability Assessment Questionnaire; MIDAS], and functional impact [Headache Impact Test; HIT‐6], where lower scores indicate better HRQL for each measure), as well as discriminant validity across migraine groups. Results.— A total of 8726 eligible respondents were classified: 5.7% CM (n = 499) and 94.3% EM (n = 8227). Subjects were mostly female (83.5%) with a mean (±SD) age of 40.3 ± 11.4, and were similar between the 2 groups. MSQ domain scores for CM and EM groups, respectively, were: RP = 61.4 ± 26.1 and 71.7 ± 24.0; RR = 44.4 ± 22.1 and 56.5 ± 24.1; EF = 48.3 ± 28.1 and 67.2 ± 26.7. Internal consistency of the overall sample for RP, RR, and EF was 0.90, 0.96, and 0.87, respectively. Similar values were observed for CM and EM. MSQ scores for the overall sample correlated moderately to highly with scores from the PHQ‐4 (r = ?0.21 to ?0.42), MIDAS (r = ?0.38 to ?0.39), and HIT‐6 (r = ?0.60 to ?0.71). Similar values were observed for CM and EM. Known‐groups validity indicated significant differences (P < .0001) in the hypothesized direction between CM and EM for RP (F = 86.19), RR (F = 119.24), and EF (F = 235.90). Conclusion.— The MSQ is a reliable and valid questionnaire in the CM population that can differentiate the functional impact between CM and EM. The MSQ can assist researchers in evaluating treatment effectiveness by obtaining input directly from the patients on multidimensional aspects other than frequency of headache days. (Headache 2012;52:409‐421)     

Low leptin levels in migraine: a case control study

Background.— Obesity has been shown to be a risk factor for transformation of episodic migraine to chronic form, and adipocytokines have been implicated to modulate some of the cytokins such as interleukin-6 and tumor necrosis factor, which also act in the neurogenic inflammation in migraine. The aim of the study was to assess leptin levels, one of the adipocytokines, in headache-free period of migraine patients and investigate its relation to vascular risk factors.
Material and Methods.— Sixty-one patients with episodic migraine headaches and 64 control subjects were enrolled in the study. Demographic data and anthropometric measurements were obtained from all participants; body mass index and fat mass values were calculated. Glucose and lipid parameters were measured by oxidase technique and cholesterol esterase enzymatic assays, and leptin levels were measured by ELISA in serum samples obtained after an overnight fasting.
Results.— Leptin levels were found significantly lower in migraineurs than controls (40.1 ± 21.2 ng/mL, 48.5 ± 24.5 ng/mL; P  < .05). Although body mass index did not differ between 2 groups, fat mass, and fat percentages were significantly lower in migraine patients (19.4 ± 8.8 kg, 26.0 ± 8.7 kg; P  < .001 and 28 ± 9%, 34 ± 5%; P  < .001, respectively).
Conclusion.— Migraine patients have low leptin levels and fat mass which may be related to the pathogenesis of migraine. The importance and impact of our findings on the prevalence, characteristics, and treatment of migraine needs to be investigated in further detailed studies.