Cluster Headaches August 30th 2004
To the Migraines & Headaches Center
The term "cluster headache"
refers to a type of headache that recurs over a period of time. People who have cluster
headaches experience an episode one to three times per day during a period of time (the
cluster period), which may last from 2 weeks to 3 months. The headaches may disappear
completely (go into "remission") for months or years, only to recur. A cluster
headache typically awakens a person from sleep 1 to 2 hours after going to bed. These
nocturnal attacks can be more severe than the daytime attacks. Attacks appear to be linked
to the circadian (or "biological") clock. Most people with cluster headaches
will develop cluster periods at the same time each year -- either in the spring or fall or
the winter or summer. Cluster headaches are one of the most severe types of headache. It
can be 100 times more intense than a migraine attack.
Who Gets Cluster Headaches?
Cluster headaches are the least common type of headaches, affecting less than 1 in 1,000
people. Cluster headaches are a young person's disease: the headaches typically start
before age 30. Cluster headaches are more common in men, but more women are starting to be
diagnosed with this problem. The male to female ratio is 2-3:1.
What Causes Cluster Headaches?
The true biochemical cause of cluster headaches is unknown. However, the headaches occur
when a nerve pathway in the base of the brain (the trigeminal-autonomic reflex pathway) is
activated. The trigeminal nerve is the main nerve of the face responsible for sensations
(such as heat or pain.)
When activated, the trigeminal nerve causes the eye pain associated with cluster
headaches. The trigeminal nerve also stimulates another group of nerves that causes the
eye tearing and redness, nasal congestion and discharge associated with cluster attacks.
The activation of the trigeminal nerve appears to come from a deeper part of the brain
called the hypothalamus. The hypothalamus is home to our "internal biologic
clock" which regulates our sleep and wake cycles on a 24-hour schedule. Recent
imaging studies have shown activation or stimulation of the hypothalamus during a cluster
attack. Cluster headaches usually are not caused by an underlying brain condition such as
a tumor or aneurysm.
What Triggers Cluster Headaches?
The season is the most common trigger for cluster headaches, which often occur in the
spring or autumn. Due to their seasonal nature, cluster headaches are often mistakenly
associated with allergies or business stress. The seasonal nature of cluster headaches
most likely results from stimulation or activation of the hypothalamus (see above).
Cluster headaches are also common in people who smoke and drink alcohol frequently. During
a cluster period, the sufferer is more sensitive to the action of alcohol and nicotine,
and minimal amounts of alcohol can trigger the headaches. During headache-free periods the
person can consume alcohol without provoking a headache.
What Are the Symptoms of a Cluster Headache?
Cluster headaches generally reach
their full force within five or ten minutes after onset. The attacks are usually very
similar, varying only slightly from one attack to another.
Type of Pain: The pain of cluster headache is almost always one-sided, and during a
headache period, the pain remains on the same side. When a new headache period starts, it
rarely occurs on the opposite side.
Severity/Intensity of Pain: The pain of a cluster headache is generally very intense and
severe and is often described as having a burning or piercing quality. It may be throbbing
or constant. The pain is so intense that most cluster headache sufferers cannot sit still
and will often pace during an attack.
Location of Pain: The pain is located behind one eye or in the eye region, without
changing sides. It may radiate to the forehead, temple, nose, cheek, or upper gum on the
affected side. The scalp may be tender, and the pulsing in the arteries often can be felt.
Duration of Pain:
The pain of a cluster headache
lasts a short time, generally 30 to 90 minutes. It may, however, last from 15 minutes to
three hours. The headache will disappear only to recur later that day. Typically, in
between attacks, people with cluster headaches are headache free.
Frequency of Headaches:
Most sufferers get one to three
headaches per day during a cluster period
(the time when the headache sufferer is experiencing daily attacks). They occur very
regularly, generally at the same time each day, and have been called "alarm clock
headaches" because they often awaken the person at the same time during the night.
Most cluster sufferers (80%-90%) have episodic cluster headaches that occur in periods
lasting seven days to one year, separated by pain-free episodes lasting 14 days or more.
In about 20% of people with cluster headaches, the attacks may be chronic, meaning there
are less than 14 headache-free days per year. Chronic cluster headaches vary from episodic
cluster headaches, as they are continuous without remission periods. Cluster headaches are
not typically associated with nausea or vomiting. It is possible for someone with cluster
headaches to also suffer from migraines.
Is There Any Way to Tell That a Cluster Headache Is Coming?
Although the pain of a cluster
headache starts suddenly, there may be a few subtle signs of the oncoming headache. Some
signs include: Feeling of discomfort or a mild, one-sided burning sensation.
The eye on the side of the headache may become swollen or droop. The pupil of the eye may
get smaller and the conjunctiva (the pink tissue that lines the inside of the eyelid) will
redden.
Nasal discharge. There may be nasal discharge or congestion and tearing of the eye during
an attack, which occur on the same side as the pain. Excessive sweating. Flushing of the
face on the affected side. Light sensitivity.
How Are Cluster Headaches Treated?
Abortive medications: The most
successful treatments are Imitrex (sumatriptan) injections and breathing oxygen through a
face mask for twenty minutes. Other choices include: Zomig (zolmitriptan) tablets,
ergotamine drugs and intranasal lidocaine.
Preventive medications: Your doctor can prescribe preventive medications to shorten the
length of the cluster headache period as well as decrease the severity of the headaches.
All cluster headache sufferers should take preventive medication unless their cluster
periods last less than two weeks. Some medications used in the prevention of cluster
headaches include: calcium channel blockers (verapamil), lithium, divalproex sodium,
corticosteroids (only short courses), methysergide, melatonin and Topamax.
Surgery:
This may be an option for people with
chronic cluster headaches who have not been helped
with standard therapy. Most of the procedures involve blocking the trigeminal nerve.
All of these treatments should be used under the direction of a doctor familiar with
treating cluster headaches. As with any medication, it is important to carefully follow
the label instructions and your doctor's advice.
Surgery
The severed nerve grows back in one year only to have the headaches start again!
Please check this information if
surgery is recommended!
http://my.webmd.com/hw/migraines/hw186776.asp
Cluster Headaches
Topic Overview
What are cluster headaches?
Cluster headaches are severe, one-sided headaches that recur in groups, or
"clusters," over a period of weeks to months. While common headaches can be
painful, cluster headaches can be debilitating. Cluster headaches are sometimes referred
to as "suicide headaches" because they are unbearably painful. Although cluster
headaches can be temporarily disabling, they do not cause permanent damage. Cluster
headaches are relatively rare, and are one of the few types of headaches that affect men
more often than women.
What causes cluster headaches?
The cause of cluster headaches is unknown. They may be genetic, since people whose parents
or siblings have cluster headaches are at increased risk for developing them.1Cluster
headaches may be caused by a problem in an area of the brain called the hypothalamus.2
This area of the brain seems to be more active in people who have cluster headaches.
If you are prone to cluster headaches, certain triggers may cause a headache or make one
worse. These triggers often include alcohol; sleep apnea (regularly stopping breathing
during sleep); stress; fatigue; or certain medications that widen blood vessels
(vasodilators) such as nitroglycerin or histamine.
http://my.webmd.com/hw/migraines/hw186789.asp
Cluster Headaches Cause
The cause of cluster headaches is not clear. They may be genetic, since you are more
likely to develop cluster headaches if a parent or sibling has them.1 Cluster headaches
may be caused by a problem in an area of the brain called the hypothalamus, although the
specific problem or abnormality that triggers cluster headaches is unclear.2 Alcohol,
sleep apnea (regularly stopping breathing during sleep), stress, fatigue, or certain
medications that widen blood vessels (vasodilators) such as nitroglycerin or histamine may
trigger cluster headaches or make them worse once a cycle of headaches begins.
http://my.webmd.com/hw/migraines/hw186806.asp
Cluster Headaches Symptoms
Symptoms of cluster headaches may include:2
� Headaches that come on suddenly without warning.
� Pain that is severe, excruciating, piercing, burning, or sharp.
� Pain that affects only one side of the face, head, and neck.
� A drooping eyelid.
� A watery, red eye and a smaller (contracted) pupil on the affected side.
� A stuffy or runny nose on the affected side.
� Headache that emerges 2 to 3 hours after falling asleep.
� Pain that quickly intensifies, peaking within 5 to 10 minutes of onset.
� Intense pain that can last from several minutes to 3 hours.
� A sweaty forehead in some people.
� A warm and red (flushed) face or forehead on the affected side.
http://my.webmd.com/hw/migraines/hw186827.asp
Cluster Headaches What Happens
Most people who have cluster headaches have 1 or 2 cycles of headaches a year, with each
cycle lasting between 1 and 3 months. After the cycle has subsided, most people are in
remission with no headaches for about 6 months to 2 years.3
Cluster headaches may begin at night, within 2 to 3 hours of falling asleep. They may
begin while you are dreaming; however, they can also occur during the daytime. You may
have 1 to 8 headaches per day. The cycle of headaches occur on only one side of the head.3
Cluster headaches cause deep, stabbing pain usually in, around, or behind one eye. The
pain may extend to the temple, forehead, cheek, upper teeth, or even the jaw on the same
side as the pain. You may also have a stuffy or runny nose, watery eye, and drooping
eyelid on the same side as the pain. The pain of cluster headaches intensifies
quickly—within 5 to 10 minutes of onset—and usually remains constant for around
30 to 45 minutes, and sometimes up to 3 hours. Cluster headaches can continue for days,
weeks, or months before symptoms completely stop (remission). You may not have another
cycle of cluster headaches for months or even years; less commonly, the headache cycles
may become chronic and continuous. During a headache cycle, you may be restless, agitated,
or unable to sit still. Some people find relief by pacing, sitting, kneeling, standing, or
jogging in place. Applying steady pressure to the painful area may provide relief. Lying
down may increase the pain. Afterward, the pain goes away, but the headache may leave you
physically and emotionally exhausted. Another headache may occur within a short time. Over
time, cluster headache cycles may become longer, and periods without headaches (remission)
may become shorter. Some people have a single cluster headache cycle and never have
another one.
During a cycle, some people have up to 8 headaches a day over 6 to 12 weeks, followed by
headache-free periods that can last for weeks, months, or years.
http://my.webmd.com/hw/migraines/hw186842.asp
Cluster Headaches What Increases
Your Risk
Risk factors for cluster headaches include:3, 5
� Having a family history of cluster headaches. You are more likely to develop these
headaches if a parent or sibling has them.
� Being male. More males than females get cluster headaches.
� Being between the ages of 30 and 40, although they can begin at any age. However, it is
rare for children age 10 or younger to develop cluster headaches.
If you have already been diagnosed with cluster headaches, the risk of triggering a
headache increases if you:
� Are a smoker or have been a smoker in the past. The majority of people with cluster
headaches are current or previous tobacco smokers.
� Use alcohol. Alcohol can trigger a headache, especially when you are having a cycle of
headaches.
� Take medications that contain histamine or nitroglycerin during a headache cycle.
� Eat certain foods, such as aged cheeses or processed meats (for example, hot dogs or
bologna).
http://my.webmd.com/hw/migraines/hw186877.asp
Cluster Headaches Exams and Tests
Your health professional will be able to diagnose cluster headaches with a medical history
and physical examination. Since cluster headaches have a classic set of symptoms, your
health professional usually can make a diagnosis based on your description of the
headaches.
If your cluster headaches are not helped by treatment, become chronic, or didn't begin
until you were over age 50, your health professional may order imaging tests to rule out
other causes for the headaches. Imaging tests may also be ordered if the pattern or
symptoms of your headaches change, you develop a serious medical condition such as cancer
or diabetes, or the headaches are triggered by physical exertion, sex, coughing, or
sneezing.
Imaging tests most often used to evaluate headaches are:
� Magnetic resonance imaging (MRI) of the head. An MRI can detect changes in the normal
structure of your brain. It may be ordered to rule out other serious medical problems such
as brain tumors, blood clots, or a bulge in the wall of a blood vessel (aneurysm).
However, most headaches are not caused by these more serious conditions.
� Computed tomography scan (CT scan) of the head. A CT produces detailed pictures of
structures inside the body. It can also detect serious but uncommon medical problems such
as brain tumors.
http://my.webmd.com/hw/migraines/hw186895.asp
Cluster Headaches Treatment
Overview
While there is no cure for cluster headaches, medications can effectively reduce the
frequency and severity of your headaches. You don't have to live with the excruciating
pain of these headaches.
It may help to identify and avoid triggers of your headaches. Common triggers include
alcohol, antihistamines, or other medications that widen your blood vessels. Alcohol
almost always triggers a subsequent headache while you are in a cycle of headaches.
High-flow oxygen inhalation—breathing in 100% oxygen through a face mask—is
another treatment that can stop a cluster headache. However, you have to start this
treatment right when the headache begins, and you'll need to repeat the treatment with
each new headache as it emerges. Initial treatmentMedications are the most effective
treatment for cluster headaches. The two types of medications used are prophylactic
medications, to prevent headaches or reduce the number of headaches in a cycle; and
abortive medications, to relieve pain and reduce the severity of symptoms once the
headaches begin. Treatment depends on the frequency of headache cycles and the severity of
symptoms during a cycle. Abortive medications most often used to stop a cluster headache
include:
� Sumatriptan (Imitrex), which is usually injected to narrow blood vessels and reduce
pressure and pain. This medication can also be taken as a nasal spray, although it may be
less effective than the injection.
� Ergotamine preparations, such as ergotamine tartrate with caffeine (Cafergot,
Wigraine), which narrow blood vessels to relieve pressure and reduce headache pain.
� Intranasal lidocaine, which is taken by nose drops to stop severe headache pain.
� 1995-2004, Healthwise, Incorporated, P.O. Box 1989, Boise, ID 83701. All Rights
Reserved.
This information is not intended to replace the advice of a doctor.
http://my.webmd.com/hw/migraines/hw186900.asp
Cluster Headaches Prevention
Currently, there is no way to prevent cluster headaches from developing since their cause
is unclear.
However, when you are having a cycle of headaches, identifying and avoiding headache
triggers may reduce the severity and duration of the headaches. Common cluster headache
triggers include:
� Alcohol.
� Smoking cigarettes.
� Irregular sleep patterns. Changes in your normal sleep patterns (especially taking
afternoon naps) seem to trigger cluster headaches.
� Stress. Some people develop headaches after a stressful event is over. Reduce stress to
prevent headaches with activities such as regular exercise. For more information, see the
topic Stress Management.
http://my.webmd.com/hw/migraines/hw186908.asp
Cluster Headaches Home Treatment
The excruciating pain from cluster headaches can be debilitating. Identifying and avoiding
triggers (such as alcohol or smoking) can reduce the severity and duration of headache
cycles.
You can manage your headaches at home by:
� Using high-flow oxygen inhalation therapy, which is inhaled through a loose face mask
and can relieve headache pain within 10 to 20 minutes in many people.
� Taking the proper dose of medication when the first headache starts.
� Keeping a headache diary, which details when the cluster headaches occur, how often
they occur, the severity of your symptoms, and any suspected triggers of the headaches.
Take your diary with you when you visit your health professional because it can provide
valuable information to guide your treatment.
http://my.webmd.com/hw/migraines/hw186913.asp
Cluster Headaches Medications
Medications may stop a cluster headache once it starts and prevent additional headaches
from occurring. Finding the right medication can take some time. You may need a
combination of medications to effectively treat your cluster headaches.
Medication Choices
Medications used to stop cluster headaches are called abortive headache medications and
most often include:
� Sumatriptan (Imitrex), which is injected to narrow blood vessels and reduce pressure
and pain. This medication can also be taken as a nasal spray, although it may be less
effective than the injection.7
� Ergotamine preparations, such as ergotamine tartrate with caffeine (Cafergot,
Wigraine), which narrow blood vessels to relieve pressure and reduce headache pain.
� High-flow oxygen inhalation therapy, which is inhaled through a face mask to quickly
relieve headache pain.
� Intranasal lidocaine, which is taken by nose drops to stop severe headache pain.
http://my.webmd.com/hw/migraines/hw186954.asp
Cluster Headaches Surgery
Surgery to relieve the pain from cluster headaches is rarely done. However, if your
headaches are not relieved with medications and always occur on the same side of your
head, you may want to discuss surgical options with your health professional.
Surgery for cluster headaches usually involves cutting or interrupting the nerves that
send pain signals to the face. Another procedure is radiation, which uses a high-intensity
beam to disrupt pain signals from the trigeminal nerve, which regulates sensation to the
face. However, not much research exists on the long-term effectiveness of these
procedures, and they are rarely done to treat cluster headaches.8
http://my.webmd.com/hw/migraines/hw186958.asp
Cluster Headaches Other Treatment
While medications may effectively control cluster headache pain or reduce the number of
headaches in a cycle, another treatment to consider is high-flow oxygen inhalation
therapy.
During high-flow oxygen inhalation therapy, you breathe in 100% oxygen through a face mask
soon after a headache begins, which usually stops the headache pain within 10 to 20
minutes. This therapy may prevent additional headaches in the cycle from occurring.
However, if another headache does occur, you will need to repeat the procedure as soon as
the next headache in the cycle begins. This treatment may be more effective in people
under the age of 50 who only occasionally develop cluster headaches. High-flow oxygen
inhalation therapy will not prevent cluster headaches. It provides only temporary relief
of headache pain. Also, you'll need an oxygen tank near you at all times for immediate
treatment when a cluster headache cycle begins; some people find this inconvenient or not
possible.
http://my.webmd.com/hw/migraines/hw186774-ConRes.asp
Cluster Headaches Other Places To Get
Help
Organizations
American Council for Headache Education (ACHE)
19 Mantua Road
Mount Royal, NJ 08061
Phone: (856) 423-02581-800-255-ACHE (1-800-255-2243)
Fax: (856) 423-0082
Web Address: http://www.achenet.org
This organization is dedicated to
advancing the treatment and management of headache and to raising the public awareness of
headache as a valid, biologically based illness. ACHE's goals are to empower headache
sufferers through education and to support them by educating their families, employers,
and the public in general. ACHE was formed in 1990 through an initiative of the American
Headache Society (AHS), an organization of 1,700 physicians, health professionals, and
research scientists.
National Headache Foundation (NHF)
820 North Orleans
Suite 217
Chicago, IL 60610
Phone: 1-888-643-5552
Web Address: http://www.headaches.org
The NHF is a nonprofit organization
dedicated to three major goals: educating the public that headaches are serious disorders
and sufferers need understanding and continuity of care; promoting research into potential
headache causes and treatments; and serving as an information resource to sufferers, their
families, and doctors who treat them. The NHF can provide lists of local doctors
specializing in headache treatment. It also has a monthly newsletter and many pamphlets on
a variety of topics related to the different headache
syndromes.Search
Headaches / Migraine
Press ReleaseFOR IMMEDIATE RELEASECONTACT: SUSAN MOELLER DENNYINFORMATION SERVICES OFFICER
(703) 739-9384
U.S. Congressman Moran & Other Members and Staff of Congress Monday Briefed By World
Leading Migraine Headache Disorder Public Health Advocates
Washington, D.C. (February 14th, 2003)- Members of Congress and their staff met this past
Monday with members of MAGNUM, The National Migraine
Association, and other international public health advocates for Migraine disease and
headache disorders from the World Headache Alliance (WHA). MAGNUM, an American member
non-government organization (NGO) of the WHA, set up meetings with the offices of U.S.
Senator John Warner (R-VA) and U.S. Congressman James P. Moran (D-VA) to brief them on
serious public health issues such as the burden of Migraine and access to appropriate
care. The WHA is a collaborative global alliance of headache organizations from 26
countries, with leading international health advocates from six nations including England,
New Zealand, & India participating in the Washington program. During Monday's meeting
with Congressman Moran, the Congressman announced to the WHA council he would be advancing
MAGNUM's draft House Congressional Resolution declaring September as the United States of
America's official "National Migraine Disease and Headache Disorder Awareness
Month". MAGNUM is also currently working with U.S. Senators Warner Warner (R-VA)
& George Allen (R-VA) to take the lead on the national awareness month on the Senate
side. These legislators have shown great compassion for those in pain supporting, some for
nearly a decade, MAGNUM's goals and objectives to help those who suffer. MAGNUM is very
pleased with the face-to-face meeting with Congressman Moran, as he illustrated the
American government's willingness to work with public health NGO's to improve the quality
of life for citizens both in the United States or abroad. It became clear to MAGNUM that
passing a strong patient bill of rights will benefit Migraineurs and pain patients in the
United States. An earlier face-to-face meeting with Senator John Warner was changed at the
last minute, as Warner, Chairman of the Senate Arms Committee, was called into an
emergency meeting due to tensions with Turkey and NATO. Senator Warner's Deputy
Legislative Director/Legislative Council Christopher J. Yianilos spent a generous amount
of time discussing head-pain public health issues with the WHA advocates. Other WHA
council meetings on Capitol Hill involved the staff of Senator George Allen (R-VA) and
Congressman Anibal Acevedo-Vila (D-PR) of Puerto Rico on Monday February 10th. The
latter's health Legislative Assistant Ileana I. Fas-Pacheco took time to meet with WHA
board members to discuss working together on Migraine disease issues in an impromptu
meeting at the end of the day.Other activities over the past weekend included the Council
Board meeting over several days, as well as a special reception & Migraine Disease
Awareness Art Exhibition at the Italian Embassy's Cultural Institute. The art exhibition
currently running at the Italian Cultural Institute features the award-winning artwork of
artists & Migraineurs Michael John Coleman and Janet McKenzie (the painter of
"Jesus of the People"; which was selected winner of the National Catholic
Reporter's global competition for a new image of Jesus at the Millennium judged by Sister
Wendy Beckett, Britain's most beloved TV art critic). The WHA Board meeting in Washington
was hosted by MAGNUM over the weekend and featured nearly a dozen world leading Migraine
disease and headache disorder medical advocates. MAGNUM is one of the two American
member-NGOs of the World Headache Alliance (along with the American Council of Headache
Education (ACHE)) and considered a leader in getting government involved in helping people
who suffer from serious head pain problems. Terri Miller Burchfield, MAGNUM's Legislative
Director, noted, "All of the advocates greatly appreciate Congressman James Moran's
gracious gesture to those who suffer from head pain by meeting with the WHA Council. We
are proud to have the opportunity to demonstrate the American government's concern for
Migraine disease and headache disorders. This kind of Congressional cooperation and
support reaches out to those who suffer from head pain on both a national and global
scale. " Migraine and headache disorder public health participants included the
following persons & NGOs; � Dr. Fred Sheftell, Chairman of WHA, New England Center
for Headache, USA � Dr. Timothy Steiner, International Headache Society, Imperial
College, UK � Mrs. Ann Turner, Migraine Action Association, UK � Mrs. Colette
Andree-Hargreaves, Swiss Migraine Trust Foundation, Switzerland � Mr. Michael John
Coleman, MAGNUM-National Migraine Association, USA � Ms. Audrey Craven, Migraine
Association of Ireland, Ireland � Ms. Annette Hallam, Migraine Sufferers Support Group,
New Zealand � Mr. Pierre Lefebvre, Fondation Quebecoise de Migraine et Cephalees, Canada
� Dr. K. Ravishankar, The Headache and Migraine Clinic, Jaslok and Lilavati � Hospitals,
India � Mr. Luis Taboas, Fundacion Puertorriquena de Dolor de Cabeza, Puerto Rico, USA �
Ms. Kary Shannon, Chief Operating Officer, WHA, Canada � Ms. Terri Miller Burchfield,
Legislative Director, MAGNUM staff, USA � Ms. Susan Moeller Denny, Information Services
Officer, MAGNUM staff, USA � Ms. Cassandra Eckert, At Large Board Member, MAGNUM staff,
USA MAGNUM was grateful for the kind support of the Italian Cultural Institute and it's
director, Dr. Martin Stiglio. To that fact, the event illustrated Italy's continued
medical leadership and compassion on pain issues, as Rome is the host city for the XI
Congress of the International Headache Society (IHC 2003). Earlier this month Italy
announced the discovery of the genetic markers for Migraine disease making Italy a leader
in Migraine medical research. For more information, visit MAGNUM's top rated and award
winning healthcare website www.migraines.org, for more on the Italian Cultural Institute
visit their website at http://www.italcultusa.org. For further information on Migraine and
headache disorders also visit the American Council for Headache Education (ACHE) at
www.achenet.org, the World Headache Alliance at www.wha.ws , and
http://www.headaches.about.com/ .
WHA Board members seen here in Congressman James P. Moran's Capitol Hill office Monday.
Posing here with the Congressman are: (L to R) American Susan Moeller Denny of MAGNUM,
England's Dr. Tim Steiner of London's Imperial Collage, Canada's Pierre Lefebvre of the
Fondation Quebecoise de Migraine et Cephalees Canada, New Zealand's Ann Hallam of MSSG,
Puerto Rico's Luis Taboas of the Fundacion Puertorriquena de Dolor de Cabeza, U.S.
Congressman James P. Moran (D-VA), and America's Michael John Coleman & Terri Miller
Burchfield directors of MAGNUM.
http://www.pslgroup.com/dg/1fa54e.htm
WELLESLEY HILLS, MA -- May 8, 2001 -- Throbbing, disabling headaches are nothing new for
28 million people suffering from migraine -- mostly 25 to 55 year-old women. And for many
sufferers, side effects of treatment may be as bad as the headache itself. Research shows
a new migraine treatment is highly effective, comparable to the most commonly prescribed
medication in its class, but with fewer side effects. The comparison study of Axert™
(almotriptan malate) tablets, a newly approved anti-migraine medication, and Imitrex�
(sumatriptan succinate) tablets was conducted by Boston Clinical Research Center in
Wellesley Hills, Massachusetts.
In a double-blind study, patients receiving Axert 12.5 mg for moderate or severe migraine
headache showed similar pain relief at two hours to patients receiving sumatriptan 50 mg.
However, patients taking Axert reported significantly fewer side effects compared to the
sumatriptan-treated group -- particularly less chest pain. "Axert is an important new
addition to our migraine treatment arsenal," said Egilius L.H. Spierings, M.D.,
Ph.D., general medical director of the Boston Clinical Research Center and Axert principal
investigator. "In our studies, it demonstrated highly effective pain relief, with an
occurrence of side effects similar to placebo."
Migraine is an intense, throbbing headache characterized by pain on one or both sides of
the head, often accompanied by other symptoms, such as nausea, vomiting, or sensitivity to
light and noise. Migraine headaches can last from four to 72 hours if left untreated. The
World Health Organization has rated migraine as one of the most disabling conditions,
giving it a rating of 7 on a scale of 1-7, where 7 is "disability as bad as
death." Dr. Spierings says side effects from medications can impact patient
compliance, efficacy of treatment, and overall patient satisfaction. "Side effects
from medications can be a real problem for migraine sufferers, causing them to delay
taking their prescriptions, or use over-the-counter medications first -- and as a result,
their headaches often become worse and more difficult to treat," says Dr. Spierings.
"A product that offers high efficacy with improved tolerability can increase
compliance, and ultimately improve treatment outcome."
SOURCE: Boston Clinical Research Center
Last Updated: November 16, 2004
Please Read Medication Advailabitiy
second
Background: Cluster headache (CH) is an idiopathic syndrome consisting of recurrent brief attacks of sudden, severe, unilateral periorbital pain. Pathophysiology: The pathophysiology of CH is not understood entirely. Its typical periodicity has been attributed to hypothalamic (particularly suprachiasmatic nuclei) hormonal influences. CH pain is thought to be generated at the level of the pericarotid/cavernous sinus complex. This region receives sympathetic and parasympathetic input from the brain stem, possibly mediating occurrence of autonomic phenomena during an attack. The exact roles in CH of immunologic and vasoregulatory factors, as well as the influence of hypoxemia and hypocapnia, are still controversial. Frequency:
Sex:
Age: CH affects middle-aged persons.
History:
Physical: The association of prominent autonomic phenomena is a hallmark of CH. Such signs include ipsilateral nasal congestion and rhinorrhea, lacrimation, conjunctival hyperemia, facial diaphoresis, palpebral edema, and complete or partial Horner syndrome (which may persist between attacks). Tachycardia is a frequent finding.
Causes: Cases of CH affecting multiple members within a single family have been reported, suggesting that a genetic predisposition may exist in some individuals.
Anisocoria
Arteriovenous malformations |
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Imaging Studies:
Medical Care: Pharmacologic management of CH may be classified as abortive/symptomatic or preventive/prophylactic. See Medication section for a detailed discussion. Surgical Care:
Drug Category: Abortive agents -- These agents are administered to abort an attack of CH. Because of the duration of the attacks, they must provide immediate relief.
Drug Category: Ergot alkaloids -- These agents are highly effective in relieving acute CH pain.
Drug Category: Anesthetics -- Local anesthetics stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents initiation and transmission of nerve impulses, thereby producing the local anesthetic action.
Drug Category: Oral opioids and other analgesics -- The short-lived and unpredictable character of CH precludes the effective use of oral narcotics or analgesics. Despite their lack of efficacy, these substances are abused by some CH sufferers.
Drug Category: Calcium channel blockers -- These agents inhibit the initial vasoconstrictive phase of CH.
Drug Category: Mood stabilizers -- Mechanism of action of lithium in CH is unclear, although preliminary evidence suggests that it may interfere with substance P and vasoactive intestinal peptide–induced arterial relaxation.
Drug Category: Corticosteroids -- These agents are extremely effective in terminating a CH cycle and in preventing immediate headache recurrence. High-dose prednisone is prescribed for the first few days, followed by a gradual taper. The simultaneous use of standard prophylactic agents (eg, verapamil) is recommended. The mechanism of action in CH is still subject to speculation.
Prognosis:
Patient Education:
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Page 3
Cluster Headache
Last Updated: November 16, 2004 Rate this Article
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Synonyms and related keywords: Bing-Horton syndrome, histaminic cephalalgia, cluster
migraine, paroxysmal nocturnal cephalalgia, red migraine, erythromelalgia of the head,
sphenopalatine neuralgia, migrainous neuralgia
AUTHOR INFORMATION Section 1 of 9
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Follow-up Bibliography
Author: Jorge Mendizabal, MD, Attending Neurologist, Corpus Christi Neurology, Corpus
Christi Medical Center, Christus Spohn Medical Center
Jorge Mendizabal, MD, is a member of the following medical societies: American Academy of
Neurology, American Headache Society, and Southern Medical Association
Editor(s): Joseph R Carcione, Jr, DO, MBA, Consultant in Neurology and Medical
Acupuncture, Medical Management and Organizational Consulting, Central Westchester
Neuromuscular Care, PC; Medical Director, Oxford Health Plans; Francisco Talavera, PharmD,
PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; James H Halsey, MD, Professor,
Department of Neurology, University of Alabama Medical Center; Selim R Benbadis, MD,
Director of Comprehensive Epilepsy Program, Associate Professor, Departments of Neurology
and Neurosurgery, University of South Florida, Tampa General Hospital; and Helmi L Lutsep,
MD, Associate Director, Oregon Stroke Center; Associate Professor, Department of
Neurology, Oregon Health Sciences University
INTRODUCTION Section 2 of 9
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Follow-up Bibliography
Background: Cluster headache (CH) is an idiopathic syndrome consisting of recurrent brief
attacks of sudden, severe, unilateral periorbital pain.
Pathophysiology: The pathophysiology of CH is not understood entirely. Its typical
periodicity has been attributed to hypothalamic (particularly suprachiasmatic nuclei)
hormonal influences. CH pain is thought to be generated at the level of the
pericarotid/cavernous sinus complex. This region receives sympathetic and parasympathetic
input from the brain stem, possibly mediating occurrence of autonomic phenomena during an
attack. The exact roles in CH of immunologic and vasoregulatory factors, as well as the
influence of hypoxemia and hypocapnia, are still controversial.
Frequency:
In the US: Exact prevalence is unknown. Kudrow estimated 0.4% in men and 0.08% in women.
Internationally: In an extensive study of 100,000 inhabitants of the republic of San
Marino, the prevalence was 0.07%.
Sex:
CH is more common in men; the male-to-female ratio is 5:1.
Age: CH affects middle-aged persons. CLINICAL Section 3 of 9
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History:
Attacks of CH are typically short in duration (5-180 min) and occur with a frequency from
once every other day to 8 times a day, particularly during sleep. As opposed to migraine,
CH is not preceded by aura, affording patients little or no warning.
Pain generally is described as excruciating, penetrating, and not throbbing.
It may radiate to other areas of the face and neck but is typically periorbital.
It may be triggered by stress, relaxation, extreme temperatures, glare, allergic rhinitis,
and sexual activity.
CH rarely is triggered by ingestion of specific foods, although tobacco or alcohol
products may precipitate an attack.
An attack of CH is a dramatic event during which the patient may be extremely restless. In
desperation, CH patients may rock, sit, pace, or bang themselves against a hard surface.
Classification of cluster headache: The International Headache Society (IHS) classifies CH
by duration as episodic or chronic.
Episodic CH occurs in periods (clusters) lasting from 7 days to 1 year; clusters are
separated by pain-free intervals lasting at least 2 weeks. Typically, a cluster lasts 2
weeks to 3 months.
Chronic CH is defined as that occurring for more than 1 year without remission or with
remissions lasting less than 2 weeks. It is subdivided into chronic CH from onset and
chronic CH evolving from episodic.
Chronic CH is notoriously difficult to treat and resistant to standard prophylactic
agents.
Symptomatic clusterlike headache should be suspected if the presentation is atypical.
Atypical features may include the following:
Absence of a periodic pattern
Residual headache between exacerbations
Incomplete or minimal response to standard therapy
Presence of lateralizing findings on exam (except for those of CH-related Horner syndrome)
Physical: The association of prominent autonomic phenomena is a hallmark of CH. Such signs
include ipsilateral nasal congestion and rhinorrhea, lacrimation, conjunctival hyperemia,
facial diaphoresis, palpebral edema, and complete or partial Horner syndrome (which may
persist between attacks). Tachycardia is a frequent finding.
A distinctive CH face is described as follows: leonine facial appearance, multifurrowed
and thickened skin with prominent folds, a broad chin, vertical forehead creases, and
nasal telangiectasias.
CH sufferers are typically tall and rugged-looking.
Causes: Cases of CH affecting multiple members within a single family have been reported,
suggesting that a genetic predisposition may exist in some individuals. DIFFERENTIALS
Section 4 of 9
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Anisocoria
Atypical Facial Pain
Basilar Artery Thrombosis
Brainstem Gliomas
Cavernous Sinus Syndromes
Chronic Paroxysmal Hemicrania
Craniopharyngioma
Headache: Pediatric Perspective
Intracranial Hemorrhage
Migraine Headache
Migraine Variants
Pituitary Tumors
Postherpetic Neuralgia
Subarachnoid Hemorrhage
Temporomandibular Joint Syndrome
Tolosa-Hunt Syndrome
Trigeminal Neuralgia
Other Problems to be Considered:
Arteriovenous malformations
Brainstem syndromes
Cyclical migraine
Hemicrania continua
Metastatic lung carcinoma
Nasopharyngeal carcinoma
Malignant and nonmalignant pain syndromes
Raeder paratrigeminal syndrome
Vertebral artery aneurysm
Quick Find
Author Information
Introduction
Clinical
Differentials
Workup
Treatment
Medication
Follow-up
Bibliography
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Related Articles
Anisocoria
Atypical Facial Pain
Basilar Artery Thrombosis
Brainstem Gliomas
Cavernous Sinus Syndromes
Chronic Paroxysmal Hemicrania
Craniopharyngioma
Headache: Pediatric Perspective
Intracranial Hemorrhage
Migraine Headache
Migraine Variants
Pituitary Tumors
Postherpetic Neuralgia
Subarachnoid Hemorrhage
Temporomandibular Joint Syndrome
Tolosa-Hunt Syndrome
Trigeminal Neuralgia
Continuing Education
CME available for this topic. Click here to take this CME.
Patient Education
Headache Center
Causes and Treatments of Migraine and Related Headaches
Cluster Headache Overview
Cluster Headache Causes
Cluster Headache Symptoms
Cluster Headache Treatment
Alternative and Complementary Approaches to Migraine and Cluster Headaches
Cluster Headache FAQs
Understanding Migraine and Cluster Headache Medications
WORKUP Section 5 of 9
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Imaging Studies:
CH is strictly a clinical diagnosis. On rare occasions, structural lesions may mimic its
presentation, prompting the need for neuroimaging study (CT scan or MRI).
The following conditions can present with findings suggestive of CH:
Meningiomas of the cavernous sinus
Arteriovenous malformations
Pituitary adenomas
Nasopharyngeal carcinoma
Vertebral artery aneurysms
Metastatic carcinoma of the lung
TREATMENT Section 6 of 9
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Medical Care: Pharmacologic management of CH may be classified as abortive/symptomatic or
preventive/prophylactic. See Medication section for a detailed discussion.
Surgical Care:
Invasive nerve blocks and ablative neurosurgical procedures (eg, percutaneous
radiofrequency, trigeminal gangliorhizolysis, rhizotomy) all have been implemented
successfully in cases of refractory CH.
More recently, gamma-knife radiosurgery has provided a less invasive alternative for
pervasive CH.
MEDICATION Section 7 of 9
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The pharmacologic management of CH may be divided into abortive/symptomatic and
preventive/prophylactic strategies. Abortive therapy is directed at stopping or reducing
the severity of an acute attack, while prophylactic agents are used to reduce the
frequency and intensity of individual headache exacerbations. Due to the fleeting,
short-lived nature of the attacks, effective prophylactic therapy should be considered the
cornerstone of treatment. The prophylactic therapy should start at the onset of a CH cycle
and continue until the patient is headache free for at least 2 weeks. The agent then may
be tapered slowly to prevent recurrences.
Drug Category: Abortive agents -- These agents are administered to abort an attack of CH.
Because of the duration of the attacks, they must provide immediate relief.Drug Name
High-flow oxygen -- Inhalation of high-flow, concentrated oxygen extremely effective for
aborting CH attack. Precise mechanism of action poorly understood. Effective alternative
to ergotamine. Despite immediate availability of oxygen in ED, its widespread use in
outpatient setting limited by impracticality.
Adult Dose 6-8 L/min concentrated (100%) oxygen by face mask for no longer than 15 min
Contraindications None reported
Interactions None reported
Pregnancy A - Safe in pregnancy
Drug Category: Ergot alkaloids -- These agents are highly effective in relieving acute CH
pain.Drug Name
Ergotamine (Cafatine, Cafergot, Cafetrate, Ercaf) -- Vasoconstrictor of smooth muscle in
cranial blood vessels, alpha-adrenergic blocker, and nonselective 5-HT agonist. PR or SL
preparations of ergotamine tartrate preferred to PO because of immediate onset of action.
Avoid exceeding maximum dosage guidelines to prevent rebound headaches.
Adult Dose 2 tabs PO at first sign of onset, followed by 1 tab q30min prn; not to exceed 6
tabs/attack or 10 tabs/wk 1 tab SL at first sign of onset, followed by 1 tab q30min prn;
not to exceed 3 tabs/24h or 5 tabs/wk 1 supp PR at first sign of onset, followed by second
dose prn after 1 h; not to exceed 2 supp/attack or 5 supp/wk
Contraindications Documented hypersensitivity
Interactions Erythromycin, troleandomycin, and other macrolide antibiotics may increase
toxicity
Pregnancy X - Contraindicated in pregnancy
Precautions Use caution in patients with history of hypertension or coronary or peripheral
arterial insufficiency; use caution in elderly, as may precipitate angina or MI or
aggravate intermittent claudication; avoid prolonged administration or excessive dosage,
since increases danger of ergotism or gangrene; patients who take for extended periods may
become dependent
Drug Name
Dihydroergotamine (D.H.E.-45 injection, Migranal) -- Available in IV or intranasal
preparations, tends to cause less arterial vasoconstriction than ergotamine tartrate.
Adult Dose Up to 2 mg IV; not to exceed 2 mg/dose or 6 mg/wk 1 mg IM/SC at first sign of
onset; not to exceed 3 mg total 1 spray (0.5 mg) into each nostril; not to exceed 6
sprays/d or 8 sprays/wk
Contraindications Documented hypersensitivity; do not use within 24 h of sumatriptan,
zolmitriptan, other serotonin agonists, or ergotlike agents; use of MAOIs within last 2 wk
Interactions May increase effects of heparin; erythromycin, clarithromycin, nitroglycerin,
propranolol, and troleandomycin may increase toxicity
Pregnancy X - Contraindicated in pregnancy
Precautions Use caution in patients with hypertension, angina, peripheral vascular
disease, or impaired renal or hepatic function
Drug Name
Sumatriptan (Imitrex); naratriptan (Amerge, Naramig) -- zolmitriptan (Zomig, Zomig-ZMT);
rizatriptan (Maxalt, Maxalt-MLT); almotriptan (Axert); frovatriptan (Frova); eletriptan
(Relpax)--As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause
vasoconstriction and reduce inflammation associated with antidromic neuronal transmission
in CH. Can reduce severity of headache within 15 min of SC injection. Intranasal form
recently introduced in US, offering attractive alternative to self-injections.
Adult Dose Sumatriptan: 6 mg SC, followed by second injection prn at least 1 h after
first; not to exceed 2 injections/d
25-100 mg PO, followed by second dose 2 h later prn; not to exceed 300 mg/d 1 spray (5-20
mg) in 1 nostril or 1 spray (5 mg) in each nostril; may repeat in 2 h prn; not to exceed
40 mg/d
Zolmitriptan: 2.5-5 mg PO; repeat after 2 h prn; not to exceed 10 mg/d
Naratriptan: 2.5 mg PO
Rizartriptan: 10 mg PO
Almotriptan: 6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d
Frovatriptan: 2.5 mg PO once at onset of migraine
Eletriptan: 20-40 mg/dose PO at onset of migraine; if initial dose ineffective, may repeat
dose once after 2 h; not to exceed 80 mg/d
Pediatric Dose Sumatriptan:
Tab: 12.5-25 mg PO prn; not to exceed 100 mg qd
Nasal spray: 5 mg NS prn
Injection: 0.02 mg/kg SC prn
Zolmitriptan: 2.5 mg PO prn; not to exceed 10 mg qd
Naratriptan: 1 mg PO prn; not to exceed 5 mg qd
Rizatriptan: 5 mg PO prn; not to exceed 30 mg qd
Almotriptan: Not established
Frovatriptan: <18 years: Not established
>18 years: Administer as in adults
Eletriptan: <18 years: Not established
>18 years: Administer as in adults
Contraindications Documented hypersensitivity, ischemic heart disease, uncontrolled
hypertension, use of MAOIs in last 2 wk
Interactions Not to be used on the same day as another ergot derivative or triptan;
toxicity increases when administered concomitantly with ergot-containing drugs, selective
serotonin reuptake inhibitors, and MAOIs
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions May cause facial flushing, numbness, paresthesias, and chest pain of
noncardiac origin; significant elevation in blood pressure, including hypertensive crisis,
has been reported in patients without history of hypertension; peripheral vascular
ischemia, colonic ischemia with abdominal pain, and bloody diarrhea have occurred
Drug Name
Methysergide (Sansert) -- Useful in patients unresponsive to lithium. Although of
ergotamine chemical class, actions differ, since has minimal ergotaminelike
vasoconstrictive properties and significantly greater serotoninlike properties. Plays
important role in CH prophylaxis. Often effective in reducing pain frequency, particularly
in younger patients with episodic CH. If no improvement after 3 wk, unlikely to be
beneficial. Do not give continuously for >6 mo. Drug-free interval of 3-4 wk must
follow each 6-mo course.
Adult Dose 2-8 mg/d PO
Contraindications Documented hypersensitivity, peripheral vascular disease, severe
arteriosclerosis, pulmonary disease, severe hypertension, phlebitis, serious infections
Interactions None reported
Pregnancy X - Contraindicated in pregnancy
Precautions Use >6 mo discouraged, since long-term therapy may cause retroperitoneal
fibrosis and fibrotic thickening of cardiac valves; drug holiday recommended to avoid
these effects; adverse GI reactions most commonly affect compliance; use caution in renal
or hepatic impairment; adverse effects include leg cramps, paresthesias, edema, and skin
discoloration
Drug Category: Anesthetics -- Local anesthetics stabilize the neuronal membrane so the
neuron is less permeable to ions. This prevents initiation and transmission of nerve
impulses, thereby producing the local anesthetic action.Drug Name
Intranasal lidocaine (4%) -- An experimental therapy in CH, blocks conduction of nerve
impulses by decreasing neuronal membrane's permeability of sodium ions, which results in
inhibition of depolarization and blockade of conduction. Effective in 2 separate clinical
trials. Intranasal administration of lidocaine drops requires specific and, for many
patients, difficult technique.
Adult Dose 4% solution intranasally; actual dose not established
Contraindications Documented hypersensitivity
Interactions May enhance effects of succinylcholine
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Use extreme caution in patients with marked hypoxia, severe respiratory
depression, or bradycardia
Drug Category: Oral opioids and other analgesics -- The short-lived and unpredictable
character of CH precludes the effective use of oral narcotics or analgesics. Despite their
lack of efficacy, these substances are abused by some CH sufferers.Drug Name
Intranasal capsaicin -- This experimental therapy successfully tested in clinical trials.
Derived from chili peppers, induces release of substance P, principal chemomediator of
pain impulses from periphery to CNS. After repeated applications, depletes neuron of
substance P and prevents reaccumulation.
Adult Dose Few drops of capsaicin solution applied to ipsilateral nostril
Contraindications Documented hypersensitivity
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Avoid contact with eyes; irritant to mucosal membranes, should be used with
caution; warn patients about nasal cavity irritation, burning, congestion, drainage, and
sneezing while using
Drug Category: Calcium channel blockers -- These agents inhibit the initial
vasoconstrictive phase of CH.Drug Name
Verapamil (Calan, Verelan, Covera-HS) -- Perhaps most effective calcium channel blocker
for CH prophylaxis, inhibits calcium ions from entering slow channels, select
voltage-sensitive areas, or vascular smooth muscle, thereby producing vasodilation.
Adult Dose Immediate release: 120-360 mg/d PO divided tid/qid
Extended release form may be given qd
Contraindications Documented hypersensitivity, sinus bradycardia, cardiogenic shock,
advanced heart block, ventricular tachycardia, congestive heart failure, atrial
fibrillation or flutter associated with accessory conduction pathways
Interactions Phenobarbital, hydantoins, vitamin D, sulfinpyrazone, and rifampin may
decrease serum concentrations by increasing hepatic metabolism; amiodarone may increase
toxicity; beta blockers may increase cardiac depressant effects on AV conduction;
cimetidine may increase serum levels; may increase cyclosporine, doxorubicin,
theophylline, carbamazepine, vecuronium, and digoxin serum levels
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Use caution in patients with sick-sinus syndrome, severe left ventricular
dysfunction, hepatic or renal impairment, or hypertrophic cardiomyopathy; monitor ECG and
blood pressure closely in patients with supraventricular tachycardia receiving IV therapy;
adverse effects include constipation and water retention; patients intolerant of verapamil
should try nimodipine, diltiazem, or nifedipine
Drug Category: Mood stabilizers -- Mechanism of action of lithium in CH is unclear,
although preliminary evidence suggests that it may interfere with substance P and
vasoactive intestinal peptide–induced arterial relaxation.Drug Name
Lithium carbonate (Eskalith, Lithane, Lithobid, Lithonate, Lithotabs) -- Effectively
prevents CH (particularly in its more chronic forms) and treats bipolar mood disorder,
another cyclic illness. Responses variable, but still recommended first-line agent in CH.
Narrow therapeutic window requires close monitoring of levels and adverse effects. Plasma
lithium level of 0.6-1.2 mEq/L measured at steady state, 12 h after last dose (ie, just
before next dose), usually sought, but optimal plasma levels for prevention of CH not
established. Thought effective in CH at serum concentrations lower than those required in
bipolar disorder (0.3-0.8 mEq/L).
Adult Dose 600-900 mg/d PO in divided doses; increase to 600-1200 mg/d divided bid/qid prn
Contraindications Documented hypersensitivity, severe cardiovascular or renal disease
Interactions Thiazide diuretics, NSAIDs, haloperidol, phenothiazines, neuromuscular
blockers, carbamazepine, fluoxetine, and ACE inhibitors may increase serum levels and
toxicity; theophylline, caffeine, and other xanthines decrease effects
Pregnancy D - Unsafe in pregnancy
Precautions Lithium toxicity can occur at therapeutic doses; use caution in patients with
cardiovascular or thyroid disease, severe debilitation, dehydration, or sodium depletion,
or in patients taking diuretics; adverse effects include tremor, polyuria, diarrhea,
nausea, fatigue, weight gain, and thyroid dysfunction; renal toxicity with tubular damage
and interstitial fibrosis may occur; CNS toxicity manifested by confusion and ataxia
Drug Category: Corticosteroids -- These agents are extremely effective in terminating a CH
cycle and in preventing immediate headache recurrence. High-dose prednisone is prescribed
for the first few days, followed by a gradual taper. The simultaneous use of standard
prophylactic agents (eg, verapamil) is recommended. The mechanism of action in CH is still
subject to speculation.Drug Name
Prednisone (Deltasone) -- Effective for treatment of CH not responsive to lithium or
methysergide. Effects in CH may occur via inhibition of prostaglandin synthesis. Long-term
use not recommended.
Adult Dose 40-60 mg/d PO in divided doses for 5 d, followed by slow taper over 2-4 wk
Contraindications Documented hypersensitivity; systemic fungal infections or serious
infections, except septic shock or tuberculous meningitis
Interactions Barbiturates, phenytoin, and rifampin decrease effects; may decrease effects
of salicylates
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Use cautiously in patients with diabetes, hypothyroidism, cirrhosis,
congestive heart failure, thromboembolic disorders, or ulcerative colitis; chronic use may
lead to gastric ulceration, immunosuppression, electrolyte disturbances, weight gain, and
osteopenia
FOLLOW-UP Section 8 of 9
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Follow-up Bibliography
Prognosis:
Eighty percent of patients with episodic CH tend to maintain the episodic form.
Episodic CH eventually transforms into chronic CH in 4-13% of patients. Intermediate
(mixed) forms may occur.
Prolonged, spontaneous remissions have been described in up to 12% of patients in some
series, particularly in episodic CH. Chronic CH is more relentless and may persist in this
form in up to 55% of cases. Less frequently, chronic CH may remit into an episodic form.
Generally, CH is a lifelong problem.
Pharmacologic intervention may play a part in the transformation of chronic CH into the
episodic form; otherwise, it does not influence outcome.
Late onset of this disorder, along with male sex and a previous history of episodic CH,
predict a less favorable course.
Patient Education:
For excellent patient education resources, see eMedicine's Headache Center. Also, visit
eMedicine's patient education articles Causes and Treatments of Migraine and Related
Headaches, Cluster Headache, Alternative and Complementary Approaches to Migraine and
Cluster Headaches, Cluster Headache FAQs, and Understanding Migraine and Cluster Headache
Medications.
BIBLIOGRAPHY Section 9 of 9
Author Information Introduction Clinical Differentials Workup Treatment Medication
Follow-up Bibliography
Ekbom K, Nappi G: Diagnosis, differential diagnosis, and prognosis of cluster headache.
The Headaches 1993; 585-589.
Kudrow L: Cluster Headache: Diagnosis and management. Headache 1979; 19: 141-148.
Mathew NT: Cluster Headache. Neurology 1992; 42 (suppl 2): 22-31[Medline].
Mendizabal JE, Umana E, Zweifler RM: Cluster Headache: Horton's Cephalalgia Revisited.
Southern Medical Journal 1998; 91: 606-617.
Page 3
Although cluster headache ("migrainous neuralgia") had been recognized for over 100 years (von M�llendorff, 1867), Sir Charles Symonds' (1956) lucid account of this disorder brought it into focus. Recognition of the clinical entity was almost certainly retarded by a variety of confusing names that were given to this condition, such as erythroprosopalgia, Raeder's syndrome, spenopalatine neuralgia, ciliary neuralgia, vidian neuralgia, and histamine cephalalgia (Sjaastad, 1986; Grimson and Thompson, 1980). Cluster headache is now firmly established as a distinctive syndrome (Table 6-1) whose recognition is important, since it is likely to be responsive to treatment. The episodic type, the most common, is characterized by one to three short-lived attacks of periorbital pain (Fig. 6-1) per day over a 4 to 8 week period, followed by a pain-free interval that averages 1 year. The chronic form, sometimes called chronic migrainous neuralgia, which may begin de novo or several years after an episodic pattern has become established, is characterized by the absence of sustained periods of remission. Each type may transform into the other. The cluster syndrome is genetically, biochemically, and clinically different from migraine; propranolol is effective in treating migraine but has not been shown to be effective in cluster headache. Lithium is beneficial for the cluster headache syndrome and ineffectual in migraine. Nevertheless, the two disorders occasionally blend into one in occasional patients (Solomon, 1986), suggesting that their mechanisms bear some degree of commonality.
Cluster headache has a prevalence of approximately 69 cases per 100,000 people, and is therefore far less common that migraine (D'Alessandro et al, 1986). Men are affected more commonly than women in a proportion of 6:1. Although most patients begin experiencing headache between the ages of 20 and 50 years (mean, 30 years), the syndrome may begin as early as the first decade and as late as the eighth decade (Fig. 6-2). Clearly, age alone is an insensitive diagnostic criterion (Krabbe, 1986). Women with cluster headache are more likely than men to begin experiencing attacks after the age of 50; among women, headaches usually do not correlate with menses, are likely to cease during pregnancy (Ekbom and Waldenlind, 1981), and may be initiated by use of oral contraception (Peatfield et al, 1982).
The pain of a cluster headache commences quickly, without warning, and reaches a crescendo within 2 to 15 minutes. It is often excruciating in intensity, and is deep, nonfluctuating, and explosive in quality; only occasionally is it pulsatile. In addition, 10 to 20 percent of patients report superimposed paroxysms of stabbing, icepick-like pains in the periorbital region that last for a few seconds and may occur once or several times in rapid succession; this paroxysmal pain usually heralds the end of an attack. The symptoms resolve in 1 to 2 minutes (Ekbom, 1975).
The pain usually begins in, around, or above the eye or the temple (Fig. 6-3); occasionally the face, neck, ear, or hemicranium may be affected (Sutherland and Eadie, 1972). It is always unilateral, and generally affects the same side in subsequent bouts. However, it may shift to the corresponding region of the opposite side in 15 percent of patients (Manzoni et al, 1983b), usually for the duration of a bout, less often switching sides within a bout. Many patients prefer to be upright and active when an attack is in progress, but this is reported with a frequency that is not high enough to be useful diagnostically (Russell, 1981).
Attacks last from 30 minutes to 2 hours (mean of 45 minutes) in about 75 percent of cases. Occasionally, attacks - especially mild ones - may be as short as 10 minutes, whereas others may last as long as several hours. Attacks range in frequency from six per 24 hours to one per week, with a mean of one to two per day. Periodicity is a characteristic feature in about 85 percent of patients: attacks of pain tend to recur at the same hour each day for the duration of the cluster bout; many individuals also experience additional attacks that occur randomly throughout the day. About 75 percent of attacks occur between 9 p.m. and 10 a.m. (Russell, 1981). Manzoni et al, (1983b) found sharp peaks for attack frequency between 1 and 2 a.m., 1 and 3 p.m., and at 9 p.m (Fig. 6-4). Patients are awakened from sleep by pain paroxysms in about 50 percent of cases, usually within 2 hours of falling asleep (Lance and Anthony, 1971; Hornabrook, 1964). Nocturnal attacks are associated with rapid eye movement (REM) sleep about one-half the time in episodic cluster headache, but only rarely in the chronic form (Plaffenrath et al, 1986; Kayed and Sjaastad, 1985).
The attacks of pain are clustered in cycles that usually last 4 to 8 weeks, and are followed by a pain-free remission in 90 percent of patients. On occasion, bouts may be as short as a few days or as long as 4 months; about 10 percent of those with established cluster tempos enter a chronic phase in which the attacks may persist for an average of 4 to 5 years (Ekbom, 1986). The later the onset of the episodic disorder, the greater the chance of it becoming chronic (Kudrow, 1980). Most patients experience one to two bouts per year; however, the interval between bouts ranges from 1 month to 2 years in 80 percent of the cases and between 6 months and 2 years in 60 percent (Kudrow, 1980). In rare instances it may be as long as 25 years (Hornabrook, 1964). Eventually, the bouts cease spontaneously, but more precise data on the natural history of the disorder are not yet available.
Lacrimation from the eye on the affected side is the most common associated symptom (Table 6-2). A blocked nasal passage, rhinorrhea, red eye, and sweating and pallor of the forehead and cheek are often found, but their absence does not exclude the diagnosis. These autonomic symptoms, although clinically apparent unilaterally, are present bilaterally, quantitaively more so on the symptomatic side (Saunte, 1984; Sjaastad et al, 1981). There is a rapid increase in heart rate at the onset of attacks and further rate variations become pronounced as the paroxysm proceeds, suggesting central autonomic regulatory instability. In general, a modest bradycardia occurs during an attack (Russell and Storstein, 1983). A transitory, partial Horner's syndrome (pupillary miosis and lid ptosis) occurs in two-thirds of patients when they are examined during attacks (Ekbom, 1970a) and is a useful sign in the differential diagnosis of facial pain. It is highly characteristic of the cluster headache syndrome and, after repeated occurrences, it may become a permanent feature (Riley and Moyer, 1971; Nieman and Hurwitz, 1961).
The localization of the sympathetic lesion is of some interest. The ocular sympathetic innervation is a three-neuron pathway, comprising a first-order neuron: posterolateral hypothalamus to cord levels of C8 to T3 (the ciliospinal center of Budge); a second-order neuron: (preganglionic) ciliospinal center to super cervical ganglion; and a third-order neuron: (post-ganglionic) superior cervical ganglion to the pupillary dilator muscle, the eyelid muscles, and the facial sweat glands. It is believed by many observers that in cluster headache, involvement of the third-order neuron accounts for Horner's syndrome, which occurs as the result of distention of the wall of the internal carotid artery in the carotid canal, thus compressing the sympathetic plexus that invests the carotid wall. This argument is supported by three lines of evidence. The first is the observation that hyphidrosis is restricted to the forehead (Watson and Vijayan, 1982), which is consistent with a third-order neuron lision whereas more proximal lesions usually produce deficient sweating of the entire face (Morris et al, 1984). Second, supersensititivity of the miotic pupil to direct-acting sympathomimetic agents appears to place the lesion postganglionically (Fanciullacci et al, 1982; Vijayan and Watson, 1982); and third, angiographic changes of the carotid siphon during a cluster headache attack (Ekbom and Greitz, 1970) is also consistent with sympathetic plexus compression at this locus. However, others (Sjaastad, 1987) argue that there is sparse validation for the effects of conjunctival drugs on patients with central lesions (Malonety et al, 1980; Lepore, 1985). In fact, pupillary responsiveness and hyphidrosis patterns in patients with Horner's syndrome on a central basis are not very different from the results obtained with cluster headache patients (Van der Wiel and Van Gijn, 1986; Salvesen et al, 1987). Since the first-order hypothalamic neuron is uncrossed and, therefore, capable of generating ipsilateral symptoms, and for other reasons (see below) is an attractive patheogenetic locus, the issue, in my view, remains open.
Focal neurologic symptoms of the type characteristic of migraine are very uncommon in patients with the cluster headache syndrome; however, occasional patients experience typical photopsia, teichopsia, facial paresthesia, or vertigo at the time of the attack.
Sensitivity to alcohol during a cluster bout occurs in at least half the patients, and cases when the bout remits (Friedman and Mikropoulos, 1958); this alternating, on-off vulnerability is pathognomonic of the cluster headache syndrome. Patients who are sensitive to alcohol note that attacks are triggered within 5 to 45 minutes after the ingestion of modest amounts of alcohol: usually less than a single cocktail or glass of wine. The vast majority have noted that their sensitivity is less than total: alcohol triggers attacks in 70 to 80 percent of exposures. This factor, together with many patients' misinterpretations regarding inquiries into their drinking habits, may account for the low incidence of alcohol sensitivity in several reported series (Sutherland and Eadie, 1972; Symonds, 1956).
A number of other precipitating factors have been noted in a smaller number of patients and include stress, relaxation, exposure to heat or cold, glare, hay fever attacks, and, occasionally, the ingestion of specific foods (chocolate, eggs, dairy products).
There is some evidence that head trauma can precipitate the syndrome. Among the 180 patients studied by Manzoni et al (1983b), previous head injury was reported by 41, with loss of consciousness occurring in 20. This is significantly more frequent than is observed among patients with other types of headache; furthermore, in all patients in whom the head injury was lateralized and loss of consciousness ensued, the side involved corresponded to the side on which cluster headache later occurred. However, the mean latency in these cases was 9 years, which poses a serious question regarding the connection between head trauma and the cause of the cluster headache syndrome. Moreover, in an additional 11 of 15 patients who had undergone previous cranio-facial surgery, the side operated on was ipsilateral to that of the site of later-appearing cluster headache attacks. The latency between these latter events averaged 5 years. Kudrow has found no evidence that head trauma can precipitate the syndrome (Kudrow, 1980).
Experimentally, attacks can be triggered in nearly all patients during a bout by the administration of 1 mg nitroglycerin sublingually (Ekbom, 1968), and in about 70 percent of patients by subcutaneous histamine (Horton, 1961). There is usually a latent period of 30 to 50 minutes before headache is triggered, whereas the peak peripheral and central vascular effects of nitroglycerin occur within 3 to 4 minutes of its administration and disappear in approximately 30 minutes (Bogaert, 1987). This, the appearance of headache does not coincide with the maximal circulatory effect of nitroglycerin, and the mechanism by which nitroglycerin causes headache remains unclear. A period refractory to pharmacologic provocation occurs after spontaneous or pharmacologically induced attacks and may persist for 2 hours or more (Ekbom, 1968; Horton, 1961). Therefore, valid provocative tests must be administered during an active bout, several hours after the attack has subsided.
Ekbom (1975) found that compression of the superficial temporal artery provided temporary relief for about 40 percent of his patients but just as often worsened the pain; carotid compression reduced the pain half the time, and worsened it in 25 percent of his cases. Vigorous physical exertion at the earliest sign of an attack can, in some patients, be remarkably effective in ameliorating or even aborting an attack (Atkinson, 1977; Ekbom and Lindahl, 1970).
Hereditary factors are significant in migraine and might be expected to be important in the cluster headache syndrome because of their mechanistic and pharmacologic similarities. However, it is uncommon to find other examples of cluster headache in the family history. Among Kudrow's (1980) 495 patients, 18 reported the presence of the syndrome in a parent. Migraine occurs no more frequently among the cluster headache population than among random population than among random populations (Andersson, 1985). When migraine predates the commencement of cluster attacks, migraine usually ceases when the cluster attacks begin (Bickerstaff, 1959); thus, although these disorders are biologically distinct, their mechanisms are probably connected.
A carefully elicited history is the key to diagnosis. There are no abnormalities to be found upon a physical or laboratory investigation other than Horner's syndrome occasionally. In approximately 70 percent of patients with cluster headaches, the carotid artery is palpably tender at several points in the neck (Raskin and Prusiner, 1977). The cluster headache syndrome, with all autonomic symptoms, on-off,alcohol sensitivity, ipsilateral tender carotid artery, and clocklike periodicity of attacks, has not been associated with any underlying intracranial structural abnormalities. There have been a few cases reported of lesions producing painful disorders resembling this syndrome, and some in which coincidental anatomic anomalies were demonstrated (Tfelt-Hansen et al, 1982; Mani and Deeter, 1982; Kurizky, 1984).
Graham (1972) formed the impression that certain physical features seemed to be characteristic of cluster headache patients. These include a ruddy complexion, multifurrowed and thickened skin, and a broad, prominent chin: all contributing to a "leonine" facial appearance. However, these observations were uncontrolled, and I have been unable to confirm them. There is no evidence that important psychological variables bear on this syndrome (Cuypers et al, 1981; Kudrow, 1980).
The traditional designation of cluster headache as a vascular headache disorder is probably inappropriate; the vascular alterations that occur appear to be epiphenomenal, as they are in migraine, resulting from a primary CNS discharge. The hypothalamus may well be the site of such activation, containing posterior cells that regulate autonomic functions and anterior nuclei that serve as the major circadian pacemaker in mammals (Moore-Ede et al, 1983), both of which are necessary to explain the clinical symptoms and the uncanny periodicity of cluster headache attacks. The "biologic clock" is serotonergically modulated (Mason, 1986) and is connected anatomically to the eye (Sadun et al, 1984). The drugs effective in the treatment of the cluster headache syndrome enhance serotonergic neurotransmission, as also occurs in the treatment of migraine.` This suggests that unstable serotonergic neurotransmission, at different loci, may be common to both disorders. In this section, we will review, among other data, the evidence supporting the tantalizing speculation that the cluster headache syndrome may be the result of an antidromically discharging biologic pacemaker.
A pacemaking mechanism in mammalian brain controls circadian rhythms (from the Latin circa diem, about 1 day), which are endogenous daily cycles. The most important of these biologic clocks is believed to be the suprachiasmatic nuclei (SCN): two small cell groups in the anterior hypothalamu7s just dorsal to the optic chiasm (Schwartz et al, 1987; Moore and Card, 1985; Turek, 1985). The pacemaker generates circadian rhythms, couples them with one another, and synchronizes them with external environmental events. Events in the internal milieu are arranged in temporal sequence to permit maximal adaptation to synchronized in phase and period, by time cues such as the daily light/dark cycle; a visual pathway from retina to the SCN is necessary to mediate entrainment (Sadun et al, 1984). The function of this system is to maintain daily order in physiologic processes, such as enzyme activities, body temperature, hormone secretion, and some behaviors. A disordered pacemaker may result in illness. For example, there is evidence that in jet lag and in manic-depressive illness, circadian rhythms may not be synchronized with one another or with the sleep-wake cycle (Wehr et al, 1983).
Under normal conditions, a rhythm generated by the pacemaker is transmitted to synapses where a receptor rhythm evokes second messenger elaboration, which, in turn, modulates neurotransmission (Kafka et al, 1983). Lithium is believed to act on this second messenger system (see below).
The SCN project to, and receive afferents from, the midbrain periaqueductal gray matter (Moore, 1983), so that a functional link to the pain-modulating system is feasible. Furthermore, serotonin-containing terminals arising from the midbrain dorsal raphe nuclei distribute in a dense plexus in the SCN and are capable of serotonin uptake. There is evidence that serotonergic mechanisms are involved in the expression rather than the generation of circadian rhythms. The SCN neurons are responsive to serotonin and its release via activation of the midbrain raphe projection to the SCN (Groos et al, 1983). Intrinsic pacemaker frequency appears to be modulated serotonergically by a mechanism that has not yet been established. It is interesting that lithium experts prominent effects upon circadian rhythms (Kripke and Wyborney, 1980; Kafka et al, 1982), possibly through an enhancement of serotonergic neurotransmission (Blier and De Montigny, 1985).
Apart from the circadian periodicity of individual attacks and the periodic recurrence of bouts of cluster headache, further evidence of the role of a central pacemaker comes from hormonal studies among patients. Dampening of secretory circadian rhythms has been shown for melatonin, cortisol, testosterone, �-endorphin, �-lipotropin, and prolactin (Waldenlind et al, 1984; Chazot et al, 1984; Facchinetti et al, 1986; Nappi et al, 1985; Waldenlind and Gustafsson, 1987) during bouts; most of these rhythms revert to normal during remissions.
Additional support for a CNS disturbance as the source of cluster attacks comes from studies of brain stem auditory-evoked potentials. Slowed conduction (increased I-V interpeak latencies) was shown ipsilateral to the painful side and became more pronounced during paroxysms of pain; lithium treatment appeared to shorten the latencies (Bussone et al, 1986). Clinically, the concurrence of cluster headache and trigeminal neuralgia, the cluster-tic syndrome, in which both disorders are ameliorated by microvascular decompression of the sensory root of the trigeminal nerve, also points to a centrally mediated pain mechanism.
Dilatation of extracerebral arteries appears to be common to both migraine and cluster headache (Sakai and Meyer, 1978); enhanced pulsation of the intraocular vascular bed occurs during cluster attacks but not during migraine attacks (H›rven et al, 1972; H›rven and Sjaastad, 1977), underlining the involvement of the internal carotid artery and its branches in the cluster headache syndrome. Evidence that part of the pain of cluster headache is derived from dilatation of intracranial branches of the internal carotid artery stems from the observation of Thomas and Butler (1946) that pain may be relieved in some patients by the intrathecal injection of saline, which increases the cerebrospinal fluid pressure to 700 mm H2O.
The importance of vascular dilatation in cluster headache has been emphasized in the past because headaches may be precipitated during a bout by vasodilators such as alcohol, histamine (Horton, 1941, 1952; Hardebo et al, 1980), and nitroglycerin (Ekbom, 1968); however regional cerebral blood flow (CBF) studies in the modern era have shown only inconsistent alterations in flow during attacks, lending no support to the idea that vasodilatation is necessary to the pain mechanism (Nelson et al, 1980; Krabbe et al, 1984). Drummond and Lance (1984) and Drummond and Anthony (1985) showed that the increase in extracranial blood flow and increased temporal artery pulsations that attended individual attacks usually followed the onset of pain in affected areas, which led them to a primary neural discharge.
Reduction of the severity of angina pectoris and limb claudication has been noted during some cluster bouts (Ekbom, 1970b), suggesting that, at least in some patients, an alteration of arterial tone outside the carotid circulation also occurs.
A search for biochemical agents has been made on the presumption that the cluster headache syndrome may be mediated by a disorder of humoral control of blood vessels. The prominence of lacrimination, perspiration, and suffusion of the conjunctivae is consistent with an excessive cholinergic discharge. This reasoning led Kunkle (1959) to examine cerebrospinal fluid for acetylcholine-like activity, which he found in 4 of 14 patients at the time of headache; it was not found in 7 patients with classic migraine.
Serotonin alterations are more subtle in patients with cluster headache than in migraine. Medina et al (1979) found modest elevations of serotonin in whole blood during attacks of cluster headache, whereas platelet serotonin levels fall precipitously during migraine attacks. Waldenlind et al, (1985) found low whole blood serotonin levels among cluster patients both during an active bout and during remissions, comparable to levels found among migraine patients.
Erythrocyte choline concentrations are low in cluster headache patients (de Belleroche et al, 1984); this is an interesting observation because lithium administration greatly increases erythrocyte choline levels, an effect that persists for months. The depressed choline level is not confined to the acute attack; it is also present between bouts. de Belleroche et al (1986) took these data a step further and showed that erythrocyte membrane phosphatidylcholine/cholesterol ratios were increased in cluster headache patients, indicating a reduced turnover of phosphatidylcholine in the red cell membrane. It is not yet clear whether these intriguing findings are related to the mechanism of the disorder.
The possibility that histamine may be involved is supported by the reportedly higher incidence of duodenal ulceration in patients with cluster headache (Ekbom, 1970b) as well as by the precipitation of attacks with small amounts of this substance. Anthony and Lance (1971) and Medina et al, (1979) have shown that there is a modest increase in whole blood histamine during an attack; furthermore, elevations of urinary histamine were found in four of eight patients during cluster attacks (Sjaastad and Sjaastad, 1970). These reports are challenged by the lack of change in the catabolic pattern of intravenously administered C14 histamine in patients with cluster headache (Beall and Van Arsdel, 1960) and, since histamine is localized peripherally to basophilic leukocytes, caution is advised when interpreting whole blood levels (Porter and Mitchell, 1972). Patients with chronic myelogenous leukemia have very high blood levels of histamine but do not report headache. Furthermore, antihistaminic agents are disappointingly ineffective, as also has been histamine desensitization.
It has been apparent for some time that there are at least two histamine receptors, since some of the effects of histamine are not blocked by the usual antihistaminic agents (Ash and Schild, 1966). Substantial evidence for two histamine-induced vasodilatation is only partly reversed by H1 antagonists (Hardebo et al, 1980), and it now appears likely that bot H1 and H2 receptors are present in the carotid vascular bed (Saxena, 1975), the availability of H2 antagonists has renewed the interest in testing the role of histamine in cluster headache. Anthony et al, (1978) and Russell (1979) have used H1 and H2 antagonists in the therapy of cluster headache, without clear success. It is possible that the elevation of blood histamine is the result of episodes of paroxysmal vascular instability, since histamine is but one of a group of diverse substances that includes the kinins, prostaglandins, and others that are released from tissues during injury or inflammatory reactions (Beaven, 1976).
Appenzeller et al (1981) found that mast cells, the major repository of histamine in many tissues, are found in increased number in the skin of the painful temporal area in cluster headache patients; this effect is particularly striking within the first 10 hours after a cluster attack. Mast cell numbers in patients outside of a cluster period are similar to those of migraineurs (Appenzeller, 1987), which suggests that these cells are increased in both types of headache as a secondary event. No differences have been found in the dermal response to histamine among cluster headache patients when the painful side was compared to the opposite side (Bogucki and Prus�nski, 1985), which lends no support to the idea that the periodic release of histamine might stimulate trigeminal nerve endings and thus be directly implicated in the mechanism of an attack.
The original therapy in this condition was based on administration of a vasoconstrictor such as ergotamine to antagonize the paroxysmal vasodilation that appeared to be the cardinal mechanism of pain production. However, the efficacy of agents that have no direct vasoactivity has cast doubt on the vasoconstrictor hypothesis. it appears more likely that the different treatment modes discussed in this section are successful because they stabilize serotonergic neurotransmission.
The most satisfactory treatment is the administration of drugs to prevent cluster attacks until the bout is over. Several effective pharmacologic options may be chosen. However, whichever agent is used, there may be a lag period of days or, occasionally, weeks before effective suppression is achieved. For this reason, it is essential to attempt to treat the individual attacks until they can be prevented. Since the attacks are so brief and have such a rapid crescendo, orally administered, slowly absorbed drugs are generally ineffectual, but inhalational agents are often useful.
The ergotamine aerosol at a dosage of 0.36 to 1.08 mg (one to three inhalations) produces peak plasma levels of ergotamine within 5 minutes (Ekbom et al, 1983) and is effective about 80 percent of the time (Speed, 1960; Kudrow, 1980). Two important aspects of the use of the aerosol are often overlooked and account for may apparent treatment failures:
Because the drug is formulated as a suspension, it is essential that the cannister be shaken vigorously before each administration.
Patients should be instructed to administer the aerosol after a forced expiration, simultaneous with the onset of inspiration. The breath should then be held in deep inspiration for several seconds and then slowly exhaled.
The inhalation of 100 percent oxygen, via a tight-fitting mask at a flow rate of 8 to 10 liters/min for 10 to 15 minutes is dramatically effective for about 80 percent of those patients for whom this approach is feasible; oxygen is particularly effective for nocturnal attacks. This mode of therapy, although recommended by Horton (1952) over 35 years ago, has only recently been substantiated by controlled trials (Kudrow, 1981; Fogan, 1985). Oxygen inhalations may be repeated up to five times per day. Sakai and Meyer (1979) have shown that marked cerebral vasoconstriction results from the administration of 100 percent oxygen during cluster headache attacks. Whether this effect is direct or is mediated centrally has not been studied. Oxygen also stimulates the synthesis of serotonin in the central nervous system (CNS) (Costa and Meek, 1974).
Kittrelle et al (1985)A showed that the intranasal instillation of 1 ml 4 percent topical lidocaine was effective in terminating attacks in four of five patients. The patients were instructed to lie supine, with their heads extended backward 45 degrees and rotated 30 to 40 degrees toward the side of the headache. One ml lidocaine was slowly dropped into the nostril ipsilateral to the pain, and the patient's position was maintained for several minutes. If nasal congestion mad it impossible to deliver the anesthetic solution to it target, the patient was initially treated with a few drops of intranasal 0.5 percent phenylephrine. These investigators believed that the lidocaine reached the sphenopalatine fossa and anesthetized the sphenopalatine ganglion. That is certainly possible but, and addition, local blockade of terminals of the trigeminal and glossopharyngeal nerves intranansally could also decrease afferent activity to the spinal trigeminal nucleus, stopping the pain because of convergence of the sensory elements of cranial nerves V, VII, IX, and X. The beneficial effect of topical lidocaine surely does not implicate the sphenopalatine ganglion in the mechanism of cluster headache. I find lidocaine to be an extremely useful therapeutic adjunct. The 1 ml dose may need to be repeated once or twice. For may patients, the application of lidocaine via the continuous pumping of a plastic nasal spray bottle is superior. In my experience, lidocaine is useful for about 60 percent of patients.
For the patient having an attack in the physician's presence, intravenous dihydroergotamine (DHE) rarely fails to about the episode within 5 minutes (Raskin, unpublished observations).
Another option that is frequently useful is the inhalation of methoxyflurane, a rapid-acting analgesic. Patients are instructed to apply 10 to 15 drops rapidly to a handkerchief, pillow case, or paper tissue, form a funnel with their hands, and inhale for several seconds. They should be seated or reclining, since light-headedness may ensue. The analgesia produced by this agent lasts but a few minutes but, if administered early, the attack may be aborted (Raskin, unpublished observations).
Phenylpropanolamine, taken orally, significantly shortens cluster attacks for many patients (Cohen, 1980). However, the rare occurrence of intracerebral hemorrhage following modest doses of this drug (Kase et al, 1987) makes it unsuitable in the face of viable safe alternatives.
The major prophylactic drugs for the cluster syndrome are prednisone, lithium, methysergide, and ergotamine. Lithium appears to be particularly effective for the chronic form of the disorder. Pizotifen, nifedipine, verapamil, nimodipine, phenelzine, ergonovine, indomethacin, and cyproheptadine all have some documented efficacy.
K. A. Ekbom (1947), Karl Ekbom's father, was the first to describe the use and effectiveness of ergotamine in preventing attacks; he used ergotamine tablets, 2 mg two to three times per day, and obtained good results in 13 of 16 patients. Two mg taken orally or 1 mg rectally 2 hours before an expected attack can be particularly effective, especially for nocturnal attacks. The advantage of ergotamine in this condition is that its clinical effect may be assessed within 24 hours, which is an obviously important consideration for patients experiencing several attacks of high-intensity pain every day. Long-term risk factors must be placed into the context of a relatively short exposure to whichever agent is chosen. It is interesting that ergotamine dependence is quite rare among cluster patients (Raskin, unpublished observations); once the bout is over, the drug is easily discontinued. I have encountered only two patients who did seem to generate additional cluster attacks during a bout through the use of large daily doses of ergotamine. The efficacy of ergotamine in treatment of the cluster headache syndrome has led many physicians to believe that here is more therapeutic overlap between this disorder and migraine than actually exists. Propranolol and amitriptyline, major drugs in migraine therapy, have no established role in the treatment of cluster headaches; conversely, lithium may exacerbate migraine (Peatfield and Rose, 1981).
Intravenous DHE, given every 8 hours, has completely stopped cluster attacks in 20 consecutive patients. For 7 of them, the bout was over following 3 days of DHE treatment, but this could have been coincidental (Raskin, unpublished observations).
For the episodic form of cluster headache, prednisone is highly effective in over 75 percent of patients (Kudrow, 1978) (Table 6-3). The value of prednisone has been established in a double-blind study (Jammes, 1975), and it is clearly a first-line drug, if not the drug of choice in this situation. The dosage has varied from 10 to 80 mg daily in various studies (Couch and Ziegler, 1978). I use 80 mg per day for 7 days and then rapidly taper the dosage over 6 days. Pain paroxysms usually cease within hours for the first dose. If there is no response after 48 hours, prednisone should be stopped and an alternative therapy instituted. If, while the dosage is being tapered, headaches return, prednisone may need to be continued for the duration of the cycle, preferably on an every other day basis, at dosages less than 140 mg weekly. Many patients have to take prednisone for 5 or 6 days, but then stop it and find that the bout is over. This has happened often enough to convince me that prednisone can actually terminate the bout for about 20 percent of patients. Watson and Evans (1987) made similar observations in 2 of 11 steroid-treated patients with the chronic form of the disorder. It is, therefore, worth treating the chronic patients with a 2-week course of corticosteroid, with the aim of interrupting the cycle, although in most headaches return when the dosage is tapered.
I have seen several patients who were unresponsive to full dosages of prednisone, but who responded spectacularly to triamcinolone at dosages of 32 mg per day.
The remarkable efficacy of corticosteroids in this syndrome is not easily explained. McEwen et al, (1986) have reviewed the many potent actions of the corticosteroids on the CNS, but these are just beginning to be defined. De Kloet et al (1986) studied the relationship of corticosteroids to the serotonergic projection from the dorsal raphe nucleus to the hippocampus in rat brain; they found that corticosteroids exerted tonic control on serotonergic neurotransmission in this system.
Methysergide is effective for about 70 percent of patients with the episodic form of cluster headache; it is far less effective for the chronic form (Kudrow, 1980) (Table 6-3). The dosage range is 4 to 10 mg/day, with occasional patients requiring as much as 16 mg/day to stop the attacks. The major, rare hazard of retroperitoneal fibrosis, which may appear after several months of use of methysergide is not an important consideration when the drug is used to treat episodic cluster attacks, which usually requires only 4 to 6 weeks of drug exposure. Improvement usually begins within the first few days of therapy; occasionally responses may be delayed for 10 to 14 days.
The discovery by Ekbom (1974a,b) of the effectiveness of lithium for the prophylaxis of cluster headache has had a major impact on the treatment of this condition. Many studies have now been published regarding the use of this agent and have been reviewed by both Ekbom (1981, 1986) and Manzoni et al (1983a). The dosage has varied from 300 to 1500 mg daily, averaging 600 to 900 mg/day. Kudrow (1980) has found that about 10 percent of patients require only 300 mg/day. Favorable responses occur within 2 weeks of commencing treatment, usually within the first week. The chronic form of cluster is particularly well-suited for lithium treatment, with about 80 percent of patients substantially improved and remaining so for substantial periods of time (Table 6-4). During successful lithium therapy, about 60 percent of patients experience bursts of short cluster periods that are generally mild and of short duration. Ergotamine added to lithium at dosages of 2 to 4 mg/day is a highly effective strategy, even when either drug alone has been ineffective (Stagliano and Gallagher, 1983). In Kudrow's (1980) experience, approximately 40 percent of his patients treated with lithium require such concomitant ergotamine prophylaxis for complete relief of headache.
In Ekbom's (1981) experience and in ours, lithium therapy blocks alcohol-provoked attacks in most patients with the chronic form of cluster. Following the cessation of lithium therapy, about 20 percent of patients experience long periods of remission, their disorder having transformed to the episodic form (Kudrow, 1980), which raises the possibility that lithium may alter the natural course of the disorder.
The episodic form of cluster is less responsive to lithium treatment when it is begun after a bout has commenced. Three-fourths of the 68 patients studied by Manzoni et al (1983a) improved by more than 60 percent (Table 6-4). However, when used for subsequent cluster cycles, lithium was considerably less effective. These investigators made the interesting observation that four of their patients who experienced and average of more than four cluster bouts annually, when treated with lithium uninterruptedly for over 1 year, sustained no further attacks during lithium treatment. When lithium was withdrawn, attacks resumed within 1 to 3 weeks. Ekbom (1981) made the same observation regarding four similarly treated patients.
Clinical Pharmacology. Lithium is readily absorbed from the gastrointestinal tract and peak plasma levels are reached 2 to 4 hours after its ingestion. It should be given in three divided doses, initially 900 mg daily, which may be decreased if side effects appear by breaking the tablet formulation of the drug into halves and adjusting the dosage downward. Gastrointestinal side effects may be considerably attenuated by using lithium citrate syrup, 300 mg/teaspoonful, which may be diluted in iced fruit juice. Lithium displaces intracellular sodium, and sodium depletion promotes its retention; the risk of intoxication is lessened by avoiding a low-salt diet and the use of natriuretic drugs (Reisgerg and Gershon, 1979). Plasma levels obtained 12 hours after the last dose should be maintained below 1.2 mEq/liter and should be measured weekly during the first few weeks of therapy, but only infrequently thereafter if the dosage is in the low range and the patient is free of side effects.
Side Effects. The most common side effects are tremor, polyuria, nausea, diarrhea, and gait unsteadiness and are dose-related. High plasma levels may produce myoclonic jerks, dysarhria, hypotension, convulsions, and renal failure; rigidity of the limbs and fasciculations are characteristic features of moderate to severe degrees of intoxication (Sansone and Ziegler, 1985). Hemodialysis is the most effective means of dealing with serious acute toxicity. Fortunately, the relatively low dosage of lithium required to treat cluster headache successfully rarely gives rise to the more serious side effects.
Lithium also suppresses thyroid function, occasionally resulting in hypothyroidism that may be irreversible (Medical Letter, 1980). The polyuria produced by lithium is mitigated by amiloride by blunting the inhibitory effect of lithium on water transport in the renal collecting tubule (Batlle et al, 1985). Irreversible renal concentrating defects occur rarely (Vestergard and Amdisen, 1981; Waller et al, 1984: De Paulo et al, 1986). Baseline studies of renal and thyroid states should be obtained before treatment is begun. Reversible intracranial hypertension has also been caused by lithium (Saul et al, 1985), so regular funduscopic examinations should be performed.
There are a number of troublesome drug interactions. Lithium intoxication can occur with the concurrent use of methyldopa, tetacycline or indomethacin; there are, in addition, isolated reports of CNS toxicity with the concurrent use of haloperidol, thioridazine, carbamazepine, or phenytoin (Medical Letter, 1980).
Mechanism of Action. Lithium has no effect on cerebral hemodynamics in patients with cluster headaches (Okayasu et al, 1984). On the other hand, there is substantial evidence that lithium stabilizes and enhances serotonergic neurotransmission in the CNS, particularly in the hippocampus, the site at which both S1 and S2 receptors are down-regulated during lithium treatment (Treiser et al, 1981; Blier and De Montigny, 1985; Hoffa et al, 1986). It is curious that serotonergic nerve fibers appear in human temple skin after lithium treatment (Dhital et al, 1985).
As discussed above (see discussion of biologic clocks), the hypothalamic pacemaker is serotonergically innervated, and perhaps it is on this basis that lithium has prominent effects on circadian rhythms, acting to slow and alter them (Kafka et al, 1982; Kripke and Wyborney, 1980). The molecular site of action for lithium is currently believed to be at a second messenger system in the CNS (Worley et al, 1987). The polyphosphoinositides are a group of membrane phospholipids that, when activated, release two products both of which act as second messengers: Diacylglocerol and inositol triphosphate. This second messenger system is particularly abundant in brain and modulates many aspects of synaptic transmission. Lithium's actions on the phosphoinositide cycle may underlie its therapeutic actions (Drummond, 1987).
That a biologic pacemaker is an important site of lithium's action is supported by the effectiveness of this agent in cyclical migraine and by a curious group of patients we have encountered over the past 10 years with "hypnic headaches." Six elderly patients, all but one men, between the ages of 65 and 77 began to be wakened from sleep regularly, at the same time each night, often during a dream, by a diffuse headache that lasted for 30 to 60 minutes, unassociated with any autonomic symptoms. In all cases, headache ceased after 300 to 600 mg of lithium was taken at bedtime (Raskin, unpublished observations).
Ekbom (1969) showed in a controlled trial with 28 patients, that 2 to 3 mg pizotifen daily produced excellent or good results in nearly 60 percent. Cyproheptadine, closely related to pizotifen pharmacologically, also has value in this disorder (K. Ekbom, personal communication), but the side effects of weight gain and sedation may be troublesome.
Chronic paroxysmal hemicrania is subgroup of the chronic form of cluster headache, is highly responsive to indomethacin. It is characterized by 15 or more focal attacks of head pain daily, each lasting for about 15 minutes. Mathew (1981) identified a transitional group of patients with the chronic form of cluster headache, who had attacks of headache of sudden onset, lasting 20 minutes, and occurring five times daily; four such patients were treated with indomethacin at 150 mg daily, with a crossover period to placebo, and clearly benefited. Similarly, Kudrow et al (1987) described six indomethacin-responsive patients with a cyclic form of paroxysmal hemicrania.
Meyer and Hardenberg (1983) and Mullaly and Livingstone (1984) have shown in small studies that verapamil, nifedipine, and nimodipine all reduce that frequency of attacks of the chronic type of cluster headache. I used nimodipine at doses up to 240 mg/day in 15 patients who were totally refractory to previous pharmacotherapy; 7 became headache-free for the 6 month duration of the open study. Nifedipine is quite effective in many patients at dosages that range between 40 and 120 mg daily.
Anthony (1985) studied 20 patients with cluster headache, 12 with the episodic and 8 with the chronic type. Blockade of the greater occipital nerve ipsilateral to the side of attacks was accomplished with lidocaine and 120 mg methyprednisolone acetate in polyethylene glycol. Attacks were arrested for 5 to 73 days; when lidocaine alone was used for the procedure, the attacks were not arrested, thus, supporting the importance of corticosteroid in the procedure. I have used steroid (betamethasone) block in 10 patients with the chronic disorder and produced remissions in 6 of them that lasted 7 to 21 days (Raskin, unpublished observations). I regard this as a useful temporary procedure for the desperate patient, to allow time for the next pharmacotherapeutic procedure to be implemented. The mechanism of this procedure is nonspecific; it involves decreasing afferent impulses to the spinal trigeminal nuclear complex.
For patients who are completely refractory to all known medical therapy and continue to experience repeated attacks of pain chronically, a number of aggressive procedures have been implemented. These include percutaneous glycerol injections into the trigeminal cistern, trigeminal sensory rhizotomy, percutaneous radiofrequency trigeminal rhizotomy, superficial petrosal neurectomy, trigeminal branch avulsion, and decompression of the nervus intermedius (Ekbom et al, 1987; Watson et al, 1983; Onofrio and Campbell, 1986; Solomon and Apfelbaum 1986). The overall benefit from these procedures is about 50 percent, with no one procedure holding superiority. Since repeated injections of local anesthetic of the gasserian ganglion may provide long-lasting but temporary relief, I have used steroid injections of the maxillary division of the trigeminal nerve in four patients with infraorbital pain. Pain relief occurred in all four, lasting 10 to 34 days (Raskin, unpublished observations).
For the patient in the throes of a first bout of cluster headache, corticosteroids and ergotamine hold the advantage that their beneficial effects can be assessed within 24 hours. A 10- day course of prednisone or triamcinolone treatment holds the promise of terminating the mechanism of the bout, and therefore, in my view, these are the drugs of choice. I also provide the patient with 4 percent topical lidocaine and inhalational ergotamine in the event that the first strategy fails. Should both ergotamine and the corticosteroids fail, methysergide, lithium, ergonovine, and phenelzine are the next therapeutic modes, to be used, in that order. Cigarette smoking should cease, at least for the duration of the bout, since in about 5 percent of patients this is a factor leading to drug refractoriness (Raskin, unpublished observations).
For the chronic cluster headache patient, lithium, nifedipine, and nimodipine are the major choices. Some of these patients are responsive to indomethacin (Watson and Evans, 1987), and I have found several responsive to phenelzine. Occasionally, chlorpromazine has been useful at dosages in the 200 to 700 mg per day range (Caviness and O'Brien, 1980).
Using positron emission tomography (PET) to examine the cause of cluster headaches, researchers found that the hypothalamic region in affected people consistently lit up, indicating activity in that part of the brain.
September 1998 , Vol. XV , Issue 9
Using positron emission tomography (PET) to examine the cause of cluster headaches, researchers found that the hypothalamic region in affected people consistently lit up, indicating activity in that part of the brain.
The investigators, who presented their findings at the 40th annual scientific meeting of the American Association for the Study of Headache in June, studied cluster headache attacks in 17 patients after administering nitroglycerin to trigger the pain.
By injecting the patients with water labeled with a radioactive tracer, the research team was able to monitor cells undergoing more activity. That activity was recorded by a PET camera, then processed and reconstructed by computer so that the areas of greatest activity "lit up" on a computer-generated image.
The scientists discovered that the hypothalamic region of the brain, the part of the central nervous system that contains the brain's biological clock, lit up more than other regions during an attack.
"This suggests we need to consider a radical reappraisal of the pathophysiology of cluster headache," said lead researcher, Peter J. Goadsby, M.D., Ph.D., professor of clinical neurology at the Institute of Neurology, Queen Square, London-CLG
Nerve Stimulation Shows Promise When Drugs Fail
By Salynn Boyles
WebMD Medical News
Reviewed by Louise Chang, MD
March 8, 2007 -- There is new hope for sufferers of an excruciatingly painful type of headache who get no relief from drugs.
Two newly published studies show a minimally invasive nerve stimulation procedure to be a safe and effective alternative to surgery for many patients with drug-resistant cluster headaches.
The pain associated with cluster headaches is considered to be among the worst that a human can experience. Sufferers often report relentless, intense burning or stabbing pain located behind one eye, generally lasting from 30 minutes to 90 minutes and recurring several times a day.
About one in 1,000 people get cluster headaches, making them far less common than migraines and other types of headaches. And unlike migraines, men get them more often than women.
"The only suicides I have ever seen due to headaches are in people who get cluster headaches. That is how painful they are," National Headache Foundation executive chairman Seymour Diamond, MD, tells WebMD. "That is why some people call them ‘the suicide headache.’"
Most cluster headache sufferers respond to drug treatments designed to prevent attacks or minimize their intensity. But the options for those who don’t respond are few, and those options are associated with troubling and even potentially life-threatening side effects, says neurologist Peter J. Goadsby, MD, PhD, of the U.K. Institute of Neurology.
Patients who are not helped with less-invasive treatments may opt for surgery to destroy nerves in the brain that carry pain signals to the face. The surgery is permanent, and it doesn’t always work, Goadsby tells WebMD.
"We really need to do better by these patients," he says. "There is no place in modern headache treatment for destructive procedures like these."
Goadsby decided to try a technique known as occipital nerve stimulation after seeing how well the therapy worked in other hard-to-treat head pain patients.
Eight patients with chronic cluster headaches who got little relief from drug treatments were recruited for the trial.
The procedure involves positioning a fine electrode under the skin at the base of the skull. This is attached to a wire leading to a pacemaker-like device implanted elsewhere in the body. An external generator controls the degree of stimulation the patients receive.
The trial participants were followed for an average of 20 months, during which time two patients reported 90% to 95% improvements in attacks. Four other patients reported more moderate improvements of between 20% and 80%.
Six of the eight patients said they would recommend the treatment to other people with drug-resistant chronic cluster headaches.
In a similarly designed study from Belgium’s Liege University, two of eight patients treated with occipital nerve stimulation reported being pain-free after follow-ups of 16 and 22 months, respectively. Three other patients reported roughly 90% reductions in headache frequency and only one patient discontinued treatment.
The studies are published in the March 8 online editions of the journals The Lancet and The Lancet Neurology.
Neurologist Jean Schoenen, MD, PhD, who co-authored the Belgian study, tells WebMD that the next step is to figure out why the stimulation treatment works.
"We really don’t know," he says. "We are hoping that brain imaging studies can tell us which areas of the brain are affected by this treatment."
Diamond, who is founder and director of the Diamond Headache Clinic in Chicago, says he would consider trying the nerve stimulation procedure in his patients with drug-resistant chronic cluster headaches.
But he dismissed the idea that it is the only minimally invasive treatment option for these patients. He tells WebMD that he has had good responses with another minimally invasive treatment.
"The main message is that there are effective treatments for the vast majority of cluster headache patients," he says.
SOURCES: Burns, B. The Lancet, March 8, 2007; online edition. Magis, D. The Lancet Neurology, March 8, 2007; online edition. Peter J. Goadsby, MD, PhD, professor of neurology, U.K. Institute of Neurology, University College London. Jean Schoenen, MD, PhD, headache research unit, department of neurology, Liege University, Liege, Belgium. Seymour Diamond, MD, executive chairman, National Headache Foundation; founder and director, Diamond Headache Clinic, Chicago.
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