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Headache

Migraine affects 15% to 17% of women and 6% of men. During migraine attacks, the "migraine generator" of the brain stem site becomes activated, then the trigeminal nerve, which innervates the larger cerebral vessels, releases serotonin and vasoactive peptides. These substances cause inflammation of the dura mater and cranial blood vessels, resulting in the symptoms of migraine.

Common Benign Headache Syndromes

Migraine

Migraine headache is often associated with nausea, vomiting, diarrhea, fatigue, and mood changes. A prodrome that begins up to 24 hours before headache onset may also occur. Photophobia, phonophobia, food cravings, mood changes, myalgia, and paresthesia may also be observed.

Migraine without aura occurs in two-thirds of patients, manifesting as attacks that last 4 to 72 hours. The attacks may recur daily, weekly, or monthly. The headache is unilateral, pulsating, of moderate or severe intensity, and aggravated by physical activity. Nausea and/or vomiting, photophobia, and phonophobia usually accompany the headache.

Migraine with aura occurs in one third of migraineurs. Aura is a warning sign of an impending migraine attack, which is often visual and may consist of flashing or zigzagging lights, a blind spot (scotoma), partial visual field loss (hemianopia), or distortion of the shape or size of objects (metamorphopsia). The aura may be accompanied by numbness or tingling in the upper extremities, face, or neck. Aura duration rarely exceeds 1 hour.

Cluster headache is an uncommon headache, which is five times more prevalent in men than in women. It is a severe, unilateral, periorbital pain that lasts 30 to 60 minutes. Onset is sudden and pain intensity increases rapidly. Resolution of the pain is sudden and dramatic. Patients may have one to three headaches per day. Associated symptoms include unilateral rhinorrhea, lacrimation, eyelid edema, ptosis, and nasal stuffiness.

Tension-type headache is a steady, aching pain of mild to moderate intensity, often characterized as a band-like pain around the head. Gastrointestinal and neurologic signs and symptoms usually do not occur.

Potential Causes of Headache

Category

Cause

Primary headache

Migraine, tension-type, cluster headache

Headache associated with trauma

Concussion, subdural hematoma, post-traumatic headache

Headache associated with vascular disorders

 

 

Ischemic stroke, subarachnoid or intracranial hemorrhage, vascular malformation, giant cell arteritis, carotid artery distention, systemic or primary central nervous system vasculitis, malignant hypertension, pheochromocytoma, cerebral venous thrombosis, preeclampsia or eclampsia

Headache associated with changes in cerebrospinal fluid pressure

Pseudotumor cerebri, post-spinal tap headache

Headache associated with intracranial infection

Meningitis, encephalitis, brain abscess, subdural empyema

Substance abuse or withdrawal headache

Ergotamine, abuse of analgesics (especially narcotics), carbon

monoxide, alcohol, caffeine

Headache associated with metabolic disorders

High-altitude sickness, sleep apnea, hypoglycemia

Headache associated with intracranial neoplasm

Primary or metastatic cancer

Headache associated with noncranial structures

Cervicogenic headache, acute angle-closure glaucoma, sinusitis, refractive errors, temporomandibular joint disease

Cranial neuralgia

Trigeminal neuralgia, postherpetic neuralgia

Headaches Caused by Serious Underlying Disease

Fewer than 1% of headaches are caused by serious underlying disease. A neuroimaging study is warranted when the history or physical suggest an underlying disease.

Subarachnoid Hemorrhage. A headache occurs in 50% of patients with subarachnoid hemorrhage, often described as the worst headache they have ever had. The headache is very localized, and meningismus, paresis of the third, fourth, or sixth cranial nerve, nausea, vomiting, altered mentation, and loss of consciousness may occur. A CT scan is essential when subarachnoid hemorrhage is suspected.

Giant Cell Arteritis

Giant cell arteritis is an autoimmune-type process, most commonly affecting the temporal artery. The inflammation may cause headache, infarction of the optic nerve, and blindness.

It almost always occurs after age 50 and is 5 to 10 times more prevalent in women. Tenderness of the temporal artery, jaw claudication, sudden onset of partial or complete blindness, and fever and weight loss may be present. The erythrocyte sedimentation rate often exceeds 50 mm/hr. Temporal artery biopsy is diagnostic, and treatment with high-dose corticosteroids is effective.

Tumors or Mass Lesions

A tumor may rarely cause headaches. Distinguishing features include focal neurologic signs, papilledema, mental status changes (eg, diminution in level of consciousness), personality changes, and seizures. In some patients, however, the neurologic examination is completely normal.

The classic presentation is a holocranial headache which is most severe in the morning on rising. Increased intracranial pressure can cause vomiting. A neuroimaging study is required whenever a tumor or mass-producing lesion is suspected.

Clinical Evaluation of Headache

Initial evaluation should exclude the presence of urgent, life-threatening conditions. If the results of the physical examination (including the neurologic examination) are normal, performance of additional diagnostic tests is not usually necessary.

Features of Migraine Headache and Headache Caused by Serious Underlying Disease

Migraine headache

Headache caused by serious underlying disease

History

• Chronic headache pattern similar from attack to attack

• Gastrointestinal symptoms

• Aura, especially visual

• Prodrome or postdrome

• Onset before puberty or after age 50 (tumor)

• "Worst headache ever" (subarachnoid hemorrhage)

• Headache occurring after exertion, sex, or bowel movement (subarachnoid hemorrhage)

• Headache on rising in the morning (increased intracranial pressure, tumor)

• Personality changes, seizures, alteration of consciousness (tumor)

• Pain localized to temporal arteries or sudden loss of vision (giant cell arteritis)

• Very localized headache (tumor, subarachnoid hemorrhage, giant cell arteritis)

Physical examination

• No signs of toxicity

• Normal vital signs

• Normal neurologic examination

• Signs of toxicity (infection, hemorrhage)

• Fever (sinusitis, meningitis, or other infection)

• Meningismus (meningitis)

• Tenderness of temporal arteries (giant cell arteritis)

• Focal neurologic deficits (tumor, meningitis, hemorrhage)

• Papilledema (tumor)

Laboratory tests and neuroimaging

• Normal results

• Erythrocyte sedimentation rate >50 mm/hr (giant cell arteritis)

• Abnormalities on lumbar puncture (meningitis, hemorrhage)

• Abnormalities on CT or MRI (tumor, hemorrhage, aneurysm)

 

Treatment of Migraine

Nonpharmacologic therapy includes identification and avoidance of triggers for headaches, adequate sleep, and regular aerobic exercise. Biofeedback and stress reduction techniques may also be useful.

Triggers or Risk Factors for Migraine

Hormonal changes

Hormone replacement

Menstruation

Oral contraceptive therapy

Pregnancy

Foods/Ingredients

Aged cheese

Alcohol

Artificial sweeteners

Caffeine (coffee, cola, tea)

Chocolate

Concentrated sugar

Fermented, pickled foods

Monosodium glutamate

Nitrates (cured meats)

Sulfites

Vegetables (beans, olives, onions, pickles, snow peas)

Exercise or exertion

Eye strain

Irregular exercise

Environmental factors

Too much or too little sleep

Bright or flashing lights

Emotion (stress, anger, depression, fatigue, anxiety)

Missed meals (hypoglycemia)

Smoke

Pharmacologic therapy for migraine is divided into acute and preventive therapies. Acute therapy is initiated at the onset of or during an attack to relieve headache pain. Preventive therapy consists of the daily use of a medication to reduce the frequency of attacks. Such therapy should be considered when attacks occur more frequently than two times per month or when attacks are severe.

Acute therapies for migraine

Drug

Dosing

Common side effects

5-Hydroxytryptamine agonists

Sumatriptan ( Imitrex), SQ

6 mg, repeat as needed after 2-4 hr

Sedation, atypical sensations, cardiovascular symptoms, chest tightness and pressure

Sumatriptan (Imitrex), oral

25, 100 mg, repeat as needed after 4 hr

Atypical sensations, cardiovascular symptoms

Sumatriptan (Imitrex), nasal

20 mg, repeat as needed

Nasal discomfort, bad taste, atypical sensations, cardiovascular symptoms

Zolmitriptan ( Zomig), oral

1, 2.5, or 5 mg, repeat for recurrent headache

Nausea, dizziness, somnolence, paresthesia

Naratriptan ( Amerge), oral

2.5 mg, repeat as needed in 4 hr

Same as zolmitriptan

NSAIDs

Ibuprofen ( Motrin)

400-800 mg, repeat as needed in 4 hr

GI upset and bleeding, rebound headache

Naproxen sodium ( Anaprox DS)

550-825 mg, repeat as needed in 4 hr

Same as above

Butalbital combinations

Aspirin 325 mg, caffeine 40 mg, butalbita l 50 mg ( Fiorinal)

2 tablets, followed by 1 tablet q4-6h as needed

Drowsiness, light-headedness, sedation, nausea, rebound headache

Acetaminophen 325 mg, caffeine 40 mg, butalbital 50 mg ( Esgic, Fioricet)

2 tablets, followed by 1 tablet q4-6h as needed

Same as above

Acetaminophen 325 mg, butalbital 50 mg ( Phrenilin)

2 tablets, followed by 1 tablet as q4-6h needed

Same as above

Isometheptene combination

Isometheptene 65 mg, acetaminophen 325 mg, dichloralphenazone 100 mg ( Midrin)

2 tablets, followed by 1 tablet as needed q4-6h prn

Dizziness, rash, rebound headache

Ergot alkaloids

Ergotamine tartrate 1 mg, caffeine 100 mg ( Wigraine), oral

2 tablets, repeat as needed after 1 hr as needed

Nausea, vomiting, abdominal pain, paresthesia, muscle cramps, rebound headache

Ergotamine tartrate 2 mg ( Ergomar), SL

1 tablet, repeat as needed after 30 min

Same as above

Ergotamine tartrate 2 mg, caffeine 100 mg ( Cafergot), rectal

½ -1 suppository, repeat as needed after 3 hr

Same as above

Dihydroergotamine ( DHEA-45, Migranol), nasal

1-2 puffs, may be repeated in 60-90 minutes

Numbness, tingling, muscle pain in extremities, nausea, vomiting

Other

Metoclopramide ( Reglan), oral

5-10 mg as needed for nausea

Restlessness, drowsiness, fatigue

Butorphanol ( Stadol NS), nasal

1-2 puffs, may be repeated in 60-90 minutes

Drowsiness, dizziness and other opioid side effects

Acute Therapy

5-HT (Serotonin) Agonists

These agents have high affinity and selectivity for 5-HT1B/1D-receptor subtypes, which are located on intracranial vessels.

Sumatriptan (Imitrex). The oral preparation causes fewer side effects than the subcutaneous preparation. Side effects include sedation, chest pressure, heaviness, tightness, or pain. Sumatriptan is contraindicated in coronary artery disease.

Zolmitriptan ( Zomig). A 2.5-mg dose of zolmitriptan provides consistent relief of acute migraine with and without aura. Zolmitriptan is effective in migraineurs who have not responded to nonsteroidal anti-inflammatory drugs (NSAIDs) and sumatriptan.

NSAIDs are fairly effective against mild headache. All NSAIDs cause gastrointestinal upset and peptic ulcer disease.

Butalbital Combinations. The barbiturate, butalbital, combined with aspirin and caffeine (eg, Fiorinal), acetaminophen and caffeine (eg, Esgic, Fioricet), or acetaminophen (eg, Phrenilin) is widely used to treat migraine. Dosing generally is one to two tablets at headache onset followed by an additional tablet every 4 to 6 hours as needed for headache relief. Total daily and weekly doses should be limited to minimize the risk of rebound headache.

Isometheptene. The combination drug containing the vasoactive agent, isometheptene mucate, acetaminophen, and the mild tranquilizer dichloralphenazone ( Midrin) is used in acute therapy. Dosage is 2 tablets at headache onset, followed by 1 tablet every 4 hours as needed; maximum 5 tablets per day or 10 tablets per week.

Ergot Alkaloids. These agents are available in oral, sublingual, rectal, parenteral, and nasal formulations. Ergotamine is available alone in sublingual tablets and in combination with caffeine in oral tablets (eg, Wigraine) and rectal suppositories (eg, Cafergot). With oral ergotamine, less than 5% of a total dose is absorbed. Such poor bioavailability, in addition to the side effect of nausea and the gastroparesis frequently associated with migraine, yields inconsistent therapeutic benefits. The maximum recommended dose of ergot alkaloids is 6 mg per day or 10 mg per week. Side effects include nausea and vomiting, abdominal pain, paresthesia, and muscle cramps. These drugs are contraindicated in coronary artery disease and pregnancy.

Narcotics. Short-term use of narcotics such as butorphanol (Stadol NS) may be helpful for acute treatment of headaches which are refractory to other therapies.

Preventive Therapies for Migraine

Tricyclic antidepressants are effective for migraine prophylaxis. At least 4 to 6 weeks of therapy is required for an effect. The most common side effect of this class of drugs is sedation, which can be minimized by starting with a daily dose of 10 or 25 mg before bedtime. Other side effects include dry mouth, morning drowsiness, weight gain, constipation, and urinary retention.

Beta blockers are widely used to prevent migraine. The different agents offer similar effectiveness. Beta blockers may be considered first-line preventive therapy in migraineurs who have hypertension, but they are contraindicated in asthma, congestive heart failure, hypotension, diabetes, or peripheral vascular disease. Adverse effects fatigue, hypotension, bradycardia, depression, and impotence.

Divalproex ( Depakote) significant reduction in migraine frequency and intensity. Side effects include weight gain, hair loss, tremor, gastrointestinal upset, and sedation. Because of the risk of neural tube defects in offspring, contraception is required in women of childbearing age.

Preventive Therapies for Migraine

Tricyclic antidepressants

Nortriptyline ( Pamelor)

50-100 mg, at bedtime

Sedation, dry mouth, weight gain, constipation, urinary retention

Amitriptyline ( Elavil)

50-100 mg, at bedtime

Same as above

Desipramine ( Norpramin)

50-100 mg, at bedtime

Same as above

Trazodone ( Desyrel)

50-100 mg, at bedtime

Same as above

Convulsant

Divalproex (Depakote)

250 mg bid for 3 days, then 500-1000 mg bid

Weight gain, hair loss, tremor, GI upset, sedation

Beta blockers

Propranolol ( Inderal)

Propranolol LA ( Inderal LA)

40-60 mg PO bid-tid [40, 60, 80 mg]

80-160 mg PO qd [80, 120, 160 mg]

Fatigue, hypotension, bradycardia, depression, impotence

Timolol ( Blocadren)

20-60 mg

Same as above

Atenolol ( Tenormin)

50-150 mg PO qd [25, 50, 100 mg]

Same as above

Metoprolol ( Lopressor)

100-200 mg qd

Same as above

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