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KEY POINTS
h Headache is a of the ICHD is very useful for optimal may be characterized as episodic (oc-
symptom with many patient care. The ICHD is available curring fewer than 15 days per month)
potential causes, and online and is continuously updated.2 or chronic (occurring 15 days or more
the International Headache is a symptom, and the clin- per month). Clinically, patients with mi-
Classification of icians task is to determine precisely graines may seem normal between at-
Headache Disorders, which type of headache(s) a patient tacks. Even interictally, however, patients
Second Edition, has. There are hundreds of causes of with migraines have abnormalities of
provides diagnostic headache, some secondary (ie, due to brain function that can be shown by
criteria, which are useful an underlying cause) and others primary tests of contingent negative variation
in making a precise (ie, sui generis, no underlying cause). and transcranial magnetic stimulation.
diagnosis.
Migraine is a primary headache dis- They have hyperexcitable brains and do
h Patients with migraines order and may occur with or without not habituate to normal stimuli.
have hyperexcitable aura. Aura is a suboptimal term be- Migraine aura occurs in only about
brains, and these cause it can occur before or during the 20% of patients with migraines. The
abnormalities are
headache, in the absence of a head- most common manifestation is visual,
present both ictally
ache, or in association with other head- often an enlarging scotoma with a shim-
and interictally. These
patients have low brain
ache types. The word migraine comes mering edge (fortification spectra or
magnesium levels and from the Greek hemi and kranion, teichopsia). Patients may also see stars,
do not accommodate to and while migraine is often hemicra- dots, wavy lines, complex patterns, shapes,
repetitive stimuli. nial, it is bilateral in about 40% of adults or visual distortions. Less common are
and 60% of children. It is a recurrent sensory auras, such as the cheiro-oral
disorder often associated with sensory aura. In this type of aura, paresthesia
symptoms (photophobia, phonophobia, begins in the hand and slowly, over
and osmophobia), nausea or vomiting, minutes, ascends to the shoulder and
and disability (Table 1-1).1,3 Migraines then may spread to the ipsilateral face
a
TABLE 1-1 Migraine Without Aura
a
TABLE 1-2 Typical Aura With Migraine Headache
KEY POINT
h While blood vessel migraine, ie, they occur with migraine Shortly after Graham and Wolff pub-
changes have long been more frequently than would be ex- lished their study, Leao5 reported on
recognized in migraine, pected based on their rates of occurrence CSD, a phenomenon that occurs in
they do not and cannot individually in the population. These lissencephalic animals. CSD, a wave of
account for all the conditions include mitral valve prolapse, neuronal depolarization followed by a
clinical phenomenology Raynaud phenomenon, stroke, epilepsy, suppression of neuronal activity with
that occurs in this and several psychiatric conditions (eg, corresponding blood flow changes
condition. The head depression, anxiety, bipolar disorder, and ( hyperemia followed by oligemia),
pain and vessel caliber social phobias). Studying the association moved across the cerebral cortex at
changes do not occur between migraine and these condi- rate of about 3 mm/min. This seemed
at the same time, drugs similar to the phenomenon Lashley4
tions may provide insights into the
that do not have
underlying mechanisms of migraine.11 reported regarding his own visual aura.
vasoconstrictive activity
Migraine was once thought to be CSD can be provoked by chemical,
may be effective in
migraine, and blood primarily a disorder of blood vessels. electrical, and mechanical stimuli. It
vessel changes do not Advances in knowledge involving ge- also can occur in the setting of energy
explain other features netics, epidemiology, clinical observa- failure.16 EEG can show this phenom-
of migraine such as tions, pharmacology, neuroimaging, and enon in lissencephalic animal models
inability to accommodate physiology have shown that the clinical but not in the convoluted human brain.
to repetitive stimuli. manifestations of migraine cannot be Substantial research has shown that CSD
accounted for simply by changes in plays an important, but not exclusive,
blood vessels. Migraine is an abnormal role in the genesis of a migraine attack.
state of the brain. Vascular changes oc- A more sophisticated understanding of
cur, but they are not primary, and while the genesis of migraine encompasses
some now prefer to call migraine a neu- knowledge of the anatomic pathways
rovascular disorder, there is ample evi- involving head pain, neurotransmitters
dence that patients with migraines have and pharmacology, neuroimaging find-
an abnormal CNS, resulting in various ings, and neurophysiology both during
well-recognized clinical symptoms.12 and between migraine attacks.
KEY POINT
h Activation of the CGRP is found in the jugular veins of involved. The clinical manifestation of
trigeminovascular patients with migraines during an attack central sensitization is cutaneous allo-
system causes peripheral (Figure 1-1).7,16,18 dynia. The patient may report scalp
sensitization of the If treated during the early stages of tenderness and facial, neck, or even
first-order neuron an attack when only peripheral sensiti- extremity pain occurring spontaneously
innervating dural blood zation has occurred, the migraine may or in response to nonpainful stimuli.
vessels, which explains be terminated fully. If the attack prog- Patients may even report that their hair
the pounding pain. With resses further, second- and third-order hurts. Once central sensitization has
prolonged duration, neurons may be activated (trigemino- occurred, the attack is much harder to
second- and third-order thalamic and thalamocortical). This is treat, and triptan drugs, such as suma-
neurons become
called central sensitization and involves triptan, may no longer work. However,
activated, potentially
the phenomenon known as wind-up. nonsteroidal anti-inflammatory drugs
resulting in central
sensitization.
Glutamatergic and NO transmission are (NSAIDs) and dihydroergotamine may
thought to be solely due to vasocon- vating the meninges prevents the re-
striction. While ergot drugs such as lease of CGRP. Stimulation of 5-HT1B
ergotamine tartrate and methysergide, receptors located on blood vessels causes
as well as the triptans (of which suma- vasoconstriction. Stimulation of these
triptan can be considered the proto- receptors in the TNC decreases central
type), are undoubtedly vasoconstrictive, neuronal signaling (Figure 1-2).18,28
NSAIDs and CGRP antagonists are ef- The triptan drugs were developed in
fective during migraine attacks in the part because of the recognition of the
absence of vasoconstrictive effects.28,29 importance of serotonin in migraine
It is now appreciated that ergot drugs pathogenesis.30,31 At the start of a mi-
are active at many receptor sites, some graine attack, blood serotonin levels
of which affect neurotransmitter re- decrease and levels of its metabolite 5-
lease. Some of these sites are the same hydroxyindoleacetic acid (5-HIAA) rise.32
ones at which triptan drugs (eg, su- Drugs that deplete serotonin such as
matriptan) are primarily active, the 5- reserpine worsen migraine and cause
hydroxytryptamine 1D and 1B (5-HT1D, depression. Administration of serotonin
5-HT1B) receptors. The 5-HT1D recep- (5-HT) during a migraine attack can
tors are presynaptic and are located on abort the attack but can cause side ef-
trigeminal neurons and elsewhere, in- fects reminiscent of carcinoid syndrome.
cluding in the TNC. Agonism of 5-HT1D The triptan drugs are essentially modi-
receptors on trigeminal neurons inner- fications of the serotonin molecule.
Case 1-1
A 41-year-old woman began having migraine attacks at the age of 14,
shortly after her menarche. Triggers for these attacks included her menses,
ovulation, and delaying a meal. One or two days before her attacks she
would feel fatigued and yawn excessively. Before some of her more severe
episodes she would experience an enlarging visual scotoma with a
shimmering edge lasting for 20 to 30 minutes, followed by a unilateral
pounding headache with nausea and sometimes vomiting. If she was
unsuccessful in treating the attack, it might last 2 to 3 days and she would
have to lie in a dark, quiet room. She has learned that treating as soon
as possible during a migraine offers her the best chance of success.
Her mother had similar attacks as does one of her two daughters. When
her obstetrician/gynecologist prescribed an estrogen-containing oral
contraceptive she experienced an increase in the frequency and severity
of her migraine attacks leading her to stop the medication.
Comment. This patient had the onset of headaches near the time of her
menarche. Estrogen is known to stimulate nitric oxide synthase, which results
in higher nitric oxide levels. She had other triggers besides her menses and
was aware of them. She also had a prodrome of yawning (a hypothalamic
phenomenon that cannot be ascribed to a vascular etiology, but rather
is dopaminergic). Sometimes she would manifest a visual aura, presumably
due to cortical spreading depression traveling across her occipital cortex.
Her attacks met ICHD-II criteria for migraine with and without aura. She had
learned she would get a better result if she treated early (before central
sensitization could occur). As is the case for many women, additional
estrogen given as an oral contraceptive worsened her headache tendency;
this also often occurs with hormone replacement therapy.
been considered infarcts, whereas primary abnormality and are not time
others seem to be transient.36,37 Typi- locked to the development of pain.
cally these lesions are subclinical and Animal models suggest that drugs that
have no obvious clinical correlate. prevent migraine seem to work at least
in part by raising the threshold for the
OTHER ABNORMALITIES initiation of CSD.
Patent foramen ovale (PFO) occurs in
about 25% of the general population USEFUL WEBSITES
but in about 50% of patients with mi- International Headache Society
www.ihs-headache.org.
graine with aura. The significance of
this finding is unclear, but it has been American Academy of Neurology
www.aan.com.
speculated that the right-to-left shunt
may circumvent the usual filtering REFERENCES
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