Introduction

Headache is a universal affliction of humans from which children are not spared. Headache is the most common reason that children are referred to child neurology practices. It is therefore essential for clinicians to have a thorough, systematic approach to the evaluation and management of the child or adolescent with the complaint of headache.

Headache may be due to primary entities, such as migraine or tension-type, or the pain may result from secondary causes such as brain tumors, increased intracranial pressure, drug intoxications, paranasal sinus disease, or acute febrile illnesses such as influenza. The evaluation of a child presenting with headache follows the traditional medical model, with extraction of the necessary history and performance of a thorough physical and neurologic examination. In most instances, this initial process will yield a diagnosis or determine the need for further ancillary testing. Once the diagnosis is established, a comprehensive treatment program can be put into place, blending pharmacologic and biobehavioral measures, and keeping both physical and emotional factors in mind.

The purpose of this chapter is to explore the symptom of headache, reviewing the epidemiology, current classification system, appropriate evaluation, and differential diagnosis.

Epidemiology

Headaches are common during childhood and become increasing more frequent during adolescence. The prevalence of headache ranges from 37 to 51 percent in 7-year-olds, gradually rising to 57–82 percent by age 15. Recurring or frequent headaches occurred in 2.5 percent of 7-year-olds and 15 percent of 15-year-olds [Bille, 1962]. Before puberty, boys are affected more frequently than girls, but after puberty, headaches occur more frequently in girls [Deubner, 1977; Sillanpaa, 1983; Dalsgaard-Nielsen, 1970; Laurell et al., 2004].

The prevalence of migraine headache steadily increases through childhood and the male:female ratio shifts during adolescence. The prevalence rises from 3 percent at age 3–7 years to 4–11 percent by age 7–11, and up to 8–23 percent during adolescence (Table 63-1). The mean age of onset of migraine is 7.2 years for boys and 10.9 years for girls [Dalsgaard-Nielsen, 1970; Lipton et al., 1994; Mortimer et al., 1992; Valquist, 1955; Small and Waters, 1974; Sillanpaa, 1976; Stewart et al., 1991; Stewart et al., 1992].

Table 63-1 Prevalence of Migraine Headache through Childhood

Data regarding tension-type headache is limited. Two studies including school-aged children of 7–19 years, and using the International Classification of Headache Disorders (ICHD-2) criteria, found the 1-year prevalence of tension-type headache to be 10–23 percent. The prevalence of tension-type headache increased with age in both boys and girls, up to age 11 years, and thereafter only increased in girls [Laurell et al., 2004; Zwart et al., 2004].

Chronic daily headache, defined as more than 15 headache days/month for more than 4 months, occurs in 1–2 percent of adolescents [Wang et al., 2006, 2009].

Classification

The International Headache Society’s comprehensive classification system for the spectrum of primary and secondary headache disorders is available on their website (http://ihs-classification.org/en) (Box 63-1). There are three major categories: the primary headaches, the secondary headaches, and the cranial neuralgias. Each headache category is carefully defined, subclassified, and annotated.

Box 63-1 International Classification of Headache Disorders (ICHD-2)

Primary Headache Disorders

1. Migraine

2. Tension-type

3. Cluster headache

4. Other primary headache disorders

Cranial Neuralgias, Central and Primary Facial Pain

13. Cranial neuralgia and central causes of facial pain

14. Other headache, cranial neuralgia, central or primary facial pain

For example, the classification for the primary headache disorder, migraine, is subclassified into migraine without aura, migraine with aura, and the childhood periodic syndromes that are commonly precursors of migraine. Migraine with aura is further divided into subgroups based upon current views of the pathophysiology of migraine. The visual, sensory, motor, or psychic phenomena that herald the onset of a migraine attack are all included under migraine with aura (Box 63-2). A migraine attack accompanied by hemiparesis (e.g., familial hemiplegic migraine [FHM]) falls in the category of migraine with aura, although alternative explanations for hemiparesis with headache must be carefully sought before the diagnosis of FHM can be accepted.

There are several “orphan” pediatric headache disorders, traditionally included within the migraine spectrum, that are omitted from ICHD-2. Alice in Wonderland syndrome is characterized by bizarre visual (e.g., macropsia or micropsia) or perceptual (e.g., prosopagnosia) experiences before the onset of a typical migraine headache. This entity is now viewed as a form of migraine with aura, in which the aura occurs in the parietal or posterior temporal cortical regions, yielding the unusual visuoperceptual phenomena.

Alternating hemiparesis of childhood (AHC) is a rare and bizarre entity, once thought to be a migrainous phenomenon. AHC is now viewed as a metabolic disorder, probably due to a mitochondrial disorder or a channelopathy. Recently, however, a novel ATP1A2 mutation within one kindred, with features that bridged the phenotypic spectrum between AHC and FHM, has been reported and may draw AHC back into the migraine spectrum [Swoboda et al., 2004; Bassi et al., 2004].

Ophthalmoplegic migraine no longer falls in the migraine category, but in the group of cranial neuralgias. While paradoxically still labeled as “migraine,” this clinical entity is characterized by transient disturbances of cranial nerves III, IV, or VI, coupled with intense peri- or retro-orbital pain, and is viewed as a transient demyelinative process.

Clinical Classification

A useful clinical classification system was proposed by Rothner; it divides headache into five temporal patterns (Figure 63-1): acute, acute recurrent, chronic progressive, chronic nonprogressive, and mixed. Each of these temporal patterns suggests differing pathophysiologic processes and has distinctive differential diagnoses (Box 63-3).

Fig. 63-1 Five temporal patterns of pediatric headache.

Box 63-3 Differential Diagnosis of the Five Temporal Patterns

Acute-Recurrent

Paroxysmal hemicrania

After seizure

Tic douleureux

Exertional

Chronic Progressive

Brain Tumor

Idiopathic intracranial hypertension

^* with superimposed migraine.

Diagnostic Criteria

The ICHD-2 established the diagnostic criteria for the primary headache disorders, incorporating many developmentally sensitive changes compared to previous criteria, and thus improving applicability to children and adolescents while maintaining specificity and improving sensitivity (Box 63-4) [Oleson, 2004]. For example, the criteria accept that pediatric migraine may be brief (approximately 1 hour), as opposed to a 4-hour duration for adults; may be bifrontal in location (under age 15 years); and may have associated symptoms of photophobia and phonophobia, which may be inferred by the child’s behavior, such as withdrawing to a dark, quiet room to rest during the headache attack.

Box 63-4 ICHD-2 Diagnostic Criteria for the Primary Headache Disorders: Migraine and Tension-Type

ICHD-2 also includes criteria for cyclical vomiting and abdominal migraine (Box 63-5 and Box 63-6).

Box 63-6 ICHD-2 Criteria for Abdominal Migraine

Description

An idiopathic recurrent disorder seen mainly in children and characterized by episodic midline abdominal pain manifesting in attacks lasting 1–72 hours with normality between episodes

The pain is of moderate to severe intensity and associated with vasomotor symptoms, nausea and vomiting

Evaluation of the Child with Headache

The evaluation of a child with headaches follows the traditional medical model and begins with a thorough medical history and complete physical and neurologic examination. The brief series of questions shown in Figure 63-2 provides a logical framework for evaluating headaches and generally yields sufficient information to diagnose most primary headaches and reveal clues to presence of secondary headache disorders.

Fig. 63-2 Key questions to ask in the evaluation of children with headaches.

(Adapted from Rothner AD. The evaluation of headaches in children and adolescents. Seminars in Pediatric Neurology 1995; 2:109–118.) [Rothner, 1995]

The role of ancillary diagnostic studies, such as laboratory testing, electroencephalography (EEG), and neuroimaging, has been extensively reviewed [Lewis et al., 2002]. This American Academy of Neurology (AAN) Practice Parameter determined that there is inadequate documentation in the literature to support any recommendation as to the appropriateness of routine laboratory studies (e.g., hematology or chemistry panels) or performance of lumbar puncture. Routine EEG is not recommended as part of the headache evaluation. Data compiled from eight studies showed that the EEG was not necessary for differentiation of primary headache disorders (e.g., migraine, tension-type) from secondary headache due to structural disease involving the head and neck, or from headaches due to a psychogenic etiology. In addition, EEG is unlikely to define or determine an etiology of the headache or to distinguish migraine from other types of headaches. Furthermore, in those children undergoing evaluation for recurrent headache who were found to have paroxysmal EEGs, the risk of future seizures is negligible.

The role of neuroimaging is better defined. Data compiled from six pediatric studies permitted the following recommendations:

1. Obtaining a neuroimaging study on a routine basis is not indicated in children with recurrent headaches and a normal neurologic examination.

2. Neuroimaging should be considered in children in whom there are historic features to suggest:

a. recent onset of severe headache

b. change in the type of headache

c. neurologic dysfunction.

3. Neuroimaging should be considered in children with an abnormal neurologic examination (e.g., focal findings, signs of increased intracranial pressure, significant alteration of consciousness), and/or the coexistence of seizures.

Care must be taken not to over- or under-interpret these recommendations. Neuroimaging may be considered in children with recurrent headache based upon clues extracted from the medical history or based upon the findings on neurologic examination. The “managed care industry” has focused only upon recommendation number 1 and failed to recognize recommendations 2 and 3, which clearly place the responsibility in the hands of the clinician to make decisions regarding ancillary testing, including neuroimaging, based upon good clinical judgment. The findings of the AAN Practice Parameter support the medical decision to perform scans, or to withhold scans, based upon clinical determinants for the individual patient.

Primary Headache Syndromes

Migraine

Migraine is the most common acute recurrent headache syndrome. The classification of migraine is shown in Box 63-2 and the cardinal diagnostic features are shown in Box 63-4.

Pathophysiology

Incompletely understood, migraine is thought to be a complex, primary, neuroglial process (Figure 63-3) [Pietrobon and Striessnig, 2003; Silberstein, 2004; Goadsby et al., 2009]. The principal underlying phenomenon of migraine is hyperexcitable neurons. Polygenic influences produce disturbances of neuronal ion channels (e.g., sodium, calcium), leading to episodes of cortical spreading depression (CSD) and activation of the “trigeminovascular system.”

Fig. 63-3 Migraine pathophysiology.

(Adapted from Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev 2003;4:386.)

CSD represents a slowly propagating wave (approximately 2–6 mm/min) of neuronal excitation, followed by depolarization, and is now viewed as cause of the migraine aura. Clinically, migraine aura represents transient, focal, somatosensory phenomena, such as visual scotomata or distortions, dysesthesias, hemiparesis, or aphasia, and is caused by regional neuronal depolarization, possibly accompanied by some degree of regional oligemia.

While CSD nicely explains the somatosensory aura, only about 30 percent of children and adolescents experience aura, so explanation of the pain requires involvement of other cerebral circuits. Clearly, the processes leading to migraine pain must occur in the absence of a perceived aura. Two mechanisms are thought to be responsible for the generation of the pain of migraine:

1. neurogenic inflammation of the meningeal vessels

2. “sensitization” of peripheral and central trigeminal afferents.

Activation of the “trigeminovascular” system by descending cortical, thalamic, hypothalamic, and brainstem nuclei, and, possibly, by ascending cervical neurons, initiates vascular dilatation with extravasation of plasma proteins from dural vessels; this, in turn, activates trigeminal meningeal afferents. These processes set the stage for “neurogenic” inflammation of the dural and pial vessels, mediated principally by neuropeptides and calcitonin gene-related peptide (CGRP). The inflammatory cascade stimulates nociceptive afferents, leading to pain.

Neurogenic inflammation alone may be an insufficient explanation for the severity and quality of pain in migraine. One of the striking symptoms experienced during an attack of migraine is that seemingly innocuous activities, such as coughing, walking up stairs, or bending over, greatly intensify the pain. This observation, coupled with elegant research, has led to the concepts of “sensitization” of trigeminal vascular afferents, whereby both peripheral and central afferent circuits become exceptionally sensitive to mechanical, thermal, and chemical stimuli. These circuits become so sensitive that virtually any stimulation is perceived as painful: the concept of “allodynia” [Burstein et al., 2000, 2004; Burstein and Jakubowski, 2004].

Therefore, the current view of the pathophysiology of migraine begins with an inherited vulnerability with hyperexcitable neuron–glial networks. A variety of stimuli may trigger episodes of CSD and, separately, activation of the trigeminovascular system, which, in turn, initiates the processes of localized, neurogenic inflammation and sensitization of both peripheral and central afferent circuitry. Controversy exists as to whether CSD is the primary initiating event producing the cascade of downstream effects through the trigeminal vascular networks. The absence of aura in two-thirds of patients calls this into question. Exciting translational research exploring the pathophysiology of migraine continues.

Clinical Manifestations

Migraine without aura

The diagnostic criteria for migraine without aura are shown in Box 63-4.

Migraine without aura is the most frequent form, accounting for 60–85 percent of all migraine in children and adolescents. Patients will often recognize prodromal features: mood changes (euphoria to depression), irritability, lethargy, yawning, food cravings, or increased thirst. Perhaps the most frequent heralding feature is a change in behavioral patterns or withdrawal from activities.

A migraine headache begins gradually and is usually localized to the frontal or temporal region. The pain may be unilateral. The quality is generally described as pounding, pulsing, and throbbing, but the key feature is its intensity. Routine activities will be interrupted. Photophobia and/or phonophobia are common, and may be inferred by the child’s desire to seek a quiet, dark place to rest or even to sleep, since sleep often produces significant relief.

Nausea, vomiting, and abdominal pain may be the most disabling features; a student with headache may be able to stay in the classroom with pain, but the onset of nausea or vomiting necessitates a visit to the school nurse.

Migraine headaches typically last for hours, even days (1–72 hours), but do not, generally, occur more frequently than 6–8 times per month. More than 8–10 attacks per month must warrant consideration of alternative diagnoses, such as organic conditions (i.e., idiopathic intracranial hypertension) or the spectrum of chronic daily headache [Gladstein et al., 1997; American College of Emergency Physicians, 1996].

The time of day when the headache occurs tends to shift through childhood. Younger children will complain in the afternoon, after school. The early teenagers will frequently begin to report their headaches about lunchtime, often precipitated by the chaos of the school cafeteria with its combination of bright lights, loud noise, and peer pressures. Older teens will acquire the more adult patterns of morning headache, which is often a cause for concern since morning occurrence frequently raises suspicion of space-occupying lesions.

While most verbal children can readily relate these symptoms, the developmentally challenged may be unable to express themselves. Caregivers will report repeated, cycling, events of quiet, withdrawn behavior with pallor, regurgitation, vomiting, and desire to rest. These stereotyped episodes may prompt investigation for epilepsy, gastroesophageal reflux, or hydrocephalus, when, in fact, they may represent migraine.

Migraine with aura

Approximately 14–30 percent of children will report visual disturbances, distortions, or obscuration before or as the headache begins (Box 63-7) [Lewis, 1995]. The aura (“cool breeze”) is, however, an inconsistent feature in childhood and adolescents. The presence of an aura must be elicited with very specific questions: “Do you have spots, colors, lights, dots in your eyes before or as you are getting a headache?”

Typically, the aura is a visual phenomenon, but, as discussed in the pathophysiology section above, the cortical spreading depression responsible for the aura may disturb virtually any cortical region, including language, motor, or sensory areas. The classic visual symptomatology during migraine includes three dominant visual phenomena:

1. binocular visual impairment with scotoma (77 percent)

2. distortion or hallucinations (16 percent)

3. monocular visual impairment or scotoma (7 percent) [Hachinshi et al., 1973].

The onset of the visual aura is gradual and lasts up to 30 minutes. Sudden images and complicated visual perceptions should prompt consideration of complex partial seizures, even if followed by headache. Young adolescents may experience bizarre visual phenomena (distortions, illusions, micropsia, and macropsia) within the spectrum of the “Alice-in-Wonderland” syndrome. Transient visual obscurations – brief episodes of near-complete blindness – are also features of idiopathic intracranial hypertension.

Alice in wonderland syndrome

Bizarre visual illusions and spatial distortions occasionally precede migraine headaches. Similar to Alice, who experienced visual distortions after eating mushroom in Through the Looking Glass, affected children will describe visual distortions before or as the headache is beginning. The children may describe bizarre or vivid visual illusions, such as:

micropsia: objects appear smaller

macropsia: objects appear larger

metamorphopsia: objects (such as faces) appear distorted

teleopsia: objects appear far away.

These patients are seldom confused or frightened by these illusions and are able to relate the experience in exquisite and enthusiastic detail. This unusual visual symptomatology is best considered as migraine with aura, though, historically, Alice in Wonderland syndrome is included as a distinct variant. This type of visual-perceptual abnormality has been reported with infectious mononucleosis, complex partial seizures, and hallucinogenic drug ingestion.

Retinal Migraine

Also referred to as ocular, ophthalmic, or anterior visual pathway migraine, this variant is uncommon in young children but can occur during adolescence. Affected patients will report brief (seconds to <60 minutes), sudden, monocular, black or gray “outs,” or bright, blinding episodes (e.g., photopsia) of visual disturbance before, after, or during the headache. A 60-minute interval between visual symptom and headache may occur. As in ophthalmoplegic migraine, the pain of retinal migraine is often described as retro-orbital and ipsilateral to the visual disturbance.

Examination of the optic fundus during an attack may disclose constriction of retinal vasculature with marked retinal pallor. An occasional patient may suffer significant visual sequelae (e.g. scotoma, altitudinal defects, or monocular blindness) in retinal migraine thought to be due to retinal infarction. Although the patient population with retinal migraine is generally much younger than those who experience amaurosis fugax from atheromatous carotid disease, evaluation for hypercoagulable states, embolic sources, and carotid dissection must be considered.

Basilar-Type Migraine

Also known as basilar artery or vertebrobasilar migraine, this clinical entity is the most common of migraine variants and is estimated to represent 3–19 percent of all migraine [Bickerstaff, 1961; Lapkin and Golden, 1978; Golden and French, 1975]. This wide range of frequency relates to the rigorousness of the definition. Some authors consider any headache with dizziness to be within the spectrum of basilar-type migraine (BTM), whereas others require the presence of clear signs and symptoms of posterior fossa involvement before establishing this diagnosis. The ICHD-2 criteria require two or more symptoms and emphasize bulbar and bilateral sensorimotor features (Box 63-8).

Box 63-8 Signs and Symptoms of Basilar-Type Migraine

Vertigo	73%
Nausea or vomiting	30–50%
Ataxia	43–50%
Visual field deficits	43%
Diplopia	30%
Tinnitus	13%
Vertigo	73%
Hearing loss	*
Confusion	20%
Dysarthria	*
Weakness (hemiplegia, quadriplegia, diplegia)	20%
Syncope	*