Migraine headaches

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Migraine headaches

• Vishal Sharma

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Overview

• Migraine and Statistics
• History
• Classification and symptoms
• Etiology and Pathophysiology
• Treatment

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Migraine and statistics

• Migraine is a neurovascular disease caused by
  neurogenic inflammation and characterized by
  severe, recurring headaches
• It usually characterized by the severe pain on
  one side of the head as compare to the pain in
  rest of the head.
• It occurs more often in Women than in men.

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History

• History goes back to 9000 years.
• First mode of treatment trepanation
• Medical intervention in which a hole is drilled
  or scraped into the human skull, exposing the
  dura mater in order to treat health problems
  related to intracranial diseases.

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History cont.

• In 2nd century AD, Pergamum a Greek physician
  used a term hemicrania.
• The brain and stomach were connected
• Migraine evolved from this term
• However, this idea was replaced by blood flow in
  17th century
• In 80s, Dr. Harold G. Wolff said that dilation of
  blood vessels is the main cause of migraine.

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Classification of Migraine headache.

• 1) Migraine without Aura or common migraine
• Does not give any warning signs before the onset
  of headache.
• It occurs in about 70 to 80 of migraine patients
• 2) Migraine with Aura
• Give some warning signs called aura before the
  actual headache begins. Approximate, 20 to 30
  migraine sufferers experience aura.
• The most common aura is visual and may include
  both positive and negative (visual field
  defects) features.

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Negative scotoma. Loss of local awareness of
local structure
Zigzag structure

Positive Scotoma. Additional structures
One side loss of perception.
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Classification of Migraine headache cont.

• 3) Retinal migraine
• It involves attacks of monocular scotoma or even
  blindness of one eye for less than an hour and
  associated with headache.
• 4) Childhood periodic syndromes that involve
  cyclical vomiting (occasional intense periods of
  vomiting), abdominal migraine (abdominal pain,
  usually accompanied by nausea), and benign
  paroxysmal vertigo of childhood (occasional
  attacks of vertigo).
• They may be precursors or associated with
  migraine.

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Classification of Migraine headache cont.

• 5) Complications of migraine describe migraine
  headaches and/or auras that are unusually long or
  unusually frequent, or associated with a seizure
  or brain lesion.

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Etiology and Pathophysiology

• The precise etiology and pathophysiology of
  migraine is unknown.
• However, neuronal dysfunction theory is most
  acknowledged theory.
• Activity in trigeminovascular system.

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Abnormal Neuronal activity
Cerebral cortex, thalamus or hypothalamus in response to stress, emotion.

Instability in release of neuropeptides e.g., Substance P, neurokinin A, calcitonin gene-related polypeptide, serotonin
Activates nociceptive trigeminovascular system and causes prolong pain
Activates trigeminovascular system, which in turn, stimulate pain stimulating neurons in brain stem and upper spinal cord
Initiate inflammatory response, sensitizes surrounding tissues and produce headache
Promote vasodilation and plasma protein extravasations.
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Abnormal Neuronal activity
Cerebral cortex, thalamus or hypothalamus in response to stress, emotion.

Releases vasoactive neuropeptides e.g., Substance P, neurokinin A, calcitonin gene-related polypeptide, serotonin
Activates nociceptive trigeminovascular system and causes prolong pain
Boss
Activates trigeminovascular system, which in turn, stimulate pain stimulating neurons in brain stem and upper spinal cord
Initiate inflammatory response, sensitizes surrounding tissues and produce prolong headache
Promote vasodilation and plasma protein extravasations.
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Serotonin

• Neurotransmittor
• Serotonin ( 5- hydroxytryptamine) is thought to
  be an important mediator of migraine.
• Unstable serotonergic neurotransmission , so has
  lower threshold for migraine.
• There are 7 classes of 5-HT receptors
• Out of 7, 2 involve in migraine pain.

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Serotonin cont.

• It is basic as amines and Ammonia
• Changes Ph of blood
• Serotonin causes
• Vasodilation
• Serotonin causes
• Vasoconstriction
• During migraine the level of serotonin is low in
  blood. (Low Ph)
• Drug target

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5- HT1 Presynaptic receptor
Serotonin binds to 5-HT1 and 5-HT2
5- HT2 Postsynaptic receptor
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How bad could migraine be

• It could distrub the normal life activities.
• Could lead to brain damage
• Recently, a woman in London had a migraine
• Lost her accent

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Treatment

• Identification and elimination of factors.
• For example, Tobacco smoke, loud noise, stress,
  caffeine, emotions, contrasty light etc.
• If they dont work then move on to medicines
• Prophylactic therapy
• Abortive therapy

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Prophylactic therapy

• Used in case of frequent migraines
• Used when abortive therapy has failed
• Medicines have to taken everyday to be effective
• On the other hand, abortive medicine are taken
  during actual migraine pain.

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Medicines used in this therapy

• 1) Medicines that block beta-adrenergic.
• For example, Propranolol, nadodol, timolol,
  atenolol, and metoprolol.
• Reduce the frequency of attacks by 50 in 60 to
  80 patients.
• Side effects- fatugue, sleep disturbance,
  depression, hypotension etc

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Cont.

• 2) Tricyclic antidepressants
• For example, amitryptiline, nortryptiline,
  doxepin, imipramine etc
• Independent of antidepressant activity.
• Antagonist of 5-HT2, thus stabelize serotonin
  neurotransmission
• 3) Methysergide-
• Semisynthetic ergot alkaloid and is 5-HT2
  antagonist.
• Gives best result when taken with meals
• Side effects- gastrointestinal intolerence,
  insomnia, and muscle cramps.

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Prophylactic therapy cont.

• Calcium channel Blockers-
• Verapmil
• Takes up to 8 weeks to show any good effect
• Side effects- Hypotension, constipation etc

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Abortive therapy

• 1) simple analgesics-
• For mild and infrequent migraine- Aspirin and
  acetaminophen
• Aspirinacetaminophenbarbiturate butabital To
  induce sleep
• aspirinacetaminophennarcotics Fiorinal
• Aspirin acetaminophencaffiene Esgic
• Drawback- Continuous use fails to provide pain
  relief.

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Abortive Therapy cont.

• 2) NSAIDs-
• Inhibit prostaglandin synthesis.
• So may prevent inflammation in trigeminovascular
  system and alleviate migraine pain
• They are effective for reducing the frequency,
  severity, and duration of migraine attacks. e,g.
  Aspirin, Ibuprofen, Naproxen etc.

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Corticosteroids mediate glucose metabolism and
inflammation
Inflammation, Asthma
Non-steroidal Anti-inflammatory
Steroidal (corticosteroid) Anti-inflammatory
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Abortive therapy cont.

• 3) Ergot family
• Ergotamine-
• It is secondary metabolite obtained from ergot
  fungus
• Dihydroergotamine- available in inject able form.
• The structure shares some similarit with
  neurotransmittor serotonin.
• Acts as agonist, bind to 5-HT1,
• More effective when given during early migraine
  attacks

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Abortive therapy

• 5) Triptan Family
• 5-HT1 receptor agonists
• Examples-
• Sumatriptan Imitrex
• Zolmitriptan Zomig
• Rizatriptan Maxalt
• Eletriptan Relpax
• Naratriptan - Amerge

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Elitriptan Sumatriptan


Rizatriptan Zolmitriptan
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Side Effects

• nausea, vomiting, dizziness, fatigue, and
  vertigo.
• Not good for hypertensive patients at all.

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Ergot and Triptan comparison

• The rates of ergotamine and sumatriptan overuse
  were 14.2 and 3.5, respectively
• Drug-induced headache could be found more
  frequently in cases of ergotamine overuse then
  drugs of triptan family.

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Miscellaneous agent

• Midrin Isometheptane dichlorophenazene
  acetaminophen
• Used in patients who do not respond to ergot and
  triptan
• Less effective then ergot and triptan familys
  drugs
• Most frequent side effects are nausea, dizziness,
  insomnia, and vomiting.

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References

• "Etymology of migraine". Online Etymological
  Dictionary. http//www.etymonline.com/index.php?te
  rmmigraine. Retrieved 27 May 2009
• http//en.wikipedia.org/wiki/Migraine
• Headache Classification Subcommittee of the
  International Headache Society (2004). "The
  International Classification of Headache
  Disorders 2nd edition". Cephalalgia 24 Suppl 1
  9160. doi10.1111/j.1468-2982.2004.00653.x.
  PMID 14979299. 

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Questions

• Name the major neurotransmitter that mediate the
  migraine pain.
• Name major medicines that act as 5-HT1 agonist
  and 5-HT antagonist.
• How does NSAIDs work?

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Questions