Definition
Headache is a pain in the head and neck region that may be either a disorder in its own right or a symptom of an underlying medical condition or disease. The medical term for headache is cephalalgia. Headaches are one of the most common and universal human ailments, described in the Bible as well as in medical writings from ancient Egypt, Babylonia, Greece, Rome, India, and China. Severe chronic headaches were once treated by the oldest known surgical procedure, known as trepanning or trephining, in which the surgeon drilled a hole as large as 1–2 in diameter in the patient's skull without benefit of anesthesia. Evidence of trepanning has been found in skulls from Cro-Magnon people that are about 40,000 years old.
Description
Contemporary doctors divide headaches into two large categories, primary and secondary, according to guidelines established by the International Headache Society (IHS) in 1988 and revised for republication in 2004. Primary headaches are those that are not caused by an underlying medical condition. There are three types of primary headaches: migraine, cluster, and tension headaches. More than 90% of all headaches are primary headaches. Secondary headaches are caused by disease or medical condition; they account for fewer than 10% of all headaches.
Primary headaches
MIGRAINE HEADACHES Migraine headaches are characterized by throbbing or pulsating pain of moderate or severe intensity lasting from four hours to as long as three days. The pain is typically felt on one side of the head; in fact, the English word "migraine" is a combination of two Greek words that mean "half" and "head." Migraine headaches become worse with physical activity and are often accompanied by nausea and vomiting. In addition, patients with migraine headaches are hypersensitive to lights, sounds, and odors.
The two most common types of migraines are known as classic and common migraine, respectively. Classic migraine, which accounts for 10–20% of the cases of migraine, is distinguished by a brief period of warning symptoms 10–60 minutes before an acute attack. This prodrome, which is known as an aura, may include such symptoms as seeing flashing lights or zigzag patterns, temporary loss of vision, difficulty speaking, weakness in an arm or leg, and tingling sensations in the face or hands. Common migraine is not preceded by an aura, although some patients experience mood changes, unusual tiredness, or fluid retention shortly before an attack. An attack of common migraine may include diarrhea and frequent urination, as well as nausea and vomiting.
Less common types of migraines include hemiplegic migraine, characterized by temporary paralysis on one side of the body; ophthalmoplegic migraine, in which the pain is felt in the area around the eye; basilar artery migraine, which involves a major artery at the base of the brain and primarily affects young women; and headache-free migraine, which is characterized by the gastrointestinal and visual symptoms of classic migraine, but does not involve head pain.
CLUSTER HEADACHES Cluster headaches are recurrent brief attacks of sudden and severe pain on one side of the head, usually most intense in the area around the eye. Other names for these headaches include histamine cephalalgia, Horton neuralgia, or erythromelalgia. Cluster headaches may last between five minutes and three hours; they may occur once every other day or as often as eight times per day. The IHS classifies cluster headaches as either episodic or chronic. Episodic cluster headaches occur over periods lasting from seven days to one year, with the clusters separated by headache-free intervals of at least two weeks. The average length of a cluster ranges between two weeks and three months. Chronic cluster headaches occur over a period longer than a year without a headache-free interval, or with pain-free intervals that are shorter than two weeks.
The pain of a cluster headache is excruciating; some patients describe it as severe enough to make them consider suicide. Patients with cluster headaches are restless; they may pace the floor, weep, rock back and forth, or bang their heads against a wall in desperation to stop the pain. In addition to severe pain, patients with cluster headaches often have a runny or congested nose, watery or inflamed eyes, drooping eyelids, swelling in the area of the eyebrows, and heavy facial perspiration. Because of the nasal symptoms and the relative rarity of cluster headaches, these episodes have sometimes been misdiagnosed as sinusitis.
TENSION HEADACHES Tension headaches are the most common headaches in the general population; other names for them include muscle contraction headache, ordinary headache, psychomyogenic headache, and stress headache. The IHS classifies tension headaches as either episodic or chronic; episodic tension headaches occur 15 or fewer times per month, whereas chronic tension headaches occur on 15 or more days per month over a period of six months or longer.
Tension headaches rarely last more than a few hours; 82% resolve in less than a day. The patient will usually describe the pain of a tension headache as mild to moderate in severity. The doctor will not find anything abnormal in the course of a general physical or neurological examination, although sore or tense areas (trigger points) in the muscles of the patient's forehead, neck, or upper shoulder area may be detected.
REBOUND HEADACHES Rebound headaches, which are also known as analgesic-abuse headaches, are a subtype of primary headache caused by overuse of headache drugs. They may be associated with medications taken for tension and migraine headaches.
Secondary headaches
Secondary headaches, which are caused by diseases or disorders, are categorized as either traction or inflammatory headaches. Traction headaches result from the pulling, stretching, or displacing of structures that are sensitive to pain, as when a brain tumor presses on the outer layer of nerve tissue that covers the brain. Inflammatory headaches are caused by infectious diseases of the ears, teeth, sinuses, or other parts of the head.
Major causes of secondary headaches include the following:
- Brain tumors. Headaches associated with brain tumors usually begin as episodic nighttime headaches that are accompanied by projectile vomiting. The headaches may become continuous over time, and usually get worse if the patient coughs, sneezes, bears down while using the toilet, or does something else that increases the pressure inside the head.
- Meningitis. Meningitis is an inflammation of the meninges, the three layers of membranes that cover the brain and spinal cord. Meningitis is usually caused by bacteria or viruses, and may produce chronic headaches.
- Head trauma. Patients may complain of headaches as well as memory problems, general irritability, and fatigue for months or even years after a head injury. These symptoms are sometimes grouped together as post-concussion syndrome. In some cases, a blow on the head may cause some blood vessels to rupture and produce a hematoma, or mass of blood that displaces brain tissue, and can cause seizures or weakness as well as headaches.
- Temporal arteritis. First described in 1890, temporal arteritis is an inflammation of the temporal artery that most commonly affects people over 50. In addition to headache, patients with temporal arteritis may have fever, loss of appetite, and blurring or loss of vision. Temporal arteritis is treated with steroid medications.
- Stroke. Headaches may be associated with several conditions that may lead to stroke, including high blood pressure and heart disease. Headaches may also result from completed stroke or from the mini-strokes known as transient ischemic attacks, or TIAs.
- Lumbar puncture. About 25% of patients who undergo a lumbar puncture (spinal tap) develop a headache from the lowered cerebrospinal fluid pressure around the brain and spinal cord. Lumbar puncture headaches usually go away on their own after a few hours.
- Sinus infections. Acute sinusitis is characterized by fluid buildup inside sinus cavities inflamed by a bacterial or viral infection. Chronic sinusitis usually results from an allergic reaction to smoke, dust, animal fur, or similar irritants.
- Referred pain. This type of pain is felt in a part of the body at a distance from the injured or diseased area. Headache pain may be referred from diseased teeth; disks in the cervical spine that have been damaged by spondylosis (degeneration of the spinal vertebrae caused by osteoarthritis); or the temporomandibular joint, the small joint in front of the ear where the lower jaw is attached to the skull.
- Idiopathic intracranial hypertension. Also known as pseudotumor cerebri, this disorder is caused by increased pressure inside the skull in the absence of any abnormality of the central nervous system or blockage in the flow of the cerebrospinal fluid. In addition to headache, patients with this disorder experience diplopia (seeing double) and other visual symptoms.
Demographics
Headaches in general are very common in the adult population in North America. The American Council for Headache Education (ACHE) estimates that 95% of women and 90% of men in the United States and Canada have had at least one headache in the past 12 months. Most of these are tension headaches. Tension headaches may begin in childhood in some patients, but most commonly start in adolescence or the early 20s. The gender ratio for episodic tension headaches is about 1.4 F:1 M; for chronic tension headaches, 1.9 F:1 M.
Migraine and cluster headaches have distinctive demographic patterns. Migraine headaches are less common than tension headaches, affecting about 11% of the population in the United States and 15% in Canada. Several studies done in the United Kingdom and the United States, however, indicate that doctors tend to underdiagnose migraine headache; thus the true number of patients with migraine may be considerably higher than the usual statistics indicate. Migraines are a major economic burden; it is estimated that the annual cost of time lost from work due to migraines in the United States alone is $17.2 billion. Most people who experience migraines have their first episode in childhood or adolescence, although some experience their first migraine after age 20. Migraines occur most frequently in adults between the ages of 25 and 55; the gender ratio is about 3 F:1 M. Although migraine headaches occur in people of all races and ethnic groups, they are thought to affect Caucasians more often than African or Asian Americans.
Currently, migraine is the only type of primary headache known to run in families. A child with one parent affected by migraines has a 50% chance of developing migraines as an adult; if both parents are affected, the risk rises to 70%. Although geneticists think that a number of different genes are involved in transmitting a susceptibility to migraine, they have recently identified two specific loci on human chromosomes 1 and 14, respectively, that are linked to migraine headaches. The locus on chromosome 1q23 has been linked to familial hemiplegic migraine type 2, while the locus on chromosome 14q21 is associated with common migraine.
Cluster headaches are the least common type of primary headaches, affecting about 0.4% of adult males in the United States and 0.08% of adult females. The gender ratio is 5–7.5 M:1 F. Cluster headaches occur most commonly in adults between the ages of 20 and 40. It is not currently known whether cluster headaches are more common in some racial or ethnic groups than in others; however, many patients with cluster headaches have a history of face or head trauma.
The demographics of secondary headaches vary depending on the disease or disorder that causes the headache.
Causes and symptoms
Causes
PHYSICAL A person feels headache pain when specialized nerve endings known as nociceptors are stimulated by pressure on or injury to any of the pain-sensitive structures of the head. Most nociceptors in humans are located in the skin or in the walls of blood vessels and internal organs; the bones of the skull and the brain itself do not contain nociceptors.
The specific parts of the head that are sensitive to pain include:
- the skin that covers the skull and cervical spine
- the 5th, 9th, and 10th cranial nerves and the nerves that supply the upper part of the neck the venous sinuses inside the head
- the large arteries at the base of the brain
- the large arteries that supply the dura mater, which is the outermost of the three meninges (membranes) that cover the brain and spinal cord
- the portion of the dura mater at the base of the skull
Tension headaches typically result from tightening of the muscles of the face, neck, and scalp as a result of emotional stress; physical postures that cause the head and neck muscles to tense (e.g., holding a phone against the ear with one's shoulder); depression or anxiety; temporomandibular joint dysfunction (TMJ); or degenerative arthritis of the neck. The tense muscles put pressure on the walls of the blood vessels that supply the neck and head, which stimulates the nociceptors in the tissues that line the blood vessels. In addition, the nociceptors in patients with chronic tension headaches appear to be abnormally sensitive to stimulation.
The pathophysiology of migraine headaches has been debated among doctors since the 1940s. Some researchers think that migraines are the end result of a magnesium deficiency in the brain or of hypersensitivity to a neuro-transmitter known as dopamine. Another theory holds that certain nerve cells in the brain cortex become unusually excitable and depolarize (lose their electrical potential) spontaneously, releasing potassium and glutamate, an amino acid. These substances then depolarize nearby nerve cells, resulting in a chain reaction known as cortical-spreading depression (CSD). CSD then leads to changes in the amount of blood flowing through the blood vessels and stimulation of their nociceptors, resulting in severe headache. More recently, the discovery of specific genes associated with migraine indicates that genetic mutations are responsible for the abnormal excitability of the nerve cells in the brains of patients with migraine.
Little is known about the causes of cluster headaches or changes in the central nervous system that produce them.
PSYCHOLOGICAL Chronic headaches are often associated with anxiety, depression, or a specific group of mental disorders known as somatoform disorders. These disorders include hypochondriasis and pain disorder; they are characterized by physical symptoms (frequently headache) that suggest that the patient has a general medical condition, but there is no diagnosable disease or disorder that fully accounts for the patient's symptoms. The relationship between psychological and physical factors in headaches is complex in that headaches may be either the cause or result of emotional disturbances, or both. Some patients find that chronic headaches disappear completely after a stressful family- or job-related situation has been resolved.
Warning symptoms
Most headaches are not associated with serious or life-threatening illnesses. Patients should, however, immediately call their primary physician if they have any of the following symptoms:
- three or more headaches per week
- need for a pain reliever every day or almost every day
- need for greater than recommended doses of over-thecounter medications (OTCs)
- stiff neck or fever accompanying the headache
- shortness of breath, hearing problems, blurry vision, or severe sore throat
- dizziness, weakness, slurred speech, mental confusion, or drowsiness headache following a head injury that is not relieved by OTCs
- headache triggered by exercise, coughing, sexual activity, or bending over
- persistent or violent vomiting
- change in the character of the headaches—for example, persistent severe headaches in a person who has previously had only mild headaches of brief duration
- recurrent headaches in a child
- recurrent severe headaches, beginning after age 50
Diagnosis
Patient history
The differential diagnosis of headaches begins with a complete patient history, including a family history. In many cases, a primary care physician can make the diagnosis on the basis of the history. The doctor will ask the patient about head injuries or surgery on the head; eye problems or disorders; sinus infections; dental problems or extensive oral surgery; and medications that the patient is taking regularly.
After taking the history, the doctor will ask the patient to describe the location and type of pain that he or she experiences during the headache. People who have tension headaches will typically describe the pain as "viselike," "tightening," "pressing," or as a steady or constant ache. Patients with migraine headaches, on the other hand, will usually say that the pain has a "throbbing" or "pulsating" character, while patients with cluster headaches describe the pain as "penetrating" or "piercing." About 85% of patients with tension headaches experience pain on both sides of the head, most commonly in the area around the forehead and temples. Patients with migraine or cluster headaches, however, are more likely to feel pain on only one side of the head.
Some primary care physicians give the patient a printed questionnaire that consists of 50–55 brief yes/no questions that cover such matters as the timing and frequency of the headaches; whether other family members have the same type of headache; whether the patient feels depressed; whether the headaches are related to changes in the weather; and so on. The answers to the questions will usually fall into a pattern that tells the doctor whether the patient has migraines, tension headaches, cluster headaches, or headaches with other causes. The doctor may also ask the patient to keep a headache diary to help identify foods, stress, lack of sleep, weather, and other factors that may trigger headaches.
It is possible for patients to have more than one type of headache. For example, patients with chronic tension headaches often have migraine headaches as well.
Physical examination
The physical examination helps the doctor identify other symptoms and signs that may be relevant to the diagnosis, such as fever; difficulty breathing; nausea or vomiting; stiff neck; changes in vision or hearing; watering or inflammation of the nose and eyes; evidence of head trauma; skin rashes or other indications of an infectious disease; and abnormalities in the structure or alignment of the patient's spinal column, teeth or jaw. In some cases, the doctor may refer the patient to a dentist, oral surgeon, or endodontist for a more detailed evaluation of the patient's mouth and jaw.
Special studies
Some laboratory tests are useful in identifying headaches caused by infections or by such disorders as anemia or thyroid disease. These tests include a complete blood count (CBC); erythrocyte sedimentation rate (ESR); and blood serum chemistry profile.
Patients who report visual disturbances and other neurologic symptoms may be given visual field tests and have the pressure of the fluid inside their eyes (intraocular pressure) tested to check for glaucoma. A lumbar puncture (spinal tap) may be done to confirm a diagnosis of idiopathic intracranial hypertension.
Imaging studies may include x rays of the sinuses to check for sinus infections; and CT or MRI scans, which are done to rule out brain tumors and cerebral aneurysms.
Patients whose symptoms cannot be fully explained by the results of physical examinations and tests may be referred to a psychiatrist for evaluation of psychological factors related to their headaches.
Treatment
Medical
TENSION HEADACHES Episodic tension headaches are usually relieved fairly rapidly by such over-the-counter analgesics as aspirin (300–600 mg every four hours), acetaminophen (650 mg every four hours), or another nonsteroidal anti-inflammatory drug (NSAID), usually ibuprofen (Advil) or naproxen (Naprosyn, Aleve). The doctor may prescribe a tricyclic antidepressant or benzodiazepine tranquilizer in addition to a pain reliever for patients with chronic tension headaches. A newer treatment for chronic tension headaches is botulinum toxin (Botox type A), which appears to work very well for some patients. As of 2003, however, Botox has not yet been evaluated in controlled multicenter studies as a treatment for chronic headaches; the data obtained so far are derived from case reports and open-label studies.
MIGRAINE HEADACHES Medications can be prescribed to prevent migraines as well as to treat the symptoms of an acute attack. Drugs that are given for migraine prophylaxis (to prevent or lower the frequency of migraine attacks) include tricyclic antidepressants, beta-blockers, and anti-epileptic drugs, which are also known as anti-convulsants. As of 2003, sodium valproate (Epilim) is the only anticonvulsant approved by the Food and Drug Administration (FDA) for prevention of migraine. Such newer anticonvulsants as gabapentin (Neurontin) and topiramate (Topamax) are presently being evaluated as migraine preventives. Moreover, a new study reported that three drugs currently used to treat disorders of muscle tone are being explored as possible preventives for migraine—Botox, baclofen (Lioresal), and tizanidine (Zanaflex). Early results of open trials of these medications are positive.
Nonsteroidal anti-inflammatory drugs acetaminophen (Tylenol), ibuprofen (Motrin), and naproxen (Aleve) are helpful for early or mild migraines. More severe or unresponsive attacks may be treated with dihydroergota-mine; a group of drugs known as triptans; beta-blockers and calcium channel-blockers; antiseizure drugs; antidepressants (SSRIs); meperidine (Demerol); or metoclopramide (Reglan). Some of these are also available as nasal sprays, intramuscular injections, or rectal suppositories for patients with severe vomiting. Sumatriptan and the other triptan drugs (zolmitriptan, rizatriptan, naratriptan, almotriptan, and frovatriptan) should not be taken by patients with vascular disease, however, because they cause narrowing of the coronary arteries.
About 40% of all migraine attacks do not respond to treatment with triptans or any other medication. If the headache lasts longer than 72 hours—a condition known as status migrainosus—the patient may be given narcotic medications to bring on sleep and stop the attack. Patients with status migrainosus are often hospitalized because they are likely to be dehydrated from severe nausea and vomiting.
CLUSTER HEADACHES Medications that are given as prophylaxis for cluster headaches include verapamil (Calan, Isoptin, Verelan), which is a calcium channel blocker, and methysergide (Sansert), which is a derivative of ergot. A new study indicates that topiramate (Topamax), an anticonvulsant, is also effective in preventing cluster headaches. Sumatriptan (Imitrex) or indomethacin (Indameth, Indocin) may be prescribed to suppress an attack.
REBOUND HEADACHES Continued use of some pain relievers or antimigraine drugs can lead to rebound headaches, which may be frequent or chronic and often occur in the early morning hours. Rebound headache can be avoided by using antimigraine drugs or analgesics under a doctor's supervision, using only the minimum dose necessary to treat symptoms. Tizanidine (Zanaflex) has been reported to be effective in treating rebound headaches when taken together with an NSAID; Botox has also been used successfully in some patients.
Diet and lifestyle modifications
One measure that people can take to lower the risk of episodic tension headaches is to get enough sleep and eat nutritious meals at regular times. Skipping meals, using unbalanced fad diets to lose weight, and having insufficient or poor-quality sleep can bring on tension headaches. In fact, the common association of tension headaches with hunger, lack of sleep, heat, and sudden temperature extremes has led some researchers to suggest that headaches developed over the course of human evolution as an internal protective response to stress from the environment.
Changes in diet may be helpful to some patients with migraine, although some experts think that the role of foods in triggering migraines has been exaggerated. Women with migraines, however, often benefit by switching from oral contraceptives to another method of birth control or by discontinuing estrogen replacement therapy.
Patients with cluster headaches are advised to quit smoking and minimize their use of alcohol, because nicotine and alcohol appear to trigger cluster headaches. Currently, the precise connection between these chemicals and cluster attacks, however, is not completely understood.
Surgical
Headaches that are caused by brain tumors, post-injury hematomas, dental problems, or disorders affecting the spinal disks usually require surgical treatment. Surgery may also be used to treat cases of idiopathic intracranial hypertension that do not respond to treatment with steroids, repeated lumbar punctures, or weight reduction.
Some plastic surgeons have reported success in treating patients with chronic migraines by removing some muscle tissue near the eyebrows, cutting a branch of the trigeminal nerve, and repositioning the soft tissue around the temples.
Psychotherapy
Psychotherapy may be helpful to patients with chronic headaches by interrupting the "feedback loop" between emotional upset and the physical symptoms of headaches. One type of psychotherapy that has been shown to be effective is cognitive restructuring, an approach that teaches people to reframe the problems in their lives—that is, to change their conscious attitudes and responses to these stressors. Some psychotherapists teach relaxation techniques, biofeedback, or other approaches to stress management as well as cognitive restructuring.
Complementary and alternative (CAM) treatments
There are a number of different CAM treatments for headache, but most fall into two major groups: those intended as prophylaxis or pain relief, and those that reduce the patient's stress level.
CAM therapies intended to prevent headaches or relieve discomfort include:
- Feverfew (Tanacetum parthenium). Feverfew is an herb related to the daisy that is traditionally used in England to prevent migraines. Published studies indicate that feverfew can reduce the frequency and intensity of migraines. It does not, however, relieve pain once the headache has begun.
- Butterbur root (Petasites hybridus). Petadolex is a natural preparation made from butterbur root that has been sold in Germany since the 1970s as a migraine preventive. Petadolex has been available in the United States since December 1998.
- Brahmi (Bacopa monnieri). Brahmi is a herb used in Ayurvedic medicine to treat headaches related to anxiety.
- Acupuncture. Studies funded by the National Center for Complementary and Alternative Medicine (NCCAM) have found that acupuncture is an effective treatment for headache pain in many patients.
- Naturopathy. Naturopaths include dietary advice and nutritional therapy in their approach to treatment, which is often effective for patients with episodic or chronic tension headaches.
- Chiropractic. Some patients with tension or migraine headaches find spinal manipulation effective in relieving their pain; however, no controlled studies of the long-term effectiveness of chiropractic in treating headaches have been done as of 2003.
CAM therapies that are reported to be effective in reducing emotional stress related to headaches include:
- yoga and t'ai chi
- prayer and meditation
- aromatherapy
- hydrotherapy, particularly whirlpool baths
- Swedish massage and shiatsu
- pet therapy
- humor therapy
- music therapy
Clinical trials
As of late 2003, there were three National Institutes of Health (NIH) trials recruiting patients with headaches: a study evaluating a new intranasal drug (civamide) for cluster headaches; a study of the effectiveness of biofeedback and relaxation training in patients with chronic migraine or tension headaches; and a study of migraine headaches in children.
Prognosis
The prognosis of primary headaches varies. Episodic tension headaches usually resolve completely in less than a day without affecting the patient's overall health. According to NIH statistics, 90% of patients with chronic tension or cluster headaches can be helped. The prognosis for patients with migraines, however, depends on whether the patient has one or more of the other disorders that are associated with migraine. These disorders include Tourette's syndrome, epilepsy, ischemic stroke, hereditary essential tremor, depression, anxiety, and others. For example, migraine with aura increases a person's risk of ischemic stroke by a factor of six.
The prognosis of secondary headaches depends on the seriousness and severity of their cause.
Resources
BOOKS
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. Washington, DC: American Psychiatric Association, 2000.
" Headache." The Merck Manual of Diagnosis and Therapy. Edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 2002.
Pelletier, Kenneth R. The Best Alternative Medicine, Part II, "CAM Therapies for Specific Conditions: Headache." New York: Simon & Schuster, 2002.
"Psychogenic Pain Syndromes." The Merck Manual of Diagnosis and Therapy. Edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 2002.
PERIODICALS
Argoff, C. E. "The Use of Botulinum Toxins for Chronic Pain and Headaches." Current Treatment Options in Neurology 5 (November 2003): 483–492.
Astin, J. A., and E. Ernst. "The Effectiveness of Spinal Manipulation for the Treatment of Headache Disorders: A Systematic Review of Randomized Clinical Trials." Cephalalgia 22 (October 2002): 617–623.
Corbo, J. "The Role of Anticonvulsants in Preventive Migraine Therapy." Current Pain and Headache Reports 7 (February 2003): 63–66.
Freitag, F. G. "Preventative Treatment for Migraine and Tension-Type Headaches: Do Drugs Having Effects on Muscle Spasm and Tone Have a Role?" CNS Drugs 17 (2003): 373–381.
Guyuron, B., T. Tucker, and J. Davis. "Surgical Treatment of Migraine Headaches." Plastic and Reconstructive Surgery 109 (June 2002): 2183–2189.
Headache Classification Subcommittee of the International Headache Society. "The International Classification of Headache Disorders," 2nd ed. Cephalalgia 24 (2004) (Supplement 1): 1–150.
Lainez, M. J., J. Pascual, A. M. Pascual, et al. "Topiramate in the Prophylactic Treatment of Cluster Headache." Headache 43 (July-August 2003): 784–789.
Lenaerts, M. E. "Cluster Headaches and Cluster Variants." Current Treatment Options in Neurology 5 (November 2003): 455–466.
Lipton, R. B., A. I. Scher, T. J. Steiner, et al. "Patterns of Health Care Utilization for Migraine in England and in the United States." Neurology 60 (February 11, 2003): 441–448.
Marconi, R., M. De Fusco, P. Aridon, et al. "Familial Hemiplegic Migraine Type 2 is Linked to 0.9Mb Region on Chromosome 1q23." Annals of Neurology 53 (March 2003): 376–381.
Mendizabai, Jorge, MD. "Cluster Headache." eMedicine, 26 September 2003. http://www.emedicine.com/neuro/topic70.htm.
Sahai, Soma, MD, Robert Cowan, MD, and David Y. Ko, MD. "Pathophysiology and Treatment of Migraine and Related Headache." eMedicine, April 30, 2002 (February 16, 2004). http://www.emedicine.com/neuro/topic517.htm.
Singh, Manish K., MD. "Muscle Contraction Tension Headache." eMedicine, October 5, 2001 (February 16, 2004). http://www.emedicine.com/neuro/topic231.htm.
Soragna, D., A. Vettori, G. Carraro, et al. "A Locus for Migraine Without Aura Maps on Chromosome 14q21.2–q22.3." American Journal of Human Genetics 72 (January 2003): 161–167.
Tepper, S. J., and D. Millson. "Safety Profile of the Triptans." Expert Opinion on Drug Safety 2 (March 2003): 123–132.
OTHER
Migraine Information Page. NINDS. 2003 (February 16, 2004). http://www.ninds.nih.gov/health_and_medical/pubs/migraineupdate.htm.
National Institute of Neurological Disorders and Stroke (NINDS). "Headache—Hope Through Research." Bethesda, MD: NINDS, 2001. (February 16, 2004.) http://www.ninds.nih.gov/health_and_medical/pubs/headache_htr.
ORGANIZATIONS
American Academy of Neurology (AAN). 1080 Montreal Avenue, Saint Paul, MN 55116. (651) 695-2717 or (800) 879-1960; Fax: (651) 695-2791. memberservices@aan.com. http://www.aan.com.
American Council for Headache Education (ACHE). 19 Mantua Road, Mt. Royal, NJ 08061. (856) 423-0258; Fax: (856) 423-0082. achehq@talley.com. http://www.achenet.org.
International Headache Society (IHS). Oakwood, 9 Willowmead Drive, Prestbury, Cheshire SK10 4BU, United Kingdom. +44 (0) 1625 828663; Fax: +44 (0) 1625 828494. rosemary@ihs.u-net.com. http://216.25.100.131.
National Headache Foundation. 820 North Orleans, Suite 217, Chicago, IL 60610. (773) 525-7357 or (888) NHF-5552. http://www.headaches.org.
NIH Neurological Institute. P. O. Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424. http://www.ninds.nih.gov.
Rebecca J. Frey, PhD