Citations

Abstract Migraine is increasingly understood to be a disorder of the brain. In susceptible individuals, a variety of ?triggers? may influence altered central excitability, resulting in the activation and sensitization of trigeminal nociceptive afferents surrounding blood vessels (i.e., the trigeminovascular system), leading to migraine pain. Transient receptor potential (TRP) channels are expressed in a subset of dural afferents, including those containing calcitonin gene related peptide (CGRP). Activation of TRP channels promotes excitation of nociceptive afferent fibers and potentially lead to pain. In addition to pain, allodynia to mechanical and cold stimuli can result from sensitization of both peripheral afferents and of central pain pathways. TRP channels respond to a variety of endogenous conditions including chemical mediators and low pH. These channels can be activated by exogenous stimuli including a wide range of chemical and environmental irritants, some of which have been demonstrated to trigger migraine in humans. Activation of TRP channels can elicit CGRP release, and blocking the effects of CGRP through receptor antagonism or antibody strategies has been demonstrated to be effective in the treatment of migraine. Identification of approaches that can prevent activation of TRP channels provides an additional novel strategy for discovery of migraine therapeutics.

Background Recent studies evaluated short-term efficacy and safety of peripheral nerve stimulation (PNS) of the occipital nerves for managing chronic migraine. We present 52-week safety and efficacy results from an open-label extension of a randomized, sham-controlled trial. Methods In this institutional review board-approved, randomized, multicenter, double-blinded study, patients were implanted with a neurostimulation system, randomized to an active or control group for 12 weeks, and received open-label treatment for an additional 40 weeks. Outcomes collected included number of headache days, pain intensity, migraine disability assessment (MIDAS), Zung Pain and Distress (PAD), direct patient reports of headache pain relief, quality of life, satisfaction and adverse events. Statistical tests assessed change from baseline to 52 weeks using paired t-tests. Intent-to-treat (ITT) analyses of all patients ( N = 157) and analyses of only patients who met criteria for intractable chronic migraine (ICM; N = 125) were performed. Results Headache days were significantly reduced by 6.7 (±8.4) days in the ITT population ( p < 0.001) and by 7.7 (±8.7) days in the ICM population ( p < 0.001). The percentages of patients who achieved a 30% and 50% reduction in headache days and/or pain intensity were 59.5% and 47.8%, respectively. MIDAS and Zung PAD scores were significantly reduced for both populations. Excellent or good headache relief was reported by 65.4% of the ITT population and 67.9% of the ICM population. More than half the patients in both cohorts were satisfied with the headache relief provided by the device. A total of 183 device/procedure-related adverse events occurred during the study, of which 18 (8.6%) required hospitalization and 85 (40.7%) required surgical intervention; 70% of patients experienced an adverse event. Conclusion Our results support the 12-month efficacy of PNS of the occipital nerves for headache pain and disability associated with chronic migraine. More emphasis on adverse event mitigation is needed in future research. Trial registration: Clinical trials.gov (NCT00615342).

Objective The prevalence, disability, progression, and treatment needs associated with chronic migraine ( CM ) mandate epidemiological, clinical, and basic research to better understand the clinical course of this disorder and to facilitate development of more effective therapies. Such efforts have been significantly impeded by lack of agreement within the headache specialist community of the most appropriate diagnostic criteria for CM . Methods This paper reviews the pertinent nosological literature and extensive field testing already performed. Results We recommend that the I nternational C lassification of H eadache D isorders‐3β criteria for CM be modified. We would remove the need for 5 prior migraine attacks and would replace “Headache considered by patient to be onset migraine and relieved by a triptan or an ergotamine derivative” with “criteria A and B for 1.5 probable migraine .” Conclusions The proposed criteria are guided by the aims of accurately characterizing patients with migraine who develop primary chronic daily headache, reflecting the large numbers of patients with CM in clinical practice, and facilitating research into a disorder that is an academic and clinical priority.

Background There is a considerable amount of practice variation in managing migraines in emergency settings, and evidence-based therapies are often not used first line. Methods A peer-reviewed search of databases (MEDLINE, Embase, CENTRAL) was carried out to identify randomized and quasi-randomized controlled trials of interventions for acute pain relief in adults presenting with migraine to emergency settings. Where possible, data were pooled into meta-analyses. Results Two independent reviewers screened 831 titles and abstracts for eligibility. Three independent reviewers subsequently evaluated 120 full text articles for inclusion, of which 44 were included. Individual studies were then assigned a US Preventive Services Task Force quality rating. The GRADE scheme was used to assign a level of evidence and recommendation strength for each intervention. Interpretation We strongly recommend the use of prochlorperazine based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a low level of evidence. We weakly recommend the use of chlorpromazine based on a moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine intranasal and meperidine, based on a low level of evidence. We found evidence to recommend strongly against the use of dexamethasone, based on a moderate level of evidence, and granisetron, haloperidol and trimethobenzamide based on a low level of evidence. Based on moderate-quality evidence, we recommend weakly against the use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we recommend weakly against the use of diclofenac, droperidol, lidocaine intravenous, lysine clonixinate, morphine, propofol, sodium valproate and tramadol.

Background Prior studies demonstrate reduced cortical thickness and volume in migraineurs. However, the effect of age on cortical thickness has not been assessed in migraineurs. In this study we investigated whether the process of aging on cortical thickness affects migraineurs differently compared to age-matched healthy controls, i.e. whether aging exacerbates cortical thinning in migraineurs. Methods Cortical thickness was estimated using a general linear model vertex-by-vertex approach for 32 healthy controls (mean age = 35.3 years; SD = 11.6) and 27 episodic migraine patients (mean age = 33.6 years; SD = 12.3). Results were modeled using a main effect analysis to estimate the effect of age on cortical thickness for each group separately, and an age-by-group analysis to estimate differences in age-related cortical thinning between migraine patients and normal controls. Results Although migraineurs and normal controls both have expected age-related thinning in many regions along the cortical mantle, migraineurs have age-related thinning of regions that do not thin in healthy controls, including: bilateral postcentral, right fusiform, and right temporal pole areas. Cortical thinning of these regions is more prominent with advancing age. Conclusion Results suggest that migraine is associated with atypical cortical aging, suggesting that the migraine disease process interacts with aging to affect cortical integrity.

Objective The objective of this study was to identify brain regions having aberrant pain-induced activation in migraineurs, thereby gaining insight into particular aspects of pain processing that are atypical in migraineurs. Methods Functional magnetic resonance imaging assessed whole brain responses to painful heat in 24 adult episodic migraineurs who were at least 48 hours pain free and 27 healthy controls. Regions differentially activated in migraineurs compared to controls were identified. Activation intensities in these regions were correlated with headache frequency, number of migraine years, and time to next migraine attack. Results Migraineurs had greater pain-induced activation of lentiform nucleus, fusiform gyrus, subthalamic nucleus, hippocampus, middle cingulate cortex, premotor cortex, somatosensory cortex, and dorsolateral prefrontal cortex, and less activation in precentral gyrus and superior temporal gyrus. There were significant correlations between activation strength and headache frequency for middle cingulate ( r = 0.627, p = 0.001), right dorsolateral prefrontal cortex ( r = 0.568, p = 0.004), left fusiform gyrus ( r = 0.487, p = 0.016), left precentral gyrus ( r = 0.415, p = 0.044), and left hippocampus ( r = 0.404, p = 0.050) and with number of migraine years for left fusiform gyrus ( r = 0.425, p = 0.038). There were no significant correlations between activation strength and time to next migraine attack. Conclusions The majority of regions with enhanced pain-induced activation in headache-free migraineurs participate in cognitive aspects of pain perception such as attending to pain and pain memory. Enhanced cognitive pain processing by migraineurs might reflect cerebral hypersensitivity related to high expectations and hypervigilance for pain.

Background The study aims to compare methods of determining headache directionality (imploding, exploding, and/or ocular headaches) in women with migraine, investigate the concordance between physician assignment and patient self‐assignment of pain directionality, and evaluate whether patients assigned their headaches to the same direction when queried using different methods. Directionality of migraine headache pain (imploding, exploding, or ocular) may reflect differences in the underlying pathogenesis of individual migraine attacks among and within individuals. Emerging evidence suggests that directionality of pain in migraine sufferers may predict response to onabotulinumtoxin A . The best method of determining headache directionality in migraine sufferers has not been systematically explored. Methods We conducted a prospective cross‐sectional survey study of 198 female patients with migraine presenting to a W omen's H ealth C linic. Patients determined the directionality (imploding, exploding, and/or ocular) of their own migraine pain by choosing among 3 pictures graphically representing directionality and also by responding to a written question regarding directionality. Clinicians then classified directionality of migraine pain using structured interviews. Concordance between clinician assignment of directionality and patient self‐assignment was determined with K appa coefficients. Results Subjects were females between the ages of 18 and 77 years (mean 48 years). According to patient selection of representative pictures, 62 (31.6%) had imploding headaches with or without ocular pain, 36 (18.4%) had exploding headaches with or without ocular pain, 78 (39.8%) had ocular pain only, and 20 (10.2%) had imploding and exploding headaches with or without ocular pain. Two subjects did not respond. According to patient responses to a written question, 80 (41.0%) had imploding headaches with or without ocular pain, 53 (27.2%) had exploding headaches with or without ocular pain, 46 (23.6%) had ocular pain only, and 16 (8.2%) had imploding and exploding headaches with or without ocular pain. Three subjects did not respond. For physician assignment, 69 (34.9%) subjects had imploding headaches with or without ocular pain, 89 (45%) had exploding headaches with or without ocular pain, 14 (7.1%) had ocular pain only, and 26 (13.1%) had imploding and exploding headaches with or without ocular pain. The concordance ( K appa coefficient) between physician assignment of headache directionality with patient response to the written question was 0.33 (weak agreement), between physician assignment and patient assignment via selection of representative pictures was 0.35 (weak agreement), and between patient assignment via written question and via selection of representative pictures was 0.35 (weak agreement). Conclusions The assignment of headache directionality varied substantially depending upon the method of determination. The concordance between clinician assignment, patient‐self assignment via answering a written question, and patient self‐assignment via choosing a representative picture was weak. Improved methods of determining pain directionality are needed.

BackgroundPostmenopausal hormone therapy (HT) increases the risk of venous thrombosis and ischemic stroke.ObjectivesWe postulated that HT might increase the risk of ischemic stroke by promoting venous clots that travel to the brain through a right to left shunt (RLS).MethodsA total of 2,389 records were studied. After eliminating the premenopausal patients, and those with TIAs and non‐ischemic strokes, the medical records of 1846 postmenopausal women hospitalized at four institutions for ischemic stroke were reviewed to identify those who had undergone an adequate study to assess for RLS. The proportion of women with a shunt in users and non‐users of HT was compared in stroke patients and in a reference population consisting of postmenopausal women undergoing elective cardiac catheterization.ResultsThere were 363 (20%) records that had complete data and were included in the analysis. A shunt was more prevalent in patients with a cryptogenic stroke than in patients with a stroke of known cause (55/88 (63%) vs. 53/275 (19%), P < 0.001). In patients with a stroke of known cause, the frequency of a shunt was similar to that in reference women 31/136 (23%), and the proportion of women with a shunt was similar in non‐users and current users of HT (14% vs. 20%, P = 0.40). However, among patients with a cryptogenic stroke, the prevalence of a shunt was 1.5 times higher in current users than non‐users of HT (82% vs. 56%, P = 0.04).ConclusionsApproximately 23% of older women have a RLS. HT in these women may increase the risk of ischemic stroke by promoting paradoxical embolism. © 2014 Wiley Periodicals, Inc.

Background It is generally felt that patient education and patient knowledge regarding triptan use for acute migraine management are important for successful and safe treatment. It is unclear how knowledgeable triptan users are regarding their triptan, how much education occurs when triptans are prescribed, and the impact patient education has on actual patient knowledge regarding triptan use. Objective The primary objective was to compare triptan users' self‐perceived knowledge and actual knowledge about triptans in patients who report having received triptan education vs patients who report not having received triptan education. Methods This was a multicenter prospective observational study of 207 migraine patients who were using triptans for abortive therapy and who were being evaluated as new patients at academic headache specialty clinics in the U nited S tates. Patients completed standardized questionnaires regarding their self‐perceived knowledge about triptans, their actual knowledge regarding triptans, and the perceived education about the triptan that they had received at the time of prescription. Results Although greater than 80% of the subjects reported receiving education about when to take the triptan and the number of doses they could take for headache, only 71.5% reported receiving education about triptan side effects, 64% for the number of triptan doses they could take each week/month, 64% for taking other medications with the triptan, and 49% for medical contraindications to triptan use. Compared with subjects who did not recall receiving education about when to take their triptan, subjects who recalled such education had a statistically significant greater actual knowledge for taking the triptan immediately after a headache begins (91% vs 77%, P = .049; confidence interval [ CI ]: 0.00–0.33), treating when pain is mild (75% vs 50%, P = .009; CI : 0.04–0.45), understanding that they do not need to fail treatment with over‐the‐counter medications before taking a triptan (74% vs 42%, P = .001; CI : 0.11–0.51), and recognizing that coronary artery disease is a contraindication to triptan use (40% vs 19%, P = .001; CI : 0.09–0.34). Conclusion This study provides evidence that patients who recall having received education at the time of triptan prescribing have greater knowledge regarding optimal triptan use. Triptan users who recalled having received this education had greater recognition of the importance of taking the triptan immediately at the onset of a headache, treating when pain is mild, not needing to fail treatment with over‐the‐counter medications before taking a triptan, and understanding that coronary artery disease is a contraindication to triptan use.

Background Optimizing patient satisfaction with their medical care and maximizing patient adherence with treatment plans requires an understanding of patient preferences regarding education and their role in decision making when treatments are prescribed. Objective To assess the congruence between patient expectations and actual practice regarding education and decision making at the time a triptan is prescribed. Methods This multicenter cross‐sectional survey was performed by headache fellow members of the A merican H eadache S ociety H eadache F ellows R esearch C onsortium at their respective tertiary care headache clinics. Migraine patients who were new patients to the headache clinic and who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years) completed questionnaires that assessed the education they received and their role in decision making at the time a triptan was first prescribed as well as their desire for education and participation in decision making when a triptan is prescribed. Results Consistent with patient preference, most participants received the majority of their education about the triptan from the prescriber's office (70.2%). In descending rank order, participants most desired to be informed about how to decide if a triptan should be taken, when during the course of migraine a triptan should be taken, possible side effects, cost, and how to obtain refills. Regarding side effects, most participants preferred to receive education about the most common side effects of a triptan rather than addressing all possible side effects. Regarding triptan dosing, participants desired to be informed in descending order of importance about taking other medications with triptans, how many doses can be taken for each migraine, how many doses can be taken each week/month, what to do if the triptan does not work, and the triptan mechanism of action. The vast majority of participants (92%) preferred that the decision to prescribe a triptan be a joint decision between the patient and the provider. In actual practice, participants were not as involved in decision making as they would like to be, with patients reporting that the prescriber was the sole decision maker 55.1% of the time. Participants had confidence in their providers (87.7%) and generally felt they did a good job educating them about the triptan (71.1%). Conclusions Based on this study, it is clear that patients prefer the shared model approach to medical decision making in regards to the prescription of triptans. The majority of patients received education that was generally consistent with their desires. Patients preferred that the prescribing provider be the primary source of information. The most desired educational topics included when/if a triptan should be taken, the number of times a triptan can be taken for a single migraine, co‐administration with other acute medications, and the most common side effects. Focusing on these topics should enhance patient satisfaction and may improve compliance.