Migraine without aura.

Migraine without aura is the commonest form of migraine in both children and adults. The diagnosis is made by applying the International Classification of Headache Disorders Third Edition subsection for migraine without aura (ICHD-3 subsection 1.1). Attacks in patients with migraine without aura are characterized by their polyphasic presentation (prodrome, headache phase, postdromal phase). The symptomatology of attacks is diverse and heterogeneous, with most common symptoms being photophobia, phonophobia, nausea, vomiting, and aggravation of pain by movement. The clinician and researcher who wants to learn about migraine without aura needs to be able to apply the ICHD-3 criteria with its specific symptomatology to make a correct diagnosis, but also needs to be aware about the plethora of symptoms patients may experience. In this chapter, the reader will explore the clinical phenotypical features of migraine without aura.

Gradually shifting clinical phenomics in migraine spectrum: a cross-sectional, multicenter study of 5438 patients.

BACKGROUND: The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum. METHODS: In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis. RESULTS: Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree's accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM. CONCLUSIONS: The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different "predominant regions" that generate attacks.

Visually guided associative learning in pediatric and adult migraine without aura.

INTRODUCTION: The Rutgers Acquired Equivalence Test is a visually guided equivalence learning paradigm that involves rule acquisition and generalization. Earlier we found impaired performance in this paradigm among adult migraine patients without aura. The aim of the study was to investigate if similar impairments can be found already in the pediatric form of the disease and to compare the performance of the pediatric study population with that of an adult study population. We hypothesized that the deficits observed in adults would be observable already in the pediatric population. METHODS: Twenty-seven children and adolescents newly diagnosed with migraine without aura and 27 age- and sex-matched healthy controls were tested with the Rutgers Acquired Equivalence Test. Their performance data were compared to each other and those of an earlier adult study population involving 22 patients and 22 age- and sex-matched healthy controls. Four parameters characterizing performance in the two main phases of the paradigm were calculated for each of the four groups. Performance parameters were compared with Mann-Whitney U test. RESULTS: In contrast to the decreased performance of the adult patients in the Rutgers Acquired Equivalence Test, no significant difference was found between pediatric patients and controls in any phase of the paradigm. CONCLUSION: Children living with migraine without aura do not exhibit the same cognitive deficits in the Rutgers Acquired Equivalence Test as their adult counterparts. It can be hypothesized that the deficit of equivalence learning is not an inherent feature of the migrainous cognitive profile, rather the result of the interference of the disease with normal development.

Migraine and cardiovascular risk factors: A clinic-based study.

OBJECTIVE: The relation between migraine and vascular risk factors is an unclear issue. Furthermore, the reasons for chronification are still unknown. Probably, the age-related risk and other factors leading to migraine progression will also change in the future. Under these questions, we aimed to investigate whether or not there is a specific association with vascular risk factors between several age groups and subtypes of migraine and also in their families. METHODS: A dataset (the Turkish Headache Database) from four tertiary headache centres in Turkey was used. This database included headache-defining features according to ICHD criteria based on face-to-face interviews and examinations by a Neurologist. Vascular risk factors of migraine without aura (MwoA), migraine with aura (MwA) and chronic migraine (CM) were compared between three age groups (under 30 years, 30-50 years and over 50 years) and in first-degree relatives of the patients. Our study included 2712 patients comprising 1868 (68.9 %), 246 (9.1 %) and 598 (22.1 %) subjects with MwoA, MwA and CH, respectively. RESULTS: This study showed that both the patients and the first-degree relatives were more frequently associated with vascular risk factors in CM than episodic MwA and MwoA. MwoA showed a weaker association with vascular risk factors than MwA and CM. CONCLUSION: Chronic migraine was associated with vascular risk factors at all ages and first-degree relatives as well. Vascular risk factors should be investigated with greater focus on chronic migraine.

Primary Empty Sella.

Primary empty sella (PES) syndrome is a misnomer as it is not a syndrome but a radiological finding with possible endocrine abnormalities. No specific headache type has been shown to be caused by PES. Endocrine screening may be considered for asymptomatic persons with PES.

Prevalence of ischemic stroke and atrial fibrillation in young patients with migraine national inpatient sample analysis.

OBJECTIVE: To estimate the prevalence of ischemic stroke (IS) and atrial fibrillation (AF) in young patients with migraine and to identify the independent predictors of IS in a large cohort of hospitalized patients. METHODS: A cohort of patients with migraine with aura (MA) and migraine without aura (MO) was identified from the National Inpatient Sample database for the years 2012 to 2015. Ischemic stroke was identified by the International Classification of Diseases-9-CM codes. Binary logistic regression and Chi-square tests were utilized. RESULTS: A total number of 834,875 young patients (18-44 years) were included in this study with a mean age of 33 years. The prevalence of IS was 1.3% and was significantly higher in patients with MA (3.7% versus 1.2%, P <0.001). The prevalence of AF was 0.9% and it was significantly higher in patients with MA (1.2% versus 0.8%, P <0.001). Migraine with aura was an independent predictor of IS (OR 3.23, 95% CI 3.05-3.42, P <0.001) and AF (OR 1.63, 95% CI 1.42-1.88, P <0.001). Other predictors of IS were hypertension (OR 2.2, 95% CI 2.12-2.3, P <0.001), diabetes mellitus (DM) (OR 1.37, 95% CI 1.31-1.42, P <0.001), peripheral vascular disease (PVD) (OR 12.08, 95% CI 11.23-12.98, P <0.001) and smoking (OR 1.37, 95% CI 1.31-1.42, P <0.001). CONCLUSION: In this relatively large study, the overall prevalence of IS in young migraine patients was low at 1.3%. The prevalence of IS and AF was significantly higher in patients with MA. Presence of PVD confers a high risk of IS in young patients with migraine. Migraine aura was observed to be an independent predictor of IS and AF in patients with history of migraine. Optimal control of vascular risk factors in migraine patients appears to be indicated despite the overall low risk.

On the utility of the trail making test in migraine with and without aura: a meta-analysis.

This meta-analytical review assesses the utility of the Trail Making Test (TMT), versions A and B, in detecting migraine-related cognitive deficits. A comprehensive literature search was performed in two electronic databases and other sources to obtain relevant studies administering TMT to migraine patients. Search terms included "migraine" and "Trail Making". Only studies in which the TMT-A, TMT-B or both were administered to adult patients suffering from migraine with and without aura were included. All pooled meta-analyses were based on random effects models. A total of 14 studies for TMT-A and 15 for TMT-B met inclusion criteria and were subjected to meta-analyses. Results showed that performance is worse in migraine patients than in controls for both the TMT-A (Hedges' g = -.28) and TMT-B (g = -.37), with no difference between migraine with and without aura. This study demonstrates the sensitivity of the TMT in detecting cognitive alterations in migraine. This test should be considered for inclusion in cognitive batteries assessing patients with migraine.

Migraine and Arterial Stiffness in the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

BACKGROUND: The mechanisms that underlie the link between migraine and cardiovascular diseases are not clear and arterial stiffness could play a role in that association. We analyzed the association between migraine and vascular stiffness measured by carotid-to-femoral pulse wave velocity (PWV-cf). METHODS: In a cross-sectional analysis of a well-defined population from the Longitudinal Study of Adult Health (ELSA-Brasil) with complete and validated information about migraine and aura according to the International Headache Society criteria, the association between arterial stiffness measured by PWV-cf was tested with multiple linear regression models [ß (95% CI)] comparing migraine without aura (MO) and migraine with aura (MA) to the reference group no-migraine (NM). Subsequent adjustments were made for mean arterial pressure, age, sex, education level, physical activity, alcohol use, diabetes mellitus, smoking, antihypertensive medication, body mass index, waist circumference, triglycerides, and LDL-c level to test the independence of the association between migraine status and pulse wave velocity. RESULTS: We studied 4,649 participants, 2,521 women (25.7% MO and 15% MA) and 2,128 men (11% MO and 4.3% MA). In NM, MO, and MA standard PWV-cf were 8.67 (±1.71) 8.11 (±1.31) and 8.01 (±1.47) m/s, respectively. Unadjusted PWV-cf differed between NM, MA, and MO (P < 0.001). After adjustment for mean arterial pressure PWV-cf in NM did not differ anymore from MA (P = 0.525) and MO (P = 0.121), respectively. Fully adjusted models also yielded nonsignificant coefficients ß (95% CI) -0.079 (-0.280; 0.122) and -0.162 (-0.391; 0.067) for MO and MA, respectively. CONCLUSION: In this large cohort of middle-aged adults, aortic PWV was not associated with migraine.

Quantification of photophobia in visual snow syndrome: A case-control study.

OBJECTIVE: To quantify photophobia in visual snow syndrome (VSS), a debilitating migraine-associated visual disturbance manifesting with continuous "TV snow-like" flickering dots in the entire visual field and additional visual symptoms, such as photophobia. METHODS: Photophobia was compared between 19 patients with VSS and 19 controls matched for age, sex, migraine and aura using the Leiden Visual Sensitivity Scale (L-VISS). RESULTS: Patients with VSS had an increased L-VISS-score compared to matched controls [(22.2 ± 5.9 vs. 4.4 ± 4.8; ANOVA, factors VSS and comorbid migraine: Main effect for VSS (F = 100.70; p < 0.001), but not for migraine (F < 0.01; p = 1.00) or the interaction (F = 1.93; p = 0.16)]. An L-VISS-score of 14 identified VSS with a sensitivity and specificity of 95% (Receiver Operating Characteristic analysis, 0.986 ± 0.014, p ≤ 0.001). CONCLUSION: Patients with VSS suffer continuously from photophobia at a level similar to chronic migraineurs during attacks. Although migraine and VSS share dysfunctional visual processing, patients with VSS might be more severely affected.

Migraine headache: Is it only a neurological disorder? Links between migraine and cardiovascular disorders.

Migraine headache (MH) is a common disorder affecting millions of people in the United States. MH is substantially more prevalent in women compared to men. An association between migraine with or without aura and risk of cardiovascular disease (CVD) has been extensively reported. There are several proposed theories that may explain the pathophysiologic relationship between MH and CVD. This review will summarize the recent literature on this topic and provide an evidence-based perspective regarding the current knowledge and controversies regarding association of MH and CVD.

PACAP27 induces migraine-like attacks in migraine patients.

INTRODUCTION: Pituitary adenylate cyclase-activating polypeptide (PACAP) is found in two functional isoforms, namely PACAP38 and PACAP27. The migraine-inducing properties of PACAP38 are well studied. However, it is not known whether the lesser-known and under-studied protein isoform, PACAP27, can also induce migraine attacks. Here, we studied the effect of human PACAP27 infusion on induction of migraine in a provocation model. METHODS: In a crossover study, 20 migraine without aura patients were randomly assigned to receive human PACAP27 (10 picomol/kg/min) or saline (placebo) infusion over 20 min. We recorded the migraine and associated symptoms. RESULTS: All patients completed the study. PACAP27 provoked migraine-like attacks in 11 patients (55%) and two developed attacks after placebo (10%) (p = 0.022). The headache intensity and duration after PACAP27 was significantly greater compared to placebo (p = 0.003). CONCLUSION: PACAP27 triggers migraine attacks without aura. These novel data strengthen the role of PACAP and its receptors in migraine pathogenesis.

A Biomarker for Discriminating Between Migraine With and Without Aura: Machine Learning on Functional Connectivity on Resting-State EEGs.

Advanced analyses of electroencephalography (EEG) are rapidly becoming an important tool in understanding the brain's processing of pain. To date, it appears that none have been explored as a way of distinguishing between migraine patients with aura (MWA) vs. those without aura (MWoA). In this work, we apply a mixture of predictive, e.g., classification methods and attribute-selection techniques, and traditional explanatory, e.g., statistical, analyses on functional connectivity measures extracted from EEG signal acquired from at-rest participants (N = 52) during their interictal period and tested them against the distinction between MWA and MWoA. We show that a functional connectivity metric of EEG data obtained during resting state can serve as a sole biomarker to differentiate between MWA and MWoA. Using the proposed analysis, we not only have been able to present high classification results (average classification of 84.62%) but also to discuss the underlying neurophysiological mechanisms upon which our technique is based. Additionally, a more traditional statistical analysis on the selected features reveals that MWoA patients show higher than average connectivity in the Theta band (p = 0.03) at rest than MWAs. We propose that our data-driven analysis pipeline can be used for resting-EEG analysis in any clinical context.

Differences in treatment response between migraine with aura and migraine without aura: lessons from clinical practice and RCTs.

Migraine is a major public health problem afflicting approximately 10% of the general population and is a leading cause of disability worldwide, yet our understanding of the basis mechanisms of migraine remains incomplete. About a third of migraine patients have attacks with aura, consisting of transient neurological symptoms that precede or accompany headache, or occur without headache. For patients, aura symptoms are alarming and may be transiently disabling. For clinicians and scientists, aura represents an intriguing neurophysiological event that may provide important insight into basic mechanisms of migraine. Several observations point toward important differences between migraine with and without aura. Compared with migraine without aura, migraine with aura has different heritability, greater association with different conditions including stroke, different alterations of brain structure and function as revealed by imaging studies. A number of studies also indicate that migraine with aura may respond differently to acute and preventive therapies as compared to migraine without aura. The purpose of this review is to provide an overview of these differences in treatment responses, and to discuss the possibility of different therapeutic strategies for migraine with vs. without aura.

Ischemic Stroke Associated With Calcitonin Gene-Related Peptide Inhibitor Therapy for Migraine: A Case Report.

Calcitonin gene-related peptide (CGRP) is involved in nociception and neurogenic inflammation in migraine, but also serves as a potent vasodilator acting on intracranial arteries. This latter effect raises concern about the possibility of drugs inhibiting CGRP precipitating cerebral ischemia. We describe a 41-year-old woman with migraine without aura who developed a right thalamic infarction following a first dose of erenumab, a CGRP-receptor blocker. Stroke onset occurred during a typical migraine. Imaging demonsrated right posterior cerebral artery near-occlusion initially with normalization of the vessel at follow-up imaging 2 months later, suggesting vasospasm as a possible mechanism. Extensive evaluation revealed no other specific cause of stroke or vascular risk factors aside from long-term use of oral contraceptive pills. CGRP inhibitors might be associated with ischemic stroke due to blockade of normal cerebral vasodilatory regulatory function.

Migraine improvement after spontaneous cervical artery dissection the Italian Project on Stroke in Young Adults (IPSYS).

OBJECTIVE: Whether migraine modifies after spontaneous cervical artery dissection (sCeAD) more than after other stroke etiologic subtypes has never been adequately investigated. METHODS: In the setting of the Italian Project on Stroke in Young Adults (IPSYS), we compared the course of migraine before and after acute brain infarct in a group of migraine patients with sCeAD and a group of migraine patients whose ischemia was due to a cause other than CeAD (non-CeAD IS), matched by sex, age (± 3 years), and migraine subtype.We applied linear mixed models to evaluate pre-event vs post-event changes and differences between sCeAD and non-CeAD IS patients. RESULTS: Eighty-seven patients per group (migraine without aura/migraine with aura, 67/20) qualified for the analysis. After the acute event, migraine headaches disappeared in 14.0% of CeAD patients vs 0.0% of non-CeAD IS patients (p ≤ 0.001). Migraine frequency (patients suffering at least 1 attack, from 93.1 to 80.5%, p = 0.001), pain intensity (from 6.7 ± 1.7 to 4.6 ± 2.6 in a 0 to 10 pain scale, p ≤ 0.001), and use of acute anti-migraine medications (patients taking at least 1 preparation, from 81.6 to 64.4%, p = 0.007) also improved significantly after CeAD as opposed to that observed after non-CeAD IS. CONCLUSION: The spontaneous improvement of migraine after sCeAD reinforces the hypothesis of a pathogenic link between the two conditions.

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks.

PURPOSE OF REVIEW: To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura. RECENT FINDINGS: The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe. The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

Migraine as possible red flag of PFO presence in suspected demyelinating disease.

OBJECTIVES: To investigate a possible association between isolated white matter lesions suggestive of demyelinating disease in magnetic resonance imaging (MRI) and patent foramen ovale (PFO) evidence in migraine patients, with or without aura. MATERIALS: 31 migraine patients, 28 females and 3 males, with MRI evidence of white matter lesions suggestive of demyelinating disease according to the Barkhof Criteria. All patients underwent further diagnostics including lumbar puncture, autoimmunity panel and cardiological evaluation to detect the presence of PFO. The mean duration of follow-up was 3.46 years and MIPAV software was used to analyze MRI imaging. RESULTS: 14 of the 31 patients (45%) had PFO. A significant association was found between PFO and migraine with visual aura (p < 0.001). No difference in lesion number, volume or area between patients with and without PFO was found, but the distribution was mainly occipital (p < 0.001) in patients with PFO. The follow-up showed a stationary lesion load in all PFO patients; no infratentorial or spinal cord lesion and no enhancement or corpus callosum lesion was ever detected. At the end of follow-up four patients developed multiple sclerosis: younger age at first MRI and oligoclonal bands were associated risk factors. CONCLUSIONS: Migraine is often one of the main symptoms leading to MRI, and in many cases white matter lesions of unspecific significance are discovered, thus placing demyelinating diseases in the differential diagnosis. Our study underlines the potential pathogenetic role of PFO in generating white matter lesions in migraine patients (45%), particularly those with visual aura and occipital lesions. For this reason, we affirm that PFO represents a cardinal point in the differential diagnosis of suspected demyelinating disease.

A trial case of medical treatment for primary headache using telemedicine.

RATIONALE: Video-based treatment in telemedicine is a potential alternative to face-to-face treatment. We describe our trial use of telemedicine to treat a patient with primary headache. PATIENT CONCERNS: A 25-year-old woman visited our branch hospital with a chief complaint of recurrent headache. Our branch hospital had no headache specialist, so a headache specialist at our main hospital provided treatment remotely. DIAGNOSES: She was diagnosed with migraine without aura by the headache specialist using telemedicine. INTERVENTIONS: The branch hospital physician and the headache specialist used video conferencing to interview and examine the patient and share cranial magnetic resonance imaging (MRI). Audio and camera angle/zoom could be adjusted during interviews, and high-quality video was continuously displayed at both hospitals simultaneously without lag between audio and video. Temporal/spatial resolution was sufficient for proper neurological evaluation. MRI had sufficient image quality and resolution for detailed interpretation. A prescription for medication was issued by the branch hospital physician and confirmed by the headache specialist. OUTCOMES: Zolmitriptan was effective in treating her migraine. LESSONS: Telemedicine was useful for treating this primary headache patient and can contribute to regional health care. Future challenges in telemedicine include expanding its use to other areas within the purview of general physicians and headache specialists, covering implementation and maintenance costs, providing adequate explanations to patients and family members, ensuring security of video transmissions, maintaining patient medical records, and supervising treatment.

Translation and Transcultural Validation of Migraine Screening Questionnaire (MS-Q).

INTRODUCTION: Between 30 to 59% of patients with migraine without aura are undiagnosed and improperly treated, because primary care physicians are either too busy or unfamiliar with criteria for diagnosing migraine. AIM: The aim of our study was to translate the Migraine Screen Questionnaire (MS-Q) to BHS (Bosnian/Croatian /Serbian) language and to test reliability and validity of the translation on a sample of primary care patients. MATERIAL AND METHODS: The study was designed as cross-sectional, multi centric, diagnostic accuracy trial of an instrument for screening patients who visit general practitioners, with an aim to reveal migraine without aura. The instrument was the MS-Q, originally written in English and validated in Spanish population, and in this study being translated to BHS language. RESULTS: Translation of the MS-Q to BHS language showed good diagnostic accuracy (sensitivity 80.0% and specificity 87.2%) and reliability (Cohen kappa 0.648) for migraine without aura, with significant screening yield among previously undiagnosed patients of 72.7%. The study also confirmed high percentage of patients with hidden MWA (52.9%) revealed by the MS-Q and ICH criteria that would otherwise remain undiagnosed. CONCLUSION: The MS-Q translation to BHS language could be considered as valid and reliable clinical instrument for revealing migraine without aura, similar by its performance to original questionnaire. It has considerable screening yield, discovering majority of patients with previously undiagnosed migraine without aura, whose definite diagnosis should later on be confirmed by the attending physicians using the ICH criteria.

Migraine and Yawning.

BACKGROUND: Yawning is considered to be a symptom that reflects dopaminergic activity, although its pathophysiological mechanism is not yet fully understood. Interestingly, repetitive yawning is seen in some patients during migraine attacks. The aim of this cross-sectional study is to investigate the frequency of yawning during migraine attacks and its association with different characteristics of migraine. METHODS: Patients with migraine with or without aura were evaluated using questionnaires and diaries to determine the characteristics of headache and accompanying symptoms. Repetitive yawning in the premonitory phase and/or during headache were determined. RESULTS: Three hundred and thirty-nine patients were included in the study. One hundred and fifty-four patients reported repetitive yawning (45.4%) during migraine attacks. Repetitive yawning was reported in the 11.2% of the patients in the premonitory phase, 24.2% during headaches, and 10% both in the premonitory phase and during headaches. Migraine with aura (46.8 vs 31.9%; P = .005), accompanying nausea (89.6 vs 75.1%; P = .001), vomiting (48.7 vs 37.8%; P = .044), osmophobia (66.7 vs 52.3%; P = .024), and cutaneous allodynia (58.2 vs 46%; P = .032) were more common in patients with yawning than without. Other dopaminergic-hypothalamic premonitory symptoms (41.6 vs 26.5%; P = .003), especially sleepiness (17.5 vs 5.9%; P = .001), irritability/anxiety (21.4% vs 11.4%; P = .019), nausea/vomiting (10.4 vs 4.3%; P = .03), and changes in appetite (18.2 vs 9.7%; P = .024), were also more frequent in patients with yawning than without. After being adjusted for all other relevant covariates, the odds of repetitive yawning were increased by the presence of nausea (OR 2.88; 95% CI 1.453-5.726; P = .002) and migraine with aura (OR 1.66; 95% CI 1.035-2.671; P = .036). CONCLUSIONS: Our results demonstrated that yawning is a common self-reported symptom leading or accompanying migraine attacks and is associated with aura, nausea and/or vomiting, osmophobia, and cutaneous allodynia in patients with migraine. Although yawning is a rather frequently seen behavior, it is a unique and reliable symptom in patients with migraine that may offer an opportunity for early treatment of migraine attacks.