Section A: What health care professionals need to know about chronic daily headache in children and adolescents
Introduction
Chronic daily headache (CDH) is a non-specific term that refers to any type of headache that occurs for 15 or more days per month. CDH is not a diagnosis. Although epidemiological studies are scarce, chronic headaches appear to be common in the pediatric age group. United Status population-based data suggest that 3.5% of adolescents experience chronic daily headache (CDH), while data from Taiwan have estimated a prevalence of 1.5%. Data on the incidence of CDH are limited, though one population-based study from Taiwan estimated the incidence at 1.13 per 100 person-years.
There are several primary headaches that can lead to a CDH phenotype. The most common primary headaches causing CDH in the pediatric age group are chronic migraine (CM) and chronic tension-type headache (CTTH) (see Table 1 for International Classification of Headache Disorders 3rd Edition diagnostic criteria and Figs. 1 and 2 for prevalence and incidence). Other primary headaches that can cause CDH in children and adolescents, but that are significantly less common, include: new daily persistent headache, hemicrania continua, chronic cluster headache, chronic paroxysmal hemicrania, chronic short lasting unilateral neuralgiform headaches with cranial autonomic symptoms (SUNA) and chronic short lasting unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT; see the “Other chronic headaches in children and adolescents” section). In this chapter, the main focus will be on describing the epidemiology, risk factors and preventive strategies pertaining to chronic migraine, considering that it is the most common cause of CDH seen in pediatric headache practice.
| Criterion | Chronic migraine | Chronic tension-type headache |
|---|---|---|
| A | Headache (migraine-like or tension-type-like) on ≥ 15 days per month for > 3 months, fulfilling criteria B and C | Headache occurring on ≥ 15 days per month for > 3 months, fulfilling criteria B–D |
| B | Occurring in a patient who has had at least five attacks fulfilling criteria B–D for migraine without aura and/or criteria B and C for migraine without aura | Lasting hours to days or unremitting |
| C | On ≥ 8 days per month for > 3 months, fulfilling any of the following:
| At least two of the following four characteristics:
|
| D | Not better accounted for by another ICHD-3 diagnosis | Both of the following:
|
| E | Not better accounted for by another ICHD-3 diagnosis |
Epidemiology of chronic migraine in children and adolescents
While the epidemiology of chronic migraine (CM) in adults has been well characterized using population-based data and data from cohort studies, comparatively very little has been published on the epidemiology of CM in the pediatric age group. The incidence of CM in adolescents in Taiwan has been estimated at 0.66 per 100 person-years using cohort data from Taitung County, with 2.7% of adolescents with episodic migraine converting to CM within 1–2 years. The prevalence of CM in adolescents in the United States was estimated at 1.75% (95% CI = 0.62–2.89) using data from the Chronic Daily Headache in Adolescents Study (C-dAS). Notably, only 0.79% (95% CI = 0.0–1.7) of these cases had CM without medication overuse, thereby indicating that, at least in the United States, more than half of the pediatric cases of CDH have medication overuse. In a population-based study of children aged 5 to 12 years living in Brazil, 0.6% of the population was diagnosed with CM. Based on available prevalence estimates, CM accounts for between 7% and 21% of the population cases of chronic daily headache (see Fig. 1 ). In the only study that has assessed CM incidence in adolescents, 58.7% of incident CDH cases met diagnostic criteria for CM (see Fig. 2 ). The observed discrepancy between the proportion of prevalent and incident cases of CDH that are accounted for by CM is likely due, in part, to differences in the populations studied and methodological differences in the studies, but may largely reflect the well-described phenomenon of migraine remission over time, either through remission to an episodic phenotype, or through complete remission. In the clinical population, the proportion of CM cases is likely higher than the proportion among population-based cases: in one clinical study, CM accounted for the majority of the cases of CDH seen in a tertiary care pediatric headache clinic. Therefore, CM is likely the most common diagnosis made in pediatric cases of CDH that present to tertiary care settings. It is unknown if this is also true in primary care settings.
According to data from the C-dAS study, in the pediatric age group, CM appears to be more prevalent among females and older adolescents. Aura is not common among adolescents with CM, with only 20% reporting that they experience aura. In addition to the prevalence of CM being higher in females as compared to males, this is also true of the incidence of CM (see Fig. 2 ).
Burden of disease associated with chronic migraine in children and adolescents
Given that migraine is the second most prevalent cause of years lived with disability among all diseases across the lifespan, one would expect that children and adolescents with CM are significantly disabled. Indeed, adolescents with CM on average have a severe level of impact on their lives attributed to migraine, and experience significant migraine-related disability. A majority of adolescents with CDH report that their headaches have a significant impact on their ability to learn in school, and data from a study using objective measures of school performance support the fact that academic performance is inferior in children with CM as compared to their peers. In addition, a small proportion of affected adolescents (though a larger proportion as compared to healthy peers) ultimately drop out of school. In addition to the educational impacts of CM on children and adolescents, these youth also experience significant disability in the home, social and extra-curricular spheres.
It is known that the costs associated with CM are significantly higher than the costs associated with episodic migraine in the adult population. Unfortunately, data on the costs associated with pediatric CM have not been estimated. Surprisingly, given the degree of disability associated with pediatric CM, population-based studies have illustrated that the majority of these children and adolescents had not visited a health care provider in the past year, and this was true both in American and Taiwanese populations. This could be due to a multitude of factors, including stigma, inadequate education in the general population around care and treatment options, or due to the fact that CM is more prevalent among adolescents of lower socioeconomic status who may not have adequate access to care. Alternately, given that it has been shown that patients with CM presenting to a tertiary care pediatric headache clinic have less confidence in their treatment plan as compared to patients with episodic migraine, patient expectations may be a barrier to accessing care for a variety of reasons (e.g., lack of knowledge about the breadth of treatment options or disillusionment due to prior unsuccessful attempts at treatment and contact with the healthcare system). In summary, based on the available data, it appears that there is an unmet treatment need reflected by the fact that the majority of children and adolescents with CM are not receiving care and it is unclear why this gap exists.
Risk factors for migraine chronification in children and adolescents
A variety of clinical parameters have been identified as risk factors for progression to chronic migraine in the adult population. The phenomenon of migraine chronification and risk factors that may contribute to this process have been understudied in children and adolescents. Preliminary evidence suggests that depression, high baseline headache frequency, acute medication overuse, obesity, and low socioeconomic status contribute to disease progression to chronic migraine in children and adolescents (see Fig. 3 ). Of the risk factors studied to date, depression appears to have the most consistent evidence supporting its role in disease progression. It remains unclear if these risk factors will be validated in other pediatric samples, and why they may contribute to disease progression. Some of the identified risk factors, such as high baseline headache frequency and medication overuse, may be linked with migraine chronification through the phenomenon of central sensitization, which can biologically predispose individuals to increasing attack frequencies. Overall, the small number of studies that have examined risk factors for progression to pediatric CM and methodological limitations in the published literature (e.g., in how outcomes and predictors were ascertained and in the external validity of the results) should compel further research into this important area. It is especially critical for the research community to identify modifiable risk factors for migraine progression, considering that early intervention in pediatric migraine may result in disease modification and a more favorable long-term prognosis.
Prevention of migraine chronification in children and adolescents
In some individuals, episodic migraine can worsen in frequency over time until the headaches are occurring 15 days or more per month, often daily or almost daily. This is considered chronification of migraine or transformed migraine (TM). Transformed migraine is considered a complication of migraine and is not a formal diagnosis on its own. By ICHD-3 criteria, this diagnosis is chronic migraine (CM). The incidence of chronic migraine in children has not been well studied. It is not clear if all people with migraine have the ability to progress to chronic migraine or if some individuals are genetically predisposed to this transformation. There are data to suggest a biologic predisposition to chronic migraine in children. In a large study in Brazil, it was found that if a mother had chronic daily headache (CDH), the risk of CDH in the child increased almost 13-fold.
Early intervention prior to migraine chronification is key to preventing migraine-related disability. This is most beneficial while the patient is still in the episodic migraine phase. Unfortunately, studies show that children and adolescents tend to have low healthcare and medication utilization for headaches, similar to findings seen in adults. Early diagnosis and treatment of migraine without aura is important in order to prevent chronic migraine. A study looking at the prognosis of children and adolescents under the care of a healthcare provider showed that the majority of patients who receive care for migraine headache tend to have good outcomes that are likely sustained in the long-term. Preventive treatment can be initiated in patients having frequent attacks or in whom the use of acute medications puts them at risk for medication overuse headache in order to reduce headache frequency and prevent transformation to chronic migraine. This can be in the form of both pharmacologic and non-pharmacologic treatment, such as lifestyle management, depending on the needs of each individual patient.
In patients who have a high frequency of headaches, it is important to avoid medication overuse. Medication overuse headache (MOH) is defined by the ICHD-3 as headache occurring 15 or more days per month in a patient with pre-existing primary headache as a result of regular overuse of acute headache medication. MOH is a common cause of migraine chronification and it is estimated that over half of the adolescents with chronic migraine in the United States also overuse acute medications. Whether this is the cause, or the effect of the chronic headaches is not well understood. Treatment is to avoid or limit use of symptomatic medications, although this does not always lead to improvement in headache frequency. Table 3 , below, lists the various acute pain medications according to their limits of use. Addition of a prophylactic medication can also be beneficial as well as consideration of psychological support for medication overuse.
It is also essential to address potential co-existing disorders that can lead to chronification in children and adolescents with migraine. The most common of these comorbid conditions that are known to be risk factors for migraine chronification in children and adolescents include depression, anxiety, and obesity. Early identification of these risk factors is important in order to determine the appropriate treatment for the patient and intervene before headaches become chronic. Children with migraine should be screened for depression and anxiety. Non-pharmacological treatments such as cognitive behavioral therapy or biofeedback should be initiated once these risk factors are identified. Patients should be referred to a psychiatrist for pharmacologic treatment of depression or anxiety as deemed necessary. A weight management program including diet and exercise may be beneficial for children and adolescents with obesity. Use of certain medications for migraine prophylaxis that address comorbidities can be advantageous for these patients, for instance, using topiramate for obesity with avoidance of medications such as tricyclic antidepressants, cyproheptadine, or divalproex which promote weight gain.
Other chronic headaches in children and adolescents
Chronic tension-type headache
Chronic tension-type headache (CTTH) is the second most common headache leading to CDH in the pediatric population, after chronic migraine. The prevalence of CTTH found in the CDH population for children is highly variable in studies. Results of the C-dAS (Chronic Daily Headache in Adolescents Study) found that CTTH frequency was only 2.8% in adolescents with CDH, compared to CM in 20.9% of adolescents with CDH, and the remainder of the CDHs were unclassified. However, in a study of 115 children and adolescents (age 3 to 15 years) with CDH, the frequency of CTTH was overwhelmingly high, with 81% of patients fulfilling criteria for CTTH. Tension-type headaches were the only headache type seen in 63.5% of the patients, while others had mixed tension-type headaches and migraine. It is important to note that in children with tension-type headaches, features of migraine can often be seen, at times making the diagnosis somewhat unclear. The diagnostic criteria of CTTH can be found in Table 1 , above. CTTH is defined as a mild to moderate headache that occurs 15 or more days per month and may have bilateral location, a pressing or tightening quality, no more than one of photophobia, phonophobia or mild nausea, and is not aggravated by routine physical activity. Children with CTTH often exhibit significant impairment in daily functioning, with high rates of school absence and low school performance. CTTH is likely caused by both internal and external stressors. Chronic diseases and stressful emotional or physical events are known risk factors for the development of CTTH. As with CM, it is important to assess for medication overuse. Treatment is similar to that of CM, with a multimodal and multidisciplinary approach including lifestyle management, psychological (cognitive behavioral therapy, relaxation, biofeedback) interventions, and prophylactic pharmacological treatment.
Chronic cluster headache
Cluster headache (CH) falls under the category of trigeminal autonomic cephalalgias (TACs), which all have similar clinical features of unilateral headache with cranial parasympathetic autonomic symptoms seen ipsilateral to the headache. The various TACs are distinguished by the frequency of attacks and also include paroxysmal hemicrania (PH), short-lasting unilateral neuralgiform headaches (SUNCT/SUNA), and hemicrania continua (HC). These will be discussed below. TACs are considered a diagnosis of exclusion, requiring neuroimaging with magnetic resonance imaging (MRI) of the brain, and with particular attention to the pituitary and cavernous sinus region. CH consists of severe unilateral pain in the orbital, supraorbital, or temporal region, lasting 15–180 min, associated with ipsilateral autonomic symptoms, and occurring at a frequency of between one every other day and 8 per day. The ICHD-3 diagnostic criteria of CH is listed in Table 2 , below. Chronic CH is characterized by cluster headaches occurring without a remission period, or with a remission period of < 3 months, lasting for at least 1 year. CH is rare in the pediatric population. It is estimated that the prevalence of CH in children aged 0–18 years is anywhere from 0.09% to 0.1% and it is estimated that 10% to 20% of these children have chronic CH, similar to the prevalence seen in adults. There are numerous case series reporting CH in children as young as 1 year of age, though in most case reports the onset of CH is in the 2nd decade of life. Unlike in adults, in which there is a male predominance, CH in children seems to have a fairly equal male to female ratio. The diagnosis is difficult to make, especially in children, as the symptoms are often misdiagnosed as other conditions. CH is often misdiagnosed as migraine as migraine is much more common in children, and symptoms of photophobia, phonophobia, and nausea may be present with CH. It may also be that autonomic symptoms are less apparent in children, making the diagnosis even more difficult in this population. Treatment of pediatric CH is based on the available data on treatment in the adult population, as there are no randomized controlled trials on CH treatment in children.
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