Etiology and Pathogenesis

The pathophysiology of headache is not fully understood. The blood vessels and meninges sense pain but refer it to the anterior or posterior scalp, explaining why pain from multiple etiologies and locations can feel similar.

The mechanism of migraine pain has been studied most extensively. Cortical spreading depression, which is associated with aura, is a rapid depolarization of neurons followed by prolonged hyperpolarization, which propagates as a wave through brain. This leads to release of ions, prostaglandins, and amino acids that irritate axon collateral nociceptors in the pia and dura mater. These nociceptors activate trigeminal and parasympathetic pain afferents in meningeal vessels, causing meningeal artery dilatation and activation of the trigeminal ganglion and then the trigeminal nucleus caudalis. The messages cross in the brainstem and continue to the ventroposterior thalamus, causing the sensation of pain (Figure 75-1).

Figure 75-1 Pathophysiology of migraine.

Clinical Presentation

Headaches have a wide variety of causes. Although many headaches are caused by primary headache syndromes, most commonly migraine and tension-type headache, an extensive history and physical examination must guide the differential diagnosis. Relevant elements of the history are listed in Table 75-1. The physical examination should include vital signs and general and neurological examinations, including visualization of the fundus. Table 75-2 outlines characteristics of many primary and secondary headaches, the recommended workup, and treatment where applicable.

Table 75-1 Headache History

MSG, monosodium glutamate.

Evaluation and Management

See Table 75-2 for workup based on specific to etiology. Indications for imaging are summarized here. Generally, magnetic resonance imaging (MRI) is preferred because it provides more detail, but CT is appropriate when looking for bony changes or bleeding or in emergent situations when MRI is not available. MR angiogram (MRA) and MR venogram (MRV) are sometimes important to obtain with MRI of the brain.

Imaging is necessary before lumbar puncture if a patient has an abnormal physical examination result to ensure that it is safe to perform lumbar puncture (no signs of herniation nor significant edema). Indications for lumbar puncture (with opening pressure) include:

Treatment

Treatment should be guided by the cause of the headache, and many of those are mentioned in Table 75-2. Most research in children has studied the use of medications for acute and preventive treatment of migraine.

Abortive Medications

These should be used at most two to three times per week to prevent medication overuse, which may transform headache from episodic to chronic. All abortive therapies should be given as soon as possible after symptom onset to maximize efficacy. Other than analgesics, studies of efficacy pertain to patients with migraine headache, and the intravenous (IV) therapies listed are generally for migraine except as noted above.

• Analgesics: remind patients of side effects; many of these are available over the counter.

• Nonsteroidal antiinflammatory drugs (NSAIDs): contraindicated in renal disease or history of gastrointestinal (GI) bleeding

• Ibuprofen

• Naproxen

• Ketorolac

• Acetaminophen: contraindicated in liver disease

• Except when other medications are contraindicated, opiates and preparations with caffeine should be avoided because they can be detrimental long term.

• Triptans: These are contraindicated in cardiovascular and liver disease, pregnancy, hemiplegic migraine, and patients with hypertension. Studies of triptans in teens with migraine have been limited by their extremely high response to placebo, making it difficult to prove statistical significance. Side effects include taste disturbance (for nasal sprays), burning (for injections), drowsiness, nausea or vomiting, dizziness, tingling, flushing, and infrequent chest tightness.

• Sumatriptan (Imitrex): oral, subcutaneous, nasal effective in adolescents

• Sumatriptan + naproxen (Treximet): no pediatric data

• Rizatriptan (Maxalt): effective but no more than placebo

• Eletriptan (Relpax): effective but no more than placebo

• Zolmitriptan (Zomig): oral and nasal effective in adolescents

• Almotriptan (Axert): oral effective in adolescents

• Naratriptan (Amerge): no pediatric data

• Frovatriptan (Frova): pharmacokinetic data only in adolescents.

• DHE (dihydroergotamine): contraindicated in cardiovascular, renal, liver disease, pregnancy, hemiplegic migraine, and patients with hypertension or recent triptan use. Open-label case series of intravenous DHE in children have shown that it is effective for the treatment of status migrainosus.

• Intranasal, subcutaneous, IV, intramuscular

• Side effects include nausea or vomiting (can be prevented by premedication with an antiemetic), vasoconstriction.

• Antiemetics: efficacious for migraine even in the absence of significant nausea. Side effects include dystonic reaction, which usually responds to diphenhydramine. Limited pediatric data.

• Prochlorperazine (Compazine)

• Metoclopramide (Reglan)

• Steroids: Limited data; a variety of doses are used. Use caution in patients with hypertension, renal disease, diabetes, active infections, and history of GI bleeding. Short-term side effects include increased appetite, weight gain, irritability or mood changes, insomnia, hyperglycemia.

• Prednisone

• Dexamethasone

• Anticonvulsants: see valproic acid below

Preventive Medications

Very little data are available on children. The best evidence for migraine prophylaxis is with amitriptyline, topiramate, and valproic acid.

• Antidepressants

• Amitriptyline

• Side effects: sedation (advise taking 2–3 h before bed), dry eyes, dry mouth, urinary retention, constipation (patients should drink plenty of water), worsening of underlying prolonged QT (check electrocardiogram [ECG] before starting), weight gain

• Other tricyclic antidepressants may have fewer side effects; these have not been studied in children

• Antiepileptics

• Topiramate

• Side effects: metabolic acidosis causing tingling (can treat with vitamin C or sodium bicarbonate supplementation), oligohidrosis or hyperthermia, weight loss, cognitive dulling and word-finding problems, uncommon kidney stones, blurred vision

• Valproic acid

• Oral for prophylaxis; can use IV to treat status migrainosus.

• Side effects: hepatic and pancreatic dysfunction, anorexia or weight gain, teratogenic, tremor, hair loss, may be linked with polycystic ovarian syndrome

• Gabapentin, lamotrigine, levetiracetam, zonisamide, carbamazepine are also used

• NSAIDs: contraindicated in renal disease or history of GI bleeding

• Naproxen: see above; prophylactic use in menstrual or other predictable headache

• Indomethacin: for hemicrania continua and paroxysmal hemicrania

• Antiserotonergic

• Cyproheptadine (may also work as calcium channel blocker and is an antihistamine)

• Side effects: sedation, appetite stimulation, weight gain

• Antihypertensive

• Calcium channel blockers

• Flunarizine has good evidence but is not available in the United States; consider verapamil

• Side effects: sedation, weight gain, depression, constipation, arrhythmia (check ECG); contraindicated in patients with heart failure

• β-Blockers (data thus far does not show clear efficacy)

• Side effects: decreased exercise tolerance, hypotension or orthostasis, low energy, depression, vivid dreams, contraindicated in patients with asthma or existing depression

• Acetazolamide: limited pediatric data

• Side effects: metabolic acidosis causing tingling (can treat with vitamin C or sodium bicarbonate supplementation), altered taste sensation, drowsiness, nausea, uncommon kidney stones

• Nonpharmaceutical

• Riboflavin (vitamin B2): limited pediatric data; adult studies have been mixed

• Side effects: turns urine bright yellow, diarrhea, polyuria

• Magnesium: uncontrolled pediatric studies have been positive; one randomized, controlled trial (RCT) was equivocal

• Side effects: diarrhea, GI upset

• CoQ10: no RCT, open-label pediatric study in patients found to be deficient showed improvement in headache frequency and disability as level normalized

• Side effects: stomach upset, procoagulant (may decrease efficacy of Coumadin)

• Butterbur: no RCTs; uncontrolled study of children found decreased frequency of migraine

• Side effects: burping, plant is toxic and can cause hepatic and pulmonary necrosis, cancer, and coagulopathy, so must use brand Petadolex, which is extracted without toxic alkaloids

Nonpharmacologic Therapies

These can be the mainstay of therapy or can complement medications.

• Lifestyle changes and avoidance of triggers: although these efforts are time consuming, they are very safe and can be quite effective. If patients find a lifestyle trigger, they often benefit from recognizing its predictability (Figure 75-3).

• Sleep hygiene: sufficient sleep, consistent bedtime and wake-up time

• Diet

• Avoid fasting; eat regularly

• Avoid dehydration; drink at least 72 oz/d of noncaffeinated fluids

• There is poor evidence for some things thought of as common dietary triggers such as chocolate; the best evidence is for caffeine, alcohol or wine, and monosodium glutamate.

• Exercise: believed to be preventive (not tested)

• Stress: recognition of stressful life events at home and school, improvement of situation where possible, learning coping mechanisms (see below); stress letdown can also trigger headaches

• Hormonal fluctuations: can be anticipated; may be appropriate to use prophylaxis for a few days around the time headache predicted

• Weather: can be anticipated; barometric changes are usually too frequent to use intermittent prophylaxis

• Odors: avoidance of smoke and perfumes

• Psychological therapies

• Meta-analysis of studies of relaxation, cognitive behavioral therapy, and biofeedback in children concluded that there is good evidence that they are effective at reducing headaches

• Biofeedback has been shown to be effective in children as young as 9 years of age

• A listing of certified biofeedback practitioners is available at http://www.bcia.org

• Acupuncture: small pediatric trials, some uncontrolled, have shown a trend in reduction of headache frequency and severity for both migraine and tension-type headache

Figure 75-3 Triggers of migraine.

Future Directions

Most of the therapies used to treat pediatric headache are used off label, and there are limited supportive data. Furthermore, studies of pediatric headache are limited by the use of adult classification schemes, which do not entirely represent pediatric headaches. Moving forward, additional research should help to characterize the efficacy of current therapies and shed light on newer treatments such as nerve blocks and botulinum toxin that as of yet are used almost exclusively in adults.