Individual Migraine Research Articles

The Safety of Celecoxib as an Acute Treatment for Migraine: A Narrative Review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first-line choice for the acute treatment of migraine attacks for decades; however, the safety of a particular NSAID is related to its treatment dose, duration, and mechanism of action. Although adverse event (AE) risks differ substantially among individual migraine treatments, increased or prolonged exposure to any NSAID elevates risks and severity of AEs. For this narrative review, we conducted a literature search of PubMed until July 2022, focusing on the history, mechanism of action, and treatment guidelines informing the safety and efficacy of celecoxib oral solution for the acute treatment of migraine attacks. Here we discuss the mechanisms of action of nonselective NSAIDs vs. cyclooxygenase-2 (COX-2) inhibitors, and how these mechanisms underlie the AEs associated with these treatments. We review the clinical trials that influenced the regulatory history of NSAIDs, specifically COX-2 inhibitors, the role of traditional and new formulations of NSAIDs including celecoxib oral solution, and special considerations in the acute treatment of migraine attacks. Low-dose formulations of NSAIDs, such as celecoxib oral solution, provide acute migraine analgesia with similar or fewer associated cardiovascular and gastrointestinal events than previous formulations.

Distinguishing persistent post-traumatic headache from migraine: Classification based on clinical symptoms and brain structural MRI data.

Persistent post-traumatic headache most commonly has symptoms that overlap those of migraine. In some cases, it can be clinically difficult to differentiate persistent post-traumatic headache with a migraine phenotype from migraine. The objective of this study was to develop a classification model based on questionnaire data and structural neuroimaging data that distinguishes individuals with migraine from those with persistent post-traumatic headache. Questionnaires assessing headache characteristics, sensory hypersensitivities, cognitive functioning, and mood, as well as T1-weighted magnetic resonance imaging and diffusion tensor data from 34 patients with migraine and 48 patients with persistent post-traumatic headache attributed to mild traumatic brain injury were included for analysis. The majority of patients with persistent post-traumatic headache had a migraine/probable migraine phenotype (77%). A machine-learning leave-one-out cross-validation algorithm determined the average accuracy for distinguishing individual migraine patients from individual patients with persistent post-traumatic headache. Based on questionnaire data alone, the average classification accuracy for determining whether an individual person had migraine or persistent post-traumatic headache was 71.9%. Adding imaging data features to the model improved the classification accuracy to 78%, including an average accuracy of 97.1% for identifying individual migraine patients and an average accuracy of 64.6% for identifying individual patients with persistent post-traumatic headache. The most important clinical features that contributed to the classification accuracy included questions related to anxiety and decision making. Cortical brain features and fibertract data from the following regions or tracts most contributed to the classification accuracy: Bilateral superior temporal, inferior parietal and posterior cingulate; right lateral occipital, uncinate, and superior longitudinal fasciculus. A post-hoc analysis showed that compared to incorrectly classified persistent post-traumatic headache patients, those who were correctly classified as having persistent post-traumatic headache had more severe physical, autonomic, anxiety and depression symptoms, were more likely to have post-traumatic stress disorder, and were more likely to have had mild traumatic brain injury attributed to blasts. A classification model that included a combination of questionnaire data and structural imaging parameters classified individual patients as having migraine versus persistent post-traumatic headache with good accuracy. The most important clinical measures that contributed to the classification accuracy included questions on mood. Regional brain structures and fibertracts that play roles in pain processing and pain integration were important brain features that contributed to the classification accuracy. The lower classification accuracy for patients with persistent post-traumatic headache compared to migraine may be related to greater heterogeneity of patients in the persistent post-traumatic headache cohort regarding their traumatic brain injury mechanisms, and physical, emotional, and cognitive symptoms.

Development and Internal Validation of a Multivariable Prediction Model for Individual Episodic Migraine Attacks Based on Daily Trigger Exposures.

To develop and internally validate a multivariable predictive model for days with new-onset migraine headaches based on patient self-prediction and exposure to common trigger factors. Accurate real-time forecasting of one's daily risk of migraine attack could help episodic migraine patients to target preventive medications for susceptible time periods and help decrease the burden of disease. Little is known about the predictive utility of common migraine trigger factors. We recruited adults with episodic migraine through online forums to participate in a 90-day prospective daily-diary cohort study conducted through a custom research application for iPhone. Every evening, participants answered questions about migraine occurrence and potential predictors including stress, sleep, caffeine and alcohol consumption, menstruation, and self-prediction. We developed and estimated multivariable multilevel logistic regression models for the risk of a new-onset migraine day vs a healthy day and internally validated the models using repeated cross-validation. We had 178 participants complete the study and qualify for the primary analysis which included 1870 migraine events. We found that a decrease in caffeine consumption, higher self-predicted probability of headache, a higher level of stress, and times within 2days of the onset of menstruation were positively associated with next-day migraine risk. The multivariable model predicted migraine risk only slightly better than chance (within-person C-statistic: 0.56, 95% CI: 0.54, 0.58). In this study, episodic migraine attacks were not predictable based on self-prediction or on self-reported exposure to common trigger factors. Improvements in accuracy and breadth of data collection are needed to build clinically useful migraine prediction models.

Lasmiditan in patients with common migraine comorbidities: a post hoc efficacy and safety analysis of two phase 3 randomized clinical trials

Objective Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT1F receptor agonist approved in the United States for the acute treatment of migraine. Methods In SPARTAN and SAMURAI (double-blind Phase 3 clinical trials), patients with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100mg, 200 mg, or placebo. Lasmiditan increased the proportion of pain-free and most bothersome symptom (MBS)-free patients at 2 h after dose compared with placebo. Most common treatment-emergent adverse events (TEAEs) were dizziness, paraesthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia. Based upon literature review of common migraine comorbidities, Anxiety, Allergy, Bronchial, Cardiac, Depression, Fatigue, Gastrointestinal, Hormonal, Musculoskeletal/Pain, Neurological, Obesity, Sleep, and Vascular Comorbidity Groups were created. Using pooled results, efficacy and TEAEs were assessed to compare patients with or without a given common migraine comorbidity. To compare treatment groups, p-values were calculated for treatment-by-subgroup interaction, based on logistic regression with treatment-by-comorbidity condition status (Yes/No) as the interaction term; study, treatment group, and comorbidity condition status (Yes/No) were covariates. Differential treatment effect based upon comorbidity status was also examined. Trial registration at clinicaltrials.gov: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Results Across all the Comorbidity Groups, with the potential exception of fatigue, treatment-by-subgroup interaction analyses did not provide evidence of a lasmiditan-driven lasmiditan versus placebo differential treatment effect dependent on Yes versus No comorbidity subgroup for either efficacy or TEAE assessments. Conclusions The efficacy and safety of lasmiditan for treatment of individual migraine attacks appear to be independent of comorbid conditions.

Effect of genetic liability to migraine on cognition and brain volume: A Mendelian randomization study.

To investigate potential causality between genetic liability to migraine and Alzheimer's disease, intelligence, and brain volume using two-sample Mendelian randomization. The exposure consisted of independent genetic variants associated with migraine in the largest (59,674 cases/316,078 controls) published genome-wide association study. Outcomes included Alzheimer's disease (71,880 cases/383,378 controls), a measure of general intelligence (n = 269,867), intracranial volume (n = 11,373), and seven subcortical brain volumes (n ∼ 13,000), all with available genome-wide association study summary statistics. Mendelian randomization effects were estimated using inverse-variance weighted analysis. Genetic liability to migraine did not associate with Alzheimer's disease (odds ratio [95% confidence interval] 1.01 [1.00-1.02], p = 0.07), intelligence (standardized beta [95% confidence interval] 0.01 [0.00-0.02], p = 0.13), or any brain volume measures (all p > 0.05). No individual migraine variant associated with any of the outcomes at genome-wide significance. These data do not support a causal effect of migraine liability on Alzheimer's disease, intelligence, or brain volume.

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

To provide evidence-based recommendations for the acute symptomatic treatment of children and adolescents with migraine. We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache free at 2 hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migraine-related phonophobia and photophobia. Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counselling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse.

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

To provide evidence-based recommendations for the acute symptomatic treatment of children and adolescents with migraine. We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache-free at 2 hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migraine-related phonophobia and photophobia. Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counseling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse.

Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors and Migraine: Should Cochrane Close the Door?

The Cochrane Collaboration completed a review entitled “Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-norepinephrine Reuptake Inhibitors (SNRIs) for the Prevention of Migraine in Adults” in 2015. In the review, they acknowledge that poor-quality research and low levels of evidence make it difficult to draw definitive conclusions, but then state that “A randomised controlled trial comparing a SSRI or a SNRI versus another drug or another non-pharmacological intervention is not a priority in the migraine research pipeline and might not exert a significant impact on the overall evidence”. A detailed evaluation of 10 of the 11 papers analysed in the Cochrane Review reveals that 9 of them use the International Classification of Headache Disorders (ICHD) system to determine their study cohorts. Despite being the current globally accepted standard for classification, diagnosis and categorization of migraine, the ICHD criteria are based on an arbitrary symptom list and offer little, if any, insight into the possible mechanisms involved in the pathophysiology of a migraine. Using the ICHD system in scientific studies which investigate the prevention and treatment of migraines, including those analyzed by the 2015 Cochrane Review, therefore results in amorphous cohort selection for those studies. This directly impacts the clinical relevance of the results drawn from the research. We acknowledge, and are grateful for, the important and highly credible contribution that the Cochrane Collaboration brings to our body of scientific knowledge. We are, however, concerned that the conclusions drawn in this important review might negatively impact on clinician ability to help individual migraine patients, not through any fault of the Cochrane Collaboration review system, but due to a fundamental flaw in the classification of migraines.

Migraine classification using magnetic resonance imaging resting-state functional connectivity data.

Background This study used machine-learning techniques to develop discriminative brain-connectivity biomarkers from resting-state functional magnetic resonance neuroimaging ( rs-fMRI) data that distinguish between individual migraine patients and healthy controls. Methods This study included 58 migraine patients (mean age = 36.3 years; SD = 11.5) and 50 healthy controls (mean age = 35.9 years; SD = 11.0). The functional connections of 33 seeded pain-related regions were used as input for a brain classification algorithm that tested the accuracy of determining whether an individual brain MRI belongs to someone with migraine or to a healthy control. Results The best classification accuracy using a 10-fold cross-validation method was 86.1%. Resting functional connectivity of the right middle temporal, posterior insula, middle cingulate, left ventromedial prefrontal and bilateral amygdala regions best discriminated the migraine brain from that of a healthy control. Migraineurs with longer disease durations were classified more accurately (>14 years; 96.7% accuracy) compared to migraineurs with shorter disease durations (≤14 years; 82.1% accuracy). Conclusions Classification of migraine using rs-fMRI provides insights into pain circuits that are altered in migraine and could potentially contribute to the development of a new, noninvasive migraine biomarker. Migraineurs with longer disease burden were classified more accurately than migraineurs with shorter disease burden, potentially indicating that disease duration leads to reorganization of brain circuitry.

Managing migraine by patient profile: role of frovatriptan.

For the last quarter of a century, triptans have been available for acute treatment of migraine but with little guidance on which of the different triptan products to use for which patient or which attack of migraine. In this article, we propose a structured approach to analysis of individual migraine attacks and patient characteristics as a means of defining and optimizing acute intervention. Assessment of patient and attack profiles includes the “5-Ps”: pattern, phenotype, patient, pharmacology, and precipitants. Attending to these five components of information can assist in developing an individualized behavioral, pharmacological, and nonpharmacological comprehensive treatment plan for most migraine patients. This clinical approach is then focused on frovatriptan because of its unique molecular signature and potential novel clinical applications. Frovatriptan like all triptans is indicated for acute treatment of migraine but its role has been explored in management of several unique migraine phenotypes. Frovatriptan has the longest half-life of any triptan and consequently is often promoted for acute treatment of migraine of longer duration. It has also been studied as a short-term preventive treatment in women with menstrual-related migraine. Given that 60% of female migraineurs suffer from menstrual-related migraine, this population is the obvious group for continued study. Small studies have also explored frovatriptan’s use in treating migraine predicted by premonitory symptoms as a preventive for the headache phase of migraine. By identifying patient and attack profiles, clinicians may effectively determine the viability of frovatriptan as an effective pharmacological intervention for migraine.

Can nitric oxide induce migraine in normal individuals?

For many years, scientists have debated the possibility that an individual "migraine threshold" determines the likelihood with which individuals may express migraine attacks. Recent discoveries provided evidence for both genetic and environmental influences on individual migraine expression. The question is whether any person may express a migraine attack given a sufficiently strong stimulus or provocation. Here, we reviewed and discussed the ability of nitric oxide to induce migraine-like attacks in normal individuals. Experimental data show that normal individuals may develop a migraine-like attack and that the human data point to different ways of further developing existing animal and human models.

Imploding and Exploding Migraine Headaches: Comparison of Methods to Diagnose Pain Directionality

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. We conducted a prospective cross-sectional survey study of 198 female patients with migraine presenting to a Women's Health Clinic. 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 Kappa coefficients. 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 (Kappa 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). 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.

Guideline Summary for Patients and Their Families

This acute migraine treatment guideline is summarized here to provide information for patients with migraine and their families. Acute migraine medications are used to treat individual migraine attacks at the time of the attack. Most patients with migraine will use an acute medication, but patients with migraine, especially if they have frequent attacks, should also consider whether they could change lifestyle factors which might be making their headache more frequent (skipping meals, not enough sleep, etc), or whether they need a migraine preventive medication. Preventive (or prophylactic) medications are quite different from acute medications. Preventive medications are taken daily to reduce the frequency (number) of migraine attacks, while acute medications are used to reduce or stop the pain of a migraine attack once it has started. It is important that acute medications not be taken too often.

Acute Migraine Treatment - Information for Patients

Acute migraine treatment usually involves taking medications to reduce the pain and other symptoms of a migraine attack. Non-medication treatment can also be used, like ice packs and relaxation or meditation, but most patients with migraine also take some sort of medication for their attacks when they happen. Acute medications (sometimes called symptomatic medications) are used to treat individual migraine attacks when they happen, and are quite different from preventive or prophylactic medications. Preventive medications are meant to be taken daily in order to make migraine attacks less frequent. Acute medications are an entirely different class of medications, and are taken only when the attack actually happens. It is important to know that acute medications can make migraine headaches more frequent if they are taken too often.

Guideline Summary for Patients and Their Families

This acute migraine treatment guideline is summarized here to provide information for patients with migraine and their families. Acute migraine medications are used to treat individual migraine attacks at the time of the attack. Most patients with migraine will use an acute medication, but patients with migraine, especially if they have frequent attacks, should also consider whether they could change lifestyle factors which might be making their headache more frequent (skipping meals, not enough sleep, etc), or whether they need a migraine preventive medication. Preventive (or prophylactic) medications are quite different from acute medications. Preventive medications are taken daily to reduce the frequency (number) of migraine attacks, while acute medications are used to reduce or stop the pain of a migraine attack once it has started. It is important that acute medications not be taken too often.

Why Triptan Treatment Can Fail: Focus on Gastrointestinal Manifestations of Migraine

Results of randomized, double-blind, controlled studies establish the efficacy of triptans in the acute treatment of migraine, but triptan benefits demonstrated in clinical trials have not consistently been realized in clinical practice. This paper explores the contribution of gastrointestinal manifestations of migraine--namely nausea (with or without vomiting) and gastroparesis--to triptan treatment failure. Migraine-related nausea and vomiting and migraine-associated gastroparesis appear to be prevalent and highly impactful and have been characterized as being among the greatest challenges affecting migraine care today. These gastrointestinal signs and symptoms have not been satisfactorily taken into account in the management of migraine, which is dominated by the use of oral therapies. Oral triptans are not the optimal therapy in the presence of migraine-related nausea because nausea predicts poor response to oral triptans and because nausea can cause patients to delay oral treatment, which can further compromise therapeutic efficacy. Oral triptans are not the optimal therapy in the presence of migraine-associated gastroparesis because these agents rely on gastric motility and gastrointestinal absorption and may be ineffective or slowly or inconsistently effective in the presence of gastroparesis. Health care providers need to work with their patients to address the still-all-too-frequent problem of treatment failure in migraine. First, health care providers need to have greater appreciation of the importance of nausea, vomiting, and gastroparesis as factors affecting migraine prognosis and treatment success. Second, health care providers need to systematically assess migraine patients for gastrointestinal signs and symptoms. Finally, patients and health care providers need to be willing to practice customized migraine care, in which patients tailor the treatment and formulation to the characteristics and context of the individual migraine episode.

Therapeutic applications for subcutaneous triptans in the acute treatment of migraine

Background:The features of migraine attacks and the contexts in which migraine attacks occur vary from attack to attack and from patient to patient. Current treatment strategies, which are dominated by the use of oral forms of migraine medication, do not address this patient-to-patient and attack-to-attack heterogeneity. While current therapies, and, in particular, oral triptan tablets can be effective for many types of migraine attacks that a patient can experience, they may not be the optimum treatment for every migraine in every patient.Scope:This clinical review of subcutaneous sumatriptan discusses its characteristics, efficacy, and tolerability and considers its place in clinical practice. The review focuses particularly on several specific clinical settings in which subcutaneous sumatriptan might be a more appropriate therapeutic choice than the oral triptan tablet.Findings:Of the triptan formulations, subcutaneous sumatriptan is the most rapidly absorbed and demonstrates a favorable pharmacokinetic profile. Data from randomized, double-blind, clinical trials and studies of patients’ perceptions and preferences suggest that subcutaneous sumatriptan can be particularly useful to help restore normal work functioning, for migraine attacks that cannot be treated early in their course, for migraine attacks associated with gastrointestinal symptoms, such as nausea or vomiting, and for difficult-to-treat migraines, including early-morning migraine and menstrual migraine. The majority of patients (9 in 10) trying subcutaneous sumatriptan indicated that they will use it again. Patients not fully satisfied with previous triptan therapy reported enhanced satisfaction with, and confidence in, treatment after trying subcutaneous sumatriptan.Conclusions:By virtue of their availability as multiple compounds and in multiple formulations including oral, intranasal, and injectable forms, triptans can be used to customize migraine therapy to the individual patient and the individual migraine attack. Due to its route of delivery and favorable pharmacokinetic profile, subcutaneous triptans may represent an attractive alternative for specific clinical settings. Subcutaneous sumatriptan can play a key role in maximizing likelihood of pain-free response and rapid return to normal daily activities and, as such, should be considered an important part of the treatment armamentarium for migraine.

The Migraine Intervention Score - a tool to improve efficacy of triptans in acute migraine therapy: the ALADIN study

The 'Migraine Intervention Score' (MIS) is a new self-administered scale that can be used to quantify the severity of specific migraine symptoms. The objective of this study was to determine if MIS could be used to improve the efficacy of frovatriptan 2.5 mg in the early treatment of migraine attacks for clinical practice. In this prospective observational study, patients suffering from migraines with or without aura were enrolled and permitted to choose the time of self-medication with frovatriptan 2.5 mg. At the time of intake of medication, patients evaluated the severity of individual migraine symptoms using MIS. The scores for each symptom were then totalled to provide an overall level of symptom severity. A total of 1620 patients completed the treatment of three migraine attacks with frovatriptan. A total of 1518 patients could be analysed with respect to the documented efficacy parameters of the third attack. Patients initiating treatment at low symptom severity levels were compared with those initiating treatment at high symptom severity levels. Time to the achievement of the primary endpoint (headache response) was significantly lower in patients who initiated treatment at low vs. high symptom severity levels (42.06 ± 32.33 vs. 49.25 ± 34.92 min; p = 0.0023). Likewise, patients who initiated treatment at low symptom severity levels achieved complete headache relief more rapidly (79.37 ± 65.33 vs. 96.05 ± 100.85 min; p = 0.0109) and required escape medication less frequently (3.88% vs. 13.73%; p < 0.0001). The initiation of attack treatment with frovatriptan at low severity of migraine symptoms is more effective than starting therapy at higher symptom levels. Together with the low recurrence headache rate, the decreased necessity for escape medication and the low number of tablets needed, these data demonstrate that operationalised intervention with frovatriptan 2.5 mg is a valuable method for improving the treatment of migraine attacks.

Modeling individual migraine severity with autoregressive ordered probit models

This paper considers the problem of modeling migraine severity assessments and their dependence on weather and time characteristics. We take on the viewpoint of a patient who is interested in an individual migraine management strategy. Since factors influencing migraine can differ between patients in number and magnitude, we show how a patient’s headache calendar reporting the severity measurements on an ordinal scale can be used to determine the dominating factors for this special patient. One also has to account for dependencies among the measurements. For this the autoregressive ordinal probit (AOP) model of Müller and Czado (J Comput Graph Stat 14: 320–338, 2005) is utilized and fitted to a single patient’s migraine data by a grouped move multigrid Monte Carlo (GM-MGMC) Gibbs sampler. Initially, covariates are selected using proportional odds models. Model fit and model comparison are discussed. A comparison with proportional odds specifications shows that the AOP models are preferred.

Neuroimaging in Migraine—Recent Advances and Perspectives for the Future

Migraine is a very common disorder that imposes substantial individual and societal costs. A better understanding of migraine mechanisms may lead to the development of new therapies and thus improve the management of migraine patients. Magnetic resonance imaging (MRI) techniques and positron emission tomography (PET) have revolutionized our understanding of migraine pathophysiology as a primary central nervous system (CNS) disorder, advanced the search for a central migraine generator, clarified the role of cortical spreading depression (CSD) and central sensitization in the pathogenesis of migraine, and revealed some potential sites of action of migraine medications. Structural imaging has shed light on relationships between migraine and stroke, white matter lesions, iron deposition, microstructural brain damage, and other gray and white matter aberrations. Emerging neuroimaging techniques, such as arterial spin labeling (ASL) and functional connectivity MRI (fcMRI), are beginning to provide further evidence of functional brain alterations in migraine patients. Ultimately, it is hoped that advanced neuroimaging will benefit the individual migraine patient by enhancing our diagnostic abilities, allowing for development of better treatments and serving as an important tool in medical decision-making.