Chapter 38 Migraine Headache and Cluster

Question 1

Migraine headache

Answer 1

represents a very common benign headache syndrome; it is sometimes referred to as a vascular headache

Question 2

The pain-generating structures of the head include

Answer 2

venous sinuses, meningeal and large cerebral arteries, basal meninges, muscles, skin, and cranial nerves V, IX, and X.

Question 3

trigeminovascular system

Answer 3

A plexus of largely unmyelinated fibers arises from the
trigeminal ganglion (cranial nerve V) and innervates the
cerebral and pial arteries, the venous sinuses, and the dura
mater

Question 4

The neurons in the trigeminovascular

system contain

Answer 4

substance P, one of the major nociceptive neurotransmitters of primary sensory neurons; calcitonin gene-related peptide (CGRP), which causes vasodilatation and when infused intravenously into susceptible individuals triggers headache; and neurokinin A, which is similar in structure and function to substance P.

Question 5

When the trigeminal ganglion is stimulated and causes antidromic activation of the trigeminovascular system,

Answer 5

these peptide neurotransmitters are released near the
blood vessels they innervate; this results in vasodilatation
with consequent extravasation of plasma, or so-called sterile
neurogenic inflammation.

Question 6

Leakage of plasma proteins

from the dilated blood vessels in turn stimulates

Answer 6

the trigeminal nerve endings and causes nociceptive orthodromic signals to the trigeminal ganglion—the end result of this sterile neurogenic inflammation is the perception of pain in and around the head.

Question 7

Neurogenic inflammation is

blocked by

Answer 7

substances that act as agonists on a subset of serotonin (5-hydroxytryptamine, or 5-HT) receptors: the 5-HT1D and 5-HT1B receptors.

Question 8

The major drugs used to

abort acute migraine attacks

Answer 8

agonists at the 5-HT1D/1B receptors. Drugs that act as agonists at these sites are thought to reduce neurogenic inflammation by inhibiting the trigeminal nerve endings and by their actions on blood vessels

Question 9

Agonists at the 5-HT1D/1B receptors

include

Answer 9

ergot alkaloids (ergotamine, dihydroergotamine) and triptans (sumatriptan and others).

Question 10

stimulation of the trigeminal ganglion, through antidromic release of neurotransmitters, results in

Answer 10

increased cerebral and extracerebral blood flow.

Question 11

Stimulation of the

dorsal raphe nucleus

Answer 11

serotonergic nucleus in the midbrain, also increases cerebral blood flow.

Question 12

stimulation of the nucleus caeruleus

Answer 12

the major source of central noradrenergic input, causes a decrease in cerebral blood flow.

Question 13

Interneurons in the spinal cord and brainstem that are part of the descending pain modulation system use what as neurotransmitters?

Answer 13

enkephalins and g-aminobutyric acid (GABA) as neurotransmitters

Question 14

An
ascending serotonergic pathway in the midbrain raphe region
relays painful stimuli to the

Answer 14

ventroposteromedial (VPM) thalamus via the quintothalamic tract.

Question 15

A descending endogenous

pain modulating system originates in the

Answer 15

periaqueductal gray region of the midbrain, one of whose major relay structures is the nucleus raphe magnus in the medulla. After this relay, the descending pain modulating system connects with the spinal tract of the trigeminal nerve and the dorsal horns of the first through third cervical nerves.

Question 16

Stimulation of the periaqueductal gray region causes

Answer 16

headache. The major neurotransmitters of this pain-modulating system are norepinephrine, serotonin, and enkephalins

Question 17

migraine with aura it is thought that the cortex,

particularly the occipital cortex, is hyperexcitable. The cause of this hyperexcitability is

Answer 17

may relate to decreased intracellular magnesium levels, to a dysfunction of brain mitochondria, or to abnormal calcium channels.

Question 18

The aura phase of migraine begins as

Answer 18

a wave of cortical neural excitation, accompanied by hyperemia, and is followed by an electrical wave of spreading neural depression and oligemia that advances at a rate of 2 to 6 mm/minute (a rate similar to that of the developing aura). During the oligemic phase, blood
flow remains above the ischemic threshold.

Question 19

Dopamine receptor hypersensitivity

may be responsible for the

Answer 19

nausea, vomiting, hypotension, and dizziness that frequently accompany, and sometimes characterize, attacks of migraine. Antiemetics, most of which are dopamine receptor antagonists (especially at the D2 receptor), are frequently useful, and sometimes
effective in and of themselves in treating migraine
attacks.

Question 20

The diagnosis of migraine is made by

Answer 20

a suggestive clinical history and a normal neurologic examination

Question 21

The classic description of migraine

Answer 21

that of a recurrent headache lasting 2 to 72 hr, of moderate to severe intensity, pulsating, aggravated by routine physical activity, and associated with nausea, emesis, photophobia, phonophobia, and/or osmophobia.

Question 22

The major subtypes of migraine are

Answer 22

migraine with aura and migraine without aura

Question 23

The most frequent migrainous aura consists of

Answer 23

visual symptoms such as bright spots, dark spots, tunnel vision, or zigzag lines (fortification spectra). Other common auras include numbness or paresthesias in one arm or side of the body

Question 24

The aura is followed (or sometimes accompanied) by

Answer 24

an intense, crescendo head pain, frequently unilateral or retro-ocular; it may be described as pounding, throbbing, pressure-like, exploding, stabbing, or vise-like

Question 25

status migrainosus

Answer 25

the headache becomes intractable and lasts a week or longer

Question 26

basilar migraine

Answer 26

A migraine whose aura seems to originate in the brainstem | or involve both hemispheres

Question 27

A typical aura in basilar migraine might present

Answer 27

with bilateral visual loss or blindness

Question 28

basilar migraine patients may complain | of

Answer 28

vertigo, dysarthria, diplopia, tinnitus, ataxia, a decreased level of consciousness, or bilateral sensory (paresthesias) or subjective motor symptoms (there should be no objective weakness); sometimes nausea and emesis are prominent. Some patients present with other types of auras such as a dysphasia, and as such may resemble a transient ischemic attack (TIA), a stroke, or an evolving neurologic catastrophe.

Question 29

Exertional migraines

Answer 29

Some patients develop severe headache, sometimes described as exploding, related to exertion

Question 30

ophthalmoplegia

Answer 30

a severe ocular headache that presents with ophthalmoplegia (usually of the oculomotor nerve and includes a dilated pupil. The ophthalmoplegia can last hours to months and is now believed to represent an inflammatory neuritis or the Tolosa–Hunt syndrome.10 Painful ophthalmoplegia usually has a dramatic presentation and always warrants a careful evaluation.

Question 31

Migraine without Aura

Answer 31

At least five headache attacks: Headaches last 4–72 hr if untreated. Has at least two of the following, but not weakness: Unilateral pain, Pulsating, Intensity is moderate to severe. Aggravated by routine physical activity Has at least one of the following: Phonophobia, Photophobia, Nausea, Emesis

Question 32

Migraine with Aura

Answer 32

At least two headache attacks that also fulfill the characteristics of migraine without aura. Headaches usually follow the aura but may begin with it and last 4–72 hr if untreated. Has at least one of the following reversible symptoms (lasting 4 min to 60 min), but no weakness Positive or negative visual symptoms such as scintillating scotomas, blind spot (scotoma), blurred vision, zigzag lines, homonymous hemianopsia. Positive or negative sensory symptoms such as tingling or numbness

Question 33

Basilar Migraine

Answer 33

At least two attacks of migraine with an aura whose symptoms are reversible and localize to the brainstem or are bihemispheric, but without weakness Symptoms can include: Dysarthria, Dizziness or vertigo Bilateral visual symptoms, including temporary blindness Diplopia, Nystagmus, Ataxia, Decreased level of consciousness, Bilateral paresthesiae, Tinnitus with or without decreased hearing

Question 34

Aura without Headache

Answer 34

At least two attacks of symptoms typical of auras, but not weakness, such as visual, sensory or speech disturbances that resolve within 1 hr and are not followed by a headache

Question 35

Hemiplegic Migraine

Answer 35

At least two attacks of migraine with a reversible aura of motor weakness that can last 1 hr to days Also includes one of the following: Positive or negative visual symptoms, Positive or negative sensory symptoms Dysphasia or dysarthria, Frequently accompanied by symptoms typical of basilar migraine. If at least one first- or second-degree relative has a migrainous aura that includes motor weakness, it is familial hemiplegic migraine and is associated with a mutation in the neuronal calcium channel. If no first- or second-degree relative has a migrainous aura that includes motor weakness, it is sporadic hemiplegic migraine

Question 36

Migraines can be treated

Answer 36

abortively (after they start) or prophylactically (with daily medication aimed at reducing the frequency or intensity of the headaches).

Question 37

Triptans (Imitrex, Maxalt, Zomig, Frova, Relpax, | Amerge, and others)

Answer 37

5-HT1D/1B receptor agonists

Question 38

How are Triptans dosed?

Answer 38

A second dose of the same preparation, taken 2 to 24 hr after the first, may again provide significant relief. A triptan should not be used again for at least 24 hr after the second dose

Question 39

Triptans should not be administered | within 24 hr of another substance with

Answer 39

vasoconstricting properties (e.g., another triptan, ergotamine, dihydroergotamine, or isometheptene).

Question 40

Triptans should not be | administered within 2 weeks of discontinuation of a

Answer 40

monoamine oxidase inhibitor or methysergide.

Question 41

Triptans should not be prescribed to patients with

Answer 41

ischemic or other heart disease or uncontrolled hypertension; they should be avoided in patients with complicated auras such as dysphasias and confusional states and in basilar migraine

Question 42

major side effects of triptans

Answer 42

sensation of chest pressure, flushing, tingling, | dizziness, and dysphoria. These usually resolve in less than 1 hr.

Question 43

Ergotamine tartrate

Answer 43

older drug with 5-HT agonist activity that also is very effective for migraine. One to 2 tablets are taken at the onset of the headache or aura, followed by 1 tablet every 30 min until the headache is gone or until a maximum of 5 tablets per headache or 10 tablets per week have been consumed

Question 44

Isometheptene (Midrin)

Answer 44

effective drug with 5-HT agonist and sympathomimetic (vasoconstrictive) activity. Midrin also contains dichloralphenazone, a mild sedative-hypnotic drug similar to chloral hydrate. One to 2 capsules are taken at the onset of the headache or aura, followed by 1 capsule every hour until the headache is gone or until a maximum of 5 capsules per headache or 10 capsules per week have been consumed

Question 45

If consumed in excess, ergotamine-containing preparations can cause

Answer 45

vasospastic complications and are emetogenic.

Question 46

Preparations containing butalbital (such as Fioricet, | which also contains acetaminophen and caffeine, or Fiorinal, which contains aspirin and caffeine

Answer 46

are effective One to two tablets can be taken every 4 hr as needed. Barbiturate-containing preparations cause drowsiness and can be habit forming if used excessively

Question 47

Narcotic-containing preparations, such as those with codeine, hydromorphone, or hydrocodone (in combination with aspirin or acetaminophen)

Answer 47

should be used only as drugs of last resort. Narcotics bind opiate receptors and mask pain, but they do not bind serotonin receptors and therefore do not interrupt the putative pathophysiologic mechanism of migraine.

Question 48

Antinauseants

Answer 48

prochlorperazine, chlorpromazine, or metoclopramide, by virtue of their effect on serotonin receptors, are effective against migraine pain. Their action as antagonists of the D2 dopamine receptor helps control the associated gastrointestinal symptoms and this makes them excellent adjuvant drugs

Question 49

Dihydroergotamine (DHE)

Answer 49

generally administered parenterally but also is available as a 4 mg/mL nasal spray. Administered by the intravenous or intramuscular route, the dose should not exceed 2 to 3 mg in 24 hr.

Question 50

Dihydroergotamine (DHE) indication

Answer 50

the drug of choice for treatment of status | migrainosus.

Question 51

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Answer 51

work for some patients with mild to moderate migraine pain. Ketorolac, which can be administered intramuscularly, and indomethacin, which also is available as a suppository, may be particularly useful. Aspirin, particularly combined with acetaminophen and caffeine (Excedrin), remains an effective and inexpensive over-the-counter treatment.

Question 52

Cambia

Answer 52

diclofenac combined with potassium bicarbonate. use for the treatment of migraine.

Question 53

Cambia indications

Answer 53

It is a drug worth considering in patients in whom vasoconstricting drugs are contraindicated or who cannot tolerate the side effects of vasoconstricting drugs.

Question 54

The chronic use (averaging at least 10 times per month over a prolonged period of time) of any of the triptans, NSAIDs, acetaminophen, butalbital, narcotics, ergotamine, DHE, and isometheptane can lead to

Answer 54

development of a medication overuse, or rebound, headache syndrome.

Question 55

Beta-blockers

Answer 55

propranolol (60 to 80 mg once per day), metoprolol, atenolol, timolol, and nadolol, are frequently effective first-line prophylactic drugs; propranolol and timolol are FDA approved for migraine prophylaxis

Question 56

Beta-blockers Side effects

Answer 56

dizziness from bradycardia or hypotension, fatigue, depression, worsening of symptoms in patients with asthma or chronic obstructive pulmonary disease, gastrointestinal distress, blunting of hypoglycemic symptoms in patients with diabetes, and vivid dreams.

Question 57

Anticonvulsants

Answer 57

valproic acid (Depakote and Depakote ER) and carbamazepine have been used as prophylaxis against migraine. Depakote and Topamax are FDA approved for migraine prophylaxis.

Question 58

Depakote ER

Answer 58

The usual starting dose for Depakote ER is 500 mg per day; the dose should be adjusted as necessary at 2- to 4-week intervals

Question 59

Valproic acid Side Effects

Answer 59

weight gain, hair loss, tremor, abdominal distress, and easy bruisability.

Question 60

Topamax

Answer 60

an inhibitor of carbonic anhydrase and it has been reported to be useful in treating the syndrome of idiopathic increased intracranial pressure (previously called pseudotumor cerebri).

Question 61

Frequent side effects of Topamax

Answer 61

mental confusion and paresthesia; another is weight loss

Question 62

Antidepressants, particularly amitriptyline

Answer 62

at a starting dose of 10 to 25 mg at bedtime, are very active prophylactic drugs. Most patients who respond to tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, or desipramine) usually do so at doses of 25 to 200 mg at bedtime; occasionally a patient may require more

Question 63

The major side effects from tricyclics relate to

Answer 63

their anticholinergic action and include a dry mouth, | excessive daytime sleepiness, dizziness, urinary retention, glaucoma, cardiac arrhythmias, and photosensitization.

Question 64

The specific serotonin reuptake inhibitors | SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs

Answer 64

tried in patients who do not respond or who develop intolerable side effects from tricyclic drugs.

Question 65

The major side effects of the SSRIs and SNRIs

Answer 65

jitteriness, tremors, gastrointestinal distress, | decreased libido, and occasionally headaches

Question 66

SSRIs and SNRIs are relatively contraindicated in | patients who use

Answer 66

``` triptans, as they may suffer from excessive serotonin stimulation (serotonin syndrome). ```

Question 67

Calcium channel blockers

Answer 67

verapamil, are occasionally useful as prophylactic agents. Calcium channel blockers are worth a try when firstline agents fail; they also appear to be more useful in patients with cluster headaches.

Question 68

Lithium carbonate

Answer 68

useful in patients with frequent | migraines who do not respond to more traditional prophylactic regimens

Question 69

The major indication for lithium

Answer 69

treatment of an ongoing cluster headache.

Question 70

``` Individualized injections of botulinum toxin A into the pericranial muscles (frontalis, temporalis, and glabellar muscles) ```

Answer 70

has been reported to increase significantly the number of headache-free days in some patients with chronic migraine. The beneficial effect may last up to 90 days postinjection

Question 71

self-help strategies that can minimize the incidence of migraines

Answer 71

If the patient consumes caffeinated beverages (coffee, tea, soda, cocoa), total caffeine should be limited to less than 400 mg per day (to avoid caffeinism) and the intake should include weekends, vacations, and holidays (to avoid a caffeine withdrawal headache).

Question 72

foods high in tyramine | (a substance metabolized to serotonin), which is thought to play a role as a migraine trigger, can be avoided.

Answer 72

chocolate, aged cheeses, | yogurt, sour cream, soy sauce, chicken liver, banana, avocado, nuts, and yeast extracts (including beer).

Question 73

Foods high in nitrates can be avoided, as these might precipitate a migraine by virtue of their vasodilating properties.

Answer 73

Some foods high in nitrates include processed meats (hot dogs, salami, bacon, ham, sausage, corned beef) and other canned, smoked, or aged meats.

Question 74

patients are sensitive to certain food additives

Answer 74

monosodium glutamate, frequently used in restaurants and added to cooked, packaged, and canned foods as a flavor enhancer, and aspartame (NutraSweet). These substances contain glutamate, an excitatory neurotransmitter.

Question 75

migraneurs are sensitive to alcoholic beverages.

Answer 75

Alcohol tends to dilate blood vessels.

Question 76

trigeminal autonomic cephalalgias (TAC)

Answer 76

represent a group of three headache disorders characterized by the occurrence of pain in the distribution of the first division of the trigeminal nerve accompanied by prominent parasympathetic autonomic features in the same distribution.

Question 77

trigeminal autonomic cephalalgias (TAC) examples

Answer 77

These headaches are: cluster, hemicrania (paroxysmal hemicrania and hemicrania continua), and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT).

Question 78

trigeminal autonomic cephalalgias (TAC) presents

Answer 78

with some combination of ocular redness, tearing, swelling, miosis, or ptosis; additional symptoms can include forehead sweating and rhinorrhea

Question 79

trigeminal autonomic cephalalgias (TAC) durations

Answer 79

Cluster headache lasts longest and presents with circadian periodicity but, overall clusters tend to occur relatively infrequently, such as yearly. SUNCT have the shortest duration but a high frequency of attacks. The duration and frequency of paroxysmal hemicrania is intermediate. Hemicrania continua is characterized by continuous pain with exacerbations.

Question 80

Cluster headache is diagnosed by

Answer 80

suggestive clinical history and a normal neurologic examination. Typically, severe pain, which lasts between 15 and 90 min, awakens the patient. The pain is unilateral and periorbital; it may include the temple, forehead, and cheek (the distribution of the first division of the trigeminal nerve).

Question 81

Cluster headache accompanied by

Answer 81

lacrimation, conjunctival injection, nasal stuffiness, ptosis (with or without eyelid edema), and miosis ipsilateral to the pain.

Question 82

Unlike patients with migraine, who seek | a dark, quiet environment, patients with cluster tend to

Answer 82

pace, scream, or appear agitated; nausea and vomiting are uncommon.

Question 83

The major limitation of drugs aimed at interrupting the cluster (drugs used in migraine prophylaxis) is

Answer 83

their slow onset of action, with most requiring 2 to 4 weeks to demonstrate activity at the initial dose, and similar intervals for subsequent dose adjustments.

Question 84

drugs are useful for interrupting the cluster- | Calcium channel blockers

Answer 84

Calcium channel blockers, such as verapamil (Verapamil usually requires administration at relatively high doses, 240 to 480 mg/day, to be effective.)

Question 85

drugs are useful for interrupting the cluster - Anticonvulsants

Answer 85

``` valproic acid (Depakote and Depakote ER) and carbamazepine can be useful to help abort a cluster. The usual starting dose for Depakote ER is 500 mg per day; the dose should be adjusted as necessary at 2- to 6-week intervals. Valproic acid can cause weight gain, hair loss, tremor, and abdominal distress. ```

Question 86

drugs are useful for interrupting the cluster - Lithium carbonate

Answer 86

can be useful in patients with cluster; in fact, cluster remains the major indication for lithium in the treatment of headaches.

Question 87

drugs are useful for interrupting the cluster -Antidepressants

Answer 87

amitriptyline at a starting dose of 10 to 25 mg at bedtime. Tricyclics help induce sleep, which may constitute one of the mechanisms by which they help patients with cluster.

Question 88

The major side effects from | tricyclics

Answer 88

relate to their anticholinergic effects and include a dry mouth, excessive daytime sleepiness, dizziness, urinary retention, glaucoma, cardiac arrhythmias, and photosensitization.

Question 89

drugs are useful for interrupting the cluster - Beta-blockers

Answer 89

propranolol, metoprolol, atenolol, timolol, and nadolol, are also used frequently for cluster. In most healthy people 60 to 80 mg once per day of a long-acting propranolol preparation can be started and the dosage can be adjusted as necessary

Question 90

Beta-blockers Side Effects

Answer 90

dizziness from bradycardia or hypotension, fatigue, depression, worsening of symptoms in patients with asthma or chronic obstructive pulmonary disease, gastrointestinal distress, blunting of hypoglycemic symptoms in patients with diabetes, and vivid dreams.

Question 91

Corticosteroids are useful as adjuvants to other drugs in breaking a cluster

Answer 91

They should be started simultaneously with one of the other prophylactic drugs. Corticosteroids are to be used for a limited time

Question 92

drugs are useful for interrupting the cluster -NSAIDs

Answer 92

indomethacin appears to be more active than others. It also can be used in anticipation of a headache to block its onset. Indomethacin can be administered in doses up to 150 mg/day but tends to irritate the gastric mucosa

Question 93

Treatment of an Acute Cluster Headache

Answer 93

inhaled oxygen remains the standard for treatment of an acute cluster headache.31 Oxygen should be administered at 12 L/minute through a nonrebreather mask for 15 min as soon after the onset of the attack as feasible.

Question 94

Paroxysmal hemicrania

Answer 94

The syndrome consists of frequent, unremitting, unilateral headaches exhibiting a frequency of a few to more than 20 per day; the headaches last 5 to 45 min each. The pain, throbbing or boring, is localized on one side of the head, around the eye and temple (in the distribution of the first division of the trigeminal nerve). As in cluster, the pain is accompanied by autonomic (parasympathetic) phenomena: redness and tearing of the eye, eyelid swelling, nasal congestion, and/or rhinorrhea.

Question 95

The hallmark of hemicrania

Answer 95

it responds completely and dramatically to indomethacin, which can be administered in doses up to 150 mg/day and, as long as it is tolerated, can be used for long periods of time.

Question 96

short-lasting unilateral neuralgiform headache with conjunctival injection (SUNCT)

Answer 96

Bursts of stabbing, throbbing, or burning pain around the eye or temple, lasts 5 seconds to 5 min and occurs in paroxysms of up to 30 per hr (with an average of 5 to 6/hr). Here too, the pain is accompanied by autonomic (parasympathetic) phenomena in the distribution of the first division of the trigeminal nerve: redness and tearing of the eye, eyelid swelling, nasal congestion, and/or rhinorrhea

Question 97

short-lasting unilateral neuralgiform headache with conjunctival injection treatment

Answer 97

prophylactic treatment with anticonvulsants | including lamotrigine and oxcarbazepine