Showing papers in "Headache in 2013"

The CARE guidelines: consensus-based clinical case reporting guideline development.

Abstract: Background A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design Objective Develop, disseminate, and implement systematic reporting guidelines for case reports Methods We used a three-phase consensus process consisting of (1) pre-meeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines Results This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent Conclusions We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery © 2013 Gagnier et al; licensee Wiley Periodicals, Inc

The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies

Abstract: Background Four ongoing US public health surveillance studies gather information relevant to the prevalence, impact, and treatment of headache and migraine: the National Health Interview Survey, the National Health and Nutrition Examination Survey, the National Ambulatory Care Survey, and the National Hospital Ambulatory Medical Care Survey. The American Migraine Prevalence and Prevention (AMPP) study is a privately funded study that provides comparative US population-based estimates of the prevalence and burden of migraine and chronic migraine. Objective To gather in one place and compare the most current available estimates of the US adult prevalence of headache and migraine, and the number of affected people overall and in various subgroups, and to provide estimates of headache burden and treatment patterns by examining migraine and headache as a reason for ambulatory care and emergency department (ED) visits in the United States. Methods We reviewed published analyses from available epidemiological studies identified through searches of PubMed and the National Center for Health Statistics. We aimed to identify information about migraine and headache burden, and treatment in national surveys conducted over the last decade. For each source, we selected the best available and most current estimate of migraine or headache prevalence, and selected associated measures of disability, health care use, and treatment patterns. Results Compared with a slightly higher proportion of 22.7% in the National Health and Nutrition Examination Survey, 16.6% of adults 18 or older reported having migraine or other severe headaches in the last 3 months in the 2011 National Health Interview Survey. In contrast, the AMPP study found an overall prevalence of migraine of 11.7% and probable migraine of 4.5%, for a total of 16.2%. Data from National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey showed that head pain was the fifth leading cause of ED visits overall in the US and accounted for 1.2% of outpatient visits. The burden of headache was highest in females 18-44, where the 3-month prevalence of migraine or severe headache was 26.1% and head pain was the third leading cause of ED visits. The prevalence and burden of headache was substantial even in the least affected subgroup of males 75 or older, where 4.6% reported experiencing severe headache or migraine in the previous 3 months. Triptans accounted for almost 80% of antimigraine analgesics prescribed at office visits in 2009, nearly half of which were for sumatriptan. Migraine is associated with increased risk for other physical and psychiatric comorbidities, and this risk increases with headache frequency. Conclusion This report provides the most current available estimates of the prevalence, impact, and treatment patterns of migraine or severe headache in the United States. Migraine and other severe headaches are a common and major public health problem, particularly among reproductive-aged women. Data about prevalence and disability from the major government-funded surveillance studies are generally consistent with results of studies such as the American Migraine Studies 1 and 2, and the AMPP study.

Sex Differences in the Prevalence, Symptoms, and Associated Features of Migraine, Probable Migraine and Other Severe Headache: Results of the American Migraine Prevalence and Prevention (AMPP) Study

Abstract: Background The strikingly higher prevalence of migraine in females compared with males is one of the hallmarks of migraine. A large global body of evidence exists on the sex differences in the prevalence of migraine with female to male ratios ranging from 2 : 1 to 3 : 1 and peaking in midlife. Some data are available on sex differences in associated symptoms, headache-related disability and impairment, and healthcare resource utilization in migraine. Few data are available on corresponding sex differences in probable migraine (PM) and other severe headache (ie, nonmigraine-spectrum severe headache). Gaining a clear understanding of sex differences in a range of severe headache disorders may help differentiate the range of headache types. Herein, we compare sexes on prevalence and a range of clinical variables for migraine, PM, and other severe headache in a large sample from the US population. Methods This study analyzed data from the 2004 American Migraine Prevalence and Prevention Study. Total and demographic-stratified sex-specific, prevalence estimates of headache subtypes (migraine, PM, and other severe headache) are reported. Log-binomial models are used to calculate sex-specific adjusted prevalence ratios and 95% confidence intervals for each across demographic strata. A smoothed sex prevalence ratio (female to male) figure is presented for migraine and PM. Results One hundred sixty-two thousand seven hundred fifty-six individuals aged 12 and older responded to the 2004 American Migraine Prevalence and Prevention Study survey (64.9% response rate). Twenty-eight thousand two hundred sixty-one (17.4%) reported “severe headache” in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders-2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, headache-related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using preventive pharmacologic treatment for headache. Conclusions In this large, US population sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to additional headache types and related factors.

Patterns of Use and Reasons for Discontinuation of Prophylactic Medications for Episodic Migraine and Chronic Migraine: Results From the Second International Burden of Migraine Study (IBMS-II)

Abstract: Objective Our objective was to characterize patterns of preventive medication use in persons with episodic migraine (EM) and chronic migraine (CM). Background Several classes of medications are used both on- and off-label for the prevention of migraine, including β-blockers (eg, propranolol, timolol), tricyclic antidepressants (eg, amitriptyline), anti-epileptic drugs (eg, topiramate, valproic acid), and neurotoxins (eg, onabotulinumtoxinA). Methods Preventive medication use and reasons for discontinuation were collected in an international, Web-based, cross-sectional survey of adults with migraine during 2010. Descriptive analyses were conducted on demographics and headache-related disability as measured by the Migraine Disability Assessment Scale, stratified by use of preventive medication, and EM or CM. Univariate and multivariate logistic regression models were constructed to assess predictors of preventive medication use. Results One thousand one hundred and sixty-five respondents completed the survey. Only 28.3% of EM and 44.8% of CM respondents were currently using preventive medication; any use of prophylaxis (prior or current) was reported by 43.4% of those with EM and 65.9% with CM. The mean number of prophylactic medications ever used was 2.92 for EM and 3.94 for CM. Antidepressants were used most frequently (EM 60.9%; CM 54.7%), followed by β-blockers (EM 35.4%; CM 36.8%) and anti-epileptics (EM 28.6%; CM 36.3%). Odds of preventive medication use were higher among CM than EM, adjusting for age, gender, race, years of daily headache, and country (odds ratio 2.72; 95% confidence interval 2.15 to 3.57). Greater headache-related disability and older age were also associated with greater odds of ever having used prophylaxis, regardless of headache frequency. Conclusions Less than half the persons with EM and CM were currently using preventive medication for migraine, with treatment rates being higher for CM, as expected. Those with CM tried more medications than those with EM, possibly reflecting higher levels of treatment need.

Spontaneous Low Pressure, Low CSF Volume Headaches: Spontaneous CSF Leaks

Abstract: Spontaneous intracranial hypotension typically results from spontaneous cerebrospinal fluid (CSF) leak, often at spine level and only rarely from skull base. Once considered rare, it is now diagnosed far more commonly than before and is recognized as an important cause of headaches. CSF leak leads to loss of CSF volume. Considering that the skull is a rigid noncollapsible container, loss of CSF volume is typically compensated by subdural fluid collections and by increase in intracranial venous blood which, in turn, causes pachymeningeal thickening, enlarged pituitary, and engorgement of cerebral venous sinuses on magnetic resonance imaging (MRI). Another consequence of CSF hypovolemia is sinking of the brain, with descent of the cerebellar tonsils and brainstem as well as crowding of the posterior fossa noted on head MRI. The clinical consequences of these changes include headaches that are often but not always orthostatic, nausea, occasional emesis, neck and interscapular pain, cochleovestibular manifestations, cranial nerve palsies, and several other manifestations attributed to pressure upon or stretching of the cranial nerves or brain or brainstem structures. CSF lymphocytic pleocytosis or increase in CSF protein concentration is not uncommon. CSF opening pressure is often low but can be within normal limits. Stigmata of disorders of connective tissue matrix are seen in some of the patients. An epidural blood patch, once or more, targeted or distant, at one site or bilevel, has emerged as the treatment of choice for those who have failed the conservative measures. Epidural injection of fibrin glue of both blood and fibrin glue can be considered in selected cases. Surgery to stop the leak is considered when the exact site of the leak has been determined by neurodiagnostic studies and when less invasive measures have failed. Subdural hematomas sometimes complicate the CSF leaks; a rebound intracranial hypertension after successful treatment of a leak is not rare. Cerebral venous sinus thrombosis as a complication is fortunately less common, and superficial siderosis and bibrachial amyotrophy are rare. Short-term recurrences are not uncommon, and long-term recurrences are not rare.

Contributions of Epidemiology to Our Understanding of Migraine

Abstract: Background During the past decade, the introduction of the second edition of the International Classification of Headache Disorders (ICHD-II) and the initiation of active campaigns to increase awareness of the high magnitude, burden, and impact of migraine have stimulated numerous studies of population-based data on the prevalence, correlates, and impact of migraine. Objective This paper provides an update of the literature on the worldwide epidemiology of migraine from studies that included the ICHD-II criteria. The aims of this paper are: (1) to review evidence regarding the magnitude of migraine; (2) to summarize information on the correlates and impact of migraine; and (3) to discuss the contributions, challenges, and future directions in the epidemiology of migraine. Evidence on the magnitude of migraine is divided into the following types of data: (1) prevalence rates of ICHD-II-defined migraine and tension-type headache from international population-based studies of adults; (2) the magnitude of migraine in U.S. studies; (3) ICHD-II-based international prevalence rates of ICHD-II-defined migraine in children; and (4) incidence rates of migraine from prospective longitudinal studies. Methods A comprehensive review of the literature on the prevalence of migraine subtypes and tension-type headache defined by ICHD-II criteria during the past decade was conducted and aggregate weighted rates across studies were derived. Results Across the 19 studies of adults that employed the ICHD-II criteria, the aggregate weighted estimates of the 12-month prevalence of definite migraine are 11.5%, and probable migraine of 7%, yielding a total of 18.5%. The cross-study weighted aggregate rate of migraine with aura is 4.4%, chronic migraine is 0.5%, and of tension-type headache is 13%. There has been even greater growth in international prevalence data on migraine in children, with a total of 21 studies of children that have employed the ICDH-II criteria. The aggregate weighted rate of definite migraine in children is 10.1% and migraine with aura is 1.6%. The well-established demographic correlates of migraine including the equal sex ratio in childhood, with increasing prevalence of migraine in females across adolescence to mid-adulthood were confirmed in these studies. Despite increasing effort to increase awareness of migraine, approximately 50% of those with frequent and/or severe migraine do not receive professional treatment. Conclusions This review demonstrates that the descriptive epidemiology of migraine has reached its maturity. The prevalence rates and sociodemographic correlates have been stable across 50 years. These developments justify a shift in efforts to the application of the designs and methods of analytic epidemiology. Retrospective case–control studies followed by prospective cohort studies that test specific associations are likely to enhance our understanding of the predictors of incidence and progression of migraine, subtypes of migraine with differential patterns of onset and course, and specific environmental exposures that may have either causal or provocative influences on migraine etiology.

Expert consensus recommendations for the performance of peripheral nerve blocks for headaches--a narrative review.

Abstract: Objective To describe a standardized methodology for the performance of peripheral nerve blocks (PNBs) in the treatment of headache disorders. Background PNBs have long been employed in the management of headache disorders, but a wide variety of techniques are utilized in literature reports and clinical practice. Methods The American Headache Society Special Interest Section for PNBs and other Interventional Procedures convened meetings during 2010-2011 featuring formal discussions and agreements about the procedural details for occipital and trigeminal PNBs. A subcommittee then generated a narrative review detailing the methodology. Results PNB indications may include select primary headache disorders, secondary headache disorders, and cranial neuralgias. Special procedural considerations may be necessary in certain patient populations, including pregnancy, the elderly, anesthetic allergy, prior vasovagal attacks, an open skull defect, antiplatelet/anticoagulant use, and cosmetic concerns. PNBs described include greater occipital, lesser occipital, supratrochlear, supraorbital, and auriculotemporal injections. Technical success of the PNB should result in cutaneous anesthesia. Targeted clinical outcomes depend on the indication, and include relief of an acute headache attack, terminating a headache cycle, and transitioning out of a medication-overuse pattern. Reinjection frequency is variable, depending on the indications and agents used, and the addition of corticosteroids may be most appropriate when treating cluster headache. Conclusions These recommendations from the American Headache Society Special Interest Section for PNBs and other Interventional Procedures members for PNB methodology in headache disorder treatment are derived from the available literature and expert consensus. With the exception of cluster headache, there is a paucity of evidence, and further research may result in the revision of these recommendations to improve the outcome and safety of these interventions.

Atypical Resting‐State Functional Connectivity of Affective Pain Regions in Chronic Migraine

Abstract: Objective.— Chronic migraineurs (CM) have painful intolerances to somatosensory, visual, olfactory, and auditory stimuli during and between migraine attacks. These intolerances are suggestive of atypical affective responses to potentially noxious stimuli. We hypothesized that atypical resting-state functional connectivity (rs-fc) of affective pain-processing brain regions may associate with these intolerances. This study compared rs-fc of affective pain-processing regions in CM with controls. Methods.— Twelve minutes of resting-state blood oxygenation level-dependent data were collected from 20 interictal adult CM and 20 controls. Rs-fc between 5 affective regions (anterior cingulate cortex, right/left anterior insula, and right/left amygdala) with the rest of the brain was determined. Functional connections consistently differing between CM and controls were identified using summary analyses. Correlations between number of migraine years and the strengths of functional connections that consistently differed between CM and controls were calculated. Results.— Functional connections with affective pain regions that differed in CM and controls included regions in anterior insula, amygdala, pulvinar, mediodorsal thalamus, middle temporal cortex, and periaqueductal gray. There were significant correlations between the number of years with CM and functional connectivity strength between the anterior insula with mediodorsal thalamus and anterior insula with periaqueductal gray. Conclusion.— CM is associated with interictal atypical rs-fc of affective pain regions with pain-facilitating and pain-inhibiting regions that participate in sensory-discriminative, cognitive, and integrative domains of the pain experience. Atypical rs-fc with affective pain regions may relate to aberrant affective pain processing and atypical affective responses to painful stimuli characteristic of CM.

Choosing wisely in headache medicine: the American Headache Society's list of five things physicians and patients should question.

Abstract: In an effort to draw attention to tests and procedures associated with low-value care in headache medicine, the American Headache Society (AHS) joined the Choosing Wisely initiative of the American Board of Internal Medicine Foundation. The AHS president appointed an ad hoc "Choosing Wisely" task force of the AHS. The committee surveyed AHS members to develop a candidate list of items for the AHS "Top 5" list of low-value care in headache medicine. Through a process of literature review and consensus, the final list of five items was chosen. Draft recommendations went through several rounds of revision and a process of outside review. The AHS Board of Directors approved the final list of "Five Things." The five recommendations approved by the AHS Board of Directors are: (1) don't perform neuroimaging studies in patients with stable headaches that meet criteria for migraine; (2) don't perform computed tomography imaging for headache when magnetic resonance imaging is available, except in emergency settings; (3) don't recommend surgical deactivation of migraine trigger points outside of a clinical trial; (4) don't prescribe opioid- or butalbital-containing medications as a first-line treatment for recurrent headache disorders; and (5) don't recommend prolonged or frequent use of over-the-counter pain medications for headache. We recommend that headache medicine specialists and other physicians who evaluate and treat headache disorders should use this list when discussing care with patients.

Barriers to the diagnosis and treatment of migraine: effects of sex, income, and headache features.

Abstract: Background.— US Headache Consortium Guidelines state that persons with migraine with headache-related disability should receive certain acute treatments including migraine-specific and other medications. However, many eligible individuals do not receive these therapies. Individuals with migraine may experience barriers to receiving minimal appropriate care. We aimed to identify barriers to care in a population sample of individuals with episodic migraine. We assessed barriers at 3 levels: medical consultation, diagnosis, and acute pharmacologic therapy use and assessed the contribution of socioeconomic, demographic, and headache-specific variables to these barriers. Methods.— We identified 3 steps that were minimally necessary to achieve guideline-defined appropriate acute pharmacologic therapy as: (1) consulting a prescribing health care professional; (2) receiving a migraine diagnosis; and (3) using migraine-specific or other appropriate acute treatments. We used data from the 2009 American Migraine Prevalence and Prevention study sample to identify persons with episodic migraine with unmet treatment needs, defined by a Migraine Disability Assessment Scale (MIDAS) score corresponding to Grade II (mild), III (moderate), or IV (severe) headache-related disability. We determined whether these individuals had consulted a health care professional for headache over the previous year, if they ever received a medical diagnosis of migraine from a health care professional, and whether they were currently using appropriate acute treatment for migraine (ie, a triptan, prescription non-steroidal anti-inflammatory drug, or an isometheptene-containing agent). We analyzed several socioeconomic, demographic, and headache-specific variables to determine if they were related to barriers in any of the 3 defined steps. Results.— Of 775 eligible participants with episodic migraine and headache-related disability, 45.5% (n = 353/775) had consulted health care professional for headache in the preceding year. Among those individuals, 86.7% (n = 306/353) reported receiving a medical diagnosis of migraine. Among the diagnosed consulters, 66.7% (204/306) currently used acute migraine-specific treatments. Only 204 (26.3%) individuals successfully completed all 3 steps. Multivariate logistic regression models revealed that the strongest predictors of current consulting for headache were having health insurance {odds ratio (OR) = 1.73 (95% confidence interval [CI], 1.07-2.79)}, high headache-related disability (OR = 1.06 [95% CI, 1.0-1.14] for a 10-point change in MIDAS score), and a high composite migraine symptom severity score (OR = 1.19 [95% CI, 1.05-1.36]). Among consulters, diagnosis was much more likely in women than men (OR = 4.25 [95% CI, 1.61-11.2]) and became increasingly likely with increasing average headache pain severity (OR = 1.44 [95% CI, 1.12-1.87]) and migraine symptom severity score. Among those who were diagnosed, annual household income was the strongest predictor of currently using guideline-defined appropriate acute treatment (OR = 1.44 [95% CI, 1.07-1.93]) followed by a 10-point change in MIDAS score (OR 1.16 [95% CI, 1.02-1.35]). Conclusions.— Among persons with migraine in need of medical care (MIDAS Grade II or greater), only one quarter traversed the 3 steps we proposed to be necessary to achieving minimally appropriate care (consulting, diagnosis, and treatment/medication use). Health insurance status was an important predictor of consulting. Among consulters, women were far more likely to be diagnosed than men, suggesting that gender bias in diagnosis may be an important barrier for men. There were economic barriers related to use of appropriate prescription medications. Public health efforts should focus on improving consultation rates, particularly in the uninsured and diagnostic rates particularly in males with migraine.

Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development.

Abstract: Calcitonin gene-related peptide (CGRP) is a ubiquitous neuropeptide found at the very centers of the migraine process, both centrally and peripherally. It has been under careful study for approximately 25 years. Several CGRP-receptor antagonists are being evaluated for acute treatment of episodic migraine. Three monoclonal antibodies are being studied for prevention of episodic migraine, and 1 monoclonal antibody is being studied for prevention of chronic migraine. In this review, we discuss the role of CGRP in normal physiology and the consequences of CGRP inhibition for human homeostasis. We then review the current state of development for CGRP-receptor antagonists and CGRP monoclonal antibodies. We close by speculating on the potential clinical role of CGRP antagonism in the acute and preventive treatment of episodic and chronic migraine.

Examination of Unmet Treatment Needs Among Persons With Episodic Migraine: Results of the American Migraine Prevalence and Prevention (AMPP) Study

Abstract: Background Despite the expanding therapeutic armamentarium, many people with episodic migraine (EM) have unmet acute treatment needs. Objective To determine the relative frequency of prespecified types of “unmet treatment needs” in persons with EM in a US population-based sample. Methods Eligible participants completed the 2009 American Migraine Prevalence and Prevention Study survey and met International Classification of Headache Disorders-2nd edition (ICHD-2) criteria for migraine with an average headache day frequency of <15 days per month (EM). We identified 5 domains of unmet treatment needs: (1) dissatisfaction with current acute treatment using 3 summary items from the Patient Perception of Migraine Questionnaire-revised edition (PPMQ-R); (2) moderate or severe headache-related disability defined by a Migraine Disability Assessment Scale score of ≥11; (3) excessive use of opioids or barbiturates defined as use on ≥4 days/month or by meeting Diagnostic and Statistical Manual for Mental Disorders-4th edition criteria for dependence; (4) recurrent use of the emergency department or urgent care clinic for headache defined by ≥2 visits in the preceding year for headache; and (5) history of cardiovascular events indicating a possible contraindication to triptan use. For each respondent, we identified their unmet treatment needs in each category and classified them as having no unmet needs or 1 or more unmet needs. Results Of 5591 respondents with EM, 2274 (40.7%) had 1 or more unmet needs; 1467 (26.2%) had exactly 1 unmet need, and 807 (14.4%) had 2 or more unmet needs. Among those with at least 1 unmet need, 1069 (47.0%) had moderate or severe headache-related disability, 851 (37.4%) were dissatisfied with their acute treatment regimen, 728 (32.0%) had excessive opioid or barbiturate use and/or probable dependence, 595 (26.2%) had a history of cardiovascular events, and 129 (5.7%) reported ≥2 visits in the preceding year to the emergency department/urgent care clinic for headache. Persons with more headache days, depression, or generalized anxiety were more likely to have unmet treatment needs. Conclusion In a population sample of individuals with EM, more than 40% have at least 1 unmet need in the area of acute treatment. The leading reasons for unmet needs, which include headache-related disability and dissatisfaction with current acute treatment, suggest opportunities for improving outcomes for persons with EM.

The Evolution of a Migraine Attack – A Review of Recent Evidence

Abstract: A migraine attack is an extraordinarily complex brain event that takes place over hours to days. This review focuses on recent human studies that shed light on the evolution of a migraine attack. It begins with a constellation of premonitory symptoms that are associated with activation of the hypothalamus and may involve the neurotransmitter dopamine. Even in the premonitory phase, patients experience sensitivity to sensory stimuli, indicating that central sensitization is a primary phenomenon. The migraine attack progresses to a phase that in some patients includes aura, which involves changes in cortical function, blood flow, and neurovascular coupling. The aura phase overlaps with the headache phase, which is associated with further changes in blood flow and function of the brainstem, thalamus, hypothalamus, and cortex. Serotonin receptors, nitric oxide, calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and prostanoids are demonstrated specific chemical mediators of migraine based on therapeutic and triggered migraine studies. A number of migraine symptoms persist beyond resolution of headache into a postdromal phase, accompanied by persistent blood flow changes in several brain regions. Although these phases of migraine have substantial temporal, neurochemical, and anatomical overlap, each represents an important window onto the pathophysiology of migraine as well as a target for therapeutic intervention. A comprehensive approach to migraine requires an understanding of the entire range of mechanisms and resultant symptoms that occur throughout the evolution of an attack.

Post-Traumatic Headaches in Civilians and Military Personnel: A Comparative, Clinical Review

Abstract: Post-traumatic headache (PTH) is the most frequent symptom after traumatic brain injury (TBI). We review the epidemiology and characterization of PTH in military and civilian settings. PTH appears to be more likely to develop following mild TBI (concussion) compared with moderate or severe TBI. PTH often clinically resembles primary headache disorders, usually migraine. For migraine-like PTH, individuals who had the most severe headache pain had the highest headache frequencies. Based on studies to date in both civilian and military settings, we recommend changes to the current definition of PTH. Anxiety disorders such as post-traumatic stress disorder (PTSD) are frequently associated with TBI, especially in military populations and in combat settings. PTSD can complicate treatment of PTH as a comorbid condition of post-concussion syndrome. PTH should not be treated as an isolated condition. Comorbid conditions such as PTSD and sleep disturbances also need to be treated. Double-blind placebo-controlled trials in PTH population are necessary to see whether similar phenotypes in the primary headache disorders and PTH will respond similarly to treatment. Until blinded treatment trials are completed, we suggest that, when possible, PTH be treated as one would treat the primary headache disorder(s) that the PTH most closely resembles.

Prevalence of Migraine in Patients With Celiac Disease and Inflammatory Bowel Disease

Abstract: Background.—European studies have demonstrated increased prevalence of headache of patients with celiac disease compared with controls. Methods.—Subjects took a self-administered survey containing clinical,demographic,and dietary data,as well as questions about headache type and frequency. The ID-Migraine screening tool and the Headache Impact Test (HIT-6) were also used. Results.—Five hundred and two subjects who met exclusion criteria were analyzed ‐ 188 with celiac disease, 111 with IBD, 25 with gluten sensitivity (GS), and 178 controls (C). Chronic headaches were reported by 30% of celiac disease, 56% of GS, 23% of IBD, and 14% of control subjects (P 65 was protective (P = .0345). Seventy-two percent of celiac disease subjects graded their migraine as severe in impact, compared with 30% of IBD, 60% of GS, and 50% of C subjects (P = .0919). There was no correlation between years on gluten-free diet and migraine severity. Conclusions.—Migraine was more prevalent in celiac disease and IBD subjects than in controls. Future studies should include screening migraine patients for celiac disease and assessing the effects of gluten-free diet on migraines in celiac disease.

Traumatic brain injury, neuroinflammation, and post-traumatic headaches.

Abstract: Concussions following head and/or neck injury are common, and although most people with mild injuries recover uneventfully, a subset of individuals develop persistent post-concussive symptoms that often include headaches. Post-traumatic headaches vary in presentation and may progress to become chronic and in some cases debilitating. Little is known about the pathogenesis of post-traumatic headaches, although shared pathophysiology with that of the brain injury is suspected. Following primary injury to brain tissues, inflammation rapidly ensues; while this inflammatory response initially provides a defensive/reparative function, it can persist beyond its beneficial effect, potentially leading to secondary injuries because of alterations in neuronal excitability, axonal integrity, central processing, and other changes. These changes may account for the neurological symptoms often observed after traumatic brain injury, including headaches. This review considers selected aspects of the inflammatory response following traumatic brain injury, with an emphasis on the role of glial cells as mediators of maladaptive post-traumatic inflammation.

IgG‐Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome

Abstract: Objectives. To evaluate therapeutic potential of the immunoglobulin G (IgG)-based elimination diet among migraine patients with irritable bowel syndrome (IBS). Background. Food elimination has been suggested as an effective and inexpensive therapeutic strategy in patients with migraine and concomitant IBS in the past studies. Methods. A total of 21 patients (mean [standard deviation] age: 38.0 [11.2] years; 85.7% females) diagnosed with migraine and IBS were included in this double-blind, randomized, controlled, cross-over clinical trial composed of baseline (usual diet), first diet (elimination or provocation diets), and second diet (interchange of elimination or provocations diets) phases and 4 visits. Results. IgG antibody tests against 270 food allergens revealed mean (standard deviation) reaction count to be 23.1 (14.1). Compared with baseline levels, elimination diet per se was associated with significant reductions in attack count (4.8 [2.1] vs 2.7 [2.0]; P < .001), maximum attack duration (2.6 [0.6] vs 1.4 [1.1] days; P < .001), mean attack duration (1.8 [0.5] vs 1.1 [0.8] days; P < .01), maximum attack severity (visual analog scale 8.5 [1.4] vs visual analog scale 6.6 [3.3]; P < .001), and number of attacks with acute medication (4.0 [1.5] vs 1.9 [1.8]; P < .001). There was a significant reduction in pain-bloating severity (1.8 [1.3] vs 3.2 [0.8]; P < .05), pain-bloating within the last 10 days (3.2 [2.8] vs 5.5 [3.1]; P < .05), and improvement obtained in quality of life (3.6 [1.4] vs 2.9 [1.0]; P < .05) by the elimination diet as compared with provocation diet. Conclusions. Our findings indicate that food elimination based on IgG antibodies in migraine patients who suffer from concomitant IBS may effectively reduce symptoms from both disorders with possible positive impact on the quality of life of the patients as well as potential savings to the health-care system.

Panic Disorder and Migraine: Comorbidity, Mechanisms, and Clinical Implications

Abstract: A growing body of literature suggests that comorbid anxiety disorders are more common and more prognostically relevant among migraine sufferers than comorbid depression. Panic disorder (PD) appears to be more strongly associated with migraine than most other anxiety disorders. PD and migraine are both chronic diseases with episodic manifestations, involving significant functional impairment and shared symptoms during attacks, interictal anxiety concerning future attacks, and an absence of identifiable secondary pathology. A meta-analysis of high-quality epidemiologic study data from 1990 to 2012 indicates that the odds of PD are 3.76 times greater among individuals with migraine than those without. This association remains significant even after controlling for demographic variables and comorbid depression. Other less-rigorous community and clinical studies confirm these findings. The highest rates of PD are found among migraine with aura patients and those presenting to specialty clinics. Presence of PD is associated with greater negative impact of migraine, including more frequent attacks, increased disability, and risk for chronification and medication overuse. The mechanisms underlying this common comorbidity are poorly understood, but both pathophysiological (eg, serotonergic dysfunction, hormonal influences, dysregulation of the hypothalamic-pituitary-adrenal axis) and psychological (eg, interoceptive conditioning, fear of pain, anxiety sensitivity, avoidance behavior) factors are implicated. Means of assessing comorbid PD among treatment-seeking migraineurs are reviewed, including verbal screening for core PD symptoms, ruling out medical conditions with panic-like features, and administering validated self-report measures. Finally, evidence-based strategies for both pharmacologic and behavioral management are outlined. The first-line migraine prophylactics are not indicated for PD, and the selective serotonin re-uptake inhibitors used to treat PD are not efficacious for migraine; thus, separate agents are often required to address each condition. Core components of behavioral treatments for PD are reviewed, and their integration into clinical headache practice is discussed.

Complementary and alternative medicine use for headache and migraine: a critical review of the literature.

Abstract: Contexts. An evidence base for complementary and alternative medicine (CAM) consumption within general populations is emerging. However, research data on CAM use for headache disorders remain poorly documented. This paper, constituting the first critical review of literature on this topic, provides a synopsis and evaluation of the research findings on CAM use among patients with headache and migraine. Methods. A comprehensive search of literature from 2000 to 2011 in CINAHL, MEDLINE, AMED, and Health Sources was conducted. The search was confined to peer-reviewed articles published in English reporting empirical research findings of CAM use among people with primary headache or migraine. Results. The review highlights a substantial level of CAM use among people with headache and migraine. There is also evidence of many headache and migraine sufferers using CAM concurrent to their conventional medicine use. Overall, the existing studies have been methodologically weak and there is a need for further rigorous research employing mixed method designs and utilizing large national samples. Discussion. The critical review highlights the substantial prevalence of CAM use among people with headache and migraine as a significant health care delivery issue, and health care professionals should be prepared to inquire and discuss possible CAM use with their patients during consultations. Health care providers should also pay attention to the possible adverse effects of CAM or interactions between CAM and conventional medical treatments among headache and migraine patients.

Biomarkers Associated With Migraine and Their Potential Role in Migraine Management

Abstract: Objective The focus of this review is to review potential diagnostic and therapeutic biomarkers associated with migraine. Background Migraine headache is a common disease that affects millions of individuals worldwide. Although well-accepted diagnostic criteria exist for migraine, it is still a complex disorder that remains both underdiagnosed and misdiagnosed. The causes of migraine are likely a mix of genetic, epigenetic, and environmental factors that, together with the individual's life history, translate into the observed clinical heterogeneity. Inherent clinical heterogeneity is an obstacle in developing more effective treatments. The lack of appropriate biomarkers is also an impediment to developing more effective therapeutic/preventive approaches. Ultimately, biomarkers may facilitate the goal of individualized medicine by enabling clinicians to more accurately diagnose and treat migraine and other types of headache. Methods A comprehensive review was conducted of PubMed citations containing the key word “marker” OR “biomarker” combined with “migraine” OR “headache.” Other key words included “serum,” “saliva,” “cerebrospinal fluid,” “genes,” “blood,” and “inflammation.” The only restriction was English-language publication. The abstracts of all articles meeting these criteria were reviewed, and full text was retrieved and examined for relevant references. Results Data from human studies have begun to identify genetic mutations/polymorphisms and altered levels of specific proinflammatory and neuromodulatory molecules that strongly correlate with migraine as well as symptom severity. Results from a smaller number of studies have identified parameters, such as the neuropeptide calcitonin gene-related peptide (CGRP), which are significantly associated with response to specific treatments for acute migraine attacks and prophylaxis. Epigenetic mechanisms may also be involved in the development of migraine, and understanding environmentally induced genetic changes associated with this disease may eventually guide the development of therapies capable of reversing these pathophysiological changes in gene function. Conclusions The understanding of the etiology of migraine is incomplete. Although the identification and validation of biomarkers has greatly advanced diagnostic precision and measures of therapeutic efficacy in other diseases, there are no currently accepted biomarkers for chronic or episodic migraine. However, the continued investigation and identification of genetic, epigenetic, and molecular biomarkers is likely to facilitate the goal of individualizing medicine by enabling clinicians to more accurately diagnose and treat migraine and other headache disorders.

Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Double-Blinded, Placebo-Controlled, Comparative Effectiveness Study of Amitriptyline, Topiramate, and Placebo in the Prevention of Childhood and Adolescent Migraine

Abstract: Background Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents. Methods CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28-day baseline and the final 28 days of treatment (weeks 20-24). Conclusions The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes.

Waning of "conditioned pain modulation": a novel expression of subtle pronociception in migraine.

Abstract: Objective To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine. Background One of the most explored mechanisms underlying the pain modulation system is “diffuse noxious inhibitory controls,” which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation. Methods Migraineurs (n = 26) and healthy controls (n = 35), all females, underwent 3 stimulation series, consisting of repeated (1) “test-stimulus” (Ts) alone that was given first followed by (2) parallel CPM application (CPM-parallel), and (3) sequential CPM application (CPM-sequential), in which the Ts is delivered during or following the conditioning-stimulus, respectively. In all series, the Ts repeated 4 times (0-3). In the CPM series, repetition “0” consisted of the Ts-alone that was followed by 3 repetitions of the Ts with a conditioning-stimulus application. Results Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM-parallel efficiency along the series for migraineurs (P = .005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM-sequential series was correlated with less reported extent of pain reduction by episodic medication (r = 0.493, P = .028). Conclusions Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine.

Improvement in headaches with continuous positive airway pressure for obstructive sleep apnea: a retrospective analysis.

Abstract: Objective.— We aimed to identify clinical features in patients with severe headaches that predicted obstructive sleep apnea (OSA) and determine clinical and sleep study characteristics that predicted headache improvement with continuous positive airway pressure (CPAP). Background.— Many patients with headaches complain of sleep symptoms and have OSA. There is often improvement of headaches with CPAP treatment. Methods.— We conducted a retrospective chart review of all patients referred to adult neurology clinic for headaches and sent for polysomnography between January 2008 and December 2009. Follow-up ranged from 18 to 42 months. Results.— Eighty-two headache patients (70 females, 12 males) were studied. Mean age was 45 ± 13 years (females 45 ± 13, males 43 ± 11) and mean body mass index was 32 ± 9. Headache types included 17% chronic migraine without aura, 22% episodic migraine without aura, 32% migraine with aura, 21% tension-type headache, 6% chronic post-traumatic headache, 11% medication overuse headache, and 7% other types. All patients were receiving standard treatment for their headaches by their neurologist. Fifty-two patients (63%) had OSA. Increasing age, female gender, and chronic migraine without aura were predictive of OSA. Of the patients with OSA, 33 (63%) used CPAP and 27 (82%) were adherent to CPAP. Headache improvement was reported by 40 patients (49%) due to either standard medical therapy or CPAP. Patients with OSA who were CPAP adherent (21/27) were more likely to have improvement in headaches than patients intolerant of CPAP (2/6), those that did not try CPAP (8/19), and those who did not have OSA (16/30) (P = .045). Of the 33 patients who used CPAP, 13 reported improvement in headaches specifically due to CPAP therapy and 10 additional patients noted benefit in sleep symptoms. The presence of witnessed apneas (P = .045) and male gender (P = .021) predicted improvement in headaches due to CPAP. Conclusions.— Headache patients should be evaluated for the presence of OSA. Treating OSA improves headaches in some patients.

Frequency and Burden of Headache-Related Nausea: Results From the American Migraine Prevalence and Prevention (AMPP) Study

Abstract: Background While nausea is a defining feature of migraine, the association of nausea with other headache features and its influence on the burden of migraine have not been quantified. Population-based data were used to elucidate the relative frequency and burden of migraine-associated nausea in persons with migraine. Methods Participants with episodic migraine who completed the 2009 American Migraine Prevalence and Prevention survey rated their headache-related nausea as occurring none of the time, rarely,

Comparison of Interictal Vestibular Function in Vestibular Migraine vs Migraine Without Vertigo

Abstract: Background Patients with vestibular migraine (VM) suffer attacks of vertigo that often occur in isolation from headache attacks. We aimed to assess and compare vestibular function interictally in patients with VM and patients with migraine without vertigo (M). Methods Thirty-eight patients diagnosed with definite VM according to the Neuhauser criteria, and 32 patients diagnosed with M according to the International Headache Society criteria were examined between attacks using a broad battery of bedside vestibular tests, a caloric test, and videonystagmography. Results Overall, 70% of the VM patients and 34% of the M patients showed abnormalities on one or more of the 14 performed vestibular tests (P = .006). Abnormal findings were more frequent in VM than in M patients on Romberg's test, test for voluntary fixation suppression of the vestibular ocular reflex and test for static positional nystagmus (P = .03, .01 and .04, respectively). There were no differences in the distribution of central and peripheral vestibular signs between VM and M patients. Conclusions Vestibular abnormalities were present interictally among both VM and M patients, but were found about twice as frequently among VM patients. This may indicate that subclinical vestibular dysfunction is an integral part of migraine pathology in general, and not solely in VM.

Migraine: The Seventh Disabler†

Abstract: On 15 December 2012, a special edition of Lancet published the principal findings of the Global Burden of Disease Survey 2010 (GBD2010). Few reports are likely to have more profound meaning for people with headache, or carry greater promise for a better future, than the seven papers (and one in particular (1)) that were presented. GBD2010 was not the first such survey to be conducted, nor the first to give some recognition to the burden of migraine. The Global Burden of Disease Survey 2000 (GBD2000), conducted 12 years ago by the World Health Organization (WHO), listed migraine as the 19th cause of disability in the world, responsible for 1.4% of all years of life lost to disability (YLDs) (2). This finding has been cited repeatedly ever since; it has fuelled attempts to generate political acceptance of headache as a public-health priority (3), and given credibility to calls for greater investment in headache care and research. It pushed headache into WHO’s field of view, and became an essential part of the platform on which the Global Campaign against Headache has

Structural and functional neuroimaging in migraine: insights from 3 decades of research.

Abstract: Modern imaging methods provide unprecedented insights into brain structure, perfusion, metabolism, and neurochemistry, both during and between migraine attacks. Neuroimaging investigations conducted in recent decades bring us closer to uncovering migraine as a multifaceted, primarily central nervous system disorder. Three main categories of structural and functional brain changes are described in this review, corresponding to the migrainous aura, ictal headache, and interictal states. These changes greatly advance our understanding of multiple pathophysiologic underpinnings of migraine, from central “migraine generating” loci, to cortical spreading depression, intimate mechanisms underlying activation of neuronal pain pathways in vulnerable patients, central sensitization, and chronification. Structural imaging begins to explain the complex connections between migraine and cerebral vascular events, white matter lesions, grey matter density alterations, iron deposition, and microstructural brain damage. Selected structural and functional alterations of brain structures, as identified with imaging methods, may represent the foundation of new diagnostic strategies and serve as markers of therapeutic efficacy.

pH-evoked dural afferent signaling is mediated by ASIC3 and is sensitized by mast cell mediators.

Abstract: Background.—Prior studies have shown that decreased meningeal pH activates dural afferents via opening of acid-sensing ion channels (ASICs), suggesting one pathophysiological mechanism for the generation of headaches. The studies described here further examined the ASIC subtype mediating pH-induced dural-afferent activation and examined whether sensitization influences pH responses. Objective.—Given the potential importance of meningeal mast cells to headache, the goal of this study was to evaluate dural afferent responses to pH following sensitization with mast cell mediators. Methods.—Cutaneous allodynia was measured in rats following stimulation of the dura with decreased pH alone or in combination with mast cell mediators. Trigeminal ganglion neurons retrogradely labeled from the dura were stained with an ASIC3 antibody using immunohistochemistry. Current and action potentials evoked by changes in pH alone or in combination with mast cell mediators were measured in retrogradely labeled dural afferents using patch-clamp electrophysiology. Results.—pH-sensitive dural afferents generated currents in response to the ASIC3 activator 2-guanidine-4methylquinazoline (GMQ), approximately 80% of these neurons express ASIC3 protein, and pH-evoked behavioral responses were inhibited by the ASIC3 blocker APETx2. Following exposure to mast cell mediators, dural afferents exhibited increased pH-evoked excitability, and cutaneous allodynia was observed at higher pH than with pH stimuli alone. Conclusions.—These data indicate that the predominant ASIC subtype responding to decreased meningeal pH is ASIC3. Additionally, they demonstrate that in the presence of inflammation, dural afferents respond to even smaller decreases in pH providing further support for the ability of small pH changes within the meninges to initiate afferent input leading to headache.

Temporarily Withdrawn: Choosing Wisely in Headache Medicine: The American Headache Society's List of Five Things Physicians and Patients Should Question.

Abstract: This paper has been temporarily withdrawn and is currently under embargo. The full text of the paper will be available on Thursday, November 21, 2013, and can be accessed at that time here: http://onlinelibrary.wiley.com/doi/10.1111/head.12233/abstract.

Higher Glutamate to Glutamine Ratios in Occipital Regions in Women With Migraine During the Interictal State

Abstract: Background Glutamate (Glu) and glutamine (Gln) are strongly compartmentalized (in neurons for Glu and in astrocytes for Gln). The visual cortex is the brain region with a higher neuron/astrocyte ratio (the highest neuronal density and the relatively lowest density of astrocytes). Elevations in extracellular Glu or potassium above certain thresholds are likely candidates to be the final common steps in the multiple distinct processes that can lead to cortical spreading depression. Astrocytes play a key role in this phenomenon, by acting as a sink for extracellular Glu and potassium, as well as generally acting as a buffer for the ionic and neurochemical changes that initiate and propagate cortical spreading depression. Objective The purpose of this study was to quantify Glu and Gln to generate Glu/Gln ratios in women with migraine during the interictal state compared with healthy control women. Methods Twenty-seven patients with migraine (8 with aura and 19 without aura) and 19 matched healthy controls were included in the study. We performed proton magnetic resonance spectroscopy in the anterior paracingulate cortex and occipital cortex (OC). Spectral analysis was performed by LCModel, allowing a separation of Glu and Gln using a 3T machine. Results The main result was a significantly higher Glu/Gln ratio in the OC of migraine patients compared with healthy control subjects (4.87 for migraineurs [standard deviation (SD) = 2.74] and 3.42 for controls [SD = 1.52], P = .042). We also observed higher Glu levels (6.98 for migraineurs [SD = 0.85] and 6.22 for controls [SD = 0.97], P = .007) and Glu/creatine + phosphocreatine ratio (1.18 for migraineurs [SD = 0.18] and 1.00 for controls [SD = 0.16], P = .001) in anterior paracingulate cortex in migraine patients but saw no differences in Glu/Gln ratio (2.79 for migraineurs [SD = 1.11] and 2.63 for controls [SD = 1.61], P = .68). Conclusion These findings are consistent with glutamatergic differences in migraine patients during the interictal period compared with healthy controls. We hypothesize that an increased Glu/Gln ratio could arise from neuronal–glial coupling of glutamatergic metabolism differences or an increased neuron/astrocyte ratio in the OC.