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Purpose of review: Despite the accumulation of a significant amount of data on pediatric headache, few studies have been conducted on its occurrence in children under 7years of age. Within primary headaches in this age, migraine especially, turns out to be a disorder affecting up to 4% of the general population. An underestimate of its true prevalence can be due to lack of specific diagnostic markers, the frequent difficulty of describing pain in childhood, and the necessity of reliable parents’ reports. Thus, migraine in children under 7years of age represents an important challenge for clinicians. The objective of this manuscript is to provide a comprehensive review of epidemiologic, clinic, and therapeutic aspects of migraine in this age. Recent findings: Current literature data show that migraine has some differences, especially in clinical and therapeutic terms, in this age group compared to subsequent ages. Furthermore, some evidences showing that an early onset of migraine may play an unfavorable role in its natural history, suggest an early identification and management of migraine in younger children. Moreover, we highlight the role that factors of prenatal and perinatal development can play in the predisposition and anticipation of migraine onset. Finally, open questions related to the several undefined features of migraine in this age are reported. Summary: Migraine in this pediatric population is absolutely not rare,represents an importan clinical challenge and probably hasa negative predictive role.

To discuss pharmacological interventions in the emergency department (ED) setting for the management of acute primary headache. Acute headache treatment in the ED has seen an expansion in terms of possible pharmacological interventions in recent years. After a thorough evaluation ruling out dangerous causes of headache, providers should take the patient’s history, comorbidities, and prior therapy into consideration. Antidopaminergics have an established role in the management of acute, severe, headache with manageable side-effect profiles. However, recent studies suggest anesthetic and anti-epileptic drugs may play roles in headache treatment in the ED. Current literature also suggest steroids as a promising tool for emergency department clinicians combating the readmission of patients with recurrent headaches. Emergency medicine providers must be cognizant of these traditional and emerging therapies in order to optimize the care of headache patients.

The goal of this review is to outline the prevalence and significance of occipital headaches in children and how they relate to neuroimaging findings. We seek to evaluate the concern that occipital headaches in children are indicative of secondary headache pathology by reviewing the yield of neuroimaging in pediatric patients with occipital headache location. Occipital headaches are a common presentation of primary headache disorders in children, seen in 7–16% of children presenting for evaluation of headache and in up to 20% of children diagnosed with migraine in the emergency department. Review of recent literature confirms that in and of itself, occipital location of headache in a child with recurrent headache and a normal physical examination should not be regarded as worrisome. Headaches with associated signs on neurologic examination should be investigated for a secondary cause, regardless of headache location. Occipital headaches that do not meet criteria for a primary headache disorder should be evaluated for site-specific occipital headache conditions. Neuroimaging for recurrent headache in children who have normal neurological examinations has an overall low yield (0–4.1%) for actionable findings in recent studies. Importantly, an abnormal neurologic examination often predicts the presence of neuroimaging abnormalities. In the absence of an atypical history or abnormalities on clinical examination, occipital headaches in children are no more likely to be associated with intracranial pathology than headaches in other locations. If the child’s headaches are otherwise consistent with migraine or another primary headache disorder, and the neurologic examination is normal, the yield of neuroimaging is low, and imaging can generally be deferred.

In contrast to well-established relationships between headache and affective disorders, the role of alcohol use in primary headache disorders is less clear. This paper provides a narrative overview of research on alcohol use disorders (AUDs) in primary headache and presents a meta-analysis of the role of alcohol as a trigger (precipitant) of headache. The majority of studies on AUDs in headache have failed to find evidence that migraine or tension-type headache (TTH) is associated with increased risk for AUDs or problematic alcohol use. The meta-analysis indicated that 22% (95% CI: 17–29%) of individuals with primary headache endorsed alcohol as a trigger. No differences were found between individuals with migraine (with or without aura) or TTH. Odds of endorsing red wine as a trigger were over 3 times greater than odds of endorsing beer. An absence of increased risk for AUDs among those with primary headache may be attributable to alcohol’s role in precipitating headache attacks for some susceptible individuals. Roughly one fifth of headache sufferers believe alcohol precipitates at least some of their attacks. Considerable study heterogeneity limits fine-grained comparisons across studies and suggests needs for more standardized methods for studying alcohol-headache relationships and rigorous experimental designs.

The purpose of this review is to revise current evidence on trigemino-vascular system (TVS) neuropeptides as potential biomarkers for chronic primary headaches, mainly for chronic migraine (CM).Within sensory neuropeptides, released by an activated trigeminal nerve, calcitonin gene-related peptide (CGRP) levels seem to be a good biomarker of acute migraine and somewhat sensitive and specific for CM. CGRP, however, is not increased in 20-30% of CM patients, which suggests that CGRP is not the only neuropeptide involved in migraine pain generation and maintenance. Data for other sensory neuropeptides are inconsistent (neurokinin, substance P) or absent (amylin and cholecystokinin-8). Among parasympathetic neuropeptides, vasoactive intestinal polypeptide (VIP) is increased interictally in CM, and in at least some migraine cases ictally, pituitary adenylate cyclase-activating peptide (PACAP) has been shown to be increased ictally in jugular blood, but interictal, peripheral data do not indicate such an increase, and there are no data for other parasympathetic peptides. Finally, S100B, as a potential marker of glial TVS activation, has been studied with inconsistent results in migraine patients. Current data on TVS neuropeptides as potential migraine biomarkers must be taken with caution, even for the promising case of CGRP. We do not know with certainty whether increased levels are the reflection of TVS activation, the reliability and homogeneity of the different laboratory tests, or what is the influence on these measurements of the short half-life of many of these peptides or of preventive treatments. One further limitation would be whether the described increases in levels of some neuropeptides such as CGRP are specific for migraine versus other headaches.

Tension-type headache (TTH) is the most prevalent headache worldwide Stovner et al. (Cephalalgia 27:193-210, 2007••); Robbins and Lipton (Semin Neurol 30:107-19, 2010••); Jensen and Stovner (Lancet Neurol 7:354-361, 2008). Despite being the most prevalent primary headache type, there is still a relative lack of epidemiologic data when compared to that for migraine Robbins and Lipton (Semin Neurol 30:107-19, 2010••). Out of the available data, it is apparent that there are wide variations and differences in tension-type headache epidemiology across different cultures Stovner et al. (Cephalalgia 27:193-210, 2007••). This review will focus on reviewing and comparing the epidemiology of episodic and chronic TTH in adult populations across varying continental regions. This will include prevalence, cultural variations and differences in study methodologies, common precipitants and prognosis. Possible explanations for such widely varying prevalence rates among different cultures and regions will also be discussed.

Tension-type headache (TTH) is the most prevalent primary headache disorder. An important factor in the long-term prognosis of TTH is the overuse of acute medications used to treat headache. There are many reasons why patients with TTH overuse acute medications, including biobehavioral influences, dependency, and a lack of patient education. Chronic daily headache occurs in 4.1% of the general population, and chronic tension-type headache and medication overuse headache (MOH) occur in approximately 2.2% and 1.5%, respectively. A proper diagnosis is essential for the treatment of these patients. Treatment should include pathological considerations concerning TTH and MOH, which include peripheral and central mechanisms. Because TTH with MOH carries the worst prognosis, more clinical studies focusing on the complex interaction and treatments of TTH and MOH are needed.

Among the established and potential comorbidities of migraine, the temporomandibular disorders (TMD) are rarely discussed, although they are of importance for several reasons. TMD may cause headaches per se, worsen existent primary headaches, and add to the burden of headache disorders. This article explores the potential comorbidity between migraine and TMD and the role of TMD as a potential factor to induce chronic migraine. We discuss the similarities between both conditions, review evidence to support the idea that both disorders are comorbid, and highlight the limited evidence suggesting that TMD influence migraine progression. Finally, we discuss the importance of cutaneous allodynia mediating the TMD/frequent headache relationship.

A history of headaches in a family is very frequently noted when evaluating a child for recurrent, episodic headaches. Oftentimes, these headaches have migraine features, although the family may deny a history of migraine. This positive family history implies an inherited or genetic basis as a component to the underlying pathophysiology of primary headaches. A variety of methodology has begun to elucidate this contribution, including historical observation, population-based studies of families and twins, gene polymorphism association studies, and specific gene identification for isolated migraine subtypes. This line of investigation should progress in the future to a better understanding of migraine and clarification of the diagnostic subtypes for a genotype-phenotype association.

Migraine and tension-type headache (TTH) are highly prevalent primary headaches that remain underdiagnosed and undertreated in clinical practice. The similarities and differences between migraine and TTH may impose diagnostic challenges as well as management difficulties. In addition, the possibility of migraine chronification or transformation in daily or near-daily headache raises the potential level of interaction between pathophysiologic mechanisms of TTH and migraine. The continuum concept is a possible key to the understanding of this association. Future studies are necessary to clarify epidemiology, pathophysiology, and management of these two most prevalent headaches.

Neuroimaging techniques can be used to investigate both functional and structural features of the brain in patients who have primary headache disorders such as migraine or cluster headache. Improved treatments are needed for both, and this goal will likely be facilitated by a better understanding of the underlying biology. Functional imaging studies have identified regions active during attacks, as well as abnormalities that are present during the interictal period. Volumetric, surface-based morphometric, and tractography studies have revealed structural changes, although whether these represent a cause or effect of the condition remains to be determined. The development of new techniques and modalities promises to yield additional insights in the future. This article aims to review the major findings and most recent advances in neuroimaging of migraine and cluster headache.

Headaches from vascular causes need to be differentiated from primary headaches because a misdiagnosis may lead to dire consequences for the patient. Neuroimaging is critical in identifying patients with vascular headaches and identifying the nature of the pathologic disorder causing these headaches. In addition, the imaging findings guide the physician regarding the optimal treatment modality for these lesions. This review summarizes the nuances of differentiating patients with secondary headaches related to vascular disease and discusses pertinent neuroimaging studies.

Tension-type headache is the most common primary headache disorder seen in adults. Although the prevalence peaks in the fourth and fifth decades of life, significant fractions of the elderly continue to experience either episodic or chronic tension-type headaches. Many secondary headache disorders may present with headaches symptomatically compatible with the diagnosis of tension-type headache. Because numerous secondary headache disorders are more likely to be seen in older adults, the diagnosis of tension-type headache requires vigilance for and exclusion of organic disease. Once the diagnosis of tension-type headache is made, numerous nonpharmacologic and pharmacologic management options are available to reduce the frequency and severity of episodes. Special dosing considerations must be considered in the elderly. Advancing age is a positive prognostic factor in the remission of episodic and chronic tension-type headaches.

The typical aura associated with migraine is characterized by visual or sensory and speech symptoms, with a mix of positive and negative features and complete reversibility within 1 hour. However, auras are not an exclusive migraine-dependent phenomenon. There have been descriptions of aura occurring in association with cluster headache, hemicrania continua, and even with chronic paroxysmal hemicrania. In addition, the occurrence of aura without headache or followed by a headache resembling the criteria of tension-type headache is encountered in clinical practice. This paper reviews the literature about auras in non-migraine headaches and the features involving this uncommon presentation. The possibility of a specific genetic origin for the auras, not related to the primary headache type, also is raised.

Cluster headache is a primary headache syndrome that is under-diagnosed and in many instances under-treated. The pain produced during a cluster headache is more severe than that generated by any other primary headache. Cluster headache is very stereotyped in its presentation and fairly easy to diagnose with an in-depth headache history. Cluster headache is easy to treat in most individuals if the correct medications are used and the correct dosages are given. The following manuscript presents information on the clinical presentation of cluster headache and both medicinal and surgical interventions.

This article reviews new advances in neuroimaging of primary headaches. Imaging of the brain is reaching a new stage of maturity as the basic neural systems that participate in the pathogenesis of headaches are identified. Given the rapid advances in functional neuroimaging, it is no surprise that recent studies have supported the neurovascular theory of migraine and cluster headache. It is clear that functional neuroimaging will continue to be of paramount importance and ultimately may serve as the bridge between molecular and clinical domains in the field of headache research.

A number of primary headache syndromes are marked by their short duration of pain. Many of these syndromes have their own unique treatment, so they must be recognized by practicing physicians. In this article, a number of the short-lasting headache disorders are reviewed, including chronic paroxysmal hemicrania, SUNCT syndrome, hypnic headache, exploding head syndrome, primary stabbing headache, and cough headache.

Although tension-type headache is the most frequent primary headache, little is known about its pathophysiology. It is a matter of debate if the pain in tension-type headache originates from myofascial tissues or from central mechanisms in the brain. This article presents a summary of available data on the pathophysiology of tension-type headache and proposes a pathogenic model. From experimental research and clinical studies, it appears that myofascial nociception is important in episodic tension-type headache; however, central mechanisms (ie, central sensitization) are preponderant in the pathophysiology of the chronic form. Understanding the mechanisms of this central sensitization could allow for more efficient prophylactic treatments to emerge.

Butalbital compounds are of proven efficacy in the treatment of tension headache. Decades of experience have established their value in the treatment of other mild-to-moderate headaches. Untold numbers of people rely on these medications as their drug of choice or use them when vasoconstrictors, opioids, or nonsteroidal anti-inflammatory agents are contraindicated. The medications are cost-effective with only occasional and minor immediate adverse effects. Their overuse may cause the evolution of episodic primary headaches to chronic daily headaches; however, removal of these agents from the market would reduce the chronic daily headache in the general population by a small fraction of 1%.

Tension-type headache (TTH) is the most common type of primary headaches, and its chronic form, chronic tension-type headache (CTTH), is affecting 0.5 to 4.8 % of the worldwide population. Although the mechanism underlying CTTH remains unclear, the role of central versus peripheral mechanisms has always been discussed while explaining the pathogenesis of CTTH. There is always a debate on differential diagnosis between CTTH and chronic migraine without aura which are regarded as different aspects of chronic daily headache spectrum because of many similarities and fuzzy boundaries. Compared with pharmacological treatments, non-pharmacological treatments have been popular as alternative interventions for CTTH in recent years. This review summaries the update knowledge on CTTH and discusses the most interested questions regarding pathogenesis and therapeutic strategies of CTTH.

Primary stabbing headache (PSH) is an under-recognized primary headache disorder, which often goes undiagnosed. It is mainly characterized by its ultrashort stabbing quality and can be easily overlooked both by patients and providers as it is often not severe enough to interfere significantly with daily life. However, PSH may be severe and require therapy, and it is important for providers to recognize this headache type, both in adult and pediatric populations, as well as to be able to distinguish it from secondary headache disorders. PSH also may be more common than previously thought.

New daily persistent headache is a primary headache disorder marked by a unique temporal profile which is daily from onset. For many sufferers this is their first ever headache. Very little is known about the pathogenesis of this condition. It might be a disorder of abnormal glial activation with persistent central nervous system inflammation and it may be a syndrome that occurs in individuals who have a history of cervical hypermobility. At present there is no known specific treatment and many patients go for years to decades without any improvement in their condition despite aggressive therapy. This article will present an up-to-date overview of new daily persistent headache on the topics of clinical presentation, treatment, diagnostic criteria, and presumed pathogenesis. It will also provide some of the authors own treatment suggestions based on recognized triggering events and some suggestions for future clinical trials.

Daily or near-daily headache is a widespread problem in clinical practice. The general term of chronic daily headache (CDH) encompasses those primary headaches presenting more than 15 days per month and lasting more than 4 hours per day. CDH includes transformed migraine (TM), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). Around 40% of patients attending a specialized headache clinic meet CDH diagnostic criteria, of which 80% are women. In these clinics about 60% of patients suffer from TM, 20% from CTTH, and 20% meet NDPH criteria. Most, some 80%, overuse symptomatic medications. One should be very cautious on extrapolating these numbers to the general population. CDH prevalence in the general population seems to be around 4% to 5% (up to 8% to 9% for women). Regarding the prevalence of CDH subtypes, NDPH is rare (0.1%), whereas the prevalence of TM (1.5% to 2%) and CTTH (2.5% to 3%) is clearly higher. In contrast to data from specialized clinics, only around a quarter of CDH subjects in the general population overuse analgesics; the prevalence of CDH subjects with analgesic overuse being 1.1% to 1.9% of the general population. Most of these patients with analgesic overuse are TM patients.

Recurrent headache is increasingly recognised in young children. Migraine and tension-type headache feature commonly amongst the primary headache disorders seen at this age. Headaches at this age are more likely than in older patients to be ‘unclassifiable’, possibly a reflection of the difficulties in obtaining a detailed headache history from a young child. Together with recent epidemiological data this review highlights the more prevalent primary headache types with advice on making a focussed headache assessment and guidance on management in this age group.

Sinus headache is not a diagnostic term supported by the academia, yet it appears to be understood by the general public and larger medical community. It can be considered both a primary and secondary headache disorder. As a primary headache disorder, most of the patients considered to have sinus headache indeed have migraine (migraine with sinus symptoms). Yet it is also possible that some attacks of sinus headache may represent a unique clinical phenotype of migraine or be a unique clinical entity. Potentially, primary sinus headache can chronify and be refractory through immune-mediated mechanisms or as a catalyst for migraine chronification through ineffective treatment or medication overuse and misuse. As a secondary headache disorder, sinus headache can be associated with a wide range of underlying etiologies such as infection, anatomical abnormalities, trauma, and immunological disease or sleep disorders. It is possible that these underlying pathophysiological processes generate long-standing activation of nociceptive mechanisms involved in headache and can lead to chronification and refractoriness of the headache symptomatology. This article explores some of the potential mechanisms and the available scientific studies that may explain how sinus headache can become chronic and present to the clinician as a refractory headache disorder.

Cluster headache (CH) is a highly disabling condition resulting in severe, recurrent unilateral bouts of pain and accompanying autonomic symptoms. This review describes some current views regarding the underlying pathophysiology covering the pain and cranial autonomic (parasympathetic) activation, and highlights the potential importance of the hypothalamus in CH. The hypothalamus is known to modulate many functions and has been shown to be involved in the pathophysiology of a variety of primary headaches, including CH. Hypothalamic structures are likely to underlie the circadian and circannual periodicity of attacks and contribute to the pain and autonomic disturbances. We discuss the hypothalamic involvement in CH and modulation of trigeminovascular processing and examine the emerging involvement of the hypothalamic orexinergic system as a possible key pathway in CH pathophysiology.

Cluster headache (CH) is a primary headache syndrome that is classified with the trigeminal autonomic cephalalgias. CH treatment involves three steps: acute attack management, transitional therapy, and preventive therapy. Greater occipital nerve block has been shown to be an effective alternative bridge therapy to oral steroids in CH. Botulinum toxin type A has recently been studied as a new preventive treatment for patients with chronic CH, with limited success.

Cluster headaches have always been among the most intriguing of the commonly recognized primary headache syndromes. This clinical interest is related to a number of factors, including the intense but short-lived nature of the pain, its sexual predilection, associated trigeminal autonomic dysfunction, and the remarkable circadian and circannual periodicity of cluster periods. Recent advances in neuroimaging and neuroendocrinology have shed light on the pivotal role of the hypothalamus in the biology of cluster headache. We discuss these revelations, along with current clinical observations in headache and sleep medicine.

We describe the various side effects occurring in dialysis sessions and indicate measures for their prevention and/or treatment. Next, we analyze dialysis headache in terms of incidence, prevalence, criteria for its inclusion in the classification of the International Headache Society, and factors related to its triggering, ie, bradykinin and nitric oxide (NO), which have increased plasma levels during dialysis. This permits a critical analysis in comparison with NO donor headache in terms of the pathophysiologic mechanisms that mediate the triggering of both conditions. A similarity is particularly detected in terms of the role of NO as the last link in the chain of events that precedes the onset of headache, which is preceded by a latency period of 3 to 4 hours, much longer than the few seconds needed to inactivate NO. A hypothesis is raised to explain this phenomenon, opening new perspectives for the study of the pathophysiology of headaches, including primary headaches.

Tension-type headache is the most prevalent type of primary headache but is frequently forgotten by the patient and doctor. This article summarizes the present knowledge about tension-type headache and discusses some of the problematic aspects. Most patients in specialized headache clinics suffer from several different primary and secondary headaches at the same time and deserve a careful characterization before a rational therapy can be initiated. In particular, it is of utmost importance to increase focus on clinical and basic research in order to develop effective treatment strategies for the most neglected and most costly type of headache.

Chronic daily headache (CDH) is an overarching term that includes multiple types of frequent primary headaches that are not trigeminal-autonomic cephalgias. The components of typical CDH can be divided into a more severe or "big" headache and a less severe or "little" headache. The big headaches tend to have features of migraine while the little headaches have features of tension-type headache (TTH). Whether this represents a spectrum or continuum or whether it is the superimposition of two unique headache entities is open to debate. For subjects with big and little headache, the concept that the TTH component is part of a spectrum seems likely. Subjects with only TTH and no migrainous component seem to represent a different entity, pure chronic TTH. These patients have a daily moderate headache that is poorly responsive to current therapies and appears to be a different TTH than the migraine tension type of CDH. The TTH component of CDH may represent multiple subdivisions of TTH.

Indomethacin-responsive headache syndromes represent a unique group of primary headache disorders characterized by a prompt and often complete response to indomethacin to the exclusion of other nonsteroidal anti-inflammatory drugs and medications usually effective in treating other primary headache disorders. Because these headache disorders can easily be overlooked in clinical practice, they likely are more common than previously recognized. Indomethacin-responsive headache syndromes can be divided into several distinct categories: a select group of trigeminal-autonomic cephalgias, valsalva-induced headaches, and primary stabbing headache (ice-pick headache or jabs and jolts syndrome). Each category can be differentiated clinically and by the extent to which the individual headache disorders respond to indomethacin. The paroxysmal and continuous hemicranias invariably respond in an absolute manner to indomethacin, whereas valsalva-induced and ice-pick headaches may respond in an equally dramatic, but somewhat less consistent fashion. Hypnic headache recently has been described as another primary headache disorder that may respond to indomethacin.

Tension-type headache is a common primary headache with tremendous socioeconomic impact. Establishment of an accurate diagnosis is important before initiation of any pharmacologic therapy. Simple analgesics and nonsteroidal anti-inflammatory drugs are the mainstays of treatment of episodic tension-type headache. The tricyclic antidepressant amitriptyline is the drug of choice in the preventive treatment of chronic tension-type headache. Progress in basic neuroscience has emphasized the importance of nitric oxide inhibition and N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid receptor antagonism in the treatment of chronic pain. It has been demonstrated that inhibition of nitric oxide is effective in chronic tension-type headache. These interesting data indicate that more specific and effective treatment possibilities will emerge in the future.

The overuse of acute medications in patients who are headache-prone poses a great challenge to headache management. Medication overuse-induced headache represents one of the most common iatrogenic disorders. It is the reason that most patients visit headache subspecialty clinics worldwide and often is the cause of an intractable or worsening headache in primary headache sufferers. The recent development of acute headache medications, especially the triptans, has provided increased migraine relief; however, the incidence of triptan-overuse headache has also increased. Awareness of medication overuse-induced headache and familiarity with the diagnosis and the treatment of this disorder are important to physicians who treat patients with headache.