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This presentation was given to first year pharmacy students as a part of course on a medical physiology and pathophysiology.
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Headache & Migraine
Brian J. Piper, Ph.D., M.S.
October 23, 2012
Goals
• Describe differences in symptomology between migraines, cluster headaches, and tension-type headaches.
• List the vascular and neural substrates of migraine/headaches.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5503a6.htm
Importance
• WHO ranks migraine among world’s most debilitating chronic illnesses
• 3rd most common reason for ER visits (U.S.)• ≈$13 billion/year in lost productivity (U.S.)• underdiagnosed & undertreated
Menken et al. (2000). Archives of Neurology, 57(3), 418-420.
Migraine Terminology• migraineurs: person who experiences migraines• aura: collection of symptoms that may precede or co-
occur; typically visual, lasts less than 1 hour– 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
DiPiro et al. (2008). Pharmacotherapy: A Pathophysiologic Approach. p. 1008.
George Cruikshank: The Head Ache (1819)
2:20: http://www.mayoclinic.com/health/migraine-aura/MM00659
International Headache Society Migraine Criteria• Migraine with aura (classic migraine)
– At least 2 attacks– Aura fulfills criteria for typical aura, hemiplegic aura, or basilar
type aura– Not attributed to another disorder
• Migraine without aura– At least 5 attacks– Headache lasts 4 to 72 hours (untreated or successfully treated)– Headache has at least 2 characteristics
• Unilateral location, pulsating quality, or moderate or severe intensity– Aggravation by or avoidance of routine physical activity
(walking, climbing stairs)– During headache, at least one of the following:
• Nausea, vomiting, or both• Photophobia and phonophobia
– Not attributed to another disorder
http://ihs-classification.org/en/02_klassifikation/02_teil1/01.00.00_migraine.html
Epidemiology: American Migraine Prevalence & Prevention Study
• Mailed Survey to 257K, response by 163K (64.9%) who are representative of U.S. population
• Migaine: IHS criteria, Chronic Migraine: >15 days/month over 3 months
Epidemiology: American Migraine Prevalence & Prevention Study
• Mailed Survey to 257K, response by 163K (64.9%) who are representative of U.S. population
• Migraine: IHS criteria, Chronic Migraine: >15 days/month over 3 months
Epidemiology: American Migraine Prevalence & Prevention Study
• Mailed Survey to 257K, response by 163K (64.9%) who are representative of U.S. population
• Migraine: IHS criteria, Chronic Migraine: >15 days/month over 3 months
• Demographic Correlates– Age (18-49)– Sex (Female)– SES: >$90K = 0.52; <$22K = 2.71; 5.2 fold!
• Primary versus Secondary (tumor, infection, stroke)
Buse et al. (2012-in press). Headache. doi: 10.1111/j.1526-4610.2012.02223.x
Pathophysiology
• limited animal models• theory: genetic (50% heritable) & neurovascular• 2 min: http://www.youtube.com/watch?v=yZr9Joe85wg• orthodromic: electrical potential following typical direction (soma
to axon)• antidromic: electrical potential traveling in the reverse direction
(axon to soma)
Neural Substrates of Migraine
• 1) meningeal vessels• 2) trigeminal: opthalmic nerve (V1)
Neural Substrates of Migraine
• 1) meningeal vessels• 2) trigeminal: opthalmic nerve (V1)• 3) pons (input from other structures)• 4) facial nerve
Neural Substrates of Migraine
Goadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.
5-HT1B: vasoconstriction5-HT1D: peripheral neuronal inhibition
Goadsby et al. (2002). New England Journal of Medicine, 346(4), 257-270.
Brainstem Activation During Migraine
• 43 year old man with history of migraine without aura
• Positron Emission Tomography completed at rest and following nitroglycerin
Bahra et al. (2001). Lancet, 357, 1016-1017.
Posterior
Anterior
Migraine Across Countries (Twins)
Mulder et al. (2003). Twin Research, 6(5), 422-431.
Genetic Contribution to Migraine
Mulder et al. (2003). Twin Research, 6(5), 422-431.
Environmental Factorsstresshead and neck infectionhead trauma/surgeryHormone changesaged cheesedairyred winenutsshellfishcaffeine withdrawalvasodilatorsperfumes/strong odorsirregular diet/sleeplight
Cluster Headache• unilateral pain• unilateral other:
– ptosis– miosis– rhinorrhoea
• circadian• males > females• brief ( < 3 hours)• rare
Dodick et al. (2001). Cluster headache. Cephalagia, 20(9), 787-803.http://ihs-classification.org/en/02_klassifikation/02_teil1/03.01.00_cluster.html
Hypothalamic & Insular Activation During Cluster Headache
• 9 patients with a history of cluster completed PET for regional cerebral blood flow at rest & following nitroglycerin
May et al. (1998). Lancet, 352(9124), 275-278.
Episodic Tension-type Headache (TTH)
A. Number of days with such headache < 180/year (<15/month) B. Headache lasting from 30 minutes to 7 days C. At least 2 of the following:
• Pressing/tightening (non-pulsating) quality• Mild or moderate intensity (may
inhibit, but does not prohibit activities)• Bilateral location• No aggravation by walking stairs
or similar routine physical activity D. Both of the following:
• No nausea or vomiting (anorexia may occur)• Photophobia and phonophobia are absent, or one but not
the other is present E. At least 10 previous headache episodes fulfilling these criteria
F. No evidence of organic disease
Substrates of TTH
Dorsal Horn: sensoryVentral Horn: motor
D
V
Tension-type Headache or Migraine
Tension-Type Migraine
Mild
Moderate
Severe
Unilateral
Bilateral
Photophobia
Nausea
Throbbing
Pressure
Aura
Vomiting
Aggravated by Activity
Comparison
• Frequency: TTH > Migraine > Cluster• Pain:
• Sex Ratio: F > M F > M M > F
Summary
• Headache and migraine are common but under-appreciated.
• Migraine & headache pathophysiology is an active, but far from complete, area of research.
0 to 1.5 min (skip ad): http://www.youtube.com/watch?v=eJZMnXG_Yw0
Medication Overuse Headache• Occurrence of rebound headache following
long-term treatment• Identification may take months, may involve
transition to prophylactic treatment (e.g. SSRI)
Smith & Stonerman (2004). Drugs, 64(22), 2503-2514.