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1.
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.Summary
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.2.
Thyra Langhagen Mirjam N. Landgraf Doreen Huppert Florian Heinen Klaus Jahn 《Current pain and headache reports》2016,20(12):67
Purpose of review
The goal of this review is to provide an actualized overview on vestibular migraine in childhood and adolescence, with focus on the epidemiology and clinical presentation as well as its treatment.Recent findings
Vertigo spells in childhood can evolve into other periodic syndromes and/or migraine types and persist even into adulthood.Summary
Vestibular migraine (VM) and benign paroxysmal vertigo are the most common causes of vertigo in children and adolescents. The diagnostic criteria for VM are dizziness and vertigo, headache, phonophobia and photophobia, and visual aura. The prevention of attacks is the treatment for children and adolescents with VM, as is recommended for migraine with or without aura. Thus, non-pharmacological measures are the first-line option; when these measures fail or daily activities are notably affected, drugs are administrated. Psychological assessment and cognitive behavioral therapy are also important therapeutic measures in this patient group. There is still insufficient research on VM in children and adolescents; future studies on clinical presentation, evolvement, and specific treatment are necessary.3.
Afrim Iljazi Cenk Ayata Messoud Ashina Anders Hougaard 《Current pain and headache reports》2018,22(4):27
Purpose of Review
Vasoactive peptides play a key role in the attack-initiating cascade of migraine. Recent studies have highlighted a potentially important role for endothelin-1, a potent vasoconstrictor peptide, in migraine pathophysiology. Here, we review the current data on endothelin’s involvement in migraine.Recent Findings
We identified 23 articles. Nine studies reported on endothelin-1 plasma concentrations in patients with migraine, eight studies investigated relevant genetic associations, five studies investigated endothelin-1 and spreading depression in animals, and one randomized controlled clinical trial tested the efficacy of an endothelin antagonist in the acute treatment of migraine in patients both with and without aura. Elevated endothelin-1 plasma levels have been reported in the early phase of migraine attacks. Genetic abnormalities related to the endothelin type A receptor have been reported in migraineurs. Endothelin-1 potently induces spreading depression in animals, which may explain the connection between endothelial irritation and migraine aura.Summary
Endothelin-1 could be a primary factor in the attack-triggering cascade of migraine attacks with and without aura. Additional studies in humans and animal models are needed to further elucidate the role of endothelin-1 in migraine.4.
Rachel E. Davis-Martin Ashley N. Polk Todd A. Smitherman 《Current pain and headache reports》2017,21(10):42
Purpose of Review
In contrast to well-established relationships between headache and affective disorders, the role of alcohol use in primary headache disorders is less clear. This paper provides a narrative overview of research on alcohol use disorders (AUDs) in primary headache and presents a meta-analysis of the role of alcohol as a trigger (precipitant) of headache.Recent Findings
The majority of studies on AUDs in headache have failed to find evidence that migraine or tension-type headache (TTH) is associated with increased risk for AUDs or problematic alcohol use. The meta-analysis indicated that 22% (95% CI: 17–29%) of individuals with primary headache endorsed alcohol as a trigger. No differences were found between individuals with migraine (with or without aura) or TTH. Odds of endorsing red wine as a trigger were over 3 times greater than odds of endorsing beer.Summary
An absence of increased risk for AUDs among those with primary headache may be attributable to alcohol’s role in precipitating headache attacks for some susceptible individuals. Roughly one fifth of headache sufferers believe alcohol precipitates at least some of their attacks. Considerable study heterogeneity limits fine-grained comparisons across studies and suggests needs for more standardized methods for studying alcohol-headache relationships and rigorous experimental designs.5.
Thomas-Martin Wallasch 《Advances in therapy》2010,27(1):56-62
Introduction
Large postmarketing surveillance (PMS) studies have demonstrated the efficacy and tolerability of frovatriptan for treatment of acute migraine in patients attending general practitioners (GPs). The aim of the ALADIN (Allegro® Anwendung durch interessierte Neurologen [Allegro® application by interested neurologists]) PMS study was to evaluate frovatriptan in patients attending neurologists or pain therapists.Methods
Patients fulfilling International Headache Society criteria for migraine, with or without aura, were enrolled. Patients completed an attack diary, including details of the attack, time to onset of action of frovatriptan, and recurrence of headache. Physicians completed a case report form detailing prior and actual migraine treatment. Frovatriptan 2.5 mg was administered for up to three consecutive attacks.Results
In total, 2160 patients were enrolled and data were obtained for 5831 attacks. Patients attending neurologists had more frequent attacks and longer history of migraine compared with those attending GPs. Median time to frovatriptan onset of action was 40 min and time to freedom from headache 70 min. An average of 1.2 frovatriptan tablets was required per attack, and mean additional analgesic use was 0.13. Recurrent headache occurred in 13.6%–15.5% of patients. Physicians as well as patients judged frovatriptan onset and duration of action as at least “good” in approximately 80% of attacks. A similar number judged the efficacy of frovatriptan against headache as “better” than previous treatment. The study drug was generally well tolerated. The frequency of adverse events was 0.6%.Conclusion
Frovatriptan, with fast onset of action and low rate of headache recurrence, was efficacious and well accepted by migraineurs attending neurologists or pain therapists. Approximately 80% of patients wished to continue migraine treatment with frovatriptan.6.
Mitchell G. Miglis 《Current pain and headache reports》2018,22(3):19
Purpose of Review
Symptoms of autonomic dysfunction are common in patients with migraine, both during and between migraine attacks. Studies evaluating objective autonomic testing in patients have found significant, though somewhat conflicting results. The purposes of this review are to summarize and interpret the key findings of these studies, including those evaluating heart rate variability, autonomic reflex testing, and functional imaging in patients with migraine. The neuroanatomy of the central autonomic network as it relates to migraine is also reviewed.Recent Findings
Several studies have evaluated autonomic balance in migraineurs, with conflicting results on the magnitude of sympathetic versus parasympathetic dysfunction. Most studies demonstrate sympathetic impairment, with a lesser degree of parasympathetic impairment.Summary
Three trends have emerged: (1) migraine with aura tends to produce more significant autonomic dysfunction than migraine without aura, (2) sympathetic impairment is more common than parasympathetic impairment, and (3) sympathetic impairment is common in the interictal period, with increased sympathetic responsiveness during the ictal period, suggesting adrenoreceptor hypersensitivity.7.
Kazumi Fujioka Minoru Oishi Akira Fujioka Tomohiro Nakayama 《Journal of Medical Ultrasonics》2018,45(4):605-610
Purpose
Migraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found.Methods
A total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography.Results
There was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39?±?0.68 vs 3.89?±?0.67 mm, respectively; p?=?0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94?±?5.72 vs 6.08?±?2.98%, respectively; p?=?0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56?±?7.36 vs 14.23?±?7.41%, respectively; p?=?0.024).Conclusion
We think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity.8.
Gianluca Coppola Antonio Di Renzo Emanuele Tinelli Chiara Lepre Cherubino Di Lorenzo Giorgio Di Lorenzo Marco Scapeccia Vincenzo Parisi Mariano Serrao Claudio Colonnese Jean Schoenen Francesco Pierelli 《The journal of headache and pain》2015,17(1):100
Background
Resting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks.Methods
Eighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores.Results
In comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally.Conclusions
The present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology.9.
Purpose of Review
This review is intended to examine how the diagnostic criteria for migraine have evolved over the past 45 years and to evaluate the strengths and weaknesses of the current diagnostic criteria promulgated by the International Classification of Headache Disorders (ICHD).Recent Findings
The ICHD is a comprehensive and systematic classification system for headache disorders. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (e.g., the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. The ICHD has allowed for more precise research study design in the field of headache medicine.Summary
The current diagnostic criteria for migraine outlined in the 3rd version of the ICHD are far more sensitive and specific than the clinical criteria proposed in 1962. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (i.e., low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities.10.
Purpose of Review
Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient “depression” of all spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy. Here, we provide an overview of the pathogenic mechanisms and propose plausible hypotheses on the involvement of SD in primary and secondary headache disorders.Recent Findings
SD can activate downstream trigeminovascular nociceptive pathways to explain the cephalgia in migraine, and possibly in secondary headache disorders as well. In healthy, well-nourished tissue (such as migraine), the intense transmembrane ionic shifts, the cell swelling, and the metabolic and hemodynamic responses associated with SD do not cause tissue injury; however, when SD occurs in metabolically compromised tissue (e.g., in ischemic stroke, intracranial hemorrhage, or traumatic brain injury), it can lead to irreversible depolarization, injury, and neuronal death. Recent non-invasive technologies to detect SDs in human brain injury may aid in the investigation of SD in headache disorders in which invasive recordings are not possible.Summary
SD explains migraine aura and progression of neurological deficits associated with other neurological disorders. Studying the nature of SD in headache disorders might provide pathophysiological insights for disease and lead to targeted therapies in the era of precision medicine.11.
S. Dreßke 《Schmerz (Berlin, Germany)》2016,30(4):333-338
Background
Every professional segment has its own typical forms of stress, which for members result in patterns of bodily conception and interpretation of pain. The way individuals cope with these typical forms of pain reflects their social identity, social status and group membership. In this study pain was investigated from a sociological perspective as a medium contributing to socialization processes in stress collectives.Objectives
Cultural conceptions of headache and migraine were investigated in members of blue collar occupations, in service professions and patients in specialized medical pain care.Materials and methods
In this study 49 qualitative biographical interviews were conducted with patients suffering from headache and migraine. The study population included persons from the general outpatient population and patients recruited from specialized inpatient pain clinics.Results
Members of blue collar occupations with specific body-oriented, mechanical stress patterns and dominant masculine attitudes, perceived headache and migraine as atypical deviations, which are contextualized as body pain. Professionals in the service sector with specific communicative-emotional work patterns perceived headache and migraine as typical and accepted deviations. Both pain conceptions represent dominant body norms and social commitments in each group; however, in specialized pain care these everyday concepts are transformed by increasing expert knowledge resulting in medicalized life styles and in identity conceptions conforming to the medical imperative.Conclusion
The success of specialized treatment of headache depends to a certain extent on the ability of patients to impose a medically regulated life style on their significant others; however, this can conflict with the demands of everyday life.12.
13.
Innocenzo Rainero Flora Govone Annalisa Gai Alessandro Vacca Elisa Rubino 《Current pain and headache reports》2018,22(5):36
Purpose of the Review
The goals of this review are to evaluate recent studies regarding comorbidity between migraine and different metabolic and endocrine disorders and to discuss the role of insulin resistance as a common pathogenetic mechanism of these diseases.Recent Findings
Recently, several studies showed that migraine is associated with insulin resistance, a condition in which a normal amount of insulin induces a suboptimal physiological response. All the clinical studies that used the oral glucose tolerance test to examine insulin sensitivity found that, after glucose load, there is in migraine patients a significant increase of both plasmatic insulin and glucose concentrations in comparison with controls. On the contrary, no association was found between migraine and type 2 diabetes, while type 1 diabetes seems to have a protective effect in the disease. Obesity and hypertension were shown to be risk factors for both episodic and chronic migraine. Metabolic syndrome has been recently associated mainly with migraine with aura and is now considered a risk factor also for medication overuse headache. Finally, a bidirectional association between migraine and hypothyroidism has been recently demonstrated, suggesting that common genetic or autoimmune mechanisms underlie both diseases.Summary
Recent studies showed that insulin receptor signaling and the related physiological responses are altered in migraine and may have a relevant pathogenic role in the disease. Further studies are warranted in order to better elucidate mechanisms underlying insulin resistance in migraine in order to develop new therapeutic strategies for this debilitating disease.14.
Guan-Yu Lin Yu-Kai Lin Jiunn-Tay Lee Meei-Shyuan Lee Chun-Chieh Lin Chia-Kuang Tsai Chi-Hsin Ting Fu-Chi Yang 《The journal of headache and pain》2015,17(1):97
Background
Although the comorbidity of migraine and restless legs syndrome (RLS) has been well-documented, the association between RLS and migraine frequency has yet to be elucidated. The present study aims to evaluate the prevalence of RLS among individuals who experience low-frequency, high-frequency, or chronic migraine presenting with and without aura.Methods
We conducted a cross-sectional, case-controlled study involving 505 participants receiving outpatient headache treatment. Standardized questionnaires were administered to collect information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were categorized into low-frequency (1–8/month), high-frequency (9–14/month), and chronic (≥15/month) headache groups. RLS was diagnosed according to the criteria outlined by the International RLS Study Group (IRLSSG). The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality and identify symptoms of anxiety and depression. Associations between migraine frequency and RLS prevalence were investigated using multivariate linear and logistic regression.Results
Univariate analysis revealed an effect of migraine frequency on RLS prevalence (p?=?0.026), though this effect did not persist following adjustment for baseline characteristics (p?=?0.256). The trend was robust in patients whose migraines presented with auras (p univariate?=?0.002; p multivariate?=?0.043) but not in those without auras (p univariate and p multivariate?>?0.05). Higher anxiety [odds ratio (OR)?=?1.18, p?=?0.019] and sleep disturbance (OR?=?1.17, p?=?0.023) scores were associated with higher RLS prevalence.Conclusions
Higher migraine frequency correlates with a higher prevalence of RLS, particularly among patients with auras.15.
Purpose of Review
Episodic migraine is common. Everyday behavioral patterns are associated with migraine attacks and disability. This paper reviews health behaviors that can be targeted in people with episodic migraine to enhance migraine-related outcomes.Recent Findings
Stressful events and perceived stress have demonstrated associations with migraine attack onset among people with episodic migraine. Consistency in daily patterns (eating, sleeping, exercise, and hydration status) is also associated with migraine activity. Sleep deprivation, fatigue, and poor quality sleep have demonstrated relationships with migraine attack onset, as well as headache frequency and headache-related disability in people with episodic migraine.Summary
The health behaviors implicated in episodic migraine are part of everyday patterns and can be targeted routinely in clinical practice to improve migraine management. Behavior change is challenging and should ideally be supported by a multidisciplinary team. Future research should focus on evaluating specific behavior change interventions and the relative impact of behavior on migraine outcomes in high- and low-frequency episodic migraine.16.
Jiyoung Kim Soo-Jin Cho Won-Joo Kim Kwang Ik Yang Chang-Ho Yun Min Kyung Chu 《The journal of headache and pain》2018,19(1):86
Background
Insomnia and migraine are closely related; insomnia aggravates migraine symptoms. This study was conducted to investigate the impact of migraine on the clinical presentation of insomnia symptoms.Methods
The data of the Korean Headache-Sleep Study (KHSS) were used in the present study. The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep in Korean adults aged 19 to 69 years. If a participant’s Insomnia Severity Index (ISI) score?≥?10, she/he was classified as having insomnia. The clinical presentation of insomnia symptoms was assessed using total and subcomponent scores of the ISI.Results
Of 2695 participants, 290 (10.8%) and 143 (5.3%) individuals were assigned as having insomnia and migraine, respectively. The proportions of migraine (12.8% vs. 4.4%, p?<? 0.001) and non-migraine headache (59.0% vs. 39.9%, p?<? 0.001) were higher among individuals with insomnia compared to those without insomnia. Among participants with insomnia, total ISI scores were not significantly different among participants with migraine, non-migraine, and non-headache [median and interquartile range: 13.0 (11.0–17.5) vs. 13.0 (11.0–17.5) vs. 12.0 (11.0–16.0), p?=?0.245]. ISI scores for noticeability of sleep problems to others were significantly higher among participants with migraine [3.0 (2.0–4.0) vs. 2.0 (2.0–3.0), p?=?0.011] and non-migraine headache [3.0 (2.0–4.0) vs. 2.0 (2.0–3.0), p?=?0.001] compared to those without headache history. Other ISI subcomponent scores did not significantly differ between headache status groups.Conclusions
Participants with insomnia had an increased risk of migraine and non-migraine headache compared to those without insomnia. Among participants with insomnia, overall insomnia severity was not significantly influenced by the headache status.17.
Zehong Cao Chin-Teng Lin Chun-Hsiang Chuang Kuan-Lin Lai Albert C. Yang Jong-Ling Fuh Shuu-Jiun Wang 《The journal of headache and pain》2015,17(1):102
Background
Migraine is characterized by a series of phases (inter-ictal, pre-ictal, ictal, and post-ictal). It is of great interest whether resting-state electroencephalography (EEG) is differentiable between these phases.Methods
We compared resting-state EEG energy intensity and effective connectivity in different migraine phases using EEG power and coherence analyses in patients with migraine without aura as compared with healthy controls (HCs). EEG power and isolated effective coherence of delta (1–3.5 Hz), theta (4–7.5 Hz), alpha (8–12.5 Hz), and beta (13–30 Hz) bands were calculated in the frontal, central, temporal, parietal, and occipital regions.Results
Fifty patients with episodic migraine (1–5 headache days/month) and 20 HCs completed the study. Patients were classified into inter-ictal, pre-ictal, ictal, and post-ictal phases (n?=?22, 12, 8, 8, respectively), using 36-h criteria. Compared to HCs, inter-ictal and ictal patients, but not pre- or post-ictal patients, had lower EEG power and coherence, except for a higher effective connectivity in fronto-occipital network in inter-ictal patients (p?<?.05). Compared to data obtained from the inter-ictal group, EEG power and coherence were increased in the pre-ictal group, with the exception of a lower effective connectivity in fronto-occipital network (p?<?.05). Inter-ictal and ictal patients had decreased EEG power and coherence relative to HCs, which were “normalized” in the pre-ictal or post-ictal groups.Conclusion
Resting-state EEG power density and effective connectivity differ between migraine phases and provide an insight into the complex neurophysiology of migraine.18.
Purpose of Review
Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future. Recognition of these symptoms by parents, guardians, teachers and carers is of importance in ensuring early and effective attack treatment.Recent Findings
A previous clinic-based questionnaire study in 103 children found a prevalence of premonitory symptoms in paediatric migraine of 67%, with a mean number of reported symptoms of two. A recent study found that in a clinic population of 100 children or adolescents with a migraine diagnosis who were preselected as having at least one premonitory symptom associated with their attacks, two or more premonitory symptoms were reported by 85% of patients. The most common symptoms were fatigue, mood change and neck stiffness.Summary
Although the population prevalence of premonitory symptoms in migraine within the paediatric population, or their ability to predict accurately the onset of an impending headache cannot be deduced from the retrospective studies performed to date, premonitory symptoms occur in children as young as 18 months old. Understanding the biological basis of these, and their heterogeneous phenotype may help future targeted therapeutic research, helping the development of drugs that act before the onset of pain, limiting the morbidity associated with the migraine attack.19.
Purpose of Review
There is growing interest in neuromodulation for primary headache conditions. Invasive modalities such as occipital nerve stimulation, deep brain stimulation and sphenopalatine ganglion stimulation are reserved for the most severe and intractable patients. Non-invasive options such as vagal nerve stimulation (nVNS), supraorbital nerve stimulation (nSONS) and transcranial magnetic nerve stimulation (TMS) have all emerged as potentially useful headache treatments. This review examines the evidence base for non-invasive neuromodulation in trigeminal autonomic cephalalgias and migraine.Recent Findings
Although a number of open-label series of non-invasive neuromodulation devices have been published, there is very little controlled evidence for their use in any headache condition. Open-label evidence suggests that nVNS may have a role in the prophylactic treatment of cluster headache and there is limited evidence to suggest it may be useful in the acute treatment of cluster and potentially migraine attacks. There is limited controlled evidence to suggest a role for nSONS in the prophylactic treatment of episodic migraine but there is no evidence to support its use in cluster headache. TMS may be efficacious in the acute treatment of episodic migraine has no controlled evidence to support its use as a preventative in any headache condition.Summary
Non-invasive neuromodulation techniques are an attractive treatment option with excellent safety profiles but their use is not yet supported by high-quality randomised controlled trials.20.
Casper Emil Christensen Samaira Younis Marie Deen Sabrina Khan Hashmat Ghanizada Messoud Ashina 《The journal of headache and pain》2018,19(1):105