Showing papers in "Headache in 2014"

Trigeminal neuralgia--a prospective systematic study of clinical characteristics in 158 patients.

Abstract: Objective To prospectively describe the clinical characteristics of classical trigeminal neuralgia (TN) in a standardized manner. Background TN is a rare disease and most clinicians only see a few patients. There is a lack of prospective systematic studies of the clinical characteristics of TN. We hypothesized that contrary to current thinking, some TN patients suffer from sensory abnormalities at neurological examination. Methods Clinical characteristics such as demographics, pain characteristics, and comorbidities were systematically and prospectively collected from consecutive TN patients in a tertiary referral center in a cross-sectional study. Results A total of 158 patients were included. Average age of onset was 52.9 years. TN was more prevalent in women (95; 60%) than in men (63; 40%), P = .011, and more often located on the right (89; 56%) than on the left side (64; 41%), P = .043. It affected solely the second and/or third trigeminal branch in 109 (69%) while the first branch alone was affected in only 7 (4%). Notably, 78 (49%) had concomitant persistent pain in addition to paroxysmal stabbing pain. Autonomic symptoms were present in 48 (31%). Patients who had not undergone surgery for TN had sensory abnormalities in 35 (29%). Conclusions This, the first study in a series of papers focusing on the clinical, radiological, and etiological aspects of TN, revealed that the symptomatology of TN includes a high percentage of concomitant persistent pain, autonomic symptoms, and sensory abnormalities. These findings offer new insights to the prevailing clinical impression of the clinical characteristics in TN.

The Relation Between Migraine, Typical Migraine Aura and “Visual Snow”

Abstract: Objective To assess the relationship between the phenotype of the “visual snow” syndrome, comorbid migraine, and typical migraine aura on a clinical basis and using functional brain imaging. Background Patients with “visual snow” suffer from continuous TV-static-like tiny flickering dots in the entire visual field. Most patients describe a syndrome with additional visual symptoms of the following categories: palinopsia (“afterimages” and “trailing”), entopic phenomena arising from the optic apparatus itself (floaters, blue field entoptic phenomenon, photopsia, self-light of the eye), photophobia, nyctalopia (impaired night vision), as well as the non-visual symptom tinnitus. The high prevalence of migraine and typical migraine aura in this population has led to the assumption that “visual snow” is caused by persistent migraine aura. Due to the lack of objective measures, alternative diagnoses are malingering or a psychogenic disorder. Methods (1) The prevalence of additional visual symptoms, tinnitus, and comorbid migraine as well as typical migraine aura was assessed in a prospective semi-structured telephone interview of patients with “visual snow.” Correlations were calculated using standard statistics with P < .05 being considered statistically significant. (2) Areas with increased brain metabolism in a group of “visual snow” patients in comparison to healthy controls were identified using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography and statistical parametric mapping (SPM8 with whole brain analysis; statistical significance was defined by P < .001 uncorrected for multiple comparisons). Results (1) Of 120 patients with “visual snow,” 70 patients also had migraine and 37 had typical migraine aura. Having comorbid migraine was associated with an increased likelihood of having palinopsia (odds ratio [OR] 2.8; P = .04 for “afterimages” and OR 2.6; P = .01 for “trailing”), spontaneous photopsia (OR 2.9; P = .004), photophobia (OR 3.2; P = .005), nyctalopia (OR 2.7; P = .01), and tinnitus (OR 2.9; P = .006). Typical migraine aura was associated with an increased likelihood of spontaneous photopsia (OR 2.4; P = .04). (2) After adjusting for typical migraine aura, comparison of 17 “visual snow” patients with 17 age and gender matched controls showed brain hypermetabolism in the right lingual gyrus (Montreal Neurological Institute coordinates 16-78-5; kE = 101; ZE = 3.41; P < .001) and the left cerebellar anterior lobe adjacent to the left lingual gyrus (Montreal Neurological Institute coordinates -12-62-9; kE = 152; ZE = 3.28; P = .001). Conclusions —Comorbid migraine aggravates the clinical phenotype of the “visual snow” syndrome by worsening some of the additional visual symptoms and tinnitus. This might bias studies on “visual snow” by migraineurs offering study participation more likely than non-migraineurs due to a more severe clinical presentation. The independence of entoptic phenomena from comorbid migraine indicates “visual snow” is the main determinant. The hypermetabolic lingual gyrus confirms a brain dysfunction in patients with “visual snow.” The metabolic pattern differs from interictal migraine with some similarities to migrainous photophobia. The findings support the view that “visual snow,” migraine, and typical migraine aura are distinct syndromes with shared pathophysiological mechanisms that need to be addressed in order to develop rational treatment strategies for this disabling condition.

Meditation for Migraines: A Pilot Randomized Controlled Trial

Abstract: Objective.—Our objective was to assess the safety, feasibility, and effects of the standardized 8-week mindfulness-based stress reduction (MBSR) course in adults with migraines. Background.—Stress is a well-known trigger for headaches. Research supports the general benefits of mind/body interventions for migraines, but there are few rigorous studies supporting the use of specific standardized interventions. MBSR is a standardized 8-week mind/body intervention that teaches mindfulness meditation/yoga. Preliminary research has shown MBSR to be effective for chronic pain syndromes, but it has not been evaluated for migraines. Methods.—We conducted a randomized controlled trial with 19 episodic migraineurs randomized to either MBSR (n = 10) or usual care (n = 9). Our primary outcome was change in migraine frequency from baseline to initial follow-up. Secondary outcomes included change in headache severity, duration, self-efficacy, perceived stress, migraine-related disability/impact, anxiety, depression, mindfulness, and quality of life from baseline to initial follow-up. Results.—MBSR was safe (no adverse events), with 0% dropout and excellent adherence (daily meditation average: 34 ± 11 minutes, range 16-50 minutes/day). Median class attendance from 9 classes (including retreat day) was 8 (range [3, 9]); average class attendance was 6.7 ± 2.5. MBSR participants had 1.4 fewer migraines/month (MBSR: 3.5 to 1.0 vs control: 1.2 to 0 migraines/month, 95% confidence interval CI [−4.6, 1.8],P = .38), an effect that did not reach statistical significance in this pilot sample. Headaches were less severe, although not significantly so (−1.3 points/headache on 0-10 scale, [−2.3, 0.09],P = .053) and shorter (−2.9 hours/headache, [−4.6, −0.02], P = .043) vs control. Migraine Disability Assessment and Headache Impact Test-6 dropped in MBSR vs control (−12.6, [−22.0, −1.0], P = .017 and −4.8, [−11.0, −1.0], P = .043, respectively). Self-efficacy and mindfulness improved in MBSR vs control (13.2 [1.0, 30.0], P = .035 and 13.1 [3.0, 26.0], P = .035 respectively). Conclusions.—MBSR is safe and feasible for adults with migraines. Although the small sample size of this pilot trial did not provide power to detect statistically significant changes in migraine frequency or severity, secondary outcomes demonstrated this intervention had a beneficial effect on headache duration, disability, self-efficacy, and mindfulness. Future studies with larger sample sizes are warranted to further evaluate this intervention for adults with migraines. This study was prospectively registered (ClinicalTrials.gov identifier NCT01545466).

CGRP and VIP Levels as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine

Abstract: Background Onabotulinumtoxin type A (onabotA) has shown efficacy in chronic migraine (CM). Its precise mechanism of action, however, is unknown. Objective To analyze a potential relationship between calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) levels and response to onabotA in CM. Methods Adult patients with CM were recruited. Matched healthy subjects with no headache history served as controls. CGRP and VIP levels were determined in samples obtained from the right antecubital vein by ELISA outside of a migraine attack and having taken no symptomatic medication prior to treatment with onabotA. OnabotA was administered according to the PREEMPT protocol every 12 weeks for at least two treatment cycles. A patient was considered as a moderate responder when both: (1) moderate-severe headache episodes were reduced by between 33 and 66%; (2) subjective benefit in a visual scale of 0-100 was recorded by the patient of between 33-66%. Patients were considered as excellent responders when both items improved >66%. Those without improvement of at least one-third in the two items were considered as nonresponders. Results We assessed plasma samples from 81 patients with CM and 33 healthy controls. CGRP and VIP levels were significantly increased in CM population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. For CGRP, a threshold of 72 pg/mL positively correlated with 95% of nonresponders. The probability of being a responder to onabotA was 28 times higher in patients with a CGRP level above the threshold of 72 pg/mL. Even though the sensitivity for the calculated threshold for VIP was poor, the probability that CM patients with low CGRP levels will respond to onabotA was significantly higher in those patients with high VIP levels. Conclusions Interictal CGRP and, to a lesser degree, VIP levels measured in peripheral blood are of great help in predicting response to onabotA.

Trigger factors and premonitory features of migraine attacks: Summary of studies

Abstract: Objective In this second of a 2-part series, we review the available literature on trigger factors and premonitory features in migraine Background In the absence of biological markers of preceding attacks of migraine, trigger factors and premonitory symptoms are valuable though methodologically challenging phenomena to study Design/Methods We focus on selected studies of retrospective surveys, diary studies, and clinical trials We review the heterogeneity of selected studies and their conclusions performed to date and highlight that prospective electronic diary studies provide most reliable information that can be used for future development of preemptive therapy Conclusion We conclude that trigger factors and premonitory symptoms are very common, but that the frequency estimates vary widely based on the study approach and population We recommend that multimodal approaches are necessary for the comprehensive study of predictive biophenotypes as determined by triggers and premonitory symptoms, including retrospective and prospective cohort studies and case-crossover studies

Obesity and headache: part I--a systematic review of the epidemiology of obesity and headache.

Abstract: Individually, both obesity and headache are conditions associated with a substantial personal and societal impact. Recent data support that obesity is comorbid with headache in general and migraine specifically, as well as with certain secondary headache conditions such as idiopathic intracranial hypertension. In the current manuscript, we first briefly review the epidemiology of obesity and common primary and secondary headache disorders individually. This is followed by a systematic review of the general population data evaluating the association between obesity and headache in general, and then obesity and migraine and tension-type headache disorders. Finally, we briefly discuss the data on the association between obesity and a common secondary headache disorder that is associated with obesity, idiopathic intracranial hypertension. Taken together, these data suggest that it is important for clinicians and patients to be aware of the headache/migraine-obesity association, given that it is potentially modifiable. Hypotheses for mechanisms of the obesity-migraine association and treatment considerations for overweight and obese headache sufferers are discussed in the companion manuscript, as part II of this topic.

Pseudotumor cerebri pathophysiology

Abstract: Pseudotumor cerebri syndrome (PTCS) is an uncommon disorder of raised intracranial pressure of unknown etiology. The signs and symptoms have been well described but the pathogenesis remains a mystery. Most of the evidence suggests increased resistance to cerebrospinal fluid outflow as being pivotal to the disorder. Any comprehensive theory on causation will have to explain the preponderance of obese women of childbearing age with primary PTCS and lack of ventriculomegaly in the disorder. It is possible that female sex hormones, along with endocrinologically active adipose tissue, directly result in the syndrome, in those genetically predisposed. Aldosterone has been proposed also as important in the development of PTCS. Vitamin A, in the form of retinoic acid, may also play a pivotal role, and is influenced by both estrogen and adipose tissue. This article reviews proposed mechanisms of PTCS.

Innervation of Rat and Human Dura Mater and Pericranial Tissues in the Parieto‐Temporal Region by Meningeal Afferents

Abstract: Objective To reinvestigate the innervation pattern of the dura mater of rat and human middle cranial fossa, the morpho-functional substrate of headache generation, and adjacent extracranial tissues with neuronal in vitro tracing. Background This study was initiated by recent structural and functional findings of meningeal afferent fibers which innervate the cranial dura mater and may project to extracranial tissues. Methods Anterograde and retrograde neuronal in vitro tracing was made in formaldehyde fixed hemisected rat and human skulls. The fluorescent tracer DiI was applied to proximally cut meningeal nerves in rat and to distal branches of the spinosus nerve in human calvaria lined by dura mater. After several weeks, the dura mater and deep extracranial tissues were examined with fluorescence microscopy. Results In addition to a network of meningeal nerve fibers, several fiber bundles were observed, leaving the skull through emissary canals and fissures to innervate the pericranial temporal, parietal, and occipital periosteum. Traced fibers were seen spreading into deep layers of the temporal and upper neck muscles. Retrograde neuronal tracing revealed labeled cell bodies exclusively in the mandibular and maxillary division of the rat trigeminal ganglion, and centrally projecting fibers were identified in the spinal trigeminal tract. Electron microscopy of the cross-sected spinosus nerve showed myelinated and unmyelinated axons with similar numbers in human and rat. Conclusions We conclude that a proportion of meningeal afferents innervates extracranial tissues like periosteum and pericranial muscles via collaterals projecting through the skull. These afferents may be nociceptive, some may subserve proprioceptive functions. The finding of extracranial projections of meningeal afferents may be important for our understanding of extracranial impacts on headache generation and therapy.

Bullying Victimization at School and Headache: A Meta‐Analysis of Observational Studies

Abstract: BACKGROUND AND OBJECTIVES: Being bullied at school is a risk factor for a variety of negative consequences, including somatic problems. The purpose of this meta-analysis is to determine the association between peer victimization and headache in the school-age population. METHODS: A systematic literature search was conducted in September 2013 to identify observational studies that examined the association between being bullied and headache in children and adolescents. Odds ratios (OR) were pooled by using a random-effects model. Moderator and sensitivity analyses were conducted. RESULTS: Twenty studies, including a total of 173,775 participants, satisfied the pre-stated inclusion criteria. Fourteen studies reported data on the prevalence of headache, which was on average 32.7% (range: 9.1-71.7%) in the bullied group and 19.1% (range: 5.3-46.1%) in the control group. Two separate meta-analyses of the association between being bullied and headache were performed on 3 longitudinal studies (OR = 2.10, 95% confidence interval = 1.19-3.71) and 17 cross-sectional studies (OR = 2.00, 95% confidence interval = 1.70-2.35), respectively. RESULTS showed that bullied children and adolescents have a significantly higher risk for headache compared with non-bullied peers. In the cross-sectional studies, the magnitude of effect size significantly decreased with the increase of the proportion of female participants in the study sample. No further moderators were statistically significant. CONCLUSIONS: The positive association between bullying victimization and headache was confirmed. Further research on the environmental factors that may influence this symptom is needed. Language: en

Neck Pain Disability Is Related to the Frequency of Migraine Attacks: A Cross-Sectional Study

Abstract: Background.—Migraine and neck pain can be critical causes of disability. The contribution of neck pain for the overall disability of individuals with migraine remains unknown. Objective.—To contrast the disability experienced by individuals with episodic and chronic migraine with and without neck pain as captured by the Neck Disability Index. Methods.—Disability due to neck pain was assessed using the Neck Disability Index in individuals with episodic or chronic migraine seen at a university-based headache center. Neck disability was defined as mild (score ranging from 5 to 14 points), moderate (15-24 points), severe (25-34 points) or complete (35 points or higher). To compare differences between groups, a chi-square test was applied. Log-binomial logistic regression was used to estimate disability as a function of headache status after adjustments for age, time since migraine onset, and headache intensity. Results.—Sample consisted of 169 individuals, 104 with episodic migraine and 65 with chronic migraine. Any disability due to neck pain happened in 69% of those with episodic migraine, relative to 92% in chronic migraine (P < .001). Individuals with chronic migraine were at a significantly increased risk to have mild (RR = 2.5; CI 95% 1.1-6.1), moderate (RR = 3.7; CI 95% 1.5-8.8) and severe (RR = 5.1; CI 95%2.1-11.9) cervical disability relative to those with episodic migraine. Relative risks remained significant after adjustments. Time since episodic or chronic migraine onset significantly influenced the model (P = .035), but age and headache intensity did not (P = .27; P = .46). Conclusion.—Neck pain significantly adds to the overall disability of individuals with episodic and chronic migraine.

Concomitant persistent pain in classical trigeminal neuralgia--evidence for different subtypes.

Abstract: Objective To describe the clinical characteristics in classical trigeminal neuralgia (TN) with concomitant persistent pain and to investigate whether TN with concomitant persistent pain represents a distinct phenotype. Background There has been much debate about the possible pathophysiological and clinical importance of concomitant persistent pain in TN. This has led to subgrouping of TN into forms with and without concomitant persistent pain in the recent 3rd International Classification of Headache Disorders beta classification. Methods In this cross-sectional study, data on the clinical characteristics were systematically and prospectively collected from consecutive TN patients. Results A total of 158 consecutive TN patients were included. Concomitant persistent pain was present in 78 patients (49%). The average intensity of concomitant persistent pain was 4.6 (verbal numerical rating scale). The concomitant persistent pain was present at onset or early in the disease course. Patients with concomitant persistent pain were on average 6.2 (P = .008) years younger at onset, but the 2 groups had the same duration of disease (P = .174). There was a preponderance of women in TN with (P < .001) but not in TN without concomitant persistent pain (P = .820). Right-sided pain was more prevalent than left-sided in TN without (P = .007) but not in TN with concomitant persistent pain (P = .907). TN with concomitant persistent pain more frequently had sensory abnormalities (P < .001) and less frequently responded to sodium channel blockers (P = .001). There were no significant differences in other clinical characteristics. Conclusions Concomitant persistent pain is very prevalent in TN and is not a consequence of paroxysmal pain. Findings support that the 3rd International Classification of Headache Disorders beta division of TN with and without concomitant persistent pain is clinically and scientifically important.

Methodological Issues in Studying Trigger Factors and Premonitory Features of Migraine

Abstract: Objective In this review, we focus on migraine as a chronic disorder with episodic attacks (CDEA). We aim to review methodological approaches to studying trigger factors and premonitory features that often precede a migraine attack. Background Migraine attacks are sometimes initiated by trigger factors, exposures which increase the probability of an attack. They are heralded by premonitory features, symptoms which warn of an impending attack. Design/Methods We review candidate predictors of migraine attack and discuss the methodological issues and approaches to studying attack prediction and suggest that electronic diaries may be the method of choice. Conclusion Establishing the relationship between antecedent events and headaches is a formidable challenge. Successfully addressing this challenge should provide insights into disease mechanisms and lead to new strategies for treatment. In the second paper in this series, we review the available literature on trigger factors and premonitory features.

Trigger point injections for headache disorders: expert consensus methodology and narrative review

Abstract: Objective/Background To review the existing literature and describe a standardized methodology by expert consensus for the performance of trigger point injections (TPIs) in the treatment of headache disorders. Despite their widespread use, the efficacy, safety, and methodology of TPIs have not been reviewed specifically for headache disorders by expert consensus. Methods The Peripheral Nerve Blocks and Other Interventional Procedures Special Interest Section of the American Headache Society over a series of meetings reached a consensus for nomenclature, indications, contraindications, precautions, procedural details, outcomes, and adverse effects for the use of TPIs for headache disorders. A subcommittee of the Section also reviewed the literature. Results Indications for TPIs may include many types of episodic and chronic primary and secondary headache disorders, with the presence of active trigger points (TPs) on physical examination. Contraindications may include infection, a local open skull defect, or an anesthetic allergy, and precautions are necessary in the setting of anticoagulant use, pregnancy, and obesity with unclear anatomical landmarks. The most common muscles selected for TPIs include the trapezius, sternocleidomastoid, and temporalis, with bupivacaine and lidocaine the agents used most frequently. Adverse effects are typically mild with careful patient and procedural selection, though pneumothorax and other serious adverse events have been infrequently reported. Conclusions When performed in the appropriate setting and with the proper expertise, TPIs seem to have a role in the adjunctive treatment of the most common headache disorders. We hope our effort to characterize the methodology of TPIs by expert opinion in the context of published data motivates the performance of evidence-based and standardized treatment protocols.

Sleep Disturbance and Affective Comorbidity Among Episodic Migraineurs

Abstract: Background Disturbances in sleep are common among migraineurs, particularly those with frequent (ie, chronic) migraine. Examination of specific types of sleep disturbance and behaviors among episodic migraineurs, however, has not been sufficiently explored. Further, few studies have investigated whether sleep disturbance is attributable to comorbid affective symptomatology. Objectives The present case-control study sought to (1) assess sleep quality, daytime sleepiness, and sleep hygiene among a large sample of episodic migraineurs; (2) quantify relations between sleep disturbance and headache-related variables; and (3) determine if these relations remain after accounting for comorbid depression and anxiety. Methods Two hundred ninety-two undergraduate students (69.9% female, mean age = 19.19, standard deviation [SD] = 3.21 years) completed measures of sleep quality, daytime sleepiness, and sleep hygiene along with well-validated measures of depression and anxiety symptomatology. Those screening positive for migraine were subsequently administered a structured diagnostic interview to verify diagnosis of migraine consistent with the International Classification of Headache Disorders, 2nd edition. Episodic migraineurs and non-migraine controls were compared on the sleep disturbance variables, and among those with migraine, relations with headache frequency, severity, and disability were quantified with linear regression analyses. Results Seventy-eight (26.7%) participants met International Classification of Headache Disorders, 2nd edition criteria for episodic migraine. Compared with participants without migraine, episodic migraineurs reported poorer sleep quality (mean = 8.90 [SD = 3.39] vs 6.63 [SD = 3.02], P < .0001), with 85.9% reporting clinically significant poor sleep quality (vs 62.0% of controls). Poor sleep quality was significantly associated with headache frequency and headache-related disability, accounting for proportions of variance (14.8% in frequency and 18.2% in disability, both P ≤ .001) similar to those attributable to depression and anxiety. These relationships remained significant after controlling for these affective symptoms, in which sleep quality accounted for 5.3% and 5.8% of unique variance in frequency and disability, respectively (P < .05). By comparison, daytime sleepiness and poor sleep hygiene were not consistently associated with migraine or migraine-related variables. Conclusions Consistent with prior studies on chronic migraine, poor sleep quality is uniquely associated with episodic migraine, and this relationship is not solely attributable to comorbid psychiatric symptomatology. Sleep quality should be preferentially assessed (vs sleepiness and sleep hygiene) when subjective self-report measures of insomnia are used in clinical headache settings. Future studies should supplement these findings by evaluating the efficacy of interventions that specifically target sleep quality and insomnia (eg, stimulus control, sleep restriction) among episodic migraineurs.

Association Between Tension-Type Headache and Migraine With Sleep Bruxism: A Systematic Review

Abstract: Aim To evaluate the association between tension-type headache and migraine with sleep bruxism (SB). Background The association between SB and headaches has been discussed in both children and adults. Although several studies suggested a possible association, no systematic analysis of the available published studies exists to evaluate the quantity, quality, and risk of bias among those studies. Methods A systematic review was undertaken, including articles that classified the headaches according to the International Classification of Headache Disorders and SB according to the criteria of the American Association of Sleep Medicine. Only articles in which the objective was to investigate the association between primary headaches (tension-type and migraine) and SB were selected. Detailed individual search strategies for The Cochrane Library, MEDLINE, EMBASE, PubMed, and LILACS were developed. The reference lists from selected articles were also checked. A partial grey literature search was taken by using Google Scholar. The methodology of selected studies was evaluated using the quality in prognosis studies tool. Results Of 449 identified citations, only 2 studies, both studying adults, fulfilled the inclusion criteria. The presence of SB significantly increased the odds (study 1: odds ratio [OR] 3.12 [1.25-7.7] and study 2: OR 3.8; 1.83-7.84) for headaches, although studies reported different headache type. Conclusion There is not enough scientific evidence to either support or refute the association between tension-type headache and migraine with SB in children. Adults with SB appear to be more likely to have headache.

Treatment Adherence in Patients With Headache: A Systematic Review

Abstract: Objective To review and critically evaluate the extant research literature pertaining to adherence in youth and adults with headache and to provide recommendations for future research. Background This article provides the first systematic review of pediatric headache adherence and updates a previous review of treatment adherence in adults with headache. Design Systematic review of empirical literature. Methods A literature search with no date restriction was conducted using PubMed and PsycINFO electronic databases and bibliographies of relevant articles. Results Adherence rates in adults with headache range considerably from 25% to 94% across treatment, assessment method, and definition of adherence utilized. Methods to assess adherence included retrospective prescription claims data, paper or electronic diaries, follow-up appointment attendance, written and verbal self-report of general adherence, verbal self-report of adherence over a specific amount of time via in person interview or telephone, validated adherence measures, adherence questionnaires without validation, and counselor ratings of homework. Each methodology and assessment tool demonstrated strengths and weaknesses. No studies have systematically examined medication adherence in children with headache, and the few available studies examining adherence to behavioral treatment have documented adherence rates ranging from 52% to 86%. Conclusions Adherence research in adults with headache is growing, but studies demonstrate a number of methodological shortcomings. Adherence research in children with headache, and adherence intervention research in both adults and children, is scant. Future research should use objective measures of adherence, consider over-the-counter medications and medication overuse, examine demographic, psychological, and behavioral correlates of adherence, assess adherence to botulinum toxin type A, and examine the efficacy of adherence interventions in individuals with headache.

Obesity and headache: Part II--potential mechanism and treatment considerations.

Abstract: Obesity and headache are both associated with a substantial personal and societal impact, and epidemiologic studies have consistently identified a positive association between obesity and headache in general, as well as obesity and migraine specifically (see part I). In the current manuscript, we will discuss the potential mechanisms for the migraine–obesity association, with a focus on the central and peripheral pathophysiological pathways which overlap between migraine and those modulating the drive to feed. We then discuss surgical, behavioral, and pharmacological treatment considerations for overweight and obese migraineurs as well as for those with idiopathic intracranial hypertension. We close by briefly discussing where future research may be headed in light of this data.

Headaches, quality of life, and academic performance in schoolchildren and adolescents.

Abstract: Background Just a few studies to date have focused on headaches, quality of life, and academic performance in children. Objective Determine the effect of headaches on the life of schoolchildren and the association between headaches and academic performance. Methods We conducted a cross-sectional study. One hundred and ninety-five students from an elementary school were randomly selected out of 355 students aged from 10 to 15 years old. Semi-structured interview, the Pediatric Quality of Life Inventory Version 4.0, the Children's Depression Inventory, and the State-Trait Anxiety Inventory were used. The variables relating to academic performance were obtained by consulting the academic records. Results Prevalence of headaches: headache: 97.3% (179/184); migraine: 51% (94/184); tension-type headache: 33% (61/184); primary stabbing headache: 7.6% (14/184); unclassified headaches: 5.4% (10/184). Migraine (relative risk: 3.11; 95% confidence interval: 1.54-6.30) and more severe headaches (relative risk: 7.93; 95% confidence interval: 2.65-23.7) were associated with lower quality of life (P .05; chi-square test and Fisher's exact test). Conclusion Headaches were found to be associated with lower quality of life and poor academic performance.

Histamine in migraine and brain.

Abstract: Background Histamine has been studied in both health and disease since the initial description a century ago. With its vasodilative effect, it was suggested early on to be involved in the pathophysiology of migraine. Over the past 25 years, much has been learned about histamine as a neurotransmitter in the central nervous system. The role of this neurotransmitter system in migraine has not been previously reviewed. Objective Discuss a potential role of the brain histaminergic system in migraine. Methods Unstructured literature search with a no specific hypothesis-driven approach. Results There is substantial evidence that systemically given histamine may elicit, maintain, and aggravate headache. The mechanisms for this are not known, and histamines do not penetrate the blood–brain barrier (BBB). However, circulating histamine may influence hypothalamic activity via the circumventricular organs that lack BBB. In the rat, prolonged activation of meningeal nociceptors induced by dural mast cell degranulation has been observed. Subcutaneous injections of N-alpha-methyl histamine, a catabolite of histamine with high affinity to the histamine H3 receptor, probably have some migraine preventive effect. A negative feedback on histamine release from mast cells in proximity to C-fiber endings has been a postulated mechanism. Most antihistamines have shown to be ineffective as acute medication for migraine. Two centrally acting potent H1 receptor antagonists (cinnarizine and cyproheptadine) have been reported to be efficacious in preventing migraine. However, the proof for this is limited, and their efficacy has been ascribed other actions than the antihistaminergic. In general, lack of specificity and side effects limit the potential use of centrally acting H1 and H2 antagonists. Brain histamine is synthesized by neurons that are restricted to the posterior basal hypothalamus, more specific to the tuberomamillary nucleus (TMN), and that project practically to the whole central nervous system. The posterior hypothalamus is a suspected locus in quo in several primary headaches. Recently, a positron emission tomography study performed in the prodromal phase of migraine attacks supported the idea of initial involvement of this area. In another recent study, the thalamic nuclei receiving trigeminal output was also shown to have direct connections with the ventral TMN. The central histaminergic system plays an important role in the complex sleep–wake cycle, promoting cortical excitability during wakening and attention, and it consolidates the wake state. The period of the day, in the evenings and during the night, when there is reduced susceptibility for migraine attacks corresponds with less central histaminergic firing. Activation of both the H3 and the H4 receptor promotes inhibitory actions on neurons. The H3 receptor causes autoinhibition of the histaminergic neurons themselves, and centrally acting H3 receptor agonist prodrugs have shown to both inhibit neurogenic inflammation in dura, to induce sleep, and to produce antinociception. There are no registered ongoing studies on H3 and H4 receptor ligands in migraine. Conclusion The role of the central histaminergic system in migraine is largely unexplored, but findings from preclinical research may be linked to several aspects of the disorder. The histaminergic system of the brain may play an important role, especially in the initial phase of an attack, and histamine H3 and H4 receptor ligands may potentially have migraine prophylactic properties. However, the basis for this is still circumstantial, and the evidence is lacking.

Epidemiology of Headache Disorders in the Asia‐Pacific Region

Abstract: Headache disorder is a major public health issue and is a great burden for the person, the health care system, and society. This article reviews epidemiological surveys of primary headache disorders including migraine and tension-type headache (TTH) among adults in the Asia-Pacific region using the International Classification of Headache Disorders (ICHD), first or second edition. Chronic daily headache (CDH), which is not an official diagnosis in the ICHD, was also reviewed. In the Asia-Pacific region, the median (range) 1-year prevalence of primary headache disorders was 9.1% (1.5-22.8%) for migraine, 16.2% (10.8-33.8%) for TTH, and 2.9% (1.0-3.9%) for CDH. The 1-year prevalence of migraine and TTH were rather consistent; however, the extremes in the 1-year prevalence of migraine in earlier studies from Hong Kong (1.5%) and South Korea (22.3%) were not repeated in later surveys (Hong Kong: 12.5%; South Korea: 6%). According to the United Nations, the estimated population of the Asia-Pacific region was 3.85 billion in 2010, equaling to headache suffers of 350 million patients with migraine, 624 million with TTH, and 112 million with CDH; many remain to be treated. The prevalence of headache disorders has remained stable over the last 2 decades in this region, where the diversity of geography, race, and development is wide. Thus, the pursuit of better headache care in this region might be our next challenge.

Pathophysiology of medication overuse headache--an update.

Abstract: The pathogenesis of medication overuse headache is unclear. Clinical and preclinical studies have consistently demonstrated increased excitability of neurons in the cerebral cortex and trigeminal system after medication overuse. Cortical hyperexcitability may facilitate the development of cortical spreading depression, while increased excitability of trigeminal neurons may facilitate the process of peripheral and central sensitization. These changes may be secondary to the derangement of central, probably serotonin (5-HT)-, and perhaps endocannabinoid-dependent or other, modulating systems. Increased expression of excitatory cortical 5-HT2A receptors may increase the susceptibility to developing cortical spreading depression, an analog of migraine aura. A reduction of diffuse noxious inhibitory controls may facilitate the process of central sensitization, activate the nociceptive facilitating system, or promote similar molecular mechanisms to those involved in kindling. Low 5-HT levels also increase the expression and release of calcitonin gene-related peptide from the trigeminal ganglion and sensitize trigeminal nociceptors. Thus, derangement of central modulation of the trigeminal system as a result of chronic medication use may increase sensitivity to pain perception and foster or reinforce medication overuse headache.

Final Results From the 16-Year Sumatriptan, Naratriptan, and Treximet Pregnancy Registry

Abstract: Objectives To monitor for a signal of major teratogenicity by determining the risk of all birth major defects following in utero exposure to sumatriptan, naratriptan, and the sumatriptan/naproxen sodium combination product (tablets marketed in the United States as Treximet [GlaxoSmithKline, Research Triangle Park, NC, USA]), and to monitor for unusual patterns of defects that might suggest teratogenicity. Background The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to anti-migraine drugs in pregnancy is likely. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry captured data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. Methods In this primarily prospective, observational study, health care professionals from anywhere in the world enrolled, on a voluntary basis, women exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen sodium combination product during their pregnancies. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The proportion of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. Results The registry enrolled 680 evaluable exposed pregnant women, which resulted in 689 infants and fetuses (outcomes). Of these outcomes, 626 were exposed to sumatriptan, 57 were exposed to naratriptan (seven were exposed to both sumatriptan and naratriptan), and six were exposed to the sumatriptan/naproxen sodium combination product. Twenty outcomes with major birth defects were reported among 528 outcomes exposed in the first trimester to sumatriptan. The estimated risk of major birth defects following first-trimester sumatriptan exposure is 4.2% (20/478 [95% confidence interval [CI] 2.6%–6.5%]). Among 52 first-trimester exposures to naratriptan, major birth defects were reported in one outcome, an infant with exposure to both sumatriptan and naratriptan [birth defect risk of 2.2% (1/46 [95% CI 0.1%–13.0%]). No major defects were reported among the five outcomes with first-trimester exposure to the sumatriptan/naproxen sodium combination products. Conclusions The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry detected no signal of teratogenicity associated with major birth defects for sumatriptan. This finding is consistent with results from other observational studies using a variety of control groups. Enrollment in the registry was insufficient to permit definitive conclusions of the risks associated with naratriptan or sumatriptan/naproxen sodium tablets, or to assess the risk of individual birth defects in any of the products studied. Low enrollment and high rates of loss to follow up within the registry over an extended period of time led the registry's scientific advisory committee to conclude that continuation of the registry beyond its 16 years would offer little additional power to rule out more moderate increases in the risk of birth defects. Data from the other ongoing surveillance sources constitute an important element of post-marketing surveillance of these medications. The lack of a signal of major teratogenicity with sumatriptan across these several sources of data is encouraging.

Giant Cell Arteritis

Abstract: Giant cell arteritis (GCA) is a medium and large-vessel vasculitis, which is an important cause of secondary headache in older adults. While GCA has a classic presentation occurring after the age of 50, atypical presentations (eg, fever of unknown origin, cough, low or normal erythrocyte sedimentation rate) may lead to a delay in diagnosis. The topography of vascular involvement has implications for disease-related complications, which can result in neurologic disease at multiple levels of the nervous system. The most feared complication, vision loss, fortunately becomes uncommon after initiation of corticosteroids. Corticosteroid treatment should not be withheld while waiting the results of a temporal artery biopsy (TAB), which remains the gold standard for GCA diagnosis. Newer diagnostic modalities, including ultrasound, magnetic resonance imaging, and positron emission tomography can play an important role in directing treatment in cases with negative TAB. After successful control of the disorder, patients should be gradually tapered off corticosteroids, with careful monitoring using both clinical and laboratory parameters to assess for relapse. Corticosteroid-related treatment complications are not uncommon in GCA. There is mixed evidence for use of adjunct corticosteroid-sparing agents (eg, methotrexate), although these should be initiated in the setting of corticosteroid-related morbidity and/or cases with frequent relapse.

Clinical aspects of medication overuse headaches.

Abstract: Medication overuse headache (MOH) is a subset of chronic daily headache, occurring from overuse of 1 or more classes of migraine abortive medication Acetaminophen, combination analgesics (caffeine combinations), opioids, barbiturates (butalbital), non-steroidal anti-inflammatory drugs, and triptans are the main classes of drugs implicated in the genesis of MOH Migraine seems to be the most common diagnosis leading to MOH The development of MOH is associated with both frequency of use of medication and behavioral predispositions MOH is not a unitary concept The distinction between simple (type 1) vs complex (type 2) forms is based on both the class of overused medication and behavioral factors, including psychopathology and psychological drug dependence MOH is a challenging disorder causing decline in the quality of life and causing physical symptoms, such as daily and incapacitating headaches, insomnia, and non-restorative sleep, as well as psychological distress and reduced functioning MOH is associated with biochemical, structural, and functional brain changes Relapse after detoxification is a challenge, but can be addressed if the patient is followed over a prolonged period of time with a combination of prophylactic pharmacotherapy, use of abortive medication with minimal risk of MOH, withholding previously overused medication, and providing psychological (cognitive-behavioral) therapy

One‐Day Behavioral Intervention in Depressed Migraine Patients: Effects on Headache

Abstract: Objective To determine whether a 1-day behavioral intervention, aimed at enhancing psychological flexibility, improves headache outcomes of migraine patients with comorbid depression. Background Migraine is often comorbid with depression, with each disorder increasing the risk for onset and exacerbation of the other. Managing psychological triggers, such as stress and depression, may result in greater success of headache management. Method Sixty patients with comorbid migraine and depression were assigned to a 1-day Acceptance and Commitment Training plus Migraine Education workshop (ACT-ED; N = 38) or to treatment as usual (TAU; N = 22). Patients completed a daily headache diary prior to, and for 3 months following, the intervention. Clinical variables examined included headache frequency/severity, medication use, disability, and visit to a health care professional. Comparisons were made between baseline findings and findings at the 3-month follow up. Results Participants assigned to the ACT-ED condition exhibited significant improvements in headache frequency, headache severity, medication use, and headache-related disability. In contrast, the TAU group did not exhibit improvements. The difference in headache outcomes between ACT-ED and TAU was not statistically significant over time (ie, the treatment by time interaction was nonsignificant). These results complement those of a previous report showing effects of ACT-ED vs TAU on depression and disability. Conclusion A 1-day ACT-ED workshop targeting psychological flexibility may convey benefit for patients with comorbid migraine and depression. These pilot study findings merit further investigation using a more rigorously designed large-scale trial.

Quality of life and health-related disability in children with migraine.

Abstract: Objective To determine whether migraine interferes with health-related quality of life (HRQL) and the degree of disability caused by this condition in the daily life of children of both genders aged 6-12 years. Background Migraine is a chronic disease with recurrent symptoms that lead to a reduction of daily activity during the crises and during the intercritical periods, with an impact on HRQL. Methods The sample consisted of 50 children with migraine without aura being treated at a childhood headache outpatient clinic (study group) and 50 children with no history of headache selected at a pediatric outpatient clinic (control group). The Pediatric Migraine Disability Score questionnaire was applied to the study group in order to determine the disability provoked by headache in daily life, and the Pediatric Quality of Life Inventory4.0 was applied to both groups to determine HRQL. Results Children with migraine were absent from school activities, did not perform household tasks, and did not participate in leisure activities for 23.9 days, on average, during the last 3 months because of migraine. Disability was absent or mild in 38% of the children, whereas 14% showed severe disability. HRQL was similar in both groups regarding self-evaluation, whereas it was perceived as being worse by the parents of children with migraine. Children with migraine had a worse school and emotional quality of life as determined by self-perception. According to the perception of the parents, children with migraine had a worse general, physical, and psychosocial quality of life. Absenteeism from school activities, household tasks, and leisure was not correlated with HRQL. Conclusion Although migraine was a cause of school absenteeism, most of the children with migraine showed little or no disability regarding daily life activities and their quality of life was similar to that of children without headache.

Opioids in Headache

Abstract: Opioid analgesics have long been used to treat head pain of various types. This has been increasing to a significant degree over the past 25 years because of a trend for more liberal use of opioids in non-malignant pain. Opioid treatment for acute headache, as well as prophylactically for refractory chronic headache, is controversial. There are a number of adverse effects associated with acute and chronic opioid treatment. Tolerance, dependence, and addiction are prominent issues. This article attempts to analyze the benefits and disadvantages for opioids in the management of migraine and other headache disorders, relying on known properties of this class of medication as well as clinical data. It will mainly focus on 2 topics: the use of opioid medication for the acute treatment of migraine attacks and continuous prophylactic use for refractory chronic migraine.

Spreading Depolarization May Link Migraine and Stroke

Abstract: Migraine increases the risk of stroke, particularly in young and otherwise healthy adults. Being the most frequent neurological condition, migraine prevalence is on a par with that of other common stroke risk factors, such as diabetes or hypertension. Several patterns of association have emerged: (1) migraine and stroke share a common association (eg, vasculopathies, patent foramen ovale, or pulmonary A-V malformations); (2) injury to the arterial wall such as acute arterial dissections can present as migraine aura attacks or stroke; (3) strokes rarely develop during a migraine attack, as described for "migrainous stroke." Increasing experimental evidence suggests that cerebral hyperexcitability and enhanced susceptibility to spreading depolarization, the electrophysiologic event underlying migraine, may serve as a mechanism underlying the migraine-stroke association. Mice carrying human vascular or neuronal migraine mutations exhibit an enhanced susceptibility to spreading depolarization while being particularly vulnerable to cerebral ischemia. The severe stroke phenotype in migraine mutant mice can be prevented by suppressing spreading depolarization. If confirmed in the clinical setting, inhibiting spreading depolarization might protect migraineurs at stroke risk as well as decrease attacks of migraine.

Response of cervicogenic headaches and occipital neuralgia to radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerve.

Abstract: Objective This article investigates the degree and duration of pain relief from cervicogenic headaches or occipital neuralgia following treatment with radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves. It also addresses the procedure's complication rate and patient's willingness to repeat the procedure if severe symptoms recur. Methods This is a single-center retrospective observational study of 40 patients with refractory cervicogenic headaches and or occipital neuralgia. Patients were all referred by a headache specialty clinic for evaluation for radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves. After treatment, patients were followed for a minimum of 6 months to a year. Patient demographics and the results of radiofrequency ablation were recorded on the same day, after 3-4 days, and at 6 months to 1 year following treatment. Results Thirty-five percent of patients reported 100% pain relief and 70% reported 80% or greater pain relief. The mean duration of improvement is 22.35 weeks. Complication rate was 12-13%. 92.5% of patients reported they would undergo the procedure again if severe symptoms returned. Conclusions Radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerve can provide many months of greater than 50% pain relief in the vast majority of recipients with an expected length of symptom improvement of 5-6 months.

Medication Overuse Headache

Abstract: Background Medication overuse headache (MOH) affects between 1% and 2% of the general population but is present in up to 50% of patients seen in headache centers. There are currently no internationally accepted guidelines for treatment of MOH. Methods A review of the current literature on MOH treatment and pathophysiology. Results We conclude that headache frequency can be reduced to episodic headache in more than 50% of the patients by simple detoxification and information. Approximately half the patients will not have need for prophylactic medication after withdrawal. Pain perception is altered in patients with MOH but can be restored to a baseline pattern, indicating a reversible mechanism in the central sensitization leading to chronic pain. The great comorbidity with depression and anxiety could be a consequence of the altered serotonin metabolism indicating a reversible and potentially treatable condition. Conclusion Increased focus on MOH is extremely important, as MOH both can and should be treated and prevented. MOH is thus a diagnosis that should be considered in all chronic headache patients as the very first step in their management strategy. In the general population, prevention campaigns against MOH are essential to minimize chronic pain disability.