Headaches - cluster
Highlights
Verapamil May Cause Heart Problems
Verapamil (Calan) is a blood pressure medication that is used "off-label" as a first-line preventive treatment for cluster headaches. However, when used for cluster headache, this drug may sometimes cause dangerous disturbances in heart rhythms (arrhythmia), according to a 2007 study in Neurology. The researchers recommend that patients who take verapamil should receive regular electrocardiograms to monitor for any signs of potential heart problems.
Zolmitriptan for Cluster Headache Treatment
Zolmitriptan (Zomig) nasal spray is a safe and effective treatment for cluster headache pain, indicates a 2007 study in Neurology. Because cluster headache pain can quickly become excruciating, researchers would like to find a treatment that can provide rapid pain relief. In a small study, patients who administered either 5 mg or 10 mg of zolmitriptan during a cluster headache attack received relief within 30 minutes. For some patients, the higher dose took effect within 10 minutes. Zolmitriptan is a triptan drug that is commonly used to treat migraine headaches.
Occipital Nerve Stimulation
Occipital nerve stimulation may be a safer alternative to deep brain (hypothalamus) stimulation. Both investigational neurostimulation techniques involve surgically implanting a wire in the brain. The wire is then attached to a small pacemaker-like device. Neurostimulation is used only for patients with intractable cluster headaches who have not responded to drug therapy. In studies published in 2007 in Lancet and Lancet Neurology, several patients who received occipital nerve stimulation became pain-free or had a reduction in the frequency of their cluster headache attacks.
Introduction
Most people have had headaches. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.
The brain is insensitive to pain, so that is not what hurts when you have a headache. Rather, the 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
Doctors categorize headaches as either primary or secondary. The category helps to distinguish the many different kinds of headaches and to determine right treatments for each.
A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: tension-type, migraine, and cluster headaches.
- Tension headache is the most common primary headache and accounts for 90% of all headaches.
- Migraines are the second most frequently occurring primary headaches. Migraine is referred to as a neurovascular headache because it is most likely caused by an interaction between blood vessel and nerve abnormalities.
- Cluster headache is a less common type of primary headache. Although it is sometimes referred to as a neurovascular headache, evidence now suggests that its cause lies in the hypothalamus, a region deep in the brain that regulates, among other functions, the biologic rhythms of the body.
Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.
The International Headache Society has developed a classification system that includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.
Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily or almost daily and they can be quite debilitating.
Chronic daily headaches are, in turn, subdivided into two categories:
- Short-duration headaches, or those lasting fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
- Long-duration headaches, which last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.
Click the icon to see an image of the different types of headache.
Cluster Headaches
Cluster headaches are among the most painful, and least common, of all headaches. The pain can be so excruciating that they are sometimes referred to as “suicide headaches." Their signature is a pattern of periodic cycles (“clusters”) of headache attacks, which may be either:
- Episodic. Attacks occur regularly for 1 week to 1 year, separated by long pain-free periods that last at least 1 month. Between 80 – 90% of patients have episodic cycles. A significant percentage of people who experience a first cluster attack do not have another one.
- Chronic. Attacks occur regularly for more than 1 year, with pain-free periods lasting less than 1 month. Between 10 – 20% of patients have chronic cluster headaches. The chronic form is very difficult to treat.
Cluster headaches usually strike suddenly and without warning, although some people experience a migraine-type aura before the attack. A stabbing pain quickly develops behind one eye or on the temple of one side of the head. The pain then spreads to the forehead, jaw, upper teeth, or neck. The pain and other symptoms usually remain on one side of the head.
Other typical symptoms include:
- Swollen or droopy eyelid
- Watery, tearing eye
- Contraction of the eye pupil
- Stuffy or runny nose
- Forehead and facial sweating
- Restlessness and agitation
- Nausea and vomiting
- Intolerance to light and sound
Timing of an Attack. Headache attacks tend to occur with great regularity at the same time of day. (For this reason, cluster headaches are sometimes referred to as “alarm clock” headaches.) About 75% of attacks occur between 9 p.m. - 10 a.m. Attacks may also peak between 1 - 3 p.m.
Duration of an Attack. A single cluster attack is usually brief but extremely painful, lasting about 15 minutes – 1.5 hours if left untreated.
Number of Attacks per Day. During an active cycle, people can experience as few as 1 attack every other day to as many as 8 attacks a day.
Duration of a Cycle. Attack cycles typically occur seasonally -- most often in spring and autumn. Usually a patient has one or two cycles per year that each last 1 - 3 months.
Headache-Free Remissions Between Cycles. Such cycles are followed by headache-free periods lasting at least several weeks, and often for many months. Sustained remissions can last for 20 years.
Migraine Headache: General Description of Its Course
Migraine is now recognized as a chronic illness, not simply as a headache. Migraines are often classified by whether they are accompanied by auras:
- Common migraines are without auras; about 75% of migraines are the common type.
- Classic migraines are those with auras.
A person may experience one or the other at different times. 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:
- 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 in 20 - 25% of patients. 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:
- 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 - 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
Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)
Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.
Tension-Type Headache
Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and may have the following characteristics:
- The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
- Depression, anxiety, and sleeping problems may accompany persistent headaches.
People who suffer from tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)
Other Primary Headaches
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 (1 - 2 minutes) and more frequent (occurring an average of 15 times a day). This headache is even rarer than cluster headache, tends to occur in women, and always responds to treatment with indomethacin.
Hemicrania Continua. Hemicrania continua occurs mostly in women. The patient generally experiences continuous low-level headache always on one side of the face. Periodic attacks can last days to weeks, which can be mild to severe, and may resemble migraines. (About 10% of patients experience remissions.) The headaches can usually be treated successfully with indomethacin, which helps differentiate if from other headaches, notably migraines.
SUNCT Syndrome. A disorder called SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) causes stabbing or burning eye pain that may resemble cluster headaches, but attacks are very brief (lasting about a minute) and may occur more than 100 times per day. Red and watery eyes, sweating forehead, and congestion are typical. This rare headache is more common in men and does not respond to other headache treatments.
Causes
Cluster headaches, like migraines, are likely due to an interaction of abnormalities in the blood vessels and nerves that affect regions in the face.
Evidence strongly suggests that abnormalities in the hypothalamus, a complex structure located deep in the brain, may play a major role in cluster headaches. Advanced imaging techniques have shown that a specific area in the hypothalamus is asymmetrical in these patients and is activated during a cluster headache attack.
The hypothalamus is involved in the regulation of many important chemicals and nerve pathways, including:
Click the icon to see an image of the hypothalamus.
- Nerve clusters that regulate the body's biologic rhythms (its circadian rhythms)
- Serotonin and norepinephrine. These are neurotransmitters (chemical messengers in the brain) that are involved with well-and appetite.
- Cortisol (stress hormones)
- Melatonin (a hormone related to the body's response to light and dark)
- Beta-endorphins (substances that modulate pain)
Circadian Abnormalities. Cluster attacks often occur during specific sleep stages. They also often follow the seasonal increase in warmth and light, beginning in summer and ending in the fall. Researchers have therefore focused attention on 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 failure in this biologic pacemaker may impair the pain control system and cause these terrible attacks.
The hormone melatonin is also involved in the body's biologic rhythms.
Alterations in Serotonin. The brain chemical serotonin is of particular interest in the study of headaches, particularly migraine and cluster headaches. This neurotransmitter (chemical messenger) affects, among other functions, well-being, sleep, and appetite. Some research has also suggested that serotonin may play an important role in the way circadian rhythms are expressed. There is some evidence of abnormal regulation of brain serotonin levels in patients with cluster headaches (although it is not as pronounced as in patients with migraine).
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 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).
- Certain substances, such as histamine and a protein called endothelin-1 that widens blood vessels and are being investigated for a possible role in cluster headaches.
Nitric Oxide. Nitric oxide is a small molecular messenger that activates nerve pathways in the brain, muscles, or elsewhere. It may contribute to major primary headaches (tension-type, cluster, and migraines) by specifically triggering inflammation and overactivity in the trigeminal nerves. (This is a major nerve pathway that runs from the brain stem to the head and face.) However, other factors must be present that make patients with cluster headaches susceptible to the actions of nitric oxide.
Immune Abnormalities. Researchers are also investigating whether overproduction of certain immune factors called cytokines may contribute to cluster headaches. Cytokines, such as interleukins, are known to cause inflammation and injury in high amounts. To date, however, there is no evidence that they play any role.
Abnormalities in the Sympathetic Nervous System. Some evidence suggests that abnormalities in the sympathetic (also called autonomic) nervous system may contribute to cluster headaches. This system regulates non-voluntary muscle actions in the body, such as in the heart and blood vessels.
About 90% of people seeking help for headaches have a primary headache. The rest have secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.
Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. 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. Both types of headache 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.)
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, which 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 pain 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).
Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also called TMD), which 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. This condition often coexists with chronic tension headache.
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.
Click the icon to see a depiction of glaucoma.
Click the icon to see an image of the slitlamp test.
Click the icon to see an image of the visual field test.
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 migraines or sinus headaches.
Hypertension. Although many people attribute headaches to high blood pressure, the weight of evidence suggests that hypertension does not cause head aches. 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.
Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.
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 way as the primary headache. 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. 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. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.
Prognosis
The pain of cluster headaches can be intolerable. 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 will end.
People with episodic cluster headaches tend to have low sexual appetites and impaired verbal memory and are more likely to suffer from anxiety. According to one study, nearly a quarter of patients with cluster headaches met the criteria for having anxiety disorders. Furthermore, the anxiety disorders occurred more frequently within the year before the onset of their cluster headaches. (None of these patients had depression or abused alcohol or drugs.) Some studies suggest that the biologic abnormalities in the hypothalamus of the brain that are associated with episodic cluster headaches may also contribute to these emotional and mental difficulties.
In rare cases, patients with cluster headaches have migraine-like aura. Headaches that are accompanied by aura may increase the risk of stroke or transient ischemic attack (TIA). A 2005 study found that patients who had headaches with auras were about four times more likely to have a stroke or TIA than patients who had headaches without aura. TIA symptoms are similar to those of stroke, but last only briefly. A TIA is often a warning sign that a person is at risk for a more severe stroke.
Headaches with auras may also increase the risk for eye retinal damage (retinopathy), which can lead to severe vision problems or blindness. The risks for stroke and retinopathy are associated with the effects of aura-related headaches on small blood vessels in the brain and the eyes.
Risk Factors
Cluster headaches are rare, affecting less than 1% of the population.
Cluster Headaches in Men. Cluster headaches are much more common in men than in women, about 85% of cluster headache sufferers are men. The peak age of onset for men is the 20s to early 30s.
Cluster Headaches in Women. Studies of cluster headaches in women report that there are two ages of peak onset, the 20s and 50s. In some studies, attacks in women were of shorter duration than in men, but the duration of the episodes and length of remission were similar. Unlike with migraines, fluctuations in estrogen and other female hormones do not appear to influence the onset of attacks, although attacks may be less frequent during pregnancy.
Cluster headaches typically start in the late twenties. In rare cases they begin in childhood, and about 10% of cases develop after age 60.
Lifestyle factors, including smoking, alcohol abuse, and stress (in particular stressful work situations), appear to play a very strong role in cluster headaches. Smoking or alcohol use can trigger attacks. In a 2006 study, 70% of people with cluster headaches were current smokers. About half reported that alcohol (most commonly red wine) triggered an attack.
Evidence for genetic factors has been weak, but there is a growing body of research suggesting a family history in about 5 - 10% of patients. Some evidence suggests that cluster headaches in women may be more likely to be genetically based, particularly when they first occur at younger ages.
One study reported that 26% of cluster headache sufferers also had a personal history of migraines, and 33% had a family history of this headache. Studies have reported that about 15% of patients have both kinds.
Head injury may also increase the risk of cluster headaches. In one study, over 13% of patients reported a history of a head injury that caused loss of consciousness, and nearly a quarter had experienced a head injury without loss of consciousness.
Cluster headaches tend to occur during specific sleep stages and have been associated with several sleep disorders, including narcolepsy, insomnia, and sleep apnea.
Sleep apnea, a disorder in which a person stops breathing during the night, perhaps hundreds of times, is of particular interest. Studies have reported sleep apnea in 30 - 80% of patients with cluster headaches. 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 during the following midday to afternoon periods. Treating patients who have both disorders with a device called CPAP, which opens the airways, may help improve both conditions. [See In-Depth Report #65: Sleep apnea.]
The following conditions and substances might trigger cluster attacks:
- Alcohol
- High altitudes (trekking, air travel)
- Bright light (including sunlight)
- Exertion
- Heat (hot weather, hot baths)
- Foods high in nitrites (such as bacon and preserved meats)
- Certain medications (including those that cause blood vessel dilation, such as nitroglycerin, and various blood pressure medications)
- Cocaine
Triggers usually have an effect only during active cluster cycles. When the disorder is in remission, such triggers rarely set off the headaches.
Diagnosis
In two surveys, patients reported a delay of 1 - 6 years in the diagnosis of their headaches. In one of the surveys, migraine-like symptoms (light and sound sensitivity and nausea) were major reasons for the frequent misdiagnosis by family doctors. About a third of the patients sought help from dentists and another third from ear-nose-throat specialists. In most cases, patients were inappropriately treated for other types of headaches (including having sinus surgery).
For an accurate diagnosis, the patient should describe:
- Duration and frequency of headaches
- Recent changes in their character
- Location of the pain
- Type of pain (throbbing or steady pressure)
- Pain intensity
- Associated symptoms (visual disturbances or nausea and vomiting)
- Behaviors during a headache
- Snoring, sleep disturbances, and daytime sleepiness (which could relate to sleep apnea, a possible risk factor for cluster headaches)
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:
- Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.
- Tracking medications is an important way of identifying so-called rebound headaches, which can arise when drugs that are taken frequently are discontinued.
- 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 or activities
3 = Distracts from work or activities
4 = Makes work or activities very difficult
5 = Incapacitating
To diagnose a chronic headache, the doctor will examine the head and neck and usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.
As part of the diagnosis, a doctor 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.
Migraines. Cluster headaches are often misdiagnosed as migraines but they are quite different:
- Frequency and Duration. Cluster headaches generally last 15 minutes to a few hours and can occur several times a day. A single migraine attack is continuous over the course of one or several days.
- Behavior. Cluster headache sufferers tend to move about while migraine sufferers usually want to lie down.
Nevertheless, in both cases, the headache suffers can be highly sensitive to light and noise, which may make it difficult to distinguish between them.
Other Headaches. Other headaches that resemble migraines include SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and chronic paroxysmal hemicrania, which are other primary headaches, and some secondary headaches notably trigeminal neuralgia (TN), temporal arteritis, and sinus headaches. Cluster symptoms, however, are usually precise enough to rule out these other types of headaches.
Tear in the Carotid Artery. A tear in the carotid artery (which leads to the brain) can cause pain that resembles a cluster headache. People with this condition may even respond to sumatriptan, a drug used to treat a cluster attack. Doctors should consider imaging tests for patients with a first episode of cluster headache in which this event is suspected.
Orbital Myositis. An unusual condition called orbital myositis, which produces swelling of the muscles around the eye, may mimic symptoms of cluster headache. This condition should be considered in patients who have unusual symptoms such as protrusion of the eyeball, painful eye movements, or pain that does not dissipate within three hours.
Imaging tests of the brain may be recommended under the following circumstances:
- If the results of the history and physical examination suggest neurologic problems
- If headaches wake patients during the night
- If new headaches develop 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)
- If headaches are becoming worse
Imaging tests are not recommended for patients with migraines and no other abnormal indications.
The following tests may be used:
- A CT (computed tomography) scan may help 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.
Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should 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 immediately call a doctor if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:
- Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
- Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
- Chronic or severe headaches that begin after age 50.
- Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
- 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).
- 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 (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
- 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).
Managing Cluster Headaches
Patients with cluster headaches face significant difficulties in the management and treatment of their problems:
- In two surveys, patients reported a delay in the diagnosis of their headaches of 1 - 6 years. In most of these cases, patients were inappropriately treated for other headaches (including having sinus surgery).
- Treatment for cluster headaches is problematic because most attacks come on suddenly and occur daily, while episodic cycles may continue for weeks or months. Most oral medications used for other headaches act too slowly to have much effect on a cluster headache, which 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. Verapamil and corticosteroid drugs are most commonly used for prevention.
- Cluster headaches are difficult to study. First, they are very uncommon, so there are few well-controlled investigations of this problem. Second, the placebo response is very high in studies on cluster headaches, with 7 - 43% of patients responding to dummy treatments.
The most effective treatments for a cluster attack are:
- Oxygen inhalation
- Triptan drugs (injections of sumatriptan)
Relief can occur in 5 - 10 minutes.
Because effective therapy for cluster headaches is limited, most research efforts focus on the prevention of attacks during cluster cycles. A number of treatments are available and may be used alone or in combination. In general, the steps for preventive management are:
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 drugs.
Maintenance Drugs. Prevention of attacks during a cluster cycle is extremely important. Although patients with episodic or chronic cluster headaches may take different medications, there does not appear to be much difference in their effectiveness for either type. The following are the most commonly used preventive drugs:
- Calcium-channel blockers. The calcium-channel blocker verapamil is most often used for preventing cluster headaches.
- Corticosteroids. Tapered doses of corticosteroids, such as prednisone, may be useful for preventing episodic cluster headaches.
- Lithium. Some studies suggest that lithium is the best drug for chronic cluster headaches.
- Methysergide. This drug is a serotonin inhibitor and is sometimes used for episodic cluster headaches.
- Antiseizure drugs. Of the antiseizure drugs, valproic acid is most often used. Others that may be useful include carbamazepine, gabapentin, and topiramate.
- Ergotamine. Some doctors start with ergotamine, which is useful as a transitional medication.
Doctors have prescribed other drugs, including indomethacin, melatonin, beta blockers, tricyclic and other antidepressants, and capsaicin. Some patients may need a combination of medicines.
Lifestyle Changes. Patients should avoid the following:
- Alcohol.
- Foods containing nitrates or nitrites (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 or even abort an attack.
Treatment for Acute Attacks
Breathing pure oxygen (by face mask, for 15 minutes or less) is one of the most effective and safest treatments for cluster headache attacks. It is often the first choice. Inhalation of oxygen raises blood oxygen levels, therefore relaxing narrowed blood vessels.
Triptans are drugs that are usually used to treat migraine headaches. They can also help stop a cluster attack. Injections of sumatriptan (Imitrex) are the standard triptan treatment. Sumatriptan injections work within 15 minutes in about three quarters of cluster attacks. The nasal spray form is also effective, and generally provides relief within 30 minutes. The spray seems to work best for attacks that last at least 45 minutes, although some people find it does not work as well as the injectable form.
Newer triptans used for cluster headache treatment include rizatriptan (Maxalt), naratriptan (Naramig, Amerge), and zolmitriptan (Zomig). Several 2006 and 2007 studies of zolmitriptan nasal spray indicated it was effective for cluster headache relief with few side effects.
Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, may include:
- Nausea
- Dizziness
- Muscle weakness
- Heaviness or pressure in the chest
- Tingling and numbness in the toes
- Rapid heart rate
Complications of Triptans. The following are potentially serious problems with triptans.
- Complications on the Heart and Circulation. Triptans narrow (constrict) blood vessels. Because of this action, spasms in the blood vessels may occur, which can cause stroke and heart attack. This is a rare but very serious side effect. Patients with a history of heart attack, stroke, angina, uncontrolled high blood pressure, peripheral artery disease, or heart disease should not use triptan drugs.
- Serotonin Syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptans, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with an SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.
The following groups should avoid triptans or take them with caution and only under doctor supervision:
- Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
- People taking antidepressants that increase serotonin levels.
- Pregnant women. Studies on the effects of triptans in this group are limited. One study suggested a higher incidence of preterm deliveries in pregnant women taking sumatriptan. No higher rates of still births or birth defects were reported. In general, pregnant women should avoid any medications if possible.
Injections of the ergotamine-derived drug known as dihydroergotamine (DHE) can stop cluster attacks within 5 minutes in many patients, offering benefits similar to injectable sumatriptan. Ergotamine is also available in the form of a nasal spray, rectal suppositories, and tablets. Ergotamine can have dangerous drug interactions with many medications. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label.
Methysergide (Sansert) is another ergot-based drug that is 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 2 weeks. Prolonged methysergide therapy can cause serious side effects, including scarring of internal organs, so it cannot be used long term. This is not usually a problem for patients with cluster headaches, since they need the drug only for about 4 - 6 weeks. Nevertheless, patients should immediately report to their doctors any of the following symptoms: cold, numb, and painful hands and feet; leg cramps on walking; any type of back or chest pain.
Lidocaine, a local anesthetic, may be useful in nasal-spray or nasal-drop form for stopping cluster attacks. Some reports suggest that it is helpful for most patients within about 40 minutes.
Preventive Medications
Calcium-channel blockers, commonly used to treat heart disease, are important drugs for preventing cluster headaches. Verapamil (Calan) is the standard calcium-channel blocker used for headache prevention. Constipation is a common side effect. Verapamil can also cause irregular heartbeats (arrhythmia), according to a 2007 study in Neurology. Patients who take verapamil for cluster headaches should have frequent electrocardiograms (EKGs) to monitor any potential development of arrhythmia.
People taking calcium-channel blockers should not stop taking the drug abruptly. Doing so can dangerously increase blood pressure. Overdose can cause dangerously low blood pressure and slow heart beats. Drinking grapefruit juice or eating grapefruit with these drugs can enhance their potency, sometimes to toxic levels that can cause heart failure in patients with heart disease.
Lithium (Eskalith, Lithane, Lithobid, Lethonate, Lithotabs), commonly used for bipolar disorder, can also help prevent cluster headaches. The patient usually receives benefit within 2 weeks of starting to take the drug, and often within the first week. Lithium may be used alone or with other drugs.
Side Effects. Side effects include:
- Trembling hands
- Nausea
- Increased urine output
- Some loss of coordination
More severe reactions, which occur at higher blood levels, are:
- Convulsions
- Uncontrolled jerky movements in arms and legs
- Blurred vision
- Vomiting
- Stupor
- Coma
Very high blood levels of lithium can be fatal.
Long-Term Side Effects. Even for patients who do not have a toxic response, long-term use of lithium is not without problems. Some patients may experience:
- An unpleasant taste in the mouth
- Hair loss
- Weight gain (a frequent reason why many patients stop taking lithium)
- Skin eruptions that can resemble acne (lithium can also worsen psoriasis in patients who have this condition)
- Thyroid problems -- Up to 20% of patients who take lithium develop symptomatic hypothyroidism (low thyroid), and another 20 - 30% develop hypothyroidism without symptoms
- Increased risk for diabetes
- Blunted sexual drive
- Dulled emotions and mental acuity
- Memory loss
- Lack of motor coordination
- Reduced sensitivity to light -- This may slightly affect color recognition and cause problems with night driving; 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:
- 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:
- Antipsychotics
- Anticonvulsants
- Calcium-channel blockers
Other Factors That Affect Lithium Levels. In addition to drugs, other factors may affect lithium levels, including:
- Seasonal change
- Menstrual cycle (lithium levels may drop during the premenstrual phase)
- Weight loss
- Changes in salt intake
- Dehydration
- Diarrhea
Patients should contact their doctor if they have any suspicious symptoms or illnesses.
Valproate. The anti-epileptic drug valproate (valproic acid, divalproex sodium, Depakene, Depakote) has been used with some success for preventing cluster headaches. It controls pain and reduces the frequency of attacks by more than half in many people with episodic or chronic cluster headaches. 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 promising. In small trials of topiramate, up to 87% of patients achieved remission, and 60% achieved a complete response. Still, about 25% of patients stop using it, either because it doesn't work or because the side effects are intolerable. They can include drowsiness, mood changes, tremor, and confusion.
Gabapentin. Another anti-seizure drug that has shown some benefit in isolated cases is gabapentin (Neurontin). Research on this drug in patients with cluster headaches, however, remains very limited.
Side Effects of Valproate and Other Anti-Seizure Drugs. The side effects given here are mostly associated with valproate. Other anti-seizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy, and then subsiding. Those of valproate include:
- Gastrointestinal problems (nausea, vomiting, heartburn)
- Visual disturbances
- Ringing in the ear
- Hair loss
- Weight changes (weight gain is a significant problem with valproate, while weight loss occurs with topiramate)
- Agitation
- Odd movements
- In women, menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
Very serious side effects are rare but include the following:
- Liver damage
- Convulsions
- Coma
- Pancreatitis (inflammation of pancreas) in adults and children
- Significant increase in risk for birth defects in pregnant women
A nasal spray form of capsaicin called civamide (Zucapsaicin) 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. In a small study, daily use of intranasal civamide resulted in more than a 50% reduction in headaches. Side effects include a burning sensation and excessive tearing.
Transitional medications are used after cluster episodes to stabilize the patient until preventive maintenance becomes effective.
Corticosteroid drugs (also called steroids) are very useful as transitional drugs for stabilizing patients after an attack until a maintenance drug, such as a calcium-channel blocker, begins to take effect. Prednisone (Deltasone) and dexamethasone (Decadron) are the standard steroid drugs used for short-term cluster headache transitional treatment. These drugs are typically taken for a week and then gradually tapered off. If headaches return, the patient may start taking the steroid again. Unfortunately, long-term use of steroids can lead to serious side effects so they cannot be taken for on-going prevention.
Angiotensin Receptor Blockers. Angiotensin receptor blockers (ARBs) are used to treat high blood pressure. Candestan (Atacand) is being investigated as a potential preventive medication for cluster headache.
Botulinum. Botulinum toxin A (Botox) injections are being used for several conditions requiring muscle relaxation, including smoothing wrinkles. (This potentially deadly toxin is very safe when minuscule amounts are injected into small muscles.) Botox has shown promise for migraine and tension headache sufferers and is now being studied for cluster headaches as well.
Melatonin. Small reports indicate that melatonin, a brain hormone that helps to regulate the sleep-wake cycle, may help prevent episodic or chronic cluster headaches. Melatonin supplements are sold in health food stories, but as with most natural remedies, the quality of different preparations varies, and they have not been rigorously tested for safety or effectiveness. Hormones such as melatonin are powerful substances, and additional studies are needed.
Glucosamine. There have been some reports that glucosamine, an alternative remedy commonly used for osteoarthritis, may prevent migraine attacks. Some researchers theorize this substance may reduce inflammation that affects nerves involved in vascular headaches. Whether it has any effect on cluster headaches is unknown.
Additional Therapies. Many patients with cluster headaches try alternative remedies for relief of pain. Treatments may include acupuncture, herbs, chiropractic, homeopathic remedies, reflexology, hypnosis, spiritual therapies, massage, aromatherapy, relaxation techniques, and yoga.
Surgery
Surgical intervention may be considered for patients with chronic cluster headaches that do not respond to treatments. Patients whose headaches have not gone into remission for at least a year may also be candidates for surgery. Most surgical approaches for cluster headache are still considered experimental. Surgy has shown limited success and can have distressing side effects. However, some surgical techniques, such as deep brain electrical stimulation, are showing promise.
Deep brain stimulation (also called neurostimulation) may relieve chronic cluster headaches in some patients who do not respond to drug therapy. A similar technique is approved for treating the tremors associated with Parkinson’s disease. The surgeon implants a tiny wire in a specific part of the hypothalamus. The wire, meanwhile, receives electrical pulses from a small generator implanted under the collarbone.
Although only a handful of patients have been treated, results to date are promising. Some patients have remained completely free of pain for an average of more than 7 months when the electrode is switched on. When the device is turned off, headaches reappear within days to weeks. The procedure is reversible and appears to be generally safe, although a few cases of fatal cerebral hemorrhage have occurred.
Occipital nerve stimulation is being investigated as a less invasive alternative to hypothalamus stimulation. Two 2007 studies in Lancet and Lancet Neurology reported promising results in a small group of patients with cluster headaches. Some patients became pain-free, while others had reduced frequency of headache attacks. Researchers suggest that occipital nerve stimulation may be less risky than deep brain stimulation.
The vagus nerve runs between the brain and the abdomen. Vagus nerve stimulation (VNS) is a surgical procedure in which a small generator is placed under the skin on the left side of the chest. A surgeon makes a second incision in the neck and connects a wire from the generator to the vagus nerve. A doctor programs the generator to send mild electrical pulses at regular intervals. These pulses stimulate the vagus nerve.
VNS is sometimes used to treat epilepsy and depression that does not respond to drugs. It is also being investigated as a possible treatment for chronic migraine and cluster headaches. In a 2005 study of six patients, VNS improved headache and helped a few patients return to work.
Percutaneous Radiofrequency Retrogasserian Rhizotomy. Percutaneous radiofrequency retrogasserian rhizotomy (PRFR) generates heat to destroy pain-carrying nerve fibers in the face. Small studies have reported good to excellence results in 83 - 92% patients. Unfortunately complications are common and include numbness, weakness during chewing, changes in tearing and salivation, and facial pain. In severe, but rare, cases, complications include damage to the cornea and vision loss.
Percutaneous Retrogasserian Glycerol Rhizolysis. Percutaneous retrogasserian glycerol rhizolysis (PRGR) is a less invasive technique than PRFR 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 headaches recurred, however, in about 40% of the patients.
Microvascular Decompression of the Trigeminal Nerve. Microvascular decompression frees the trigeminal nerve from any blood vessels that are pressing against it. 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 and blood vessel injury and spinal fluid leakage. It does not, however, have the common nerve damage effects in the face that PRFR does.
Resources
- www.i-h-s.org -- International Headache Society
- www.headaches.org -- National Headache Foundation
- www.americanheadachesociety.org -- American Headache Society
- www.aan.com -- American Academy of Neurology
- www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
- www.ouch-us.org -- Organization for Understanding Cluster Headaches
- www.clusterheadaches.com -- Support group for people with cluster headaches
References
Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients. Lancet. 2007 Mar 31;369(9567):1099-106.
Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol. November 2006. [Epub ahead of print 11 September 2006]
Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007 Aug 14;69(7):668-75.
Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet Neurol. 2007 Apr;6(4):314-21.
Rapoport AM, Mathew NT, Silberstein SD, Dodick D, Tepper SJ, Sheftell FD, Bigal ME. Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study. Neurology. 2007 Aug 28;69(9):821-6.
Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007 May 15;68(20):1694-700.
Schurks M, Kurth T, de Jesus J, Jonjic M, Rosskopf D, Diener HC. Cluster headache: clinical presentation, lifestyle features, and medical treatment. Headache. 2006 Sep;46(8):1246-54.
Sostak P, Krause P, Forderreuther S, Reinisch V, Straube A. Botulinum toxin type-A therapy in cluster headache: an open study. J Headache Pain. 2007 Sep 24; [Epub ahead of print]
Van Vliet JA, Eekers PJ, Haan J, Ferrari MD; Dutch RUSSH Study Group. Evaluating the IHS criteria for cluster headache -- a comparison between patients meeting all criteria and patients failing one criterion. Cephalalgia. 2006 Mar;26(3):241-5.
Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
