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

Generalized

Fever

Systemic infection

Central nervous system infection

Toxins: lead, CO

After seizure

Electrolyte imbalance

Hypertension

Hypoglycemia

Post lumbar puncture

Trauma

Embolic

Vascular thrombosis

Hemorrhage

Autoimmune/Collagen vascular disease

Exertional

Localized

Sinusitis

Otitis

Ocular abnormality (glaucoma)

Dental disease

Trauma

Cranial neuralgia (occipital)

Temporomandibular joint dysfunction

Acute-Recurrent

Migraine

Complex migraine

Migraine variants

Cluster

Paroxysmal hemicrania

After seizure

Tic douleureux

Exertional

Chronic Progressive

Brain Tumor

Idiopathic intracranial hypertension

Brain abscess

Subdural hematoma

Hydrocephalus

Hemorrhage

Hypertension

Vasculitis

Chronic Nonprogressive and Mixed*

Chronic daily headache (chronic migraine)

Chronic tension-type

Chronic Hemicrania continuum

Conversion disorder

Malingering

After concussion

Depression

Anxiety

Adjustment reaction

^* with superimposed migraine.

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?”

Box 63-7 Forms of Migraine Aura

Visual

Negative scotoma

“Fortification” scotoma

Field deficits

Hemianopsia

Quadrantanopsia

Photopsia

Visual distortions

Teichopsia

Metamorphopsia

Prosopagnosia

“Alice in Wonderland”

Sensory

Paresthesias

Dyesthesias

Perioral and/or hand numbness (chiro-oral)

Motor

Hemiparesis

Monoparesis

Aphasia

Psychic

Confusion

Dysphasia

Amnesia

Dysequilibrium

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).

The onset of BTM tends to be in younger children, with the mean age being 7 years; however, the clinical entity probably may appear as early as 12–18 months of age, as episodic pallor, clumsiness, and vomiting, and evolving from one of the periodic syndromes, benign paroxysmal vertigo.

Children with BTM have recurrent attacks of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia. These early, transient features last minutes up to an hour and are then followed by the headache phase. The headache may be occipital in location. The quality of the pain may be ill defined and terms such as pulsing or throbbing may not be used. A small subset of patients with BTM will have their posterior fossa symptoms after the headache phase is well established.

The pathogenesis of BTM is not well understood. While focal cortical processes, oligemia, or depolarization can explain the deficits in hemiplegic migraine, the posterior fossa signs of BTM are more problematic. A single case report of a 25-year-old woman with BTM exists, wherein transcranial Doppler and single-photon emission computed tomography (SPECT) were performed through the course of a BTM attack. These data suggest decreased posterior cerebral artery perfusion through the aura phase at a time when the patient described was experiencing transient bilateral blindness and ataxia [La Spina et al., 1997].

The sudden appearance of diplopia, vertigo, and vomiting must prompt consideration of disorders within the posterior fossa, such as arteriovenous malformations, cavernous angiomas, tumors (medulloblastoma, ependymoma, brainstem glioma), congenital malformations (e.g., Chiari, Dandy–Walker), or vertebrobasilar insufficiency (e.g., vertebral dissection or thrombosis). Acute labyrinthitis or positional vertigo can mimic BTM. Complex partial seizures and drug ingestions must be considered at any age. Rarely, metabolic diseases such as Hartnup’s disease, hyperammonemias (urea cycle or organic acidemias), or disorders of pyruvate/lactate metabolism may present with episodic vertigo, but these inborn errors of metabolism usually have some degree of altered consciousness, even coma.

Hemiplegic Migraine

Alternating Hemiplegia of Childhood

Traditionally, this rare entity has been considered a variant of hemiplegic migraine, but more recent perspectives suggest other mechanisms and the ICHD-2 has omitted it from the migraine spectrum. Affected patients have their initial symptoms before 18 months of life, and have repeated attacks of hemiplegia involving either side of the body, paroxysmal movement disorders (dystonia, oculomotor disorders, autonomic), and a background pattern of developmental delay. Curiously, the symptoms abate upon sleeping.

Children with AHC have attacks of paralysis: hemiparesis, monoparesis, diparesis, ophthalmoparesis, or bulbar paralysis, which may be accompanied by variable tone changes (flaccid, spastic, or rigid). A variety of paroxysmal involuntary movements, including chorea, athetosis, dystonia, nystagmus, and respiratory irregularities (hyperpnea), can be seen. The attacks of paralysis can be brief (minutes) or prolonged (days), and are potentially life-threatening during periods of bulbar paralysis. Curiously, the attacks generally subside following sleep. Affected children are frequently developmentally challenged [Verret and Steele, 1971; Aicardi et al., 1995].

A recent comprehensive report of 103 children who met existing criteria for AHC focused on the earliest manifestations of symptoms and evolution of features over time. Paroxysmal eye movements were the most frequent early symptom, manifesting in the first 3 months of life in 83 percent of patients. Hemiplegic episodes appeared by 6 months of age in 56 percent of infants. Distinct convulsive episodes with altered consciousness, believed to be epileptic in nature, were reported in 41 percent of patients. Static features of AHC included ataxia (96 percent) and cognitive impairment (100 percent). MRI studies were generally normal (78 percent). Treatments included flunarizine, benzodiazepines, carbamazepine, barbiturates, and valproic acid. Flunarizine was the most effective agent, but perceived improvement occurred in only 60 percent of patients [Sweney et al., 2009].

The link to migraine was tenuous, but was based upon the presence of a high prevalence of migraine in the families of affected children and upon cerebral blood flow data that suggest a “migrainous” mechanism. In 1997, an international workshop was conducted to address the various hypotheses surrounding AHC and proposed mechanisms, including channelopathy, mitochondrial cytopathy, and cerebrovascular dysfunction. Channelopathy was suggested as the most likely explanation [Rho and Chugani, 1998]. A novel ATP1A2 mutation in a kindred with features that bridged the phenotypic spectrum between AHC and FHM has been reported. This observation may draw AHC back into the migraine spectrum; however, at this point the underlying molecular mechanisms of AHC are unknown [Wang et al., 2006].

Investigations into the etiology of this entity should include aggressive evaluation for vascular disorders, inborn errors of metabolism, mitochondrial encephalomyopathies, migraine (FHM 1) or epileptic variants.

Management is difficult; it may target the attacks of hemiparesis, or address the associated seizures or movement disorder. For the episodes of hemiparesis, flunarizine (5–10 mg/day), not available through U.S. pharmacies, can be effective in reducing attack frequency and severity.

Confusional Migraine

Omitted from the ICHD-2 classification system is the entity “confusional migraine,” which most likely represents a hybrid or overlap between hemiplegic and basilar-type migraine. Perhaps the term “confusional migraine” may disappear in the near future; those patients who have attacks associated with language disturbances, hemiparesis, and confusion are likely to be considered to have hemiplegic migraine, and those with bilateral blindness, vertigo, and confusion will be classified as having basilar-type migraine, dependent upon which symptoms predominate in individual patients.

The clinical entity was first described in 1970 by Gascon and Barlow, who reported a series of children, aged 8–16 years, with acute confusional states lasting 4–24 hours, and associated with agitation and aphasia. The authors suggested that the confusional state was a manifestation of juvenile migraine [Garcon and Barlow, 1970]. Ehyai and Fenichel later introduced the term acute confusional migraine [Ehyai and Fenichel, 1978]. Subsequent reports have broadened the clinical phenomenology to include blindness, paresthesias, hemiparesis, and amnesia. Amnesia can be such a prominent feature that Jenson proposed the term transient global amnesia of childhood, but amnesia is only part of the clinical spectrum [Jensen, 1980].

Affected children, more commonly males, become agitated, restless, disoriented, and, occasionally, combative for minutes to hours. Once consciousness has returned to baseline, the patients may describe an inability to communicate, frustration, confusion, and loss of orientation to time, and may not recall a headache phase at all. A strong family history of migraine is elicited in 75 percent of patients.

There is clear link to head trauma in many cases [Ferrera and Reicho, 1996]. The term “footballer’s migraine” is applied in Europe when a soccer player, after “heading” the ball, develops acute confusional state with headache. Similar phenomena may follow other causes of minor head injury. This variant should be viewed within the spectrum of trauma-triggered migraine.

Acute confusional states in children and adolescents warrant aggressive investigation for encephalitis, brain abscess, drug intoxication, cerebrovascular disease, vasculitis, or metabolic encephalopathies [Amit, 1988]. Particular attention must be focused on the possibility of complex partial seizures or postictal states.

Cyclical Vomiting Syndrome

Cyclical vomiting syndrome (CVS) is a disorder characterized by recurrent, self-limiting-episodes of intense vomiting (more than four emeses/hour), recognizable by their stereotypical time of onset, duration, and symptomatology within the individual (see Box 63-5). The vomiting is uniquely intense and the subjective nausea disabling; the resultant dehydration often necessitates hospital-based treatment. The attacks are accompanied by pallor, listlessness, anorexia, abdominal pain, retching, headache, and photophobia. The interval between attacks is 2–4 weeks and a typical attack lasts 24–48 hours. The children are, by definition, healthy between attacks.

Boys and girls are equally affected by CVS. The usual age of onset is 5 years, but the diagnosis is often delayed until age 8 and many, if not most, children will “outgrow” these attacks by age 10.

A recent practice guideline provides expert opinion regarding the evaluation and treatment of children with CVS [Li et al., 2008]. A thorough diagnostic evaluation must be performed to rule out intermittent bowel obstruction, elevated intracranial pressure, epilepsy, and metabolic disorders, such as urea cycle defects and organic acidurias. There is clearly a subset of children with a cyclic vomiting pattern who have underlying metabolic disorders.

The link to migraine is based upon natural history data that suggest the evolution toward more typical migraine, parallels drawn based upon autonomic data (i.e., “neurocardiac”), and presence of family history of migraine in children with CVS.

The management of CVS involves both acute strategies and preventative measures. For acute treatment of attacks, patients must be volume-replenished with solutions containing glucose (approximately 10 percent). Pharmacologic measures have not been systematically investigated, but anecdotal information suggests a role for antiemetics (e.g., ondansetron, promethazine, or prochlorperazine) and sedation (e.g., diphenhydramine, benzodiazepine). Subcutaneous sumatriptan (2–4 mg) has been used, but no controlled trials have been conducted. Preventive strategies include lifestyle changes plus agents such as cyproheptadine, amitriptyline or nortriptyline, valproate, topiramate, propranolol, or verapamil; these have all been utilized, but again, no clinical trials have been reported.

Abdominal Migraine

Abdominal migraine is an addition to the ICHD-2. The diagnostic criteria for abdominal migraine are listed in Box 63-6. This clinical entity is characterized by recurrent episodes of midline, epigastric abdominal pain lasting 1–72 hours. The pain is of moderate to severe intensity and is associated with vasomotor symptoms (e.g., flushing, pallor), as well as nausea and vomiting. The patients are well between attacks. Thorough gastrointestinal and renal investigations must be conducted before this diagnosis can be entertained. In a recent series of patients with idiopathic chronic abdominal pain collected from an academic pediatric gastrointestinal clinic, 4–15 percent were found to meet diagnostic criteria for abdominal migraine, suggesting that abdominal migraine is an underdiagnosed cause of recurrent abdominal pain in children in the United States.

Benign Paroxysmal Vertigo of Childhood

Benign paroxysmal vertigo of childhood is common and occurs in young children as abrupt, brief episodes of unexplained unsteadiness, with the child appearing to be “off balance” or falling. Careful observation may disclose nystagmus. Older children may be able to report symptoms of dizziness, clumsiness, headache, and nausea. The attacks may occur in clusters and typically resolve with sleep. In a small series of patients with long-term follow-up, most of the children had resolution of the episodes of vertigo, but later developed migraine.

The diagnosis of benign paroxysmal vertigo is one of exclusion. Epilepsy, otologic pathology, and central nervous system pathology should be considered.

Management of benign paroxysmal vertigo can include symptomatic treatment, such as antiemetics, although sleep will abort the attack in most patients. For a child in whom frequent events are occurring, a trial of cyproheptadine prophylaxis may be helpful in aborting attacks. A dosage of 2–4 mg nightly may be all that is required and medication should be discontinued after the attacks have stopped. The majority of patients will not require any treatment. Reassurance regarding the benign nature of the condition may be all that is required.

Benign Paroxysmal Torticollis

Benign paroxysmal torticollis (BPT) is a rare paroxysmal dyskinesia characterized by attacks of head tilt alone or tilt accompanied by vomiting and ataxia, which may last hours to days [Chaves-Carballo, 1996]. Other torsional or dystonic features, including truncal or pelvic posturing, were described by Chutorian [Chutorian, 1974]. Attacks first manifest during infancy, between 2 and 8 months of age.

The original descriptions of BPT by Snyder suggested a form of labyrinthitis and demonstrated abnormal vestibular reflexes [Snyder, 1969]. A recent case series of 10 patients followed longitudinally, plus a literature review of another 93 cases, has expanded our understanding of BPT. The authors found that attacks usually lasted for less than 1 week, but often recurred every few days or every few months. The episodes improved by age 2 years and typically ended by age 3. There was a very frequent family history of migraine. Developmental assessments, available only in the authors’ 10 cases, showed accompanying gross motor delays in 50 percent of children, with additional fine motor delays in 30 percent. Curiously, as BPT improved, so did the gross motor delays and the fine motor delays in about one-half to one-third of the children. The authors concluded that BPT is likely an “age-sensitive, migraine-related disorder, commonly accompanied by delayed motor development” [Rosman et al., 2009].

The link to migraine is strengthening. In addition to a frequent family history of migraine, intriguing molecular genetic information has been reported, in which four children with benign paroxysmal torticollis were shown to be linked to familial CACNA1A mutations [Giffin et al., 2002]. BPT is likely a migraine precursor within the spectrum of basilar-type migraine and benign paroxysmal vertigo.

The differential diagnosis must include gastroesophageal reflux (e.g., Sandifer’s syndrome), idiopathic torsional dystonia, and complex partial seizure, but particular attention must be paid to the posterior fossa and craniocervical junction, where congenital or acquired lesions may produce torticollis. Rarely, trochlear nerve dysfunction produces compensatory head tilt.

The management is unclear; there are no clinical trials reported. There may be no need for treatment in most patients, beyond reassurance. If the episodes are judged to be very frequent or painful, a trial of cyproheptadine may be a safe measure.

Chronic Daily Headache

CDH is formally defined as spanning a period of more than 4 months, during which the patient has more than 15 headaches per month, with the headaches lasting more than 4 hours per day. Many adolescents will report having headaches virtually every single day, sometimes during every waking hour. This chronic, nonprogressive, unremitting, daily or near-daily pattern of headache represents one of the most difficult subsets of headache. The estimated prevalence of CDH in adolescents is about 1–2 percent, and may be as high as 4 percent in the adult population [Abu-Arefeh and Russell, 1994; Lipton and Stewart, 1997; Castillo et al., 1999]. CDH is very common in referral headache centers, where up to 15–20 percent of patients will present with daily or near-daily head pain [Viswanathan et al., 1998].

Understandably, the quality of life of patients with CDH is significantly impaired. The negative impact extends beyond the affected patient to their family, friends, and society as a whole. The extensive disability that results from CDH can be measured in school absences, abstinence from after-school activities, and the family discord that invariably results. Therefore, early diagnosis and management of frequent or chronic daily headaches are essential.

Four primary chronic headache categories have been identified:

Chronic migraine is the most common form of CDH in adolescents, and evolves slowly from an episodic migraine pattern to daily migraine. Similarly, chronic tension-type headaches evolve from episodic tension-type headaches. Quite frequently, there is a mixed pattern, with daily background tension-type headache and interspersed episodes of more typical migraine, but rarely a moment of headache freedom.

The new daily persistent headaches appear to represent a unique entity, in which the daily headache pattern starts quite abruptly, de novo, without any history of previous headache syndrome. Uncommon in children, hemicrania continua represents a cluster variant with daily or continuous unilateral pain and conjunctival injection, lacrimation, rhinorrhea, and, occasionally, ptosis. One of the key features of hemicrania continua is remarkable and prompt responsiveness to indomethacin (25–50 mg orally twice a day).

Each of these four types of CDH is further separated into those with or without superimposed analgesic overuse (>5 doses/week of over-the-counter ANALGESICS). The medications implicated in this analgesic overuse syndrome include most over-the-counter ANALGESICS (e.g., acetaminophen, aspirin, ibuprofen), opioids, butalbital, isometheptene, benzodiazepines, ergotamine, and triptans [Mathew et al., 1990].

Secondary causes of the CDH pattern in children and adolescents include neoplasm, idiopathic intracranial hypertension (pseudotumor cerebri), hydrocephalus, chronic subdural hematomas, chronic sinusitis, glaucoma, malocclusion, and temporomandibular dysfunction, as well as psychological conditions. The “medicolegal headache” will fall into this category, as pending litigation tends to exacerbate stress levels and contribute to prolongation of the headache syndrome. Since the patient and family who present with the complaint of CDH are understandably concerned about the possibility of organic causes, it is critical to consider and exclude possible secondary causes for their headache. No treatment regimen will be successful until clear and confident reassurances as to the absence of serious underlying disease are provided. Parental skepticism can compound the clinical problem immeasurably.

Breaking the cycle of CDH is the principle goal of management. Pharmacologic efforts used in isolation, however, will be uniformly unsuccessful. Therefore, initiation of a multidisciplined approach, with emphasis upon preventive strategies, takes precedence over the use of intermittent ANALGESICS. This population of patients has already likely been overusing over-the-counter analgesic agents, so a fundamental change in treatment philosophy must be taught to the patient and family.

An integral part of the educational process will be the incorporation of wholesale lifestyle changes, such as regulation of sleep and eating habits, regular exercise, identification of triggering factors, stress management biofeedback-assisted relaxation therapy and biobehavioral programs, and psychological or psychiatric intervention (see Box 63-9) [Rothrock, 1999].

The genesis and persistence of the CDH pattern may have its roots in psychosocial factors. Therefore, a thorough social and educational history must then be obtained. Exploring issues relating to life at school (e.g., bullying, learning disabilities), family conflict (parental discord or impending divorce), grief and loss (grandparent’s illness, break-up of personal relationship), drug and alcohol use, and other factors in the teenager’s world will help the practitioner, the patient, and the family understand some of the obstacles that may complicate management.

For the CDH population, a group of lifestyle changes must be incorporated into the treatment plan. This essentially constitutes maintenance of a healthy lifestyle, and includes five major components:

The pharmacologic treatment of CDH requires an individually tailored regimen with the judicious use of appropriate prophylactic and analgesic agents. Recognizing the degree of disability will help guide the aggressiveness of the management. Unfortunately, no controlled studies have explored the pharmacologic management of CDH in children.

For the population of children and adolescents with CDH, preventative therapy takes center-stage and represents the mainstay of drug treatment (see Tables 63-3 and 63-4). Since the majority of children with CDH has chronic migraine or prominent migrainous features, a modification of standard migraine therapy is appropriate, but emphasis must be placed on prevention measures rather than analgesic or abortive strategies. The one exception may be the patients with a recent onset of CDH attributed almost exclusively to analgesic rebound. In this infrequent group, a trial of an analgesic-free period, as noted above, may be the sole successful treatment.

Preventative therapies used for CDH include tricyclic antidepressants, antiepileptic agents, beta-blockers, serotonergic agents, calcium channel blockers, and other miscellaneous treatments; however, none of these medications has been subjected to controlled trials and none is currently approved for the prevention of headaches in children [Redillas and Solomons, 2000].

When making the clinical decision regarding choice of pharmacologic agents, it is important to consider comorbid conditions. For the patient with difficulty falling asleep, amitriptyline at bedtime may provide dual benefits. Similarly, if there are mild to moderate affective issues, amitriptyline, valproic acid, or one of the selective serotonin reuptake inhibitors (SSRIs) may be beneficial. It there is comorbid obesity, topiramate may decrease the appetite. Alternatively, if the patient’s appetite is low, valproate often stimulates the appetite.

Tension-Type Headache

Tension-type headache (TTH) may be episodic or chronic, the differentiation being a lower frequency (fewer than 15 days/ month) in episodic TTH and greater frequency (≥15 days/month) in chronic TTH. Episodic TTH may be the most prevalent type of all primary headaches, but infrequently prompts referral to subspecialty clinics. Pathophysiologically, tension-type and migraine headaches may be similar, and there is a growing appreciation that the two may fall within a spectrum, with milder, less disabling headaches being classed as tension-type, and more severe patterns being classed as migraine. The diagnostic criteria for TTH (Box 63-4) emphasize the distinction from migraine. Generally, nausea and vomiting are not present in TTH; either photophobia or phonophobia may be present, but not both. On occasion, associated symptoms, such as tiredness, sleep disturbances, and lightheadedness, may occur with episodic TTH.

The management of TTH has not been rigorously studied, but simple over-the-counter ANALGESICS are commonly used. Various agents, such as acetaminophen (15 mg/kg), ibuprofen (7–10 mg/kg), or naproxen (7–10 mg/kg), may be very helpful; however, overuse of these medications (5 doses/week) is a major concern. Chronic TTH is often associated with a significant degree of stress and anxiety for the child and family, given the frequent, unrelenting nature of this type of headache (see CDH above).

Cranial Neuralgias

Cluster Headache

The trigeminal autonomic cephalalgias (TACs) represent a group of primary headache disorders associated with excruciating head pain, accompanied by autonomic features such as lacrimation, ptosis, rhinorrhea, and vasomotor changes. Cluster headache is an uncommon TAC in children and adolescents. The prevalence of childhood onset of cluster headache is approximately 0.1 percent [Lampl, 2002]. The diagnostic criteria require at least five attacks of severe unilateral orbital pain lasting 15–180 minutes, with a sense of restless agitation accompanied by ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, forehead sweating, miosis, or ptosis. Cluster headaches may be episodic or chronic, and attacks occur in series that last for weeks or even months. A cluster may be precipitated by alcohol, histamine, or nitroglycerine. Males are three times more likely to be affected than females.

The management is difficult. Acute treatments include inhalation of 100 percent oxygen at 8–10 L/min for 10–15 minutes through a non-rebreathing facemask; sumatriptan 6 mg subcutaneous injections or 20 mg intranasally, zolmitriptan nasal spray 5–10 mg; and intravenous, intramuscular, or subcutaneous injections of dihydroergotamine, 0.5–1.0 mg, at headache onset. Prophylactic medications useful in preventing attacks during cluster cycles include verapamil, sodium valproate, topiramate, melatonin, lithium carbonate, methysergide, and ergotamine tartrate [Newman et al., 2001; Rosen, 2009].

Paroxysmal Hemicrania

This TAC is characterized by intense attacks of periorbital pain lasting only 5–30 minutes; these can occur as many as dozens of times per day. In distinction to cluster headaches, the attacks are generally brief and can occur multiple times in succession. Like cluster headaches, there may be accompanying autonomic symptoms (lacrimation, rhinorrhea). The most striking feature is the exquisite responsiveness to indomethacin (25–50 mg/day), which has prompted the alternative nosology, “indomethacin-sensitive” headache. When evaluating a child with brief intense attacks of pain in and around the face or orbit, it is reasonable to consider a trial of oral indomethacin as a diagnostic challenge.

Temporomandibular Joint Dysfunction

Temporomandibular joint dysfunction presents with unilateral pain just anterior or inferior to the ear. The pain is aggravated by chewing, teeth clenching, or yawning. The patients may describe a clicking or locking of their jaw. Family members may describe bruxism and there may be antecedent trauma. Examination reveals tenderness over the temporomandibular joint and limitation of mouth opening. Treatment includes nonsteroidal anti-inflammatory drugs, muscle relaxation, and avoidance of provocative processes like chewing of gum or hard candy. Major oral surgery is rarely necessary.

Post-Traumatic Headache

Headache following closed head injury or neck trauma in children is one of the most common secondary headache syndromes, but has not been systematically studied. No epidemiological data are available. Post-traumatic headache is divided into acute and chronic, patterns based upon duration of symptoms, less than 3 months being acute and more than 3 months being chronic.

Acute post-traumatic headache must immediately raise concerns for traumatic brain injury, such as cerebral hematoma (subdural or epidural), subarachnoid hemorrhage, cerebral contusion, or skull fracture, and warrants urgent neuroimaging, particularly if associated with alteration of consciousness, seizures, or Glasgow Coma Scale <13. If post-traumatic headache is suspected, emergent noncontrast computed tomography (CT) of the head and cervical spine x-rays are warranted. If focal neurologic symptoms or signs are present, then evaluation for vascular injury (i.e., carotid dissection) may be indicated and detection may require specific MRI sequences (MRA). CSF leaks following meningeal tears can lead to positional, or “low-pressure,” headaches.

Post-traumatic headache is defined as headache that begins within 2 weeks of closed head injury. It is, furthermore, divided into acute post-traumatic headache if the symptoms have been present for less than 3 months, and chronic if symptoms have been present for more than 3 months.

Trauma-triggered migraine can be initiated by mild head injury. The key features are aura (e.g., visual, cognitive, motor, or sensory), duration of 1–72 hours, frontal or unilateral location, moderate to severe pain, aggravation by routine activities, nausea and/or vomiting, and photophobia and phonophobia. A particular subset of post-traumatic migraine is termed “confusional” or “footballer’s migraine,” wherein mild head injury triggers an acute confusional state, often with agitation, and accompanied by a headache with migraine features.

Chronic post-traumatic headache may be part of a global postconcussive syndrome, with behavioral changes (e.g., hyperactivity, hypoactivity), dizziness, tinnitus, vertigo, blurred vision, memory changes, sleep disorder, irritability, and attentional disorders. The duration of symptoms is variable, with some patients having brief, self-limited syndromes, and others suffering from headaches for more than 6–12 months. One retrospective study of 23 children with chronic post-traumatic headache found a mean duration of 13.3 months (range 2–60 months, median 7 months) [Callaghan, 2001]. The headache forms span the spectrum from tension-type, migraine, CDH, neuralgias (e.g., occipital neuralgia), temporomandibular joint dysfunction, and even, on rare occasions, cluster headache.

A recent prospective study of 117 children (81 males, 36 females; range 3–15 years [mean age 8.5 yrs]) admitted with closed head injury (minor 79 percent, major 21 percent) found that 8 (7 percent) children (5 males, 3 females; mean age 10.5 yrs) reported chronic post-traumatic headache. Five (4 percent) children had episodic tension-type headache and 3 (2.5 percent) had migraine with or without aura. Headache resolved over 3–27 months in all patients [Kirk et al., 2008].

Many athletes competing in contact sports experience post-traumatic headache as part of a postconcussion syndrome. A common question concerns when it is safe to return to full contact. Three organizations – the AAN, the American College of Sports Medicine, and the British Association of Sport and Exercise Medicine – have provided guidelines regarding return to activities, which range from 1 to 4 weeks [Quality Standards Subcommittee, 1997; American College of Sports Medicine, 1991; McCrory et al., 2009]. These guidelines are available online. See http://aappolicy.aapublications.org/cgi/content/full/pediatrics and http://www.acsm.org.

The management of post-traumatic headache requires an appreciation of the degree of disability produced by the headache. Post-traumatic tension-type headaches can generally be managed with nonsteroidal anti-inflammatory agents, such as ibuprofen or naproxen sodium. Post-traumatic migraine is treated as discussed earlier, with a balance of analgesic or “triptan” agents and, if warranted, daily preventative therapies. For patients with frequent or daily headaches, the management strategies discussed in the CDH section apply, with daily preventative programs, both pharmacologic and nonpharmacologic, as well as ANALGESICS for episodes of intense pain.

There are no outcome data on post-traumatic headache in children and adolescents, but typically, 3–6 months is the anticipated course of recovery. Pending litigation may exacerbate stress levels and contribute to prolongation of the headache syndrome.

Idiopathic Intracranial Hypertension

Also known as pseudotumor cerebri, idiopathic intracranial hypertension (IIH) produces a global, daily, pounding headache (approximately 94 percent) and is an important consideration in the differential diagnosis of CDH. The incidence of IIH is 3.5–19 per 100,000, with a majority of patients being female. Neck stiffness (30–59 percent) and transient visual disturbances may be present. The key finding on physical examination is papilledema. Neuroimaging will likely be normal. The pathogenesis of IIH is unclear but somehow involves impairment of CSF reabsorption. IIH can be caused by multiple disorders, including endocrinopathies (e.g., hypothyroidism, Addison’s disease, oral steroids), pregnancy, drugs (e.g., tetracycline, oral contraceptive agents), vitamin A intoxication, anemia, systemic lupus erythematosus, chronic sinopulmonary infection, and obesity, or may be idiopathic.

Other secondary headaches that present with CDH include intoxications (lead or other heavy metals), chronic carbon monoxide poisoning, chronic meningitis with such pathogens as tuberculosis, fungi, or spirochetal syphilis, or Lyme disease. A chronic daily pattern can also be seen, with central nervous system leukemia/lymphoma or leptomeningeal metastasis. Rarely, diffuse “butterfly” gliomatosis of the brain can produce this picture, but cognitive decline and pyramidal tract signs would be expected. Uncontrolled hypertension can lead to optic disc changes with headache, but this would be uncommon during adolescents. Chronic sinusitis or venous sinus thrombosis can also produce a pattern of slowly increasing intracranial pressure with normal CT scan.

The diagnostic criteria for IIH in the prepubertal child include normal mental status; symptoms and signs of generalized intracranial hypertension (e.g., papilledema); documented elevated intracranial pressure measured in the lateral decubitus position (<8 years, 180 mm H₂O; ≥ 8 years, 250 mm H₂O); normal CSF composition; absence of evidence of hydrocephalus; mass, structural, or vascular lesion on neuroimaging (narrowing of the transverse sinuses is allowed); and no other identified cause of intracranial hypertension [Rangwala and Liu, 2007]. The diagnostic test of choice for IIH is lumbar puncture, with measurement of opening pressure. Given a normal CT scan, the test can be accomplished safely, even though the examination shows a sixth nerve palsy, since this can be a “false localizing” sign, indicative of diffuse increase in intracranial pressure.

For adolescents, the normal CSF opening pressure is <180 mm H₂O. Patients with IIH may have CSF opening pressure exceeding 200 mm H₂O, and often 400 mm H₂O. CSF must be collected for glucose, protein, cell counts, and cultures (bacterial, fungal, tuberculosis), but special studies, such as cryptococcal antigen, Venereal Diseases Research Laboratory test (VDRL), neuroborreliosis, and CSF cytopathology, may be an option.

The lumbar puncture not only provides critical diagnostic information, but also the relief of pressure usually provides significant decrease in headache symptoms. The volume of CSF to be removed is controversial. Generally, removal of sufficient volume to lower the pressure down to about 200 mm H₂O is valid and safe. Care must be taken to limit the risk of “post-lumbar puncture” headache by keeping the patient recumbent for several hours following the procedure.

Once the diagnosis of IIH is established, the carbonic anhydrase inhibitor, acetazolamide, can be used to lower CSF pressures, probably by a diuretic mechanism. The side effects are few but include paresthesias, polyuria, and sedation. The dose is typically 250 mg twice a day up to 1000 mg per day. There is a once-daily preparation available. The recovery is slow, over weeks or months. If obesity is a contributing factor, a weight loss program is strongly recommended, though difficult to institute. If the visual symptoms are severe or progressive, or if there is visual compromise, ophthalmologic intervention may be necessary, with performance of an optic nerve sheath fenestration.

Intracranial Hypotension

Low-pressure headache may occur following lumbar puncture or other processes that cause a tear in the dura mater, including penetrating trauma or cranial surgery. The cardinal clinical feature is orthostatic or positional headache, in which a severe, pounding, nauseating headache occurs immediately upon standing or sitting up from a reclined position. Importantly, the symptoms resolve when the patient lies back down. Specific ICHD-2 diagnostic criteria include neck stiffness, tinnitus, hyperacusia, and photophobia. The CSF opening pressure will be approximately 60 mm H₂O in the sitting position.

While the majority of post-spinal tap headaches resolve spontaneously, persistence of disabling symptoms may necessitate consideration of a “blood patch” or other technique to repair the source of the CSF leak; this may take 72 hours to be effective.

Brain Tumor Headache

About two-thirds of children with brain tumors will have headache as a presenting symptom. There is, however, no invariable “brain tumor headache” profile. A steady, gradual rise in intracranial pressure typically produces the chronic progressive pattern, but, on occasion, an anaplastic tumor or hemorrhage into tumor may cause an acute pattern (see Figure 63-1). Several historic clues suggest space-occupying lesions, such as brain tumors, but may also be present in other expanding masses, such as brain abscess, hematoma, or vascular anomaly. Morning headache or headaches that awaken the child from sleep are classic symptoms of the dependent edema of intracranial lesions. Likewise, nocturnal or morning emesis, with or without headache, suggests increased intracranial pressure and is a particularly common symptom of tumors arising near the floor of the fourth ventricle. Head pain aggravated by exertion or the Valsalva maneuver suggests a mass lesion. In addition to headache, parents may note behavioral or mood changes, cognitive changes, or declining school performance.

Accompanying symptoms may suggest localized disturbances of neurologic function. Ocular symptoms are common: loss of vision (e.g., craniopharyngioma, optic pathway tumor) or diplopia (e.g., brainstem glioma, medulloblastoma). Disorders of coordination, such as truncal ataxia (e.g., medulloblastoma, ependymoma) or dysmetria (e.g., cerebellar astrocytoma), suggest posterior fossa tumors. The presence of seizures indicates cortical disturbances, often localized to the temporal lobes.

The key physical examination signs that indicate brain tumor include:

papilledema

abnormal eye movements

hemiparesis

ataxia (truncal or appendicular)

abnormal tendon reflexes [The Childhood Brain Tumor Consortium, 1991].

As stated in the AAN Practice Parameter, neuroimaging (MRI or CT) is therefore appropriate for children with headache in whom there are historical features to suggest the recent onset of severe headache, a change in the type of headache, or focal neurologic dysfunction. Neuroimaging should also 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.

Chiari Malformation

Chiari malformations (type I) are, arguably, among the most common incidental findings when performing MRI in children with headache, and are the source of great controversy. Tonsillar ectopia of 5 mm or less is not considered pathological. When symptomatic, children with Chiari I malformation may complain of occipital headache, neck pain or stiffness, arm weakness, and gait abnormalities. The headache may be aggravated by neck flexion or extension, or the Valsalva maneuver. Basal skull abnormalities or scoliosis may be identified. In a retrospective MRI analysis of 49 children with Chiari I malformation, 57 percent of children were asymptomatic. Headache and neck pain were the most frequent complaints. Syringomyelia was detected in 14 percent of patients and skull-base abnormalities in 50 percent. The magnitude of tonsillar ectopia (5–23 mm) correlated with severity score (p = 0.04), but not with other clinical measures. Children with greater amounts of tonsillar ectopia on MRI are more likely to be symptomatic [Wu et al., 1999]. Extreme care must be exercised before embarking upon surgical decompression. MRI with CSF flow studies may help to determine whether suboccipital decompression is necessary.

Metabolic Causes of Headache in Children