++
The two most common patterns of migraine are migraine with aura,
formerly called classic migraine, and migraine without aura, or
common migraine. Approximately 18% of women and 6% of
men in the United States are plagued by migraine, and 15% will
experience an aura with some of their migraine attacks.1
+++
Clinical Features
and Differential Diagnosis
++
Blau has described five phases of migraine that are not universally
present and may variably occur during different attacks in the same
individual.2 The first phase, or prodrome, occurs
in 40% to 60% of migraineurs. It consists of altered
mood, irritability, depression or euphoria, fatigue, yawning, excessive
sleepiness, craving for chocolate, or other vegetative symptoms,
all of which suggest origin of these symptoms in the hypothalamus,
perhaps as a result of excessive dopamine stimulation. These symptoms
usually precede the headache phase of the migraine attack by several
hours or even days, and experience teaches the patient or observant
family that the migraine attack has begun.
++
The second phase of migraine is the aura, consisting of either
visual or sensory phenomena (the two most common aura symptoms)
or motor weakness, incoordination, or dysphasic symptoms, such as
word-finding difficulty. The aura symptoms usually precede the headache
phase of the migraine attack, but occasionally occur simultaneously.
Sometimes, two aura symptoms occur in the attack, usually visual
and sensory symptoms that may occur simultaneously or consecutively. The
aura symptoms appear gradually over 5 to 20 minutes and usually
subside just before the headache begins.
++
When examining a patient who has recently experienced only one
or two such attacks for the first time, the clinician must determine
whether these focal neurologic symptoms represent migrainous aura
or manifestations of transient ischemic attack (TIA) or even a focal
sensory seizure. Passage of time, repeated identical attacks, and
diagnostic testing may be required to obtain certainty, but certain
features are more typical of migraine aura. Firstly, visual and
sensory symptoms of TIA and seizures usually develop more rapidly
than the gradual progression of an aura over 5 to 20 minutes. Secondly,
migraine aura is characterized by a combination of negative and
positive symptoms; the migraineur experiences a visual scotoma or
hole in the vision (negative symptoms) and dazzling, glimmering,
scintillating lights (positive phenomena). TIA, such as amaurosis fugax
or hemianopic scotoma, usually manifests as a black or blank negative
visual loss.
++
Sometimes, especially in the elderly, the visual aura occurs
repeatedly without any headache. C.M. Fisher described these features
as “late life migraine accompaniments.”3 Sometimes
these elderly patients experienced more typical migraine in youth,
with the migraine subsiding for many years only to recur as migraine
aura without headache in later life. In this setting, the clinician
may be more secure in the diagnosis. However, these late life migraine
accompaniments often develop with no previous history of migraine.
Patients with new late-life migraine symptoms must be carefully
evaluated to rule out cerebrovascular disease, structural hemispheric
disease, or even retinal detachments.
++
The sensory auras of migraine usually consist of numbness (negative
sensory symptoms) and positive symptoms of tingling or paresthesia.
Again, these sensory symptoms usually progress over 5 to 20 minutes
and are followed by the headache phase, which is the third phase
of the migraine attack, and usually the most dramatic. It is the
headache phase of migraine for which most patients consult physicians.
++
Chapter 17 outlines the International Headache Society (IHS)
system for diagnosing migraine, but it is important to remember
that these strict criteria were designed chiefly for purposes of
finding a uniform population of migraine patients to be entered
into investigational drug trials. The experienced clinician uses
the IHS criteria as a guide but is not rigidly bound by them. Furthermore, both
migraine and tension-type headache are very common, and when patients
report symptoms of both, there may be overlapping features that
make it difficult to tell where one ends and the other begins. In
fact, the IHS system of classification is being revised and will
be more accurate and complete.
++
Often, the patient does not initially describe the headache characteristics
well, and the skillful clinician must take the time to extract important
but subtle historical points. For example, some patients spontaneously
report only pressure-type occipital pain, but by digging a little
deeper, the examiner can help the patient recall that the worst
headaches, occurring infrequently, build to an intense throbbing
and radiate to one periorbital region. Patients often report that,
because they are unsure at the outset whether the headache will
build to severe intensity, they fail to take acute-care medication
early and, consequently, obtain less effective relief than if they
had treated the migraine earlier in the attack.
++
The headache of migraine is unilateral in 60% of cases
and usually alternates sides from one attack to the next.4 Often,
patients state that the headache is always on one side but when
pressed recall that rarely, perhaps 10% of the time, the
headache occurs on the opposite side. This alternating hemicrania, however
infrequent, makes the clinician more secure in the diagnosis of
migraine. Some migraineurs report that the headache is bilateral,
but worse on one side. The headache usually builds over a period
of 30 minutes to several hours but may occur with sudden intensity.
Although the pain of migraine is usually moderate to severe, many
patients report milder headaches, which they refer to as “sinus
headaches” or “regular headaches” and
which, in reality, are milder migraine attacks. Similar benign recurring
headaches are much more likely to be migraine or tension-type headache
than sinusitis. Sometimes radiography is needed to settle the issue,
and computed tomographic (CT) scanning of the sinuses is superior
to sinus x-rays in diagnosing acute sinusitis. Many patients are
test oriented and anxious to know what the x-ray showed. They may fail
to appreciate the knowledgeable opinion of an experienced clinician
in making a diagnosis based on a thorough history and examination.
++
To be sure, clinicians must always be aware of so-called migraine
mimics—paroxysmal headaches caused by arteriovenous malformations,
pheochromocytoma, repeated exposure to carbon monoxide, transient
increased spinal fluid pressure resulting from a colloid cyst of
the third ventricle, adult-onset of headaches caused by type II
Arnold-Chiari malformations, or other structural brain disease.
In the elderly, temporal arteritis must always be considered. Primary
central nervous system angiitis may manifest as frequent headaches
before other symptoms, such as encephalopathy, seizures, or infarctions,
occur as a result of the vasculitis.
++
The following danger signals warn the clinician that a headache
may be more serious than a migraine1:
++
- 1. Headache that is changing or different from previous
headaches may herald a brain tumor superimposed on a long-standing
primary headache disorder, such as migraine or tension-type headache.
- 2. Headache with progressive worsening over 24 hours or several
days suggests a mass lesion or infectious disease such as meningitis,
abscess, subdural or intracerebral hematoma, or vasculitis.
- 3. Headache precipitated by exertion, bending over, coughing,
or sneezing may result from transient blockage of cerebrospinal
fluid (CSF) flow or increased intracranial pressure.
- 4. Sudden onset of headache during exercise or sexual activity
can occur with subarachnoid hemorrhage or with benign exertional
headache.
- 5. Vomiting may result from a brain tumor or other mass lesion
with increased intracranial pressure.
- 6. Early morning headache can occur with obstructive sleep
apnea and hypertension.
- 7. Any abnormal physical or neurologic finding must be considered
suspect: fever, stiff neck, rash, lymphadenopathy, scalp tenderness,
altered sensorium, or focal neurologic signs. Any patient who presents
with his or her “first or worst headache” is cause
for alarm.
++
The young, healthy patient with a textbook history of migraine
and a normal examination seldom requires diagnostic investigation.
If, however, the patient fails to respond as expected to treatment efforts,
diagnostic testing may be wise.
++
Unsuspected granulomatous inflammations, such as sarcoidosis,
meningeal malignancy, and cryptococcal, tuberculous, or Lyme meningitis,
can be diagnosed only by CSF examination. Elevated opening spinal
fluid pressure may confirm the diagnosis of pseudotumor cerebri.
++
For structural brain lesions, magnetic resonance imaging (MRI)
is much more sensitive than CT scanning and is always preferable
unless bone windows are desired. CT scanning is more sensitive for
demonstrating subarachnoid hemorrhage in the first 24 hours, whereas
MRI becomes more sensitive after 48 hours. Unenhanced CT scans made
within 24 hours of subarachnoid hemorrhage demonstrate blood in
90% of cases, but in only 70% of cases after 5
days.5 If a small subarachnoid hemorrhage, a so-called
sentinel bleed, is being considered, CSF examination is essential
even when results of the CT are normal. The presence of fresh blood
or xanthochromia should prompt angiography. Cerebral angiography
is also required if primary central nervous system granulomatous
angiitis is suspected. Magnetic resonance angiography is sensitive
for identifying unruptured aneurysms as small as 3 to 4 mm, and
angiography would be definitive.5
++
There is a high familial incidence of aneurysms; unsuspected
asymptomatic intracranial aneurysms were found in 9% of
396 persons having a first-degree relative with an aneurysm.5 A
careful family history is, therefore, important if a warning leak
is suspected.
++
CT scanning of the sinuses is more sensitive than sinus x-rays
or MRI. Clinicians must not omit dental disease or jaw dysfunction
as a cause of head or facial pain, or localized eye disease, such as
glaucoma, which can cause unilateral orbital pain. Cervical spine
disease or lesions at the foramen magnum may cause suboccipital
pain, and plain x-rays or imaging may be considered.
++
Certain medications, such as nonsteroidal anti-inflammatory drugs
(NSAIDs), estrogen, progestins, selective serotonin reuptake inhibitors
(SSRIs), or certain calcium channel blockers, may cause headache.
Because these drugs are often used to treat headaches, sorting out
the diagnosis may be difficult.
++
Blau’s fourth phase of migraine is the headache termination.
Sleep, even a brief nap of 1 or 2 hours, is the most common natural
method of resolution, but biofeedback and relaxation exercises may
also be beneficial. Today, pharmacologic treatment is the most common
medical treatment to terminate an acute migraine attack.
++
The fifth phase of migraine, the postdrome, was reported by 94% of
Blau’s patients, but these symptoms have not been widely
studied. Postdrome symptoms may last about 24 hours and range from
feeling drained or exhausted to an unusual sense of elation or euphoria.
++
The first step in treating the patient with migraine, or any
medical condition, is to establish an accurate diagnosis. The diagnosis
must be conveyed to the patient who, very often, is fearful of a tumor
or aneurysm, or may erroneously believe he or she has a chronic
sinus or psychiatric condition. Many of these patients have been
discouraged in the past by physicians who have ignored their complaints
of headache. Headache is a common complaint, and many busy physicians
are reluctant to take the time required to obtain an adequate headache
history, or they may view headache as being a result of nervousness
or stress. The busy physician may choose to direct the brief office
visit at management of hypertension, diabetes, or arthritis. Headache
treatment begins with educating patients about the nature of migraine
and reassuring them that this is a biologic disorder caused by altered
brain biochemistry with secondary vascular changes, and usually
a hereditary predisposition. Patients often are relieved that at
last they have found a physician who is knowledgeable about headaches
and who expresses an interest in helping them. Sometimes it is helpful to
have the spouse present and explain to the couple that headaches,
and migraine in particular, are often provoked by hormonal changes,
certain food triggers, missing meals, irregular sleep patterns,
travel, or specific environmental changes. Visual and sensory stimuli,
such as bright lights, excessive noise, cigarette smoking, certain
perfumes or smells, or other stimuli, may act as migraine triggers.
Some medications, both over-the-counter and prescription drugs,
can precipitate headache (Table 20-1). There is also an underlying
predisposition for people with migraine to have a biochemical comorbidity
of depression or anxiety.
++
++
In a specialty headache practice, there is usually a nurse or
physician’s assistant who instructs the patient to keep
a headache calendar, watch for repeated food or environmental triggers,
and record the amount of medication taken and response to treatment.
Having this accurate record enables the physician to alter pharmacologic
treatment depending on the response. The power of the written word
cannot be overemphasized, and publications are available that describe
and explain many of these issues for the migraineur. Information
is available free of charge from the American Council for Headache
Education (ACHE) (by phone at 1-800-255-ACHE) and the National Headache
Foundation (NHF), (1-800-843-2256).
++
Some headache patients express a desire to be treated without “drugs” or
prefer to take “natural” substances, such as herbal
or vitamin supplements. Biofeedback training can be beneficial in
conjunction with, or without, medication. Biofeedback training teaches
relaxation skills as part of overall headache management. Patients
learn to be aware of skeletal muscle status and how to relax general
and specific muscle contraction and tension; they learn breathing
techniques and how to enhance blood flow to the peripheral vessels,
producing hand warming. With practice, patients can alter autonomic
nervous function to produce measurable temperature changes in the hands.
These exercises may reduce afferent sensory volleys from peripheral
muscular pain and modulate sensory impulses ascending through cervical
segments into the trigeminal nerve complex in the brainstem.
++
Cognitive therapy using behavioral modification can help patients
deal with the headache condition in a positive way. If the patient
spontaneously asks about stress or if he or she recognizes anxiety
or depression as significant problems, consultation with a behavioral
psychologist may be very helpful.
++
Physical therapy with heat or cold applications, ultrasound,
myofascial release, and massage therapy are beneficial for some
patients. Attention to nutrition and observing for food triggers,
especially alcohol, are important. Nutrasweet (Equal, aspartame)
has been reported to trigger migraine, and one of the authors has
observed this in patients who chew gum containing aspartame.6 Correcting
irregular eating and sleep habits may be beneficial.
++
Some of these measures, such as keeping an accurate headache
calendar, practicing biofeedback exercises, and paying attention
to diet, have the added benefit of insisting that the patient play
an active role in the treatment program. Many patients express a
sense of empowerment and satisfaction that they are contributing
to management of the headache condition and gaining more control over
their lives and the condition.
++
Pharmacotherapy of migraine may be divided into three types:
(1) treatment with nonspecific analgesics; (2) acute care treatment
with drugs that have specific pharmacologic affinity to bind to certain
serotonin receptors and alter the neurochemical, inflammatory, and
vascular process of migraine; and (3) the daily use of preventive
medications.
++
Common analgesics, such as aspirin, acetaminophen, or NSAIDs
(e.g., naproxen sodium), often provide relief to patients with mild
migraine headaches, especially if taken early in the attack. A double-blind
placebo-controlled study found Excedrin Extra-Strength was significantly
superior to placebo in treating mild to moderate migraine headaches.7 Combination
analgesics, such as Midrin, Fioricet, and Fiorinal, also may be
beneficial in migraine if taken early. These compounds have the
potential to cause analgesic rebound headache (see later discussion)
if taken too often, such as more than three times a week, but they
can be very helpful and are safe to take for migraine attacks that
occur three or four times a month. Analgesic rebound is more likely
related to frequent dosing of these drugs, rather than to the total
number of doses that may be taken safely in a week.
++
Treatment of acute migraine attacks was revolutionized in the
United States in 1993 with the introduction of sumatriptan and,
in 1998, by other triptans—zolmitriptan, naratriptan, and
rizatriptan. Dihydroergotamine has been available since 1945 as
an injection, but was not widely used until 15 years ago; a nasal
spray formulation, Migranal NS, was introduced in 1997.
++
All of these drugs are effective because of their specific pharmacologic
affinity to bind to certain serotonin (5-HT) receptors and interrupt
the neurochemical, inflammatory, and vascular changes that occur
in migraine. There are differences in lipophilicity of some of the
triptans, with variable ability to cross the blood-brain barrier,
but whether any central action contributes to meaningful migraine
relief remains uncertain. The slight molecular differences of each
triptan confer different pharmacologic properties, such as bioavailability,
time to peak concentration, onset of action, metabolic half-life,
and excretion, among others (Table 20-2). Sumatriptan, zolmitriptan,
and rizatriptan are metabolized by the enzyme monoamine oxidase-A
(MAO-A) and, therefore, these drugs are contraindicated in patients
taking MAO inhibitors. Naratriptan and dihydroergotamine are not
so contraindicated.
++
++
Triptan metabolism may be inhibited by cimetidine, birth control
pills, and propranolol, resulting in higher blood levels and, in
turn, increasing the risk of adverse effects. All the triptan drugs share
similar adverse effect profiles. Most effects are mild and transient;
however, the primary concern with this class of drugs, as well as
with dihydroergotamine, is that these compounds can cause coronary
vasoconstriction. A few serious and life-threatening cardiac events
have been reported in patients using triptans, and caution should
be exercised in prescribing any of the triptans or dihydroergotamine
for patients with cardiac risk factors. In vitro studies of isolated
human coronary artery segments demonstrate that these drugs are
unlikely to cause myocardial ischemia at therapeutic concentrations
in healthy subjects8; they are safe for young,
otherwise healthy patients with migraine. The triptans and dihydroergotamine
have improved the lives of people formerly disabled and suffering
several times a month from migraine pain. Because of the pharmacologic
differences, one triptan may be very helpful to a patient even if
treatment with another triptan has failed.
++
Rescue treatment refers to using potent opioid analgesia or sedation
for an acute attack when specific acute care treatment for migraine
fails. Markley provides a thorough review of the appropriate use
of opioid analgesics and recommends sound guidelines for the use
of these drugs.9 We agree that it is unfair and
unethical to deny patients with intractable pain effective analgesia; however,
clinicians must also assume the responsibility to monitor the patient’s
response and use of these drugs. Once again, we emphasize the importance
of having the patient keep an accurate headache calendar, recording
the number and severity of headaches and number of and response to
acute care medications, including opioids.
++
Preventive medications may be taken daily by migraineurs who
suffer frequent attacks (e.g., three or four times a month or more)
or by those who become disabled for 48 to 72 hours even once or twice
a month. Only the patient can determine if he or she wishes to take
daily preventive medication. Some patients express concerns about
side effects or habituation, and clinicians must always monitor
continuous medication use in young women who might become pregnant,
and caution them of potential harm to the fetus. Patients who are
reluctant to take daily medication should be reassured that the
drug can be discontinued if they experience any adverse reactions
or if their migraine symptoms are not reduced after a trial period.
We explain that we begin with a low dose, which can gradually be
increased, but at least 4 to 6 weeks of treatment should occur before deciding
on effectiveness. The most commonly used preventive medications
are listed in Table 20-3. The exact mechanism of action of these
medications is not always known, but most have in common the pharmacologic
affinity to bind to and downregulate the 5-HT2 family of
serotonin receptors.
++
++
Choice of preventive medicine should be determined by consideration
of the patient’s overall medical condition and any comorbid
illnesses. For example, a beta blocker would be a good choice if
the patient has mild untreated hypertension, has coexisting essential
tremor, or is nervous and excitable. On the other hand, beta blockers
should be avoided if the patient has asthma or depression or is
taking other vasoactive antihypertensive drugs. Tricyclic antidepressants
might be especially helpful for patients who have sleep disturbance,
depression, or loss of appetite. Divalproex sodium might be the
drug of choice for migraine patients who have obsessive-compulsive
traits or are bipolar or who have had seizures in the past, but
this drug should be avoided if the patient has known liver disease.