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Primary Headache Disorders
Migraine is the second most common primary headache disorder and has a prevalence of about 12%. It affects women disproportionately (approximately 18.2% of women versus 6.5% of men in the United States) and commonly afflicts the population during the most productive years of life (peak prevalence, 25 to 45 years old).
Migraine falls into two categories: migraine without an aura (previously called common migraine), which occurs in about 85% of patients, and migraine with an aura (previously called classic migraine), which occurs in about 15% of patients. Migraine patients with and without an aura may report prodromal symptoms that begin 24 to 48 hours before a headache attack. These symptoms can include hyperactivity, mild euphoria, lethargy, depression, craving for certain foods, fluid retention, and frequent yawning. Prodromal symptoms should not be confused with the migraine aura that consists of transient episodes of focal neurologic dysfunction appearing 1 to 2 hours before the onset of a migraine headache and resolving within 60 minutes. The aura symptoms may be of different types, and more than a single symptom type may be present within a given aura. Typical aura symptoms include homonymous (rarely monocular) visual disturbance, classically an expanding scotoma with a scintillating margin; unilateral paresthesias and or numbness, often affecting the distal ends of the extremities or the perioral region of the face; unilateral weakness; and dysphasia or other language disturbances. Sometimes aura symptoms localize to the brain stem and may include vertigo, dysarthria, tinnitus, fluctuating hearing loss, diplopia, bilateral weakness, ataxia, bilateral paresthesias, and a decreased level of consciousness. Basilar migraine is the diagnosis in patients in whom brain stem symptoms predominate. In many patients, basilar attacks are intermingled with more typical migraine attacks. Dizziness is frequently reported as a feature of an otherwise typical attack of migraine without an aura. Bilateral paresthesias can also occur with anxiety and hyperventilation.
The headache phase of a migraine attack (with or without aura) consists of 4 to 72 hours of unilateral throbbing head pain that is of moderate to severe intensity, that is worsened by routine physical exertion, and that is associated with nausea, photophobia, and phonophobia. Complicated migraine or migraine with a prolonged aura refers to migraine attacks associated with aura symptoms that persist for more than 1 hour but less than 1 week with normal neuroimaging studies. If symptoms persist for more than 1 week or result in neuroimaging abnormalities, migrainous infarction is likely. In general, migrainous infarction develops in the context of stereotypic aura symptoms.
Migraine attacks that persist for longer than 72 hours despite treatment are classified as status migrainosus . During status migrainosus, headache-free periods of less than 4 hours (sleep not included) may occur. Status migrainosus is usually associated with prolonged use of analgesics and may require inpatient treatment with detoxification.
A higher than expected prevalence of migraine has been observed in the relatives of migraine patients. In one large family study drawn from the general population, the risk of migraine in relatives of patients with migraines was three times higher than the risk among controls. Data from large twin registries have consistently revealed higher concordance rates for migraine in monozygotic twins than in dizygotic pairs. One study of more than 2500 monozygotic and 5000 dizygotic twin pairs estimated that 40 to 50% of the susceptibility to migraine is genetically based. Although migraine is widely thought to reflect an autosomal dominant condition, segregational analysis has failed to identify any single mendelian pattern of transmission. During the past few years, several novel migraine susceptibility genes have been identified in families by linkage analysis. These novel polymorphisms map to loci on chromosomes 1 (19p13), 6 (6p12.2-21.1), X(Xq24-28), and 4(q24) for the more common types of migraine, whereas loci for uncommon subtypes have been proposed on chromosomes 19(p13) and 1(q21-23;1q31), as discussed later.
Perhaps the most compelling genetic evidence to date comes from the identification of specific gene loci for familial hemiplegic migraine. Familial hemiplegic migraine is an autosomal dominant disorder characterized by transient hemiplegia
Migraine therapy includes nonpharmacologic and pharmacologic interventions. Nonpharmacologic treatment includes behavior modification techniques such as the avoidance of triggering factors (e.g., the ingestion of particular foods or food additives, strong smells, glaring light) and establishment of regular meals and consistent sleeping patterns. Other techniques to minimize the effects of environmental stress, such as biofeedback, relaxation training, rational motive therapy, self-hypnosis, and meditation, are sometimes helpful.
Pharmacologic treatment of migraine includes abortive therapy given to shorten the attack or decrease the severity of the headache. In patients with infrequent and uncomplicated attacks, abortive medications are often sufficient. If migraines cause disability more than 3 days per month, daily prophylactic treatment may be taken to decrease the frequency and, less often, the severity of attacks. If taken at the time of attacks, prophylactic agents are usually ineffective, and agents used for treatment during an attack provide little protection against subsequent attacks. The use of analgesic medications for more than 3 days per week (including over-the-counter formulations) may increase headache's frequency and severity. In some cases, intermittent migraine progresses to a syndrome of daily severe headaches despite the use of escalating prophylactic medication or analgesics. Only nonsteroidal anti-inflammatory drugs (NSAIDs), ergotamine, and valproic acid are useful during an attack and for prevention.
Patients should be provided with a variety of treatments that may be taken in a manner appropriate to the severity of their symptoms. Mild attacks may be treated with simple analgesics such as acetaminophen (suggested dose, 650 to 1000 mg) or NSAIDs (aspirin, 900 to 1000 mg; ibuprofen, 1000 to 1200 mg; naproxen, 500 to 825 mg; and ketoprofen, 100 to 200 mg). Mild to moderate attacks during pregnancy may be treated with acetaminophen if nonpharmacologic treatments are ineffective. Moderate headaches may respond to the combination of acetaminophen, isometheptene mucate (a mild vasoconstrictor), and dichloralphenazone (a mild sedative). Infrequent headaches of moderate to severe intensity may be treated with butalbital, a barbiturate, combined with caffeine, aspirin, or acetaminophen. Oral opiates have little place in the treatment of chronic, recurrent, primary headaches and should be avoided until alternatives, including NSAIDs and serotonin agonists such as dihydroergotamine or sumatriptan, have been considered. However, opiates may be the only viable option during pregnancy or in patients with severe vascular disease; if so, they should be used with caution, and the risks associated with opiate use, including rebound headaches and dependency, should be discussed with patients before treatment is initiated.
A number of abortive agents with vasoconstrictive properties are available, but patients with uncontrolled hypertension or a history of coronary artery disease or angina should not be given any of these drugs. Moderate to severe attacks may be treated outside the hospital with dihydroergotamine (1 to 2 mg intranasally), with oral, intranasal, or subcutaneous formulations of 5-HT
Very severe attacks sometimes require the administration of intravenous or intramuscular agents in the emergency department. Dihydroergotamine, an injectable hydrogenated ergot, has less potent peripheral arterial vasoconstrictive effects than ergotamine and is usually effective even when given well into an attack. Dihydroergotamine may be administered subcutaneously or intravenously. Given intravenously, dihydroergotamine causes less nausea than ergotamine does, but an antiemetic is still required before intravenous use. Meperidine, an opioid analgesic, is frequently administered intramuscularly, especially in combination with an antiemetic, to treat severe migraine attacks. With alternatives available, the use of parenteral opioids should be limited to patients with infrequent, severe attacks for whom other treatments are contraindicated. The recent identification of 5-HT
For patients who are nonresponsive or have contraindications to vasoactive abortive agents, intravenous neuroleptics may be given to treat severe or prolonged migraine attacks. Intravenous chlorpromazine, 10 mg, may be used in this setting and repeated in 1 hour if no response is seen.
In general, preventive treatment is recommended if headaches limit work or normal daily activity 3 or more days per month, if the symptoms accompanying headache are severe or prolonged, and if previous migraine was associated with a complication (e.g., cerebral infarction). Preventive treatment is largely empiric, and the drugs currently used were discovered serendipitously while being developed for the treatment of other disorders. Increased appetite and weight gain are common side effects of most prophylactic agents. Treatment should be initiated at low doses and gradually titrated to headache improvement or the onset of side effects. Groups 1 to 5 are generally considered first-line agents and tend to be associated with fewer or less potentially serious side effects. The prophylactic agents fall into seven groups:
β-Adrenergic blockers: propranolol (40 to 240 mg), atenolol (50 to 150 mg), nadolol (20 to 80 mg), timolol (20 to 60 mg), and metoprolol (50 to 300 mg)
NSAIDs: aspirin (1000 to 1300 mg), naproxen (480 to 1100 mg), ketoprofen (150 to 300 mg)
Tricyclic antidepressants: amitriptyline (10 to 120 mg), nortriptyline (10 to 75 mg)
Calcium channel antagonists: verapamil (120 to 480 mg), flunarizine (5 to 10 mg)
Anticonvulsants: divalproex sodium (750 to 1000 mg), gabapentin (900 to 1800 mg), topiramate (100 to 400 mg)
Serotoninergic drugs: methysergide (4 to 8 mg), cyproheptadine (8 to 20 mg)
Monoamine oxidase inhibitor: phenelzine (30 to 60 mg)
Angiotensin II receptor blocker: candesartan (16 mg)
Unfortunately, comparative data on prophylactic treatments are sparse, and the decision to use one versus another is currently most often based on the practitioner's experience or the presence of comorbid illnesses, which would be an indication or contraindication to a specific type of drug.
Cluster headache, which is much less common than tension-type headache or migraine, affects 0.4 to 2.4 persons per 1000 in the general population. Unlike patients with migraine headaches, patients with cluster headaches usually seek medical consultation because of the intense pain that accompanies their attacks. As a result, physicians encounter cluster headache more commonly than would be predicted from its actual prevalence. The condition is more common in men than in women (male-to-female ratio of 6:1) and usually begins in the third through the sixth decades of life. Although cluster headaches may cease during pregnancy, attacks seldom correlate with menses.
Cluster headaches consist of recurrent episodes of unilateral, orbital, supraorbital, or temporal head pain usually accompanied by ipsilateral autonomic signs, including conjunctival injection, lacrimation, rhinorrhea, nasal congestion, ptosis, miosis, eyelid edema, and facial sweating. The attacks last 15 minutes to 3 hours and occur as infrequently as every other day to as frequently as eight attacks per day. The syndrome derives its name from the characteristic clusters, or periods of frequent headache, that last weeks to months and are separated by periods of months or years of headache-free remission. Chronic symptoms without remission may develop in about 10% of patients. During a cluster period, the headache attacks often assume a temporal cyclicity, with occurrence at almost the same time every day. Exposure to small amounts of nitrates or alcohol may trigger an acute attack during a cluster period.
The cause of cluster headaches is not defined. Like other vascular headaches, they are presumed to develop from events that ultimately activate the trigeminovascular system. In the complete form of the disease, patients with cluster headache manifest pain referred to the first and second trigeminal divisions, sympathetic dysfunction (i.e., Horner's syndrome), sympathetic activation (i.e., sweating of the forehead and face), and parasympathetic activation (i.e., lacrimation and nasal congestion). This constellation of symptoms and signs is best explained by the presence of a single lesion at the point at which fibers from the ophthalmic and maxillary trigeminal division converge with projections from the superior cervical and sphenopalatine ganglia. This plexus is located within the cavernous sinus, and narrowing of the cavernous carotid artery has been observed in selected cases of cluster headache. PET-based functional imaging studies of blood flow during acute cluster attacks show areas of increased flow in the inferior portion of the hypothalamus on the same side as the headache. This finding is consistent with the clinical cyclicity exhibited by cluster headaches reported by many patients.
There is an increased concordance of cluster headache in monozygotic twins. Moreover, studies of relatives of patients with cluster headache have found a frequency 13 times higher than expected by chance.
During cluster headaches, oxygen inhalation (100%) delivered at a rate of 8L/minute for 15 minutes through a loose-fitting face mask is a safe and effective treatment for acute attacks, particularly in patients younger than 50 years who have episodic cluster headaches. Patients who respond to oxygen usually do so within 10 minutes. Inhalation of oxygen does not cause nausea and is not contraindicated in patients with coronary artery disease or peripheral vascular disease. Ergotamine tartrate, the classic treatment of cluster headache, is effective and well tolerated by many patients. Because of more rapid absorption, sublingual administration is generally preferred to oral administration. Intranasal dihydroergotamine reduces the severity of cluster headaches, but not their duration. Subcutaneous administration of sumatriptan (6 mg) is usually successful in alleviating acute cluster headaches and reduces pain and conjunctival injection within 15 minutes in most patients. Vasoconstrictive medications such as ergotamines and sumatriptan should be used with caution for cluster headache in patients who are at increased risk for coronary artery disease.
Ergotamine tartrate was for many years the only prophylactic agent used for cluster headache. It is effective and well tolerated in doses of 2 to 4 mg/day given orally or by suppository. The ergot derivative methysergide is effective in about 70% of episodic cases. Retroperitoneal, pleural, or pericardial fibrosis is a severe potential side effect of long-term use. Because patients with cluster headache usually require treatment for less than 2 to 3 months, methysergide can be used with more safety than in migraine. Lithium carbonate, which was effective in chronic cluster headache in more than 20 open-label clinical trials, may also be beneficial in the episodic form of the disease. Because of the narrow range between toxic and therapeutic doses, it is important to monitor the serum lithium level 12 hours after the last dose. The usual therapeutic range is from 0.3 to 0.8 mmol/L, but low lithium levels may still be therapeutic. NSAIDs and thiazide diuretics may increase serum lithium levels. Average daily doses of lithium carbonate (600 to 900 mg) should be titrated according to the serum lithium level. Verapamil is often effective as a prophylactic agent against cluster headache; it has relatively few side effects when compared with other prophylactic agents, and a double-blind trial found it to be as effective as lithium. Prophylactic medication dosages are usually tapered and then discontinued within 3 to 6 weeks after recurrent cluster headaches cease.
Corticosteroids are frequently used to treat the episodic and the chronic forms of cluster headache, even though evidence for their effectiveness is largely limited to open trials. Prednisone is frequently used in dosages of 60 to 80 mg/day for 1 week, followed by a taper in dosage over a period of 2 to 4 weeks.
Tension-type headache is the most common of the primary headache disorders, with a lifetime prevalence between 30 and 78%. Tension-type headaches are more common in women than in men and most often begin in the second decade of life. In both sexes, the prevalence decreases with increasing age, and socioeconomic factors do not contribute to risk. Although no studies have been conducted in twins, genetic factors are not as prominent in the condition as in migraine or other headache syndromes.
Tension-type headache is not well understood and defies a single or simple pathophysiologic explanation. In one model, headache pain is viewed as the sum of nociceptive input onto brain stem neurons from vascular structures, myofascial and muscular sources, and descending supraspinal modulation. The relative importance of these three factors varies among patients and among attacks in the same patient.
Tension-type headache occurs in episodic and chronic forms, which differ in their response to treatment and possibly in their pathophysiology. Pericranial muscle spasm or tenderness may or may not be present in either form. Episodic tension-type headache consists of recurrent attacks of tight, pressing (band-like), bilateral, mild to moderate head pain that last from minutes to days. Tension-type headaches do not worsen with routine physical exertion and are not associated with nausea, although photophobia or phonophobia may be present. In the chronic form, characteristic tension-type headaches occur at least 15 days per month.
Episodic tension-type headaches usually respond to simple analgesics such as acetaminophen (650 to 1000 mg) or to NSAIDs such as aspirin (900 to 1000 mg), ketoprofen (12.5 to 75 mg), ibuprofen (200 to 800 mg), and naproxen (250 to 500 mg). More severe, episodic tension-type headaches may respond to higher doses of NSAIDs or to combination remedies that contain isometheptene mucate or butalbital. Frequent use of analgesics can increase the number of headaches, so caution is advised whenever analgesic use regularly exceeds three days per week. Chronic tension-type headaches occasionally require prophylactic treatment. Tricyclic antidepressants decrease the frequency and the severity of attacks; amitriptyline is the drug of choice. Amitriptyline's use may be limited by sedation, dry mouth, or other anticholinergic side effects. To avoid these side effects, therapy should be started at low doses (10 mg) given at bedtime and increased slowly until satisfactory improvement is achieved or intolerable side effects appear. Nortriptyline, doxepin, maprotiline, and fluoxetine are other antidepressants that are sometimes effective in chronic tension-type headache.
The term chronic daily headache may be applied to any headaches occurring more than 15 days per month for at least 1 month. By this definition, the term includes several clinically distinct syndromes, including cluster headache, hemicrania continua, chronic paroxysmal hemicrania, and chronic tension-type headache. Chronic daily headache is often used more narrowly to include headaches that occur on a daily or almost daily basis (>4 days/week), have features of migraine and tension-type headache, and are frequently but not always associated with overuse of analgesic medications. Patients meeting these criteria account for a major proportion of those seen in headache specialty clinics and are often the most difficult headache patients to treat. The typical patient with chronic daily headache is a woman in her 30s or 40s with a history of episodic migraine or tension-type headache beginning in the teens or 20s. Over a period of months to years, the patient's headaches gradually increase in severity and frequency to the point where consecutive headache-free days are rare. The headaches are often of two types. More frequent headaches are of mild to moderate intensity and have a pressure-like or mildly throbbing quality and mild photophobia or phonophobia but no associated nausea or vomiting. The duration of these milder headaches is variable and ranges from several hours to constant (although waxing and waning). Superimposed are severe attacks that occur as frequently as three times per week and as infrequently as once or twice per month. The more severe attacks are usually, but not always, throbbing and may be associated with nausea, photophobia, phonophobia, and sometimes, vomiting. Severe attacks may be preceded by a migrainous aura. The patient often exhibits features of depression or anxiety. Frequently, the patient is taking one or more daily analgesics, sometimes in an effort to preempt a headache. Chronic daily headaches are called transformed migraine when the migrainous component is prominent. When headaches begin without antecedent migraine or tension-type headache but with many features of tension-type headache, they are often labeled new daily per sistent headaches. Chronic daily headache is often accompanied by other paroxysmal symptoms that are frequently as distressing as the head pain. These symptoms may include dizziness (i.e., vertiginous and nonspecific forms), tinnitus, extreme phonophobia, fluctuating fatigue or mood alteration, and feelings of depersonalization. It is unclear whether these symptoms are fragments of underlying migraine or a mood disorder; they often resolve with improvement in the headaches.
Overuse of medications is the most common exacerbating factor in chronic daily headache, and withdrawal of the overused medication usually improves the condition. The medications most often overused include butalbital combinations, ergotamines, oral analgesics containing caffeine in combination with acetaminophen or NSAIDs, and opiate combinations. However, chronic daily headache may develop in the absence of medication, and it does not always improve after analgesic withdrawal.
Chronic paroxysmal hemicrania is an uncommon syndrome with many features of cluster headache, including severe intensity, unilateral orbital or temporal location, and autonomic signs (e.g., conjunctival injection, tearing, rhinorrhea) ipsilateral to the pain. It is shorter in duration (5 to 20 minutes) than cluster headache and has a higher attack frequency (generally more than five per day). The syndrome is more predominant in females and may be responsive to indomethacin (150 mg/day or less).
Hemicrania continua is an unusual headache syndrome in which constant unilateral head pain of moderate to severe intensity underlies unprovoked brief episodes of sharp jabbing pain in a similar location.
Benign cough headache consists of severe bilateral head pain of sudden onset that follows coughing or other Valsalva maneuvers. It is a benign disorder that responds to indomethacin in about 90% of cases. However, the diagnosis of benign cough headache requires the exclusion of structural lesions with MRI because cough headache may sometimes result from posterior fossa tumors or the Arnold-Chiari malformation.
In some individuals, exertion or various types of exercise may trigger bilateral throbbing or pressure-like headaches that persist for several minutes up to 48 hours. Headaches may also develop during sexual activity, including coitus and, less frequently, during masturbation. These headaches usually begin with bilateral nonthrobbing pain that escalates as sexual excitement increases and reaches a crescendo at orgasm. Exertional and orgasmic headaches may occur in the absence of intracranial disorders; however, in rare cases, coital headache may be associated with unruptured cerebral aneurysms. The possibility of aneurysm should be excluded. Exertional headache can sometimes be prevented by ingestion of ergotamine or indomethacin before the planned exertion.
Hypnic headaches constitute a rare primary headache syndrome of the elderly (mean age of onset, 60 years or older). Hypnic headaches, which persist for 15 to 60 minutes and typically awaken patients from sleep about the same time each night, are in some ways similar to cluster headaches. However, unlike cluster headache, hypnic headaches are more diffuse, are often bilateral and throbbing, and are not associated with the autonomic symptoms of cluster headache. The differential diagnosis includes temporal arteritis and mass lesions. After exclusion of organic disease with an imaging study and erythrocyte sedimentation rate (ESR), treatment with low-dose lithium (30 mg every night) or caffeine may induce remission. If headaches return, careful titration of the dosage upward may be necessary. Lithium should be used with caution in older patients, especially in the presence of dehydration, renal disease, and diuretic or NSAID therapy.
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Cecil Textbook of Medicine, 22nd ed.
By: F. Michael Cutrer, Michael A. Moskowitz © 2005 ELSEVIER Inc. All Rights Reserved |
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