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Headaches: Cluster

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WHAT IS HEADACHE?

The brain itself is insensitive to pain. Headache pain occurs in the following locations:

The tissues covering the brain.
The attaching structures at the base of the brain.
Muscles and blood vessels around the scalp, face, and neck.

Headache is generally categorized as primary or secondary.

Primary Headache. A headache is considered primary when a disease or other medical condition does not cause it.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Neurovascular headaches are the second most frequently occurring primary headaches and include migraines (the more common) and cluster headaches. Such headaches are caused by an interaction between blood vessel and nerve abnormalities.

Secondary Headache. Secondary headaches are caused by other medical conditions, such as sinusitis infection, neck injuries or abnormalities, and stroke. About 2% of headaches are secondary headaches caused by abnormalities or infections in the nasal or sinus passages (sinus headaches). [ See Box Causes of Secondary Headache .]

It is not uncommon for someone to experience a combination of headache types.

WHAT IS A CLUSTER HEADACHE?

Cluster Cycles and Subgroups

Cluster headaches are among the most painful of all headaches. The signature is a pattern of periodic cycles of headache attacks, which may be episodic or chronic. (It should be noted that a significant percentage of people who experience a first cluster attack do not have another one.)

Episodic Cluster Headache. Between 80% and 90% of these headache patients have episodic cluster headache cycles. Such patients experience the following:

_ Cycles of daily or near daily attacks that may last from one week to one year.

_ During an active cycle, sufferers can experience one or more bouts a day, or as few as one every other day. The attacks themselves are usually brief but extremely painful.

_ Such cycles are followed by headache-free periods lasting at least fourteen days.

[See Box Typical Episodic Cluster Patterns.]

Chronic Cluster Headache. About 10% of cluster headache patients have a chronic form, which lasts more than a year and remissions that last less than 14 days. Two chronic subtypes have been defined:

Chronic cluster headache that is unremitting from the onset. This type may be more associated with heavy alcohol use.
Chronic cluster headache that has evolved from episodic cluster. One study found a higher risk for this in patients who developed cluster headaches in their thirties or older and who had more frequent attacks and shorter remissions than average. Another study suggested that this condition occurs more often in heavy smokers, although the link is uncertain.

Symptoms of Cluster Headache

Cluster symptoms tend to occur during months that are warmer and have more daylight. The course of symptoms varies and may include the following:

About 10% of patients experience so-called premonitory symptoms from one day to 8 weeks before a cluster headache attack. They can include fatigue, neck ache, stiffness, odd sensations in the limbs, an extreme sensitivity in the area where the headache will develop.
When the actual attack occurs, symptoms typically increase rapidly (within about 15 minutes) to intense levels. People often awaken with them a few hours after they go to bed.
The attack typically causes very severe, stabbing or boring pain centered in one eye. Pain may also occur above the eye, near the temples, or on one side of the head.
Facial sweating is common.
Associated symptoms include pupil changes, excessive tearing, a drooping eyelid, and one stuffy or runny nostril. All of these symptoms appear on the same side as the pain.
Migraine-like symptoms (sensitivity to light and sound, auras and rarely, nausea and vomiting) may occur. Women have a higher risk for nausea and vomiting than men do.
The pain then often radiates to other parts of the head, shoulders, and neck.
Feelings of intense restlessness are usual (unlike migraine attacks, during which the tendency is to sleep).
People in the throes of a cluster headache may pace the floor or may even bang their heads against the wall in an attempt to cope with the pain.

Typical Episodic Cluster Cycles

Time and Duration of Attacks: Headache attacks tend to occur with great regularity, occurring at the same time of day. About 75% occur between 9 PM and 10 AM. Peaks also reported between 1 PM and 3 PM. The attacks usually last between 30 to 90 minutes.

Number of Attacks per Day during the Cycle : Usually a patient has one or two attacks (typically one that wakes a person from sleep) per day but some people have up to eight or more attacks.

Frequency of Daily Attacks during a Cycle: A person may experience an attack series each day to every other day.

Number of Cluster Cycles per Year: Usually a patient has one or two cycles per year that each last one to three months. (Often cycles occur during the period that corresponds to daylight savings time.) In rare episodic cluster cases, a cycle lasts up to a year. (If it lasts a year, the patient is considered to have chronic cluster headache.)

Headache-Free Remissions between Cycles: Typical remissions last one month to two years but they can be as short as fourteen days.

CAUSES OF SECONDARY HEADACHES

About 90% of people seeking help for headaches have a primary headache disorder. The balance of secondary headaches, however, is caused by an underlying disorder that produces the headache as a symptom. Many conditions cause headache as a symptom. There are over 300 disorders that can cause secondary headaches. Some of the most common are listed below.

Sinus Headache. Many primary headaches, including migraine, are misdiagnosed as sinus headache. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis; they even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.) [For more information, see the Report #62, Sinusitis.]

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve. This is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side; even if it affects both sides of the head it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck). Whiplash injuries involve the neck and can cause constant tension headaches, which, according to a 2001 British study, resolve within three weeks in 85% of patients.

Temporomandibular Joint Dysfunction (TMJ). TMJ is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Brain Tumor. Fear of brain tumor is common among people with headaches, but headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraine or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the two are rarely associated. An exception is malignant hypertension, an uncommon medical emergency, in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention. It is important to determine if a clot or bleeding is causing the stroke, since treatments are very different.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same ways. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. In very rare instances, ordinary physical strain may injure or weaken the meninges, causing a leakage of cerebrovascular fluid (the fluid that bathes the brain). This can cause severe headache and nausea, which are relieved by lying flat. The condition is very treatable. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain, which may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion.

OTHER PRIMARY HEADACHES

Migraine Headaches: General Description of its Course

Migraine is now recognized as a chronic illness, not simply as a headache. In general, there are four symptom phases to a migraine (although they may not all occur in every patient): the prodrome, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Such prodrome symptoms can include the following:

Sensitivity to light or sound.
Changes in appetite.
Fatigue and yawning.
Malaise.
Mood changes.
Food cravings.

Auras. Auras are sensory disturbances that occur before the migraine attack occurs. Although some studies estimate that up to half of migraine sufferers have auras, some recent evidence suggests that only about 20% experience them. Visually, auras are referred to as being positive or negative.

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma . They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include the following:

Speech disturbances.
Tingling, numbness, or weakness in an arm or leg.
Perceptual disturbances such as space or size distortions.
Confusion.

Migraine Attack. If untreated, attacks usually last from 4 to 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity.
Nausea, sometimes with vomiting.
Visual symptoms.
Facial tingling or numbness.
Extreme sensitivity to light and noise.
Looking pale and feeling cold.

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

[For more information see the Report #97, Migraine Headache.]

Tension-Type Headache

General Description. Tension-type headache (also called muscle contraction headache) is the most common of all headaches. It is may have the following characteristics:

Tension-type headache is often experienced in the forehead, in the back of the head and neck, or in both regions.
It is commonly described as a tight feeling, as if the head were in a vise. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.
Sufferers of tension-type headaches are more sensitive to light than the general population, even between attacks. They also may suffer from visual disturbances. (Neither of these symptoms is as intense as in people with migraines. Tension-type headaches also do not cause nausea or limit activities as migraine headaches do.)
Tension-type headaches can last minutes to days.

Chronic Daily Headaches. The International Headache Society has developed a classification called chronic daily headache, which includes tension headache and is any benign headache that occurs more than 15 days a month and is not associated with a serious neurologic abnormality. Chronic, daily headaches affect about 4% to 5% of the population.

Chronic daily headache is, in turn, subdivided into two categories:

Short-duration headaches (those lasting less than four hours). The most common short-acting chronic headaches are cluster headaches.
Long-duration (lasting more than four hours). Tension-type headaches are the most common long-duration chronic headaches, and, in fact, the most common chronic headaches in general.

[For more information see the Report #11, Tension-Type Headache. ]

WHAT CAUSES CLUSTER HEADACHES?

Cluster headaches, like migraine, are likely to be due to an interaction of abnormalities in the blood vessels and nerves that affect regions in the face.

Dilation of Blood Vessels

Cluster headaches are associated with dilation (widening) of blood vessels and inflammation of nerves behind the eye. In both cluster and migraine headaches blood vessels dilate, but in cluster headaches only the blood vessels behind the eyes pulsate. What causes these events and how they relate to cluster headaches are still unclear:

Because blood vessel dilation appears to follow, not precede, the pain, some central action originating in the brain is likely to be part of the primary process.
Some experts believe that at least some of the pain is caused by dilation in branches of the carotid artery (a major artery that supplies the brain with blood).
Some research suggests that a sensitivity to histamine, a chemical found in all body tissue, may play some role. Histamine opens blood vessels and can cause swollen membranes.

Abnormalities in the Hypothalamus

The root cause of cluster headaches is unknown but researchers are zeroing in on areas in the brain where primary abnormalities occur. Evidence now strongly suggests that abnormalities in the hypothalamus of the brain may play a role.

The hypothalamus is a complex brain structure located deep in the brain. It is involved in the regulation of many important brain chemicals, including the following:

Serotonin and norepinephrine. These are neurotransmitters (chemical messengers in the brain) that are involved with well-being and appetite.
Cortisol (stress hormones).
Melatonin (related to sleep).
Beta endorphins (involved with pain).
Nerve clusters that regulate the body's biologic rhythms (its circadian rhythms).

Circadian Abnormalities . Cluster attacks often follow the seasonal increase in warmth and light, beginning in summer and ending in the fall. In studying cluster headaches, then researchers are particularly interested in circadian rhythms, and in particular small clusters of nerves in the hypothalamus that act like biologic clocks. The most important nervous cluster is the suprachiasmatic nuclei (SCN), which appears to help coordinate the body's activities (sleep/wake) with the environment (dark/light). Some studies support the idea that some impairment in this biologic pacemaker may cause these terrible attacks.

Alterations in Serotonin. As with other headaches, particularly migraines, alterations in serotonin are of particular interest. This neurotransmitting hormone (chemical messenger in the brain) affects, among other functions, well being, sleep, and appetite. In cluster patients, there is some evidence of abnormal serotonin levels (although not as pronounced as in migraines). Some research has also suggested that serotonin may play an important role in the way circadian rhythms are expressed.

HOW SERIOUS ARE CLUSTER HEADACHES?

Pain

The pain of cluster headaches can be intolerable, and, in fact, a higher-than-average rate of suicide has been reported in men with these headaches. Eventually, the attacks cease, but experts cannot predict when or how they end.

A Description of a Cluster Headache Attack

"The pain was tearing, gnawing, boring, throbbing. The eye became so sensitive that it could not support the light, it became inflamed, spasmodically contracted and tearing, the temporal vessel [blood vessel in the temples] pulsated uncommonly strongly. In no position of the body did I find rest, and the pain became so insupportable that I rolled on the floor, afraid at any moment of getting convulsions. I had already resolved to open a vein in the afternoon when the noon bell tolled twelve o'clock and with this tolling sound there was momentaneous relief."

By John Muller, a German physician (written in the early 1800s)

Effects on Mental and Emotional Functioning

People with episodic cluster headaches tend to have low sexual appetites, impaired verbal memory, and a higher than average association between anxiety disorders and episodic cluster headaches. According to one 1999 study, for example, nearly a quarter of the patients met the criteria for having anxiety disorders. Furthermore the anxiety disorders occurred more frequently within the year before the onset of the cluster headaches. (None had depression disorders or abused alcohol or drugs.) Some studies suggest that the physiologic abnormalities associated with episodic cluster headaches may also contribute to these emotional and mental difficulties. All of these deficits are associated with the hypothalamus, the area in the brain that regulates the serotonin and norepinephrine neurotransmitter systems, which are involved with well-being and stress. A 2000 study suggested that the use of antidepressants that regulate serotonin and sleep may reverse mental impairment as well as improve well-being.

WHAT ARE THE RISK FACTORS FOR CLUSTER HEADACHES?

Gender

Cluster headache is, fortunately, rare, affecting about 9.8 out of every 100,000 Americans.

Cluster Headaches in Men. The ratio the headaches in men compared to women is about six or seven to one. The peak age of onset in men is the early thirties.

Cluster Headaches in Women. A 2001 study of cluster headaches in women reported that there were two ages of peak onset, the twenties and fifties. The attacks in women were of shorter duration than in men but the duration of the episodes and length of remission were similar. A related headache, chronic paroxysmal hemicrania, occurs mainly in females, but is even less common than cluster headaches.

Age

Cluster headaches typically start in the late 20s. In rare cases they begin in childhood, and about 10% of cases develop over age 60.

Life Style Factors

Cluster headaches appear to be more prevalent in those who are sociable, active, and responsible, and so a cluster headache is sometimes called "the executive headache." Lifestyle factors, including smoking, alcohol abuse, stress (in particular stressful work situations) do appear to play a very strong role in this headache. In one study, cluster headache patients tended to have more stressful jobs and be self-employed. A particularly high association exists between smoking and cluster headaches.

Family History and Genetic Factors

Although evidence for genetic factors has been week, there are some studies suggesting a role, at least in certain cases. A 2001 study, for example, reported a high occurrence in specific Italian families. Another study reported that 7% of patients with cluster headaches had a relative with the disorder.

Head Injury

Head injury may also increase the risk. In one study over 13% reported history of a head injury with loss of consciousness and nearly a quarter had experienced a head injury without loss of consciousness.

Sleep Apnea

Sleep apnea has been associated with cluster headache symptoms in many patients. In one study, 80% of cluster headache patients had sleep apnea. Sleep apnea is a disorder in which a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer. In most cases the person is unaware of these events, called apneas, although sometimes they awaken and gasp for breath. The condition is usually accompanied by snoring. One study suggested that in some people apneas may trigger cluster headache during the first few hours of sleep, making patients susceptible to follow-up attacks at midday to afternoon. Although the condition inevitably causes daytime sleepiness, people who have sleep apnea may not even be aware of it.

Some Factors that Trigger Cluster Attacks

Note: Triggers usually have an effect only during active cluster cycles. When the disorder is in remission, such triggers rarely set off the headaches.

Alcohol consumption.
High altitude (trekking, air travel).
Bright light (including sunlight).
Exertion.
Heat (hot weather, hot baths).
Foods high in nitrites.
Certain medications. (Those that cause blood vessel dilation, such as nitroglycerin, and various blood pressure medications.)
Cocaine.

HOW IS CLUSTER HEADACHE DIAGNOSED?

Medical and Personal History

For an accurate diagnosis, the patient should describe the following:

Duration and frequency of headaches.
Recent changes in their character.
The location of the pain.
The type (eg, throbbing or steady pressure).
The intensity of the headache.
Associated symptoms, such as visual disturbances or nausea and vomiting. (These are seen most often with migraines.)
Behaviors during a headache.
Sleep disturbances and daytime sleepiness (which could relate to sleep apnea, a possible risk factor for cluster headaches.)

Headache Diary to Identify Triggers

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches. Some tips include the following:

Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache. Experts are investigating triggers of headaches to determine if certain ones are more likely to set off different primary headaches.
Tracking medications is an important way of identifying possible rebound headache or transformed migraine.
Be sure to attempt to define the intensity of the headache. It may be indicated by using a number system:

1 = mild, barely noticeable.

2 = noticeable, but does not interfere with work/activities.

3 = distracts from work/activities.

4 = makes work/activities very difficult.

5 = incapacitating.

Physical Examination

In order to diagnose a chronic headache, the physician will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The physician may ask questions to test short-term memory and related aspects of mental function.

Ruling Out Other Headaches and Medical Disorders

As part of the diagnosis the physician should rule out other headaches and disorders. If the results of the history and physical examination suggest other or accompanying causes of headaches or serious complications, extensive, imaging tests are performed.

Chronic Paroxysmal Hemicrania. Chronic paroxysmal hemicrania is a close relative of cluster headache and very similar. It causes multiple, short, and severe daily headaches with similar symptoms. Unlike cluster headaches, the attacks are shorter (one to two minutes) and more frequent (occurring an average of 15 times a day). This headache tends to occur in women and always responds to treatment with indomethacin.

Tear in the Carotid Artery. Of note, in one case a tear in the carotid artery (which leads to the brain) caused a headache that very closely resembled a cluster headache and even responded to sumatriptan, a drug used to treat a cluster attack. Physicians should consider imaging tests for patients with a first episode of cluster headache in which this event is suspected.

Other Headaches. Other common headaches that might resemble cluster headaches are migraine, trigeminal neuralgia (TN), temporal arteritis, and sinusitis headache. Cluster symptoms, however, are usually precise enough to rule out these other headaches. [ See Boxes, Headache Symptoms of Serious Underlying Disorders and Causes of Secondary Headaches.]

Imaging Tests

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headache that wakes them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headache.

They are not recommended for patients with migraine and with no other abnormal indications. [ See Box, Headache Symptoms that Could Indicate Serious Underlying Disorders.]

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

Headache Symptoms that Could Indicate Serious Underlying Disorders

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition believing it to be one of their usual headaches. Such patients should call a physician promptly if the quality of a headache or accompanying symptoms has changed. Everyone should call a physician for any of the following symptoms:

Sudden, severe headaches that persist or increase in intensity over 24 hours.
Sudden, very severe headache, worse than any headache ever experienced (possible indication of stroke caused by bleeding, with a hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age fifty.
Headaches accompanied by memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs.
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma, which is excessive eye pressure).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender. A headache that is more likely in elderly people, particularly those with polymyalgia rheumatica, and is due to abnormal immune functioning. Untreated, it can cause blindness or even stroke.
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

WHAT ARE THE GENERAL GUIDELINES FOR MANAGING CLUSTER HEADACHES?

Of major concern was a 2000 Internet survey that reported an average delay of over six years before patients with cluster headache were accurately diagnosed. Such patients were often first inappropriately treated for other headaches (including having sinus surgery) and many were denied the appropriate treatments by their physician or insuring companies.

Treating Attacks

The most effective treatments for a cluster attack are the following:

Oxygen inhalation.
Triptans (injections of sumatriptan).

Relief can occur in five to 10 minutes. Of note, there is some thought that treatments which appear to relieve cluster headache symptoms may only be a delaying tactic and simply be postponing the attack.

Treatment for cluster headaches is very problematic because most attacks come on suddenly, occur daily, and episodic cycles may continue for weeks or months. Oral medications act too slowly to have much effect on a headache that typically lasts about an hour. Injected or intravenous headache medications may work but they cannot be used on a daily basis. The emphasis in managing cluster attacks, therefore, is in preventing them.

Preventing Attacks

Because effective therapy for cluster headaches is limited, most research efforts focus on the prevention of attacks during cluster cycles. A number of agents are available and may be used alone or in combination. In general, the steps for preventive management are as follows:

Transitional Medications. Patients should use headache medications (typically a triptan, a corticosteroid, or ergotamine) to control any attacks during the transition to on-going maintenance agents.

Maintenance Agents. Prevention of attacks during a cluster cycle is extremely important. Some experts recommend that the following agents for prevention be tried in this order:

Calcium-channel blockers. (At this time, evidence suggests that the best preventive agent for episodic cluster headaches is the calcium-channel blocker verapamil.)
Methysergide (this agent is also useful for episodic cluster headaches.)
Ergotamine (some experts start with ergotamine, which is useful in any case as a transitional medication).
Lithium (the best agent for chronic cluster headaches).
Corticosteroids for episodic cluster headaches in tapering form. (Some experts believe they should be used before some of the others.)
Antiseizure agents (valproic acid or topiramate).

Occasionally, indomethacin is effective. Other agents tried include melatonin, capsaicin, and beta blockers.) Combinations may be needed.

Life-Style Changes. Patients should avoid the following:

Alcohol.
Foods containing nitrates (such as smoked meats). No other dietary factors appear to play a role, for good or ill, in this disease.
Medications containing nitrates (such as nitroglycerin).
Smokers who can't quit should at least stop at the first sign of an attack and not smoke throughout a cycle.

One study suggested that vigorous physical exertion at the sign of an attack onset may help reduce and even abort an attack.

Surgery

Surgery may be considered for patients with chronic cluster headaches that do not respond to medications. It should be noted, however, that surgery is also limited in its effectiveness.

WHAT ARE THE TREATMENTS FOR CLUSTER ATTACKS?

Oxygen Treatment

Breathing pure oxygen (by face mask, for 15 minutes or less) is one of the most effective and safest treatments for cluster headaches. It is often the first choice. Inhalation of oxygen, which raises blood oxygen levels and therefore relaxes constricted blood vessels. Between 57% to 93% of patients have found it to be beneficial. It should be noted that pure oxygen can be toxic to the lungs when used for long durations.

Triptans

Triptans are migraine agents that are proving to have an important role in stopping a cluster attack. Injections of sumatriptan (Imitrex) are the standard treatments. In one 1998 analysis of 2031 attacks in 52 patients, it was successful in 88% attacks, and 42% of patients were pain-free within 15 minutes in over 90% of their attacks. (The nasal spray form is not as effective.) Other triptans, including rizatriptan (Maxalt) and zolmitriptan (Zomig), may prove to be good alternatives. In one study, zolmitriptan brought significant relief within 30 minutes for many episodic (but not chronic) cluster patients.

Side Effects and Complications of Triptans. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, can include the following:

Nausea.
Dizziness.
Muscle weakness.
Other effects include tingling, a warm sensation, heaviness in the chest, and discomfort in the ear, nose, and throat.

The following are potentially serious problems.

Complications on the Heart and Circulation. Triptans narrow (constrict) blood vessels. Because of this effect, very rarely spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are not only rare but occur primarily in patients with an existing history or risk factors for these conditions.
Serotonin Syndrome. Triptans also affect serotonin and so people taking antidepressants that increase serotonin levels (which are most antidepressants) should avoid taking both. The effects of such combinations may cause a so-called serotonin syndrome, which causes mental changes, restlessness, tremor, chills, sweating, and colitis. Some physicians believe, however, that the risk for the syndrome from taking both classes of drugs is very small.

Ergotamine

DHE injections have stopped cluster attacks within five minutes in many patients. Ergotamine aerosols or ergotamine suppositories with caffeine may be useful. When using the aerosol the patient usually inhales two or three times. They should be sure to shake the canister vigorously and administer the spray while making an inhalations immediately after a forced exhalation. The patient should then hold the breath for several seconds before slowly exhaling. Proper administration can produce an effective response 80% of the time. (Oral and under-the-tongue preparations of ergotamine are ineffective because of the brevity of cluster attacks.)

Local Anesthetics

Lidocaine, a local anesthetic, may be useful in nasal-spray or nasal-drop form for cluster attacks. Some reports suggest that it is helpful for most patients within about 40 minutes.

WHAT ARE THE MEDICATIONS USED FOR PREVENTING CLUSTER HEADACHES?

Calcium-Channel Blockers

Calcium-channel blockers are important agents for preventing cluster headaches. They are among the most useful agents for episodic chronic cluster headaches and may be useful for chronic cluster headaches. Verapamil (Calan) is the standard calcium-channel blocker used for headache prevention. Constipation is a common side effect. No one taking any calcium-channel blocker should withdraw abruptly, because such action could dangerously increase blood pressure. Overdose can cause dangerously low blood pressure and slow heart beats. It should be noted that drinking grapefruit juice or eating grape fruit with these drugs could increase their effects, sometimes to toxic levels. However, some of its effects can cause heart failure in patients with heart dysfunction.

Methysergide

Methysergide (Sansert) is also used for preventing episodic cluster headaches. (It is not very effective for chronic cluster headaches.) Improvement usually occurs within a few days although it may be delayed for up to two weeks. Prolonged methysergide therapy can cause serious side effects, including scarring of internal organs. This is not usually a problem for cluster headache patients, since they only require the drug for about four to six weeks. Nevertheless, patients should report any of the following symptoms immediately: cold, numb, and painful hands and feet; leg cramps on walking; or any type of back or chest pain.

Lithium

Lithium (Eskaith, Lithane, Lithobid, Lethonate, Lithotabs), commonly used for bipolar disorder, is beneficial for cluster headaches and is the most effective agent for chronic cluster patients. The patient usually experiences benefits within the two weeks, often within the first week. It is not clear how or why it works for cluster headache patients. Lithium may be used alone or with other drugs.

Toxic Effects. Minor toxic reactions include the following:

Trembling hands.
Nausea.
Increased urine output.
Some loss of coordination.

More severe reactions, which occur at higher blood levels, are the following:

Convulsions.
Uncontrolled jerky movements in arms and legs.
Blurred vision.
Vomiting.
Stupor.
Coma.

Very high blood levels of lithium can be fatal.

If toxicity occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on severity:

Patients are given fluids and drugs to increase excretion of lithium salts.
Gastric lavage, a procedure that rinses the stomach may be used to treat very recent overdoses.
Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.

Long-Term Side Effects. Even for patients who do not experience a toxic response, long-term use of lithium is not without problems. Some patients may experience the following:

An unpleasant taste in the mouth.
Hair loss.
Weight gain. In one study 16% of patients gained weight. It is a frequent reason for noncompliance and for relapse.
Skin eruptions that can resemble acne. (It can worsen psoriasis in patients who also have this condition.)
Thyroid problems. Up to 20% of patients who take lithium develop symptomatic hypothyroidism, and another 20% to 30% develop hypothyroidism without symptoms.
An increased risk for diabetes.
A blunted sexual drive.
Dulled emotions and mental acuity.
Memory loss.
Lack of motor coordination.
An increased risk for diabetes associated with kidney impairment.
Reduced sensitivity to light.
A reduced sensitivity to light that affects color recognition slightly. This might cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include the following:

Nonsteroidal anti-inflammatory drugs (NSAIDs).
Thiazide diuretics.
ACE inhibitors.

There have been reports of interactions between lithium and certain drugs commonly used in combination, including the following:

Antipsychotics.
Anticonvulsants.
Calcium-channel blockers.
It should be noted that the risks associated with these drugs are very low, but caution is needed.

Other Factors that Affect Lithium Levels. In addition to drugs, other factors may affect lithium levels, including the following:

Seasonal change. For instance, one study suggested that lithium levels may be higher in summer.
Menstrual cycle. Lithium levels may drop during the premenstrual phase.
Weight loss.
Changes in salt intake.
Dehydration.
Diarrhea.

Patients should be sure to contact their physician if they have any suspicious symptoms or illnesses.

Anti-Seizure Drugs

Valproate. The anti-epileptic drug valproate (Depakene, Depakote) has been used with some success. One center reported that the majority of patients with chronic cluster headaches who took valproate for an average of 11 months had a response that was greater than 50%, and 28% of them had a complete response to the medication. Side effects include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). It can also cause birth defects and, in rare cases, liver toxicity.

Topiramate. Other, newer anti-seizure drugs that have fewer side effects are being investigated for chronic headaches. Studies on topiramate (Topamax) are the most promising. For example, in a 2001 study of patients who had failed all other treatments, topiramate induced remissions within one day to three weeks that lasted an average of 1.4 weeks. In other small trials topiramate, 87% of patients achieved remission and 60% achieved a complete response.

Capsaicin

A nasal spray form of capsaicin has shown promise in the prevention and treatment of cluster headaches. Capsaicin is a component of hot red peppers that seems to reduce substance P, a chemical in the body that contributes to inflammation and the delivery of pain impulses.

Transitional Agents

Certain medications are useful as transitional agents. These medications are used after cluster episodes to stabilize the patient while the preventive maintenance can become effective.

Ergotamine. Drugs containing ergotamine (sometimes called ergots) causes contractions of smooth muscles, including those in blood vessels, and are commonly used for migraine. Taking them before an expected cluster attack produces good results for many patients. One ergot-derived drug called dihydroergotamine (D.H.E.) is administered by injection, which can be performed by the patient at home. It is also available as a nasal spray (Migranal), which may have fewer side effects than the injection. Ergotamine itself is available in oral tablets (Ergomar, Wigraine, Ercaf) and in rectal suppositories (Cafergot). Cafergot, Wigraine, and Ercaf contain caffeine. An ergotamine inhaler is being investigated. Side effects of ergotamine include nausea, dizziness, tingling sensations, muscle cramps, and chest or abdominal pain. Ergotamine has toxic effects at high levels. It also causes persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke. Pregnant women, people over 60, and those with serious, chronic health problems, particularly those of the heart and circulation, should avoid these medications altogether. As with other migraine drugs, if ergotamine is taken more than twice a week, the patient is at risk for rebound headaches when the drug is withdrawn, although cluster patients appear to be at lower risk for this effect than other headache patients.

Corticosteroids. A corticosteroid is very useful as a transitional agent for stabilizing patients after an attack until they a maintenance agent, such as a calcium-channel blocker, begins to take effect The corticosteroid drug prednisone is effective in up to 90% of episodic cluster headaches. The drug is typically taken for a week and then gradually tapered off. If headaches return, then it may be administered again. Unfortunately, long-term use of steroids can lead to serious side effects so they cannot be taken for on-going prevention.

Other Drugs Investigated for Prevention

Methylergonovine. Methylergonovine maleate (Methergine) is an ergot derivative being investigated to prevent cluster headaches. In one trial in which it was added to other preventive therapies, 95% of the patients reported a more than 50% reduction in the frequency of headaches within a week of initiating the drug. Patients with high blood pressure, who are pregnant, or have allergies, should not use it.

Baclofen (Lioresal). Baclofen is a drug that relaxes muscle spasms. Small studies are reporting some success. For example, in a 2001 study, 12 out of 16 patients reported an end of attacks within a week and another one became headache-free by the second week. (The remaining three patients became worse, however, and required other agents.) Three of the patients who improved experienced an additional cluster cycle, which cleared when they took another course of baclofen.

Botulinum. Botulinum toxin A (Botox) injections are being used for a number of conditions requiring muscle relaxation. (This potentially deadly toxin is very safe when minuscule amounts are injected into small muscles.) Botox has been promising for migraine sufferers, and is now being studied for cluster headaches. It is too early yet to gauge any real benefits.

Glucosamine. There have been some reports that that glucosamine, an alternative agent used for osteoarthritis, may prevent migraine attacks. Some researchers theorize this substance may reduce inflammation that affects nerves involved in vascular headaches. Whether this agent has any effect on cluster headaches is unknown.

Histamine Desensitization. Because cluster patients may be sensitive to histamine, some research has engaged in using antihistamines and histamine desensitization procedures. In general, such treatments have been disappointing. In one 1999 study, however, patients with intractable cluster headaches were given intravenous histamine as way of desensitizing their immune system to histamine. After treatment, which included other therapies, over 80% of the patients improved and the headache index, a measure of severity, dropped from 74.7 to 18.2 per month. Many of those who responded to the treatment were free of headaches for 16 to 17 months.

Treatment for Sleep Apnea

Patients with cluster headaches and who suffer from daytime sleepiness should consider seeking a possible diagnosis of sleep apnea. Anyone who has both should then strongly consider treatment for the apnea as possible therapy for cluster headaches.

In one case study, a patient with both cluster headaches and apnea was treated with nasal continuous positive airway pressure (CPAP) and experienced substantial reduction in the frequency and severity of cluster headaches. Currently, CPCP is the best treatment for severe obstructive and mixed sleep apnea. It works in the following way:

The treatment employs a machine weighing about five pounds that fits on a bedside table.
A mask containing a tube connects to the device and fits over just the nose.
The machine supplies a steady stream of air through a tube and applies sufficient air pressure to prevent the tissues from collapsing during sleep. [For more information see the Report #65, Sleep Apnea .]

WHAT ARE SURGICAL TREATMENTS FOR CLUSTER HEADACHES?

Surgical intervention may be considered for patients with chronic cluster headaches that do not respond to treatments at all or when they have not gone into remission for at least a year. Surgery has limited success, however, and can have distressing side effects.

Radiofrequency Retrogasserian Rhizotomy

The standard surgical approach uses a technique called percutaneous radiofrequency retrogasserian rhizotomy (PRFR) that creates heat to destroy the pain carrying nerve fibers in the face. Unfortunately complications are common and include numbness, weakness during chewing, changes in tearing and salivating, and facial pain. In severe cases, it may effect the cornea and cause vision loss.

Percutaneous Retrogasserian Glycerol rhizolysis

Percutaneous retrogasserian glycerol rhizolysis (PRGR) is a less invasive technique and has fewer complications. It involves injections of glycerol to block the facial nerves that cause the pain. In one study, 83% of patients reported immediate relief after one or two injections. Cluster headache recurred, however, in about 40% of the patients.

Microvascular Decompression of the Trigeminal Nerve

Microvascular decompression of the trigeminal nerve may be an option. With this procedure, the surgeon frees the trigeminal nerve from any blood vessels that are pressing against it. (The trigeminal nerve is the major nerve responsible for facial sensation.) In one study, over 73% of patients reported at least 50% relief. Half of these patients reported 90% relief but the level of benefit fell to less than 50% over time. Repeat procedures are rarely successful. The procedure is risky, and possible complications include nerve blood vessel injury and spinal fluid leakage. It does not have the common nerve damage effects in the face that PRFR does, however.

WHERE ELSE CAN HEADACHE SUFFERERS GET INFORMATION?

National Headache Foundation, 428 West St. James Place, 2nd Floor, Chicago, IL 60614-2750. Call (888-NHF-5552) or (312-388-6399) or on the Internet (http://www.headaches.org)

Publishes an excellent quarterly newsletter, Head Lines , containing news, research reports, book reviews, letters and other items, is included in the $20 annual membership fee. For information on specific headaches, send a self-addressed #10, double-stamped envelope. Briefly describe symptoms; the foundation has over 200 separate fact sheets on different types of headaches.

American Headache Society (http://www.ahsnet.org/) and affiliated organization American Council for Headache Education (http://www.achenet.org/)

19 Mantua Road, Mt. Royal, NJ 08061. Call (609-423-0258)

AHS Publishes the journal Headache (http://ahsnet.org/journal/)

American Academy of Neurology, 1080 Montreal Avenue, St. Paul, Minnesota 55116. Call (651-695-1940) or on the Internet (http://www.aan.com/)

Web site offers good information and provides names of neurologists for specific locations.

National Institute of Neurological Disorders and Stroke, PO Box 5801, Bethesda, MD 20824. Call (301-496-5751) or on the Internet (www.ninds.nih.gov)

Internet support group (http://www.clusterheadaches.com/)