AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Children frequently experience headaches, which can be age specific or the beginning of a lifelong syndrome. The approach of headache in this age group is peculiar in several ways, as follows: (1) in a discipline where diagnosis is based on history, an underestimation is inevitable; (2) the verbal expression of pain itself is language-dependent and other behavioral indicators have to be relied upon; (3) frequently symptoms other than pain may be at the forefront of the clinical picture; (4) except in young children, the frequency of secondary headaches is lower than in adults; and (5) in young patients, pharmacotherapeutic interventions are limited but nonpharmacologic interventions can be more efficient. No headache classification exists that is specific for children, and they are underrepresented in the headache literature. Migraine is the most frequent chronic headache in children; therefore, it will receive most of the attention in this article.

Pathophysiology

Although much remains to be discovered, the pain in migraine attacks supposedly is due to activation of the trigeminovascular system (see Media file 1). Synaptic boutons of the perivascular branches of the trigeminal nerve at the level of meningeal and basal cerebral vessels release the following proinflammatory mediators when the nerve is stimulated: substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP). The initial triggers are still poorly understood. The mediators create neurogenic inflammation, including local rupture of the blood-brain barrier, and trigger vasodilatation, further stimulating the trigeminal nerve terminals.

On the other end, pain afferent messages are transmitted centrally. Whether this system is abnormal in migraineurs versus healthy people, and whether it is genetically determined, is not known. Evidence exists of cortical hyperexcitability in migraineurs, which may be linked to a defect in the central catecholaminergic systems. Low magnesium levels also may play a role.

In 1993, a gene mutation was found on chromosome 19, locus p13 in a pedigree experiencing familial hemiplegic migraine. Later, other families mapped to chromosome 1. Defects in ion channels explain the effect of the mutation, which play a role in the aura. Cases of migraine due to a single mutation remain the exception.

White matter T2 MRI hyperintensities are observed in higher frequency in migraineurs, especially in the posterior circulation territories. The pathophysiological implication remains unclear.

Chronic transformation of migraine is believed to be due to spatial and temporal, central and peripheral sensitization, which correlates clinically with cutaneous allodynia.

Tension-type headache pathophysiology is still poorly understood; a combination of muscular factors, abnormal pain perception mechanisms, and central emotional abnormalities exist, all possibly linked to brainstem serotonergic interneurons. Furthermore, central and peripheral sensitization is involved. Contrary to the usual belief, the relevance of muscle contraction itself is marginal, especially in the chronic form.

Frequency

United States

Throughout the medical literature, estimates of overall frequency of headache in children vary among authors. Starfield screened 2500 children and found that 11% experienced chronic morbidity; among those children, about 20% had headache, roughly one half of which had migraine.

International

In a widely cited study, Bille analyzed a questionnaire of 8993 children aged 7-15 years in the city of Uppsala in Sweden and found that 59% had a headache in their life. Also, in a systematic questionnaire of 2941 children, the prevalence of headache was 37% at age 7 years, increasing to 69% by 14 years; migraine accounted for 2.7% and 10.6%, respectively. Per Sillanpaa, at puberty (age 13 y) migraine prevalence is around 11% but increases over time. Secondary headaches are the most frequent encountered before age 5 years. (Migraine) headache can occur as early as a few months of age. A higher prevalence of migraine seems to exist in city dwellers. Chronic daily headache in a pediatric headache clinic is about 5-6% prevalent. Long-term prognostic studies are scarce; Brna et al recently reported 73% of a 20-year follow-up cohort to still have headaches.

Mortality/Morbidity

• No mortality is associated with primary headaches and that of secondary headaches depends purely on the underlying cause.
• Morbidity includes psychological impairment and decreased quality of life, especially for persons who experience chronic migraine. It was recently emphasized again how children who suffer from migraine are more impaired than children who do not suffer from headaches or even children who suffer from tension-type headache, in terms of medication use, school nurse visits, and school absences.
• Migraine in general but especially migraine with aura (any type [typical aura, hemiplegic migraine, basilar migraine]) seems to be associated with a slightly increased risk of stroke but overall the risk remains very low. Other conditions comorbid with migraine have been observed, including irritable bowel syndrome, anxiety disorder, depression, sleep disorders, and lupus erythematous. Recent reports indicate a higher incidence of ataxia, whether clinical or subclinical during provocation tests. These could correlate with white matter lesions on MRI, especially in the cerebellum.

Race

No specific report exists of differential incidence according to race in children, but migraine is more frequent in Caucasian adults than in Asian adults.

Sex

Before puberty, males are affected slightly more by migraine than females; thereafter the relationship is inversed, with 3 times more female than male migraineurs in adulthood. Other headache types are distributed more evenly.

Age

In a systematic survey of close to 3000 children, Sillanpaa showed the increase in frequency with age, from 37% at age 7 years to 69% by age 14 years.

CLINICAL

Section 3 of 11  

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History

Besides the impairment caused by the headache itself, pediatric patients are seen by a physician because of parental concerns. In 25%, the physician is a pediatric neurologist, but frequently another specialist may be the initial consultant because symptoms might suggest an underlying cause. Often, it will be the ophthalmologist because migraine presents with prominent or worrisome visual symptoms.

• No formal classification of headaches that is specific for children exists. Improving on the initial classification from 1988, although still far from ideal, a new classification of headache disorders was published in 2004 by the International Headache Society as part of the second edition of the International Classification of Headache Disorders (ICHD-II). However, many unique aspects of childhood syndromes are not mentioned and have been emphasized in epidemiologic studies such as that of Wober-Bigol et al. In particular, lack of throbbing and lateralization components and variations in the duration of the attack are common differences with adult presentation of migraine. Winner et al proposed a revised version in 1995. If wider time criteria for migraine attacks are adopted as in DeGrauw et al, a significant increase exists in the incidence of migraine.
• One of the most important features to inquire about is the notion of recurrent and fairly stereotyped episodes of head pain associated with autonomic dysfunction. The latter are frequently at the forefront of the clinical picture with little or no headache. Autonomic dysfunction consists of nausea, vomiting, dizziness, hypotension, bradycardia, pallor, diaphoresis, and diarrhea. Syncope can even be part of the picture, to distinguish from the loss of consciousness as part of the aura in basilar migraine.
• The essential symptomatology of migraine is the attack, which consists of the following features:
• • Premonitory symptoms typically occur between one or more hours (rarely a few days), before onset of the pain phase. Most symptoms point to a hypothalamic dysfunction. Premonitory symptoms include mood changes (depression, irritability, rarely elation), changes in appetite (hunger and especially craving for sweets), alteration in arousal (tiredness, yawning), or altered water balance (polydipsia, thirst).
  • Aura only occurs in migraine with aura, which represents about a fifth of all migraines. This is a sudden and self-limited neurologic dysfunction lasting generally a few minutes; sometimes several can occur simultaneously or sequentially. The following symptoms can occur:
  • • Visual - Scotomas, phosphenes that look like stars, straight or broken lines (fortification spectra), colors, illusions of shape (micropsias, macropsias, dysmorphopsia), rarely hallucinations (more complex pictures)
    • Sensory - Paresthesias, rarely dysmorphopsia (impression one's body is deformed)
    • Motor - Paresis or hemiplegia, especially prominent in familial hemiplegic migraine
    • Speech or language disturbance - Dysarthria, aphasia
    • Other cognitive - Confusion or amnesia
    • All these symptoms have been attributed to cortical dysfunction. In a few instances, the aura supposedly has a brainstem origin, although it has never been proven (eg, loss of consciousness, ophthalmoparesis, vertigo).
  • Headache phase is the most obvious and well-known part of the attack and the most disabling. Often, it is the only phase the patient is aware of. The therapeutic approach mainly addresses this phase.
  • • Patient often has severe pain, usually throbbing; typically covering a large area of the skull but predominates on one side.
    • Pain is worsened by physical activities such as running, bending over, or straining in the bathroom.
    • Patient complains of sensitivity to light, sound, and smells (ie, photophobia, phonophobia, and osmophobia).
    • Variable degrees of GI derangement are present such as anorexia, nausea, and vomiting.
    • An overall feeling of exhaustion exists, and the patient typically tends to rest in the recumbency position.
  • Postdromes - After the main headache phase, patients can experience fatigue, depression, and fluid loss (diuresis). This typically lasts a few hours.
• Other variants of migraine that typically occur in children include the following:
• • Basilar migraine originally was described by Bickerstaff whose name sometimes is given to the syndrome. Basilar migraine typically starts in the early teens.
  • • Basilar migraine presents with prominent aura symptoms such as vertigo, tinnitus, diplopia, bilateral visual field defects, alternating hemiplegia, dysarthria, and loss of consciousness, which secondarily can be followed by a seizure. These symptoms supposedly are due to brainstem dysfunction, although it has never been proven.
    • The initial term of basilar artery migraine coined by Bickerstaff belies the fact that the role of a vascular component has never been established clearly. These patients respond better to calcium channel blockers, especially verapamil, than other drugs.
  • Familial hemiplegic migraine starts in childhood but continues into adulthood and is characterized by prominent motor deficits with the aura, as well as often alteration of consciousness or encephalopathy. Other neurologic deficits also are frequent.
  • Ophthalmoplegic migraine is a rare syndrome, probably fewer than 1% of migraines with aura; it involves a third nerve palsy, which curiously often takes place at the time of the resolution of the headache phase.
  • Confusional migraine has the striking and worrisome presentation of a confused and often obtunded child and can be associated with paroxysmal activities on EEG. The confusion can last for more than a day. This is of course a diagnosis of exclusion that can be based upon repeated observations and negative workup results. The boundaries between this entity and familial hemiplegic migraine are not always clear.
  • Prolonged aura and complicated migraine are terms reserved for when the aura persists, at least to some degree, beyond an hour or forever, respectively.
• It has long been known that before they develop a clear migraine history, patients often experience manifestations in childhood that might actually already be the expression of their migraine or that of a common underlying dysfunction. These are called childhood periodic syndromes or migraine equivalents. Considerable overlapping exists between these syndromes, and several have features in common with the aura or accompanying features of migraine in its common adult forms. For example, vertigo has been observed in as many as 23% of children with clearly established migraine attacks. Migraine equivalents include the following:
• • Cyclic vomiting is characterized by repeated episodes of a few hours to a few days of vomiting, pallor and diaphoresis, photophobia, and sometimes low-grade fever, without any other explanation. It usually occurs at age 3 or 4 years. A recent appraisal shows that up to one half of patients with this syndrome have migraine diathesis.
  • Periodic colic pain episodes consist of episodic abdominal cramps with nausea, vomiting, pallor, and sometimes aspecific headache. In one series, as many as 20% of migraineurs had this manifestation versus 4% of control subjects. It can be linked to lactose intolerance, which happens to be known as a potential migraine trigger.
  • Benign paroxysmal vertigo of childhood syndrome occurs in children aged 1-4 years and is expressed by brief (1-5 min) episodes of vertigo with nausea, pallor, and sweating, usually 3-4 times a month, and is self-limited. Electronystagmography is normal. Long-term follow-up study questions the true relation with migraine.
  • Benign paroxysmal torticollis is less frequent; it typically is seen in infants.
  • Motion sickness is a frequent precursor of migraine; it tends to persist through adulthood.
  • Besides the above, in some instances, febrile seizures have been suspected to be linked to that group of syndromes, although obviously significant heterogeneity is present. The prevalence of sleep disorders is increased in migrainous children and adolescents.

Physical

Thorough general and neurologic physical examination is necessary and particular attention should be given to signs of intracranial hypertension and mass effect.

Causes

Etiologies of headaches can be multiple and virtually all systemic medical conditions can be accompanied by headache.

• Distinguishing between causes and triggers is important, the latter act merely as precipitants of the headache condition, most often migraine.
• Likewise, it should be clarified that although true migraine is a primary headache disorder, sometimes a migrainelike headache can be secondary to a metabolic or vascular disease. For instance, this is the case of MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke), a mitochondrial cytopathy, or CADASIL (cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy), a genetically determined disease of small vessels in the brain. The headache attacks in these disorders are indistinguishable from those of primary, true migraine, but, of course, the other symptoms and disease features make the difference.
• A note should be mentioned on posttraumatic headaches because of their frequency. The acute phase usually is not a significant concern because it does not change the initial assessment or management; this headache phase usually is considered nociceptive. However, later, it can become a chronic, lingering head pain. This syndrome is variably associated with autonomic symptoms and often akin to a primary headache syndrome, such as migraine and tension-type headache. It is believed that the trauma has acted as a trigger or exacerbating factor in the genesis of that primary headache. Frequently, psychologic disturbances are present and need to be specifically addressed for therapeutic success.
• Ear, nose, and throat (ENT) causes should be considered, although it likely will not be high on the list.
• Toxic causes have to be reviewed as well, including medications.
• Other diagnostic considerations
• • Often suspected, rarely implied, sinusitis has to be ruled out, although typically acute sinusitis presents with systemic and otorhinolaryngology (ORL) symptoms and signs and chronic or allergic sinusitis almost never are responsible for headaches.
  • Tumors, especially in the posterior fossa, are to be kept in mind, although neurologic abnormalities will be at the forefront of the clinical picture. Although rarely involved, refractive abnormalities potentially can be considered.

DIFFERENTIALS

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Other Problems to be Considered

Sinusitis
Tumors

WORKUP

Section 5 of 11  

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Lab Studies

• Routine CBC and chemistries can help on an individual basis when specific etiologies, such as infection, are considered; however, they rarely are indicated.

Imaging Studies

• Neuroimaging usually is not indicated for the routine care of patients with headache except may be in the very young child and if absolutely no family history can be found despite thorough review.

Other Tests

• Clinical neurophysiologic testing has little to offer in clinical practice contrary to research.

Procedures

• Consider spinal tap specifically if meningitis is suspected. Cerebrospinal fluid (CSF) studies should include a measure of pressure, CBC, protein, glucose (always correlate with blood glucose), and microbiology. A tap also can give a CSF pressure value in case benign intracranial hypertension is considered.

TREATMENT

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Medical Care

Treatment of a secondary headache is focused on its specific cause, but an additional symptomatic therapy might be useful as long as the cause is not eradicated yet. As for a primary headache, always consider both a preventative treatment and a symptomatic therapy.

• Although consensus does not exist regarding the criteria to start prophylactic treatment, frequency and severity will be the main factors to guide the decision. Also, the efficacy of the symptomatic treatment and the opinion of child and parents should be considered. The drug should be chosen carefully according to headache type (eg, beta-blockers or cyproheptadine for migraine, amitriptyline for migraine or tension-type headache), frequency (eg, amitriptyline more for frequent/chronic headache), type of symptoms (cyproheptadine if prominent vomiting), side effect profile (eg, no beta-blockers if asthma), and individual tolerance and efficacy guides adjustments. Finally, it is advisable to include comorbidity in the choice, such as depression and insomnia, which a tricyclic antidepressant helps to control along with migraine.
• Multiple levels of symptomatic therapy exist. The current opinion is that rather than a step-care treatment starting with the least expensive drugs then stepping up as needed, the stratified care approach is best; up front the patient situation is assessed and the severity and level of care needed is taken into account to decide upon the most effective and overall cost-containing treatment. Adjusting treatment is recommended until the most efficient regimen is found, which treats all symptoms, including the headache itself but also other complaints such as nausea, vomiting, and photophobia.
• Besides medical therapy, a number of nonpharmacologic measures have been proven efficient for migraine or tension-type headaches.
• • Relaxation techniques with biofeedback of either cutaneous temperature with a finger probe or muscular contraction with an electromyography (EMG) needle are very helpful as adjunct therapy or can even prevent headache on their own in the older child granted that an adequate cooperation can be obtained.
  • Recommended treatment is 2-3 times a week for 4-8 weeks. Usually, a physical therapist or sometimes a psychologist with cognitive-behavioral skills performs this technique.

Surgical Care

Surgical approach is necessary for specific secondary headaches such as tumors. It is exceptionally indicated for primary headaches (eg, neuralgias) and is primarily in the adult population. An exception is shunting and/or optic nerve fenestration for benign intracranial hypertension.

Consultations

• Patients with headache are referred to a specialist whenever appropriate, especially when a specific underlying cause (eg, orbital disease, severe sinusitis, tumor) is suspected.
• Note that an ophthalmologic consultation frequently is requested to evaluate for refractive abnormalities; although this scenario is possible, an excessive tendency exists to attribute headaches to this problem.

Diet

• Much has been written as to which food item can trigger headaches, especially migraine but there is a high degree of variability. Individual patients should know what foods to avoid that are associated with their headaches. Good scientific explanation for these correlations is rare. Causative items most often contain multiple potential triggers.
• Avoid food triggers, such as old fermented cheese, citrus fruits, and monosodium glutamate (found not only in Chinese food but also widespread in commercial preparations). In the author's opinion, chocolate is by far more frequently a consequence of sugar craving, part of migraine premonitory symptoms, than a trigger. Caffeine excess and especially caffeine withdrawal can precipitate migrainous headaches.

Activity

Regular life hygiene and schedules are paramount for migraineurs and other frequent/chronic primary headache disorders.

• Regular physical activities are especially useful in the case of tension-type headaches but also to reduce the level of stress, which can cause migraine.
• Regular sleep schedules, especially adequate amounts of sleep, also have an effect on migraine control. A common tendency exists for teenagers to not sleep enough.

MEDICATION

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Therapies for secondary headaches depend on the cause, such as antibiotics for sinusitis, and are not the subject of this article. Only treatment of primary headaches is reviewed. Migraine is reviewed first, then tension-type headache, then less common syndromes. When a treatment is prophylactic and when it is symptomatic is clarified because this is critical.

Drugs exist that can be considered individually but cannot be recommended on a routine basis because either (1) they have not been studied specifically or used regularly in the pediatric population, or (2) they are not available in the United States. These medications are migraine preventatives: flunarizine, a calcium channel blocker (5 mg PO qd); gabapentin (100-300 mg PO tid); riboflavin (400 mg PO qd); and metoprolol (50-100 mg PO qd slow-release form). This list is not exhaustive.

Drug Category: Beta-blockers

Effective in prophylactic therapy possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues.

Drug Category: Antihistamines

Compete for H1 receptor sites on effector cells in blood vessels and other target tissues.

Drug Category: Anticonvulsants

Those that interact with the GABA-ergic system seem to have a positive effect in reducing migraine attacks.

Drug Category: Calcium channel blockers

May relax smooth muscles and increase oxygen delivery during vasospasms.

Drug Category: Antiemetics

Used as adjuncts or directly useful in symptomatic relief of migraine attacks.

Drug Category: Triptans

Specific serotonin 1 A and B agonists, they relieve not only pain but also nausea, vomiting, photophobia, and phonophobia.

Drug Category: Tricyclic antidepressants

Prevention of tension-type headache. Used for migraine prophylaxis because it decreases the incidence and severity of attacks.

Drug Category: Carbonic anhydrase inhibitors

Treatment of benign intracranial hypertension.

Drug Category: Steroids

May decrease intracranial pressure in benign intracranial hypertension.

Drug Category: Analgesics

Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients in pain.

FOLLOW-UP

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Further Inpatient Care

• Inpatient care for headaches is reserved to the intractable chronic daily headaches after outpatient treatment has indeed failed. It usually is intended to initiate prophylaxis while giving intravenous symptomatic therapy and, sometimes, intravenous fluids in case of severe nausea and vomiting. Also, status migrainosus can justify a brief hospital stay for symptomatic treatment.
• Headaches of unclear etiology but severe and worsening, as well as worrisome symptoms and signs also can justify hospitalization in certain cases.

Further Outpatient Care

• It is paramount to observe patients, especially when given daily prophylactic medications, to monitor progress and adverse effects, and to be able to adjust regularly and appropriately. Migraine medications frequently have to be reviewed and modified.
• Physical therapy, relaxation biofeedback, and other nonpharmacologic therapies are often tried for migraine and tension-type headaches, but, unfortunately, definitive evidence is still lacking.

In/Out Patient Meds

• The following must be considered: prophylaxis, usually one only; rarely does one need to combine several medications for that purpose; and symptomatic treatment.

Complications

• The main complications of primary headaches are the chronic daily headache transformation for which adequate and early treatment is the best prevention.
• Complications of secondary headaches are those of their underlying cause.

Prognosis

• Primary headache conditions are notorious for their waxing/waning course, and long-term follow-up care is usually necessary. Short-term remissions are not uncommon, but long-term ones are rare.

Patient Education

• Reinforcing good health hygiene is the most important educational step; sleep hygiene is particularly paramount (see Activity).
• For excellent patient education resources, see eMedicine's Headache Center. Also, visit eMedicine's patient education articles Causes and Treatments of Migraine and Related Headaches; Migraine Headache in Children; Migraine Headaches, Vision Effects; and Understanding Migraine and Cluster Headache Medications.

MISCELLANEOUS

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Medical/Legal Pitfalls

• One of the common errors would be to simply consider that a neurologic deficit occurring at the time of a throbbing headache with GI symptoms is by definition a migraine with aura. These cases need to be thoroughly characterized and investigated if the description does not fit the classic picture of migraine with aura.

Special Concerns

• The possibility of pregnancy should be considered in the appropriate setting especially if prophylactic medication is prescribed.

MULTIMEDIA

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Media file 1:  Trigeminovascular system. The trigeminal nerve fibers around basal cerebral and meningeal vessels are triggered (various stimuli are possible), and a vicious circle starts where the nerve terminals release calcitonin gene-related peptide (CGRP), substance P, vasoinhibitory peptide (VIP), and other mediators of local neurogenic inflammation and vasodilatation. The latter further stimulates the nerve endings. On the other end of the nerve, painful messages are transmitted toward central centers, including thalamus and cortex, and the sensation of pain arises. Modern drugs, such as the triptans, act at 3 levels, via 5-HT 1 B and D receptors; they vasoconstrict the vessels, they reduce the release of the above-mentioned mediators, and they decrease the central transmission of pain impulses.
	View Full Size Image
Media type:  Image

REFERENCES

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Article Last Updated: May 9, 2006