Short Notes on Headache
Number Seven
Cluster Headache
In contrast to migraine and the other primary headache disorders, the intensity of
a cluster headache is best described as excruciating. Cluster headaches have
been called suicidal headaches because patients with cluster have often
committed suicide. If the duration of the individual cluster headache were much
longer than the usual 30–45 minutes, probably most of the patients with cluster
would resort to suicide. I have been called to see a patient with cluster who was
admitted to the psychiatric ward after an unsuccessful suicide attempt. When
you are asked to see a patient with suspected cluster, it is an emergency and
treatment should be given immediately. Fortunately most patients with cluster
can be helped.
Cluster headaches occur in 0.3 % of the young adult population, and are thus
much less common than migraine. There is on a minimal increased occurrence
in families. Cluster occur 3–4 time more frequently in males than females, the
reason for this sex difference being unknown since there is no apparent relation
to hormonal dysfunction. The onset is usually in the third or fourth decade, but
recurrent cluster may continue in subsequent years. In the literature there are
reports of the age of onset ranging from 1– 80 years of age. In one study the
incidence in 18 year olds was 0.09%. The onset is rare in children and younger
teenager.
Kunkle and Pfieffer at Duke in 1952 first used the term “cluster” to describe the
headaches as occurring in bunches followed by weeks, months or even as long
as 20 years before the next series of daily headaches might occur. Between
these clusters the patient might experience very infrequent, less intense, but
otherwise typical cluster pain lasting only a single day, leading them to fear that
another full blown cluster is starting.
In 80-90% of cluster patients the headaches are episodic, occurring as bouts or
“clusters” of daily headaches usually lasting 6–14 weeks which spontaneously
cease. At the onset or near the termination of one of these clusters the intensity
of pain might be less and the headaches might occur only once a day. The
severity and frequency rapidly increases after the cluster begins to become 3-4
excruciating headaches each day, the individual headaches lasting 15-180
minutes. In the other 10-20% of patients with cluster, the condition is chronic.
The classification committee of the International Headache Society defined
chronic cluster as lasting for longer than one year without remission or with
remissions lasting less than one month.
The diagnosis of cluster is quite simple and does not require imaging or any
laboratory studies. It is based on the history. When the patient is seen, he
usually is not having an attack. The patient should have a complete history,
review of systems and neurological examination to exclude other conditions.
Careful inquiry should be made into previous medications taken for the
headaches and possible medications that are being used daily for other
conditions.
The headaches are unilateral and localized to the eye and temple. Occasionally
the pain is described as spreading up from the neck or down into the neck. Often
the pain is circadian, occurring at or near the same time each day. A frequent
time of onset is 2- 3 AM and another peak occurs at 9AM. The reason for this is
unknown, but points to the suprachiasmatic nucleus, the site of the biologic clock.
In contrast to a severe migraine headache which often causes the patient to
remain motionless in a darkened room, the patient having a cluster headache
feels the urge to get up and move about, even strike their head on the bedroom
wall and breaking the drywall in their bedroom. Fifty percent of patients describe
their pain as pulsating and up to 70% note mild photophobia or phonophobia.
There is no nausea or vomiting, no aura or other migrainosus features. The pain
reaches maximum intensity after 5-10 minutes, too fast to allow for relief with an
oral medication. The individual headache pain rapidly subsides and between the
daily clusters the patient has no symptoms other than fear of the next attack.
Predominately unilateral changes of function of the autonomic nervous system
on the same side as the pain occur in 97% of the headaches. In the other 3%
autonomic changes might have been present but were not noted by the patient or
those around them. Increased lacrimation is the most frequent (90%), with
conjunctival injection, ptosis, miosis and rhinorrhea each noted in 75% of the
patients. Facial flushing, sweating and nasal congestion are less frequent.
These represent unilateral loss of sympathetic nervous system function and
increases parasympathetic nervous system activity. The reason for this variation
in autonomic changes and the site where the dysfunction occurs is not known.
The underlying etiology of cluster is unknown. When headache free, the
neurological examination is normal. During an attack there are changes reported
on PET scans of the suprachiasmatic nucleus. This is not surprising since there
often is a circadian pattern, indicating something is occurring in the body’s
biological clock. Occasionally imaging studies on patients with cluster reveal
asymptomatic brain tumors or AV malformations at various sites in the brain,
either on the same side or the opposite side from the headaches. As will be
discussed later, a subsequent series of cluster headaches might occur on the
side opposite from the original site. Brain tumors and other structural lesions do
not jump from side to side. Cluster headaches might be precipitated by alcohol,
nitroglycerine and intravenous histamine, but these observations do not point to a
specific chemical etiology. Intravenous sumatriptan, the 5HT1B/1D agonist used
for stopping a migraine, will terminate a cluster headache, but this does not
reveal the chemical basis and does not prevent the next headache which might
start a few hours later.
Unusual and unexplained presentations of cluster are seen. The patient’s
spouse might note the onset of ptosis and myosis 30 minutes before the onset of
headache. There are a few reports of a visual or sensory aura prior to the
headache. After recurrent clusters on one side, 14% of patients experience a
subsequent cluster on the opposite side. Infrequently the headaches might shift
sides during a single cluster. The pain might start in the neck and spread up to
the eye. As mentioned there may be absence of the ipsilateral autonomic
dysfunction in up to 3% of cases, thought this may be due to lack of proper
observation. There are a few reports of patients with the typical autonomic
changes who deny a headache. A patient might describe minimal pain in the
opposite eye. There may be low grade pain between the clusters of excruciating
pain.
There are two other headache patterns with the same unilateral changes of
function of the autonomic nervous system but these are easy to distinguish from
cluster. The first is paroxysmal hemicrania, a condition which occurs in both an
episodic and chronic form but is three times more frequent in females than
males. The pain is not as intense as cluster. It is unilateral, but might spread
beyond the eye and temple. The individual headaches are shorter, 2-30 minutes
in duration, and occur once every other day to as often as eight times a day. The
patient with paroxysmal hemicrania does not have the urge to be up and move
about. In contrast with cluster headaches, the patients with paroxysmal
hemicrania have an immediate response to indomethacin 25-100 mg t.i.d. After
the patient is headache free for a few weeks following indomethacin, attempts
should be made to reduce or discontinue the drug.
The other headache condition with unilateral changes of the autonomic nervous
system is the extremely rare SUNCT syndrome (Short-lasting Unilateral
Neuralgiform headache attacks with Conjunctival injection and Tearing). The
pains last 5 seconds to 2 minutes and are orbital, supraorbital or temporal and
may occur 3-200 times per day. These may be a manifestation of lesions in the
posterior fossa or around the pituitary gland. Often they do not respond to drug
therapy.
Throughout the years physicians have tried almost every medication in the hope
of providing relief. There is no therapy for cluster headaches which has been
proven by adequate studies with comparison to placebo. The rapid increase to
peak intensity excludes the use of oral medications to stop a headache. As
mentioned previously intravenous sumatriptan will terminate a headache, but
does not prevent the next headache that will occur later in the day. There is a
limit on the number of injections of sumatriptan which can be administered in a
single day and the drug is expensive. Therefore therapy must be selected to
prevent the next attack.
This author has found the following regimen will stop 70+% of clusters. First the
patient should immediately be given prednisone 50 mg every 12 hours for 5
days, following which the drug is abruptly stopped. If the pharmacy does not
have the 50 mg tablets, then the patient can alternate 60 mg and 40 mg doses.
The onset of action is rapid. Patients have reported that if a headache starts 3-4
hours after the initial dose, the pain will be only brief and minimal and thereafter
they are headache free for the following 5 days. Using a brief course of high
dose prednisone without subsequent tapering does not cause Addison’s disease
or other complications. On the same day that prednisone was started, the
patient should be started on oral verapamil, using 40 mg t.i.d. the first day, 80 mg
t.i.d. the second day, 120 mg t.i.d. the third day and 160 mg t.i.d. thereafter. This
is about twice the dose of this calcium channel blocker than that which is used to
treat hypertension. The use of 80 mg tablets provides a higher blood level than
the once a day 240mg capsules. By the sixth and seventh day the patient is off
prednisone and usually headache-free. If cluster headaches return on the sixth,
seventh or eighth day, the verapamil should be increased to 640 mg per day or
even 720 mg per day. Goadsby and his coauthors have recently stated that
there is no need for a baseline EKG unless the daily dose exceeds 700 mg. His
group had given 960 mg daily without complications and there was one report
from Sweden of a patient using 1300 mg without ill effects. After the patient has
remained headache free on verapamil and he is beyond the duration of his
previous clusters, the verapamil can be progressively reduced and terminated by
the fourth or fifth day. If the patent begins another series of daily cluster
headaches in later months or years, the prednisone/ verapamil regimen can be
repeated.
Prior to the development of prednisone the standard treatment was the inhalation
of 100% oxygen at 7-10 liters per minute flow. This provided partial or complete
termination of a headache in about 70% of the subjects who used it. It can be
used if the prednisone/verapamil approach fails. The patient would have to keep
a small portable tank of 100% oxygen with him at all times.
Lithium carbonate starting at 300 mg bid is reported to help patients with episodic
cluster and chronic cluster. The onset of action is noted in about one week and
the drug needs to be adjusted by following blood levels. There are multiple side
effects from using lithium, so it would be advisable to have the assistance of
someone who has previous experience with the drug.
Methysergide is still mentioned in some books as a treatment of both migraine
and cluster but fortunately has been taken off the marked. It caused major side
effects including retroperitoneal and pericardial fibrosis.
In the May 2011 issue of HEADACHE there was an article describing 50%
successful treatment of chronic cluster using daily warfarin sufficient to obtain an
INR of 1.5 - 1.9, slightly less than the dose used for atrial fibrillation and other
problems.
Since it often is impossible to find a satisfactory drug treatment for chronic
cluster, various neurosurgical and radiation techniques have been used. These
have included radiofrequency thermocoagulation of the trigeminal nerve,
injections of glycerol into the gasserian ganglion, cutting (lesioning) the trigeminal
nerve at the root entry zone, microvascular decompression of the trigeminal and
gamma knife radiation. Apparently none of these procedures have yielded
perfect results, complications vary and reoccurrence of the cluster headaches on
the same side have often been reported. In the 14% of patients who might
develop subsequent cluster headache on the opposite side, these procedures
would not be beneficial.
In summary cluster headaches are a medical emergency and most often can be
helped, the first treatment to try is the combination or prednisone and verapamil.
revised October 26, 2012