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Reviewed January 25, 2005

Robert S.
Kunkel, MD

Department of
Neurology

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Many causes of headache have been described in the medical literature over the years. In 1988, the International Headache Society published a long, detailed classification of headache, which has proved helpful for research purposes because it has led to more reproducible and reliable studies in the field of headache. This classification was recently revised and updated.¹ For practical clinical purposes, however, all headaches can be classified as one of the primary headache syndromes or as a headache that is caused by or secondary to an underlying disease process or condition.

Because primary headaches are the most common, this discussion focuses on the diagnosis and management of those syndromes.

Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Therapy

Outcomes

References

DEFINITION

None of these headaches are associated with demonstrable organic disease or structural neurologic abnormality. Laboratory and imaging test results are generally normal; however, if an abnormality is found, it most likely is not the cause of the headache. Similarly, physical and neurologic examination results also are usually normal, but abnormalities found are not related to the headache. During the headache, however, cluster and migraine patients may have some abnormal clinical findings, and many patients with tension-type headache will have demonstrable tightness in the cervical muscles, with limitation of neck motion and/or scalp tenderness.

Secondary headaches are usually of recent onset and associated with abnormalities found on clinical examination. Laboratory testing and/or imaging studies will confirm the diagnosis. Recognizing headaches related to a condition or disease is critical not only because treatment of the underlying problem will usually eliminate the headache but also because the condition causing the headache may be life-threatening.

Primary headaches account for more than 90% of all headache complaints and, of these, episodic tension-type headache is the most common. Almost everyone has had an occasional headache of this type. Although chronic tension-type headache occurs in only slightly more than 2% of the population, it accounts for a large number of visits to the physician's office and missed work days.^2,3 Several epidemiologic studies conducted in various areas of the world indicate that the prevalence of migraine headache ranges from 12% to 18% of the population.^3,4 Migraine is three times more common in females. The prevalence of cluster headache is not known. This uncommon condition probably affects less than 0.5% of the population but is underdiagnosed and is often believed to be a sinus problem. Cluster headache affects men eight to ten times more frequently than women.

Because the three primary headache syndromes tend to begin in persons younger than 50 years, anyone older than 50 with a recent onset of headaches should have a thorough examination and testing to look for an underlying cause.

The pathophysiology of migraine, cluster, and tension-type headaches is not well understood. Both migraine and cluster headaches are thought to initially begin in the brain as a neurologic dysfunction, with subsequent involvement of the trigeminal nerve and cranial vessels. In cluster headache, most, but not all, sufferers have overactivity of the parasympathetic system. Tension-type headache may be primarily a central neurologic disturbance similar to migraine or may occur as the result of increased cervical and pericranial muscle activity, such as that caused by flexion-extension injury of the neck, poor posture, or anxiety with increased clenching or grinding of the teeth.

Migraine is an inherited condition in which there appears to be an episodic instability of the neurovascular system (where serotonin and other neurotransmitters play a role).⁵ Available serotonin may be diminished or neuronal receptors for serotonin and other neuroactive substances may at times become less sensitive to these agents. Periodically, the nuclei of the trigeminal nerve appear to become hyperactive. Efferent impulses over branches of this nerve go to the innervated cranial vessels, promoting release of substances causing perivascular inflammation and vascular dilation. Dysfunction of other areas of the brainstem and hypothalamus account for the other associated symptoms of migraine, such as nausea, photophobia, phonophobia, and osmophobia.

Cluster headache also is an episodic neural dysfunction but more likely involves areas in the hypothalamus. There is a marked increase in blood flow through the internal carotid artery on the headache side during the attack of pain.

Migraine
Most migraine patients do not have an aura; migraine with aura occurs in only 15% to 20% of sufferers. The aura is a well defined visual or neurological deficit lasting less than 1 hour and is followed by the headache within an hour. Most auras are visual, with photopsia (flashing lights) being most common. The aura is initially small, then enlarges or moves across the visual field. A typical migraine aura may occur without a headache. This phenomenon tends to begin later in life. Occasionally, a neurologic aura will occur, with a tingling or weakness that slowly spreads up or down an extremity.

Many patients with migraine will have prodromal symptoms for many hours or even a day or so before the onset of an attack. These prodromal symptoms are generally changes in mood or personality. Fatigue also is common, and occasionally hyperactivity occurs.

The migraine attack lasts 6 to 72 hours. This pounding, throbbing pain of moderate to severe intensity is generally unilateral, but some patients will experience bilateral pain. Pain caused by migraine worsens with physical activity. Photophobia and phonophobia are very common, with sensitivity to odors being a little less common. Migraine is a sick headache. Nausea occurs in most patients, and vomiting is very common. Dehydration may occur, which will increase the pain and disability of the condition. Migraineurs want to be quiet, inactive, and in a darkened area during the attack. Approximately 60% of women experience their worst migraine attacks in conjunction with their menstrual period.

Tension-Type Headache
Tension-type headache is characterized by generalized pressure or a sensation of tightness in the head. The discomfort level is usually mild to moderate and does not worsen with activity. Although nausea and photophobia or phonophobia may occur, they generally are not prominent features. Tension-type headache can be episodic (less than 15 days a month) or chronic (more than 15 days a month). Some patients with tension-type headache will exhibit evidence of increased muscle tension with prominent scalp tenderness, muscle tenderness in the temporomandibular joint muscles, and/or tight, tender cervical and trapezius muscles. Poor posture is often evident, which may play a role in causing tension-type headache. If no evidence of increased pericranial or cervical muscle tightness (no tenderness or limitation of motion in the neck) is seen during clinical examination, this suggests that the pain originates centrally.

Cluster Headache
Cluster headache causes intense pain that is generally steady and boring behind one eye. The pain may spread to the temple, face, and even back into the upper neck. It is so intense that most sufferers will pace the floor or do vigorous exercises during the attack. The attacks are short (usually less than 3 hours in duration) and often last only 30 to 45 minutes. They occur from one to several times a day for a period of several weeks or months, then remit, leaving the patient pain free for several months or years, only to recur. During a cluster headache cycle, the attacks of pain often occur at the same time each day, most often waking the patient in the early morning hours. Eighty percent of cluster sufferers experience unilateral tearing, with conjunctival injection and ipsilateral nasal congestion. About 20% of cluster patients have a partial Horner's syndrome with ptosis and meiosis of the affected eye. These symptoms clear as the attack leaves. Alcohol will bring on an attack within a few minutes in a patient who is in a cluster headache cycle, but it will not induce an attack when the patient is in remission.

Chronic Daily Headache
Daily headache may occur as a chronic tension-type headache, but is often a combination of tension-type and migraine (as often seen in headache clinics). This type of combination headache does not appear in the current IHS (International Headache Society) classification, but will be added in the revised version to be published in 2003 or 2004. Most often, this type of combination or "mixed" headache occurs in an individual who initially had typical episodic migraine but in whom develops, over several years time, a chronic daily or almost daily headache.

Migraine attacks will occur in addition to the daily headache. Many times, this daily headache seems to develop because of the frequent use of analgesics, especially those combined with caffeine and/or butalbital. A daily or near-daily migraine headache may occur from the frequent use of ergotamine tartrate or any of the triptan drugs. This headache pattern has been called rebound headache or medication overuse headache.

Secondary Headaches
Secondary headache may be caused by many different diseases. However, neurologic symptoms and signs are almost always present before there is significant headache in patients who have a mass lesion in the brain.

Temporal arteritis generally occurs in persons older than 50 years and may be associated with any type of headache. Pain usually is not throbbing and, although it is usually situated in the temples, can be nonlocalized. Fatigue and a low-grade fever are often present. The erythrocyte sedimentation rate is high—usually above 60. Diagnosis is confirmed by a temporal artery biopsy, which typically shows giant cell inflammation. Treatment should begin with 60 mg to 80 mg of prednisone per day as soon as the diagnosis is suspected, even before the confirmation by biopsy. A recent study suggests that methotrexate may be effective in allowing treatment with a lower dose of steroids.⁶ If not treated, 20% to 30% of patients with this disease will have partial or complete visual loss in the affected eye. Therefore, prompt treatment is essential.

Aneurysms do not cause recurring headache unless compressing a cranial nerve. They present with a severe pain at the time of rupture. Occasionally, an arteriovenous malformation will mimic migraine, particularly if located in the occipital lobe, but these lesions are more apt to cause seizures or bleed. Headaches with a postural component need to be evaluated to exclude a lesion in the posterior fossa. Currently, an MRI scan is the best tool to evaluate the posterior area of the brain. Pericranial inflammation such as sinus infection, ear infection, or dental disease is evident on examination and usually of a more recent, acute onset. Systemic conditions such as endocrine disorders, anemia, sepsis, and hypertension can present as a nonlocalized headache, but more often will exacerbate an underlying migraine or tension-type headache.

The diagnosis of primary headache syndromes is based on the history of the condition and the symptoms described by the patient. After talking with the patient, the clinician usually has a fairly good idea of what type of headache or headaches the person is experiencing.

Any abnormal physical or neurologic examination findings must be investigated. Laboratory studies may be useful in excluding metabolic or endocrine factors that may play a role. A high erythrocyte sedimentation rate in a patient older than 50 years with new headache onset suggests temporal arteritis. This diagnosis must be confirmed by temporal artery biopsy. Scans can be performed to exclude intracranial causes of headache or to rule out lesions that cause neurologic or visual abnormalities associated with headache. Computerized tomography scanning of the paranasal sinuses is useful in evaluating the role of acute or chronic sinus infection in the etiology of the headache. Magnetic resonance imaging is currently the best scan for viewing the posterior fossa and occipital areas of the brain.

If a headache is due to an underlying condition, the neurologic or systemic problem should be treated and the headache will resolve. Most patients with tension-type, migraine or cluster headache will need to be treated with medication. Some patients, particularly those with tension-type headaches may benefit from relaxation techniques or biofeedback training if stress is an important factor. Physical therapy may also decrease chronic neck pain if due to increased cervical muscle spasm or postural abnormalities.

Migraine Management
Some migraine headaches can be relieved with the use of cold packs, pressure on the temple, and sleep; however, most require preventive or abortive medication.

Educating the migraine patient to recognize and avoid headache triggers helps to reduce the frequency of attacks. Common migraine triggers include weather changes, the estrogen cycle, bright lights, strong odors, stress, foods, food additives, and the skipping of meals. Migraineurs do better and have fewer headaches by following regular eating and sleeping patterns.

Migraine Preventive Medication
The use of daily prophylactic medication should be considered whenever migraine attacks occur several times a month or are very severe and do not respond well to abortive medication. Essentially seven classifications of drugs are useful for migraine prophylaxis: beta-blockers, calcium channel blockers, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, antiepileptic drugs, and the serotonin agonist methysergide (Table 1) (Methysergide is no longer available in the United States). A few people may benefit from using large doses (400 mg) of riboflavin (vitamin B-2) or magnesium oxide, 400 mg daily. The beta-blockers propranolol HCl and timolol maleate, the anticonvulsant divalproex sodium, topiramate, and methysergide currently are the only drugs approved by the US Food and Drug Administration for migraine prevention. A few newer anticonvulsants such as gabapentin, and tiagabine are being evaluated for their effectiveness in the prevention of migraine. They are being used "off label" clinically for migraine prevention. The injection of botulinum toxin type A into the forehead also has been found to decrease the frequency and severity of migraine in about 50% of patients.⁷

Migraine Abortive Medication
All migraine patients suffering an acute attack need to take an abortive drug, whether or not they are taking a prophylactic agent (Table 2). For mild attacks, over-the-counter analgesics (especially those containing caffeine) may be useful. Effective agents available by prescription include a combination of isometheptene mucate, dichloralphenazone, and acetaminophen; ergotamine tartrate combined with caffeine; dihydroergotamine mesylate, and the triptans. Large doses of rapid-acting NSAIDs, such as meclofenamate, ibuprofen, or naproxen sodium, can also prove helpful in mild attacks.

Ergotamine tartrate combined with caffine (oral, suppository) is quite effective but often causes nausea. Dihydroergotamine (DHE 45) is a very effective abortive agent when used parenterally. It is also available as a nasal spray.

A big revolutionary breakthrough in acute migraine treatment occurred about 12 years ago with the development of sumatriptan succinate. The triptan drugs are agonists that affect the 1B and 1D serotonin receptors located in neurons and cerebral vessels. Seven triptan agents are available in the United States: sumatriptan succinate (oral, nasal, injectable), rizatriptan benzoate (oral), zolmitriptan (oral, nasal), naratriptan HCl (oral), almotriptan (oral), frovatriptan (oral), and eletriptan (oral). All are very well tolerated by patients; however, like ergotamine, the triptans should not be used in patients with coronary artery disease, peripheral vascular disease, or uncontrolled hypertension. Triptan drugs are effective in 60% to 65% of patients, completely or significantly relieving migraine pain and associated symptoms within 2 hours of administration. Side effects are generally mild, the most common being dizziness, sedation, or mild upper chest tightness that is noncardiac in origin. Headache recurs within 24 hours in up to 30% of users, necessitating an additional dose. Frovatriptan has a significantly longer half life than the others with less recurrence of headache. Using a nonsteroidal drug with a triptan can be useful in giving better relief with less recurrence of the headache. At times a rescue medication such as an opiate or butalbital combination drug may be needed, but with the large number of non habituating preparations now available, the need to use such drugs is now much less than in the past.

The use of some oral abortive agents, especially the ergotamines, often causes nausea and vomiting and may limit their use. However, preceding the use of an abortive agent with metoclopramide may control the nausea and enhance the effectiveness of the abortive drug. Other antinauseant agents also may be helpful, including prochlorperazine, hydroxyzine pamoate, promethazine HCl, or trimethobenzamide HCl. In recent years, parenteral non-narcotic medications have been very useful in aborting severe migraine attacks. Intravenous DHE, prochlorperazine, divalproex sodium, magnesium and ketorolac can be very effective in stopping a migraine attack without resorting to the use of narcotics.

Tension-Type Headache Management
The occasional tension-type headache can be alleviated by a hot shower, massage, sleep, and through patient recognition and avoidance of stress factors. Episodic tension-type headache is usually well treated with analgesics such as aspirin, acetaminophen, and NSAIDS or combinations of these agents with caffeine or sedating medications. Some patients, particularly those with tension-type headache caused by stress, may benefit from relaxation techniques or biofeedback training. Physical therapy may decrease chronic neck pain caused by increased cervical muscle spasm or postural abnormalities. When tension-type headache becomes chronic, treatment can be challenging, especially if the patient overuses analgesics and opiates. Treatment will not be effective until the patient stops taking these acute pain-relieving agents. Patients suffering from chronic tension-type headache often need counselling and psychotherapy to help define and work through long-standing psychologic issues.

The most effective group of drugs for treatment of chronic tension-type headaches is the tricyclic antidepressants. Amitriptyline HCl, doxepin HCl, and nortriptyline HCl are most commonly used. They are usually taken at bedtime due to their sedating effects. Morning sedation, weight gain, dry mouth, and constipation are common side effects. Less sedating drugs in this group include desipramine HCl and protriptyline HCl. Serotonin reuptake inhibitors, such as fluoxetine HCl, sertraline HCl, paroxetine HCl, and citalopram hydrobromide, are better tolerated and have fewer side effects than the tricyclics, but as antidepressants, they do not appear to be as effective in easing headache unless the headache is a manifestation of underlying depression. Venlafaxine HCl, a serotonin and norepinephrine uptake inhibitor, may be helpful in chronic pain conditions, including headache. Muscle relaxants such as cyclobenzaprine HCl, orphenadrine citrate, and baclofen may be helpful at times, particularly if increased muscle spasm is present. In recent clinical trials, the central-acting muscle relaxant tizanidine HCl was found to be effective in treating chronic headache, either tension-type or coexisting migraine and tension-type.⁸

Cluster Headache Treatment
Because the onset of cluster headache attacks is rapid and may occur several times a day, the best approach to treatment is with daily preventive drugs. Effective prophylactic medications include verapamil HCl, prednisone, lithium carbonate, methysergide (not available in the US), and the antiepileptic drugs divalproex and topiramate. High doses of verapamil (480 mg to 720 mg/day) may be necessary. Prednisone and methysergide work quickly and often will be used with verapamil or lithium at onset for a quick response and then tapered while the verapamil or lithium is continued. Prednisone is usually prescribed at 60 mg/day initially and then tapered over 2 to 3 weeks. There are reports that topiramate is helpful is controlling cluster but no controlled studies have been published.

The use of 100% oxygen by mask at a flow rate of 8 to 10 L/min for up to 10 minutes will abort an acute cluster headache in 50% to 60% of patients. Ergotamine tartrate, DHE, and any of the triptans usually are very effective, but are inappropriate in patients who suffer several attacks a day. Fortunately, cluster headache patients do not appear to develop rebound headaches from frequent use of ergotamine tartrate or the triptans, as do migraine sufferers.

Methysergide is the only drug approved for the treatment of cluster headache (it is no longer marketed in the US). It is not used very often because of the possible development of retroperitoneal fibrosis or other fibrotic complications. Methysergide should not be used for longer than 4 to 6 months without giving the patient a 4-to-6-week drug holiday. Once the patient is free of attacks for a few weeks, prophylactic drugs should be tapered and discontinued.

Although few long-term follow-up studies have been conducted, trial findings indicate that inpatient treatment of chronic headache sufferers is associated with approximately a 50% improvement rate in treated patients.⁹ Comprehensive outpatient treatment programs are now being used by many headache clinics; however, definitive outcome data is not yet available. Patients in these programs usually are suffering from chronic daily headaches and medication overuse. Most programs include detoxification from analgesics and narcotics and the initiation of preventive medicines as well as psychotherapy, physical therapy, the teaching of relaxation and biofeedback techniques, and educating patients to recognize triggers and be aware of the causes of their headaches.

Other recent studies demonstrate that acute migraine patients treated with sumatriptan experience a reduction in visits to the doctor's office and emergency room and fewer days lost at work.^10,11(Other triptan drugs would have the same benefit). Migraine treatment with the newer, more specific drugs such as the triptans should greatly reduce the disability associated with this condition.

Comprised of representatives of seven organizations, the US Headache Consortium recently published evidence-based guidelines for migraine headache based on a review of the literature.¹² These guidelines are available online. These guidelines are an attempt to evaluate the validity of studies done with various abortive and preventive drugs and to rate the effectiveness of these drugs based on those studies in the literature. Nonpharmacologic treatments of migraine are also evaluated and rated.

Return to Medicine Index

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