Migraine is a common, chronic, incapacitating neurovascular disorder, characterized by

1

• Migraine is a common, chronic, incapacitating
  neuro-vascular disorder, characterized by
• attacks of severe headache,
• autonomic nervous system dysfunction, and in some
  patients,
• an aura involving neurologic symptoms.

2
Any severe and recurrent headache is most
likely to be a form of migraine, and to be
responsive to antimigraine therapy. In 15
percent of patients, migraine attacks are usually
preceded or accompanied by transient focal
neurologic symptoms.
3
64 Percent of patients with migraine had only
migraine without aura, 18 percent had only
migraine with aura, and 13 percent had both types
of migraine (the remaining 5 percent had aura
without headache).
4

• The incidence peaks in early to mid-adolescence.
• In the West the one-year prevalence of migraine
  is 11 percent overall 6 percent among men and
  15 to 18 percent among women.
• The median frequency of attacks is 1.5 per
  month, and the median duration of an attack is 24
  hours.
• At least 10 percent of patients have weekly
  attacks, 20 percent have attacks lasting two to
  three days. Thus, 5 percent of the general
  population have at least 18 days of migraine per
  year, and at least 1 percent have at least 1 day
  of migraine per week.

5

• Most patients with migraine
• have not seen a physician for headache during
  the previous year,
• have never received a medical diagnosis of
  migraine, and
• use over-the-counter medications to the exclusion
  of prescription drugs.

6

• A recent survey by the WHO rates severe migraine,
  along with quadriplegia, psychosis, and dementia,
  as one of the most disabling chronic disorders.
• This ranking suggests that in the judgement of
  the WHO, a day with severe migraine is as
  disabling as a day with quadriplegia.

7
Migraine is best understood as a primary disorder
of the brain. It is a form of neurovascular
headache a disorder in which neural events
result in the dilation of blood vessels, which,
in turn, results in pain and further nerve
activation. Migraine is not caused by a primary
vascular event.
8
Migraine probably results from a dysfunction of
brain-stem or diencephalic nuclei that are
involved in the sensory - particularly
noniceptive - modulation of craniovascular
afferents.
9
Aura is characterized by a wave of oligemia that
passes across the cortex at the
characteristically slow rate of 2 to 6 mm per
minute. A short phase of hyperemia precedes this
oligemia and is likely to be a correlate symptoms
as flashing, jagged lights.
10

• PAIN MECHANISMS
• Three key factors merit consideration
• the cranial blood vessels,
• the trigeminal innervation of the vessels, and
• the reflex connections of the trigeminal system
  with the cranial parasympathetic outflow.

11

• Nonpharmacologic therapies include
• education of the patient about the disorder, its
  mechanisms, approaches to treatment, and changes
  in lifestyle involved in the avoidance of
  triggers of migraine
• in patients with migraine, the brain does not
  seem to tolerate the peaks and troughs of life
  well. Thus, regular sleep, regular meals,
  exercise, avoidance of peaks of stress and
  troughs of relaxation, and avoidance of dietary
  triggers can be helpful.

12
The patient should aim for a certain regularity
of habits, rather than adhere to a long list of
prohibitions of foods and activities.
13
The same manipulations intended to avoid
triggering migraine will lead to different
outcomes on different days.
14

• Drugs for the treatment of migraine can be
  divided into
• drugs that are taken daily whether or not
  headache is present to reduce the frequency and
  severity of attacks, and
• drugs that are taken to treat attacks as they
  arise.

15
Treatment for attacks can be further divided into
nonspecific and migraine-specific treatments.
Nonspecific treatments, such as aspirin,
acetaminophen, nonsteroidal antiinflammatory
drugs, opiates, and combination analgesics, are
used to treat a wide range of pain disorders.
16
Specific treatments, including ergotamine,
dihydroergotamine, and the triptans, are
effective for treating neurovascular headaches,
such as migraine and cluster headache, but not
for treating other types of pain, such as pure
tensiontype headache or atypical facial pain.
17
Given that there are responses to placebo in
patients with migraine, that there is a
significant rate of nonresponse to oral drugs,
and that triptans have not been studies
systematically in patients with such problems as
subarachnoid hemorrhage or meningitis, triptans
should not be used as diagnostic testing agents
in patients with headache.
18
PREVENTATIVE THERAPY If headaches occur one or
two days per month, there is usually no need for
preventive therapy it they occur three to four
days per month, preventive therapy should be
considered if the patient has five or more
attacks per month, preventative therapy should be
considered seriously.
19
Each drug should be started at a low dose, and
the dose should be gradually increased to a
reasonable maximum.
20
PREVENTATIVE THERAPY FOR MIGRAINE DRUG DOSE
SELECTED SIDE EFFECTS PROVEN OR WELL
ACCEPTED ß-Adrenergic-receptor
antagonists Propranolol 40-120 mg twice
Reduced energy, tiredness, postural - daily
symptoms, contraindicated in patients
Metroprolol 100-200 mg daily with
asthma Amitriptyline 25-75 mg at bedtime
Drowsiness Divalproex (valproate) 400-600 mg
twice Drowsiness, weigt gain, tremor, hair
daily loss, fetal abnormalities,
hematologic and liver abnormalities Fluna
rizine 5-15 mg daily Tiredness, weight gain,
depression,
parkinsonism Serotonin antagonists Pizotyline
(pizotifen) 0,5 - 3 mg daily Drowsiness,
weight gain Methysergide 1-6 mg daily
Drowsiness, leg cramps, hair loss, ret-

roperitoneal fibrosis WIDELY
USED BY WITH POOR EVIDENCE OF BENEFIT Verapamil
160-320 mg daily Constipation, leg
swelling, atrioven- tricular conduction
disturbances Selective serotonin-reuptake
Anxiety, insomnia inhibitors

21
TREATMENT OF ACUTE ATTACKS ANALGESIC AND
NONSTEROIDAL ANTIINFLAMMATORY DRUGS The drug
should be taken as soon as the headache component
of the attack is recognized. The dose of drug
should be adequate for example, 900 mg of
aspirin, 1000 mg of acetaminophen, 500 to 1000 mg
of naproxen, 400 to 800 mg of ibuprofen, or
appropriate doses of a combination of these
drugs.
22
Antiemetic drugs Overuse of these drugs should
be avoided. Intake should be restricted to no
more than two or three days a week, and a
headache diary should be kept. As a rule, avoid
the use of opiates.
23
ERGOT DERIVATIVES Low cost are associated with
adverse vascular events, and the high risk of
overuse syndromes and rebound headaches.
24
THE TRIPTANS Selective pharmacology, simple and
consistent pharmacokinetics, evidence-based
prescription instructions, established efficacy
based on well-designed controlled trials,
moderate side effects, and a well established
safety record. The most important disadvantages
of the triptans are their higher cost and the
restrictions on their use in the presence of
cardiovascular disease.
25
The triptans are serotonin 5- HT-receptor
agonists.
26

• Triptans have three potential mechanisms of
  action
• cranial vasoconstriction,
• peripheral neuronal inhibition,
• and inhibition of transmission through
  second-order neurons of the trigeminocervical
  complex

27
There are five triptans in routine clinical
use sumatriptan, naratriptan, rizatriptan,
zolmitriptan, and almotriptan.
28
The oral absorption of many drugs is delayed, so
there may be an advantage to non-oral methods of
administration, such as the use of nasal sprays,
inhalers, suppositories, or injections. Most
patients, however, prefer oral formulations.
29
Tolerability refers to the extent of medically
unimportant but clinically irritating side
effects of drugs, such as tingling, flushing, and
sensations of pressure safety is assessed on
the basis of records of medically important side
effects.
30
The triptans differ from one another in terms of
tolerability but not in terms of safety. The
most frequent side effects are tingling,
parasthesias, and sensations of warmth in the
head, neck, chest, and limbs less frequent are
dizziness, flushing, and neck pain or stiffness.
It may cause symptoms, sometimes closely
mimicking angina pectoris.
31
Sensible contraindications of ischemic heart
disease, uncontrolled hypertension, and
cerebrovascular disease apply to the entire
class.
32
Meta-analysis, using data from 24 089 patients
in 53 controlled clinical trails of triptans,
were recently performed.
33
I. IMPROVEMENT IN TWO HOURS
34
The headache (pain) response at two hours was the
primary end point in nearly all trials of
triptans. As compared with 100 mg of
sumatriptan, 10 mg of rizatriptan and 80 mg of
eletriptan were significantly more effective,
whereas 2.5 mg of naratriptan, 20 mg of
eletriptan, and 2.5 mg of frovatriptan were less
effective.
35
Although the freedom from pain is the currently
recommended primary end point, 80 mg of
eltriptan, 12.5 mg of almotriptan, and 10 mg of
rizatriptan were more effective than 100 mg of
smatriptan, whereas 25 mg of sumatriptan, 2.5 mg
of naratriptan, and 20 mg eleptriptan were less
effective than 100 mg of sumatriptan.
36
2. SUSTAINED FREEDOM FROM PAIN
37
Freedom from pain at 2 hours with no rescue
medication and with no recurrence of headache
within 24 hours. These rates were higher with 10
mg of riztriptan, 80 mg of eletriptan, and 12.5
mg of almotriptan than with 100 mg of
sumatriptan, and lower with 20 mg of eletriptan
than with 100 mg of sumatriptan.
38
3. INTRAPATIENT CONSISTENCY OF RESPONSE
39
Efficacy in at least two out of three treated
attacks was found in 67 percent of patients given
100 mg of sumatriptan and 65 percent of those
given 50 mg of sumatriptan. The rates of
consistency in patients who received rizatriptan
were the highest for any of the triptans the
rates of response and freedom from pain were 86
percent and 48 percent.
40
4. TOLERABILITY
41
The rates of adverse avents with most triptans
other than sumatriptan overlap with those found
with 100 mg of sumatriptan there were lower
values for 2.5 mg of naratriptan and 12.5 mg of
almotriptan.
42
PARENTAL SUMATRIPTAN Subcutaneous sumatriptan,
at a dose of 6 mg, has the best pharmacokinetic
profile (time to maximal concentration, 10
minutes bioavailability, 96 percent), clinical
efficay (a response rate of 76 percent and a rate
of freedom from pain of 48 percent at 60 minutes
after administration), and intrapatient
consistency in multiple attacks (up tot 90
percent).
43
The main limitations are that patients must
inject themselves and that the incidence of
adverse events is higher and their intensity is
greater than with oral sumatriptan.
44
Migraine is a heterogeneous disorder, so the
selection of initial treatment for acute attacks
depends on the severity and frequency of the
attacks, the associated symptoms, the preference
of the patient, and the history of treatment.
45
In patients with substantial disability, it is
appropriate to prescribe a triptan early in the
course of treatment, in keeping with a
stratified approach to care.
46
Patients prefer not to have attacks at all.
Current prophylactic therapies for migraine are
relatively nonspecific, their efficacy is
moderate, and they have substantial side effects.
47
Drug Therapy of Migraine

• Migraine is an episodic headache that is
• unilateral or bilateral,
• pulsating in quality,
• moderate to severe in intensity
• Migraine headaches, tension-type headaches, and
  chronic pain syndromes remain challenges for
  clinicians and patients alike in terms of finding
  the most effective and safest therapies
  

48

• Associated symptoms include
• nausea or vomiting
• photophobia
• phonophobia
• Goals of migraine treatment are amelioration of
  the symptoms of an acute attack and prevention of
  further attacks, either by behavioral or
  pharmacological means

49

• Distinguishing between migraine without aura and
  episodic tension headache is difficult, and it is
  uncertain whether migraine with aura and migraine
  without aura are the same disorder as far as
  treatment is concerned

50
Analgesic Drugs

• Aspirin, acetaminophen, propoxyphene, and codeine
  are all superior to placebo
• Effervescent formulations
• Because gastric stasis often accompanies migraine
  attacks, metoclopramide enhances the
  effectiveness of analgesic drugs
• These drugs occasionally cause tardive dyskinesia
  which may be irreversible, and patients should be
  informed of this risk before beginning treatment

51
Analgesic drugs (cont)

• Two types of combined medications are often used
  in the treatment of migraine
• isometheptene in combination with acetaminophen
  and dichloralphenazone
• aspirin in combination with caffeine and
  butalbital
• There is no evidence that these preparations are
  more effective than other analgesics

52
Nonsteroidal Anti-inflammatory Drugs

• Nonsteroidal anti-inflammatory drugs can be the
  first choice of treatment for patients with
  mild-to-moderately-severe migraine attacks
• Naproxen
• Aspirin in oral doses of 500 mg
• Ketorolac

53
Ergot Preparations

• In controlled trials, ergotamine has proved to be
  effective in no more than 50 of patients when
  given orally, sublingually, rectally, or nasally
• The addition of caffeine to ergotamine enhances
  its absorption and possibly its vasoconstrictive
  activity
• Ergotamine is best absorbed rectally
• Metoclopramide may improve the absorption of
  ergotamine administered orally
• Contraindicated in patients with coronary artery
  or peripheral vascular disease

54
Dopamine Antagonists

• Migraine was relieved in 67 of patients given a
  10 mg intravenous dose of metoclopramide, as
  compared with 19 of those given placebo

55
Preventive Migraine Therapy in addition to Acute
Treatment?

• The consensus at this time is when the disability
  is sufficient to disrupt normal function
• Two severe disabling headaches per month not
  relieved with acute abortive treatment are
  sufficient to warrant preventive medication
• 8 mild to moderate headaches per month that are
  easily relieved by distraction, mild medication
  that does not create rebound headaches, or change
  of lifestyle would not necessarily warrant
  preventive medications

56
Migraine Acute Treatment

• The majority of patients took over-the-counter
  medications or prescription medications that are
  not specific for migraine headaches
• Only 12,6 of patients took medications that
  were specific for migraine of these, only 4
  took triptans for their headaches

57
Choice of Symptomatic Treatment

• A simple analgesic or nonsteroidal
  anti-inflammatory drug is appropriate for
  mild-to-moderate attacks, and ergotamine or
  sumatriptan for moderate-to-severe attacks
• If these treatments fail, metoclopramide,
  prochlorperazine, or chlorpromazine can be used
• Acute attacks may by so frequent and the
  patients pain so severe and continuous that
  hospitalization is required
• In these cases, dihydroergotamine given
  intravenously for 3 to 4 days, discontinuation of
  all other drugs, and amininstration of
  intravenous fluids may prove effective

58
Prevention of Migraine

• Preventive treatment should be considered only
  when
• attacks of migraine occur more than 2/3 times a
  month
• attacks are severe and limit normal activity
• the patient is unable to cope with the attacks
• symptomatic therapies have failed or had serious
  side effects
• attempts at nonpharmacologic prevention have
  failed

59
Prevention of migraine (cont)

• Each medication should be given for an adequate
  time to judge its effectiveness
• For patients with frequent migraine, this period
  is usually 2 to 3 months
• Preventive medication is usually continued for 6
  months or longer and gradually withdrawn after
  the frequency of headaches diminishes
• 5-HT-influencing drugs
• methysergide and amitriptyline

60
Beta-Adrenergic Antogonists

• Numerous clinical trials have shown that
  beta-adrenergic-antagonist drugs are effective in
  preventing migraine
• They should be considered the treatment of choice
  for patients whose attacks of migraine are
  related to stress
• Are effective in no more than 65 of patients

61
Hormonal Therapy

• Menstrual migraine, defined as an attack
  occurring in association with menses, is
  frequently refractory to treatment
• May benefit from preventive treatment - for
  example, propranolol or amitriptyline - limited
  to the time of their menses
• Percutaneous estradiol gel, applied just before
  and throughout menses, has reduced the frequency
  of headaches

62
Hormonal therapy (cont)

• For woman already taking estrogen who have
  frequent migraine attacks, it may be beneficial
  either to stop or to increase the hormones
• Treatment strategies are aimed at preventing
  either a decrease or a substantial fluctuation in
  serum estrogen levels

63
NB Headache

• Severe headache in a previously well patient
• Headaches that disturb sleep, exertional
  headaches, and late-onset paroxysmal headaches
  are also more suggestive of an underlying
  structural lesion, as are headaches accompanied
  by neurologic symptoms

64
Migraine

• Classic migrainous headache is a lateralized
  throbbing headache that occurs episodically
  following its onset in adolescence or early adult
  life
• Migrainous headaches may be lateralized or
  generalized, may be dull or throbbing, and are
  sometimes associated with anorexia, nausea,
  vomiting, photophobia, phonophobia, and blurring
  of vision
• The usually build up gradually and may last for
  several hours or longer

65
Migraine (cont)

• Focal disturbances of neurologic function may
  precede or accompany the headaches and have been
  attributed to constriction of branches of the
  internal carotid artery
• Visual disturbances occur quite commonly and may
  consist of field defects
• Luminous visual hallucinations

66
Migraine (cont)

• Patients often give a family history of migraine
• Attacks may be triggered by
• emotional or physical stress
• lack or excess of sleep
• missed meals
• specific foods (e.g.. Chocolate)
• alcoholic beverages
• menstruation
• use of oral contraceptives

67
Basilar Artery Migraine

• Blindness or visual disturbances throughout both
  visual fields are initially accompanied or
  followed by dysarthria, disequilibrium, tinnitus,
  and perioral and distal paresthesias and are
  sometimes followed by transient loss or
  impairment of consciousness or by a confusional
  state
• This is followed by a throbbing (usually
  occipital) headache, often with nausea and
  vomiting

68
Ophthalmoplegic Migraine

• Lateralized pain - often about the eye - is
  accompanied by nausea, vomiting, and diplopia due
  to transient external ophthalmoplegia

69
Rarerely...

• Neurologic or somatic disturbance accompanying
  typical migrainous headaches becomes the sole
  manifestation of an attack (migraine
  equivalent)
• Very rarely, the patient may be left with a
  permanent neurologic deficit following a
  migrainous attack

70

• During acute attacks, many patients find it
  helpful to rest in a quiet, darkened room until
  symptoms subside
• A simple analgesic (e.g.. Aspirin) taken right
  away often provides relief, but treatment with
  extracranial vasoconstrictors or other drugs is
  sometimes necessary

71

• It is estimated that 40 of the worldwide
  population suffers with severe, disabling
  headache at least annually.

72
The most important information in the accurate
diagnosis of headache and facial pains comes from
the patients history. Indeed, frequently one
must first reverse a self-diagnosis of sinus
headache reached by the patient, before a more
thorough history can be attained and more
accurate diagnosis reached.
73

• Tension-Type Headache
• most common type of headache
• occurs in 69 of men and 88 of women over a
  lifetime
• episodic TTH (ETTH) or chronic TTH (CTTH)
• 30 Minutes to 7 days
• patients who acknowledge the role of stress in
  the etiology of their headaches, especially
  those with ETTH, are frequently well managed by
  biofeedback and stress reduction techniques
• low dose amitriptyline once daily
• abortive medications include aspirin,
  acetaminophen, asprin-cafeine-butalbital or
  phenacetin combinations or short half-life
  non-steroidal anti-inflammatory medications
  (NSAIDs).

74

• triggering factors may include stress, menses,
  pregnance and oral contraceptive pills, infection
  in the head and neck, trauma or surgery, red
  wine, agted cheeses, vasodilating medications,
  strong odors, irregular diet or leep and bright
  sunlight or flckering lights
• Abortive therapy
• (1) Prochlorpeazine IV push that may be repeated
  in 20 minutes if no effect
• (2) dihydroergotamine IV push followd by IV
  prochloperazine
• (3) chlorpromazine IV push, may repeat in 20
  minutes if needed
• (4) haloperidol IV push followed by lorazepam IV
  push.
• Options (1) and (3) should not be combined, but
  may be followed by (2) or (4) if necessary.
• complete prophylaxis for an averageof 4.1 months
  duration after the injection of botulinum toxin
  type A (BOTOX) into the facial and scalp
  musculature (additional 38 obtained a partial
  response)

75

• Cluster Headache
• Characterized by intensely severe pain (sometimes
  termed suicide headache) with boring or burning
  qualities located unilaterally peri-orbit
• 15 tot 180 minutes, associated with at least one
  symptom of autonomic hyperactivity conjunctival
  injection, lacrimation, nasal congestion,
  rhinorrhea, forehead and facial sweating, moists,
  ptosis, or eyelid edema
• Male preponderance, alcohol use and intolerance
  both episodic and chronic
• Calcium channel blockers, low dose daily
  ergotamine (Bellergal), lithium carbonate.
  Methysergide. Oxygen inhalation, 6-10 liters per
  minute administered by face mask seems to be
  particular effective in young patients with
  attacks primarily at night. Intranasal lidocaine
  administered either 4 topical or 2 viscous at
  the posterior aspect of the inferior turbinate
  affecting a sphenopalatine block may be effective
  in terminating an acute attack.

76

• Temporal Arteritis
• Daily headaches of moderate to severe intensity,
  scalp sensitivity, fatigue and various
  non-spesific complaints with a general sense of
  illness
• 95 are over 60 years old
• Usually unilateral, continuous ache with
  superimposed sharp, shooting head pains
• Erythocvte sedimentation rate (ESR) is markedly
  elevated
• High dose steroid therapy usually precipitates
  a dramatic decrease in head pain. Steroids
  should be started immediately to avoid vision
  loss, most common complication of the disorder
  occurring in 30 of untreated cases
• Disease is usually active for 1-2 years, during
  which time steroids should be continued to
  prevent vision loss.

77

• Chronic Daily Headache
• at least 6 days a week for a period of at least
  6 months, present throughout the day
• associated with the overuse and abuse of many
  common over-the-counter pain medications
• increasing need for medications and the
  emergence of a chronic headache that is
  qualitatively distinct from the headache for
  which is was originally taken - a transformed
  migraine
• The treatment centers on the withdrawal of the
  causative medication.
• (1) The patient must understand the syndrome
• (2) the offending medication should be tapered
  over 10 days and completely ceased for a minimum
  of 2 months
• (3) the substitution of other agents that may
  perpetuate the disorder must be avoided
• (4) antidepressant medications prescribed at
  gradually incresed dosages aid in withdrawal of
  the offending medication
• (5) adjuvant therapy such as physical therapy or
  biofeedback should be employed

78

• Trigeminal Neuralgia
• tic dolereux
• paroxysmal pain attacks lasting from a few
  seconds to less than two minuts - severe, and
  distributed one or more of the branches of the
  trigeminal nerve with a sudden, sharp, intense
  stabbing or burning quality
• may be precipitated from trigger areas or with
  certain daily activities such as eating, talking,
  washing the face or brushing the teeth
• most common in patients over 50
• Carbamazepine, gabapentin, baclofen, phenytoin,
  or sodium valproate. Tricyclicantidepressants
  (TCA) and NSAIDs may be used as adjuvant therapy.
  Surgical treatment is occasionally necessary.
  Glossopharyngeal neuralgia is characterized by
  pain attacks similar to these in trigeminal
  neuralgia, but located unilaterally in the
  distribution of the glossopharyngeal nerve.