• Lifetime prevalence of any type of headache is
• > 90% in men
• > 95% in women.
Tension type headache
Systemic or brain infection
Ischaemic or haemorrhagic
Lumbar puncture headache
Scalp and aponeurosis
Middle meningial arteries
Proximal segments of the large pial arteries
According to ICHD-3
PART ONE : PRIMARY HEADACHE
2. Tension type headache
3.Cluster headache and other trigeminal-autonomic
4. Other primary headaches
• PART TWO: THE SECONDARY HEADACHES
• 5. Headaches attributed to head and / or neck trauma
• 6. Headache attributed tocranial or cervical vascular
• 7. Headache attributed to non-vascular intra-cranial
• 8. Headache attributed to a substance or its withdrawal
• 9. Headache attributed to infection
• 10. Headache attributed to disorder of homeostasis
• 11. Headache or facial pain attributed to disorder of
cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or
other facial or cranial structures
• 12. Headache attributed to psychiatric disorder.
◦ PART THREE: CRANIAL NEURALGIAS, CENTRALAND
PRIMARY FACIAL PAIN AND OTHER HEADACHES
Cranial neuralgias and central causes of facial pain
14. other headache, cranial neuralgia, central or primary
The term ‘Migraine’ is of French origin derived from a
Greek name ‘hemikranios’, meaning unilateral
Migraine is a common disabling primary headache
Epidemiological studies have documented its high
prevalence and high socio-economic and personal
In the Global Burden of Disease Survey2010,
migraine was ranked as the third most prevalent
disorder and seventh-highest specific cause of
• In a survey it was seen that > 90% patients reported
of impaired ability of function during migraine
attacks, 53% reported severe disability requiring bed-
rest. About 31% missed atleast 1 day from work or
school due to migraine.
Initial attacks occur mostly in adolescents.
Usually when the attack begins denovo in older people,
migraine is unlikely.
In children, there is a little preponderance in males.
After puberty it is female predominant.
Evidence of positive family history is present in >90% cases.
Migraine tends to recur with varying frequency throughout
life, attack gets milder and less frequent in older age groups.
◦ ICHD-3rd ed (Beta version)
1.1 Migraine without aura
1.2 Migraine with aura
1.2.1 Migraine with typical aura
18.104.22.168 Typical aura with headache
22.214.171.124 Typical aura without headache
1.2.2 Migraine with brainstem aura
1.2.3 Hemiplegic migraine
126.96.36.199 Familial hemiplegic migraine (FHM)
188.8.131.52.1 Familial hemiplegic migraine type 1
184.108.40.206.2 Familial hemiplegic migraine type 2
220.127.116.11.3 Familial hemiplegic migraine type 3
18.104.22.168.4 Familial hemiplegic migraine, other loci
22.214.171.124 Sporadic hemiplegic migraine
1.5 Probable migraine
1.5.1 Probable migraine without aura
1.5.2 Probable migraine with aura
1.6 Episodic syndromes that may be associated with
1.6.1 Recurrent gastrointestinal disturbance
126.96.36.199 Cyclical vomiting syndrome
188.8.131.52 Abdominal migraine
1.6.2 Benign paroxysmal vertigo
1.6.3 Benign paroxysmal torticollis
True pathogenesis of migraine is still not clear.
Previously vascular theory was supposed to be the cause,
True In the vascular theory it was thought that
vasoconstriction followed by vasodilatation explained the
causes of aura followed by headache.
IN FAVOUR-Radioactive xenon cerebral blood flow studies
show significantly reduced regional blood flow through cortex
during aura stage of migraine.
1.functional MRI studies show that a phase of focal hyperemia
precedes the phase of oligemia during migraine attack
2. headache may begin while the cortical blood flow remains
Now-a-days neurophysiological and neurofunctional studies
support a primary neuronal theory, according to which a
neuronal hyperexcitability is the biological basis for
susceptibility to migraine.
Migrainous brain is qualitatively and quantitatively different
from nom-migrainous brain, that cause thresold of
susceptibility governed by some factors, resulting in neuronal
hyperexcitability and spontaneous depolarisation.
Instability in release of
Substance P, neurokinin A,
surrounding tissues and
which in turn, stimulate
pain stimulating neurons
in brain stem and upper
system and causes
Cerebral cortex, thalamus or
hypothalamus in response to
The factors include deficit in mitochondrial oxidative-
phosphorylation, alteration in neuronal voltage gated calcium
channel function, intracellular magnesium defficiency.
The electrical event produced by this neuronal hyperexcitability is
known as cortical spreading depression. It is more aptly described as
spreading activation followed by depression, which the cause of
visual schintillation followed by positive scotoma.
Spreading cortical depression can directly activate trigeminal
vascular nociceptive afferents.
Once activated impulse are transmitted centrally to trigeminal
nucleus caudalis, there from relay in thalamic centres and then
to parietal cortex.
At the same time neuropeptides like substane P, calcitonon
gene related peptide, neurokinin A are released from widely
branching trigeminal axon nerve terminals.
This results in neuronal inflammation and explains the cause
of pain im migraine.
Serotonin ( 5- hydroxytryptamine), a neurotransmitter
is thought to be an important mediator of migraine.
Unstable serotonergic neurotransmission, has lower
threshold for migraine.
There are 7 classes of 5-HT receptors
Out of 7, 2 involve in migraine pain.
Serotonin causes vasodilation in large artery
Serotonin causes vasoconstriction in small artery and capillary
During migraine the level of serotonin is low in blood.
Migraines the second most common cause of headache,
affecting approximately 15% of women and 6% of men.
It is usually an episodic throbbing headache,associated with
certain features like, sensitivity to light, sound or movement,
nausea and vomiting often accompanies the headache.
So migraine is benign, recurring syndrome of headache
associated with other neurological dysfunctions with varying
It has been suggested that migraine episode can be divided into
five distinct phases:
• Premonitory symptoms
• Headache and associated symptoms
It is also known as ‘common migraine’
It is not preceded or accompanied by any neurological
May be preceded by alteration in mood or enegy level,
excessive yawning, thirst, hunger. Headache may occur within
hours or in the next day.
Pain is usually unilateral and supraorbital but may be
Pain is throbbing in nature.
May be associated with nausea, vomiting photophobia etc.
Here aura precedes the headache.
Aura consists of transitory visual, sensory or language
disturbances or other focal cerebral or brainstem symptoms.
Aura occurs in 20-25% of the migraineurs and generally does
occur in every attack.
Classically visual symptoms occurs first, followed by
sensory symptoms and then by language symptoms.
Most common aura is the visual disturbance known
as “schintillating scotoma” or “teichopsia”. This
generally starts as an arc of white or coloured light,
having definite zigzag pattern, then gradually
expands from a point to involve a quadrant or
hemifield of vision in both the eyes.
Negative scotoma. Loss of local awareness of local
Positive Scotoma. Additional structures One side loss of perception.
Positive scotoma is followed by a spreading zone of
vision loss ie, negative scotoma.
Usually congruent homonymous field defect.
Visual disturbances causes reading and driving
There may be change in perception of shape of
viewed objects, called ‘metamorphopsia’.
Though uncommon, there may be retinal
dysfunction too, which leads to unilateral flashes of
light, scattered areas of vision loss, altitudinal
defects or transient unilateral vision loss. When
headache follows such uniocular vision loss, it is
called ‘retinal migraine’.
Sensory aura is second most common following
visual aura, and is again characterised by positive
symptoms (paraesthesia) followed by negative
Paraesthesia of migraine has prediliction for face and
hands, probably because of large representation of
these structures in the sensory cortex or thalamus.
The rate of spread of a sensory aura is important
to distinguish it from a sensory seizure and the
sensory disturbance of a TIA
Language aura, which can be expressive or
receptive type. Alexia and agraphia can also occur.
There may be mild confusion and difficulty in
There is an other variant called hemiplegic migraine,
in which there is weakness of limbs or facial muscles
on one side of body
When a visual, sensory, motor, or psychic disturbance
characteristic of migraine aura is not followed by a headache,
the episode is termed migraine aura without headache, a
migraine equivalent, or acephalgic migraine.
Most commonly encountered in patients who have a past
history of migraine with aura, the episodes can begin de novo,
usually after 40 years of age,
First encountered in childhood or adolescence.
Prevalence is almost equal in men and women.
Headache is usually severe and occipital.
Aura starts with typical migrainous disturbance of
vision, lasting for 10-45 mins, and is bilateral.
Tingling sensation of face, lip, hands occur often,
ataxia of gait, ataxia of speech, vertigo, tinnitus,
dysarthria also occurs.
Brainstem reticular function involvement may cause
impairment of consciousness in childhood.
Headache usually subsides after sleeping.
Gradually with increased maturation of nervous
system, it becomes less common, and generally
replaced by migraine without aura.
Onset in childhood
Recurrent attacks are stereotypical
Begins with unilateral orbital or retro-orbital pain,
accompanied by vomiting, that lasts for 1-4 days.
During the painful stage or after the pain has
subsided, ipsilateral ptosis occurs, and within a few
hours it progresses to complete paralysis of III rd
Rarely IV th and VI th cranial nerves may also be
involved. N Neural deficit may remain hors to several
Familial hemiplegic migraine is a form of migraine
headache that runs in families.
Along with the other features of migraine with aura,
in familial hemiplegic migraine some other features
may be seen like, fever, seizures, prolonged
Although most people with familial hemiplegic
migraine recover completely between episodes,
neurological symptoms such as memory loss and
problems with attention can last for weeks or months
About 20 percent of people with this condition develop
mild but permanent difficulty coordinating movements
(ataxia), which may worsen with time.
There may be involuntary eye movements .
The worldwide prevalence of familial
hemiplegic migraine is unknown. Studies
suggest that in Denmark about 1 in 10,000
people have hemiplegic migraine.
Familial hemiplegic migraine type 1
Familial hemiplegic migraine type 2
Familial hemiplegic migraine type 3
Mutations in the CACNA1A, ATP1A2, SCN1A,
and PRRT2 genes have been found to cause familial
The first three genes provide instructions for making
proteins that are involved in the transport of charged
atoms (ions) across cell membranes.
The movement of these ions is critical for normal
signaling between nerve cells (neurons) in the brain and
other parts of the nervous system.
The function of the protein produced from
the PRRT2 gene is unknown, although studies suggest
it interacts with a protein that helps control signaling
Researchers believe that mutations in
theCACNA1A, ATP1A2, and SCN1A genes can upset
the balance of ions in neurons, which disrupts the
normal release and uptake of certain neurotransmitters
in the brain.
Although the mechanism is unknown, researchers
speculate that mutations in the PRRT2 gene, which
reduce the amount of PRRT2 protein, also disrupt
normal control of neurotransmitter release.
The resulting changes in signaling between neurons
lead people with familial hemiplegic migraine to
develop these severe headaches.
This condition is inherited in an autosomal dominant
In most cases, affected individuals have one affected
However, some people who inherit an altered gene
never develop features of familial hemiplegic migraine.
(This situation is known as reduced penetrance.)
A related condition, sporadic hemiplegic migraine, has
identical signs and symptoms but occurs in individuals
with no history of the disorder in their family.
Criteria adapted from the Headache Classification
Subcommittee of the International Headache Society
Familial hemiplegic migraine (HM) is a category of
migraine with aura (MA).
Diagnostic criteria for HM are as follows:
Headaches fulfill criteria for MA
Aura includes some degree of hemiparesis and may be
prolonged but fully reversible.
HM is categorized as familial if at least one first degree
relative (i.e., parent, sib, and/or offspring) or second degree
relative has identical attacks.
HM is sporadic if no first- or second degree
relative meets criteria for hemiplegic migraine.
Targeted variant analysis
Deletion or duplication analysis
Sequence analysis of the entire coding region
Mutation scanning of entire coding region
Chronic migraine, was previously referred to as
Characterized by headaches (tension-type and/or
migraine) on 15 or more days per month, with at least 8
days per month fulfilling International Headache
Society diagnostic criteria for migraine for at least 3
months in the absence of ongoing medication overuse
(Olesen et al., 2006).
Patients with chronic migraine usually have a history
of episodic migraine that began in their second or
Though in majority evolution from episodic to
chronicity is gradual, in
The prevalence of a family history of migraine was
recognized in the 17th century.
Most striking evidence of a genetic basis for migraine
has come from investigations of familial hemiplegic
In 1993, FHM was mapped to chromosome 19p13 in
About 50% of tested families have mutations in
CACNA1A, a gene located on chromosome 19p13
that codes for the α1-subunit of a brain-specific
voltage-gated P/Q-type calcium channel (Ophoff et
Recent reports (Terwindt et al., 2001) not only
implicate CACNA1A in FHM, but it may be
overrepresented in patients with migraine without
Gardner et al. (1997) reported another locus for FHM
on chromosome 1q31 in a 39-member four-
generation pedigree showing a clear FHM phenotype.
This region on chromosome 1 contains a neuronal
calcium channel α1E-subunit gene.
Subsequent studies in other families have found two
additional mutations linked to FHM. One that mapped to
chromosome 1q21-q23 (De Fusco et al., 2003) is located
in a gene coding for a subunit of a sodium/potassium
Another mutation identified on chromosome 2q24 is
located in a gene that encodes a sodium channel subunit
(Dichgans et al., 2005).
A recent study based on a genome-wide screen of 50
multigeneration yielded significant evidence of linkage
between the migraine with aura phenotype and marker
D4S1647 located on chromosome 4q24 (Wessman et
DURATION OF HEADACHE :
Migraine : 3 hours to 3 days
Tension type headache : 30 mins to 3 wks to 3 years
Cluster headache : 30 mins to 3 hours
Paroxysomalnhemicranias : 3-30 min
SUNCT : 3 seconds
Status migrainous : > 3 days
Chronic headache : > 3 months
Acute or subacute and progressive headache
New onset headache in adult life (>40 years)
Change in headache pattern : intensity, frequency, new features or
decreased response to treatment
Headache associated with,
Nause, vomiting not explained by migraine or illness
Nocturnal occurance or morning awakening
Worsening by change in posture or valsalva
Confusion, seizure or weakness
Repeated attacks of headache lasting for 4-72 hours in patients
with a normal physical examination, no other reasonable cause
for the headache, and :
Atleast 2 of the following features:
◦ Unilateral pain
◦ Throbbing pain
◦ Aggravation by movement
◦ Moderate or severe intensity
Plus at least 1 of the following features:
• nausea /vomiting
• Photophobia and phonophobia
Neuroimaging used in some cases to exclude
secondary causes of headache or ischemic
Migraine is an independent risk factor for ischemic
• change in headache pattern
• side-locked headaches (unilateral headaches that
never change sides)
• new onset of chronic daily headache.
• prolonged aura
• Higher possibility of ischemic complication
(women with migraine with aura ,younger than 45
years and use of estrogen containing oral
CT SCAN is of extremely low yield in patients who
undergo imaging for chronic headachewithout
CTPerfusion may be very useful to analyze acute
attacks perfusion regional changes.
It is more sensitive than CT in the detection of an
CT study of apatient within
amigraine attack with prolonged
NECT is normal.
CTPerfusion showed areas of
hypoperfusion in left frontal and
• White matter hyperintensities are more
prevalent in– migraineurs compared to the
generalpopulation (12–47% of all patients).
– More than 60% of migraineurs with aura
– Patients with frequent attacks
When the attack is finished, theneurologic deficit
usually resolves fully
• Unilateral symptoms may switch sides between
• MRI finding
– cortical hemispheric thickening (hyper in T2)
– No vascular territory
– No contrast enhancement or diffusion
– Midline shift and sulcal effacement
PET scan showed brainstem activation during the
Maximum activation was around the dorsal midbrain,
which contains the dorsal raphe nucleus and
periaqueductal grey matter, and the dorsolateral pons,
which contains the locus coeruleus.
Should be started as early as possible during the aura phase,
should not wait for headache to begin.
Once the attack is fully developed, the oral preparations are
Aspirin, acetaminophen, naproxen, ibuprofen,or oral analgesic
in combination with caffeine may be effective.
Caffeine helps by inducing vasoconstriction, and reduces the
firing of serotonergic brainstem neurons.
But caffeine containing analgesic use foe more then 2 days in
a week, increases headache.
New class of antimigraine drugs, having selective agonistic
activity on 5 HT1B and 5 HT1D receptors.
Activity on 5 HT1B causes vasoconstriction, on 5 HT1D
inhibits sensory neuropeptide release from perivascular
Activation of 5-HT1B/5-HT1D receptors can attenuate the
excitability of cells in the TNC, which receives input from the
5-HT1B/5-HT1D agonists may act at central as well as
peripheral components of the trigeminal vascular system.
1. local reaction at the injection site, usually of mild or
moderate severity, and a transient tingling or flushed sensation
that may localize or generalize.
2. unpleasant sense of heaviness or pressure in the neck or
3. has been shown to produce a minor reduction incoronary
Patients with any history suggestive of coronary insufficiency.
Untreated hypertension or peripheral vascular disease and
Those using ergot preparations.
Women during pregnancy
Hemiplegic migraine or basilar-type migraine.
Though now is supplemented by newer agents, ergots still
have role in symptomatic patients.
Mechanism of action: agonistic activity on 5 HT receptors
Have both vasodilator and vasoconstriction effects depending
on dose and resting tone of target vessels.
Mode of administration : oral, parenteral, rectal. Oral route is
The ergot preparation can be repeated in 60 minutes if needed.
If more than 6 mg of ergotamine is required per week, use an
Coronary artery disease
Peripheral vascular disease
In patients having aura for prolonged time or any neurologic
Gepants (olcegepant, telcagepant)
A novel CGRP antagonist is currently undergoing evaluation
in human trials. If found to be efficacious and safe, the CGRP
antagonist, which has little vasoconstrictive effect on vascular
smooth muscle, benefit patients in whom triptan and
ergotamine use is precluded because of comorbid coronary
A preventive program is appropriate when attacks
occur weekly or several times a month, or when they
occur less often but are very prolonged and
The most effective prophylactic agents available
typically reduce headache frequency by at least 50%
in approximately 50% of patients.
β-Adrenergic antagonists are widely used for prophylaxis of
Propranolol in doses of 80 to 240 mg/day, if tolerated, should
be given a trial of 2 to 3 months. Compliance increases with
the use of a long-acting form of propranolol given once daily.
Side effects: not severe- Lethargy or depression may occur.
Hypotension, bradycardia, impotence, insomnia, and
nightmares can occur.
Contraindication: patients having asthma severe depression
should be used with caution in patients using insulin or oral
hypoglycemic agents, because it may mask the adrenergic
symptoms of hypoglycemia.
Amitriptyline and other tricyclic antidepressants can be
helpful in migraine prophylaxis.
Mechanism of action: Blockade of noradrenaline uptake at
catecholamine terminals and inhibition of serotonin reuptake
may be related, but the action of antidepressants in migraine is
unclear at present.
The benefit seems to be independent of their antidepressant
Dosage : Amitriptyline 10 to 150 mg at night
Morning drowsiness, dryness of mouth, weight gain,
tachycardia, and constipation are common.
The anticholinergic side effects may decrease with time. If
tolerated, give the tricyclic agents a trial of at least 3 months
after reaching a therapeutic dose.
The optimal dose for migraine prophylaxis is determined by
titration to the effective or maximum tolerated dose within the
therapeutic range (usually 40-150 mg)
Drugs used: verapamil, Flunarizine, sometimes
Prevent platelet aggregation and alterations in release
and reuptake of serotonin.
Verapamil in doses of 80 to 160 mg 3 times a day
reduces the incidence of migraine with aura, but it is
not as useful in migraine without aura.
Flunarizine is weak calcium channel blocker that also
inhibits Na channels. Frequency of attacks are
reduced, but effect on intensity and duration is less
It is claimed to be cerebro-selective calcium channel
blocker, may benefit by reducing intracellular
calcium overload due to brain hypoxia and other
Side effect: sedation, constipation, dryness of mouth,
hypotension, flushing, weight gain, rarely extra-
Their mechanisms of action in migraine prophylaxis
Valproic acid, given in the form of divalproex
sodium, is generally effective at a range of 500 to
1750 mg/day taken in divided doses.
Sedation, dizziness, increased appetite, increased
bleeding time, increased fragility of hair, and an
asymptomatic increase in liver function test values.
women who are at risk for becoming pregnant,
because it is associated with an increased risk for
neural tube defects.
Gabapentin is effective in the reduction of migraine
incidence (Mathew et al., 2001)
It appears relatively well tolerated, although dizziness
and sedation may limit its use in some patients.
The usual therapeutic dose range for gabapentin is
900 to 2400 mg/day.
Topiramate is a recent addition to the antimigraine.
Topiramate has effects not only on γ-aminobutyric acid
(GABA) but also on non-NMDA glutamate and carbonic
Side effects :It may have prominent sedating and cognitive
side effects. paresthesia and weight loss, mildly increased risk
for kidney stones.
Slow gradual titration of the drug (15-25 mg/wk initially) to
the therapeutic range of 75 to 200 mg/day the most successful
Cyproheptadine is a peripheral serotonin antagonist.
It has weak anti-bradykinin activity and prevents
In adults, it has a minor role in prevention of
migraine, but it is more effective in children.
Side effect:-it causes drowsiness
significant weight gain.
Riboflavin administered orally in a dose of 400 mg/day
has been shown to be effective in migraine prophylaxis
in a prospective randomized controlled study
Till date BTX-A is available with good amount of
thrapeutic trial, BTX-B and BTX-F are also expanding
Causes chemo-denervation, muscle paralysis, interferes
with the release of acetylcholine from the presynaptic
Muscle paralysis from BTX-B was not as complete or
long-lasting as that from BTX-A
Patients resistant to BTX-A often initially respond to
Onabotulinumtoxin A injection exert its effect by reducing the
release of proinflammatory and vasodilating neuropeptides
from nociceptive terminals.
Botulinum toxin blocks the release of glutamate from nociceptive
terminals and therefore may reduce or inhibit the development
of peripheral and central trigeminal sensitization.
Doses of approximately 150 units are injected in muscles of the
forehead, as well as the temporalis, splenius capitis, and
The effect, when it occurs, usually appears within 7 to 10 days
and persists for up to 3 months.
Side effects are minimal when avoiding lateral forehead injection.