HEADACHE - MIGRAINE

DR.S.PRANAVENDRA NATH,
JUNIOR RESIDENT,
DEPT. OF INTERNAL
MEDICINE,
KIMS & RF.
OBJECTIVES
 History
 Introduction
 Epidemiology
 Classification
 Pathophysiology
 Treatment
HISTORY
 Hippocrates - 400 B.C.
 Headache could be triggered by exercise or intercourse and
migraine resulted from vapors rising from the stomach to
the head and that vomiting could partially relieve the pain
of headache.

 Aretaeus of Cappadocia – Greek Physician

 Second century
 Unilateral headaches
 Associated with vomiting
 The term migraine derives from the ancient
Greek word, hemi-kranios, which means
“half head,”
 Galen of Pergamon – Rome Physician
 Unilateral pain and originated
-meninges and vasculature of the head.

 Migraine was distinguished from common

headache by Tissot in 1783.

 Abu Bakr Muhammed Ibn Zakariya Râzi of
Persia - Physician
 Association between migrane and
hormones
 In the “Bibliotheca Anatomica, Medic, Chirurgica” - London in 1712
 Migraine was described along with other major types of headaches

 In the late 1930s, Graham and Wolff reported that ergotamine tart could
relieve migraines

 1950- Harold Wolff – blood vessel abnormalities associated with migraine

INTRODUCTION

 Headache
---Most common reason to seek medical attention.
---Responsible for more disability than any other neurologic problem.
 Migraine - the second most common cause of headache
---Most common neurologic cause of disability in the world.
 Migraine is a familial disorder characterized by
---Recurrent attacks of headache.
---Variable in intensity, frequency and duration.
 Attacks are commonly unilateral
---Usually associated with anorexia, nausea and vomiting.
EPIDEMIOLOGY
 Migraine has a one-year prevalence of 12% in
the general population
-18% of women
-6% of men
 Prepubescent boys and girls- similar frequency
 Puberty, the incidence of migraine
preferentially high in girls
 Lifetime prevalence
-33% in women
-13% in men
CLASSIFICATION
 PAIN SENSITIVE STRUCTURES IN HEAD
• Extra-cranial pain
sensitive structures:
– Sinuses
– Eyes/orbits
– Ears
– Teeth
– TMJ
– Blood vessels
– 5,7,9,10 cranial nerves
carry pain from this
structure
• Intra-cranial pain
sensitive structures:
– Arteries of circle of willis
and proximal dural
arteries,
– Dural Venous sinuses
– Meninges
– Dura
 Migraine Terminology
• Migraineurs: person who experiences migraines
• Aura: a focal visual, sensory, or motor neurologic disturbance that may
occur with or without headache.
– positive features
• scintillations: a rapidly oscillating pattern of visual distortions
• photopsia: perception of flashes of light
• teichopsia: spot of flickering light
– negative features
• scotoma: an area of diminished vision within the visual field
• hemianopsia: blindness in half of the visual field, may involve
one or both eyes
– hemiplegic aura: occurring on one side of body
– basilar type aura: aura is localized to the brainstem
PATHOPHYSIOLOGY

 Headache pain
--- initiated by primary trigeminal afferents.
--- innervate the blood vessels, mucosa, muscles, and tissues.
 The sensory sensitivity that is characteristic of migraine
--- due to dysfunction of monoaminergic sensory control systems.
--- located in the brainstem and hypothalamus.
GENETIC BASIS
 Migraine has a strong genetic component.
--- First-degree relative with a history of migraine.
--- Risk is increased 4-fold in relatives of people who have migraine with aura.
 Familial hemiplegic migraine (FHM)
Vascular Theory
 Migraine Headache due to Dilatation of blood vessels.

 The aura of migraine resulted from vasoconstriction.

 This no longer considered viable.

 Vasodilatation is probably an epiphenomenon resulting from instability in the central

neurovascular control mechanism.
Cortical Spreading Depression
 Phenomenon known as Cortical Spreading Depression of Leão.

 It is a self-propagating wave of neuronal and glial depolarization that spreads

across the cerebral cortex.

 Cortical spreading depression is hypothesized to:

 Cause the aura of migraine
 Activate trigeminal nerve afferents
 Alter blood-brain barrier permeability by matrix metalloproteinase activation and
upregulation
 The activation of trigeminal afferents by CSD in turn causes inflammatory changes in
the pain-sensitive meninges headache of migraine through central and peripheral
reflex mechanisms.

 The likely molecular cascade of events by which pain sensitive trigeminal afferent
neurons are activated by cortical spreading depression involves the opening of
neuronal pannexin-1 megachannels and subsequent activation of caspase-1, followed
by the release of the proinflammatory mediators, activation of nuclear factor kappa-B
in astrocytes, and transduction of the inflammatory signal to trigeminal nerve fibers
around pial vessels.

 Thus, this pathway links cortical spreading depression, the phenomenon thought to
underlie the migraine aura, to prolonged activation of trigeminal nociception, which
generates the pain of the migraine headache.
Trigeminovascular system 
 Consists of small caliber pseudounipolar sensory neurons that originate from the
trigeminal ganglion and upper cervical dorsal roots.

 These sensory neurons project to innervate

-large cerebral vessels,
-pial vessels,
-dura mater,
-large venous sinuses.

 Most of the innervation of the anterior structures is via the ophthalmic division of the
trigeminal nerve with a greater contribution of upper cervical roots to posterior
structures.
 Trigeminal nucleus caudalis - convergence of the projections from the upper cervical
nerve roots and the trigeminal nerve.

 This convergence can explain the distribution of migraine pain.

 From the trigeminal nucleus caudalis, fibers that are involved in the localization of pain
ascend to the thalamus (mostly to the ventroposterior medial nucleus of the thalamus)
and to the sensory cortex.
 Stimulation of the trigeminal ganglion results in release of vasoactive neuropeptides,
including substance P, calcitonin gene-related peptide, and neurokinin A.

 Causes neurogenic inflammation, important in the prolongation and intensification of

the pain of migraine.

 The two main components of this sterile inflammatory response are vasodilation (CGRP
is a potent vasodilator) and plasma protein extravasation.
The Migraine Generator

 There is an area in the lower part of the brain (brain-stem) in which nerve cells turned
on at the beginning of the migraine, remained on for the length of the migraine and
clicked off at the end of the migraine.

 This center is known as the migraine generator.

 The exact location for the generator may be the dorsal raphe nucleus of the brainstem.
Sensitization
 Process in which neurons become increasingly responsive to nociceptive and
non-nociceptive stimulation:
---response thresholds decrease,
---response magnitude increases,
---receptive fields expand,
---spontaneous neuronal activity develops.

 Peripheral sensitization in the primary afferent neurons and central sensitization within
second order neurons in the trigeminal nucleus caudalis and higher order neurons in
the central nervous system are thought to play a role within individual migraine attacks
and, perhaps, even in the transformation of episodic migraine to chronic migraine.
 Responsible for many of the clinical symptoms of migraine, including the
->throbbing quality of the pain,
->the worsening of pain with coughing, bending, or sudden head movements,
->hyperalgesia (increased sensitivity to painful stimuli),
->allodynia (pain produced by normally non-noxious stimulation).
Serotonin
 The serotonin receptor (5-hydroxytryptamine [5-HT]) is the most important receptor in
the headache pathway.
 It is a neurotransmitter that can both excite and inhibit.
 5-HT1 receptors are negative or inhibitory receptors.
 5-HT2 receptors are positive or excitatory receptors.
 When serotonin binds to the excitatory 5HT2 receptors near the migraine central
generator, it turns on the migraine.
 Serotonin, activating the 5-HT1D receptor, may help get rid of migraine pain by
inhibiting CGRP release.
 Therefore, when the serotonin binds to both 5-HT1B and 5-HT1D receptors, both
mechanisms of migraine, blood vessel dilation and inflammation, are turned off.
 5-HT1B : vasoconstriction
5-HT1D : peripheral neuronal inhibition
Dopamine
 Dopamine hypersensitivity is present in patients with migraine
 Yawning, nausea, vomiting, hypotension
 Involved in hypothalamus activation
 Dopamine antagonists are helpful
Calcitonin gene-related peptide 
 The calcitonin gene-related peptide (CGRP) has a key role in migraine pathophysiology.

 CGRP is a 37 amino acid neuropeptide that is expressed in trigeminal ganglia nerves and
is a potent vasodilator of cerebral and dural vessels.

 CGRP appears to mediate trigeminovascular pain transmission from intracranial vessels

to the central nervous system.

 Vasodilatory component of neurogenic inflammation.

 Stimulation of the trigeminal ganglion induces the release of CGRP, and CGRP infusion
can trigger a migraine attack in migraineurs.
Four Phases
• Hours before headache
Premonitory • Yawning, polyuria, mood change, irritability, light
sensitivity, neck pain, and concentration difficulties

Aura • Immediately precedes or accompanies headache

Headache

Post-drome • After resolution of headache

Migraine Attack
SIMPLIFIED DIAGNOSTIC CRITERIA
(Meritt’s neurology)
• Repeated attacks of headache, lasting 4-72 hrs
• Normal physical and neurological examination
• No other reasonable cause

Headache Accompanied w/
At least 2 of …. At least 1 of ….
Unilateral pain
Throbbing Nausea/vomiting
pain Photophobia & phonophobia
Aggravation by movement
Moderate to severe intensity
POUND MNEMONIC
• Pulsatile quality of headache
• One-day duration(4-72 hours)
• Unilateral location
• Nausea or vomiting
• Disabling intensity
SECONDARY HEADACHE
Migraine Secondary Headache
Past History Multiple Stereotypical Attacks New Onset, esp. older than 50
Duration 4-72 hours > 72 hours
Symptoms Gradual onset of headache or
onset neck pain Sudden onset

Neurological
symptoms/ begin and progress gradually last Vision, sensory, and language
Aura ≤1 hr (typical aura) symptoms lasting >1 hr

NE Normal between attacks Abnormal

Other Family history of headache fever, systemic illness
DIAGNOSIS

 History and Examination

 CBP
 ESR
 CRP
 CSF Analysis
 CT Brain
 MRI Brain
TREATMENT
Lifestyle
Oral
Acute/Abortiv
e
IV(at ED)
Pharmacologic Therapy

Long-term/Preventive
STRATEGIES FOR MIGRAINE TREATMENT
LIFESTYLE
• Avoid triggers
• Healthy and regular diet
• Regular sleep pattern
• Avoid excess caffeine and alcohol
• Reduce stress level(meditation, yoga)
• Avoid certain medication if possible
EXACERBATING MEDICATION LIST
• Oral Contraceptive
• Post-menopausal hormone replacement
• SSRIs
• Nasal decongestant
• Regular use of analgesic medications
• Opioids
• Barbiturates
• Caffeine
ACUTE/ABORTIVE TREATMENT
• The sooner, the better
• Take the medicine as soon as the headache starts

• Mild attack can be managed by oral agents

• Response rate 50-70%

• Severe attack may require intranasal or IV treatment

CATEGORIES

• 5-HT 1B/1D agonist (Triptan, Ergots)

• Acetaminophen, NSAIDs

• Dopamine antagonist (Chlorpromazine, metoclopramide,

prochlorperazine)
• Impaired GI motility during attacks even without nausea/vomiting

• Combination analgesics (Acetaminophen–aspirin–caffeine,

sumatriptan–naproxen)
ACUTE MEDICATION Rapid onset, short duration
Chest or facial muscle tightness, lightheadedness
Triptan Contraindicated in CAD
5-HT 1B/1D Nasal or SC delivery may be more effective than PO if vomiting
Agonist Ergots Nausea, dizziness
contraindicated in CAD

Minimal with intermittent use May be more effective in

Acetaminophen
combination with antiemetic agent
Analgesic Gastric irritation, excessive bleeding
NSAID May have additive benefit when taken with triptan
Chlorpromazine
Dopamine Metoclopramide Sedation, restlessness (akathisia), dystonic reactions
Antagonist Prochlorperazine
sCombination Acetaminophen–aspirin– Caffeine may have increased potential for overuse
Combination therapy is more effective than
caffeine Sumatriptan–naproxen
individual agents in some patients
ACUTE MANAGEMENT AT ED

• IV hydration may be considered if there is dehydration due to vomiting.

• Principle: Avoid opioid analgesics

• Recurrence rate: 75% within 48 hours of discharge

• Oral naproxen 500mg and/or sumitriptan 100mg upon discharge
ED TREATMENT ALGORITHM
Sumatriptan 6-12mg SC and/or Ketorolac 30-60mg IV

Metoclopramide 10-20mg IV
Dopamine Antagonists Prochlorperazine 10mg IV

Dexamethasone Dexamethason 8–24 mg IV

Valproic acid Valproic acid IV 10mg/kg over 30 mins

ACUTE MANAGEMENT AT ED
• Triptan: should not be offered to those who have used ergotamine, DHE, or a
triptan medication within the previous 24 hours.
• Dopamine antagonists: unpleasant side effects including akathisia and
drowsiness.
• Dexamethasone 8–24 mg IV to prevent recurrence of migraine.

Avoid Diphenhydramine, Hydromorphone, Morphine, Lidocaine

LONG-TERM/PREVENTIVE THERAPY
• Indication:
• Increasing frequency, usually > 4 times/month
• Also depend on severity and duration
• Individualized, discussed with patients
• Response rate: ~50-70%
• Should be taken daily
• Onset time: 2-12 weeks
• If stable, continue for 6-12 months and then taper.
• Monoclonal antibodies to the CGRP receptor (erenumab) or to the peptide
(eptinezumab, fremanezumab, and galcanezumab) have all proven effective and
well tolerated in migraine and should be available soon as preventive agents.
 COMMON MEDICATIONS FOR PREVENTION
Propranolo Hypotension, exercise intolerance, sexual dysfunction
l
Beta- Metoprolol
May be useful in patients with hypertension, tachycardia,
or anxiety
Blocker Timolol
Atenolol
Topiramat
Anti-Epileptic e
Paresthesias, weight loss, cognitive dysfunction, depression

Tremor, weight gain, hair loss, fetal neural-tube defects

Drug Valproate May be efficacious, but adverse effects limit its use

Tricyclic Amitriptyline Dry mouth, sedation, weight gain, urinary retention

Low doses are typically used (10 to 50 mg)
Antidepressants Nortriptyline may be useful in patients with insomnia

Less Common Candesartan(ARB)

Flunarizine (CCB)
NON-PRESCRIPTION SUPPLEMENT
• Evidence is weak

• Riboflavin
• Magnesium
• Coenzyme Q10
• Melatonin
LOCAL INJECTION
• For chronic migraine only (defined as headache occurring on more than 15 days
per month, with migraine features on at least 8 of those days.)

• Tenderness over the occipital nerve and forward radiation of pain on pressure
over the occipital nerve are predictors of benefit from occipital injections

• OnabotulinumtoxinA is a Food and Drug Administration (FDA)– approved

therapy
WHICH OF THE FOLLOWING IS NOT PAIN -
SENSITIVE?
1. Internal carotid artery.
2. Dura matter.
3. Paranasal sinuses.
4. Parietal lobe.
5. Frontalis muscle.
WHICH OF THE FOLLOWING IS NOT PAIN -
SENSITIVE?
1. Internal carotid artery.
2. Dura matter.
3. Paranasal sinuses.
4. Parietal lobe.
5. Frontalis muscle.
THANK YOU