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nose and throat. The temporal artery may appear dilated
and pulsating. Neurologic symptoms should be evaluated
with computed tomographic scanning.
Features of Migraine Headache and Headache
Caused by Underlying Disease
Migraine headache Headache caused by seri-
ous underlying disease
History
" Chronic headache pat- " Onset before puberty or
tern similar from attack after age 50 (tumor)
to attack " "Worst headache ever"
" Gastrointestinal symp- (subarachnoid hemorrhage)
toms " Headache occurring after
" Aura, especially visual exertion, sex, or bowel
" Prodrome movement (subarachnoid
hemorrhage)
" Headache on rising in the
morning (increased
intracranial pressure, tu-
mor)
" Personality changes, sei-
zures, alteration of con-
sciousness (tumor)
" Pain localized to temporal
arteries or sudden loss of
vision (giant cell arteritis)
" Very localized headache
(tumor, subarachnoid hem-
orrhage, giant cell arteritis)
Migraine headache Headache caused by seri-
ous underlying disease
Physical examination
" No signs of toxicity " Signs of toxicity (infection,
" Normal vital signs hemorrhage)
" Normal neurologic ex- " Fever (sinusitis, meningitis,
amination or other infection)
" Meningismus (meningitis)
" Tenderness of temporal
arteries (giant cell arteritis)
" Focal neurologic deficits
(tumor, meningitis, hemor-
rhage)
" Papilledema (tumor)
Laboratory tests and neuroimaging
" Normal results " Erythrocyte sedimentation
rate >50 mm/hr (giant cell
arteritis)
" Abnormalities on lumbar
puncture (meningitis, hem-
orrhage)
" Abnormalities on CT or MRI
(tumor, hemorrhage, aneu-
rysm)
II.Pathophysiology of migraine
A.Migraine headache is probably generated by a nucleus
in the brainstem. The central generator is the contralateral
dorsal raphe nucleus of the midbrain. After the dorsal raphe
central generator turns on, there is an activation of the
trigeminovascular system. This system connects the
generator to the meningeal blood vessels, which dilate and
become inflamed, a process referred to as neurogenic
inflammation.
B.Two key serotonin (5-HT) receptors, 5-HT1B and 5-HT1D
, reverse the migraine processes. The 5-HT1D receptors are
vasoconstrictive and are located in the lumen of the
meningeal vessels.
III.Treatment of migraine
A.5-HT1D receptor agonists ("Triptans")
1.Rizatriptan (Maxalt)
a.Rizatriptan (Maxalt) is a high-efficacy, quick-onset
triptan, like sumatriptan and zolmitriptan. Oral
bioavailability is more than 40%.
b.Rizatriptan has two doses, 5 and 10 mg, and two
forms, traditional tablet and mint-flavored, orally
dissolvable tablet or melt. Two-hour headache
response for the optimal dose (10 mg) is 67-77%.
Recurrence rate is 30-47%.
c.The melt is not absorbed through the buccal
mucosa, but rather dissolves on the tongue, is
swallowed, and then is absorbed in the gastrointes-
tinal tract. Its efficacy is the same as the traditional
tablet, with a two-hour headache response of 66-
74%. Adverse events for rizatriptan are similar to
those seen with sumatriptan and zolmitriptan
tablets.
d.Propranolol raises the circulating rizatriptan level,
so patients on propranolol should be given the 5-mg
rizatriptan dose. Others should take the 10-mg
dose. The maximum rizatriptan dose is 30 mg per
24 hours, but 15 mg per 24 hours for patients on
propranolol.
2.Almotriptan (Axert)
a.Almotriptan works as well as sumatriptan; how-
ever, it is better tolerated. Almotriptan causes less
chest pain than sumatriptan; however, it remains
contraindicated in patients with ischemic heart
disease or uncontrolled hypertension as are all
triptans. It comes in 6.25 and 12.5 mg tablets.
b.Most patients should take 12.5 mg at the onset
of a migraine. Patients with hepatic or renal impair-
ment should start with 6.25 mg. Patients should not
take more than 2 doses in 24 hours.
3.Sumatriptan (Imitrex)
a.Sumatriptan (Imitrex) is available in three forms:
subcutaneous injection, nasal spray, and oral tablet.
Injectable sumatriptan comes as a 6 mg dose for
use with an autoinjector. Subcutaneous sumatriptan
is the most effective triptan. It works extremely
quickly with 50% headache response at 30 minutes,
a one-hour headache response of 77%, and more
than 80% at two hours. Recurrence of migraine
within 24 hours after a headache response with
injectable sumatriptan is 34-38%. Recurrence with
the spray and tablet is 35-40%.
b.Nasal spray sumatriptan. 20 mg is the optimal
dose, with a two-hour headache response of 64%.
Almost 40% have headache response at 30 min-
utes. The spray comes in a single-use device.
When sniffed, it causes a terrible taste in the back
of the throat; therefore, patients should spray it once
in one nostril and not sniff in.
c.The sumatriptan oral tablet has a bioavailability
of 14%. The optimal starting dose is 50 mg, with a
61% headache response at two hours.
d.Maximum sumatriptan dosages are two 6-mg
subcutaneous doses, two 20-mg nasal sprays, or
four 50-mg tablets per 24 hours. However, if a
patient needs to switch, she can use one injection
or one spray plus two tablets in the same day, or
one injection plus one spray in 24 hours.
e.All triptans can cause subjective "triptan sensa-
tions," which include heat feelings and flushing,
numbness, paresthesias, tiredness and tightening,
and heaviness of neck, jaw, and chest. Triptans can
narrow coronary arteries. These drugs are contrain-
dicated in coronary artery disease, vascular dis-
ease, uncontrolled hypertension, basilar or
hemiplegic migraine or within 24 hours of another
triptan or ergot.
f.Sumatriptan is the most used triptan. The injection
has the fastest onset for a triptan, and the highest
overall efficacy.
4.Zolmitriptan (Zomig)
a.Zolmitriptan has an oral bioavailability of 40%.
Zolmitriptan is contraindicated with MAO-A inhibi-
tors. The optimal dose is 2.5 mg. The maximum
dose is 10 mg per 24 hours. Two-hour headache
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